One of the characteristics of type 2 diabetes is insulin resistance, which refers to the inability of cells in the body to respond appropriately to the hormone insulin.  Among the cells in the body that normally respond to insulin are nerves in a region of the brain known as the hypothalamus.  New data, generated in rats, by Hiraku Ono and colleagues, at Albert Einstein College of Medicine, New York, has provided insight into a molecular pathway in the hypothalamus that contributes to the development of insulin resistance.

Insulin plays a key role in controlling the amount of glucose in the body through its ability to make cells, such as liver and fat cells, take up glucose from the blood and store it for future use.  Insulin also prevents liver cells from releasing stored glucose, partly through its effects in the hypothalamus.  In the study, if rats were fed a high-fat diet for a short period of time the ability of insulin to prevent liver cells releasing stored glucose was reduced.  This was associated with both a decrease in insulin-induced signaling and an increase in activation of a protein known as SK6 in the hypothalamus.  The importance of SK6 activation in the hypothalamus in suppressing the ability of insulin to prevent glucose release from liver cells was confirmed by two sets of experiments.  First, it was shown that enforced SK6 activation in the hypothalamus had the same effects as feeding rats a high-fat diet; second, blocking the effects of SK6 activation restored the ability of insulin to prevent glucose release from liver cells, even when rats were fed a high-fat diet.  These data lead the authors to speculate that the earliest stages of diet-induced insulin resistance might be prevented by inhibition of S6K in the hypothalamus.

Antibodies are proteins that are a crucial component of the immune system.  They are produced in large amounts by immune cells known as plasma cells, which live in just a few parts of the body, including the bone marrow and special areas of the various parts of the body that are exposed to the outside (e.g., the gut, nose, and airways).  These areas are known as mucosa-associated lymphoid tissue (MALT) and include tissues such as the tonsils, but what regulates plasma cell survival in MALT has not been determined.  Now, however, Bertrand Huard and colleagues, at Geneva University Medical Center, Switzerland, have provided new insight into the molecular mechanisms controlling plasma cell survival in MALT.

In the study, analysis of tonsils and MALT from the lower gut indicated that a protein known as APRIL is important for promoting the survival of plasma cells in human MALT.  APRIL was found to work by increasing plasma cell expression of proteins that protect cells from a form of death known as apoptosis.  Expression of APRIL was shown to be greater in tonsils infected with a microbe than in noninfected tonsils and the cells producing the increased APRIL were identified as immune cells known as neutrophils that had been recruited to the site of infection.  APRIL from the neutrophils was retained in the tonsils bound to molecules known as heparan sulfate proteoglycans, creating an APRIL-rich niche for the plasma cells to survive in.  The authors therefore suggest that the longevity of plasma cells in MALT is controlled, in part, by APRIL-secreting neutrophils recruited to sites of infection.

Atherosclerosis is a disease of the major arterial blood vessels that is often known as hardening of the arteries; it is one of the main causes of heart attack and stroke.  An important first step in the disease is a process known as intimal thickening, whereby the intimal layer of arterial blood vessels becomes thicker because cells known as smooth muscle cells (SMCs) migrate to the area and proliferate.  The protein sLRII is thought to play a key role in this process, although its specific mechanisms of action and significance are poorly understood.  In a new study, Hideaki Bujo of the Chibe University Graduate School of Medicine, Japan, Wolfgang Schneider of the Medical University of Vienna, Austria, and their colleagues reveal that sLRII is important for SMC migration.

Levels of sLRII in the bloodstream were shown to be associated with intimal thickening in patients with poorly-regulated abnormal levels of fat in the blood.  Furthermore, intimal thickening was markedly reduced in mice lacking sLRII.  SMCs from these mice failed to migrate in response to stimulation, indicating that the reduced intimal thickening probably results from reduced SMC migration.  The authors therefore suggest that sLRII may serve as a novel marker for intimal thickening and atherosclerosis

Xiao-Jing Wang and colleagues, at Oregon Health & Science University, Portland, have provided new insight into the role of the signaling molecule Smad2 in skin cancer by analyzing human skin cancer tissue and a mouse model of skin cancer.

