We all know that people can be influenced in complex ways by their peers.  But two new studies in the September 11th issue of Current Biology, a Cell Press publication, reveal that the same can also be said of fruit flies.

The researchers found that group composition affects individual flies in several ways, including changes in gene activity and sexual behavior, all mediated by chemical communication.

“Many take for granted that communication among insects is hard-wired,” said Joel Levine of the University of Toronto Mississauga.  “We have observed that communication may be influenced by relationships even in insects like fruit flies, which have not been traditionally considered to be social insects.  We have seen individual responses that appear to be altered quickly–within a day of joining a group.  This level of spontaneity or plasticity is complex because it occurs on many levels: involving neural and non-neural tissues, changes in gene expression and physiology, and changes in behavior, all of which are inter-related.”

That connection between an individual and its environment, both social and otherwise, reveals a depth that is often missing in experiments that focus exclusively on one or the other, he said.

In one study, the researchers reveal that specialized cells of the fly called oenocytes, which produce chemical signals known as pheromones, operate according to an internal circadian clock.  However, the “ticking” of that clock varies depending upon the social environment the flies find themselves in: Males in mixed company—meaning in the company of other flies that were less similar at the genetic level—produced different chemical signals than did males in genetically uniform group, they found.

Those signals had a clear effect on behavior: flies in genetically more mixed social groups had more sex than those in more uniform groups did.

To further explore the connection between chemical communication amongst fruit flies and their physical and social environments, the researchers examined in a second study the chemical composition of pheromones produced by flies in mixed versus homogeneous groups.  Those tests were conducted in flies under conditions of constant darkness and in those under a normal light-dark cycle.

Their results showed important effects on flies of both the physical and social environment.  Moreover, they found a strong interaction between the genetic background of individual flies and their social environments.

“The response of an individual male to others like him depends on his neighbors,” Levine said.  “That response is quite specific because it affects some of the chemicals made by a fly, but not others.”

The results suggest that chemical communications is a rather “fickle” trait, depending heavily on the influence of a fly’s peers.

The findings also challenge the traditional view of the relationship between behavior and the underlying mechanisms that control that behavior, Levine noted.

“The bottom line is that membership in the same social group trumps genotype as a predictor of chemical displays,” he said.  “At a general level the surprise comes from appreciating that molecular function is altered by behavior.  Behavior is not only the product of molecular mechanisms, it is also a player in those mechanisms.”

Breakthroughs in cytogenetic technologies, which focus on subtle alterations in genes and chromosomes, are enabling a new level of detail and accuracy in the diagnosis of complex and unexplained developmental problems in children.

The availability of this new information can help clinicians shift to a “genotype first” model of diagnosis, according to David H. Ledbetter, PhD, Woodruff professor of human genetics at Emory University and director of the Division of Medical Genetics.

Ledbetter’s editorial on “Cytogenetic Technology–Genotype and Phenotype,” is published online this week by the New England Journal of Medicine.  It accompanies an article by Heather Mefford and colleagues about using new cytogenetic technologies to identify microdeletions and microduplications in a specific region of chomosome 1q21.1 in patients with unexplained mental retardation, autism or congenital anomalies

Cytogenetic arrays that reveal DNA microdeletions and additions, including single-copy changes of a few hundred base pairs, beadchips that detect single-nucleotide polymorphisms (SNPs) and tests called comparative genomic hybridization have led to an exciting renaissance of genetics-based syndrome delineation, says Ledbetter in his editorial.

“In the early 1960s we began discovering the relationship between chromosome imbalance and diseases and syndromes, such as Down syndrome,” says Ledbetter.  “This was based on identifying multiple patients with the same cytogenetic abnormality and similar clinical symptoms.  Ever since then, technology breakthroughs have allowed us to identify new syndromes and ever more subtle genetic differences.”

The current proliferation of new genetic information has led researchers to discover that many small genetic variations are common and mostly benign in the human population.  This means the relationship between DNA variations and disease must be analyzed even more carefully in order to find accurate connections.  In order to prove that a genetic difference is directly related to a particular syndrome, notes Ledbetter, researchers must show that the difference is never found in normal control individuals or at least is found with significantly less frequency.

Also, researchers have found that a particular genetic variation may have only a mild effect in a parent but a much more severe effect in a child who inherits the same variant.  And a group of children may have a variety of different problems resulting from the same gene variation.  Whole-genome cytogenetic arrays are becoming much more common, however, which is bringing genetic testing to the level of everyday medicine.

“So many variations of developmental disorders and syndromes have been discovered that genetic testing has become essential for making a specific clinical diagnosis,” says Ledbetter.  “Although more information has made the job of a diagnostician even more challenging, it also is leading to more accurate diagnoses and should lead to much more effective treatments.”

