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Week Ending FRIDAY January 14, 2011---------News Archive

First Sequenced Gut Microbes for Pre-term Baby

Scientists have for the first time sequenced and reconstructed the genomes of most of the microbes in the gut of a premature newborn and documented how the microbe populations changed over time.

By Robert Sanders
The microbes in the gut of a premature infant change radically from day 10 and days 16-21, as indicated by the colored bars keyed to different microbial groups. Even day to day, the relative proportions of microbes shifts, and probably continues to change as the baby encounters new environments, people and pets.

The microbes in the gut of a premature infant change radically from day 10 and days 16-21, as indicated by the colored bars keyed to different microbial groups.

Even day to day, the relative proportions of microbes shifts, and probably continues to change as the baby encounters new environments, people and pets.

Further studies involving more infants could eventually help researchers understand the causes of various intestinal problems that afflict preemies, in particular the sometimes fatal necrotizing enterocolitis, according to researchers at the University of California, Berkeley, the University of Pittsburgh School of Medicine and Stanford University. One unresolved question is whether these illnesses are caused by pathogenic strains of bacteria or just an imbalance in the microbe populations in the gut.

The study was posted online Dec. 29 in advance of print publication in the journal Proceedings of the National Academy of Sciences.

While this is not the first time that microbes in the human intestinal tract have been sequenced as a community, this is the first comprehensive look at a time series documenting colonization of the gut of a premature newborn, and one of few completely assembled community genomic datasets, said Jill Banfield, a UC Berkeley professor of earth and planetary science and of environmental science, policy and management.

“Sequencing of microbial communities has become exceedingly common, but many researchers work with essentially unassembled data and often analyze very short contiguous DNA sequences – genome fragments,” she said. “We actually go in and work out where the assemblies failed and fix them – what’s called curating the data – so we can build very complete genomes for most of the microbes.”

Pediatric surgeon Michael J. Morowitz, until recently at The University of Chicago Medical Center but now with Children’s Hospital of Pittsburgh of the University of Pittsburgh Medical Center and an assistant professor of surgery at the University of Pittsburgh School of Medicine, first approached Banfield because of her pioneering work over the past decade sequencing microbial communities in extreme environments, such as the acid drainage from underground mines. He suggested that she tackle a unique human environment, the newborn intestinal tract. Unlike the adult gut, which may contain a couple of thousand microbial species, the newborn’s intestinal tract may be colonized by only a handful, making it feasible to sequence the entire community.

His interest stemmed from work with premature infants, most of whom spend anywhere from two weeks to six months in the intensive care unit before they’re deemed healthy enough to go home. Between 5 and 10 percent of these preemies develop symptoms of necrotizing enterocolitis (NEC), which requires rounds of antibiotics to halt, and perhaps a third of these babies eventually require surgery to remove parts of their intestines that have died.

“The actual impact of necrotizing enterocolitis in the ICU is even larger, because feeding routines and other care are conducted around a fear of NEC developing,” Morowitz said.

Previous studies, however, have produced conflicting results about NEC’s cause. Some have found pathogenic bacteria associated with NEC, while others have found no difference between the bacteria in babies with and without NEC. Banfield, Morowitz and their collaborators suspect that these results reflect the fact that researchers have looked broadly at species or families of bacteria in the gut, rather than at variants or strains. Although coexisting strains may have genes that are 99 percent identical, their genomes could be sufficiently distinct to make one bad and the other good.

“We already know that just a few genes can make one strain a pathogen and one beneficial or commensal,” meaning that the microbes live amicably with their host, Banfield said. “We expect that a lot of the issues with the colonization process in the gut that leads to disease may be tracked to subtle differences in strains,” she said. “So one question on the table is, ‘Are these very closely related strains physiologically distinct, and in what ways’?”

The only way to get at these differences, she said, is to sequence the entire genomes of the intestinal microbiota – not merely DNA fragments or short DNA tags, which can be used to identify the genus or even species of a microbe, but not the specific strain.

“Although a primary target of our research is NEC, it’s become very apparent that there are some fundamental unanswered questions just about the colonization process under normal circumstances,” Morowitz added. “It’s really important to get a handle on what the normal process is first, and then, eventually, we can look closely at babies with NEC and see if they deviate from what appears to be the normal colonization process.”

Other human diseases, including asthma, diabetes and obesity, have been linked to problems with microbial colonization of the gut, and several papers have reported symptomatic improvement after “transplanting” fecal material from healthy individuals to patients with a range of intestinal disorders.

Banfield, Morowitz and their colleagues followed a single premature infant that had been delivered by cesarean and identified three distinct communities of intestinal microbes present at different times during the first month of the infant’s life. The microbe populations in these communities seemed to change after alterations in medication and feeding, Morowitz said. Although it was presumably sterile at birth, the infant’s gut was quickly colonized by a set of known intestinal microbes – bacteria and Archaea, primarily, but also viruses, bacterial viruses (phage) and the naked lengths of DNA called plasmids. When the baby went off antibiotics and switched from breast feeding to intravenous feeding, the microbe populations completely changed, with minor microbial members suddenly dominating and dominant members declining.