In the study, human squamous cell skin cancer samples were found to frequently lose expression of Smad2.  In particular, Smad2 expression was lost in all samples characterized as “poorly differentiated” (which means they had progressed to become aggressive tumors).  Consistent with this, mice lacking Smad2 in cells of the skin known as keratinocytes developed chemically induced skin cancer more rapidly than normal mice, and the cancers were all characterized as “poorly differentiated”.  The mouse cancers also underwent a process known as epithelial-mesenchymal transition (EMT) and this was found to contribute to the accelerated progression of the skin cancer to an aggressive form.  These data identify Smad2 as a suppressor of skin cancer development and progression to an aggressive form, and future studies will investigate in more detail the mechanisms underlying the role of Smad2 loss in human skin cancer progression.

Although prostate cancer is the second most common cause of death from cancer in the US, it is not the tumor in the prostate that usually causes death.  Rather, death mainly occurs as a result of the tumor spreading to the bones, where it is known as an osteoblastic bone metastasis.  Treatments that deprive the tumor of male sex hormones (androgens) are usually effective, but only briefly as the tumors typically develop the ability to grow in the absence of androgens and the diseases progresses.  New data, generated using two prostate cancer cell lines that lack expression of androgen receptors and that were derived from the bones of an individual with osteoblastic bone metastases, by Nora Navone and colleagues, at The University of Texas MD Anderson Cancer Center, Houston, have provided new insight into the mechanisms by which prostate cancer osteoblastic bone metastases progress.

The androgen receptor–negative prostate cancer cell lines generated by the authors grew when transplanted into immunocompromised mice and generated osteoblastic bone metastases.  A protein known as FGF9 was found to be expressed at higher levels in these cells lines than in other bone-derived prostate cancer cells and induced bone formation in an in vitro organ culture assay.  Further, as blocking FGF9 reduced the osteoblastic bone metastases in mice transplanted with the cell lines and FGF9 was found to be expressed in all human prostate cancer osteoblastic bone metastases analyzed, the authors suggest that FGF9 has an important role in prostate cancer progression to osteoblastic bone metastases.  The cells lines generated are also likely to be an important preclinical model for researchers developing therapeutics for osteoblastic bone metastases in individuals with prostate cancer.

Being male increases your risk of diseases caused by the inappropriate formation of a blood clot (a process known as thrombosis), such as heart attack and stroke, but the reasons for this are not completely understood.  However, Ethan Weiss and colleagues at the University of California, San Francisco, have used a mouse model of thrombosis to shed new light on this matter.

Thrombosis-related proteins are made in the liver, where expression of the genes containing the information needed for their generation is regulated by growth hormone (GH), which is secreted in a sex-specific manner — males secrete GH in a pulsatile fashion, whereas females secrete GH continuously.  In this study, GH-deficient mice were protected from thrombosis in the model of disease.  When female GH-deficient mice were given pulsatile GH (to mimic the manner in which GH is secreted in males) their ability to form blood clots resembled male mice.  Conversely, when male GH-deficient mice were given continuous GH (to mimic the manner in which GH is secreted in females) their ability to form blood clots resembled female mice.  The authors therefore conclude that sex-specific patterns of GH release mediate the gender-associated differences observed in susceptibility to diseases caused by inappropriate thrombosis, information that they hope will be of help in the development of sex-specific treatments for thrombosis.

Researchers from the European Molecular Biology Laboratory (EMBL) discovered a new way to make use of drugs’ unwanted side effects.  They developed a computational method that compares how similar the side effects of different drugs are and predicts how likely the drugs act on the same target molecule.  The study, published in Science this week, hints at new uses of marketed drugs.

Similar drugs often share target proteins, modes of action and unpleasant side effects.  In reverse this means that drugs that evoke similar side effects likely act on the same molecular targets.  A team of EMBL researchers now developed a computational tool that compares side effects to test if they can predict common targets of drugs.

“Such a correlation not only reveals the molecular basis of many side effects, but also bears a powerful therapeutic potential.  It hints at new uses of marketed drugs in the treatment of diseases they were not specifically developed for,” says Peer Bork, Joint Coordinator of EMBL’s Structural and Computational Biology Unit.

The approach would prove particularly useful for chemically dissimilar drugs used in different therapeutic areas that nevertheless have an overlapping, so far unknown protein target profile.  Similar strategies have proven successful in the past.  For example, the drug marketed as Viagra was initially developed to treat angina, but its side effects of prolonged penile erection led to a change in its therapeutic area.