The level of nutrients in soil determines how many different kinds of plants and trees can thrive in an ecosystem, according to new research published by biologists and mathematicians today (10 September) in Nature.

For the first time ever mathematicians have modelled all the different possible relationships between nutrients and biodiversity in lab-based experimental ecosystems.  They found that although nutrient availability definitely has an impact on biodiversity, the precise relationship between the two depends on which species are present in the ecosystem.  This means that in some cases low levels of nutrients can lead to high levels of biodiversity.

The new study involved biologists from the University of California Santa Cruz running a lab experiment to find out how different levels of nutrients affected how many species evolved in an ecosystem.  Mathematicians from Imperial College London and the University of Bath then devised a model to show how far the results could be applied to real world scenarios.

The experiments set up by the biologists in the USA consisted of mini ecosystems full of E. coli bacteria and a parasite that lives on the E. coli.  These simple communities of hosts and pathogens represent complex ecosystems in the real world, like forests, in which hosts such as trees live and evolve alongside pathogens such as fungi, bacteria and viruses.

The overall aim of the study was to shed new light on the mystery of why some ecosystems such as tropical rainforests are teeming with thousands of different plant species, whereas others, like the pine forests of northern Europe, support significantly fewer types of plant life.  However, investigating this phenomenon in the field can be difficult, time consuming and results hard to interpret.

Instead, the researchers used the series of mini-ecosystems in the lab, which consisted of test tubes containing E. coli bacteria, a sugary Lucozade-like liquid for the E.coli to eat, and a parasite that lives on the E. coli.

To mimic different environments, the scientists varied the amount of sugar in each different ‘ecosystem’, and then recorded how many new strains of bacteria and parasite evolved in the sugary broth over the course of 150 generations, which took 17 days.

Their results showed that as the levels of sugar in the ecosystem changed, so did the extent to which new strains evolved.  This experiment showed that the highest biodiversity resulted from a low level of nutrients.

Professor Laurence Hurst from the University of Bath’s Department of Biology explains: “The results in the lab showed that varying the level of sugary food in these mini-ecosystems caused the amount of biodiversity in the ecosystems to change.  This suggests that the availability of nutrients is one of the factors that affect how many different plant species live in different parts of the world.  This has been shown in a lab before, but what we wanted to do was use maths to show how these results, which refer to one kind of bacteria and its parasite, can be applied to other organisms and ecosystems in the real world.”

The team from Bath and Imperial constructed a model to work out whether this inverse relationship would be the same in all ecosystems – whether in the lab or in the real world.  They found that although nutrients do affect biodiversity, the precise relationship between the two varies from one ecosystem to the next, depending on what species are present.

Dr Rob Beardmore from Imperial College London’s Department of Mathematics explains: “Although there was a clear link between nutrients and biodiversity in the lab, our mathematical model showed that in some ecosystems you will find that higher levels of nutrients lead to more biodiversity, which is opposite to what our biologist colleagues found in the lab.  It turns out that the precise nature of this nutrient-diversity relationship varies from one ecosystem to another, and it depends on the complex interactions between species evolving alongside each other.”

The mathematical model can be used to predict what impact different levels of nutrients will have on biodiversity in any given lab-based ecosystem.  The team say their results are very important for scientists who use small scale lab experiments to investigate phenomena in the real world.

The study also provides the first real evidence that a theory known as “geographic mosaic co-evolution hypothesis” holds up in real world ecosystems.  Co-author on the paper, Dr Ivana Gudelj from Imperial College, explains: “This complicated-sounding theory basically says that nutrient availability will only have an impact on the diversity of an organism, if the organism is involved in a co-evolutionary arms race with pathogens or competitors, like our E.coli was with its parasite.  Our biologist colleagues have shown evidence for this in the lab, and our mathematical model suggests that the theory will also hold up in real world ecosystems too.”

A new study suggests that although humans may have developed complex thought processes that can help to regulate their emotions, these processes are linked with evolutionarily older mechanisms that are common across species.  The research, published by Cell Press in the September 11th issue of the journal Neuron, provides new insight into way the brain manages fear and may guide exploration of novel pharmacological and therapeutic treatments for anxiety disorders.

“The ability to eliminate, control or diminish negative emotional responses is important for adaptive function and critical in the treatment of psychopathology,” says study author, Dr. Mauricio Delgado from Rutgers University.  “Recent research examining the neural mechanisms for diminishing fears has focused on two techniques: extinction, which has been explored across species, and cognitive emotion regulation strategies, which are unique to humans.”  Previous work in rodents and humans has implicated activity in the amygdala and ventral medial prefrontal cortex (vmPFC) in extinction.  In contrast, neural circuits underlying cognitive strategies to regulate emotions are not as well understood.

