Energy No-Brainer: Pluggable Hybrid Automobiles

First of all, what is a pluggable hybrid? Also called a Plug-in Hybrid, a pluggable hybrid is a car that can be powered by either internal combustion engine or electric motor--but it has larger batteries than conventional hybrids, and you can plug it in overnight to use inexpensive power grid energy for your daily commute. That constitutes a major shift in energy use from petrol to grid electricity. If the grid electricity comes from renewables (or nuclear), you can commute to work all week in a pluggable hybrid, without burning fossil fuel.

Among those who follow energy trends, the pluggable hybrid has become quite popular. Which makes many people wonder, why has Toyota gone to great lengths to distance itself from the pluggable hybrid concept?

On Tuesday, a Toyota representative wrote to an individual, "we do not currently have any announced plans to introduce a plug-in hybrid Toyota vehicle in the U.S." Find an expert who could say if that's intentionally evasive. (See our chronology of all automakers comments in the past year at http://www.calcars.org/carmakers.html .)

In a story broadcast today on NPR All Things Considered, you can hear spokeswoman Cindy Knight say, "You can certainly make a vehicle that will run, but you can't necessarily make a vehicle that people will buy.... Toyota went to great lengths to address the drawbacks of battery vehicles so that people do not have to plug our hybrids in, and our customers tell us that that is one of the features they like about the vehicle, they don't have to plug it in."

If the big carmakers distance themselves from this obviously winning concept, smaller players will rush in to fill the gap. Jim at the Energy Blog keeps close track of developments in pluggable hybrids, and he has a full array of energy links. Jim's place is an excellent site for following the progress in this war of the vehicular power plants.

Check out this Al Fin post for some of the underlying energy issues involved in the transition from internal combustion engines to fuel cell/supercapacitor/battery powered electric motor vehicles. The pluggable hybrid is a very useful intermediate step in the transition. No matter what the big auto manufacturers do, they cannot stop it from happening.

Boolean Gene Expression Map of the Brain: Logic of Expression

The basic genes of the human genome are mapped, and the gene variants that contribute to human disease are being mapped. That is a good start, but the really difficult work of understanding gene expression lies ahead. I am talking about the complex interactions of gene expression, and the many "maps" that must be compiled to detail gene expression. From MIT's Richard A.Young:

Each cell is the product of a specific gene expression program. Complex processes such as development of an organism from a single cell are the product of many cells executing many precise programs of gene expression in a temporally exact manner. These programs are controlled by transcriptional regulatory networks, and these networks are fundamental to all living processes. Such networks describe the factors that control the expression of each gene in the network, permitting the consequences of genetic or disease abnormalities to be analyzed in depth. Thus the eluciation of transcriptional regulatory networks in living organisms would be a substantial advance that could greatly contribute to the development of therapeutics and human health.

This recent newsrelease discusses the development of a Brain Gene Expression Map (BGEM) of the mouse at St. Jude Children's Research Hospital.

By St. Jude Children's Research Hospital, Scientists at St. Jude Children's Research Hospital have given investigators around the world free access to a powerful tool for studying brain development. The Internet-based tool, called the mouse Brain Gene Expression Map (BGEM), is one of the largest gene expression maps of an organ ever developed, according to the St. Jude researchers. They say the map will likely help scientists discover the genetic origins of brain cancers, which could speed development of novel drugs to treat them.

The continual updating and completion of the BGEM Web site will be crucial to scientists. More than half of the approximately 25,000 genes in the mouse are thought to be involved in the development and function of the nervous system, but scientists have determined the function of only 30 percent of them. Many brain disorders, such as tumors and some psychiatric diseases, are also believed to be caused by gene mutations that arise during development of this complex organ.

A report on the development and availability of the BGEM appears in the March 28 issue of PLoS Biology. The Web site is http://www.stjudebgem.org/

Read much more here.

Gene expression is far from straightforward. Not only do different genes interact in controlling each other, but each gene itself has differenct controller molecules and nucleotide segments, that interact in a Boolean fashion. This newsrelease discusses the Boolean nature of the regulation of gene expression:

It is easy to think of a gene acting like a light bulb, switching either on or off, remaining silent, or being transcribed by the RNA-making machinery. The region of DNA that controls the gene's output is called its regulatory region, and in this simple (and too simplistic) scenario, that region would act like a simple on–off switch.

But the regulatory regions of real genes are more complex, and act more like molecular computers, combining the effects of multiple inputs and calibrating the gene's output accordingly. The inputs are the various molecules that affect gene activity by binding to sites in the regulatory region. These molecules combine their effects in complex ways. Sometimes the gene remains silent unless both are present. Sometimes they are additive, such that the output when two factors are present is twice the output when only one is present. Sometimes they cancel each other out—in the presence of either, the gene is transcribed, but in the presence of both, it is not.

Thus, the regulatory region acts as a Boolean logic function, whose simple ANDs, ORs, and NOTs combine to determine the output of the gene. In a new study, Avi Mayo, Uri Alon, and colleagues show that mutations in the regulatory region affect this logic function in a simple and well-studied genetic system, the lac operon in Escherichia coli bacteria, whose suite of genes regulate metabolism of lactose.

Read more details at the source.

At Al Fin, we often discuss the introduction of genes into cells, to change gene expression. But it should be clear that there are many alternative mechanisms of changing gene expression, and scientists are a long way from both learning about and understanding them all.

Forced Entry: The Clever Sneaks of Gene Therapy

Sneaking genes into cells without causing damage or harm requires cleverness and skill. The first story details work by Ames (Iowa) Laboratory researchers, who have developed a very clever porous silica nanosphere that can be taken up by a cell, and deliver its payload of genes or other molecules on command.

Currently, scientists have difficulty introducing chemicals or genes into cells without either damaging the cell or causing a chain-reaction of events that can’t be tracked.

“With current gene therapy, it’s possible to switch genes on and off, but you don’t really know if you are affecting other parts and processes of the cell as well,” Lin said. “You may be able to get a plant cell to produce a certain desired product, but the yield may drop significantly.”

By using externally controlled nanospheres, Lin explains that it may be possible to sequentially release genes, chemical markers and other materials within cells in order to track what happens and what specific changes take place. This phase of Lin’s research ties into a larger plant metabolomics project at Ames Laboratory.

Read the entire fascinating report here. This report fascinated me due to the exquisite level of control it promises, at the cellular level. This approach will bear watching.

The second report on gene smuggling comes from this Eurekalert newsrelease on research from the University of North Carolina, Chapel Hill, and the University of Pittsburgh. In this case, the reserchers are using a customized vector called adeno-associated virus (AAV) to introduce the dystrophin gene into muscles of boys suffering from Duschenne Muscular Dystrophy (DMD).

The trial was launched March 28, at Columbus Children's Hospital in Ohio, an affiliate of Ohio State University's School of Medicine. In the trial, six boys with DMD will receive replacement genes for an essential muscle protein.

Each of the boys will receive replacement genes via injection into a bicep of one arm and a placebo in the other arm. Neither the investigators nor the participants will know which muscle got the genes. After several weeks, an analysis of the injected muscle tissue's microscopic appearance, as well as extensive testing of the health and strength of the trial participants, will reveal whether gene therapy for DMD is likely to be safe and whether it's likely to result in persistent production of the essential protein in muscle cells.

Muscular dystrophies are genetic disorders characterized by progressive muscle wasting and weakness that begin with microscopic changes in the muscle. As muscles degenerate over time, the person's muscle strength declines.

Duchenne muscular dystrophy is a genetic disease that begins in early childhood, causes progressive loss of muscle strength and bulk, and usually leads to death in the 20s from respiratory or cardiac muscle failure. DMD occurs when a gene on the X chromosome fails to make the essential muscle protein dystrophin. One of nine types of muscular dystrophy, DMD primarily affects boys.

Currently, the best medical therapy can only slow the progressive muscle weakness of DMD.

The gene for dystrophin is one of the largest genes in the human body, and miniaturizing it, while retaining the crucial elements of its set of DNA instructions, has been among the greatest challenges to the gene therapy field.

The new Biostrophin therapy uses a novel combination of advanced technologies, including a miniaturized replacement dystrophin gene and nano delivery technology called biological nanoparticles. Developed from a virus known as adeno-associated virus (AAV), the nanoparticles are engineered specifically to target and carry the "minidystrophin" gene to muscle cells.

Read more at the source. This approach uses a virus-derived vector particle that should be safer than the virus itself as a vector. Expect to see more of this type of custom vectors, derived from a number of different viruses.

The final report on forced entry of therapeutic genes comes from this eurekalert newsrelease detailing research on Alzheimer's Disease from UT Southwestern Medical Center. The "vector" in this case was gold nano-particles.

By pressure-injecting the gene responsible for producing the specific protein – called amyloid-beta 42 – the researchers caused the mice to make antibodies and greatly reduce the protein's build-up in the brain. Accumulation of amyloid-beta 42 in humans is a hallmark of Alzheimer's disease.

"The whole point of the study is to determine whether the antibody is therapeutically effective as a means to inhibit the formation of amyloid-beta storage in the brain, and it is," said Dr. Roger Rosenberg, the study's senior author and director of the Alzheimer's Disease Center at UT Southwestern.

The gene injection avoids a serious side-effect that caused the cancellation of a previous multi-center human trial with amyloid-beta 42, researchers said. UT Southwestern did not participate in that trial. In that earlier study, people received injections of the protein itself and some developed dangerous brain inflammation.

The new study is available online and appears in an upcoming issue of the Journal of the Neurological Sciences.

Here is the full report. This report interested me due to the fact that it was the gene for the errant protein, rather than the protein itself, that elicited the antibodies against the protein. In this case, the gene was not injected into the cells, but rather elicited an immune response from the extracellular space--the gene was utilised as a vaccine.

There you have it. Three different methods of introducing genes and therapeutic molecules. The clever cat burglars and drug smugglers of molecular and cell biology. We can only urge them on.

Brave Feminists Rage against the Testicle

Recent news stories about finding stem cells in the testicles of mice and humans has prompted a backlash from courageous feminist professors of Women's Studies at Balwynne College. Dr. Letisha Snotsberry and Dr. Nadine Bulsnort have graciously agreed to be interviewed by Al Fin, on this important issue.

AF: Thank you for speaking with me today. I wonder if you can each summarize your objections to the latest stem cell news, starting with Dr. Snotsberry.

LS: The issue is very simple, Al. Feminism in the western world is based upon the fact that all bad things in the world come from the human testicle. Testosterone is the maker of war, the source of domestic abuse, and the reason for the subjugation of women everywhere . . .

NB: . . . Not only that, but the testicle produces sperm, and sperm causes pregnancy which stops many women from achieving their potential. You have no idea how many women drop out of school, or even careers, just to have a sniveling little baby. It's uncivilized.

AF: But surely you can see the necessity of propagating the species, after all if there were no babies, the entire human race would . . . .

NB: . . . Don't give me that nonsense, Al. If women stopped allowing men to use them as babymakers, men would have to invent another way to have babies. Women are just too convenient . . .

LS: . . . Getting back to the topic of the human testicle, I think it's pretty clear that it already had two strikes against it. Now with the news of stem cells being derived from the human testicle--well it's simply too much! The testicle simply contains too many things--it could lead us all back to the patriarchy again.

AF: Excuse me, you are saying that because the human testicle is turning out to be the Swiss Army Knife of human organs, it should be downgraded somehow?

LS: Well, obviously, Al. For one thing, why do all men have two testicles?

NB: Exactly, Tish! It's total overkill. One testicle is plenty--maybe even too much. We've had discussions in national committee about a "Testicles-Optional Policy", or TOP for short. All newborn males would come under the policy, all overseen by a Bioethics Committee staffed by professors of Women's Studies from the local college or university.

AF: Wait a minute, Doctor. Are you suggesting neutering baby boys when they are born?

LS: Let me answer that. No, Al, you are making it sound worse than it is. The informed consent would clearly give the option of retaining one testicle or none. The parents are given a vote in the matter, along with each member of the Bioethics Committee. It is all quite democratic.

AF: But what would be done with the testicles that are removed?

The two professors exchange a quick glance, then check their watches for the time.

LS: Oh dear, Al, it seems to be getting quite late. We have another appointment--if you'll please excuse us . . .

NB: . . . Yes, we're in a big hurry Al, sorry.

AF: But surely you have some plans for the little boys' testicles?

NB: You're making too much of a big deal out of this, Al. We already told you that testicles are the source of everything bad in the world. What would we want with testicles? You seem to be insinuating . . .

AF: . . . No, not at all. I am simply curious . . .

LS: Thank you so much, Al. We have both really enjoyed this.

The professors walk away whispering furiously to each other.

AF: Well, ladies and gentlemen, I certainly appreciate the professors' sharing their thoughts. Apparently the human testicle is more controversial than I had thought previously. Please stay tuned for further developments.

Human Heart, Brain, Bone and Cartilage Cells from Stem Cells Found in Adult Male Testes

First a German team found pluripotent stem cells in mouse testes, and now a California Lab has found pluripotent stem cells in human testes.

In a breakthrough for stem cell research and cellular replacement therapies, PrimeGen Biotech LLC (www.primegenbiotech.com) today announced that its researchers have successfully developed the first human adult therapeutic germ stem cell. Derived from adult stem cells but with the advantageous genetic characteristics of embryonic stem cells, PrimeCells have successfully been transformed into human heart, brain, bone and cartilage cells -- cardio, neuro, osteo and chondrocytes.

Therapeutically reprogrammed from germ line stem cells found in the testes of adult human males, PrimeCell(TM) is the first non-embryonic stem cell showing the potential to become any type of cell from any organ, something previously thought possible only for embryonic stem cells -- the definition of true pluripotency.

This week, the company's researchers are scheduled to present a summary of their complete data and manuscript in a poster presentation at the Serono Symposia International's Therapeutic Potential of Stem Cells In Reproductive Medicine conference in Valencia, Spain. PrimeGen first presented its preliminary human experimental data at the 1st International Symposium on Germ Cells, Epigenetics, Reprogramming and Embryonic Stem Cells, held in November 2005 in Kyoto, Japan.

"We have demonstrated that there's a novel source of adult stem cells which, aside from having a role in reproduction, can be reprogrammed and used therapeutically," said Thomas C.K. Yuen, PrimeGen chairman and CEO. "We have taken the most well-preserved, highest-quality stem cell and made it pluripotent -- representing one of the most significant breakthroughs in regenerative medicine. These cells advance the potential for cellular replacement therapy for everyone."

To form PrimeCell(TM), PrimeGen extracts cells from the most protected adult stem cell source in the body -- the "germ," or reproductive, cell line, which intrinsically only can form sperm and eggs. Then, PrimeGen uses a proprietary process to reprogram the cells to become pluripotent, giving them the ability to transform into virtually any other cell type.

Because it started as a germ-line stem cell, PrimeCell retains the most conserved, highest-quality DNA generated by an organism. It suffers no damage from aging, chronic disease or injury. It is also shielded from free radical, ribosomal and mitochondrial damage -- all inherent limitations of adult stem cells, until now.

PrimeGen's mouse model Proof of Concept is similar to that referenced in an article published by German researchers in this month's issue of the journal Nature, and described in a March 24 Reuters article. But PrimeGen is further along -- company researchers have already begun creating therapeutically viable cell lines from human tissue. In a paper currently submitted for peer-review, PrimeGen describes the first evidence of isolation and therapeutic reprogramming of adult human germ line stem cells into heart, brain, cartilage and bone cells.

PrimeGen obtains its human tissue samples from consenting adult males between the ages of 26 and 50. For women, PrimeGen currently is reviewing the work of Jonathon Tilly, who has shown that female germ cells exist after birth, contrary to popular belief. The company is developing a female model to attempt to reproduce the results achieved using male germ line stem cells.

"We are very pleased to see that the laboratory in Germany has independently confirmed our results -- which we first described and presented in Singapore in 2005 -- on the therapeutic reprogramming of post-natal germ cells," said Francisco Silva, PrimeGen's executive vice president of research and development, and the lead researcher for the PrimeCell initiative. "Our initial research is extremely promising and we have every reason to believe that our human PrimeCells will show true pluripotentiality, as we have observed in our mouse model."

"We've already been able to reproducibly differentiate heart, brain, bone and cartilage cells, and we are excited to begin testing how these cells incorporate into tissues," Silva said. "Our goal is to create the most potent cell lines to enable the most effective treatments and therapies for as many diseases as possible. Our human PrimeCells represent a significant step in that direction."

As you can see from reading the entire report, the California lab actually preceded the German lab in terms of actual results and reporting of the results.

Thanks to Anne Leonard, whose excellent Stem Cell Research Blog has done a fine job of following this story.

As I discussed in this post, there are many sources of stem cells. Eventually, it is quite likely that virtually any cell type will have the potential to turn into just about any other cell type, given the proper sequence of inducements.

The many new sources of stem cells should stimulate new research in the area of organ regeneration in situ, and organ regrowth for transplantation. Replacing old, tired organs should get easier as the number of replacement methods multiplies.

DNA Surprises: Gene Research Goes into High Gear

Thanks to Snowcrash for pointing to this CIT newsrelease that details new discoveries in "gene interaction."

The difficulty lies in the fact that two genes can pair up in a gigantic number of ways. If an organism has a genome of 20,000 genes, for example, the total number of pairwise combinations is a staggering total of 200 million possible interactions.

Researchers can indeed perform experiments to see what happens when the two genes interact, but 200 million is an enormous number of experiments, says Weiwei Zhong, a postdoctoral scholar at the California Institute of Technology. "The question is whether we can prioritize which experiments we should do in order to save a lot of time."

....a genetic-interaction network provides a faster and better way at determining how certain genes interact. Such a network also provides information about whether anyone has ever done an experiment to determine the interaction of two particular genes in one of several species.

"This process works like a matchmaking service for the genes," says Zhong. "It provides you with candidate matches that most likely will be interacting genes, based upon a number of specified features."

The benefit, she adds, is that biologists do not need to do a huge number of random experiments to verify if two genes indeed interact. Therefore, instead of the experimenter having to run 20,000 experiments to see if two genes randomly chosen from the genome of a 20,000-gene organism interact, they might get by with 10 to 50 experiments.

"The beneft is that you can be through in a month instead of years," says Sternberg Read the entire report here. Hat tip Biosingularity Blog.

The next story deals with advances in developing transgenic plants--getting plants to make proteins from other species--in this instance getting tobacco plants to make human albumin. This is from a Bio.com newsrelease:

Agricultural engineer, Alicia Fernández San Millán, has developed a novel technique in Spain - plastidial transformation, in order to produce, in a recombinant form, human albumin from tobacco plants. According to her PhD thesis, plastidial transformation is an economically viable alternative, as it enables increasing the levels of HSA by between 10 and a 100 times, compared to levels obtained by nuclear transformation. Read the entire newfeature for more information.

The following story deals with "junk DNA", the 98% of all human DNA that does not code for protein. Buried within the junk DNA is hidden treasure--epigenetic control sequences that influence the gene expression of the 2% of coding DNA.

The notion that mutations in enhancers play a role in human disease progression has been difficult to confirm because usually enhancers are located in the 98 percent of the human genome that does not code for protein, termed non-coding DNA. Unlike DNA sequences that code for protein, non-coding DNA, sometimes referred to as "junk" DNA, follows few rules for organization and sequence patterns and therefore is more difficult to study.

"The difficulty with human genetic approaches to common disease is that we lack the power to precisely localize DNA sequences that are associated with disease, often leaving us immense stretches of DNA to look at," says one of the study's corresponding authors, Andy McCallion, Ph.D., an assistant professor in the McKusick-Nathans Institute. Most often one is limited to looking in the most obvious places, which may not yield the best results. "Until now," he says, "we've only been able to look under the lamplights for the car keys."

....The system is a significant advance over current methods in this model species, allowing researchers to study more sequences in a shorter period of time. Read the entire news report here.

This report discusses a discovery of a gene variant--always think "hapmap" when hearing the term "gene variant"--that affects the onset of cancer.

Normally our genes have to be divided into two perfectly identical copies when a cell divides. The unfortunate variant causes a defect in the division of the genetic material (mitosis), which means that a daughter cell may get too few or too many genes.

If a daughter cell does not receive a gene that prevents cancer, a so-called tumour suppressor gene, then a cancer can grow. One defence mechanism against cancer is for a cell that gets faulty genes to commit suicide (apoptosis).

The defect caused by the unfortunate variant when it divides the genes is so tiny that the suicide mechanism does not detect the fault, which allows the cell to continue its growth into a cancer. Read the rest here.

Finally, here is a glimpse into the distant past, toward the possible origin of life on earth. This Eurekalert newsrelease discusses experiments attempting to delve into possible origins of the DNA-RNA encoding system that supports all known life.

This "evolutionary conversion" provides a modern-day snapshot of how life as we understand it may have first evolved out of the earliest primordial mix of RNA-like molecules-sometimes referred to as the "pre-RNA world"-into a more complex form of RNA-based life (or the "RNA world") and eventually to cellular life based on DNA and proteins. Nucleic acids are large complex molecules that store and convey genetic information, but can also function as enzymes.

While the transfer of sequence information between two different classes of nucleic acid-like molecules-between RNA and DNA, for example-is straightforward because it relies on the one-to-one correspondence of the double helix pairing, transferring catalytic function is significantly more difficult because function cannot be conveyed sequentially. The present study demonstrates that the "evolutionary conversion" of an RNA enzyme to a DNA enzyme with the same function is possible, however, through the acquisition of a few critical mutations.

The study was released in an advance online version of the journal Chemistry & Biology. Read more here.

This posting covers only a small cross section of ongoing genetic research. Al Fin has covered several of these topics previously. All of those past postings are available via the archives on the sidebar. Most people would feel overwhelmed if they had attempted to look deeply into any of these reports. No one is expected to know everything about everything, after all.

Gender Difference: The Gap that Will Not Close

At the elite levels of sports and athletics, the gender gap is prominent and resists closure. There is an approximate 15 minutes difference in the best times of elite male marathoners, and elite female marathoners. Other sports show similar differences at the elite level.

Remember when it was predicted that intensive training for women in athletics would close the gender gap in performance? Some years ago, when the marathon was first becoming a competitive event for women, the rapid improvement in female times led some to predict that female performances would soon equal those of men in the marathon. This has not happened, and it won't. The current world record for women is 2:21, compared to 2:06:50 for the men, a difference in speed of about 10%. This same 10% gap is present across the distance running performance spectrum The reason for the performance gap is not that women don't train as hard as men. There are some important physiological differences between the sexes that can't be overlooked or overcome.

....The "typical" young untrained male will have an absolute VO2 max of 3.5 liters/min, while the typical same-age female will be about 2 liters/min. This is a 43% difference! Where does it come from? Well first, much of the difference is due to the fact that males are bigger, on average, than females. Us humans are all (sort of) geometrically similar, so heart size scales in proportion to lean body size . If we divide VO2 by bodyweight, the difference is diminished (45 ml/min/kg vs 38 ml/min/kg) to 15 to 20%, but not eliminated.

....It is important to make note of the fact that these differences are "on average". In reality, there are many women with significantly higher VO2max values than average men. However, if we look at the "best of the best", the differences persist. Using XC skiing as an example from here in Norway, the highest reliable values for VO2 max recorded in national team XC skiers are about 90 ml/min/kg. The very best Norwegian woman has been measured at 77 ml/min/kg, a 17% difference. So, while this woman will outperform 99.9% of all men, she will not out-perform the national team level males.

Read more here.

A number of studies have demonstrated that boys inherit a performance advantage in athletics, for both pre-puberty, and even more so in post-puberty.
The stopwatch does not lie, and whether in swimming, running, weightlifting, shot put, bicycling etc. the superior VO2 max and muscle mass of males prevents the gender gap in athletics from closing. The only way to narrow the gap is to train the elite athlete girls and confine the elite athlete boys in restraints to encourage muscle atrophy and loss of VO2 max.