Applying the new method to 746 marketed drugs, the scientists found 261 dissimilar drugs that in addition to their known action also likely bind to other unexpected molecular targets.  20 of these drugs were then tested experimentally and 13 showed binding to the targets that were predicted by side effect similarity.  Testing 9 of these drugs further in cellular assays they all showed activity and thus a desired effect on the cell through their interaction with the newly discovered target proteins.

The results reveal that side effects can help find new, relevant drug-target interactions that might form the basis of new therapies.  The brain enhancer Donepezil, for example, proved to share a target with the anti-depressant Venlafaxine, supporting that Donepezil could be also used to treat depression.

The big advantage of marketed drugs is that they have already been tested and approved for safe use in patients.  This means they can move a lot faster from bench to bedside than newly discovered drugs that often take up to 15 years before they can be applied in patients.

“With some more tests and refinement our method could in future be applied on a bigger scale.  New drugs could routinely be checked in the computer for additional hidden targets and potential use in different therapeutic areas.  This will save a lot of money and would speed up drug development tremendously,” concludes Bork.

A well-nursed prejudice in scholarly communication is that researchers avoid journalists and are disappointed with the coverage when they do have contact with the media.  A current study in the specialist journal Science shows the opposite to be true: more than half of the researchers questioned described their contact with journalists as predominantly good.  Four out of ten found coverage in the public-sector beneficial to their career.  The idea of the “ivory tower of science” can therefore no longer be upheld.

“The second prejudice we need to dispense with is that German researchers tend to find dealing with journalists more difficult and are less motivated to report on their research in the public sphere than their colleagues in the USA”, said head of the study Prof.  Hans Peter Peters from Forschungszentrum Jülich, a member of the Helmholtz Association.  The number of interactions with the media was similarly high in all of the countries investigated.  More than two thirds of the researchers had contact with the media over a period of three years.  Their experience in all of the countries was also positive.  “The main reason for the similarity in this pattern can be seen in the social need for a public legitimation of science.”

The fact that media presence and management positions clearly go hand-in-hand also backs up this point.  “Being a leading researcher now requires a readiness to liaise with the mass media”, explained Peters.  This can be construed from the clear correlation between the number of contacts with the media and those holding management positions.  “In other words, it is not left up to the discretion of each scientist as to whether they want to forge links with the media”, explained Peters.  “In certain positions and situations, it is expected of them.  Subjective attitudes only play a secondary role.”

The study which has now been published is the first comprehensive international survey of scientists in the world on this topic.  It was conducted by Forschungszentrum Jülich and partners in France, the United Kingdom, Japan, and the USA.  The sample consisted of around 1,350 biomedical researchers from the five largest science nations who produced at least two pertinent publications in their field between 2002 and 2004.  For reasons of comparability, all of those interviewed were selected from two clearly defined fields of research – epidemiology and stem-cell research.

Researchers at the Joslin Diabetes Center have demonstrated for the first time that transplanted muscle stem cells can both improve muscle function in animals with a form of muscular dystrophy and replenish the stem cell population for use in the repair of future muscle injuries.

“I’m very excited about this,” said lead author Amy J. Wagers, Ph.D., Principal Investigator in the Joslin Section on Developmental and Stem Cell Biology, principal faculty member at the Harvard Stem Cell Institute and Assistant Professor of Stem Cell and Regenerative Biology at Harvard University.  “This study indicates the presence of renewing muscle stem cells in adult skeletal muscle and demonstrates the potential benefit of stem cell therapy for the treatment of muscle degenerative diseases such as muscular dystrophy.”

The study was designed to test the concept that skeletal muscle precursor cells could function as adult stem cells and that transplantation of these cells could both repair muscle tissue and regenerate the stem cell pool in a model of Duchenne muscular dystrophy, she said.  The research is published in the July 11 issue of Cell.

Duchenne muscular dystrophy is the most common form of the disease and is characterized by rapidly progressing muscle degeneration.  The disease is caused by a genetic mutation and there is currently no cure.

The data from this new study demonstrate that regenerative muscle stem cells can be distinguished from other cells in the muscle by unique protein markers present on their surfaces.  The authors used these markers to select stem cells from normal adult muscle and transferred the cells to diseased muscle of mice carrying a mutation in the same gene affected in human Duchenne muscular dystrophy.

“Once the healthy stem cells were transplanted into the muscles of the mice with muscular dystrophy, they generated cells that incorporated into the diseased muscle and substantially improved the ability of the treated muscles to contract,” said Wagers.  “At the same time, the transplantation of the healthy stem cells replenished the formerly diseased stem cell pool, providing a reservoir of healthy stem cells that could be re-activated to repair the muscle again during a second injury.”