Vincent Denef, a post-doctoral researcher in Banfield’s lab who contributed to the study, noted that such real-time studies are powerful because “very rarely do we have the opportunity to observe the dynamics of a naturally occurring system, such as the infant GI tract, as it is transformed from sterile to functionally diverse.”

The populations again shifted when intravenous feeding was replaced by formula. Morowitz stopped collecting feces from dirty diapers after 21 days, and the infant was sent home healthy after 9 weeks in the ICU.

Though fecal samples were taken nearly every day, a complete genome analysis was performed only for samples collected on days 10, 16, 18 and 21. For the other days, the microbial community was estimated based on DNA tags (16S rRNA) that identify microbe families and species, but not specific strains.

What surprised the researchers is that the microbial population was comprised of members of at least 20 groups, many of which include harmful as well as benign organisms. These included Staphylococcus, a frequent cause of hospital infections; Pseudomonas, “the cause of an enormous amount of morbidity in ICU patients, both children and adults,” Morowitz said; Serratia, a common cause of sepsis in general; and Citrobacter, which can cause meningitis in babies. Yet, the baby in this study appeared healthy throughout.

“The gut populations are highly dynamic, with large shifts through three stages over time, but we saw an overabundance of gram-negative organisms that we often associate with disease,” he said. “Particularly striking was the dominance of Pseudomonas for several days, though the infant was clinically stable.”

The seeming contradiction of a healthy infant with disease-causing bacteria in her gut could be explained if the strains in the infant’s gut were benign, or if the balance of other microbes prevented pathogenic microbes from causing problems.

Citrobacter, for example, is one type of bacteria that is reportedly associated with NEC: one study found Citrobacter in three of four infants with NEC, but in no control infants. Yet, in the current study, sequencing of the gut microbiome on days 16, 18 and 21 revealed the presence of two strains of Citrobacter, which fluctuated significantly in proportions on the three days. “Those big shifts could potentially have been very important for the medical state of that baby,” Banfield said. “Fortunately, the baby was fine.”

The researchers found that those two strains were 99 percent similar over areas of the genome that could be compared.

“Of particular interest were hot spots of rapid DNA evolution within and between genes. Those potentially could be very important and interesting,” she said. “Though the two Citrobacter genotypes are very, very similar over most of the genome, the results suggest that they could be functioning in different ways because their genomes are regulated differently.”

Banfield noted that the intestinal community of the infant no doubt would continue to shift repeatedly for a year or more after birth, as the child encounters new microbes – courtesy of family, friends and pets. These populations shift with the influx of new strains and species and potentially because the resident microbes themselves evolve by picking up new traits from the plasmids and phages living alongside them.

“This is an ecological study,” she emphasized. “One of the things we are trying to do is bring into the field of medicine a high resolution, ecological approach.”

Other coauthors of the study are Brian C. Thomas of UC Berkeley, Valeriy Poroykoa of the University of Chicago Pritzker School of Medicine, and David A. Relman and Elizabeth K. Costello of the Stanford University School of Medicine.

The work was funded by National Institute of Allergy and Infectious Diseases of the National Institutes of Health, the Department of Energy, the Surgical Infection Society and The March of Dimes.

BPA and Polycystic Ovary Syndrome

Women with the polycystic ovary syndrome (PCOS), the most common hormone imbalance in women of reproductive age, may be more vulnerable to exposure to the chemical bisphenol A (BPA), found in many plastic household items, according to a new study.

The results will be presented Sunday at The Endocrine Society’s 92nd Annual Meeting in San Diego. The article, "Endocrine disruptors and polycystic ovary syndrome (PCOS): Elevated serum levels of Bisphenol A in women with PCOS," appears in the March 2011 issue of JCEM.

The study found that BPA, a known hormone disrupter, is elevated and associated with higher levels of male hormones in the blood of women with PCOS compared with healthy women. These findings held true for both lean and obese women with PCOS, said Evanthia Diamanti-Kandarakis, MD, PhD, study co-author and professor at the University of Athens Medical School in Greece.

“Women with the polycystic ovary syndrome should be alert regarding this environmental contaminant’s potential adverse effects on reproductive aspects of their health problem,” she said.

Excessive secretion of androgens—masculinization-promoting hormones—occurs in PCOS. The syndrome raises the risk of infertility, obesity, Type 2 diabetes and heart disease.

Past studies show that BPA is elevated in women who have had recurrent miscarriages. This chemical can leach into the bloodstream from food and beverage containers that are made of polycarbonate hard plastic or lined with epoxy resins, or from some dental sealants and composites.

In the new study, the researchers divided 71 women with PCOS and 100 healthy female control subjects into subgroups matched by age and body composition (obese or lean). Blood levels of BPA, compared with those of controls, were nearly 60 percent higher in lean women with PCOS and more than 30 percent higher in obese women with the syndrome.

Also, as the BPA blood level increased, so did the concentrations of the male sex hormone testosterone and androstenedione, a steroid hormone that converts to testosterone, Diamanti-Kandarakis reported.