Dr. Delgado, Dr. Elizabeth A. Phelps from New York University, and their colleagues were interested in examining the similarities and differences of diminishing fear through both techniques.  They used similar experimental paradigms with different means of controlling fear to directly compare the neural mechanisms that mediate extinction and emotional regulation.  A typical fear conditioning method was paired with a measurement of physiological arousal to examine extinction, while a cognitive emotion regulation strategy was also implemented.  Functional magnetic resonance imaging (fMRI) was used to compare the neural activation patterns of extinction and emotional regulation.

The researchers observed that the lateral prefrontal cortex regions engaged by cognitive emotion regulation strategies influenced the amygdala and diminished fear through similar vmPFC connections that are thought to inhibit the amygdala during extinction.  Taken together, the findings indicate that there is overlap in the neural circuitry of diminishing learned fears through emotion regulation and extinction and that vmPFC may play a general regulatory role in diminishing fear across a range of paradigms.

“Our results suggest that even though humans may have developed unique capabilities for using complex cognitive strategies to control emotion, these strategies may influence the amygdala through phylogenetically shared mechanisms of extinction,” explains Dr. Phelps.  “Extinction and cognitive emotion regulation may be, in part, complementary in that they rely on a common neural circuitry and, perhaps, similar neurophysiological and neurochemical mechanisms.”

New research identifies a few critical neurons that initiate sex-specific behaviors in fruit flies and, when masculinized, can elicit male-typical courtship behaviors from females.  The study, published by Cell Press in the September 11th issue of the journal Neuron, demonstrates a direct link between sexual dimorphism in the brain and gender differences in behavior.

In the fruit fly, Drosophila melanogaster, males display a series of complex and stereotypic behaviors when they are courting a female.  Males chase the female while vibrating their wings, producing a love song that has an aphrodisiac influence on the female, who would otherwise take action to escape the male’s advances.  Later steps in the male courtship behavior involve the initiation and completion of copulation.

“Although previous studies have identified a few key brain areas, such as the dorsal posterior brain, that appear to play a pivotal role in initiating male sexual behavior, nothing is known about the identity of neurons and their circuits in the brain sites which are central to the generation of male courtship behavior,” says lead study author Professor Ken-ichi Kimura of the Hokkaido University of Education in Japan.

Professor Kimura and colleagues made use of a sophisticated technique that allowed them to identify, manipulate, and study small groups of cells in the fruit fly brain.  The researchers focused on neurons that expressed a gene called fruitless (fru), a known sex-determination gene.  The male-specific Fru protein is expressed in the brains of male flies, but not females.  Studies have indicated that fru functions in parallel with another sex-determination gene called doublesex (dsx) and that fru may function as a kind of master control gene to direct organization of brain centers for sexual behavior.

A fru/dsx-expressing cell cluster, known as P1, was identified as an important site for initiating male courtship behavior.  P1 cells are fated to die in females through the action of a feminizing protein called DsxF.  Interestingly, genetic manipulation of females so that they possessed male P1 neurons effectively provoked male-typical courtship behavior in the females, even when other parts of the brain were not masculinized.

“P1 is located in the dorsal posterior brain and is composed of 20 neurons that have projections which communicate with the bilateral protocerebrum,” explains Professor Kimura.  “We found that the masculinizing protein Fru is required in the male brain for correct positioning of the projections from the P1 neurons.”

Taken together, these findings demonstrate that the coordinated action of sex-determination genes dsx and fru confer the unique ability to initiate male-typical sexual behavior on P1 neurons.  This research represents one of only a few examples presenting direct evidence for sexually dimorphic mechanisms that underlie gender-specific behavior and is the first to identify a specific cluster of cells that initiate courtship.

A surprising interaction may enable development of new HIV treatment strategies by exploiting infection with multiple pathogens.  The research, published by Cell Press in the September 11th issue of the journal Cell Host and Microbe, demonstrates that a drug commonly used to treat herpes directly suppresses HIV in coinfected tissues and thus may be beneficial for patients infected with both viruses.

Commonly, individuals infected with HIV are infected also with other microbes.  Infection with human herpesvirus (HHV), especially with herpes simplex virus-2 (HSV-2), is often associated with HIV.  These HHV infections may be either active or dormant, but HIV infection makes HHV reactivation more likely.

For many years, acyclovir (ACV), a well-studied drug, has been used safely to treat HHV in humans.  “HHV has a unique ability to phosphorylate ACV to activate it, making the drug quite specific for HHV and, for the same reason, relatively non-active against other viruses, including HIV,” offers senior study author Dr. Leonid Margolis from the National Institute of Health.  Nevertheless, some patients coinfected with HIV and HSV-2 exhibit lower HIV levels after ACV treatment.