According to the paper, these cells provide an effective source of immediately available muscle regenerative cells as well as a reserve pool that can maintain muscle regenerative activity in response to future challenges.

“This work demonstrates, in concept, that stem cell therapy could be beneficial for degenerative muscle diseases,” Wagers said.

Wagers also said the study will lead to other studies in the near-term that will identify pathways that regulate these muscle stem cells in order to figure out ways to boost the normal regenerative potential of these cells.  These could include drug therapies or genomic approaches, she said.  In the long-term, the idea will be to replicate these findings in humans.

“This is still very basic science, but I think we’re going to be able to move forward in a lot of directions.  It opens up many exciting avenues,” she said.

The Wagers Lab at Joslin studies both hematopoietic stem cells, which constantly maintain and can fully regenerate the entire blood system, as well as skeletal muscle stem cells, involved in skeletal muscle growth and repair.  The work is aimed particularly at defining novel mechanisms that regulate the migration, expansion, and regenerative potential of these two distinct adult stem cells.

Common genetic variations affecting nicotine receptors in the nervous system can significantly increase the chance that European Americans who begin smoking by age 17 will struggle with life-long nicotine addiction.  Published July 11 in the open-access journal PloS Genetics, this research – led by scientists at the University of Utah together with colleagues from the University of Wisconsin – highlights the importance of preventing early exposure to tobacco through public health policies.

These common genetic variations, or single nucleotide polymorphisms (SNPs), are changes in a single unit of DNA.  A haplotype is a set of SNPs that are statistically linked.  The researchers found that one haplotype for the nicotine receptor put European American smokers at a greater risk of heavy nicotine dependence as adults, but only if they began daily smoking before the age of 17.  A second haplotype actually reduced the risk of adult heavy nicotine dependence for people who began smoking in their youth.

The researchers studied 2,827 long-term European American smokers, recruited in Utah and Wisconsin, and to the National Heart, Lung, and Blood Institute’s Lung Health Study.  They assessed the level of nicotine dependence for all smokers, recording the age they began smoking daily, the number of years they smoked, and the average number of cigarettes smoked per day.  DNA samples were taken from all smokers, and the researchers recorded the occurrence of common SNPs, grouped into four haplotypes, which had been identified earlier in a subset of participants.

They found that people who began smoking before the age of 17 and possessed two copies of the high-risk haplotype had from a 1.6-fold to almost 5-fold increase in risk of heavy smoking as an adult.  For people who began smoking at age 17 or older, presence of the high-risk haplotype did not significantly influence their risk of later addiction.

Although the authors caution that different haplotype frequencies would likely be observed in different ethnic populations, Robert Weiss, Ph.D., professor of human genetics at the University of Utah and lead author of the study, explains: “We know that people who begin smoking at a young age are more likely to face severe nicotine dependence later in life.  This finding suggests that genetic influences expressed during adolescence contribute to the risk of lifetime addiction severity produced from the early onset of tobacco use.”

“This study adds to recent advances in understanding how genetic variation can affect susceptibility to nicotine addiction, success or failure of smoking cessation treatments, and the risk of disease associated with tobacco use,” says National Institute on Drug Abuse (NIDA) Director Dr. Nora Volkow.  “As we learn more about how both genes and environment play a role in smoking, we will be able to better tailor both prevention and cessation programs to individuals.”  The study was funded in part by NIDA and the National Heart, Lung, and Blood Institute (NHLBI), parts of the National Institutes of Health (NIH).

In the wild, mammalian coat color is essential for camouflage and plays a role in social behavior.  Coat color also strongly influences the animals we choose to breed both as livestock and as pets.  Understanding the genetic determinants of coat color in livestock species such as sheep, specifically bred for their coat color, is critical for improving efficient selection of the desired trait.

Classical genetics has associated alternative forms, or alleles, of the agouti signaling protein gene (ASIP) with coat color variation in a number of mammals including mice, rats, dogs, cats, pigs, and sheep.  However, most research has been focused on the mouse, with little understood about the genetic basis for coat color in economically important livestock species such as sheep.