In the cognitive realm, you see a similar phenomenon in the measures of spatial ability and mathematical ability at the elite levels. Although hope springs eternal that training will narrow the gap, as in athletics, sometimes it seems that the only way to narrow the gap is to train the elite girls and prevent the elite boys from training somehow.

One can be excused for wondering why all the excitement about male superiority in a small area of elite cognitive performance? The number of jobs involved is minimal. Certainly an intelligent businesswoman, female physician, or female lawyer, can make much more money than an elite mathematician, physicist, or engineer. What is all the near-hysteria about?

Average intelligence levels of men and women test virtually identical. A 1995 study examined the performance of more than 100,000 American adolescents on various mental tests. The study found that on average, females performed slightly better than males on tests of reading comprehension, writing, perceptual speed, and certain memory tasks. Males tended to perform slightly better than girls on tests of mathematics, science, and social studies. In almost all cases, the average sex differences were small.

And here is how developmental psychologist David C. Geary puts it:

There was no sex difference on the IQ test, but males showed significantly higher mean scores on the arithmetical computations, arithmetical reasoning, and spatial cognition measures. A series of structural equation models indicated that individual differences in arithmetical reasoning were related to individual differences in IQ, spatial abilities, and computational fluency. Moreover, the results suggested that the male advantage in arithmetical reasoning is mediated by the male advantages in both computational fluency and spatial cognition.

Women are graduating from schools of higher education at a rate of 6 to 4 vs. men. Women have achieved virtual parity in schools of medicine and law, and make up about 70% of graduate psychologists. Women are achieving phenomenally in the modern world, and if any gender should be worried about current trends, it is the males. A few men are holding on under siege, to a small sliver of cognitive excellence, and all that many psychologists can think of doing is to try to eliminate the small gap within that tiny sliver of cognitive performance.

It is a fascinating study in academic frustration--the data will simply not behave in a politically correct fashion. Many more research studies and outreach programs will be mandated, however, to erase that gap. But I can tell the gender psy-sers exactly how to erase the gap, and I will not charge for the valuable information. Simply prescribe pro-androgenic drugs that cross the placental barrier, to pregnant women in their second trimester, who are carrying female fetuses. Some additional androgenic supplementation may be necessary at different time periods after birth--and there will be potentially unpleasant side effects. Hirsutism, deep voice, skin blemishes, a certain manly aggressiveness, etc. But all of that would be a small price to pay to erase the gender gap in this one small remaining area of academics, no?

Just as there are elite women athletes who can defeat 99% of males in their sport, there are women mathematicians and physicists who are better at their trade than 99% of males. But they are not competing against those 99%. They are competing against the elite males, a very small number, but a significantly greater number than the number of elite females in those vocations. That is the hump that the gender Procrusteans are incapable of leveling. The relatively tiny number of male elites in a relatively tiny number of fields who will simply not go away.

Lawrence Summers paidwith his job, for making a very timid suggestion about possible biological gender or sex differences in that very small, elite sliver of academic professorship in a few top rank schools. The politics of this subject are absolutely deadly to anyone in a public position who lets down his guard for even a moment.

But why? I will deal with the real reasons for the excitement in a later posting.

Not Just Hot Air: Wind Energy Getting Bigger, Cheaper

As we convert from a dependency on fossil fuels to using renewable energy to power our societies, it is good to take stock of our progress from time to time. Jim from The Energy Blog has provided this report that wind energy now costs less than conventional power sources.

....Xcel’s 33,000 Windsource customers, who until late 2005 were paying $6 more each month for their electricity, are now paying slightly less than those using conventional electricity, which comes mostly from natural gas and coal. To meet fast-growing demand, Xcel is currently soliciting proposals from wind developers for up to 775 megawatts of new wind power generation, enough to supply 232,000 Colorado homes with electricity.

Wind energy is also proving a boon to small ranchers, who will earn royalties from the energy generated by wind turbines placed on their property.

.... When Xcel announced it would develop several hundred megawatts of additional wind-generating capacity, it got the attention of ranching communities throughout wind-rich eastern Colorado. In tiny ranch-country towns like Grover, near the Wyoming border, ranchers welcomed a proposed 300-megawatt wind farm that would span some 30 ranches.

With a large, advanced-design wind turbine generating easily $100,000 worth of electricity per year, even a 3-percent royalty would earn ranchers $3,000 a year from leasing a quarter-acre of ranchland. And they can still run cattle on the land. If the proposed project is approved as expected, these 30 or so ranchers will have an average of seven turbines each, yielding roughly $21,000 a year in additional income. A decade from now, there may be thousands of ranchers who will be earning more selling electricity than they do selling cattle.

....Wind energy is emerging as a centerpiece of the new energy economy, because it is abundant, inexpensive, inexhaustible, widely distributed, clean, and climate-benign. Three of the 50 states—North Dakota, Kansas, and Texas—have enough harnessable wind energy to satisfy national electricity needs. The cost of wind-generated electricity has fallen from 38¢ per kilowatt-hour in the early 1980s to 4¢ to 6¢ today, offering an almost endless supply of cheap energy.

Read much more from this report from the Earth Policy Institute.

Renewable energy such as wind, solar, hydroelectric, geothermal, wave, tidal, OTEC, and others, are developing solidly in the background, while the rest of the world continues to talk peak oil, and a war of the titans over oil.

Extreme Gene Expression: Taking Proteomics to the Next Level

Researchers are moving beyond mere genomics into proteomics--where most of the work of the cell is actually done. This newsrelease from the University of Toronto reports on the newest discoveries in protein-protein interactions.

The findings, which will be released in the March 30 issue of Nature, reveal how researchers used sophisticated proteomic techniques to identify close to 4,000 proteins and 550 protein complexes involved in 7,123 protein-protein interactions in yeast cells, about half of which are novel. Many of the same complexes and protein interactions that go awry in human disease are also found in yeast. While living yeast cells have only 6,000 genes compared to a human’s 25,000, the structures of their encoded proteins and interactions among the proteins are virtually identical to ours.

“Human proteins involved in disease and protein interactions gone awry found in humans are often found in yeast,” says Professor Andrew Emili of U of T’s Banting and Best Department of Medical Research, the study’s co-author. “By studying and mapping out sets of protein interactions within this basic organism, we are providing the foundation to move into a more complex organism such as a mouse and then a human.”

To map the protein complexes within the cell, researchers combined purification techniques with analysis using mass spectrometry, a technique that breaks down and identifies chemical substances within molecules. Using the combined approach of purification and mass spectrometry, the researchers were able to ensure accuracy and reveal more than 250 complexes that have not yet been reported in previous public databases. The researchers have posted their current findings on a publicly available comprehensive database (http://tap.med.utoronto.ca) and hope the findings will spur further advances within the scientific community. “This database will be linked with other sites, so that results can be compared and contrasted,” says co-author Professor Jack Greenblatt, also of U of T’s Banting and Best Department of Medical Research. “The methods we used to identify protein interactions and protein complexes in yeast appear to be the best currently available, and so are likely to be used soon to identify protein interactions involved in human disease.”

....The next step, according to Emili, is to analyse these new complexes to determine their roles in living cell functions. “Now that we have the pieces of the puzzle, we have to put them together to get the overall picture,” Emili says. “It is painstaking work, but it brings us closer to answer science’s most fundamental question: how does life operate?”

Read more here.

For more on proteomics and genomics, read here and here. For more on mass spectrometry, read here.

Hat tip Biosingularity Blog.

Important Advance in Genetic Research: RNA Tools to Silence Genes

Genetics researchers have used various methods to determine the functions of different genes, in the course of determining useful therapeutic targets for gene therapy. One method is to create a "knockout" animal, where the target gene is permanently silenced. That method has been effective, but now there is a better method that is capable of temporarily silencing genes--RNAi, RNA interference. RNAi is a form of non-coding RNA, a very exciting field of research.

This Eurekalert newrelease details the new tools that have been made available to researchers by the Broad Institute of MIT and Harvard.

An international public-private research team led by scientists at the Broad Institute of MIT and Harvard announced today the construction and availability of an extensive library of molecular reagents to silence most human and mouse genes. As described in the March 24 issue of Cell, this library consists of small RNA molecules that can switch off genes individually, allowing the user to dissect the genetic underpinnings of normal biology and disease. These RNA-interference (RNAi)-based gene inhibitors are packaged in lentiviruses, enabling their use in virtually all types of human and mouse cells. This work springs from the RNAi Consortium (TRC), a unique collaboration among academic research institutions and leading life science companies with the mission to build comprehensive RNAi libraries and make them available to scientists worldwide.

"Switching off a single gene through RNAi reveals how that gene functions in a particular biological process. When RNAi's potential is applied to thousands of genes – as it has been in fruit flies and nematodes – it can provide a more complete picture of that process," said David Root, a senior author of the Cell paper and the director of TRC and the RNAi platform at the Broad Institute. "Thanks to this unique public-private effort, we now have new tools to enable the entire research community to realize the potential of RNAi in the two most important species in biomedicine."

"The RNAi library developed by TRC is a rich resource for biological discovery," said Nir Hacohen, assistant professor at Massachusetts General Hospital and Harvard Medical School, associate member of the Broad Institute and a senior author. "Ongoing studies in my own laboratory to understand how the immune system senses pathogens and appropriately targets its response will be accelerated using these tools."

RNAi gives scientists the ability to turn off an individual gene. Its workhorses are small RNA molecules, each of which is tailored to match a fragment of a gene's unique DNA. This RNA can then bind to its gene target, rendering it inactive. In order to get the small RNAs into cells, TRC scientists packaged them in lentiviruses. "Across the spectrum of biomedicine, there is a need for tools that can be applied to diverse cell types. This is particularly true in cancer research," said Bill Hahn, assistant professor at Dana-Farber Cancer Institute and Harvard Medical School, associate member of the Broad Institute and a senior author of the study. "For TRC's library, lentiviral delivery is an especially effective means to meet this need."

The parallel analysis of thousands of genes using RNAi allows researchers to more readily pinpoint the genes that control a biological process. Therefore, TRC developed the high-throughput techniques and quality-control measures required for such genome-scale studies. "It is a distinct challenge to achieve consistent and cost-effective RNAi methods and we placed a strong emphasis on this part of the process," said David Sabatini, member of Whitehead Institute for Biomedical Research, assistant professor at Massachusetts Institute of Technology, associate member of the Broad Institute and a senior author. "In the quest to develop comprehensive tools for gene discovery in mice and humans, this technology will be a key piece in the puzzle."

Read more here.

This is an important advance, made available now to biolabs all over the world. For more background information on RNAi, check out this website, or this resource. For an animation of RNAi, go here.

As the tools of discovery become more sophisticated and more available, eventually the point is reached where the new tools make possible newer and better tools, and so on. This is the exponential process of discovery that Kurzweil talks about.

Glycation in Diabetes and Aging: Routes to Life Extension and Longevity

High blood sugar levels, as are seen in diabetes, insulin resistance, and other forms of hyperglycemia, leads to a process called glycation. Glycation changes the shape and properties of proteins. Crosslinking reduces the flexibility, elasticity, and functionality of the proteins. Furthermore, the chemical modifications of glycation and crosslinking can initiate harmful inflammatory and autoimmune responses. "AGE and nonenzymatic crosslinks are demonstrated to signal inflammatory cytokines, extracellular matrix expansion, angiogenesis, and growth factors." [deGroof] Glycation has been found in connective tissue collagen, arterial collagen, kidney glomerular basement membrane, eye lens crystallins, nerve myelin proteins and in the circulating low-density lipoprotein (LDL) of the blood.

Prolonged glycation leads to creation of advanced glycation end products, AGE. The end result of AGE is all the deadly complications that lead to excessive morbidity and mortality in diabetic patients. Blindness, renal failure, arteriosclerotic heart disease, neuropathies, loss of limbs, etc.

What is not generally known, is that the same process of glycation and AGE formation occurs in normal people, at a much slower rate. You may think that that giant soda, or huge piece of pie is not doing anything bad to your body, but you would probably be wrong. Your connective tissues are being cross-linked beneath your level of awareness. You are ageing prematurely.

This article in Scientific American discussed this issue a few years ago. This brief background article gives more information, with links to more sources.

Various drugs and nutriceuticals have been used to treat glycation and AGE. This article discusses the use of ginger in preventing diabetic kidney damage.
An estimated 19 million people are affected by diabetes in the EU, equal to four per cent of the total population. This figure is projected to increase to 26 million by 2030.

The rhizome of the ginger plant (Zingiber officinale) is a rich source of antioxidants, including gingerols, shogaols, zingerones and other ketone derivatives. It has long been used as a remedy for nausea, especially associated with morning sickness.

The new study, published on-line in Food Chemistry (doi: 10.1016/j.foodchem.2006.01.013), assessed the effects of ginger on the blood antioxidant levels and kidney health of diabetic rat models.

Twenty-four male rats were divided into three groups of eight. The first group (control 1) were healthy rats, the second group (control 2) were diabetic and non-supplemented, and the third group (test) was diabetic and had the diet supplemented with ginger powder as five per cent of the daily food intake.

After eight weeks of supplementation the researchers, led by Dr Ali Taghizadeh Afshari from the Emam Khomeini Hospital, reported: “Antioxidant capacity in the ginger supplemented rats was higher when compared to the other groups.”

The primary drug used to treat glycation and AGE is aminoguanidine. Over the counter nutraceuticals used to treat AGE include carnosine, pyridoxamine, and various forms of thiamine. Ginger may also provide some benefit in preventing diabetic complications, but that research is ongoing.

Glycation end products also accumulate in the brain in Alzheimer's Disease. Scientists are still trying to define any relationship between AGE accumulation in the CNS and neuronal apoptosis. The recent discovery that lower brain insulin may predispose to Alzheimer's Disease probably has something to do with accumulation of AGE.

I will be writing much more on this topic in the future, since it is of great importance in the overall strategy of retarding the ageing process.

Lipid Nano Structures Used for Gene Therapy

For a decade or more, scientists at UC Santa Barbara have been working to develop lipid DNA complexes for inserting genes into cells. Such nano structures are considered safer than viruses, although less efficient. This Eurekalert newsrelease details the latest lipid nano structure developed by the UCSB group.

For more than two decades, gene delivery has been accomplished by using engineered viruses as a vehicle to get into diseased cells and 70 percent of clinical trials worldwide continue to use this method. But, the viruses used for gene delivery occasionally evoke severe immune responses, so scientists continue to search for non-viral delivery vehicles.

Reporting in an article to appear in the March 29 print edition of the Journal of the American Chemical Society (published on-line on March 8), the authors describe the synthesis of the new lipid molecule.

Lipid DNA complexes are attracting increasing attention as non-viral DNA delivery vehicles. They have been described as one of the "hottest new technologies" for gene therapy, accounting for nearly 10 percent of ongoing clinical trials.

Lipids are molecules with two parts, a water-liking "headgroup" and oily tails that assemble together to avoid water. Lipids, along with carbohydrates and proteins, constitute the main structural material of living cells.

The novel lipid molecule created at UC Santa Barbara has a tree-shaped, nanoscale headgroup and displays unexpectedly superior DNA-delivery properties. "It generates a honeycomb phase of lipid DNA complexes," said Cyrus R. Safinya, a professor of materials; of molecular, cellular and developmental biology; and of physics at UCSB. The new molecule was synthesized in Safinya's laboratory by first author Kai K. Ewert, a synthetic chemist who is a project scientist in the research group.

"We've been trying to get a lipid-based honeycomb lattice for a long time," said Ewert. The structure of lipid DNA complexes strongly affects their ability to deliver DNA.

"Complexes containing sheets or tubes of lipids have been known since Safinya's group found these structures in 1997 and 1998, but no one had ever seen nanoscale cylinders such as the ones in our honeycomb lattice," Ewart said. The scientists proved the formation of this novel structure with X-ray scattering experiments. Ewert designed and synthesized the new lipid by manipulating the size, shape and charge of a series of molecules. He explained that the new lipid molecule has 16 positive charges in its tree-shaped headgroup, the largest number by far in the field of gene delivery.

The process of delivering a gene of interest into the cell is known as "transfection." In the paper, the authors describe transfection efficiency studies carried out in four cancer cell lines using the new molecule. Two of these are mouse cell lines and two are human cell lines. The honeycomb structure turned out to be highly effective.

Read the entire report here.

By intelligent selection and design, researchers are developing better and safer transfection methods for inserting genes into cells, for many therapeutic purposes.

This article will give more details and links to different aspects and targets of gene therapy. This is a rapidly changing field, like much of biotechnology, and promises unimaginable therapeutic advances in the foreseeable future.

A Brief Primer on Pin1, Amyloid Beta, and Alzheimer's

Pin1 is an enzyme, that can twist the joints of proteins in specific places, so that they may change shape. While it has been known that the enzyme Pin1 can prevent the formation of tangles inside neurons in Alzheimer's Disease, it now appears that Pin1 also can block formation of extracellular plaques. Pin1 is a protein of the parvulin family within the peptidyl-prolyl cis-trans isomerase (PPIase) group of proteins and was the first member of this family to be found in humans.

This newsreport from Beth Israel Deaconess Medical Center, Boston, discusses new research findings supporting the protective effect of the enzyme Pin1 against amyloid beta (abeta) plaques (via amyloid precursor protein, APP) and Alzheimer's Disease. The newsreport describes a paper published in Nature.

The researchers, in collaboration with Linda Nicholson at Cornell University, observed through NMR that when APP was phosphorylated (a process in which an extra phosphate is acquired) it became misshapen and could not be easily restored to its original condition. However, once Pin1 was introduced, APP returned to its normal shape – with dramatic speed.

“We had previously proposed that Pin1 was regulating protein function by greatly accelerating structural changes, but this activity had never actually been visualized,” explains Lu. “Now, for the first time, we were able to actually see this process as it occurred.”

Using cell models the authors next went on to examine the effects of Pin1 on Abeta production, says Lu explaining, “We were able to show that while upregulation of Pin1 reduced Abeta generation, removing the Pin1 gene dramatically increased Abeta production by shifting APP processing away from the normal pathway into the pathological pathway.”

....“Because the effects of Pin1 knockout are age-dependent, we compared Abeta levels in the brains of the mice at different ages,” explains Lu. And indeed their results showed that Pin1 knockout again switched APP processing away from the normal pathway into the pathological pathway in the mouse brains. Moreover, he adds, while Pin1 knockout did not significantly change the levels of Abeta40, it did selectively increase levels of insoluble Abeta42 by a significant 30 to 50 percent in two separate mouse models, to an extent that is similar to what would be found in the brains of Alzheimer’s patients and in mouse models of the disease.

The most common cause of dementia among the elderly, Alzheimer’s disease affects an estimated 4 million individuals in the United States, a number that is expected to increase significantly in the coming years with the aging of the baby boomer generation.

“As was earlier shown with tau proteins, it appears that Pin1 acts to restore misshapen amyloid precursor proteins to their original healthy shape, possibly preventing the onset of neurodegeneration and development of dementia,” says D. Stephen Snyder, PhD, of the Etiology of Alzheimer’s Disease program at the National Institute on Aging, which supported this study. “This finding offers important new insights into the molecular events that lead to Alzheimer’s as we work to develop therapies for the treatment of this widespread disease.”

Read the entire report here.

Here is a brief primer on Pin1 with several links to research papers on Pin1. It provides a review by Julian Thorpe of the above paper in Nature by Lu. Here are some excerpts:

"....Lu and colleagues have previously shown that available, soluble Pin1 is depleted in tangle-bearing neurons of AD brain. Very importantly, they also showed that, in vitro, Pin1 could restore the ability of tau to re-associate with, and reconstitute the integrity of, the microtubules. In this latest research, their hypothesis of a potentially neuroprotective role for Pin1 has been strengthened. Not only do they show that there are lower levels of Pin1 protein in susceptible regions of normal human brain, but also that there is an inverse correlation of neuronal Pin1 and tangle content in AD-affected brain. Finally, and most notably, they have shown that aged Pin1 knockout mice have behavioural and motor deficits, neuronal loss and an accumulation of phosphorylated proteins, including tau that forms filaments and assumes a tangle-like conformation.

Overall, this work establishes Pin1 as an important protein in AD and, implicitly, the other tauopathies. Future work should also provide insights into the effects of Pin1 levels on the course of neurodegenerative disease progression through its control of transcription, translation, endocytosis and apoptosis.”

Here is more background on Pin1 from Julian Thorpe. Here is more on Pin1 involvement in amyloid precursor protein proteolysis and plaque formation.

More pieces of the puzzle seem to be falling into place. More potential therapeutic targets. The most fascinating thing about Pin1 appears to be its association with both neurofibrillary tangles (intracellular) and amyloid plaques (extracellular),the major tissue manifestations of Alzheimer's disease.

Can Cancer Vaccine plus Nanotechnology Stop Cancer?

Cancer scientists have been working on cancer vaccines for decades. Presently there is active development work for vaccines against prostate cancer, breast cancer, leukemia, cervical cancer, and others.

This newsrelease discusses recent work at the Karolinska Institute in Sweden, in isolating a useful tumor antigen that is more accessible to the immune system T cells than many more elusive tumor antigens.

The researchers have identified a short peptide molecule that the T cell in the study recognises. Using this peptide, the researchers can vaccinate and protect against the spread of tumours from different tissues, including melanoma, colon cancer, lymphoma, and fibrosarcoma.

"So far we've only conducted research on mice, so it's too early to get out hopes up too much," says research scientist Elisabeth Wolpert at the Microbiology and Tumour Biology Centre. "However, the study does point towards new possible ways of developing a treatment for advanced tumour diseases."

Nanotechnology is also being brought into the fight, to aid cancer vaccine research. The US National Cancer Institute's (NCI) Center for Cancer Research, is using nanotechnology in several ways.

CCR’s Nanobiology Program (CCRNP) promotes multidisciplinary research that leads to the development of tools for nanoscale, biologically based strategies to prevent, diagnose, and treat cancer, AIDS, and biodefense-related viral diseases. The CCRNP works to understand the structure and function of biomolecules to aid in the design of nanodevices for in vivo imaging, diagnostics, and targeted drug delivery systems.

Principle investigators who are active in the program have several areas of interest, including membrane structure and function, protein interactions, biomedical image and database analysis, structural bioinformatics, structural glycobiology, molecular information theory, and computational RNA structure.

CCRNP investigators have formed collaborative partnerships with CCR investigators in other programs, labs, and branches, including the Molecular Imaging Program, the Radiation Oncology Branch, the Laboratory of Cell Biology, and the Laboratory of Medicinal Chemistry.

Using nanoparticles to "tag" dendritic cells, cancer researchers can keep better track of those important immune system cells.

In a later posting, I will discuss oncogenes and tumor suppressor genes, and how they may relate to cancer vaccines.

Virtual Schools Win Real Victory in Court

Virtual schools won a major victory in a Wisconsin courtroom recently. The largest teachers union in Wisconsin had filed suit against Wisconsin Virtual Academy in 2004, but Judge Joseph McCormack ruled against the union.

The Wisconsin Education Association Council claimed that virtual schools rely on parents to do some teacher duties instead of using state-certified teachers.

It also said such schools misuse the state's open enrollment program.

But the judge dismissed the council's arguments, saying the School Board is within its rights to figure out how to partner teachers and parents for the best interest of students.

He also says the open enrollment program doesn't prohibit students from using the Internet to get a public education.

Virtual schools are run by several states, including Wisconsin, Texas, and Florida. South Carolina legislators are considering a bill to establish a statewide virtual school. Some universities are also running virtual schools.

This CSM article discusses some of the issues involved in virtual schooling, and how the concept relates at times to the charter school and home school movements.

For those readers who want to delve more deeply into the history, and more technical details of virtual schooling, take a look at this pdf study from one of the foremost experts on virtual schooling.

I like the idea of educational choice. Corruption in government education has become much too blatant and destructive toward students, taxpayers, and the body politic. Being able to sidestep that corruption in any way possible, is not a bad thing.