“We decided to investigate this phenomenon experimentally using small blocks of human tissues” says Dr. Margolis.  “Drs.  Andrea Lisco and Christophe Vanpouille who performed this work in my laboratory found that although ACV doesn’t inhibit HIV in ’sterile’ cell lines, it does, surprisingly, suppress HIV in tissues that carry no HSV-2 but various other HHVs.”  In collaboration with a prominent AIDS researcher Dr. Raymond Schinazi from Emory University and Dr. Matthias Gotte from McGill University, the researchers found that phosphorylated ACV that is formed in HHV-infected cells directly inhibits the HIV-1 reverse transcriptase (RT), thus preventing HIV from copying itself.

These results not only help to explain the response to ACV seen in patients coinfected with HSV-2 and HIV, but also suggest that ACV may be used against HIV in patients infected with various other HHVs, including the low-pathogenic and ubiquitous HHV-6 and HHV-7.  Moreover, in collaboration with Drs.  Balzarini from Catholic University of Leuven and McGuigan from Cardiff University, Dr. Margolis and his team demonstrated that new strategies for development of novel HIV inhibitors based on ACV structure can now be developed.  “We provide definitive experimental evidence of inhibition of HIV-1 RT activity by phosphorylated ACV and demonstrate that ACV phosphorylation occurring in human tissues infected by various HHVs transforms this widely-used inexpensive anti-herpes drug into a direct HIV inhibitor,” concludes Dr. Margolis.

Some of the most challenging obstacles limiting the reprogramming of mature human cells into stem cells may not seem quite as daunting in the near future.  Two independent research papers, published by Cell Press in the September 11th issue of the journal Cell Stem Cell, describe new tools that provide invaluable platforms for elucidating the molecular, genetic, and biochemical mechanisms associated with reprogramming.  The new findings also offer considerable hope toward making the reprogramming process more therapeutically relevant.

Although scientists have successfully reprogrammed mature human skin cells into induced pluripotent stem (iPS) cells by expressing a few key transcription factors, the conversion has been extremely inefficient.  “Little is known about the mechanisms by which reprogramming occurs, in part because of the low efficiency,” says senior study author Dr. Konrad Hochedlinger from the Harvard Stem Cell Institute.  In addition, the iPS cells created thus far have been generated with retroviruses and noninducible lentiviruses, both of which have major limitations that are not compatible with clinical applications.

The Hochedlinger group created a drug-inducible viral system to generate human iPS cells that were molecularly and functionally similar to human embryonic stem cells.  This method was unique in that it allowed the researchers to create iPS cells by using the drug doxycycline to control expression of the necessary factors that had been delivered to the cells with viruses.

The researchers then found that when doxycycline was removed and these “primary” iPS cells differentiated to mature cells, another exposure to the drug reactivated the genes required for reprogramming and induced generation of “secondary” iPS cells at a frequency that was far greater that the initial “primary” conversion.  The idea of generating these secondary cells was conceived in previous experiments with mice performed in the lab of Dr. Rudolf Jaenisch from the Massachusetts Institute of Technology.

“The secondary system will enable chemical and genetic screening efforts to identify key molecular constituents of reprogramming, as well as important obstacles in this process, and will ultimately lend itself as a powerful tool in the development and optimization methods to produce human iPS cells,” explains Dr. Hochedlinger.

In a separate paper, Dr. Jaenisch’s group reports on their success in deriving human secondary iPS cells using doxycycline-inducible transgenes.  “The drug-inducible system we describe represents a novel, predictable, and highly reproducible platform to study the kinetics of iPS cell generation,” says Dr. Jaenisch.  “Further, the genetic homogeneity of secondary cells makes chemical and genetic screening approaches to enhance reprogramming efficiency or to replace any of the original reprogramming factors feasible.”

Both research teams found that generation of secondary human iPS cells required less time than the initial reprogramming.  Interestingly, the time required to generate iPS cells varied among the types of skin cells that were used.  For instance, human fibroblasts required several weeks, while keratinocytes required only about 10 days.  “The fast kinetics of reprogramming observed for keratinocytes suggests that these cells would be useful for development and optimization of methods to reprogram cells by transient delivery of factors,” suggests Dr. Hochedlinger.

The combined results from both research groups represent a major advance toward more efficient strategies for reprogramming differentiated human cells into iPS cells.  The methods described here will not only provide critical insight into the reprogramming process, but also, because of the abbreviated time frame, may lead to the generation of cells that will be amenable for therapies, as reprogramming might be achievable without the prohibitive viruses or genetic modifications.

Yeast, the essential microorganism for fermentation in the brewing of beer, converts carbohydrates into alcohol and other products that influence appearance, aroma, and taste.  In a study published online today in Genome Research, researchers have identified the genomic origins of the lager yeast Saccharomyces pastorianus, which could help brewers to better control the brewing process.