The wild-type coat color of sheep is typically dark-bodied with a pale belly, however sheep raisers have strongly selected for a uniformly white coat domestic sheep.  A problem for the sheep industry is a recessive black “non-agouti” allele of the ASIP gene carried by white sheep that cannot be distinguished within the flock, resulting in black coat color at a low, but persistent frequency.  Determining the exact genetic differences at the ASIP locus could assist in efficient selection for white coat color.

Scientists at the CSIRO Queensland Bioscience Precinct in Australia have now taken this step and identified the molecular mechanisms underlying white and black coat color in domestic sheep.  The researchers investigated the genetic architecture of the ASIP gene in several sheep breeds by sequencing the ASIP locus and measuring gene expression.  “Surprisingly what we found was in fact that the genetic cause of domestic white and black sheep involves a novel tandem duplication affecting the ovine agouti gene and two other neighboring genes, AHCY and ITCH,” explains Dr. Belinda Norris, lead author of the study.  “We discovered a novel mechanism in which the dominant white sheep is caused by the ubiquitous expression of a duplicated agouti coding sequence located immediately downstream of a duplicated ITCH gene promoter region.”  It was found that recessive black sheep harbor only poorly expressed non-duplicated agouti alleles, likely a result of a defective single-copy ancestral agouti gene promoter.  The researchers also studied the ASIP locus in Barbary sheep, an ancient species exhibiting a tan body and pale belly.  They confirmed in this ancient sheep that expression of a single-copy agouti gene determines coat color patterning, similarly to findings previously described in mice and pigs.

Norris notes that this work will aid in the development of gene copy number detection and analysis methods in the mapping and association of heritable traits in livestock animals.  For sheep raisers, this could ultimately mean a genetic test that would identify carriers of the black non-agouti allele.  Furthermore, these findings will help to unravel the events leading to the domestication of sheep, and future work may be able to pinpoint when the dominant Agouti mutation occurred, and whether it occurred as single or multiple events.

Many of the seemingly disparate mutations recently discovered in autism may share common underlying mechanisms, say researchers supported in part by the National Institute of Mental Health (NIMH), a part of the National Institutes of Health (NIH).  The mutations may disrupt specific genes that are vital to the developing brain, and which are turned on and off by experience-triggered neuronal activity.

A research team led by Christopher Walsh, M.D., Ph.D., and Eric Morrow, M.D., Ph.D., of Harvard University, found two large sections missing on chromosomes in people with autism and traced them to likely inherited mutations in such genes regulated by neuronal activity.  They report their findings in the July 11, 2008 issue of Science.  The study was also supported in part by the NIH’s National Center for Research Resources, National Human Genome Research Institute, Eunice Kennedy Shriver National Institute of Child and Human Development, and the National Institute on Neurological Disorders and Stroke.

The study breaks new ground for complex disorders like autism, taking advantage of a shortcut to genetic discovery by sampling families in which parents are cousins.  The researchers found genes and mutations associated with autism in 88 families from the Middle East, Turkey and Pakistan in which cousins married and had children with the disorder.

“The emerging picture of the genetics of autism is quite surprising.  There appear to be many separate mutations involved, with each family having a different genetic cause,” explained NIMH Director Thomas R. Insel, M.D. “The one unifying observation from this new report is that all of the relevant mutations could disrupt the formation of vital neural connections during a critical period when experience is shaping the developing brain.”

Earlier studies had suggested that the individually rare mutations are present in at least 10 percent of sporadic cases of autism, which is the most common form.

The researchers used a technique that pinpoints from a relatively small group of families genes responsible for disorders that can be amplified by parenthood among relatives, which can increase transmission of recessive diseases.  Evidence had hinted at such transmission in autism, and the large amount of genetic information obtainable from such families reduced the need for a much larger sample including many families with multiple affected members.

The ratio of females to males with autism – normally one female to four males – was less lopsided in such families in which parents share a common recent ancestor.  This ratio equalized even more in a subset of these families with more than one affected member, suggesting a doubling of the rate of autism, due to recessive causes on non-sex-linked chromosomes.  Also, autism-linked spontaneous deletions and duplications of genetic material were relatively uncommon in these families, suggesting recessive inherited causes.

The researchers found multiple different genetic causes of autism in different individuals with little overlap between the families in which parents shared ancestry.  Yet a few large inherited autism-linked deletions, likely mutations, in a minority of families stood out.  The largest turned out to be in or near genes regulated, directly or indirectly, by neuronal activity.