Mmmmmmm! Cabernet! Quercetin, Resveratrol, and Cancer Apoptosis

Many plants and fruits are rich in anti-oxidant and anti-inflammatory compounds. Recently, scientists have focused on resveratrol due to its possible role in reduced cardiovascular morbidity and mortality. A closely related flavonoid, quercetin, apparently plays a strong role in the inducing of apoptosis in various cancer lines, including prostate cancer and leukemia.

This doctoral dissertation by Susanne U. Talcott is a very rich source of information on the topic of apoptosis induction by compounds contained in the cabernet and muscadine grapes. I cannot recommend it highly enough. You will find it worth your time to look through the text, tables, figures, and sources.

Here is Dr. Talcott describing this line of research, from another presentation:

The consumption of fruits and vegetables has been associated with a lowered risk for several chronic diseases including coronary heart disease and several types of cancer, which has been demonstrated in several epidemiological and intervention studies. In part, this risk reduction has been associated with the occurrence of antioxidant phytochemicals such as polyphenolics in these foods. Several of the polyphenolics have been demonstrated to have cancer-preventive and anticarcinogenic effects in in vitro and in vivo experiments. Underlying mechanisms include antioxidant effects, which prevent chemical or stress-induced damage to cells, and the induction of apoptosis in cancer cells through intracellular signal transduction. Recent research efforts include the investigation of the relationship between the antioxidant capacity of polyphenols or polyphenol-containing foods and their in vivo disease-preventive potential. Limitations of this approach arise from aspects of bioavailability and post-absorptive metabolism leading to the generation of metabolites, which have been shown to differ from their parent compound in antioxidant capacity and mechanism of action. This presentation will give an overview of recent advances and limitations in the area of anticancer effects of polyphenolics. In addition, data demonstrating the anticarcinogenic effects of red wine polyphenolics in cell culture experiments with cancer cell lines and consumption trials with human subjects will be discussed.

I discussed quercetin and resveratrol in previous postings in relation to anti-ageing properties. Finding such innocuous natural substances that both contribute to life extension AND provide protection from multiple cancer types, is like finding a four leafed clover, or winning the lottery.

Alzheimer's, Beta Amyloid, and the Choroid Plexus

The Choroid Plexus is a complex of capillary rich cells located in the ventricles of the brain, which produce cerebral spinal fluid, and perform other functions protective of the brain. This Purdue University newsrelease discusses a recent research finding that links the choroid plexus to the function of filtering beta amyloid from brain fluid and CSF.

The researchers found that the choroid plexus acts as a sort of "fishnet" that captures the protein, called beta-amyloid, and prevents it from building up in the cerebrospinal fluid, which surrounds and bathes the brain and spinal cord. Moreover, tissue in the organ is able to soak up large amounts of the protein and may contain enzymes capable of digesting beta-amyloid, said Wei Zheng (pronounced Way Zsheng), an associate professor in the School of Health Sciences at Purdue University.

The findings represent the first time that researchers have identified the potential existence of a natural mechanism in the brain for removing beta-amyloid.

"This newly uncovered pathway may help explain how normal brains balance this protein and how an imbalance caused by aging, genetic or environmental factors may lead to or worsen Alzheimer's disease," Zheng said.

Researchers had already known that the cerebrospinal fluid in the brains of Alzheimer's patients contains abnormally high quantities of beta-amyloid fragments. Beta-amyloid deposits accumulate over a period of years, resulting in abnormal clumps, or plaque, typical of Alzheimer's disease. Scientists do not yet know whether the disease is caused by the plaque formations or beta-amyloids themselves.

The discovery suggests that a malfunctioning choroid plexus could allow too much of the protein to build up in the brain.

Read the rest here. For further study, this helpful article further details choroid plexus malfunction and breakdown in ageing and Alzheimer's disease.

In this article, I discussed some recent research evidence linking beta amyloid to memory loss and neuron death in Alzheimer's. Today's Purdue report adds more information to the overall picture.

It is important to understand the complete dynamic story of beta amyloid, from its formation to its action on neurons, to its breakdown and removal, if we are to understand all of our potential therapeutic choices in reducing the detrimental effect of this protein.

Math: More Getting What You Need

Most of you will probably agree that government schools--and schools in general--are shortchanging our children, particularly in the areas of math, science, and in world view perspectives. For now, we will concentrate more on math. As a follow-on to my previous post, I wanted to explain that reading wikipedia-math for 15-30 minutes daily is not just for adults who want to brush up and round off their math knowledge. It might be particularly helpful for those young brains that are in the middle of the pruning process. A good parent will lead his children to such resources, and help the child to utilise them, while the children are still young enough to have faith in the parents' judgment.

Here is a good essay on "how to read mathematics." It is meant to aid in reading math journal articles and texts, but it can also be adapted to the wikipedia and mathworld approach.

A reading protocol is a set of strategies that a reader must use in order to benefit fully from reading the text. Poetry calls for a different set of strategies than fiction, and fiction a different set than non-fiction. It would be ridiculous to read fiction and ask oneself what is the author's source for the assertion that the hero is blond and tanned; it would be wrong to read non-fiction and not ask such a question. This reading protocol extends to a viewing or listening protocol in art and music. Indeed, much of the introductory course material in literature, music and art is spent teaching these protocols.

Mathematics has a reading protocol all its own, and just as we teach students to read literature, we should teach them to read mathematics.This article categorizes some of the strategies for a mathematics reading protocol. I am sure my readers will think of many strategies that I missed. The point is that there *is* such a protocol, that we all know and use it, and that we should make an attempt to share the secret with our students.

....."Reading Mathematics is not at all a linear experience ...Understanding the text requires cross references, scanning, pausing and revisiting" (ibid page 16).

Don't assume that understanding each phrase, will enable you to understand the whole idea. This is like trying to see a painting by staring at each square inch of it from the distance of your nose. You will get the detail, texture and style but miss the picture completely. A math article has a story! Try to see what the story is before you delve into the details. You can go in for a closer look once you have a framework to fill with details, just as you might reread a novel.

....Mathematics says a lot with a little. The reader must participate! At every stage, he must decide whether or not the idea presented was clear. Why is it true? Do I really believe it? Could I convince someone else that it is true? Why didn't the author use a different argument? Do I have a better argument or method of explaining the idea? Why didn't the author explain it the way that I understand it? Is my way wrong? Do I really get the idea? Am I missing some subtlety? Did this author miss a subtlety? If I still can't understand the point, perhaps I can understand a similar but simpler idea? Which simpler idea? Is it really necessary to understand the idea? Perhaps I will just accept this point without understanding the details? Perhaps, my understanding of the whole story will not suffer from this?

Putting too little effort into this participation, is like reading a novel without concentrating. After half an hour, you wake up to realize the pages have turned, but you have been day dreaming and don't remember a thing you read.

....Reading mathematics too quickly, results in frustration. A half hour of concentration in a novel buys you 20-60 pages with full comprehension (depending on how experienced you are at reading novels). The same half hour in a math article buys you 0-3 lines (depending on how experienced you are at reading mathematics). There is no substitute for work and time. You can speed up your math reading skill by practicing, but be careful. Like any skill, trying too much too fast can set you back and kill your motivation. Imagine trying to do an hour of high energy aerobics if you have not worked out in two years. You may make it through the first class, but you are not likely to come back. The frustration from seeing the experienced class members effortlessly do twice as much as you, while you moan the whole next day from soreness, is too much to take.

And so on. Scan through the essay as you can, then apply the approach to your next 15 minute math session. Persistence plus good technique. It takes time to learn the right technique for you--the best approach--but persistence is there for everyone, for just a little willpower.

You might also want to check out something called Visual Math. Math can be very beautiful, visually and esthetically. Here are some links to visual geometry.

Finally, here is a math reference website, to add to all the others in my previous posting, and the ones on the sidebar.

Combining the information in this posting and the previous one, you may be in a better postion to compensate for any deficits in your own math education, and to prevent large gaps from forming in your children's math educations. Math is not all they will need to know, but it will be a key part.

Math: Getting What You Need

If you want to succeed in the modern world, you need to know some math. In many of the hottest research and technology fields, you have to know a lot of math. Corporate executives in North America constantly complain at the lack of well trained engineers and scientists within their applicant pool. Poor math skills among college graduates leads corporations to hire from abroad, and outsource jobs overseas.

This blog post relates the tale of a programmer who found that he needed to go back and brush up on his math skills. It provides suggestions for self teaching of math that can prove useful. Many of the comments following the posting are also helpful.

I think the best way to start learning math is to spend 15 to 30 minutes a day surfing in Wikipedia. It's filled with articles about thousands of little branches of mathematics. You start with pretty much any article that seems interesting (e.g. String theory, say, or the Fourier transform, or Tensors, anything that strikes your fancy. Start reading. If there's something you don't understand, click the link and read about it. Do this recursively until you get bored or tired.

Doing this will give you amazing perspective on mathematics, after a few months. You'll start seeing patterns — for instance, it seems that just about every branch of mathematics that involves a single variable has a more complicated multivariate version, and the multivariate version is almost always represented by matrices of linear equations. At least for applied math. So Linear Algebra will gradually bump its way up your list, until you feel compelled to learn how it actually works, and you'll download a PDF or buy a book, and you'll figure out enough to make you happy for a while.

Read the rest here.

One of the commenters suggested that Mathworld might be just as helpful as Wikipedia, but other commenters felt that Wikipedia was better for self-teaching math.

I agree with Steve that math is not taught well in school, generally. By the time students get to college, they are so disillusioned with math--due to poor preparation in K-12--that they opt out of the career paths that require a lot of math. Following Steve's suggestion not only gives you gradual familiarity with math topics, but by jumping into the topic daily, you reinforce the material and are more likely to retain it in a meaningful, subconscious way.

For further study online, after you have exhausted Wikipedia and Math World, go here, here, and here for links to quite a few free online math texts. Also feel free to follow links to math resources and tutorials in the right hand sidebar here.

Math geeks are very much in demand in the high tech world. Government schools are wasting a lot of potential tech workers by absurdly poor preparation in the early years, and by often substituting political indoctrination for basic learning. The way that present government schools fail to prepare students for the future is a recipe for societal suicide.

Fortunately, human ingenuity is constantly devising paths around the institutional obstacles and corruption that are a constant threat to any middle-aged society.

Solar Power from Outer Space

Whatever happened to the idea of using satellites to harvest solar power 24 hours a day? Jim from the Energy Blog has an update from the Space Island Group (SIG) and their current project to place photovoltaic arrays in orbit.

The Space Island Group, Inc. (SIG) will design and finance two categories of space hardware to make these results possible. Both categories will incorporate components now used on NASA’s space shuttles and other launch vehicles, and on today’s communications satellites. This is not an R&D project. Because we will not develop new rocket engines, guidance systems or other components and because we’ll manage the program with private industry procedures, our development costs will be far below those of comparable government efforts.

The first hardware category will be very large structures up to several kilometers wide called solar power satellites and solar reflectors, which will be assembled in space.

The second will be very low-cost manned and unmanned launch vehicles, and very large, low-cost living quarters in orbit able to comfortably house several hundred occupants at a time. These occupants will, among other tasks, assemble and maintain the orbiting solar satellites and solar reflectors.

....This is not a government program. We feel that taxpayers have already funded most of the hardware we’ll use.

Now it’s our job to use that proven hardware to let a broad range of industries profitably capitalize on that investment. Along the way, we expect that we and these industries will create millions of high-paying American jobs that overseas competitors won’t be able to take away for decades. In fact we’ll make those American jobs a lease-condition for our tenants.

These jobs will start with the defense contractors. Some 90% of our development funds will go to the firms that now build shuttle components for NASA. Tens of thousands of current aerospace jobs will end when the shuttles retire in 2010. Our first launch in 2008 or 2009 will not only absorb those employees, but will increase their numbers many times over during the following decade. Many of the same firms will build our space hardware, but we’ll use simpler, commercial procedures rather than the more complex ones used for government work.

Read more at the SIG website. SIG has quite a few plans for their solar satellites, including energy production, hurricane control, reflecting sunlight to croplands to prolong the growing season, and many more . . . They have a section discussing global warming, ice age, and many other fascinating topics.

Read more about solar power satellites, and other peaceful uses of outer space, here. This might be a good time to go back and review my posting about access to space. You have to get there before you can do all these things. This post from Power From Space blog provides links to all the companies involved in the race to place solar power satellites in orbit.

The main limit to human progress is the limit of the human brain. Humans are presently intelligent enough to get into a lot of trouble. If you are a singularitarian, you are pinning your hopes on intelligent machines, nanotechnology, and the exponential increase in knowledge. Personally, I prefer the idea of enabling more intelligent humans. Either approach holds risks, but the alternative is to let things take their current course. There are also problems with that approach.

DNA Methylation: Reversible Gene Expression in Cancer and Development

DNA methylation is one way that gene expression is controlled. In a previous post I discussed the use of hypomethylating drugs to de-methylate tumor suppressor genes, thus reactivating them, as a good way to treat cancer.

DNA methylation is involved from the very beginning of human embryonic development. In early development (fertilisation to 8-cell stage), the eukaryotic genome is demethylated. From the 8-cell stage to the morula, de novo methylation of the genome occurs, modifying and adding epigenetic information to the genome. By blastula stage, the methylation is complete. This process is referred to as "epigenetic reprogramming".

This newsrelease discusses new findings in DNA methylation--how methylation can be thought of more as a dimmer switch, and less as an on-off switch.

A gene is like a long sentence that describes the structure of a protein. The letters in the sentence are spelled out in the building blocks of the DNA strand of which the gene is part.

Like a sentence, a gene has a well-defined starting point, called the start site. Unlike a sentence, a gene has a second region that runs to the left of the start site. That region is known as the promoter, and this is the off-and-on switch for the gene.

DNA methylation involves chemical changes that take place in the promoter region. These changes alter the gene so that it cannot be turned on. Usually, these chemical changes occur in areas of the promoter that are close to the start site, and that’s where others have looked for them in the C/EBPa gene.

Plass and his colleagues, however, looked two to three times farther from the start site than usual.

“We were surprised to find that methylation had occurred along this region far upstream from the start site,” Plass says.

DNA methylation is very complex, and central to both animal development, and gene expression of the mature animal. Methylation can shut down oncogenes--preventing cancer--and methylation can shut down tumor suppressor genes--allowing cancer to progress. The B-vitamin Folic Acid is intimately involved in DNA methylation, and this article provides useful background to the critical role of folate in both preventing and promoting cancers.

DNA methylation falls into the category of epigenetics. Epigenetic regulation of gene expression can largely determine the difference between a chimpanzee and a human.

Perhaps mastering epigenetics will reduce the need for vectored gene therapy, at least in the short run.

Stalking the Stealthy Atom

Have you ever stood in a long line at airport security, thinking to yourself, "there has got to be a better way?" We all understand the need for caution. A pressurised aluminum shell at 12,000 meters cannot take very much stress before it disintegrates, spilling its precious cargo across the countryside--that means you. Finding the explosives before the explosives find you, becomes very important to a frequent flyer. That is one application of cavity ring-down spectroscopy--a type of laser absoption spectroscopy. Cavity ring-down spectroscopy is an excellent way of detecting materials, but it is limited to measuring a narrow spectrum of 1 nm at a time.

A recent breakthrough described in this newsrelease allows the simultaneous scanning of wavelengths spanning 100 nm (750-850nm)--from the visible into the near infra-red.

Described in the March 17 issue of Science,* the new technology is an adaptation of a conventional technique, cavity ring-down spectroscopy, for identifying chemicals based on their interactions with light. The JILA system uses an ultrafast laser-based "optical frequency comb" as both the light source and as a ruler for precisely measuring the many different colors of light after the interactions. The technology offers a novel combination of a broad range of frequencies (or bandwidth), high sensitivity, precision and speed. A provisional patent application has been filed.

...."What a frequency comb can do beautifully is offer a powerful combination of broad spectral range and fine resolution," says NIST Fellow Jun Ye, who led the work described in the paper. "The amount of information gathered with this approach was previously unimaginable. It's like being able to see every single tree of an entire forest. This is something that could have tremendous industrial and commercial value."

Frequency combs are an emerging technology designed and used at JILA, NIST and other laboratories for frequency metrology and optical atomic clocks, and are being demonstrated in additional applications. NIST/JILA physicist John (Jan) Hall shared the 2005 Nobel Prize in physics in part for his contributions to the development of frequency combs [www.nist.gov/public_affairs/newsfromnist_frequency_combs.htm]. In the application described in Science, the frequency comb is used to precisely measure and identify the light absorption signatures of many different atoms and molecules.

The JILA system described in Science offers exceptional performance for all four of the primary characteristics desired in a cutting-edge spectroscopic system:

* The system currently spans 125,000 frequency components of light, or 100 nanometers (750-850 nm) in the visible and near-infrared wavelength range, enabling scientists to observe all the energy levels of a variety of different atoms and molecules simultaneously.

* High resolution or precision allows scientists to separate and identify signals that are very brief or close together, such as individual rotations out of hundreds of thousands in a water molecule. The resolution can be tweaked to reach below the limit set by the thermal motion of gaseous atoms or molecules at room temperature.

* High sensitivity--currently 1 molecule out of 100 million--enables the detection of trace amounts of chemicals or weak signals. With additional work, the JILA team foresees building a portable tool providing detection capability at the 1 part per billion level. Such a device might be used, for example, to analyze a patient's breath to monitor diseases such as renal failure and cystic fibrosis.

* A fast data-acquisition time of about 1 millisecond per 15 nm of bandwidth enables scientists to observe what happens under changing environmental conditions, and to study molecular vibrations, chemical reactions and other dynamics.

By comparison, conventional cavity ring-down spectroscopy offers comparable sensitivity but a narrow bandwidth of about 1 nanometer. A more sensitive "optical nose" technique developed at NIST can identify one molecule among 1 trillion others, but can analyze only one frequency of light at a time. Other methods, such as Fourier transform infrared spectroscopy, provide large bandwidths and high speed but are not sensitive enough to detect trace gases.

In a previous posting I discussed the use of mass spectrometry for similar purposes. Both techniques have their advantages, and each will find niches of opportunity.

It is important that we be able to sense the world around us in very fine detail, given the potential dangers we face in our lives and travels. As we delve more deeply in the worlds of bio-engineering and nanotechnology, the need for more sensitive detection instruments becomes even more acute.

G Makes the World Go Round

Hat tip to Kevin at Intelligence Testing (IQ Corner) for linking to this exceptional review article by CF Chabris on the cognitive and neurobiological underpinnings of "g", general intelligence. The article came to Kevin via GNXP blog. Here are links to other articles by Chabris.

The timing of Kevin's posting was fortuitous for me, as I am currently reading the book Behavioral Genetics in the Postgenomic Era by Plomin et al, which contains several chapters on related topics. I enjoy reading about topics that interest me from the perspective of several disciplines simultaneously, if possible.

For those new to the topic, I recommend reading this introduction by Linda Gottfredson first, then the review article above. Here is a gentle introduction to the genetic basis of intelligence which takes a very evenhanded approach to the nature-nurture debate. This is a discussion of intelligence as it may relate to human similar or human equivalent machine intelligence, and other non-human intelligence, from the viewpoint of a singularitarian at the Singularity Institute. The author takes the viewpoint that a machine intelligence will be the first "superintelligence" that humans encounter. He discusses the possible fallout from that encounter. Here is the Singinst.org description of levels of organization of general intelligence.

If the mean IQ in the developed world were ten points lower, it would not be the developed world that we know. Hospitals would be far more primitive, scientific research would be at a very retarded stage in comparison with modern science, there would not be enough intelligent engineers and technicians to maintain our complex technologies. G makes the world go around.

Robots Just Don't Get Any Respect

Have you ever wondered why there are conspiracy tales about black helicopters, and virtually none at all about robots? Humans tell jokes about robots. It is a question of being taken seriously. Everyone knows that helicopters are capable of swooping down just about anywhere on earth and carrying people away. But robots are tied down to a power cord. Robots have no mobility, and are slow and clunky besides.

The University of Texas at Dallas wants to change all that. Last year, UTD won a $750,000 grant to develop artificial muscles that run on chemical fuel, rather than electricity. Now, UTD is announcing the development of working artificial muscles that can run on alcohol and hydrogen. Robots powered by such muscles could carry their own fuel with them, and be mobile like a person.

The new muscles simultaneously function as fuel cells and muscles, according to Baughman, corresponding author of the Science article. A catalyst-containing carbon nanotube electrode is used in one described muscle type as a fuel cell electrode to convert chemical energy to electrical energy, as a supercapacitor electrode to store this electrical energy and as a muscle electrode to transform this electrical energy to mechanical energy. Fuel-powered charge injection in a carbon nanotube electrode produces the dimensional changes needed for actuation due to a combination of quantum mechanical and electrostatic effects present on the nanoscale, Baughman said.

In another of the described artificial muscles – currently the most powerful type – the chemical energy in the fuel is converted to heat by a catalytic reaction of a mixture of fuel and oxygen in the air. The resulting temperature increase in this “shorted fuel-cell muscle” causes contraction of a shape memory metal muscle wire that supports this catalyst. Subsequent cooling completes the work cycle by causing expansion of the muscle.

“The shorted fuel cell muscles are especially easy to deploy in robotic devices, since they comprise commercially available shape memory wires that are coated with a nanoparticle catalyst. The major challenges have been in attaching the catalyst to the shape memory wire to provide long muscle lifetimes, and in controlling muscle actuation rate and stroke,” said Baughman. “Students and scientists of all ages will be working on optimizing and deploying our artificial muscles, from high school students in our NanoExplorer program to retired technologists in our NanoInventor program.”

Read the full report here.

These artificial muscles are linear actuators, like animal muscle. Linear actuators better enable the type of motion that humans are capable of, including swimming, climbing, running, jumping, lifting, and carrying. It is easy to imagine robo-cops, robo-firefighters, robo-soldiers, robo-miners, and robo-construction workers, all built with this type of artificial muscle. Of course, having the ability to carry its own fuel gives this type of robot staying power, and respect.

Here is a good source of information about artificial muscles, from the University of New Mexico. Registration to view the videos is free, and the research papers are available without registration.

Here is a website for a commercial enterprise developing artificial muscles, a spinoff of SRI International.

This is a NASA website discussing some fascinating applications of artificial muscle. It contains videos, a video lecture, and articles, images, and links for artificial muscle information.

The UTD muscle that runs on chemical fuel is the type of breakthrough needed to create mobile robots. If a robot can run on alcohol, why not sugar, protein, or fat? The convergence of robotics, artificial intelligence, and advanced nano-chemo-energetics promises to bring about robots with the potential to be truly fearsome.

We humans need to become smarter, or robots will be telling human jokes soon.

Update: Be sure to check out Chris Chatham's post on military robots at Develintel Blog. If that does not make you a bit uneasy, check your body temperature to see if it is above ambient level.

Beta Amyloid and Alzheimer's: What it Does, How to Stop it

Beta Amyloid protein, Abeta, is involved in neuron damage in several diseases, including Alzheimer's. A recent report from Johns Hopkins has solidly established the association between Beta Amyloid and memory loss in a mouse model of Alzheimer's.

A research team that included members from The Johns Hopkins University and the University of Minnesota Medical School has for the first time identified a substance in the brain that is proven to cause memory loss. This identification gives drug developers a target for creating drugs to treat memory loss in patients with dementia.

....The researchers hypothesized that there was a substance in the brain that causes memory decline that is present even before nerve cells begin to die. To test that hypothesis, the team used mice whose genetic makeup was manipulated to develop memory loss much in a way people develop subtle memory problems before the earliest stages of Alzheimer's disease. Using mice that showed early signs of memory loss and had no plaques or nerve cell loss in the brain, they discovered a form of the amyloid-beta protein that is distinct from plaques. They extracted and purified this newly found protein complex and injected it into healthy rats. The rats suffered cognitive impairment, confirming that this protein has a detrimental effect on memory.

Read the full report here.

We learn even more about beta amyloid, and how it kills brain cells in alzheimer's, from this research report from Children's Hospital and Recearch Center, Oakland.