For thousands of years, ale-type beers have been brewed with Saccharomyces cerevisiae (brewer’s or baker’s yeast).  In contrast, lager beer, which utilizes fermentations carried out at much lower temperature than for ale, is a more recently developed alcoholic beverage, appearing in Bavaria near the end of the Middle Ages.  Lager beer gained worldwide popularity starting in the late 1800s, when the advent of refrigeration made year-round low-temperature fermentations possible.  Saccharomyces pastorianus, the yeast used in lager brewing, is a “hybrid” organism of two yeast species, Saccharomyces bayanus and S. cerevisiae.  It is thought that the contributions of both parent species resulted in an organism able to out-compete other yeasts during the cold lager fermentations.

Though early brewers understood that different brewing conditions would produce a unique beer, scientists are now unlocking the genetic differences between yeast strains that produce variation in flavor, color, and aroma.  By comparing the genomic properties of yeast strains sampled from breweries around the world, Drs.  Barbara Dunn and Gavin Sherlock of Stanford University have measured the genetic contribution of the parent yeasts to strains of S. pastorianus and revealed new insights into the events that brought about the evolution of lager yeast.

Surprisingly, the researchers found evidence that S. pastorianus strains used by brewers today may not have arisen from a single hybridization event, as was previously believed.  “There were two independent origins of today’s extant S. pastorianus strains,” said Sherlock.  “It is likely that each of these groups derived the S. cerevisiae portions of their genomes from distinct but related ale yeasts, and that these natural hybrids were then selected by brewers due to their abilities to ferment at cold temperatures.”

While this work identified two distinct groups of S. pastorianus, Sherlock noted that they observed significant genetic variation and flexibility within the groups as well.  Dunn and Sherlock speculated this genomic flexibility could have implications for the unique properties of each brewer’s beer.  “The fact that lager yeasts isolated from different breweries each seem to have a unique genomic make-up may indicate that the yeasts are adapting to the conditions specific to each brewery,” explained Dunn.

Furthermore, this work paves the way for the characterization of specific genetic features of each strain that could aid in the brewing process.  “Our discovery that unique genomic structures may be characteristic to each brewery and/or beer type could lead to insights on how to directly control flavor and aroma in beer,” said Dunn.

Heart disease is the leading cause of death worldwide.  However, many people with cardiovascular disease have none of the common risk factors such as smoking, obesity and high cholesterol.  Now, researchers have discovered a new link between gum disease and heart disease that may help find ways to save lives, scientists heard today (Tuesday 9 September 2008) at the Society for General Microbiology’s Autumn meeting being held this week at Trinity College, Dublin.

In recent years chronic infections have been associated with a disease that causes “furring” of the arteries, called atherosclerosis, which is the main cause of heart attacks.  Gum disease is one of the most common infections of humans and there are now over 50 studies linking gum disease with heart disease and stroke.

“A number of theories have been put forward to explain the link between oral infection and heart disease,” said Professor Greg Seymour from the University of Otago Dunedin, New Zealand.  “One of these is that certain proteins from bacteria initiate atherosclerosis and help it progress.  We wanted to see if this is the case, so we looked at the role of heat shock proteins.”

Heat shock proteins are produced by bacteria as well as animals and plants.  They are produced after cells are exposed to different kinds of stress conditions, such as inflammation, toxins, starvation and oxygen and water deprivation.  Because of this, heat shock proteins are also referred to as stress proteins.  They can work as chaperone molecules, stabilising other proteins, helping to fold them and transport them across cell membranes.  Some also bind to foreign antigens and present them to immune cells.

Because heat shock proteins are produced by humans as well as bacteria, the immune system may not be able to differentiate between those from the body and those from invading pathogens.  This can lead the immune system to launch an attack on its own proteins.  “When this happens, white blood cells can build up in the tissues of the arteries, causing atherosclerosis,” said Professor Seymour.

“We found white blood cells called T cells in the lesions of arteries in patients affected by atherosclerosis.  These T cells were able to bind to host heat shock proteins as well as those from bacteria that cause gum disease.  This suggests that the similarity between the proteins could be the link between oral infection and atherosclerosis,” said Professor Seymour.

This molecular mimicry means that when the immune system reacts to oral infection, it also attacks host proteins, causing arterial disease.  These findings could fundamentally change health policy, highlighting the importance of adult oral health to overall health and wellbeing: control of gum disease should be essential in reducing the risk of heart disease.

“This is a significant step towards a more complete understanding of heart disease and improving treatment and preventive therapies,” said Professor Seymour.  “An understanding of all the possible risk factors could help lower the risk of developing heart disease and lead to a significant change in disease burden.”

Yeast fungus cells that kill thousands of AIDS patients every year escape detection by our bodies’ defences by hiding inside our own defence cells, and hitch a ride through our systems before attacking and spreading, scientists heard today (Tuesday 9 September 2008) at the Society for General Microbiology’s Autumn meeting being held this week at Trinity College, Dublin.