“Autism symptoms emerge at an age when the developing brain is refining the connections between neurons in response to a child’s experience,” explained Walsh.  “Whether or not certain important genes turn on is thus dependent on experience-triggered neural activity.  Disruption of this refinement process may be a common mechanism of autism-associated mutations.”

By injecting purified stem cells isolated from adult skeletal muscle, researchers have shown they can restore healthy muscle and improve muscle function in mice with a form of muscular dystrophy.  Those muscle-building stem cells were derived from a larger pool of so-called satellite cells that normally associate with mature muscle fibers and play a role in muscle growth and repair.

In addition to their contributions to mature muscle, the injected cells also replenished the pool of regenerative cells normally found in muscle.  Those stem cells allowed the treated muscle to undergo subsequent rounds of injury repair, they found.

“Our work shows proof-of-concept that purified muscle stem cells can be used in therapy,” said Amy Wagers of Harvard University, noting that in some cases the stem cells replaced more than 90 percent of the muscle fibers.  Such an advance would require isolation of stem cells equivalent to those in the mouse from human muscle, something Wagers said her team is now working on.

Satellite cells were first described decades ago and have since generally been considered as a homogeneous group, Wagers said.  While anatomically they look similar under a microscope, they nonetheless show considerable variation in their physiology and function.  In a previous study, Wagers’ identified a set of five markers that characterize the only subset of satellite cells responsible for forming muscle, which they also refer to as skeletal muscle precursors or SMPs.

In the new study, the researchers analyzed the stem cell and regenerative properties of those SMPs.  When engrafted into muscle of mice lacking dystrophin, purified SMPs contributed to up to 94 percent of muscle fibers, restoring dystrophin expression and significantly improving muscle structure and contractile function, they report.  (The dystrophin gene encodes a protein important for muscle integrity.  Mice lacking dystrophin, also known as mdx mice, are a model for Duchenne Muscular Dystrophy, the most prevalent form of muscular dystrophy.)

” Importantly, high-level engraftment of transplanted SMPs in mdx animals shows therapeutic value—restoring defective dystrophin gene expression, improving muscle histology, and rescuing physiological muscle function,” the researchers said.  “Moreover, in addition to generating mature muscle fibers, transplanted SMPs also re-seed the satellite cell niche and are maintained there such that they can be recruited to participate in future rounds of muscle regeneration.

“Taken together, these data indicate that SMPs act as renewable, transplantable stem cells for adult skeletal muscle.  The level of myofiber reconstitution achieved by these myogenic stem cells exceeds that reported for most other myogenic cell populations and leads to a striking improvement of muscle contraction function in SMP-treated muscles.  These data thus provide direct evidence that prospectively isolatable, lineage-specific skeletal muscle stem cells provide a robust source of muscle replacement cells and a viable therapeutic option for the treatment of muscle degenerative disorders.”

Wagers noted however that there may be complications in the delivery of cell therapy in humans, particularly for those with conditions influencing skeletal muscle throughout the body.  Even so, the new findings present an “opportunity to understand what happens [to these regenerative cells] in disease and identify factors and pathways that may boost their activity,” she said.  “We may get a handle on drugs that could target muscle impairment” not only in those with muscular dystrophies, but also in elderly people suffering from the muscle wasting that comes with age.

However much the likes of Jamie Oliver or Gordon Ramsay might want to shake up our diets, culinary evolution dictates that our cultural cuisines remain little changed as generations move on, shows new research, published today, Thursday, 10 July, 2008, in the Institute of Physics (IOP)’s New Journal of Physics (NJP).

The research, ‘The non-equilibrium nature of culinary evolution’, shows that three national cuisines British, French and Brazilian – are affected by the founder effect which keeps idiosyncratic and nutritionally ambivalent, expensive and sometimes hard to transport ingredients in our diets.

Using the medieval cookery book, Pleyn Delit, and three authoritative cook books from Britain, France and Brazil, the New Penguin Cookery Book, Larousse Gastronomique and Dona Benta respectively, the researchers from the University of Sao Paulo, Brazil, compiled statistics which could be compared to see how time and distance effect the three different national cuisines.

Time, the number of ingredients used, the number of recipes published in each cook book and the ratio between the number of ingredients and the number of recipes in the books were used as variables to assess how our diets have evolved.

Three editions of Dona Benta, from 1946, 1969 and 2004, were evaluated to see how the Brazilian diet has changed over the past half century, amidst the change from a regional to a more globalised food consumer profile, and found that the rank and importance of certain idiosyncratic ingredients, such as chayote, an edible plant that is a frequent ingredient in Central and South American diets, remained much the same.