In a study published in the February 28th issue of the Proceedings of the National Academy of Sciences, lead scientist Hani Atamna, Ph.D., found that alterations in the production of heme (a molecule that contains iron) may be the key to understanding why excessive amyloid-beta is toxic to brain cells. Dr. Atamna had previously discovered that Alzheimer's patients have abnormal amounts of heme in their brains. In new research results, Atamna's team showed that amyloid-beta readily binds with heme to form a compound that can be flushed from cells. When there is insufficient heme or too much amyloid-beta, however, the amyloid-beta forms large toxic "clumps" that the cell cannot dissolve and eliminate.

Though heme binding with amyloid-beta can be beneficial, if too much heme is bound up with amyloid-beta, there may be insufficient heme available for the cell to properly function. When this happens, the cell's mitochondria, which are the tiny structures inside brain cells that produce the energy the cells need to function, begin to decay. Dr. Atamna refers to this phenomenon as a "functional heme deficiency" because the cells are still forming heme, but it is trapped within an amyloid-beta/heme compound.

When they examined the heme/ amyloid-beta compound researchers in the Atamna laboratory were surprised to discover it was a peroxidase--a type of enzyme that reacts harmfully with biological materials essential for proper brain function such as serotonin and L-DOPA. Dr. Atamna believes that the combination of functional heme deficiency, which harms mitochondria needed to produce energy, together with the increase in oxidative damage caused by the peroxidase, is what eventually kills the cell.

So we can see that beta amyloid first causes confusion and memory loss, then it binds heme and triggers oxidative damage to neurons, and mitochondrial dysfunction leading to apoptosis of the neuron. Now we need to look at ways to prevent and arrest those processes before the damage is irrevocable.

In this research report, we learn how researchers used Herpes Simplex Virus (HSV) as a vector for gene therapy, to inhibit amyloid beta production and accumulation.

We generated replication-defective herpes simplex virus (HSV) vectors that inhibit Abeta accumulation, both in vitro and in vivo. In cell culture, HSV vectors expressing either (i) short hairpin RNA directed to the APP transcript (HSV-APP/shRNA), or (ii) neprilysin, an endopeptidase that degrades Abeta (HSV-neprilysin), substantially inhibited accumulation of Abeta. To determine whether these vectors showed similar activity in vivo, we developed a novel mouse model, in which overexpression of a mutant form of APP in the hippocampus, using a lentiviral vector (LV-APP(Sw)), resulted in rapid Abeta accumulation. Co-inoculation of LV-APP(Sw) with each of the HSV vectors showed that either HSV-APP/shRNA or HSV-neprilysin inhibited Abeta accumulation in this model, whereas an HSV control vector did not. These studies demonstrate the utility of HSV vectors for reducing Abeta accumulation in the brain, thus providing useful tools to clarify the role of Abeta in AD that may facilitate the development of novel therapies for this important disease.Gene Therapy advance online publication, 16 March 2006

Read more here.

There is a great deal more involved with Alzheimer's than what is discussed in these three articles. You may be wondering where the beta amyloid protein came from in the first place. This useful review article will help to answer that question, and discusses several present and future treatments for Alzheimer's as well. It may take an hour or two to read and digest, but while doing so, be thankful you have that capacity.

There are many, many unanswered questions remaining. But since Alzheimer's is considered a priority by most western governments, well designed research that addresses those questions is very likely to be funded.

The Seven Deadly 'Xins of Botulinum

Clostridium Botulinum is a bacterium that produces seven deadly toxins, A through G. These toxins block the neuromuscular junction and cause paralysis of muscles. The botulinum toxin A, or BoTox, can either kill or heal. When used as a biological weapon, the toxin is deadly. When used to treat pain, it can be a godsend.

This newsrelease details how scientists from UW Madison, and the University of Texas, have determined exactly how the deadly botulinum toxin A can gain entry into neurons to block their function.

Writing in the current online edition of Science, a team of researchers at the University of Wisconsin-Madison and the University of Texas report that botox latches onto a protein known as SV2 to gain entry into neurons.

"Our work shows that botox is really smart and clever," says senior author Edwin Chapman, a UW-Madison professor of physiology and an investigator of the Howard Hughes Medical Institute. "It uses SV2 to sneak into nerves like a Trojan horse."

"Botulinum neurotoxins are among the six most dangerous bioterrorism threats," adds lead author Min Dong, a UW-Madison postdoctoral researcher in the department of physiology. "Knowing the protein receptor for [botulinum toxins] can pave the way for developing anti-toxin reagents which may block the entry of toxins into cells."

The botulinum toxins, of which there are seven types, are made by a bacterium commonly found in soil, known as Clostridium botulinum. Of the seven-identified by the letters A through G--botox A lasts a particularly long time in neurons. While that feature makes it especially useful in the clinic, it also means that botox A may pose a particularly dangerous threat as a biological weapon.

The toxin enters neurons by binding to nerve endings and preventing the release of crucial chemical messengers, known as neurotransmitters, that communicate with muscles. When enough nerve endings are invaded, botox can lead to paralysis and death. ....

Chapman and his team located the exact molecular gateway through which botox penetrates cells by gathering clues from earlier research that pointed to the potential importance of tiny neural storage bins known as "synaptic vesicles." Situated at nerve endings, synaptic vesicles continually work to store and release neurotransmitters. Dozens of proteins, including SV2, work to ensure that vesicles function properly. With standard screening experiments known as "entry assays," the scientists were able to zero in on SV2. To confirm that result, they acquired mice that were genetically engineered to carry reduced amounts of SV2. Without that protein around, the researchers found that botox was unable to wreak havoc.

The entire report is here.

For those who wish to learn the bioscience of botulism, this outline with links is most helpful. Botulinum toxin has killed many people who ingested the toxin unawares. Entire families have died within hours of eating badly preserved food that contained the toxin. The new findings discussed above may help to prevent and treat this toxicity. Because the next time you hear about botulinum toxicity may be on the civil defense channel. This is not a drill.

In Search of the Wild Molecule

We are swimming in a sea of molecules, unaware. That woman walking by has undiagnosed liver cancer, if we could only smell it. That student with a backpack is carrying explosives but who could tell? Those men working in that tunnel are being slowly poisoned by toxic gas, but who will warn them?

Purdue University researchers have developed a device that might open our collective eyes. The device is a miniature mass spectrometer, run on batteries. It has the potential for use at airport security, in hospital labs, and for environmental quality monitoring.

Researchers at Purdue University have shown how a new ultra-fast chemical-analysis tool has numerous promising uses for detecting everything from cancer in the liver to explosives residues on luggage and "biomarkers" in urine that provide an early warning for diseases.

The analytical chemists have most recently demonstrated how the technology, called desorption electrospray ionization, or DESI, rapidly detects the boundaries of cancerous tumors, information that could help ensure that surgeons remove the entire tumor.

"I wouldn't be surprised if pathologists are using this in operating rooms within two years," said R. Graham Cooks, the Henry Bohn Hass Distinguished Professor of Analytical Chemistry in Purdue's College of Science.

The technology has made it possible to speed up and simplify the use of a mass spectrometer, an analytical device that in its conventional form has been long established in modern laboratories. But while ordinary mass spectrometry is both time- and labor-intensive, the Purdue group has modified the technology to make it faster, more versatile and more portable.

.....A review paper about DESI and related techniques, which enable the direct chemical analysis of objects in an ordinary environment, will appear in the Friday (March 17) issue of the journal Science. The paper was written by Cooks, associate research scientist Zheng Ouyang, visiting scholar Zoltán Takáts and doctoral student Justin Wiseman, all in Purdue's Department of Chemistry. Several technical papers have been published about DESI experiments since the method was announced by the same laboratory in Science less than two years ago, but the new Science paper provides the first overall review of DESI and related techniques.

Mass spectrometry works by first turning molecules into ions, or electrically charged versions of themselves, which can be detected and analyzed.

"Having a charge enables you to not only detect molecules but also to measure their masses, which you can't do with neutral molecules," Cooks said.

Conventional mass spectrometers analyze samples that are specially prepared and placed in a vacuum chamber. The key DESI innovation is performing the ionization step in the air or directly on surfaces outside of the mass spectrometer's vacuum chamber.

In addition to DESI, Cooks' research group has designed and built a portable instrument that is roughly the size of a shoebox and weighs about 10 kilograms (22 pounds), compared to about 30 times that weight for a conventional mass spectrometer. The lightweight instrument can run on batteries, which means it can be carried anywhere....[it] promises to have applications in everything from airport security to medical diagnostics.

Read the rest here. Parallel research is going on at Oak Ridge National Lab.

Mass spectrometry has been around for several decades, but it is far more useful and powerful now. Soon, portable battery powered instruments will be used in the field, virtually anywhere.

Here is a brief primer on mass spectrometry. Here is a set of links to mass spectrometry resources, including tutorials.

Evolution gave us eyes, ears, noses, tongues, fingers, and other means of detecting and interpreting our environment. All sensory roads lead to the brain. The brain wants more information than our senses can give, thus the increasingly sophisticated analytical instruments and methods. The next step is a better brain.

China: The Ticking Time Bomb?

I recently posted on an interesting Foreign Policy article that looked at the dark side of China's rise. A few days ago, Winds of Change blog's Joe Katzman posted a look at some specific problems that China is facing.

We'll start with the rural time bomb:

"A peasant "time bomb" threatens to stunt China's rise to global economic superiority unless immediate measures are taken to fix the problem, say experts. The Chinese state has lost much of its legitimacy with the country's rural majority, a turnaround that could have increasingly adverse effects on the long-term socio-economic development of the country, according to Joshua Muldavin, an Asian studies expert at Sarah Lawrence College in New York.

With greater land seizures by the state and reduced levels of rural subsistence, more peasants are having to migrate to urban areas in search of work where disappointment often awaits, making "peasant landlessness ... a time bomb for the state," Muldavin told an audience Thursday at the Carnegie Endowment for International Peace.

"There are two Chinas," he said. One is for investors, and the other is the "rural hinterlands," where official corruption, a growing gap between rich and poor and unemployment led to some 87,000 incidents of unrest in China last year, said Muldavin. It is believed that many more go unreported."

......So, on to the demographic/ pension/ investment time bomb:

China's pension system is facing a demographic time bomb -- the consequence of the one-child policy -- which could seriously damage its future economic prospects, says a new report from Deutsche Bank's research department.

"Low retirement age compounds the demographic problem. China is graying fast but at a very low income level. Low effective retirement ages will see the working age population already reaching its peak between now and 2010 and will lift the old-age dependency ratio much higher than conventionally thought," says the report.

In effect, China is getting the demographic profile of an advanced industrial country with a mature welfare system, but with an economy still clambering out of developing status. And repairing the existing pension crisis is going to cost a minimum of 7 percent of its gross domestic product.

The DB survey lists three structural challenges in today's system that need to be addressed. The first is that the pension system is burdened by a large amount of legacy debt (i.e. unfunded liabilities from the old pension system).

The second is that decentralization of economic planning has led to fragmentation and a lack of transparency; and the third is that China's "immature capital markets make it difficult to find suitable investments with high returns."

Joe's post elicited several fascinating comments, including links to much more commentary and other articles. Read it all here.

Most investors get little gold bars in their eyes when they think of China's billion consumers. Anyone who tries to anticipate the geopolitical trends of the next decade or so needs to think more realistically.

The magnificent scientific achievements of (mostly) western research laboratories rests upon the economies of the western nations. If western economies fall like a house of cards due to a collapse of the Chinese banking system, then all of these miracle cures and devices that are just around the corner, will fail to materialise.

There is a point of no return, after which Communist Chinese corruption and Islamist fanaticism cannot stop the expansion of knowledge and human growth. But we are decades from that point, and very vulnerable yet. Keep a realistic eye on what is happening in those unstable, but critical parts of the world. If caught unprepared, many hundreds of millions of people could easily die in a short period of time. That is what critical instability means, in the modern world. The potential for more dead people than most persons can count.

It will be necessary to "look around" the news media--consider the news media a major obstacle to the acquisition of the valid states of the world. Be very skeptical, develop your own model of the world independent of journalists and journalism. Collect several sources of information and play them against each other.

Eating Germs to Stay Well

Consider this: you come down with productive cough, fever, chills. The chest Xray indicates an infiltrate in your lung fields. Your doctor prescribes antibiotics, and the symptoms subside, you feel better. What do you do next? According to this newsrelease, you should probably eat some germs. Lactobacilli to be specific. Normal gut flora that make vitamins for you and keep the bad bacteria and yeast from setting up shop in your belly. Read on:

Once outside the womb, we are bombarded by microbes and soon we have 10 times more microbes in our body than the number of cells that make up the human body.

It is the bad microbes that cause disease. Good microbes work with the body's immune system to keep the bad microbes at bay by crowding them out. In the symbiotic relationship between good and bad microbes, recent research has uncovered the importance of these good microbes.

“The good microbes - and this is where probiotics come in - keep the bad microbes in small numbers. But they also stimulate the immune system and improve our digestive function. That's the subject of research that has been going on for years,” Huffnagle says.

Probiotics are bacteria that we eat and they're good for our health. They are found in a number of foods that are readily available in the supermarket, and they taste good. You can support probiotic growth by increasing the amount of cultured dairy products you eat, such as cheeses and yogurt, and the foods that encourage probiotics from these dairy products to multiply even further: spices, tea, red wine, berries, apples and beans.

Huffnagle says that most of these good microbes exist within our body in the digestive track, with the largest number occurring in the small and large intestines.

“It's the job of these good microbes to stimulate our immune system, and the other job they do is to stimulate good digestive health,” he says.

Not only that, but the good bacteria are capable of producing antibiotics that attack bad bacteria. Follow along from this newsreport:

Nisin, a peptide, contains 34 amino acid residues and the unusual amino acids lanthionine, methyllanthionine, dehydroalanine and dehydro-amino-butyric acid. The latter are made by post-translational modification of proteins.

Nisin works well against Gram-positive bacteria and food-borne pathogens that cause botulism and listeriosis because it punches holes into cell membranes and binds to essential molecules in the disease-causing bacteria. Hitting on at least two targets reduces the risk of resistance occurring, van der Donk said.

The researchers synthesized nisin simply in a test tube by using a single cyclase enzyme to re-create the process that normally occurs in a strain of the bacterium Lactococcus lactis found naturally in milk. They demonstrated how just one protein (NisC) makes 10 new chemical bonds in a stereochemically defined fashion. Specifically, they showed that NisC is responsible for the formation of five characteristic thioether rings required for nisin's biological activity.

"Despite all the progress in synthetic chemistry, we cannot come close to making a compound like nisin efficiently," van der Donk said. "Synthetic chemists in the past needed 67 steps to make it, while nature uses just two enzymes. One of these is the cyclase whose activity we have demonstrated in this paper."

Read more here.

When you are born, your gastrointestinal tract is sterile. As soon as you began eating, your gut was colonised by bacteria. If you were breast-fed, you were lucky enough to receive booster nutrients that promoted bifidobacteria, which prevent colonisation by pathogenic bacteria. Other food sources, although nutritious enough, lack that advantage.

Gut bacteria produce vitamins B12 and K for us, as well as keeping out the bad germs. Genetically engineered gut bacteria could do much more for us, and would be a natural way of introducing genetically engineered resveratrol, curcumin, or capsaicin or other natural substances known to counter cancer or promote longevity.

Most of us do not like to think about what goes on inside of us, until we get sick, then we definitely want a physician to think very hard about what is inside of us and how to make it better. But would it not be better to stay well, if you had the choice?

Hot Chili Peppers Prostate Cancer to Death

You can find places in the world where the measure of a man is how well he holds his chili peppers. According to this news report, men who like their chilis are less apt to suffer from prostate cancer than their less manly fellows. From the newsrelease:

Capsaicin induced approximately 80 percent of prostate cancer cells growing in mice to follow the molecular pathways leading to apoptosis. Prostate cancer tumors treated with capsaicin were about one-fifth the size of tumors in non-treated mice.

"Capsaicin had a profound anti-proliferative effect on human prostate cancer cells in culture," said Sören Lehmann, M.D., Ph.D., visiting scientist at the Cedars-Sinai Medical Center and the UCLA School of Medicine. "It also dramatically slowed the development of prostate tumors formed by those human cell lines grown in mouse models."

Lehmann estimated that the dose of pepper extract fed orally to the mice was equivalent to giving 400 milligrams of capsaicin three times a week to a 200 pound man, roughly equivalent to between three and eight fresh habañera peppers – depending on the pepper's capsaicin content. Habañeras are the highest rated pepper for capsaicin content according to the Scoville heat index. Habañero peppers, which are native to the Yucatan, typically contain up to 300,000 Scoville units. The more popular Jalapeño variety from Oaxaca, Mexico, and the southwest United States, contains 2,500 to 5,000 Scoville units.

....Apoptosis is a normal cellular event in many tissues that maintains a balance between newer replacement cells and aged or worn cells. In contrast, cancer cells seek to be immortal and often dodge apoptosis by mutating or deregulating the genes that participate in programmed cell death.

"When we noticed that capsaicin affected NF-kappa Beta, that was an indication that we might expect some of the apoptotic proteins to be affected," said the study's senior author, Phillip Koeffler, M.D., director of Hematology and Oncology, Cedars-Sinai Medical Center, and professor at UCLA.

The pepper extract also curbed the growth of prostate cancer cells through regulation of androgen receptors, the steroid activated proteins that control expression of specific growth relating genes.

In prostate cancer cells whose growth is dependent on testosterone, the predominant male sex steroid, capsaicin reduced cell proliferation in a dose-dependent manner. Increased concentrations of capsaicin caused more prostate cancer cells to freeze in a non-proliferative state, called G0/G1.

Prostate cancer cells that are androgen independent reacted to capsaicin in a similar manner. Capsaicin reduced the amount of androgen receptor that the tumor cells produced, but did not interfere with normal movement of androgen receptor into the nucleus of the cancer cells where the steroid receptor acts to regulate androgen target genes such as prostate specific antigen (PSA). Capsaicin also interfered with the action of androgen receptors even in cells that were modified to produce excess numbers of androgen receptors.

The hot pepper component also reduced cancer cell production of PSA, a protein that often is produced in high quantities by prostate tumors and can signal the presence of prostate cancer in men. PSA content in the blood of men is used as a diagnostic prostate cancer screening measure. PSA is regulated by androgens, and capsaicin limited androgen-induced increases of PSA in the cancer cell lines.

Read the entire report here.

I hardly need an excuse to eat hot chilis, but this research report gives me a reason to look into the epidemiology of chilis and cancer a bit more. Stay tuned.

Why so Afraid, Little Flower? Is it your Amygdala Again?

We are all at the mercy of our genes. Your genes determine the color of your eyes, your hair, your approximate height, and much of your personality. Are you sanguine? Are you cheerful? Are you fearful? Activation of your amygdalae has a lot to do with serotonin levels in synapses, and the level of negative emotions you experience. Serotonin levels in the synapse are largely determined by your genes. "How Genes Make up Your Mind" is an interesting article in the Science and Consciousness Review.

Genes control the development of neurons to make up brains, but they also govern neuronal gene expression during our daily lives. The sleep-waking cycle is controlled by neurochemicals emerging from cells at the base of the brain. Genes control how neurons communicate with serotonin, dopamine or other neurotransmitters (cache). Genes are responsible for every step of the neurotransmitter cycle, including the formation, transport, pre-synaptic expression and post-synaptic reception of the transmitter (see Figure 1). Genes work at every level of the neural process. They are the fundamental building blocks for both the structure and the functioning of the brain.

....How do genes influence the emotional workings of brains? Recent studies now show that naturally occurring genetic variations - called polymorphisms (cache) - which code for serotonin affects our emotional reactions and thoughts. Humans have two common variations of a promoter region of the serotonin transporter gene (5-HTTLPR); a short (s) and a long (l) version. It has been shown that two allelic (cache) copies of the long variant leads to higher concentration of 5-HTT mRNA, which leads to a doubled reuptake of serotonin, compared to one or two short allelic variations. People who have two copies of the long genetic sequence in this region have less serotonin available in the synapse, due to the higher reuptake of the neurotransmitter.

....The researchers found that the actvation of the two amygdalas differed between the two groups (see Figure 4). The s group showed a significantly higher amygdala activation than the l group. In other words, the level of amygdala activation depended on what genetic makeup a person had. Having a short version of the 5-HTT genetic code leads to a higher level of synaptic serotonine, which again leads to a higher level of amygdalar response to aversive stimuli. This is consistent with the prediction described above.

While these results have provided us new information about how genes regulate brain function, one can ask: does this have any effect on thought and behaviour? Indeed it has! Studies demonstrate that carriers of the s allele, compared to l allele carriers, are more likely to show abnormal levels of anxiety (5) develop affective illness (6) and even acquire conditioned fear responses (7). Variations in the genetic makeup of the serotonin system has profound influence on our experience and behavior. Thoughts are shaped by genes.

The original article contains several useful links. Check it out.

Not everyone wins the genetic lottery. At least now we are beginning to understand what happens, and what might be done to bring the advantages of good genes to the amygdalas of everyone.

Nanotech that Heals Brain Damage

In a recent post I described a peptide bio-gel that promotes cell growth, and acts as a three dimensional scaffold for tissue healing and cell culture. Now a cognitive science researcher at MIT has developed a liquid solution of peptide chains that self assembles into nano-fibres inside damaged brain. These nano-fibres then form a scaffold for the re-growth of severed nerves--an incredible achievement in the central nervous system. Here is the report:

Although victims of stroke and traumatic brain and spinal cord injuries sometimes recover through rehabilitation, they often have permanent disabilities, in part, because scar tissue and regulatory chemicals in the brain slow nerve growth, preventing nerve tissue from repairing itself. Now a treatment that has restored lost vision in lab animals appears to overcome these obstacles, allowing a mass of nerve cells to regrow after being cut.

"We think this is the basis of reconstructive brain surgery -- which is something nobody has ever heard of before," says Rutledge Ellis-Behnke, a researcher on the project and a brain and cognitive sciences researcher at MIT.

The treatment, described online this week in the Proceedings of the National Academy of Sciences and performed at MIT, Hong Kong University, and Fourth Military Medical University in China, may be available to humans in trials in as little as three years if all goes well in large-animal studies, the researchers say.

In their experiments, the researchers first cut into a brain structure that conveys signals for vision, causing the small lab animals to be blinded in one eye. They then injected a clear fluid containing chains of amino acids into the damaged area. Once in the environment of the brain, these chains, called peptides, bind to one another, assembling into nano-scale fibers that bridge the gap left by the damage. The mesh of fibers prevents scar tissue from forming and may also encourage cell growth (the researchers are still investigating the mechanisms involved).

As a result, nerve cells restored severed connections, allowing 75 percent of the animals to see well enough to detect and turn toward food. The treatment restored around 30,000 nerve connections, compared with 25-30 connections made possible in other experimental treatments, Ellis-Behnke says.

Read the rest here.

Repairing damage in the brain and spinal cord has always been virtually impossible, due to the resistance to regrowth of CNS neurons. Clearly something in the peptide fibres encourages the nerves to regrow, and reconnect. Just like something in the peptide gel of the tissue scaffold in the earlier article encourages cultured cells to grow.

In those two research projects, we can see the beginnings of the development of both the growing of artificial replacement organs, and the repair of central nervous system damage in the brain and spinal cord. Now we need to watch for research that replicates these findings, and takes them further.

Global Warming? It's the Water, Stupid!

Getting excited about global warming at this early stage in understanding of climate science has always struck me as rather premature. There are quite a few scientists who feel the same way, although for political reasons they may feel the need to keep a low profile on that topic. Vladimir Shaidurov is a member of the Russian Academy of Sciences, and his theory of global warming says that the warming of the past several decades is due to changes in the composition of water in the atmosphere, rather than carbon dioxide. Here is a report on this unconventional theory.

However, the most potent greenhouse gas is water, explains Shaidurov and it is this compound on which his study focuses. According to Shaidurov, only small changes in the atmospheric levels of water, in the form of vapour and ice crystals can contribute to significant changes to the temperature of the earth's surface, which far outweighs the effects of carbon dioxide and other gases released by human activities. Just a rise of 1% of water vapour could raise the global average temperature of Earth's surface more then 4 degrees Celsius.