Cells of the Cryptococcus yeast responsible for one of the three most life-threatening infections that commonly attack HIV infected patients, causing cryptococcal meningitis, are using a previously unknown way to avoid detection, according to scientists from the University of Birmingham, UK.

“We have shown that these airborne yeast cells can hide inside our bodies’ own white blood cells, called macrophages, and then use them as vehicles to travel around inside our bodies, using them just like a bus,” said Miss Hansong Ma of the University of Birmingham.  “The yeast cells then escape from inside the macrophages when they arrive at the right destination – but importantly, they do this without killing the macrophage, which would trigger alarm bells.”

When a host’s cells are invaded by bacteria, fungi or viruses the invaders usually use the opportunity to multiply inside the cells and escape by bursting out, killing the host and releasing thousands of copies of the pathogen to attack other cells.  The death of the host cell releases debris and by-products which usually triggers our bodies into mounting an immune response, causing inflammation.

“This new method of remaining inside the host cells means that the pathogen can spread more efficiently round our bodies and is protected from the natural defences in our bloodstream that would normally kill the yeast or other invader,” said Hansong Ma.  “Yeast cells avoid killing or damaging the macrophages.  They leave by a method that we call ‘vomocytosis’; the yeast cells are acting like spies rather than terrorists, and go unnoticed, giving them more time to establish an infection.”

Although the use of antiretroviral drugs is cutting the number of AIDS patients with Cryptococcus infections there is still a major epidemic in Southeast Asia and Africa.  Up to 30% of AIDS patients there are infected, and up to 44% will die from the disease within 8 weeks.  Even in the USA or European countries like France where antiretroviral drug treatments are readily available, one in ten infected patients will die.

“We badly need to better understand the interaction between hosts, viruses and attacking pathogens like the yeast fungus to help us find new drug targets and so design new ways to treat these patients,” said Hansong Ma.

“We used time-lapse microscope photography to identify this new escape mechanism, and watched the yeast cells escaping into the fluid surrounding cells or, remarkably, directly into other host cells through cell-to-cell transmission, continuing to avoid detection by using this extremely rapid vomocytosis,” said Hansong Ma.  “Worryingly, this enables the cryptococci to avoid antifungal drugs and other treatments as well as our normal immune system, and may allow the yeast to become latent, achieving a long-term infectious state which could then be spread even further, to other individuals, without anyone realising.”

Bacteria found in compost heaps able to convert waste plant fibre into ethanol could eventually provide up 10% of the UK’s transport fuel needs, scientists heard today (Tuesday 9 September 2008) at the Society for General Microbiology’s Autumn meeting being held this week at Trinity College, Dublin.

Researchers from Guildford, UK, have successfully developed a new strain of bacteria that can break down straw and agricultural plant waste, domestic hedge clippings, garden trimmings and cardboard, wood chippings and other municipal rubbish to convert them all into useful renewable fuels for the transport industry.

“The bioethanol produced in our process can be blended with existing gasoline to reduce overall greenhouse gas emissions, help tackle global warming, reduce dependence upon foreign oil and help meet national and international targets for renewable energy,” said Paul Milner, Fermentation Development Manager of TMO Renewables Ltd, based in Surrey Research Park, Guildford.

The new strain of bacteria allows ethanol to be produced much more efficiently and cheaply than in traditional yeast-based fermentation, which is based on the beer-brewing process and forms the basis for most current commercial bioethanol production.

“Conventional ethanol production is energy-intensive, expensive, and time-consuming as the barley malt or other material being brewed needs to be heated up as a mash in feedstock pre-treatment.  Then it is significantly cooled from that high temperature to a lower temperature for yeast fermentation, only to be re-heated when it is later distilled into ethanol.  Our process is much more energy-efficient.”  Said Paul Milner.

TMO’s microbiologists screened thousands of different wild types of bacteria, looking for one that could survive high temperatures and that liked feeding off a wide variety of plant based materials.

“We found some heat-loving bacteria in a compost heap, from the Geobacillus family, which in their wild form produce lactic acid as a by-product of sugar synthesis when they break down biomass,” said Paul Milner.  “We altered their internal metabolism, adapting them to produce substantial amounts of ethanol instead”.

“Our new microorganism, called TM242, can efficiently convert the longer-chain sugars from woody biomass materials into ethanol.  This thermophilic bacterium operates at high temperatures of 60oC-70oC and digests a wide range of feedstocks very rapidly,” said Paul Milner.

The scientists estimate that some 7 million tons of surplus straw is available in the UK every year.  Turning it into ethanol could replace 10% of the gasoline fuel used in this country.  “As our process uses agricultural waste materials such as straw, wood, paper and plants and other cellulosic fibre from domestic and municipal waste, it provides significantly greater environmental and economic benefits than crop-derived biofuels which some believe have contributed to the increased prices of basic food in so many countries,” said Paul Milner.