Although BPA is a weak estrogen, excessive secretion of androgens, as seen in PCOS, interfere with BPA detoxification by the liver, leading to accumulation of blood levels of BPA, Diamanti-Kandarakis explained.

“BPA also affects androgen metabolism, creating a vicious circle between androgens and BPA,” she said.

Diamanti-Kandarakis said women with PCOS may want to limit their exposure to BPA.

“However,” she said, “no one has proved that by reducing BPA levels in PCOS, it will have beneficial effects.”


Test Triples Genetic Info from Newborn Screenings

Archived blood could be used to study population health patterns and diseases present at birth

Van Andel Research Institute (VARI) researchers have developed a method that can yield more information from archived newborn blood that has implications for a vast array of research, including population health studies and answering questions about diseases in infants and children.

In a recent study published in Pathology International, VARI researchers detected approximately 9,000 activated genes in samples from adult blood spots on Guthrie cards that had been archived anywhere from six months to three years. Researchers say their modified method uses commercially available tools and can be easily adopted by others in the scientific community for use on newborn blood spots.

"Genetic information from Guthrie cards is a valuable resource," said VARI Distinguished Scientific Investigator Jim Resau, Ph.D. "It opens doors to examine risk factors and potentially diagnose diseases before the clinical features are present. One such disease might be Cerebral Palsy, which currently can't be diagnosed until a child is nearly two. The information could also be used to study pediatric cancers such as neuroblastoma, which is known to be present at birth in many cases."

Guthrie cards have been used for the past 20-30 years to collect blood for mandatory newborn screening programs in the United States, Australia, New Zealand, Japan, and most countries in Europe and South America.

Blood is usually collected through a heel prick 24 to 48 hours after birth and is placed on the cards, which may be archived after screening. Although genetic material in blood from Guthrie cards has been presumed to be degraded because of varying storage conditions, VARI researchers were able to detect more than 3,000 activated genes in each sample in a 2009 study, and recently, they were able to detect three times that amount using the new method.

"We were looking for the best possible way to extract the most information from blood on Guthrie cards using the least amount of this precious resource," said Resau.

"Showing that mRNA is reasonably well preserved in archived filter paper blood spots, whether frozen or not, opens up a very important avenue for clinical and translational research, especially in child health, because the largest such archive is samples used for newborn genetic screening," said Nigel Paneth, M.D., M.P.H., University Distinguished Professor in the Departments of Epidemiology and Pediatrics & Human Development at the Michigan State University College of Human Medicine.

Messenger ribonucleic acid or mRNA is a molecule that carries instructions from DNA to protein making structures in cells.

Since archived blood spots can be more than 20 years old, the researchers' next step is to investigate the power of activated gene detection in various archival periods. Resau said the cards could also be used for population studies, such as finding out when a particular virus first appeared in a specific region, or levels of compounds in that region that could be affecting public health.

The researchers gratefully acknowledge support of this work by the National Institute of Neurological Disorders and Stroke (R01NS055101) via Michigan State University. The contents of the study are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health or NINDS.

About Van Andel Institute: Established by Jay and Betty Van Andel in 1996, Van Andel Institute (VAI) is an independent research and educational organization based in Grand Rapids, Mich., dedicated to preserving, enhancing and expanding the frontiers of medical science, and to achieving excellence in education by probing fundamental issues of education and the learning process. VARI, the research arm of VAI, is dedicated to probing the genetic, cellular and molecular origins of cancer, Parkinson and other diseases and working to translate those findings into effective therapies. This is accomplished through the work of over 200 researchers in 18 on-site laboratories and in collaborative partnerships that span the globe. VARI is affiliated with the Translational Genomics Research Institute, (TGen), of Phoenix, Arizona.


THURSDAY January 13, 2011---------News Archive

Top 10 Most Interesting Genetic Findings of 2010

23andME, a leading USA personal genomics company, reviews last year's genetic milestones on the journey to understanding the role of genetics in personal health, human development and ancestry.

23andMe has released its first annual list of what it felt to be the 10 most interesting and significant genetic findings in 2010, as part of an ongoing journey to understand the role of genetics in personal health and human development.

"Our understanding of the human genome is accelerating at a phenomenal rate," stated Anne Wojcicki, co-founder and CEO of 23andMe. "Below we have compiled a list of our top ten favorite genetic discoveries from 2010. We look forward to exploring more discoveries in 2011."

Customers of 23andMe have the opportunity to learn about how their genetics can influence their individual health traits, risk for developing certain diseases and conditions, reactions to a variety of medications, and ancestry. Throughout the year, 23andMe monitors scientific publications for studies that provide exciting glimpses into these areas. The company provides information on these developments to its customers through continual updates to their Health and Traits reports, as well as "SNPwatch" postings to the company's public blog, "The Spittoon."

While 23andMe provides updates on genetic research on a regular basis, it recognizes and cautions that in most cases more studies are needed before the research can provide information of specific value to individuals.

REFLECTING ON 2010

1. Genetics influences whether your body shape is "apple" or "pear" — and which shape you are has implications for disease.