The role of water vapour in controlling our planet's temperature was hinted at almost 150 years ago by Irish scientist John Tyndall. Tyndall, who also provided an explanation as to why the sky is blue, explained the problem: "The strongest radiant heat absorber, is the most important gas controlling Earth's temperature. Without water vapour, he wrote, the Earth's surface would be 'held fast in the iron grip of frost'." Thin clouds at high altitude allow sunlight to reach the earth's surface, but reflect back radiated heat, acting as an insulating greenhouse layer.

Water vapour levels are even less within our control than CO2 levels. According to Andrew E. Dessler of the Texas A & M University writing in 'The Science and Politics of Global Climate Change', "Human activities do not control all greenhouse gases, however. The most powerful greenhouse gas in the atmosphere is water vapour, he says, "Human activities have little direct control over its atmospheric abundance, which is controlled instead by the worldwide balance between evaporation from the oceans and precipitation."

As such, Shaidurov has concluded that only an enormous natural phenomenon, such as an asteroid or comet impact or airburst, could seriously disturb atmospheric water levels, destroying persistent so-called 'silver', or noctilucent, clouds composed of ice crystals in the high altitude mesosphere (50 to 85km).

Read the entire report here.

Peak oil and global warming are custom made catastrophes that get a great deal of political spin in the media. That makes them neither right nor wrong, merely suspect. Anything that journalists consider significant or newsworthy should always be viewed skeptically.

New Screening Test 100,000 Times Better for Early Cancer Detection

This is a very significant development in the search for better ways to detect cancer early, while it is still treatable. A new screening method called FACTT (for Florescent Amplification Catalyzed by T7-polymerase Technique) is 100,000 times more sensitive for detecting proteins than the current method, ELISA (enzyme-linked immunoadsorbent assay).

This newsbrief from Innovations Report gives more details:

Senior author Mark I. Greene MD, PhD, the John Eckman Professor of Medical Science, Hongtao Zhang, PhD research specialist; Xin Cheng, PhD, research investigator, and Mark Richter, a research technician in Greene’s lab, report their findings in the advanced online publication of Nature Medicine.

"The current ELISA tests can only detect proteins when they are in high abundance," says Zhang. "But the problem is that many of the functional proteins – those that have a role in determining your health – exist in very low amounts until diseases are apparent and cannot be detected or measured at early stages of medical pathology. It was important to develop a technique that can detect these rare molecules to detect abnormalities at an early stage."

The FACTT technology uses a different enzyme amplification system so quantitative signals can be obtained from even a few protein molecules compared to ELISA. "The technology is remarkably adaptable to any protein and can be performed in an automated format," notes Greene. He states that the technology will soon be robotized so as to be able to screen for many rare disease-causing proteins using tiny amounts of blood. "It is even possible that one could screen for multiple diseases at the same time and produce a precise accounting of whether disease-causing molecules are present at an early time when disease can be readily treated," adds Greene.

....The researchers compared detection of Her2/neu in the blood between ELISA and FACTT. Her2/neu proteins were in fact first identified by the Greene laboratory in the early 1980s, and the Her2/neu gene was found by other scientists to be overexpressed in breast cancer. Her2/neu is normally a low-abundance molecule that becomes overexpressed in more than 30 percent of primary breast, ovarian, and pancreatic tumors. Part of the Her2/neu molecule is shed from the surface of tumor cells and has been detected in the blood of breast-cancer patients. Higher blood concentrations of Her2/neu correlate with a lower response rate to chemotherapy and shorter survival time after relapse.

....Greene’s laboratory established many of the principles of targeted therapy for Her2/neu tumors and the prototype antibodies that led to the development of Herceptin, a similar antibody molecule that was created by Genentech. The Greene laboratory also previously showed that early treatment of Her2/neu tumors with targeted monoclonal antibodies in animal models led to far more significant prevention of tumor growth as well as tumor emergence and reoccurrence.

Greene stresses that early treatment is far more effective than treating advanced tumors with the same antibodies. Recent clinical trials support the notion that early treatment prevents tumor reoccurrence in women with breast tumors. FACTT technology represents a way to couple early diagnosis with early treatment to prevent tumor emergence.

Read the entire report here.

In years past, detecting cancer earlier was not always better, given the severe limitations on treatment choice. The direction of research is toward treatments that can eradicate a tumor before it is large enough for detection, except through chemical means of detecting biomarker proteins. In other words, treatments will be both effective enough and benign enough to use on a patient, long before the tumor is large enough to detect with xray or physical exam. That is the sort of treatment that is needed to take advantage of this tremendous advance in detection sensitivity.

Women on the Verge of a Solar Energy Revolution

One of the principal problems with using solar energy is that the sun only shines part of the day. When the sun is not shining, its energy cannot be used, unless it has been stored. A lot of methods have been proposed for storing the sun's energy after sundown, for later use.

One of the more interesting proposals has won a prestigious NSF award for Dr. Sherine Obare, a chemist at Western Michigan University. From WMU News:

Obare's project, "Rationally Assembled Nanoparticles for Multi-Electron Transfer Processes," seeks to create nanoscale materials that trap and store the sun's energy and use that energy to carry out chemical reactions for specialized purposes, including breaking down pollutants in groundwater and generating hydrogen for use as an alternative fuel. She is focusing on nanomaterials--materials organized atom by atom or molecule by molecule--because they are have unique properties that can be manipulated and exploited for important applications such as those.

The project is inspired by how nature is able to use intricate pathways to carry out important reactions, Obare says, noting as an example that plants use sunlight to carry out photosynthesis. But what makes her research novel is that she is using nanomaterials to store the energy as electrons, and then initiate chemical reactions even when sunlight is not present.

Very fascinating. Read the entire report here.

Another chemist who is pursuing research in a similar area of study is Dr. Norma Tacconi at University of Texas Arlington. From Dr. Tacconi's webpage:

The coupling of reduction and protonation is an essential feature in most natural light-activated energy-storing processes and these complexes may ultimately be capable of driving proton-coupled, multi-electron transfer reaction of the type desired for facile H2 production or O2 reduction.

These scientists are working to create chemical and nanoparticle complexes that can store solar energy in the form of electrons, for use in fueling chemical reactions of various types, including the generation of hydrogen, and breaking down pollutants.

Nature is prolific in generating energy from the sun, using photosynthesis. Science is learning to do similar tricks using solar power.

Resurrecting Tumor Suppressors to Combat Cancer

The human body is prone to developing cancer, from a very early stage of life, until the end of life. The human genome has several built in tumor suppressor genes, whose protein products suppress the formation of tumors. It is important for these tumor suppressor genes to continue expressing their tumor suppressor proteins as long as the person lives. Over time, DNA can be damaged or altered, leading to loss of function of these protective genes. One way these genes can lose their ability to make protective proteins is through methylation.

Methylation is the gradual addition of chemical units known as methyl groups to genes, and as these groups accumulate, the gene gradually shuts down. Some drugs prevent the methylation process, releasing the gene to produce its tumor suppressor. In fact, methylation is a salient characteristic of cancer cells, and can be used as a biomarker for cancer.

Fortunately, researchers are developing new drugs called "hypomethylating agens" that have the ability to remove the methyl groups and restore function to tumor suppressor genes. This Bio.com report discusses one of these new drugs:

The drug, decitabine, is designed to turn on genes that cancer had switched off, and in this study, patients who were treated with it achieved a significantly higher overall response rate, compared to patients receiving supportive care, which includes transfusions of red blood cells and platelets.

Results of the randomized Phase III clinical trial, published March 13, 2006 in the online version of the journal Cancer, also concluded that in treated patients who responded to the drug, the median time to progression of the disease, or death, was 17.5 months, compared to 9.8 months in patients who did not.

"This is a very promising drug that we believe works even better when patients use it for a period that is longer than that tested in this trial," says lead author, Hagop Kantarjian, M.D., chair of the Department of Leukemia at M. D. Anderson.

....Decitabine is a "biological disease modifier" that was given fast-track approval by the Food and Drug Administration in April 2003.

It is a DNA hypomethylating agent that fights cancer by reversing a chemical process (methylation) that turns off tumor-suppressor genes that protect cells from becoming cancerous.

Other hypomethylating agents are being used and developed for several other types of malignancy including leukemia and breast cancer.

These drugs work by turning back time, as it were--gene time. Other drugs are being developed to turn back time for the entire genome. It is a race against the clock, but then, it always has been.

Programming Plant Cells to make Human Vaccines

Humans have coexisted with plants and microbes from the beginning of human evolution. As humans learned to domesticate various plants, their food supply exploded. Early shamans and healers learned to use herbs for healing. In the modern era, microbes have jumped ahead of plants in the biotech production of gene-engineered pharmaceuticals, but plant scientists are determined that plants can be useful pharm-factories of gene engineered medicines and vaccines.

This Eurekalert newsrelease reports on efforts to design a vaccine against HIV in plants.

By creating fusion molecules, the researchers have found a way to make plants produce more of the molecules (antigens) needed for vaccines. At the same time, they may also have discovered a way of producing better targeted vaccines. Obregon and her colleagues in Dr Julian Ma's laboratory are working with the p24 core protein of the Human Immunodeficiency Virus (HIV). This protein plays a central role in eliciting the immune response to HIV infection, and is therefore likely to be an integral part of any multicomponent vaccine for HIV.

Plants have already been used to produce many types of vaccine molecules, but a consistent problem has been achieving adequate levels of protein expression in order to make them viable as bioreactors for vaccines.

Obregon and her colleagues have found a way to significantly boost HIV-1 p24 protein production in plants by producing an entirely new molecule – a fusion of the HIV-1 p24 protein and part of another protein, human immunoglobulin A (IgA) - a major component of the immune system. The team found that the HIV-1p24 antigen produced in this way elicited appropriate immune response in mice.

This brief report discusses early efforts to develop a vaccine against avian flu, using plants. This blog reports on efforts to use the tobacco plant to develop a vaccine against the black plague, yersinia pestis.

Transgenic plants are becoming more and more useful as plant scientists develop their techniques. The mitigation of many modern problems lies in the intelligent use of transgenic plants, animals, and microbes. In this posting I briefly discussed the use of engineered plants for mitigating global warming. The limits of the human imagination are currently restricting the human vision of a cleaner and healthier world.

Stem Cells On the Rag, In the Teeth, and more

Remember when most people thought the only source for stem cells was an embryo? You can certainly get totipotent stem cells from embryos, but it will be some time before researchers can control totipotent stem cells to everyone's satisfaction. Sometimes stem cells from more mature tissues will satisfy a need. It is important to hunt down these stem cell sources so that we can learn how useful those cells can be.

Stem Cell Research Progress Blog does a very good job of following the news in stem cell research. In recent posts, here and here, Anne Leonard discusses alternative sources of stem cells that are being evaluated.

Researchers in Japan have been looking for alternative sources of stem cells which may be of help in promoting the growth of heart muscle tissue. They have found stem cells in menstrual blood and in umbilical cord blood which have the cardiac gene expression and protein expression necessary for repairing muscles (as opposed to blood vessels). The menstrual blood has the additional advantages of being easily obtainable and rich in stem cells.

She goes on to discuss research with stem cells derived from pig fat and human bone marrow. In the second post, she discusses stem cells from teeth:

Two Asian newspapers are reporting that researchers in Japan at Osaka University and National Institute of Advanced Industrial Science and Technology’s Research Institute for Cell Engineering used stem cells derived from the germ of human wisdom teeth to repair damaged liver and bones in rats. The story was originally published in the Japanese paper the Daily Yomiuri and reprinted with slight variations on the Chinese site Xinhua. The article reports that the tooth germ can be changed into bone, liver, or nerve cells by stimulating it with hormones, and that the stem cells grow far more quickly than those taken from bone marrow.

Today's Stem Cell Research reports on umbilical cord blood stem cell extraction and isolation, and offers a video. Here is a report on spinal cord regeneration stem cell research, and here are some educational materials for teaching about stem cells, from the same website. Check out the Virtual Stem Cell Laboratory.

Stem cells are being found in many locations, even in the human placenta. Embryonic stem cells taken at the proper stage can potentially develop into any cell type. But at the rate that cell biologists are learning to control differentiation and de-differentiation of cells, that characteristic might not set embryonic stem cells apart for long. Stay tuned.

Thinking Makes it Happen

When the brain is working, it generates electromagnetism. A well designed detector of electricity or magnetism can monitor the action of the brain. That is simple EEG or MEG. But if you provide the brain with feedback of its own behaviour, while continuing to monitor the brain, you create a neurofeedback loop.

Clever neuroscientists and computer scientists in Berlin have developed a device that allows persons to operate a computer keyboard using their brainwaves.
This device comes under the category of brain-machine interfaces. It is easy to imagine that if a person can control a computer keyboard with his thoughts, then anything that can be interfaced with an electrical or electromagnetic actuator can be controlled by a person's thoughts.

I find the concept of a wearable robotic exoskeleton, to be one of many things that could be controlled by brainwaves. It would not be hard to equip such an exoskeleton with actuators and brainwave interfaces.
JW Bats of Our Technological Future, reports on this robot hand that detects nerve impulses and moves accordingly. The hand contains pressure sensors, allowing it to pick up and handle very delicate objects.

If one were to combine the brainwave interface with an actuator-equipped exoskeleton, with pressure detecting sensors on the robotic appendages, you might have the basis for an ambulatory device that could replace the wheelchair--for paraplegics, quadriplegics, and victims of disabling neuro/musculo/skeletal diseases. Neurofeedback has a lot of potential.

As I made clear in this post, I prefer biological solutions over hardware solutions. But as I suggested here, and in other posts, I am agreeable to using hardware solutions as a stopgap, while the biological solutions are still being worked out. The goal is full functionality--and more. Getting from here to there will be a winding road.

Hat tip Singularity News.

Peeping Toms of Neuroscience: No More Secrets

We are fortunate these days, to have available the expertise of legions of neuroscientists, all for the price of a mouse click. Eide Neurolearning Blog reports on the obvious neuro-image differences in brain activity between the pro golfer and the beginning golfer.
This fMRI image taken from ScienceDaily, illustrates sex or gender differences in the amount of gray and white matter used for general intelligence.
While there are essentially no disparities in general intelligence between the sexes, a UC Irvine study has found significant differences in brain areas where males and females manifest their intelligence.

The study shows women having more white matter and men more gray matter related to intellectual skill, revealing that no single neuroanatomical structure determines general intelligence and that different types of brain designs are capable of producing equivalent intellectual performance.

“These findings suggest that human evolution has created two different types of brains designed for equally intelligent behavior,” said Richard Haier, professor of psychology in the Department of Pediatrics and longtime human intelligence researcher, who led the study with colleagues at UCI and the University of New Mexico. “In addition, by pinpointing these gender-based intelligence areas, the study has the potential to aid research on dementia and other cognitive-impairment diseases in the brain.”

Functional MRI, or fMRI, is a powerful imaging technology that looks inside the brain while it works. Not only will it tell you what part of the brain is working at any given time, it will also give you an idea of how hard that part of the brain is working.

This excellent article discusses the use of fMRI in intelligence studies, and has some incredible graphic images. The thoughtful sensitivity of the authors when discussing societal implications of the research, and necessary ethical concerns of researchers, is encouraging. And if that masterful review only served to whet your appetite for more, consult these neural correlates of reasoning.

The human brain sits exposed. If the person lies, his brain will show a different picture than if he tells the truth. If the person has to work harder to solve a problem than his sister did, his brain image will give him away. It is getting harder to hide from the peeping Toms of neuroscience.

Inventions of Memory

Chris Chatham of Developing Intelligence Blog has a dynamite posting today on "Visualizing Working Memory." Chris finds that the conventional view of human memory as pictured above, is deficient in several ways, that he details in his post.

Although hugely influential, the model has a few unfortunate shortcomings.

Most importantly, memory is not a static process. Memory decays unless it follows the cycle of learning, encoding, recall, and recoding. In contrast, the classic "modal" model distinguishes storage functions from processing functions - i.e., one is a "black box" and one is a "black arrow." Unfortunately, this distinction is artificial, because the brain contains only arrows: processing (activation) and memory (synaptic efficacy) are two sides of the same coin, and memory itself is a process.

Second, all arrows are not created equal. "Architectural" differences (such as the synaptic efficacy of recurrent connections) among different parts of the brain lead to different processing profiles. These profiles can differ in terms of bandwidth, or in other words, how much information they are capable of holding at a time. Orthogonal to bandwidth, these profiles can also differ in terms of decay rate (or alternately, vulnerability to interference): that is, some regions are capable of maintaining information indefinitely while others are capable of maintaining memories for less than one second.

Third, multiple processing paths require gating functions. Perhaps the largest advantage of removing the "boxes" from the traditional "box and arrow" diagram is that one must become explicit about the functions performed at every step. As a result, such diagrams will be more likely to provide a nice one-to-one relationship between cognitive functions and neuroanatomy. And pure-arrow diagrams remove the need for some elusive "executive functioning" box to coordinate and configure the processes; instead, one need only posit a gating function at the intersection of every arrow with another, in which some process allows information to pass along from one arrow to the next (probably based on dopamine fluctuations).

Then Chris describes his own developing model of memory, which is pictured below and to the left. He has drawn his own model to better reflect the physiological realities of memory as he has discovered them to be.
Sensory Memory. As you can see from the image ...., incoming sensory information has an extremely high initial bandwidth, and a rapid rate of decay, as indicated by the fat, short arrows. Furthermore, there is no rehearsal process, and sensory memory is constantly overwriting itself. This is indicated visually by the multiple arrows which overlap, and quickly diminish in width.

Working Memory. This process slowly transitions into a relatively low-capacity - and low-decay - polymodal short-term/working memory process, as indicated by the smaller width of the arrows in the middle of the diagram. Importantly, the width of this arrow does not shrink over time, indicating that the rate of decay is extremely low; indeed, we can hold somewhere between 4 and 7 items in working memory (depending on modality) without decay.

This short-term/working memory process feeds two unique rehearsal processes, each of which is relatively robust to decay yet limited in bandwidth: an articulatory rehearsal process, as well as an "inner scribe" which supports imagery functions (such as mental rotation). These rehearsal processes essentially "refresh" short-term/working memory with previous information, allowing it to be maintained over time.

Long Term Memory. Finally, the entire diagram rests above the base of one massive arrow that folds back on itself: this represents long-term memory. Long-term memory has an essentially unlimited capacity, as indicated by this arrow's enormous base width, but is subject to decay and interference over time. Items can be retrieved from long-term memory, at which point a "gating function" permits us to actively think about the past (i.e., rehearse it), or to merely let it recur and disappear again from our "mind's eye."

Read the entire article here.

I am not surprised that Chris has referred to work from Gerald Edelman's lab in previous posts. This model reminds me of some of Edelman's concepts of memory, as described by Rosenfeld in The Invention of Memory. Chris has some very impressive postings on his blog. Be sure to look through them.

Nanotube Supercapacitors--Energy Density vs. Power Density

Stories like this and this are plentiful today around the web. It is exciting to see features of nanotechnology incorporated into energy technology, to aid the transition away from a petroleum economy. The new carbon nanotube-supercapacitors will be a huge leap above what is currently available.

If you look at the graphic above, and the graph to the left, you will notice various energy sources plotted with horizontal axis energy density by vertical axis power density. The power density is how much power the device can supply, and the energy density represents how long the device can supply the power. If you will notice, a supercapacitor is high in the top left corner, representing a high power density, but a low energy density. A supercapacitor can supply a lot of power for a short time.

The fuel cells and battery systems have lower power density, but higher energy density. They can supply lower power but for a longer time. A fuel cell car, for example, might go a long distance if supplied with enough fuel, but it would have difficulty accelerating quickly.

We tend to compare energy delivery systems against the internal combustion engine (ICE), which occupies the upper right hand corner--signifying both high energy density and high power density. An ICE powered automobile can go a long distance, AND accelerate quickly. Any practical substitute for the ICE powered auto would need to do the same.

How can you replace the internal combustion engine's superlative qualities? Obviously, there is no single replacement technology that will do the job. The ultracapacitor gives out too quickly, and the fuel cells lack power boost. But there is a possibility that the combination of nano-supercapacitors with advanced fuel cells, or advanced storage batteries, would come close enough to the performance of an ICE. Using cleaner fuels to generate the capacitor/battery charge, and to provide the fuel for the fuel cell, will help the environment tremendously in comparison with the pollution from an ICE.

If you want more graphs to illustrate the contrasting concepts of energy density and power density, go here. This article has more ideas on using nanotech to improve energy storage. This is a general discussion of ultracapacitors (supercapacitors).

See related Al Fin posts here, and here.

Dancing Molecules of Life Extension

It has been known for over a decade that the Insulin Growth Factor 1(IGF-1) signaling was involved in longevity. Reducing IGF-1 signaling in knockout mice led to longer lived mice, but the mice developed as dwarves. Now scientists are learning how to influence the IGF-1 signaling system to prolong lifespan, without interfering with normal growth and development, and other vital systems.

This newsrelease discusses the discoveries of Salk Institute researchers, into the IGF signaling system and its relationship to ageing.

Within a hormone-triggered cascade of molecular signals that plays a crucial for a wide range of physiological functions, researchers for the very first time have identified a protein that functions specifically to extend lifespan and youthfulness -- without disrupting fertility, immunity or the organism's response to stress.

"In past experiments, meddling with this versatile pathway to exploit its beneficial effects on aging and life span inevitably invited a host of problems," says Andrew Dillin, Ph.D., an assistant professor in the Molecular and Cell Biology Laboratory at the Salk Institute for Biological Studies and leader of the study, reported in the March 9 issue of the journal Cell.

The Salk scientists discovered the protein in studies with worms, a commonly used lab model in genetics; since this signaling cascade including the newly identified protein is conserved across many species, including humans, these findings raise the prospect that one day it might be possible to medically tweak this pathway to slow aging and improve the quality of life without harmful consequences to the body.

Read the entire report here. Here is a related SENS abstract.

The intricate dance of interacting molecules described in the report is fascinating, but it is typical of the complexity of biological systems. It is only now, when the tools of science and bioinformatics are growing so sophisticated, that scientists could hope to dig so deeply into the workings of cellular and organismic systems.

Computers Hack Resistant AIDS Virus--HIV Naked Before Researchers

Computers are finding many uses in modern scientific research. Newer, more powerful computers are being programmed to simulate complex proteins and other large molecules and complex systems. One of the proteins being simulated is the HIV protease, a molecule vital to HIV replication inside the cell. Protease inhibitors are commonly used to treat HIV infections, but some HIV strains have grown resistant to protease inhibitors. In order to understand this resistance, researchers have used computer simulations to mimic the particular HIV proteases that are resistant--so that they can find a weakness to target.

For more than a year, researchers watched patiently as a few computer-simulated HIV protease molecules squirmed into more than 15,000 slightly different shapes. In real time, this contortion takes only a fraction of a second. In the end, however, this suspended animation paid off, as the simulations uncovered a potential new drug target to fight drug-resistant AIDS.

Howard Hughes Medical Institute (HHMI) scientists made the discovery while studying how one rare strain of HIV can evade a commonly prescribed class of drugs used to treat the virus that causes AIDS. The strain of HIV contained mutations that are often seen after failure of treatment with protease inhibitors, drugs that block the action of the enzyme protease and prevent the virus from making mature, infective copies of itself. When protease inhibitors fail -- as they often do with a fast-mutating virus like HIV -- new drug targets become vital.

"Recognizing these variations in conformation -- the three-dimensional arrangement of the amino acids that make up a protein -- is the first step in identifying a new drug target," said Alex Perryman, first author of the study published early online in the journal Biopolymers on February 28, 2006.

....Perryman used a computer simulation program called AMBER that performs several different types of calculations. The x-ray crystal structure of the molecule is used as the input, and the various motions and shapes sampled are governed by Newtonian physics, the electric forces among atoms, the complementarity or clash of the different shapes that the enzyme takes, and penalties or bonuses for creating or relieving geometric strain.