“We have recently completed commissioning the UK’s first cellulosic ethanol demonstration facility – one of just a handful worldwide,” said Paul Milner.  “We are constantly researching new, better ways to produce biofuels.  We also believe that our process can be used successfully beyond biofuels to produce other high-value chemicals and drug ingredients that are currently derived from oil.”

Individuals who have a genetic mutation associated with high body mass index (BMI) may be able to offset their increased risk for obesity through physical activity, according to a report in the September 8 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

There is a widely acknowledged genetic component to BMI and obesity, according to background information in the article.  Recently, a strong association has been shown between BMI and variants of one gene, known as the fat mass and obesity associated (FTO) gene.  The mutations associated with obesity are present in about 30 percent of European populations and are associated with a 1.75-kilogram (about 3.9 pounds) increase in body weight.  Lifestyle factors such as diet and physical activity are also important contributors to weight gain, but it is unknown exactly how they interact with genetics.

Evadnie Rampersaud, M.S.P.H., Ph.D., then of the University of Maryland School of Medicine in Baltimore and now of the University of Miami, and colleagues analyzed DNA samples of 704 healthy Amish adults (average age 43.6, 53 percent men and 47 percent women) recruited from 2003 to 2007.  Participants also underwent a series of physiological tests, including a seven-day measurement of physical activity using an instrument known as an accelerometer.

A total of 54 percent of the men and 63.7 percent of the women were overweight, and 10.1 percent of the men and 30.5 percent of the women were obese.  In the genetic analysis, 26 single-nucleotide polymorphisms (SNPs, or changes in a single base letter of DNA) in the FTO gene were associated with BMI.

The researchers then divided participants into two groups based on their physical activity levels and assessed the relationship between BMI and the two strongest SNPs.  Both SNPs were associated with BMI only in individuals who had low physical activity scores for their age and sex; they had no effect on those with above-average physical activity scores.

“Activity levels in the ‘high-activity’ stratum were approximately 900 calories [860 calories for women and 980 calories for men] higher than in the ‘low-activity’ stratum, which, depending on body size, corresponds to about three to four hours of moderately intensive physical activity, such as brisk walking, house cleaning or gardening,” the authors write.

“In conclusion, we have replicated the associations of common SNPs in the FTO gene with increased BMI and risk to obesity in the Old Order Amish,” they conclude.  “Furthermore, we provide quantitative data to show that the weight increase resulting from the presence of these SNPs is much smaller and not statistically significant in subjects who are very physically active.  This finding offers some clues to the mechanism by which FTO influences changes in BMI and may have important implications in targeting personalized lifestyle recommendations to prevent obesity in genetically susceptible individuals.”

A team including researchers at the HudsonAlpha Institute and Stanford University, together with colleagues from a number of other organizations, today publishes a comprehensive analysis of genomic variation in the brain cancer glioblastoma. These results are the first from the Cancer Genome Atlas (TCGA) research network, a collaborative effort funded by the National Cancer Institute and the National Human Genome Research Institute of the National Institutes of Health. Glioblastoma is the most common and most aggressive of the primary brain tumors: Notably, U.S. Senator Edward M. Kennedy was diagnosed with glioblastoma earlier this year.Drs. Devin Absher and Rick Myers, with their labs at HudsonAlpha and Stanford, measured changes in the genetic code of both normal and cancer samples. They specifically looked at regions that either gained or lost large chunks of DNA, larger than 1000 bases, to determine the molecular differences between a normal and glioblastoma genome. The data were analyzed in collaboration with Drs. Gavin Sherlock and James Brooks at Stanford, and Dr. Jun Li at the University of Michigan.

Tumors generally accumulate gains and losses in DNA as they grow, and measuring these changes in a number of samples can illuminate which changes are necessary for tumor development. Targeting genes affected by these changes can lead to improved diagnosis and more specific therapies, with fewer side effects to normal cells in the brain.

The HudsonAlpha and Stanford data on genomic changes were integrated with data from institutions around the country measuring changes in other types of genomic variation and in epigenomic variation. Epigenomic variation refers to molecules that are added to our genome to regulate how genetic instructions are processed in the cell. We know these changes are important to cancer cells, but previous studies have not integrated genomic and epigenomic measurements on such a large scale.

According to Absher, “This is a paradigm shift in how cancer is analyzed. These comprehensive genomic and epigenomic analyses on a set of common tumors stringently assessed by research organizations across the country will ideally increase our fundamental understanding of cancer, and help us develop better diagnostic tools and treatments.”