This fall, 23andMe reported on new research connecting common genetic variants with propensity towards apple- and pear- body shapes. The Genetic Investigation of Anthropometric Traits (GIANT) consortium investigated how genetics influence waist and hip size in nearly 200,000 people from more than 50 studies. Published in Nature Genetics, the report identified 14 single nucleotide polymorphisms (SNPs, or common genetic variants) — 13 new and one previously reported — associated with body fat distribution. These findings have health implications because "apples", whose weight concentrates around their middles, appear to be at greater risk for developing heart disease and type 2 diabetes than their pear counterparts.

2. Genetic variations newly associated with risk for childhood asthma

Chromosome 1 variants, identified by The Children's Hospital of Philadelphia (CHOP) researchers, affected the odds of childhood asthma in different ways depending on ethnicity. Versions of the SNPs associated with increased risk in African Americans were associated with decreased risk in the European sample. This is not unusual in genetic studies, and often reflects differences in the genetic backgrounds of different populations.

In a second study, researchers identified associations between variants on chromosomes 2, 6, 9, 15, and 22 and asthma in individuals with European ancestry, seeing stronger effects for childhood asthma. They also observed that a previously reported association between a region on chromosome 17 and asthma was specific to childhood asthma only. When the researchers looked for genetic associations with allergy susceptibility (a condition that is often linked to asthma) they found very little overlap, suggesting that allergy sensitivity may be an effect of asthma rather than its cause.

The two studies' findings could lead eventually to the development of new types of treatments for childhood asthma.

3. New Variants Influence Risk for Rheumatoid Arthritis

Rheumatoid arthritis is a common autoimmune disease in which the individual's own immune system attacks the lining of the joints, causing stiffness and muscle aches. Like other autoimmune diseases, development of rheumatoid arthritis is likely caused by a complex combination of genetic and environmental factors. Recent research into the genetics of the disease has identified many of the genetic factors, and new studies continue to implicate additional variants that may influence risk.

This year, SNPwatch presented a pair of studies published in Nature Genetics which found several new genetic variants associated with rheumatoid arthritis. A research team in Japan at the RIKEN Center for Genomic Medicine identified a variant, rs3093024, associated with rheumatoid arthritis risk in Japanese individuals. The second study, from Brigham and Women's Hospital in Boston, confirmed the same association in individuals with European ancestry. In both studies, each copy of the A version of the variant increased an individual's odds of the disease by 1.1 to 1.2 times.

The RIKEN team demonstrated that the different versions of rs3093024, already connected to risk of Crohn's disease, affect the behavior of the CCR6 gene, providing a potential biological explanation for the variant's contribution to rheumatoid arthritis risk. The Brigham and Women's team also found several other genomic regions associated with rheumatoid arthritis in people with European ancestry, some of which had not yet been linked to autoimmune disease.

4. Understanding Alzheimer's disease

Until very recently, mutations in only one gene - APOE - had been conclusively associated with the more common late-onset form of Alzheimer's (other mutations are associated with early-onset, or familial Alzheimer's disease). In the last few years, however, research groups studying large numbers of people have identified variants in several new genes with small effects on the disease.

As 23andMe reported in SNPwatch, researchers pulled together the results of several studies to find new Alzheimer's associated risk variants. The scientists results appear online in the Journal of the American Medical Association. The findings suggest that these variants may be important for unraveling the underlying biology of Alzheimer's, essential in the quest to find new methods of treatment. The combined analysis also provided support for previously identified associations in the CLU and PICALM genes, but failed to confirm a third previously reported association in the CR1 gene with Alzheimer's disease.

5. One size doesn't fit all — personalizing treatment

It turns out that one size doesn't fit all when it comes to drug response, and for some people, certain drugs might be more effective, not work at all, or even produce serious side effects.

The growing body of pharmacogenomics research has helped us understand that, at least in part, genetics play a role in how well some drugs work for different people. The 23andMe Drug Response reports link customers' genetics to the way they might respond to certain drugs and medications. The results range from whether you're likely to benefit from a drug, need a different dose due to sensitivity, experience toxic or adverse effects, or even have increased risk for other conditions.

23andMe cautions that its Drug Response reports should not be used to independently establish, abolish, or adjust medical treatment and medications but should be discussed with your physician. Only a medical professional can determine whether a particular drug or dose is appropriate for you.

6. No clue yet to how long Boomers can expect to live

A 2010 genome-wide study of extreme longevity published in the journal Science, received a lot of press attention. At first glance the results appeared quite extraordinary as the authors identified significant evidence for living past the age of 100.

They constructed a model for predicting exceptional longevity that had 77% accuracy in an independent set of individuals.

However, a closer reading by 23andMe pointed to some errors in analyses of genome-wide datasets. The study did contain an interesting association of rs2075650 near the APOE gene. APOE is an established susceptibility gene for Alzheimer's disease.

7. Baby's First Tooth May Be A Health Predictor

All of the SNPs associated with first tooth eruption or teeth by age 1, were identified in this study of 6,000 infants. Each infant had been followed by epidemiologists beginning early in their mothers' pregnancies. All the SNPs identified are located in or around genes known to have roles in organ formation, growth and development - or sometimes cancer. This finding suggests that studies of teething and other aspects of infant development may have far reaching implications.