Ranking the importance of certain food types by their frequency of use in each national cuisine and comparing them to ingredients which have an equivalent rank in one of the other two foreign cuisines led to patterns emerging which suggest that all our menus evolve in similar ways.

So, whether it’s the Irish with potatoes, the French with frogs’ legs, the Germans with sauerkraut, the Ghanaians with plantains or the Japanese with fish stock, it seems a global food culture has not shifted some die-hard culture-based eating habits.

As the authors, from the Department of Physics and Mathematics at Sao Paulo University, write, “Some low fitness ingredients present in the initial recipes have a strong difficulty of being replaced and can even propagate during culinary growth.  They are like frozen “cultural” accidents.”

Neuroscientists at Georgetown University Medical Center have solved a mystery that lies at the heart of human learning, and they say the solution may help explain some forms of mental retardation as well as provide clues to overall brain functioning.

Researchers have long puzzled over why a gene known as brain-derived neurotrophic factor (BDNF), which is crucial to the ability of neurons in the hippocampus to grow and connect to each other – forming the basis of memory and learning – produces two different transcripts, which then each fabricate identical proteins.

In the July 11 issue of Cell, the scientists report the answer, and it has to do with transportation.  They found that the longer of the two transcripts (messenger RNAs, or mRNAs) include extra sequences that “motor” molecules attach to, in order to move the information far away from the nucleus of the cell and toward the long, tree-like branches of the nerve cell known as dendrites.  There, protein-synthesizing machines use that mRNA to produce protein that helps small protrusions (called dendritic spines) on these dendrites grow.

The shorter of the mRNAs are also moved from the nucleus into the cytoplasm of the neuron, but they do not need to be transported to dendrites.  These transcripts produce an identical protein, but in this case, investigators believe they help the axon, the long cable-like body of a neuron, grow.

Learning occurs when both axons and dendritic spines grow and touch each other, forming connections, and existing connections are strengthened.  The scientists’ findings provide a critical understanding of how dendritic spines grow and mature, but this understanding may be more broadly applied.

That’s because as exciting as the findings are for understanding the function – and dysfunction of BDNF as it relates to human learning, they also are relevant for other genes and proteins, says the study’s lead investigator, Baoji Xu, Ph.D., an assistant professor in the Department of Pharmacology at Georgetown.

“The fascinating thing is that many genes produce multiple transcripts for the same protein – and no one has known why,” he says.  “So what we found here is likely very applicable to other genes.  It reveals a mechanism for differential regulation of subcellular functions of proteins.”

In this study, Xu and his research team, which included investigators from the National Institute of Child Health and Human Development (NICHHD), Emory University, and the University of Colorado, looked at why a neuron needs two “species” of BDNF mRNAs.

The gene produces a growth factor that makes neurons grow, and is vital to initial development of the brain; mice born without BDNF have developmental deficits and soon die.  BDNF is also secreted by neurons in adult brains when needed, and that is usually when synaptic junctions between neurons require strengthening, a condition known as “synaptic plasticity” that underlies memory and learning.  “If BDNF is deleted in an adult animal’s brain, the animal will struggle to learn new tasks,” Xu says.

Scientists had found that protein translation occurs in dendrites, and they believed that this protein production was important for synaptic plasticity, “but it has been difficult to study local protein synthesis only in dendrites,” Xu says.  “When you change protein synthesis in dendrites, you also affect protein production in other parts of the neuron.”

To solve that problem, Xu and the scientists managed to create mouse mutants in which the long BDNF mRNA variant is converted to the shorter mRNA form.  They found that in these mice, dendritic spines form normally, but do not mature properly and aren’t “pruned” as they need to be.  “This process is important for the normal function of the brain.  Without it, the mice can’t refine neuronal connections in response to learning,” he says.

Some people diagnosed with mental retardation suffer from the same problem, Xu adds.  “At a certain stage of development, maturation of dendritic spines is frozen.  For example, in Fragile X Syndrome, there are too many immature dendritic spines.

“What we see in our mutant mouse and in Fragile X is similar,” he says.  “If we could find a way to increase BDNF synthesis in dendrites, it may be helpful to people with mental retardation.

“That, of course, is just a theory, but now that we understand the function of these two different mRNAs, we can begin to explore what issues their dysfunction causes in humans,” Xu says.