Myers added, “The excitement in this study is the integration of so many teams, taking multiple ways of measuring our genome and producing such a broad picture of cancer genetics. My laboratory at HudsonAlpha plans to continue studying cancer genetics, working with local physicians as well as our important collaborators at Stanford and Michigan.”

The tumor suppressor gene pRb2/p130 may provide the first independent prognostic biomarker in cases of soft tissue sarcoma (STS), according to an international collaboration of researchers, including scientists at the Sbarro Institute for Cancer Research and Molecular Medicine at the College of Science and Technology at Temple University in Philadelphia, PA, the Department of Human Pathology and Oncology, University of Siena and the Center of Oncological Research of Mercogliano (CROM) in Avellino, Italy.The research appears in the latest issue of Clinical Cancer Research (www.aacrjournals.org).

The findings show that a reduction in the expression of pRb2/p130 can mean a higher risk of recurrence and death from STSs. The gene pRb2/p130, a member of the retinoblastoma family of genes, regulates a portion of the cell cycle.

Clinicians have long sought a prognostic test for the disease, which can be highly aggressive and unpredictable, making it difficult to determine the most beneficial course of chemotherapy and/or radiation treatments following surgery.

A prognostic indicator will help doctors determine which patients have a higher risk of recurrence of the disease and who might benefit from a more aggressive adjuvant therapy.

In the study, researchers examined specimens taken from 41 patients with STS. In a subset of 31 cases of nonmetastatic cancers, they found a direct relationship between pRb2/p130 expression and the clinical outcome of patients.

“We found that pRb2/p130 expression was lost or decreased and significantly correlated with recurrence of disease and poor survival rates in the subset of patients with nonmetastatic tumors,” said Valeria Masciullo, M.D., Ph.D., lead author of the study.

“A prognostic test could define the natural history of STSs, while also helping to identify possible targets for new kinds of therapies,” said Antonio Giordano, M.D., Ph.D., the Director of the Sbarro Institute, Professor of Molecular Biology at the College of Science and Technology at Temple University in Philadelphia, PA and Full Professor of Pathological Anatomy and Histology of the University of Siena.

The researchers noted that the reliability of pRb2/p130 as a potential marker in the clinical routine assessment and management of patients with STS deserves to be further evaluated in long-term follow-up studies on a larger number of cases.

A team of researchers from Dartmouth’s Thayer School of Engineering and Mascoma Corporation in Lebanon, N.H., have made a discovery that is important for producing large quantities of cellulosic ethanol, a leading candidate for a sustainable and secure alternative to petroleum-derived transportation fuel.  For the first time, the group has genetically engineered a thermophilic bacterium, meaning it’s able to grow at high temperatures, and this new microorganism makes ethanol as the only product of its fermentation.

The study was published online during the week of Sept. 8, 2008 in the journal Proceedings of the National Academy of Science.

“Our discovery is one potential avenue for research to facilitate turning inedible cellulosic biomass, including wood, grass, and various waste materials, into ethanol,” says Lee Lynd, the Paul E. and Joan H. Queneau Distinguished Professor in Environmental Engineering Design at the Thayer School of Engineering at Dartmouth.  “In the near term, the thermophilic bacterium we have developed is advantageous, because costly cellulase enzymes typically used for ethanol production can be augmented with the less expensive, genetically engineered new organism.”

Lynd explains that this discovery is only the first step, a proof of concept, for future development of ethanol-producing microbes that can make ethanol from cellulosic biomass without adding enzymes.  Lynd is the corresponding author on the study and the chief scientific officer and co-founder of Mascoma Corporation, a company working to develop processes to make cellulosic ethanol.

All of the ethanol currently used in this country as an additive to gasoline comes from corn.  However, it is widely recognized that cellulosic biomass has significant advantages over corn as a raw material for ethanol production, provided that a cost-effective technology for converting cellulosic materials can be developed.

There are several features that make cellulosic ethanol attractive.  The raw material, cellulosic biomass, is available on a large scale, does not include food crops, and is cost-competitive with petroleum on both an energy and a mass basis.  The technology to convert cellulosic biomass to ethanol is steadily improving, and it also has the potential to be cost-competitive with gasoline production.  Environmental benefits include a sustainable carbon cycle with near-zero net greenhouse gas emissions, because the carbon dioxide captured growing the biomass roughly equals what is emitted while running an engine.  In addition, ethanol has excellent performance and compatibility with existing internal combustion engines as well as fuel cell-powered vehicles of the future.

Innovative technology for ethanol production from cellulosic raw materials has been a central focus of Lynd’s, who won the inaugural Lemelson-MIT Sustainability Award in 2007, a top honor for inventors.

“I’m not sure if it was a good or a bad sign that I knew alternative energy would be so important today when I started this work 30 years ago,” says Lynd.  “At that time, tools of molecular biology were in a nascent state of development.  Now we can make much faster progress, and I anticipate more exciting advances soon.”