As the study authors explained, "the discoveries of genetic and environmental determinants of human development will help us to understand the development of many disorders which appear later in life. We hope also that these discoveries will increase knowledge about why fetal growth seems to be such an important factor in the development of many chronic diseases."

8. Before you call that relative a "Neanderthal"...

A study of the Neanderthal genome, published in the journal Science presented strong evidence from genome sequencing that humans and Neanderthals interbred.

Summarizing the evidence, John Timmer from Ars Technica says, it "became apparent when the Neanderthal genome was paired against human genomes from different parts of the globe. The Neanderthal DNA consistently matched European and Asian samples better than it did African; the difference was small, but consistent. It suggested that the Neanderthals, which were restricted to Europe and Asia at the time modern humans originated in Africa, had interbred with humans once they began migrating out of Africa."

Because African human populations are older, they tend to have more divergent genomes. But the human-Neanderthal split is older still, so the authors figured that any areas of the genome where variation was larger in populations outside of Africa may have entered the human genome through interbreeding. If they did arise through interbreeding, then the non-African segments should match Neanderthals. Researchers found at least 10 regions that fit these predictions.

9. A Fresh Look at Latino Genetic Ancestry

As the 2010 Census measured the continued increase in the US Latino population over three decades, an interesting study reported in the Proceedings of the National Academy of Sciences investigated DNA from 100 people, each with ancestry from one of four Latin American populations: Colombian, Dominican, Ecuadorian, and Puerto Rican.

The study found that Latino populations differ markedly in the contribution made by their source populations. In Ecuador and Colombia, typically little African contribution to ancestry is found, most individuals are genetic mixes of European and Native American. But in the Caribbean islands of Puerto Rico and the Dominican Republic, at the western reach of the African slave trade, people typically include substantial African ancestry.

Medical genetic research can be more difficult in diverse populations. In the case of association studies, two groups of people are compared who differ only with respect to whether they have or do not have the disease of interest; for best comparison, the disease group should have the same mix of age, gender, and ancestry as the non-disease group.

The genetic diversity of Latin American populations may hinder such studies because of the difficulty in building genetically-matched groups. The study's authors suggest that new techniques may need to be developed to carry out genetic research in Latino populations.

10. Web-based research works!

23andMe proudly announced that its new web-based research paradigm (23andWe) works and unveiled its first peer-reviewed scientific study.

The results were published last spring in PLoS Genetics.

Over 9,000 people contributed data to the study of 22 separate traits. Novel SNP associations were revealed for hair curl, asparagus anosmia (the inability to detect the scent of certain asparagus metabolites in urine), the photic sneeze reflex (the tendency to sneeze when entering bright light), and freckling. Previously identified genetic associations between nine genes and certain pigmentation-related traits (hair color, eye color, and freckling) were replicated.

At the annual American Society of Human Genetics meeting in November of 2010, 23andMe scientists announced preliminary results from several studies, including research into the genetics of Parkinson's disease.

23andMe received its first NIH Small Business Innovative Research Grant (SBIR) in late 2010. It will use this grant to continue its web-based approach to pharmacogenomics research. The NIH is the largest source of medical research funding in the world. Through its support of innovative training programs and scientific projects, the NIH facilitates medical discoveries that lead to improved health and quality of life.

The first phase of this effort is to demonstrate that 23andMe can replicate known genetic associations using web-based survey data volunteered by its customers, now numbering over 60,000.


All 23andMe study results are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice and individuals should always seek the advice of their physician or other appropriate healthcare professional with any questions regarding diagnosis, cure, treatment or prevention of any medical condition.

23andMe, Inc. is a leading personal genetics company dedicated to helping individuals understand their own genetic information through DNA analysis technologies and web-based interactive tools. The company's Personal Genome Service® enables individuals to gain deeper insights into their ancestry and inherited traits. The vision for 23andMe is to personalize healthcare by making and supporting meaningful discoveries through genetic research. 23andMe, Inc., was founded in 2006, and the company is advised by a group of renowned experts in the fields of human genetics, bioinformatics and computer science. More information is available at www.23andme.com.


WEDNESDAY January 12, 2011---------News Archive

Looking Good On Greens

New research suggests eating vegetables gives you a healthy tan.

Left face shows the effect of sun tanning. Middle face shows natural color. Right face shows the effect of eating more carotenoids. Participants thought the carotenoid color looked healthier.

The study, led by Dr Ian Stephen at The University of Nottingham, showed that eating a healthy diet rich in fruit and vegetables gives you a more healthy golden glow than the sun.

The research, which showed that instead of heading for the sun the best way to look good is to munch on carrots and tomatoes, has been published in the Journal Evolution and Human Behaviour.

Dr Ian Stephen, from the School of Psychology, University of Nottingham, Malaysia Campus, led the research as part of his PhD at the University of St Andrews and Bristol University. He said: “Most people think the best way to improve skin colour is to get a suntan, but our research shows that eating lots of fruit and vegetables is actually more effective.