The scientists depict the protease enzyme in a brightly colored cartoon, with features that resemble a fat cat face. From the front or the back, the identical halves of the enzyme have an ear and cheek protrusion on each side. (See illustration.) Frayed whiskers even appear to sprout from the bottom. The similarity to a face ends at the top of the molecule, where two flaps open to reveal a cavity. That is where enzymes and other proteins are cleaved into the parts necessary to assemble infectious virus particles. Structural studies of this cavity helped scientists find the original protease inhibitors. Other scientists are trying to design drugs to bind to the whiskers and or to lock down the flaps by binding to their top.

Perryman's first results, which were published in the April 1, 2004, issue of Protein Science, showed that the mechanism of drug resistance seemed to involve the motion of the flaps. More specifically, the double-mutant virus displayed larger flap motions, especially at the tips. These larger movements seem to make it more difficult for the current drugs to function, since they must force the flaps to close and remain closed in order to prevent the enzyme from working. It probably takes more energy for the drugs to close the more mobile flaps of the mutant.

Perryman and his colleagues also observed that the flaps opened in a seesaw motion on each side, pinching the "cheek and "ear" together. That observation suggested to them that a small molecule might be able to wedge between the ear and cheek, blocking the flap opening.

"Some drugs act by binding to the active site of a target molecule, such as the site that an enzyme normally uses to catalyze reactions," McCammon said. "But increasingly, scientists are finding that other binding sites can be important. For HIV/AIDS, an important class of drugs called non-nucleotide inhibitors for reverse transcriptase typically bind at such alternate sites."

Once Perryman had a hypothesis to test in a second round of simulations -- the proposed mechanics of the protease enzyme's nanomachinery--he used artificial restraints in the computer program to block the flaps from opening by expanding the gap between "ear" and "cheek." A new type of drug that binds there and controls flap motion could enhance the ability of the current protease inhibitors to bind to the active site, or it could offer a new way of inhibiting protease activity from afar by itself, Perryman suggested.

This type of computer simulation can certainly be used to locate a wide range of molecular targets. Read the entire report, including other potential target molecules being simulated, here.

Conventional von Neumann computers are actually pretty stupid. But they are very fast calculators, and can model some complex systems. Computers are getting faster all the time, and more sophisticated designs incorporating massive parallelism and neural net architectures can do some impressive things. Expect a lot more in the future.

Collapse of Jared Diamond: A Modern Eco-fantasy

Jared Diamond is a talented writer who has had some success in the publishing world. His recent book Collapse, chronicles the rise and fall of the unfortunate Polynesian tribes of Easter Island, off the coast of Chile. Diamond's sad tale of eco-collapse has been taken up by Peak Oilers and other modern prophets of eco-doom as a cautionary tale for our own time. There is just one problem--Diamond's story may be turning out to be more fantasy than fact.

JD at Peak Oil Debunked Blog has looked into the story behind the story, and suggests the whole thing is a myth. JD links to this article from yahoonews:


Crucial to the conventional account of events on Easter Island is the time when settlers first arrived. If colonization didn't begin until 1200 AD, then the island's population wouldn't have had time to swell to tens of thousands of people.

"You don't have this Garden of Eden period for 400 to 800 years," Hunt said in an accompanying Science article. "Instead, [humans] have an immediate impact."

Also, the few thousand people Europeans encountered when they first arrived on Easter Island might not have been the remnants of a once great and populous civilization as widely believed. The researchers think a few thousand people might have been all the island was ever able to support.

"There may not have actually been any collapse," Lipo told LiveScience. "With only 500 years, there's no reason to believe there had to have been a huge [population] growth."

Europeans and rats to blame

The researchers also dispute the claim that Easter Island's human inhabitants were responsible for their own demise. Instead, they think the culprits may have been Europeans, who brought disease and took islanders away as slaves, and rats, which quickly multiplied after arriving with the first Polynesian settlers.

"The collapse was really a function of European disease being introduced," Lipo said. "The story that's been told about these populations going crazy and creating their own demise may just be simply an artifact of [Christian] missionaries telling stories."

The story of European disease causing disaster in a naive population is very familiar to any student of world history. Diamond himself thoroughly discussed the phenomenom in his bestseller, Guns Germs and Steel.

In science, it is only natural for theories to be proposed, then receive challenges, then either overcome the challenges--or be discarded as wrong. When politics gets caught up with science, the stakes widen and the participants are less likely to let go of a bad theory. The story of Easter Island is still being scrutinized, but it would not be surprising for Diamond's Collapse to be a modern anthropological fantasy, much as Margaret Meade's Samoan tales.

Sex Differences in the Brain

Male and female brains are anatomically and functionally different, statistically. This is well established, scientifically, although politically it is a combination of quicksand and dynamite. Doreen Kimura is one of several prolific women cognitive scientists who are brave enough to buck the political storm in order to pursue scientific truth. Camilla Benbow is another.

In this article published in Sexualities, Evolution and Gender, Kimura plainly lays out the basic argument and evidence.

Many reliable anatomical brain differences have been found to differentiate men and women, from basic structures such as the hypothalamus, to differences in systems connecting the two hemispheres, such as the anterior commissure. Some of these have been reviewed in my book......We don’t yet know the significance of such differences for cognitive function, but to describe them as fiction is to deny the careful investigations of many respected scientists (e.g., Allen and Gorski 1990, 1991; Allen, Hines, Shryne and Gorski 1989; Allen, Richey, Chai and Gorski 1991). Although we now have a fair understanding of how brain systems work in mediating certain cognitive functions such as memory, language, and the like, we are still far from understanding how individual differences, the variation in such functions from one type of person to another, are mediated by the brain. However, it must follow that if two groups (such as males and females, left-handers and right-handers, or masculine and feminine gender types) differ reliably in some behaviour not simply dependent on physical differences, then their nervous systems must also differ in some way. Where else could the behavioural differences reside? This is just as true of learned as of unlearned behaviours. Brain differences underlying cognitive differences need not, however, be visible in simple structural features. They may take the form of differing organizational mechanisms not apparent by simply viewing the external brain.

This Scientific American article by Kimura presents the argument more methodically, and at greater length.

Men and women differ not only in their physical attributes and reproductive function but also in many other characteristics, including the way they solve intellectual problems. For the past few decades, it has been ideologically fashionable to insist that these behavioral differences are minimal and are the consequence of variations in experience during development before and after adolescence. Evidence accumulated more recently, however, suggests that the effects of sex hormones on brain organization occur so early in life that from the start the environment is acting on differently wired brains in boys and girls. Such effects make evaluating the role of experience, independent of physiological predisposition, a difficult if not dubious task. The biological bases of sex differences in brain and behavior have become much better known through increasing numbers of behavioral, neurological and endocrinological studies.

Read the entire article here, it is quite fascinating.

This is a brief list of scholarly research supporting the concept of "innate differences" in neuroanatomy and cognition in males and females. It is a very abbreviated list, but it serves to introduce the evidence. For a much longer list, consult this reference list from one of Kimura's articles. Scroll down to the list, and continue scrolling. There are 111 citations, and that list is far from complete.

I have posted on this topic before--here, here, and here.

The research continues, and the weight of research--new and old--points to significant cognitive sex differences, or if you prefer, gender differences or gender disparities.

Politically, this is not a popular topic, and politically inclined "scientists" will more easily cling to the political line. It is difficult to get funding for this type of research, and publishing in some mainstream journals is difficult. Even university presidents can fall from grace if they forget the politically correct stance, and deviate from it. This has not discouraged the very persistent women and men of cognitive science.

Neither men nor women are superior to the other as groups. Both groups have statistical strengths and weaknesses. A wise society will seek to understand its members, rather than try to sweep under the rug any scientific findings that are inconvenient to a dominant political viewpoint.

Addendum: This Guardian article by Simon Baron-Cohen contains a link to a test you can take to determine if you have a male brain or a female brain. Just looking at your genitalia or your chromosome map will not tell you that. Regardless of your chromosomes, your brain has a mind of its own, perhaps of a different gender than your body. Are you willing to find out?

Metabolic Syndrome: Mitochondria in Diabetes and Heart Disease

In a previous post, I discussed the relationship of mitochondrial dysfunction to neurological disorders such as Alzheimer's, Huntington's, Parkinson's disease, and ALS. In another post, I discussed mitochondrial biomarkers of aging. Now evidence is mounting that mitochondria are involved in metabolic syndrome, including diabetes, obesity, heart disease, and related disorders including hypertension and hyperlipidemia. This syndrome accounts for millions of deaths around the world yearly, and accounts for the ongoing disability of many millions more yearly.

In this JCI research article, scientists from Howard Hughes Medical Institute, and Yale University School of Medicine discovered that there were 38% fewer mitochondria in the muscles of healthy but insulin resistant offspring of diabetic parents. This reduction in muscle mitochondria apparently led to a 60% increase in intramyocellular fat, inside the muscle cells, which likely contributes to insulin resistance, and eventually type 2 diabetes. That is an intriguing finding. Read the entire article online here.

Furthermore, Douglas Wallace at UCI has received a sizable grant to study how genetic changes in mitochondria can lead to metabolic disorders, such as type 2 diabetes. According to this newsreport:

"Our receipt of this prestigious Doris Duke Charitable Foundation award is the direct consequence of UCI's vision of becoming a world leader for the new biomedical discipline of mitochondrial medicine," said Wallace, director of the Center for Molecular and Mitochondrial Medicine and Genetics (MAMMAG) at UC Irvine and National Academy of Sciences member.

Mitochondrial medicine offers innovative new perspectives and approaches for addressing the common age-related diseases associated with the metabolic syndrome as well as with forms of blindness, deafness, movement disorders and dementias -- clinical problems that remain elusive to traditional biomedical concepts and approaches.

With the Doris Duke Clinical Interfaces Award -- which will provide funding for five years -- Wallace will lead a multidisciplinary team of UCI researchers, which include physicians Dr. Ping Wang, Dr. Lee-Ming Chuang and Dr. Jay Gargus; biomedical engineer Bruce Tromberg, director of the Beckman Laser Institute; and atmospheric chemists Donald Blake and F. Sherwood Rowland, who received the Nobel Prize in Chemistry in 1995.

The team will study genetic variation in the DNA of mitochondria and its association with the various symptoms of the metabolic syndrome. Wang, Chuang and Gargus will collect mitochondrial samples from metabolic syndrome patients of Chinese heritage in Taiwan and in Southern California. Wallace's team at MAMMAG then will conduct extensive molecular and biochemical studies of these samples to see if variations in mitochondrial DNA as well as environmental factors affect individual predisposition to the clinical symptoms of metabolic syndrome.

Read more here.

Because of the intimate connection to both aging and many debilitating and fatal diseases, mitochondrial medicine presents a tremendous opportunity. Reversing the age-related changes in mitochondria is one of the seven prime interventions of the SENS rejuvenation approach.

Hat tip to New Hope Cancer Blog.

China's Impending Fall

The growth in China's economy over the past two decades has been very impressive. One might be forgiven for assuming that China will soon overtake the US as world economic leader. Is it time to brush up on your Mandarin and Cantonese? Should you think about sending your children to Peking University? Maybe not. Foreign Policy journal has a short piece by Minxin Pei entitled "The Dark Side of China's Rise."

The only thing rising faster than China is the hype about China. In January, the People’s Republic’s gross domestic product (GDP) exceeded that of Britain and France, making China the world’s fourth-largest economy. In December, it was announced that China replaced the United States as the world’s largest exporter of technology goods. Many experts predict that the Chinese economy will be second only to the United States by 2020, and possibly surpass it by 2050.

Western investors hail China’s strong economic fundamentals—notably a high savings rate, huge labor pool, and powerful work ethic—and willingly gloss over its imperfections. Businesspeople talk about China’s being simultaneously the world’s greatest manufacturer and its greatest market. Private equity firms are scouring the Middle Kingdom for acquisitions. Chinese Internet companies are fetching dot-com-era prices on the NASDAQ. Some of the world’s leading financial institutions, including Bank of America, Citibank, and HSBC, have bet billions on the country’s financial future by acquiring minority stakes in China’s state-controlled banks, even though many of them are technically insolvent. Not to be left out, every global automobile giant has built or is planning new facilities in China, despite a flooded market and plunging profit margins.

And why shouldn’t they believe the hype? The record of China’s growth over the past two decades has proved pessimists wrong and optimists not optimistic enough. But before we all start learning Chinese and marveling at the accomplishments of the Chinese Communist Party, we might want to pause for a moment. Upon close examination, China’s record loses some of its luster. China’s economic performance since 1979, for example, is actually less impressive than that of its East Asian neighbors, such as Japan, South Korea, and Taiwan, during comparable periods of growth. Its banking system, which costs Beijing about 30 percent of annual GDP in bailouts, is saddled with nonperforming loans and is probably the most fragile in Asia. The comparison with India is especially striking. In six major industrial sectors (ranging from autos to telecom), from 1999 to 2003, Indian companies delivered rates of return on investment that were 80 to 200 percent higher than their Chinese counterparts. The often breathless conventional wisdom on China’s economic reform overlooks major flaws that render many predictions about China’s trajectory misleading, if not downright hazardous.

Behind the glowing headlines are fundamental frailties rooted in the Chinese neo-Leninist state. Unlike Maoism, neo-Leninism blends one-party rule and state control of key sectors of the economy with partial market reforms and an end to self-imposed isolation from the world economy. The Maoist state preached egalitarianism and relied on the loyalty of workers and peasants. The neo-Leninist state practices elitism, draws its support from technocrats, the military, and the police, and co-opts new social elites (professionals and private entrepreneurs) and foreign capital—all vilified under Maoism. Neo-Leninism has rendered the ruling Chinese Communist Party more resilient but has also generated self-destructive forces.

To most Western observers, China’s economic success obscures the predatory characteristics of its neo-Leninist state. But Beijing’s brand of authoritarian politics is spawning a dangerous mix of crony capitalism, rampant corruption, and widening inequality. Dreams that the country’s economic liberalization will someday lead to political reform remain distant. Indeed, if current trends continue, China’s political system is more likely to experience decay than democracy. It’s true that China’s recent economic achievements have given the party a new vibrancy. Yet the very policies that the party adopted to generate high economic growth are compounding the political and social ills that threaten its long-term survival.


Command and Control

After a quarter century of gradual economic reform, has China succeeded in transforming its old command economy into a genuine market economy? Not nearly as well as most people would guess. Although China was one of the earliest socialist economies to begin serious reform, recent data on the country’s regulation, international trade, fiscal policy, and legal structure place China in the bottom third of 127 countries surveyed for economic freedom, below most Eastern European countries, India and Mexico, and all of its East Asian neighbors, save Burma and Vietnam.

The Chinese state remains deeply entrenched in the economy. According to official data for 2003, the state directly accounted for 38 percent of the country’s GDP and employed 85 million people (about one third of the urban workforce). For its part, the formal private sector in urban areas employed only 67 million people. A research report by the financial firm UBS argues that the private sector in China accounts for no more than 30 percent of the economy. These figures are startling even for Asia, where there is a tradition of heavy state involvement in the economy. State-owned enterprises in most Asian countries contribute about 5 percent of GDP. In India, traditionally considered a socialist economy, state-owned firms generate less than 7 percent of GDP.

Read the entire four page article here.

I have posted on this topic here, and here.
It is always good to maintain a skeptical view of anyone who proposes an indefinite continuation of any trend. Most things behave cyclically, particularly in the field of economics.

In the short run, China is running a huge accounts surplus, with lots of cash. If China can reform its banking system, and thus its corrupt government practices, it may be able to maintain its fabulous run a bit longer.

Cognitive Psychology and the Study of Human Intelligence

A big tip of the hat to Kevin at Intelligence Testing Blog, for his posting on this article in the European Journal of Cognitive Psychology by Cesare Cornoldi at the University of Padova, Italy.

This evening I stumbled across a wonderful/glorious synthesis article in the European Journal of Cognitive Psychology by C. Cornoldi, the editor of a special issue devoted to the contributions of cognitive psycholgoy to the study of intelligence. The complete reference is:

* Cornoldi, C. (2006). The contribution of cognitive psychology to the study of human intelligence. European Journal of Cognitive Psychology, 18 (1), 1-17

Cornoldi provides a concise historical and comtemporary overview of psychometric theories of intelligence, appropriately emphasizing the work of Cattell-Horn and Jack Carroll. This overview of the psychometric models is alone worth reading the article. More importantly, Cornoldi then tackles, in broad strokes (which is what many of us need to make the leap; or to ascertain if we have been on the correct path in our own conceptual leaps), how cognitive psychology can address a serious problem with hierarchical psychometric theories (like CHC).

Kevin then goes on to quote Cornoldi:

"In particular hierarchical theories based on psychometric evidence pose one serious problem: It is not clear to which psychological processes the highest stratum or components correspond. Cognitive Psychology has isolated powerful cognitive mechanisms that appear to be critical predictors of high level intelligence and underlie different cognitive tasks. Reference to these mechanisms could help in the specification of the most central components of human intelligence."

Cornoldi then proceeds to summarize the cognitive psychology research that has been zeroing in on the contsructs of of working memory (Gsm-MW), processing speed (Gs), and executive function...as explanatory mechanisms necessary to understand human intelligence and to allow for the integration of psychometric and information processing models. He also provides a coherent synthesis of various brain imaging studies and how they relate to all of this (e.g., the neural efficiency hypothesis).

In my brief overview of the article, my opinion matches Kevin's--it is an excellent review of the subject. Thanks for the information, Kevin.

Is This Sexist? Why not?

In North America, women make up about 60% of the student population in higher learning institutions. Women are doing very well in education, and it is not clear that there are any significant institutional barriers to their progress in any field whatsoever. Perhaps all that is different in Europe, but I doubt it.

Here is an interesting project aimed at bringing more women into nanotechnology. It is being funded by the EU. Is focusing on one particular gender or ethnic group a valid use of public funds? If the same outreach were directed toward males, would it be accepted?

The WomenInNano project aims to encourage women to take a more active interest in science, and especially nanotechnology, using experienced researchers in the field as ambassadors.

Eleven women from Germany, Romania, Sweden, Spain, Slovenia, the UK, Bulgaria, Italy and France will act as 'ambassadors for women and science': The ambassadors believe that women scientists in many countries lack contact with role models, which makes it more difficult for them to achieve their ambitions. The team plan to publicise their work in order to provide the necessary role models and demonstrate that it is possible to be a senior figure in science and also be a woman. The ambassadors intend to:

- encourage women to work in nanotechnology;
- attract young people to the field;
- build networks of women already working in nanotechnology;
- encourage women to participate in EU programmes;
- develop gender equality in scientific research;
- build a dialogue between science and society.

Dr Annett Gebert from the Leibniz-Institute for solid state and materials research in Dresden is the coordinator for the project, and talked to CORDIS news. 'I am strongly involved in the scientific community. Our industry is dominated by males, at all levels, including decision-making, conference organisation, project funding, etc. We also feel that younger girls do not consider the natural sciences as a career path. Girls feel that they have no talent in this field, and we want to address this. After talking about this with colleagues, we decided to do something about it.'

CORDIS News asked Dr Gebert why gender stereotypes persist today. 'I am from Eastern Germany, and so my history is a little different from my colleagues, but I feel it is a traditional thing, and not driven by politics. Society looks at what roles people should play, and this pushes women into the social sciences, but not natural or engineering sciences,' she said.

The project is grouped into three stages. In stage one, the team will establish the project's framework, identify competencies in the field and draw up a list of women working in nanotechnology throughout Europe.

In stage two, the media campaign begins, with public events, workshops and visits to schools. The third and final stage involves meeting decision-makers to develop best practice in the recruitment of researchers.

The 30-month project will receive 500,000 euro in funding under the Science and Society priority of the Sixth Framework Programme (FP6). The contract was signed in 2006, and the project is already into stage one.

For further information, please visit:
http://www.ifw-dresden.de/women-in-nano/

Might it be more appropriate to allocate funds in recruiting well qualified students--regardless of gender or ethnicity , rather than focusing on one particular group--particularly if you are using general tax funds in your promotion?

Update:
Here is a related posting dealing with an investigation into the shortage of women at top positions in academic medicine. Given that within the past decade or so, women have achieved virtual parity in admissions to medical schools in North America, one might expect the numbers to correct themselves with time. Certainly in Obstetrics, women are virtually taking over the entire field. Given the current political climate of political correctness, it is not clear if the investigators are aware of the inevitable time lag involved between parity at the medical school level, and parity at the top levels of academic medicine.

Hotter Than the Sun--Z Pinch Points to Small Nuclear Fusion Generators

In an earlier posting here, I briefly mentioned the Z Pinch machine at Sandia Labs. Now the Z machine has achieved plasma temperatures hotter than the interior of a star. This finding suggests that smaller than predicted fusion generators may be possible.

ALBUQUERQUE, N.M. -- Sandia's Z machine has produced plasmas that exceed temperatures of 2 billion degrees Kelvin -- hotter than the interiors of stars.

The unexpectedly hot output, if its cause were understood and harnessed, could eventually mean that smaller, less costly nuclear fusion plants would produce the same amount of energy as larger plants.

The phenomena also may explain how astrophysical entities like solar flares maintain their extreme temperatures.

The very high radiation output also creates new experimental environments to help validate computer codes responsible for maintaining a reliable nuclear weapons stockpile safely and securely -- the principle mission of the Z facility.

"At first, we were disbelieving," says Sandia project lead Chris Deeney. "We repeated the experiment many times to make sure we had a true result and not an 'Ooops'!"

The results, recorded by spectrometers and confirmed by computer models created by John Apruzese and colleagues at Naval Research Laboratory, have held up over 14 months of additional tests.

A description of the achievement, as well as a possible explanation by Sandia consultant Malcolm Haines, well-known for his work in Z pinches at the Imperial College in London, appeared in the Feb. 24 Physical Review Letters.

Sandia is a National Nuclear Security Administration laboratory.

What happened and why?

Z's energies in these experiments raised several questions.

First, the radiated x-ray output was as much as four times the expected kinetic energy input.

Ordinarily, in non-nuclear reactions, output energies are less -- not greater -- than the total input energies. More energy had to be getting in to balance the books, but from where could it come?

Second, and more unusually, high ion temperatures were sustained after the plasma had stagnated -- that is, after its ions had presumably lost motion and therefore energy and therefore heat -- as though yet again some unknown agent was providing an additional energy source to the ions.

Sandia's Z machine normally works like this: 20 million amps of electricity pass through a small core of vertical tungsten wires finer than human hairs. The core is about the size of a spool of thread. The wires dissolve instantly into a cloud of charged particles called a plasma.

The plasma, caught in the grip of the very strong magnetic field accompanying the electrical current, is compressed to the thickness of a pencil lead. This happens very rapidly, at a velocity that would fly a plane from New York to San Francisco in several seconds.

At that point, the ions and electrons have nowhere further to go. Like a speeding car hitting a brick wall, they stop suddenly, releasing energy in the form of X-rays that reach temperatures of several million degrees -- the temperature of solar flares.

The new achievement -- temperatures of billions of degrees -- was obtained in part by substituting steel wires in cylindrical arrays 55 mm to 80 mm in diameter for the more typical tungsten wire arrays, approximately only 20 mm in diameter. The higher velocities achieved over these longer distances were part of the reason for the higher temperatures.

(The use of steel allowed for detailed spectroscopic measurements of these temperatures impossible to obtain with tungsten.)

Haines theorized that the rapid conversion of magnetic energy to a very high ion plasma temperature was achieved by unexpected instabilities at the point of ordinary stagnation: that is, the point at which ions and electrons should have been unable to travel further. The plasma should have collapsed, its internal energy radiated away. But for approximately 10 nanoseconds, some unknown energy was still pushing back against the magnetic field.