Dr Stephen and his team in the Perception Lab found that people who eat more portions of fruit and vegetables per day have a more golden skin colour, thanks to substances called carotenoids. Carotenoids are antioxidants that help soak up damaging compounds produced by the stresses and strains of everyday living, especially when the body is combating disease. Responsible for the red colouring in fruit and vegetables such as carrots and tomatoes, carotenoids are important for our immune and reproductive systems.

Dr Stephen said: “We found that, given the choice between skin colour caused by suntan and skin colour caused by carotenoids, people preferred the carotenoid skin colour, so if you want a healthier and more attractive skin colour, you are better off eating a healthy diet with plenty of fruit and vegetables than lying in the sun.”

Dr Stephen suggests that the study is important because evolution would favour individuals who choose to form alliances or mate with healthier individuals over unhealthy individuals.

Professor David Perrett, who heads the Perception Lab, said: “This is something we share with many other species. For example, the bright yellow beaks and feathers of many birds can be thought of as adverts showing how healthy a male bird is. What’s more, females of these species prefer to mate with brighter, more coloured males. But this is the first study in which this has been demonstrated in humans.”

While this study describes work in Caucasian faces, the paper also describes a study that suggests the effect may exist cross culturally, since similar preferences for skin yellowness were found in an African population.

The work was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and Unilever Research, and published with support from the Economic and Social Research Council (ESRC) and the British Academy and Wolfson Foundation.

See: http://perception.st-and.ac.uk/ or Perceptionlab.com for demos or to participate in face experiments.

Popular Drugs Can Induce Loss of Libido in Men

Drugs for hair loss and benign prostatic hyperplasia (BPH or enlarged prostate) may result in loss of libido, ED in men.

Male pattern baldness
Researchers from Boston University School of Medicine (BUSM), in collaboration with colleagues at Lahey Clinic and from Denmark and Germany, have found that popular hair loss drugs like Propecia™ , produce significant negative effects in some men including loss of libido, erectile dysfunction (ED), ejaculatory dysfunction and potential depression.

These findings, which currently appear on-line in Journal of Sexual Medicine, suggest that extreme caution should be exercised prior to prescribing 5a-reductase inhibitors (5a-RIs) therapy to patients for hair growth or for BPH symptoms.

Drugs containing 5a-RIs, finasteride (Propecia™) and dutasteride, have been approved for treatment of lower urinary tract symptoms as they can reduce an enlarged prostate (BPH).

Finasteride is also approved for treatment of hair loss (androgenetic alopecia). Although the adverse side effects of these agents are thought to be minimal, the magnitude of adverse effects on sexual function, gynecomastia (breast enlargement in men), depression, and quality of life remains are poorly defined.

In order to determine the potential extent of this problem, researchers examined data from various clinical studies concerning side effects of finasteride and dutasteride. After a review of the literature, they found prolonged adverse effects on sexual function, including erectile dysfunction and diminished libido, in a subset of men, which raises the possibility of a causal relationship with the drugs.

Although the adverse side effects of 5a-RIs on sexual function, gynecomastia and the impact on the overall health have received minimal attention, in some patients, these side effects are persistent with regard to sexual function and with an emotional toll including decreased quality of life.

"The potential widespread use of 5a-RIs for treatment of BPH, prostate cancer and male pattern hair loss may produce undesirable adverse side effects on overall health and in particular, vascular health and sexual function in a subgroup of susceptible patients, " said lead author Abdulmaged M. Traish, MBA, PhD, a professor of biochemistry and professor of Urology at BUSM. "Furthermore, treatment of hair loss, a benign condition with 5a-RIs may produce persistent side effects in a number of young patients," he added.

"Honest and open discussion with patients to educate them on these serious issues must be pursued prior to commencing therapy because, in some patients, these adverse effects are persistent and may be prolonged and patients do not recover well after discontinuation from drug use," cautioned Traish.

The researchers believe additional clinical and preclinical studies are warranted to determine the reason why some of these adverse effects persist in some individuals.

Funding for this study was provided by BUSM's Department of Urology.


TUESDAY January 11, 2011---------News Archive

Taking Snapshots Of A Protein As It Folds

Scientists have invented a way to ‘watch’ a protein fold into the elaborate twisted shape that determines its' function - in less than thousandths of a second.

The function of barstar (pink) is to bind tightly to barnase (blue), preventing it from chopping up RNA.
People have only 20,000 to 30,000 genes, but those genes make more than 2 million proteins - and protein molecules do most of the work in the human cell.

Proteins are created as chains of amino acids, and these chains usually fold spontaneously into what is called their “native form” in milliseconds. A protein’s function depends on its shape. Misfolded proteins can lead to neurodegenerative diseases such as Alzheimer’s, Parkinson's and mad cow. Predicting how chains of amino acids will fold from scratch requires powerful supercomputers or even harnessing the power of thousands of people participating in online programs such as Folding@home.

Either way, prediction is time-consuming and often inaccurate, so much so that it is slowing the understanding and use of DNA sequence data for advancements in medicine and biotechnology. This latestest method for capturing how a protein folds and unfolds may finally provide the kind of detail needed to improve protein structure prediction - and enhance medical translation of DNA data.

In a recent issue of the Journal of the American Chemical Society, scientists, led by Michael L. Gross, PhD, professor of chemistry in Arts & Sciences and of medicine and immunology in the School of Medicine at Washington University in St. Louis, describe a new approach to watch the folding of a small protein called barstar.

What they have captured is similar to the "stills" captured by the first slow motion camera (a stroboscope) as it caught the imperceptible movements of animals running. But the “strobe light” used for protein fold capture is a temperature change and the “camera” is a fast chemical reaction measured by a sensitive mass spectrometer.

Why folding is a complex problem

Modern biology believes that the sequence of amino acids determines how a protein will fold. Consequently, if the amino acid sequence is known, it should be possible to calculate the protein’s final structure from scratch. But it’s harder than it looks.

“Think of a protein as thousands of atoms connected together by springs,” says Gross, who is also director of the National Institutes of Health/ National Center for Research Resources (NIH/NCRR) Mass Spectrometry Resource “If you were to suspend this object with a string from the ceiling and let it flop around, imagine how many shapes it could take. An enormous number, because it is free to move in so many different ways.”

In practice, scientists often predict protein structure by analogy. They sift through large databases for proteins with similar sequences of amino acids and assume similar amino-acid chains will fold in similar ways.

“But,” says Gross, “at some point any method for predicting protein structure has to be checked against experimental evidence that shows how proteins actually do fold.”

Gross used the barstar protein because its “native state” is known, as is its primary structure - the sequence of protein subunits called amino acids. What wasn’t known is how barstar's amino-acid chain twists and coils to form its final structure.

Fortunately, barstar is unfolded at zero degrees Celsius and begins to fold as it warms, unlike most proteins. And, when warmed, the folding takes place in microseconds (thousandths of a second).

How the method works

Gross's team injected a cold solution of barstar and a tiny amount of hydrogen peroxide into an optical fiber. The fiber was then hit with two laser pulses in quick succession. The first pulse heated the solution just enough to begin the protein fold. The second pulse broke some of the hydrogen peroxide molecules in two, each becomming a very reactive hydroxyl radical. These radicals then use oxygen atoms to stick to parts of the protein.

“Imagine,” says Gross,“that you suspended a styrofoam model of a partially folded protein and spray-painted it blue. The outside parts would be painted blue; those buried within would remain white.”

Within a microsecond, a scavenger amino acid cleared away any remaining hydroxyl radicals, preventing them from breaking bonds and altering the protein’s twisting shape. Repeating the process 500 times, “snapshots” of the protein’s quickly changing shape were captured producing an extremely accurate picture of each twist and turn barstar endured towards its final "native" appearance.

Weighing the painted proteins

“We collect each drop of marked protein as it emerges from the fiber,” says Gross. “Then we digest the protein very slowly and carefully with an enzyme that cleaves the amino acid chains at specific locations, creating a known set of protein fragments, called peptides."

Each peptides is then “weighed” by a mass spectrometer to see whether it has picked up oxygen atoms. “Detecting an extra oxygen is child’s play for a modern mass spectrometer,” says Gross. By following barstar through its turns until it reached its native state, they demonstrated that the new technique can follow folding on a submillisecond time scale.

‘Massive amounts of detail’

Gross is the first to say that this proof-of-principle experiment stands at the end of a long line of elegant experiments of a similar type, called pump-probe experiments. Other techniques probe the change in protein structure by monitoring the absorption or emission of light. But, they can provide only global information, such as the rate of a folding reaction.

“Because we use a chemical rather than a physical probe, we can see what’s going on in much greater detail,” says Gross. “We can say which part of the structure closes first, which second, and so on.”

The new technique caught the attention of protein scientist Martin Gruebele of the University of Illinois, who spotlighted it in the Dec. 2, 2010, issue of the journal Nature.

It “could provide truly massive amounts of detail about fast protein folding,” wrote Gruebele, which might finally allow scientists “to correctly predict the biologically active structure of a protein starting from the unfolded state.”

Cerebral Palsy Cord Blood Study Open

A study to evaluate children with cerebral palsy (CP), who receive a single intravenous infusion of their own umbilical cord stem cells, is underway at Duke University. The study will evaluate whether the stem cell infusions will cure or at least lessen the severity of the disease.

For decades, Dr. Joanne Kurtzberg, Director of Duke’s Pediatric Bone Marrow and Transplant program and Director of the Carolinas Cord Blood Bank, has been investigating the therapeutic use of umbilical cord blood stem cells, specifically to treat, and sometimes reverse and even cure, some genetic disorders in children.

Now, in a major effort to illustrate improvement in functional status of children with CP, Dr. Kurtzberg, Dr. Jessica Sun, the study’s sub-investigator, and the research team are moving forward with the first placebo-controlled, randomized, crossover clinical trial of its kind.

“We are very excited to have initiated this very important study,” says Dr. Kurtzberg, “which will help us learn whether infusions of a child's own cord blood can lessen the symptoms of cerebral palsy. While there are many anecdotes suggesting that cord blood helps children with CP, it is essential to prove in a randomized trial, whether this is true. If this study shows that cord blood is beneficial, it will have a huge impact on the practices of cord blood collection and banking at birth.”