Haines' explanation theorizes that Z's magnetic energies create microturbulences that increase the kinetic energies of ions caught in the field's grip. Already hot, the extra jolt of kinetic energy then produces increased heat, as ions and their accompanying electrons release energy through friction-like viscous mixing even after they should have been exhausted.

High temperatures previously had been assumed to be produced entirely by the kinetic flight and intersection of ions and electrons, unaided by accompanying microturbulent fields.

Z is housed in a flat-roofed building about the size and shape of an aging high-school gymnasium.

This work has already prompted other studies at Sandia and at the University of Nevada at Reno.

The Z pinch has figured in some fascinating speculation, concerning potential nuclear fusion, and hyperspace star drives. Achieving temperatures this high should stimulate a good deal of further research. Where it eventually leads is impossible to say.

Dynamic Cancer Protein and Flexible tRNA

Here are two interesting research items. First, from the biological researcher who won the Sexiest Name of 2005 Biolabs Contest, we learn about an exciting new method of monitoring the dynamic movement of nuclear protein in a cell. According to Purdue's Sophie Lelievre,

"When you look at cells that don't yet have a specific function - aren?t differentiated, compared to fully differentiated cells, which are now capable of functioning as breast cells - the organization of proteins in the nucleus varies tremendously," Lelièvre said. "Then looking at how the proteins in malignant cells are distributed, it's a totally different pattern compared to normal differentiated cells."

The research team's study on the imaging technique and its use in 3-D mapping and analysis of nuclear protein distribution is published this week online in Proceedings of the National Academy of Sciences. Ultimately, the scientists want to use the technique to determine not only if a lesion is malignant but also the exact kind of cancer, how likely it is to spread and the most appropriate treatment for a particular patient.

"The major problem exists in the pre-malignant stages of abnormal cells in determining whether cancer will develop, what type and how invasive it will be," Lelièvre said. "The decision then is whether to treat or not to treat and how to proceed in these preliminary stages because only a certain percentage of these patients will ultimately develop cancer.

"We want to use this technique to identify subtypes of cells within lesions that potentially could become more aggressive forms of cancer."

Very exciting news for cancer research. I wish them well in their rapid development of a workable method for hospital labs.

The second report sheds light on why sometimes A-U and G-U pairs in transfer RNA are sometimes mismatched as A-C or G-U pairs in the nucleotide chain. William McClain at UW Madison explains:

Scientists have long known that transfer RNA - which adds amino acids to a growing chain during protein synthesis - holds a surprising secret when it comes to its base pairs: occasionally, instead of the expected A-U or G-C pairs, there exists instead a mispair of A-C or G-U. However, the role and importance of mispairs has never been well understood, says McClain.

McClain, who has spent his career investigating how transfer RNA selects specific amino acids during protein synthesis, was curious about how mispairs affect the function of RNA. In the study reported in PNAS, he altered the position of a G-U mispair in a bacterial plasmid - by literally moving the mispair up and down the molecule’s cloverleaf structure -- and demonstrated that the mutation increases the ability of the RNA to accept amino acids and improves its efficiency at moving through the ribosome, the cellular organelle where translation occurs. In fact, removing the mispair or repairing it to make it a correct matched pair inactivated the molecule completely.

"The wobble pairs fit together at an angle and the bonds are much less stable than matched pairs," McClain explains. "This makes the molecule more likely to come undone, and therefore more reactive."

This is crucial because DNA and RNA molecules are not the static, flat images that are depicted in textbooks, McClain notes. "They flex, move and come apart all the time," he says. "And mispairs promote this movement. My interpretation is that nature conserves these mispairs because they enhance protein synthesis."

This research is published in NAS Proceedings.

The textbooks can never keep up with the research. Even the journals cannot keep up. Only electronic information methods can even try. The quantity of information being generated by modern bioresearch labs around the world is immense. Correlating and making sense of it all is virtually impossible. I suspect that many information scientists have got their hopes pinned on the development of more capable machine intelligences, to data mine the research, sort it out, interpret it, then make suggestions for fruitful areas of future investigation. Because it is not just bioresearch that is exploding, it is science and technology research in general.

This is the legacy of Aristotle, Avicenna, Galileo, and Newton. It is a prolific but fragile generator of knowledge. It rests upon a narrow foundation. That is the subject of this blog, the foundation that makes the knowledge generation possible. Many things try to destroy the foundation, from religion to mass media to political correctness. But the foundation supports us all, including those who try to destroy it.

Flunking at Math

There are primitive tribes whose members cannot count past three. Within their own environment, they function well. A member of a modern industrial society with that incapacity would be diagnosed with dyscalculia--analogous to dyslexia. Not surprisingly, there are specific regions of the brain that must function well to avoid dyscalculia--just as specific brain dysfunction is responsible for dyslexia.

This physorg.com news report discusses the research that located the dyscalculia brain regions, using brain imaging.


It is the discovery of the part responsible for counting or numerosity that is a major finding for Professor Brian Butterworth, who also published ‘The Mathematical Brain’ and is an authority on dyscalculia. He believes his finding is the key to diagnosis of dyscalculia.

Professor Butterworth, of the UCL Institute of Cognitive Neuroscience, said: “Now that we know where to look for the differences in brain activation between those who suffer from dyscalculia and those who don’t have the learning disorder, we will be able to come up with better diagnosis and insights.

“Some years ago, my colleague, Professor Uta Frith, found the part of the brain responsible for dyslexia. That discovery has led to a much better understanding of the condition, promising better diagnosis and treatment. We hope our discovery will lead to similar insights into dyscalculia – a similar learning disability but one that is still relatively unknown to the general public.”

.... Professor Butterworth said: “There are two ways of counting things. Imagine assessing how many men versus women are in a room by counting them at the door as they enter the room, let’s say three women and four men, and then try assessing the difference by looking at the room when everyone is present. Both methods of assessing the number of people should produce the same result. Instead of assessing numbers of men and women, subjects saw blue and green squares shown in a sequence or blue and green squares shown on screen at the same time. We found that both methods activated the same brain region.

“But when we showed subjects the colours merged and appearing either as a continuously changing square or as one cloudy coloured rectangle different results were produced and a different brain network lit up. This is because the brain was no longer able to try to count the objects. Instead it had to assess how much colour was in the block and guess whether there was more of one colour or another.

“By comparing these two types of stimulus, we identified the brain activity specific to estimating numbers of things. We think this is a brain network that underlies arithmetic and may be abnormal in dyscalculics.”

Read more here.

In the modern world, a person without basic counting skills is lost. Fortunately, most people are able to count change from a purchase, and pay their bills accurately. More advanced math skills are going to be more difficult to locate with brain imaging, but perhaps not impossible. Real time functional brain imaging is still in its early stages. There is much more to learn about functional brain locations and interaction between brain centers.

Our interest here at this blog is generally in the more advanced math skills necessary for scientific and technological progress. A shortage of those skills in a society would leave it helpless before the future. Statistically, more males score in the upper tail of the distribution in math than females, particularly at the very highest levels. A woman has not won the highest math honor, the Fields Medal. Most top professors of math and physics at the elite schools are men, as expected from the research. It would be best if we could keep politics out of this matter, since the scientific and technological challenges to society are so pressing. Unfortunately, the Lawrence Summers affair illustrates the type of self-defeating and vicious infighting that continues to waste so many resources.

Biological Nanomachines--First in their Class

Life as we know it would not exist if not for incredible numbers of tiny bio-machines, molecular sized powerhouses that work at fantastic speeds, and with amazing efficiencies. I recently discovered a fine nano-blog by Will Ware, a software engineer who writes software for nano-engineering and development. This past New Year's Eve morning, Will wrote a fine posting on "Nanomachines in Nature," that I recently discovered. Will lets us know that there are indeed people in the nanotech culture who admire nano-biomachines, and who are willing to learn from them.

Kinesin and dynein are proteins that move along a microtubule and can drag along a mechanical load (another molecule). They are among several molecular motors found in nature. Another example is the flagella that push bacteria around in pond water, driven by a motor that looks like it came from a mechanical parts catalog.

....Some people are using these molecular machines to plan nanotechnology roadmaps, and there has been some laboratory progress. We won't have real nanotechnology any time soon, but these are excellent steps in that direction. Biomechanics hints at a lot of interesting things we can do with available cellular mechanisms.

To people thinking about the long term, as I like to do, these efforts are stepping stones. We'll use them to build tools, and use those tools to build other tools, with the eventual goal of a manufacturing infrastructure that permits us to build large rationally-designed products to atomic precision.

I am encouraged to see such enthusiasm for bio-nano from Will, and others like him. Read Will's entire posting, with great links and a fine graphic, here.

There has been a bit of discussion at The Speculist, and at Responsible Nanotechnology, about two previous postings "Nanotechnology Learns from Biology" and "Holy Grail of Enzymatics." Will's posting adds quite a bit to that discussion.

Update: Here is a link to an excellent set of publications from Bionano.neu.edu. It comes from one of the links obtained from Wills post above. There is far more activity on this front than I previously realised. Thanks again to Will Ware.
For anyone interested in the NSTI Bio Nano conference in Boston this May, here is the website for that event.

Update 13 March 2006: Here is a bizjournal article discussing the explosion of patent applications for bio-nano.

Edelman's Darwin VIII Discovers Neural Synchrony

Chris Chatham at Develintel Blog has added another post in his series on neural synchrony and oscillatory activity. The latest one deals with experiments in artificial intelligence from Gerald Edelman's lab, the complex neural net machine named Darwin VIII. Interestingly enough, Darwin VIII demonstrated synchronous activity during training, so long as the model's connections were left intact. The following is a bit technical:

The details of the implementation are as follows: the physical anatomy of Darwin VIII includes a CCD camera for vision, microphones for audition, infrared detectors for navigation, effectors for movement, and a 12 unit Beowulf cluster for the number crunching. Darwin's synthetic neuroanatomy consists of more than 53,000 units and over 1.5 million synaptic connections, with layers corresponding to V1, V2, V4, inferotemporal cortex (IT), superior colliculus, and ventral tegmental area (including a dopamine-like neuromodulatory system, based on an algorithm similar to temporal differences). For simplicity, the primary visual layer responds preferentially to green, red, horizontal, vertical and diagonal lines; all subsequent visual layers are bidirectionally connected and have increasingly large receptive fields (until IT, in which representation is non-topographic). The robot's orientation is guided by a topographic activity map in the superior colliculus layer, which also receives direct excitatory input from tones with specific amplitude and frequency picked up by the stereo microphones (this represents an a priori drive or bias for "target tones"). The dopamine system modulates synaptic efficacy between itself and IT, as well as between IT and superior colliculus, with effects that last several processing cycles. All areas contain both recurrent excitatory connections and lateral inhibition.

Neural activity was modeled via a mean firing rate model, with one small addition: a phase parameter "provides temporal specificity without incurring the computational costs associated with modeling of the spiking activity of individual neurons in real-time." All synaptic connections were modeled as phase-dependent, such that new phases are chosen at random unless the a unit's presynaptic input phases surpass a threshold, after which phase changes are first sent through a nonlinear "squashing" function and then scaled by a phase learning rate. This implementation causes postsynaptic phase to be influenced in the direction of the most active presynaptic units' phases. Synaptic efficacy is modified both with traditional firing-rate dependent credit/blame assignment, as well as with phase-dependent credit/blame assignment, in which units with tightly coupled phases are subject to potentiation, and those with uncoupled phases are subject to depression.

The experiment was divided into training and testing phases; during training, Darwin autonomously explored an environment consisting of one target item and three distractor items which share multiple attributes with the target item. For example, if a red diamond was the target, red squares and green diamonds would be distractor items. At the beginning of each training phase (which was repeated for three different Darwin "subjects"), all weights were randomized. Throughout the training phases, sounds were emitted from speakers which caused Darwin to orient towards the target. In the testing phase, these speakers are turned off and Darwin is allowed to explore its environment for another 15,000 cycles.

The authors measured Darwin's ability to locate the targets in its environment: each simulated subject was able to do so over 80% of the time. As the authors point out, " It should be noted that successful performance on this task is not trivial. Targets and distracters appeared in the visual field at many different scales and at many different positions as Darwin VIII explored its environment. Moreover, because of shared properties, targets cannot be reliably distinguished from distracters on the basis of color or shape alone."
At each timestep in the experiment, the researchers took a "snapshot" of the activity in every unit, and the weight of every connection. Results showed self-synchronization among neurons with recurrent connections within only 15 cycles; when reentrant connections were lesioned, no synchrony occurred within 10,000 cycles. Most importantly, multiple simultaneous synchronous firing patterns were observed within the active units of both IT, superior colliculus, and the value system (dopamine) layer, with both more synchrony and higher firing rates in circuits corresponding to targets or target features; in their own words, "the simultaneous viewing of two objects clearly evoked two distinct sets of circuits that were distributed throughout the simulated nervous system and distinguished by differences in the relative timing of their activity." In other words, multiple polyphase patterns of synchronous firing can self-organize inside a network with the proper architecture and environment.

You can find more information from Edelman's group here.

Thanks to Chris for alerting us to this remarkable finding. Neural net models apparently show emergent behaviour similar to that of actual neuron groupings in brains. Will the scientists find more similarity the more faithfully their models copy biological brains? Quite possibly. Then what? Then you might find more neuroscientists using neural net models to test their theories of brain function. When the information flows in both directions, the potential for important breakthroughs increases.

Remarkable Advance in Cell Culture, Tissue Engineering

Tissue engineering has long been in need of biological "fill material." Blood vessels, nerves, and other small structures lie in a "matrix" of tissue that supports it and facilitates necessary growth of biological structures. A recent news report details the creation of a new type of "bio-gel" that may suit the need.

Scientists at The University of Manchester have created a new type of 'bio-gel' which provides a pH neutral environment for culturing cells in 3D, as published in the journal Advanced Materials (March 2006).

The gel is the first pH neutral material made from combinations of dipeptides (pairs of amino acids) to provide an environment in which cells can be cultured under physiological conditions.

Uniquely, the gel mimics the properties of cell scaffolds which naturally occur in the body and has potential applications for wound healing and tissue engineering.

Cell scaffolds, known as the extra cellular matrix (ECM), are naturally produced by the body to grow new cells in order to repair damaged tissue. Like the ECM, the gel acts like a scaffold in which cells can grow.

In their paper, 'Nanostructured Hydrogels for Three-Dimensional Cell Culture Through Self-Assembly of Fluorenylmethoxycarbonyl-Dipeptides', Dr Rein Ulijn and collaborators describe how the gel is created through a process of self-assembly.

Dr Ulijn said: "We have used combinations of modified dipeptides which act like building blocks and spontaneously assemble into nanometer sized fibres when exposed to physiological conditions, to create a fibrous gel-like structure in which cells can be cultured. Because this material is made up of 99% water and is pH neutral, it is compatible with biological systems.

"By using dipeptide building blocks instead of much larger oligo-peptides used by other researchers, we have greater control over the fibrous architecture and the physical properties of the gels. These materials offer us great potential for future applications in wound healing and regenerative medicine."

Dr Ulijn and his collaborators have successfully cultured cartilage cells using the gel. They found that both the properties of the gels formed and the cell response to the gels could be controlled by using different combinations of di-peptides. The team recently received a £630k award from EPSRC to develop the gels further.

This is good news for tissue engineers, and forward thinking plastic surgeons. With improvements in collagen synthesis, cartilage production, and other basic level tissue engineering processes, the creation of functioning lab-grown organs, complete with support tissue, is much closer.

Killing Neurons with Excitement

We know that much of the damage from strokes comes from an overload of glutamate, an excitatory neurotransmitter. Neurodegenerative changes in Alzheimer's Disease is probably also due to glutamate overexcitation, at least in part. Now scientists are beginning to tease apart the mechanism of excitative neurotoxicity. This news release give more information:

For neurons, overexcitement is deadly. To avoid this, brain cells must sop up unneeded neurotransmitters from the synapse through membrane-bound transporters. If these transporters fail, neurons and other brain cells get excited to death-- a phenomenon that may contribute to brain damage during stroke and Alzheimer's disease.

Indeed, brain deterioration after stroke is associated with elevated levels of glutamate -- the major excitatory neurotransmitter in the mammalian central nervous system (CNS) -- in the plasma and cerebral spinal fluid. One possible explanation for this glutamate build-up, reported online on March 6th in The Journal of Experimental Medicine, is a mutation in the gene encoding the glutamate transporter protein EAAT2.

This mutation --- a single nucleotide change in the promoter region of the EAAT2 gene -- was equally prevalent in healthy individuals and stroke patients. But among stroke patients, those with the mutated allele had higher plasma levels of glutamate and were more likely to suffer from post-stroke neurological problems than those with the normal allele.

The mutation changed a binding site for the activating transcription factor AP-2 into a binding site for the repressor GCF2 -- a swap that inhibited promoter activity in transfected rat brain cells. Whether the mutant promoter decreases EAAT2 expression in the human brain, as would be predicted, remains to be tested.

Little by little, gene by gene, protein by protein, science is learning why humans suffer the way they do. And little by little science is finding ways to do something about it.

Gene Therapy: Cancer, Heart Disease, Life Extension

Since before Crick and Watson, people have been dreaming about making changes to the human genome. First of all, watching a child die from an inherited disorder is heart-wrenching. Most parents and physicians would do almost anything to change that child's destiny. Then, the knowledge that many adults get sick and die prematurely, lose their strength and their minds prematurely, leads many physicians and scientists to think about changing the genes that cause that early decline. Finally, the knowledge that the degenerative changes of most common disease, including cancer and heart disease--and of aging itself--are moderated by genetic processes, led many scientists to think of adjusting the genetic compliment routinely.

With the discovery of restriction enzymes and practical methods of gene sequencing, the race to map the genes was on. It was important to understand the normal human genome before scientists could identify the genes that led to disease. Once all the disease genes were identified, it was thought that perhaps substituting healthy genes for the disease genes might cure the underlying problem.

But the story was not that simple. Early attempts to introduce genes into human subjects met with unforeseen obstacles. And when it was discovered that there were only 25,000 to 30,000 human genes--instead of the expected 100,000--it began to dawn on scientists that there was more to the story than just the genes. Epigenetic factors play into gene expression, which complicated the plot significantly.

Protein interaction, gene regulator proteins, non-coding RNA, and glycomics--among other things--influence gene expression and the ultimate fate of the cell. Of course, in humans, cells exist within tissues, tissues within organs, and organs within the human organism. Complex interactions occur at every level.

To introduce new genes into a cell with defective genes, you must have a vector. Gene vectors are typically viral, since viruses make a living by introducing their genes into an animal cell for its own replication. There are also non-viral vectors that can be used to introduce genes into cells. Viruses have a billion+ year advantage as gene vectors, but nonviral methods are improving despite the challenges.

Besides introducing genes into cells, modern gene therapy also involves silencing of genes by various means. Sometimes it involves activating dormant genes that are already present. And sometimes it means delivering the entire cell--genes, nucleus, cytoplasm, and all.

Human Gene Therapy journal has made an entire issue freely available on the internet. The latest news on gene therapy is available through various sources. A recent article in The Scientist discussed future directions of gene therapy.

The SENS approach to life extension involves interventions against seven causes of aging: Cell depletion, Unwanted Cells, Chromosomal Mutations, Mitochondrial Mutations, Protein Crosslinks, Extracellular Junk, and Intracellular Junk. None of them are insurmountable, and much of the new knowledge from molecular biology, stem cell biology, cell biology, and other areas of biotechnology, are applicable to these challenges.

The very proliferation of new knowledge in all of these areas present a difficulty. Bioinformatics has evolved to keep track of the impossible quantity of data being generated, but what is actually needed is a super-human intelligence to make sense of it all, and to prioritise new research. In lieu of that, we will have to muddle through. Bit by bit, we seem to be succeeding. It would go much faster with some next-level supervision, but such is life.

Peak Oil: Meet Athabasca Oil Sands

The Athabasca oil sands region lies in northern Alberta Province, in Canada. The Chevron oil company has been involved in oil recovery efforts in Athabasca for several years. Now Chevron is moving into the region in a big way, having recently acquired several oil sands leases, for land with over 7 billion barrels of oil in place.

The new leases are approximately 76 miles west of Fort Mackay in northern Alberta, and 24 miles south west of AOSP.

Chevron will use Steam Assisted Gravity Drainage (SAGD), an in-situ technology that uses steam and horizontal drilling to extract the bitumen. Shell Canada and Western Oil Sands will each have the right to elect to acquire a 20% working interest in these leases.

The SAGD process involves drilling pairs of horizontal wells in the oil sands reservoir. Steam is injected through an upper well—about 3 to 10 meters above the lower—and contacts the bitumen. The heated bitumen becomes mobile and flows with condensed water from the steam chamber to the lower well through gravity drainage. Thence it is lifted to the surface for upgrading.

Each well pair is typically 2,500 to 3,000 feet in length, and optimally produces 1,000 to 1,500 barrels per day. Well pairs are drilled parallel to one another, and spaced 300 to 650 feet apart.

Read the full article here.

Oil sands are a heavy oil resource, requiring special refining methods, and not nearly as well suited for gasoline production as sweet crude oil. Along with shale oil, oil sands represent a huge and relatively untapped oil resource.

In addition to oil sands and shale oil, coal is another fossil fuel that can be converted to liquid hydrocarbon fuel form. Cleaner methods of processing and buring coal are a top priority in the industrial nations.

Peak Oil Debunked is an excellent source of information about Peak Oil Hype. Go on over and give them a look.

I am a big fan of renewable energy, having helped install a number of solar and wind home energy systems. Fossil fuels and nuclear fission should be seen as only a stopgap measure until renewable methods of energy production can take over.

One other source of gasoline that I should mention--cow dung! Japanese scientists have learned to make gasoline from the dung of cattle. They are a bit short on details at the moment, but it seems they are in earnest.

Update 6 March 06: Here is an update on the Chevron oil sands venture:

On Friday I was at the Stanford Institute for Economic Policy Research’s Economic Summit (some videos available), where among other things I learned that the oil sands of Canada are, unfortunately, more accurately thought of as “tar sands”. But Chevron has announced a $60 million deal to develop these sands. The Motley Fool’s Jack Uldrich speculates on why they are willing to take this big project on:

“The risky venture could ultimately cost tens of billions of dollars and take up to a decade to develop, since the tar in the oil sands isn’t easily converted to usable oil. But Chevron may have a very tiny ace up its sleeve, thanks to its involvement with nanotechnology…

“Chevron’s work in creating new nanoparticles offers the greatest promise. If the company can produce new nanoparticles with unique catalytic capabilities, it may be able to more effectively and efficiently refine the thick, gooey tar-sands into highly refined — and profitable –oil.

“Headwaters (NYSE: HW) is already developing nanocatalysts to convert heavy oils into higher-yield oils, and I have reason to believe that Chevron is doing the same. If the company succeeds, these powerful new nanocatalysts could make extracting oil from the tar sands profitable, even at prices lower than $35 a barrel. And if oil prices stay high, a cheaper extraction process will only bolster Chevron’s profit margins. It’s yet another small solution to a potentially big risk.”

The use of nanoparticles as catalysts to make the oil sands more productive, is just one timely synergy of technological development. There will be many more, that improve both the economy and the environment. The key is for the active members of society to think like problem solvers, rather than doomsayers.

Free Medical Textbooks--The Amedeo Challenge

Here at Al Fin, we value the free access of electronic information--as you can see by scanning the sidebar links. It is good to hear about the Amedeo Challenge to medical authors to write and publish free, high quality medical textbooks. Amedeo operates websites that provide free medical textbooks, free medical journals, and free medical information. Two recent medical books made freely available, are Influenza Report 2006, and HIV Medicine 2005.

Here is the story behind Bernard Sebastian Kamps, the human force behind Amedeo and other information ventures.

Story source.

Neural Oscillations and the Virtues of Automaticity

Two good postings on brain function today. One from our old friend Chris at Develintel, titled Models of Active Maintenance as Oscillation. This excellent post continues the series on neural oscillation and synchrony.

Lisman and Idiart, Luck and Vogel, and Nelson Cowan have all suggested that working memory could be the result of the multiplexing of gamma oscillations (20-60 Hz) by theta oscillations (5-10 Hz) in the prefrontal cortex, such that capacity is determined by the number of gamma cycles that can occur within a single theta cycle.

Supporting this highly reductionistic claim are the observations that gamma oscillations are made more prominent by focused attention, that gamma oscillations are known to be important for transmitting information across large cortical distances and for visual binding of features into singular objects. Gamma synchrony is also known to increase performance in target detection as well as recall. Further, by playing auditory "clicks'" at near-gamma frequencies, it is possible to upwardly or downwardly entrain gamma rhythms and directly observe their effects on working memory span - exactly this was done by Burle and Bonnet.

Read the entire post here.

The second post on brain function is from Eide Neurolearning Blog, titled In Praise of Automaticity. Automaticity is when subconscious brain assets take over many tasks for the conscious brain. The Eides point out that conversion of conscious tasks into automaticity saves a great deal of work, and allows for natural progression of learning.

When academic or motor skills don't become automatic, a whole host of problems present themselves. Dyslexic students who have trouble remembering how to form letters automatically, can overload with essay writing, taking notes, or math problem sets (dysgraphia). If math facts, spelling or grammar conventions aren't known to the point of automaticity, then even very intelligent students can find themselves overwhelmed by higher order activities based on these building block skills. As a result, if we don't look for opportunities to accommodate, we may never discover a student's creative or critical thinking strengths.

For us adults, automatic expertise helps us carry out most of our activities of daily living and multi-tasking. It's a beautiful system because it allows us to rest while still getting plenty of work done.

Hat tip to Kevin at Intelligence Testing Blog.

It is helpful to look at brain activity from the different perspectives of neural networks, and developing human organisms.

Virtual Humans--The Reality

Now we are ready to take a closer look at virtual humans, and what is being done with them. The Virtual Human Project grew from research staff discussions at the US Oak Ridge National Lab (ORNL). This review article from ORNL provides a useful history.

....The beauty of a computer model of a human is that it can be customized for a specific person at any point in time. At least, that's the long-term vision shared by Easterly and his colleagues. Customization is important because of evidence that men, women, and children respond differently to various drugs, drug dosages, and other treatments, as well as environmental insults.

"From our earlier work in modeling children's organs," Ward says, "we see the need to build human models for different ages, sizes, and sexes. By using equations and changing some parameters, we can make the heart smaller or larger. We can make a human model or phantom grow with age." Use of a customized model—a computerized clone of you that includes your genetic makeup—will make it possible to predict how you might respond to different doses of radiation, chemicals, and drugs, or what damage you might suffer if you were in an automobile accident or airplane crash.

Researchers are using virtual humans to monitor human response to drugs, other chemical stimuli, and physical stimuli. The US National Institute for Occupational Safety and Health (NIOSH) is using virtual humans to study hazardous interations, as between an operator and a machine. Toyota uses virtual humans to predict injuries from various types of accidents, so as to design safer vehicles. The University of Pennsylvania has developed a Virtual Human Testbed for studying the ergonomics and kinematics of various work environments.

The Visible Human Project has spawned the Virtual Human, a set of CT scan images from cadavers, showing the whole body inside and out, making the images available to researchers for use in computer models.

The US Defense Advanced Research Projects Agency (DARPA) has developed the Virtual Soldier Project,

The DARPA Virtual Soldier Project will investigate methods that will revolutionize medical care for the soldier. The project will produce complex mathematical models to create physiological representations of individual soldiers. These holographic medical representations (known as Holomers) can be used to improve medical diagnosis on and off the battlefield.

The Holomers coupled with predictive modeling software, will facilitate a new level of integration in medical procedures. The Virtual Soldier will provide multiple capabilities, including automatic diagnosis of battlefield injuries,prediction of soldier performance, evaluation of non-lethal weapons, and virtual clinical trials.

Links to affiliated projects of The Virtual Human Project can be found here.

Simulations of humans are now used for medical training of future physicians and surgeons, for entertainment, in advertising, in research as substitutes for using human or animal subjects, even as substitutes for physical dummies in automobile crash research. Police departments are using virtual humans for training police officers.

In a previous posting, I took a more light-hearted view of virtual humans. In reality, simulated humans are now mainstream technology in several fields. How real can the simulations get? Some of them are going to the cellular and molecular levels. In the other direction, simulating the actions of groups of humans might also be enlightening.

It is important to understand that the model is not the real thing. The map is not the territory. Computer modelling is still relatively primitive, and it is always best to confirm the predictions of a model whenever possible.

Virtual Humans, Virtual Sex, Robot Sex

Singularity News (multipolarity memes) reports on the use of virtual humans in movies, games, and now for testing of digital prototypes based on CAD models. From their source in Betterhumans:

The well known company Caterpillar, which manufactures heavy equipment, uses a digital human called Santos for testing:

"They (Caterpillar) have an interest in serviceability and mental ability," said Abdel-Malek. "We can ask Santos to change an oil filter on a dump truck or some similar task. As he goes about doing the job, we can query any part of his body functions, such as heart rate, temperature, muscle load and others. At the same time, we can watch him work onscreen and observe any problems he might encounter." (Wired, Feb. 22, 2006)

The U.S. Army also uses Santos for testing new designs for body armor and other protective gear. When Santos moves in response to commands, information is relayed regarding his heart rate, comfort level, restrictiveness of the outfit, and joint angles.

The rather fetching virtual image at the multipolarity memes site quite naturally got me thinking about the growing popularity of virtual sex. In Canada:

young Canadians are practicing a new style of safe sex and the only touching required involves a keyboard.

Of more than 2,500 university and college students polled across Canada, 87 percent of them are having sex over instant messenger, webcams or the telephone, according to results of a national survey released on Monday.

"We were very surprised," Noah Gurza, a founder of Toronto-based CampusKiss.com, an online dating community for students, which commissioned a Canadian CampusKiss & Tell Survey.

"We did realize that new technologies are always embraced by younger individuals, but we didn't think it would've reached such a high number."

Gurza said most post-secondary school students grew up using computer technology, and their lives currently revolve around technology, so it makes sense that it would extend to their sex lives.

"It's now extended within their sexual world, whether it be as a social lubricant as a means to then engage in something that's more real, in more real time, or if it's just a means in itself of pleasuring here and there," he said.

Some 2,684 students from more than 150 university and college campuses across Canada took part in the survey. Fifty-one percent of the participates were female and 49 percent were male.

Of those surveyed, 53 percent of students enjoyed sex over instant messenger, while 44 percent did the deed using a webcam and over the phone.

But why stop there? Certainly in this enlightened age we are now ready for sex with . . . . . . robots? For this, the Germans seem to have an advantage:

A German inventor claims to have created the world's most sophisticated robot sex doll.

The sex androids developed by aircraft mechanic Michael Harriman from Nuremberg have 'hearts' that beat harder during sex.

They also breathe harder and have internal heaters to raise the body temperature - but their feet stay cold "just like in real life", according to Harriman.

He said: "They are almost impossible to distinguish from the real thing, but I am still developing improvements and I will only be happy when what I have is better than the real thing."

The dolls sold under the Andy brand name are on offer for £4,000 each for the basic model, with extra charges for adaptations like extra large breasts.

Of course, if you spend that much for a robot doll, you should keep a close eye on him or her. It would not do for your doll to fall for another person--or even another robot. That is quite a lot of money to just walk out the door.

Cancer Tracking Stem Cells and Cytokines that Kill Tumors

It is important to be able to track down specific cell types, and deliver a treatment specifically to that type of cell. Whether the treatment is meant to kill the cell, or merely to introduce a genetic or pharmacologic therapy, it is important to be able to reach out and touch that one specific cell type. This report details the use of neural stem cells as "cancer trackers"--to hunt down glioma tumor cells and deliver a killing dose of the cytokine interleukin 23 (IL-23).

Gliomas are highly invasive tumors with poorly defined borders that intermingle with healthy brain tissue, making complete surgical removal nearly impossible. Furthermore, cells separate from the main tumor and migrate to form satellites that escape treatment and often lead to recurrence.

Researchers at the Maxine Dunitz Neurosurgical Institute documented several years ago that some neural stem cells - "immature" cells that can differentiate into central nervous system cells - have the ability to target and track glioma cells in the brain, even as they migrate. The researchers identified the mechanism that enables certain neural stem cells to develop this tracking ability and genetically engineered neural stem cells to transport several cytokines - proteins that regulate immune responses - to track down and destroy glioma cells.

....This study provides the first documentation that the marrow-derived stem cells possess the same tumor-tracking capability of other neural stem cells. It also includes the first report on the use of the cytokine interleukin-23 (IL-23) as a potential gene-delivered therapy against glioma.

"The paper recapitulates our previous data demonstrating that the neural stem cells - in this case from bone marrow - were able to track to the tumor very efficiently and, like a heat-seeking missile, deliver a killer depot," said John S. Yu, M.D., neurosurgeon, co-director of the Comprehensive Brain Tumor Program at the Maxine Dunitz Neurosurgical Institute, and the article's senior author. "We obtained the stem cells from bone marrow, mirroring what we want to do clinically, which is to take bone marrow cells from a patient, make them into neural stem cells, put in the gene of interest and treat the patient."

In this case, the gene of interest produces IL-23, which appears to be very well suited for attacking gliomas. Earlier studies used IL-4, IL-12, and tumor necrosis factor related apoptosis inducing ligand (TRAIL).

"Each cytokine has unique functions. What we want to do is marry the function with the therapeutic response we want to achieve. Interleukin-23 promotes the function of dendritic cells and memory T-cells, important components in an immune response to tumor cells. The earlier cytokines produced good results, but IL-23 is even more potent," Yu said.

"Most anti-tumor gene strategies attempt to deliver genes directly to tumor cells, but gliomas are especially challenging because of their highly invasive and migratory characteristics," said Keith L. Black, M.D., director of the Maxine Dunitz Neurosurgical Institute, director of Cedars-Sinai's Division of Neurosurgery, and co-director of the Comprehensive Brain Tumor Program. "By combining the tumor-tracking properties of bone marrow-derived neural stem cells with interleukin-23, we are able to initiate a very powerful anti-tumor response that tracks to migrating glioma islands and offers long-term protection - all of which would make this a very attractive therapeutic option."

In the animal study, bone marrow-derived neural stem-like cells (BM-NSC) genetically engineered to produce IL-23 were injected into intracranial gliomas and other areas of the brain. Treated animals survived significantly longer than those in control groups. In fact, of those receiving BM-NSC-IL-23, 60 percent survived beyond day 120 tumor-free. Only 20 percent of those treated with IL-23 that was not attached to neural stem cells survived, and no animals survived if they received neural stem cells without IL-23.

Even after additional glioma cells were injected, BM-NSC-IL-23-treated animals remained tumor free, evidence of the long-term immunity provided by IL-23's generation of memory T-cells.

Read the entire report here.

In the future, therapies will be increasingly targeted to specific cells. This will limit side effects and increase therapeutic effects. This report is merely documenting the early steps of this process.

Aging Biomarkers Focus on Mitochondrial Mutations and Mitomap

Aging cells show their age in different ways. Their telomeres shorten, they accumulate nuclear DNA errors, and mitochondrial DNA deletions accumulate. Medical researchers, drug researchers and cosmetic researchers, all want to find ways to monitor the efficacy of their treatments and products. To that end, they are contributing to the mapping of the mitochondrial DNA genome, called the mitomap. The state of the mitochondrial genome, with its point mutations and deletions, will constitute biomarkers, to indicate cellular age.

The new biomarkers are changes to the DNA of cellular organelles called mitochondria. Mitochondria, which have their own DNA that is distinct from the DNA in the cell's nucleus, serve as the "power plants" of the cell. They manufacture energy in the form of the molecule ATP. Energy generation includes, as a byproduct, the production of reactive oxygen species, which can damage the DNA present in mitochondria, Sligh said.

Some theories of cellular aging -- why and how cells age -- center on mitochondria and decreased energetic capacity resulting from mitochondrial DNA mutations, Sligh explained. In addition, mutations in mitochondrial DNA have been associated with tumor development.

....The investigators searched for mitochondrial DNA deletion mutations in skin samples from patients having non-melanoma skin cancer removed in the Vanderbilt Mohs Clinic. Mohs micrographic surgery is a treatment for skin cancer, particularly the most common forms: basal and squamous cell carcinomas.

Sligh and colleagues were surprised to find a panel of mitochondrial DNA deletions in the tumor-free skin that was adjacent to the tumors, but not in the tumors themselves. The tumor samples were more likely to have full-length mitochondrial DNA, with point mutations rather than significant deletions, Sligh said.

The mitochondrial DNA mutations in the tumor-free skin correlated with the aging process, Sligh said. The newly identified deletion mutations will now go into "Mitomap," a database of all known human mitochondrial genome changes.

"Unraveling the molecular clues as to why aging cells function differently than young cells requires that we have molecular markers that we can track," Sligh said. "It won't be long before other investigators who have other human tissue specimens -- brain, lung, heart, for example -- look for these changes and report back.

Read the entire report here.

The mitomap is one more biomolecular database that will be immensely helpful in the continued quest to understand the effect of age on the human organism.

Fighting Alzheimer's Disease: The One-Two Punch

An experimental drug called AF267B has been shown to curb both the intracellular (neurofibrillary tangles) and extracellular (amyloid plaque) manifestations of Alzheimer's disease.

What's more, AF267B also appeared to reverse cognitive declines in mice genetically designed to mimic Alzheimer's disease. Mice appeared to gain renewed powers of memory and learning after treatment, the researchers report in the March 2 issue of Neuron.

AF267B "does exactly what one would hope a drug for Alzheimer's is going to do -- it's a disease-modifying compound that's not only able to treat symptoms, but was able to reverse the onslaught of the pathology in these mice," said study senior author Frank LaFerla, a professor of neurobiology at the University of California, Irvine (UCI).

He explained that AF267B is an "M1 agonist" -- a drug that acts by stimulating the muscarinic receptor lying on the surface of nerve cells.

"It's been known for about 30 years that there's a selective loss of neurons in the brains of Alzheimer's patients, neurons that produce a neurotransmitter chemical called acetylcholine," LaFerla explained.

One way to boost flagging acetylcholine activity is to stimulate the M1 receptor, which is designed to interact with the neurotransmitter.

AF267B does just that. It was developed by noted Alzheimer's researcher and study co-author Abraham Fisher, of the Israel Institute for Biological Research, in Ness-Ziona, Israel.

....About two years ago, LaFerla's team developed a genetically engineered mouse model that mimics human Alzheimer's disease more closely than any previous rodent strain. That's because these mice develop both plaques and tangles.

"Models used up till now have only developed the plaques," LaFerla pointed out.

"It's a model that a lot of people are excited about," added William Thies, vice president of medical and scientific affairs at the Alzheimer's Association. Because it so closely resembles human disease, the new mouse model "shows promise for broadening what we can measure in animal studies," he added.

The UCI team tested AF267B in the new mouse model.

"We found that when we stimulated the muscarinic receptor, we were able to reduce the two major neuropathological lesions -- plaques and tangles," LaFerla said.

What's more, mice given AF267B began to perform much better in tests meant to assess memory and learning, reversing previous Alzheimer's-linked cognitive dysfunction. Later examination of brain tissue confirmed that the drug appears to target neurons in exactly those brain centers affected by the disease.

....Although many experimental drugs are being targeted to remove plaques, "we know that tangles, by themselves, can clearly cause dementia and neurological disease," La Ferla said. "So, the sooner you can get rid of both lesions, the better."

Thies said he's cautiously optimistic about AF267B. "In this case, you have some evidence that the agent modifies both amyloid and tau -- that's something you want to see in a therapeutic agent," he said.

But he also cautioned that animal findings don't always translate to humans. "A mouse is never a person, even when you put in a lot a human genes," he said.

Read the entire article here. Or go to HealthDay News, the original source. Hat tip to Mental Health Net.

I am skeptical that simply stimulating muscarinic receptors will abolish the histological and neurological manifestations of Alzheimer's disease. If these promising results are replicated in human trials, I would begin looking for other additional sites of action for AF267B.

Mitochondrial Dysfunction and Disease

Mitochondria are the powerhouses of the cell. The better your mitochondria perform, the more energy you will have. All of your cells need well-functioning mitochondria, or they will suffer. Mitochondria were probably bacteria, originally. They contain much of their own DNA, and divide like bacteria, with both copies retaining the genome.

Not surprisingly, mitochondria are sensitive to certain antibiotics, like bacteria. In fact, one approach to cancer chemotherapy is to develop an antibiotic that specifically targets the mitochondria of cancer cells. Causing sufficient damage to mitochondria can induce apoptosis of the cell. A lot of research is currently being conducted to clarify the connection of mitochondria with caspase releae and subsequent apoptosis.

Mitochondrial dysfunction participates in neurodegeneration of Huntington disease (HD), Friedreich ataxia, hereditary spastic paraplegia, and rare familial forms of Parkinson disease (PD), Alzheimer disease (AD), and amyotrophic lateral sclerosis (ALS). Although this is only one of the many molecular pathways to neurodegeneration, it is a potentially important one.

In a previous post, I referred to the speculation that chronic fatigue syndrome was related to mitochondrial dysfunction, which could theoretically be caused by any number of micro-organisms including Epstein Barr Virus (EBV). Chemical insult can also cause mitochondrial dysfunction.

The scope of mitochondrial dysfunction is very broad. Some disorders are inherited and manifest in infancy or childhood, many others are acquired in later life. Several dozen known diseases are related to mitochondrial dysfunction.

The good news is that science is getting a better understanding of how mitochondria resist damage.

The SENS approach to life extension includes the preservation of mitochondrial function as one of its basic tenets.

What if we could all have the mitochondrial function of a Lance Armstrong or a champion Iron Man triathlete? That is the short term goal. Longer term, who knows?

Helping CD4+ Cells Survive: Stealth Vectors, Antisense RNA, HIV/AIDS

HIV/AIDS is an increasingly severe worldwide problem. If the infected person can keep his CD4+ count high enough, he will probably not get AIDs. Anti-retroviral drugs have helped millions of HIV infected persons stave off AIDS, where the drugs are available, but a better method of restoring the CD4+ cell population is needed--one that does not require taking so many expensive pills on a daily basis.

Enzo Biochem has developed a "gene construct" consisting of three anti-sense genes, which are introduced into blood stem cells that are destined to become CD4+ T cells. These new CD4+ T cells will be resistant to the HIV retrovirus because the antisense genes they contain will neutralize the HIV gene products that are necessary for the virus to infect the cell. The more CD4+ T cells that survive, the less likely the person is to develop full blown AIDS.

Here is the report from Enzo Biochem (NYSE:ENZ):

In the upcoming trial, which is expected to get underway shortly, Enzo’s StealthVector® HGTV43™ gene construct will be used to transfer three antisense genes designed to interfere with the growth of HIV-1 into blood stem cells. These cells are expected to replicate and differentiate within the body of the HIV-1 infected individual to produce CD4+ T-cells, the main target of infection by HIV-1. The novel aspect of the current study is to increase the percentage of CD4+ cells that contain the anti-HIV-1 antisense genes with a protocol designed to partially reduce the patient’s blood stem cells before infusion of the engineered cells. The trial is intended to determine whether this procedure will create a supply of HIV-1 resistant CD4+ cells large enough to materially defer the disease progression of these HIV-1 infected individuals into AIDS

The Phase I study that took place at UCSF demonstrated the safety of the procedure and showed that the engineered stem cells were able to survive long term in vivo and to produce a low number of CD4+ cell progeny containing functioning antisense genes. Although there was no increase in the CD4+ cell count or reduction in the viral load, the yield of engineered cells has remained approximately constant over a number of years, in the case of one individual for as long as five years, supporting the conclusion that stable engraftment of anti-HIV-1 antisense RNA-producing blood stem cells occurred and the antisense genes continued to function.

....The HGTV43™ vector was developed by Enzo to include a proprietary delivery system designed to overcome a major challenge in gene medicine, namely the efficient and safe delivery of the medicine to the appropriate target. The benefits of Enzo’s “Stealth” vector technology are that it achieves efficient delivery of the genes into the patient’s cells, and that it is “silent” and unlikely to trigger an immune response. In addition, during the development of the vector two critical safety features were incorporated to minimize the possibility of inadvertently turning on deleterious genes in the subject.

“The Phase I trial demonstrated the safety of the HGTV43™ gene construct in 5 subjects and the ability of the engineered cells to survive and continue to function in vivo.

Read the full Enzo release here.
Hat tip medgadget.

Anti-sense RNA gene constructs are just one form of non-coding RNA. HIV/AIDS is such a complex infection, that it has been difficult for scientists to find the best way to attack it. Approaches to developing working vaccines have not been productive so far, but there is more than one way to skin this cat. Molecular biology has just begun to flex its muscles. Microbes, even HIV, do not stand a chance, in the long run--if.

If what? If western civilisation can continue to support its vast scientific research infrastructure. Given all the ongoing threats, that is not guaranteed.

Epstein Barr Virus and Chronic Fatigue Syndrome

Australian scientists have been following people who were infected by three microbes, including Epstein Barr Virus (EBV) to determine if there were any long term complications from the infections.

New evidence on chronic fatigue causation:

The 'Dubbo Infection Outcomes Study'

A seven-year tracking study has prompted scientists to suggest that chronic fatigue syndrome could be the result of brain injuries inflicted during the early stages of glandular fever.

Australian researchers have put the suggestion in this week's Journal of Infectious Diseases, which reveals new findings from the 'Dubbo Infection Outcomes Study'. Since 1999, a team led by UNSW Professor Andrew Lloyd have been tracking the long-term health of individuals infected with Epstein-Barr virus (EBV), Ross River virus (RRV) or Q fever infection. Their goal is to discover whether the post-infection fatigue syndrome that may affect up to 100,000 Australians is caused by the persistence of EBV, a weakened immune system, psychological vulnerability, or some combination of these.

Glandular fever – sometimes called 'the kissing disease' – is caused by Epstein-Barr virus (EBV). Transmitted via saliva, its acute symptoms include fever, sore throat, tiredness, and swollen lymph glands. Most patients recover within several weeks but one in ten young people will suffer prolonged symptoms, marked by fatigue. When these symptoms persist in disabling degree for six months or more, the illness may be diagnosed as chronic fatigue syndrome (CFS).

The researchers followed the course of illness among 39 people diagnosed with acute glandular fever. Eight patients developed a 'post-infective fatigue syndrome' lasting six months or longer, while the remaining 31 recovered uneventfully. Detailed studies of the activity of the Epstein-Barr virus in the blood and the immune response against the virus were conducted on blood samples collected from each individual over 12 months.

Commenting on the findings, Professor Lloyd says: "Our findings reveal that neither the virus nor an abnormal immune response explain the post-infective fatigue syndrome. We now suspect it's more like a hit and run injury to the brain.

"We believe that the parts of the brain that control perception of fatigue and pain get damaged during the acute infection phase of glandular fever. If you're still sick several weeks after infection, it seems that the symptoms aren't being driven by the activity of the virus in body, it's happening in the brain."

The research team comprising scientists from the University of New South Wales, the University of Sydney and the Queensland Institute of Medical Research plan to test their 'brain injury' hypothesis by doing neurological tests on the study participants.

Read the full report here.

"Parts of the brain that control perception of fatigue and pain get damaged . . . " This is only a preliminary finding, understand. People with chronic fatigue syndrome (CFS) know very well that it is not "all in their heads." The fatigue is real and debilitating. But if the brain is misreading the true state of the body, and relaying false impressions to the conscious mind, it would be difficult for the person to tell the difference.

I suspect the true picture is more complex. It is more than just the conscious mind that is misreading the state of the body. It is likely that several brain centers are involved. Furthermore, since the brain is involved in heart rate, respiratory rate, body temperature, perspiration, and motor control--among other things related to perception of fatigue--the deception could be incredibly thorough.

Mitochondria dysfunction is a very real possibility with CFS. I will post more on mitochondrial dysfunction later.