The team hopes that as a result of their work, more parents will bank their child’s cord blood and that public cord blood banks will hold a child’s blood long enough to treat the child (if needed), before it is released into the inventory for public use.

Kurtzberg also points out, that ultimately the goal of this trial is as much about finding a treatment for CP as it is about discovering what cord blood can do - such as reduce inflammation in the brain, produce new hormones to repair damaged brain cells, or possibly evolve into new brain cells to replace CP damaged ones.

So far, Dr. Kurtzberg has been pleased with the study’s progress, and is especially excited about its public reception.

“All children in this study will receive an infusion of their own cord blood,” she explains. “Some will receive the infusion at the start of the study and others will receive their cord blood one year later. Knowing this, parents have been very willing to allow their children to participate in the study to learn whether cord blood is beneficial.”

The team recruited its first participant in July 2010, and since then has enrolled 12 more (as of 12/06/2010), steadily closing in on the recruiting goal of 120 subjects.

The first infusion was performed in September, 2010, and the team is on track to complete its final infusion in July, 2012. The study is slated for completion July, 2013.

Recruiting efforts remain underway of children, ages 12 months to 6 years, diagnosed with spastic cerebral palsy, and whose cord blood cells were banked at birth. To learn more, contact June Allison, RN, at 919-668-1100,allis006@mc.duke.edu. ClinicalTrials.gov Identifier NCT01147653.

In March, 2010, the Robertson Foundation awarded Duke University $10.2 million to develop a state-of-the-art Translational Cell Therapy Center (CT2), a shared resource facility advancing cell-based therapy research—partly in support of the translational work of Drs. Joanne Kurtzberg, Gordon Worley, Ricky Goldstein, and Mohamad Mikati.


MONDAY January 10, 2011---------News Archive

New Drug to Treat Fragile X Syndrome?

The first drug to treat the underlying disorder instead of the symptoms of Fragile X, the most common cause of inherited intellectual disability, shows some promise according to a new study published in the January issue of Science Translational Medicine. Researchers from Rush University Medical Center helped design the study and are now participating in the larger follow-up clinical trial.

The data from the early trial of 30 Fragile X patients, found the drug, called AFQ056, made by Novartis Pharmaceuticals, helped improve symptoms in some patients. Patients who had the best response have a kind of “fingerprint” in their DNA that could act as a marker to determine who should get treatment.

“This is an exciting development. It is the first time we have a treatment targeted to the underlying disorder, as opposed to supportive treatment of the behavioral symptoms, in a developmental brain disorder causing intellectual disability. This drug could be a model for treatment of other disorders such as autism,” said pediatric neurologist Dr. Elizabeth Berry-Kravis, a study author and director of the Fragile X Clinic and Research Program and the Fragile X-Associated Disorders Program at Rush.

The drug is designed to block the activity of mGluR5, a receptor protein on brain cells that is involved in most aspects of normal brain function, including regulation of the strength of brain connections, a key process required for learning and memory.

Fragile X patients have a mutation in a single gene, known as Fragile X Mental Retardation-1 or FMR1. The mutation prevents FMR1 from making its protein, called FMRP, such that FMRP is missing in the brain. FMRP normally acts as a blocker or “brake” for brain cell pathways activated by mGluR5. When FMRP is missing, mGluR5 pathways are overactive resulting in abnormal connections in the brain and the behavioral and cognitive impairments associated with Fragile X.

The research team, led by Sebastien Jacquemont of Vaudois University in Switzerland in collaboration with Baltazar Gomez-Mancilla of Novartis, found no significant effects of treatment when the entire group of 30 patients was analyzed.

However, in a subsequent analysis, seven patients who had a fully methylated gene, a gene that was fully shut down, presumably resulting in no FMR protein in the blood or brain, showed significant improvement in behavior, hyperactivity and inappropriate speech with the treatment compared to placebo.

“The treatment period in this pilot study was very short and longer treatment might have been needed to see improvement in the whole group of patients. Importantly, the drug was well-tolerated and there were no safety problems,” said Berry-Kravis.

A larger study of the drug is now underway that will recruit 160 patients worldwide and test the effects of a longer period of treatment. Rush University Medical Center is one of the participating sites.

Fragile X affects 1 in 4000 males and 1 in 6000 females of all races and ethnic groups. It is the most common known single gene cause of autism or “autistic-like” behaviors. Symptoms also can include characteristic physical and behavioral features and delays in speech and language development. The impairment can range from learning disabilities to more severe cognitive and intellectual disabilities.

The Fragile X Clinic at Rush was started in 1992 to serve the unique needs of the Fragile X population. The clinic and research center is dedicated to helping people with Fragile X syndrome and their families, as well as furthering understanding of the syndrome, and developing new treatments targeted to the neural basis of the disorder. Dr. Elizabeth Berry-Kravis has been involved in research and clinical work with individuals with Fragile X syndrome for 14 years, and has been honored with the National Fragile X Foundation Jarrett Cole Clinical Award.

Improving Bone Marrow Transplants for Leukemia

Researchers at the University of California, Santa Cruz, have identified a key molecule for establishing blood stem cells in their niche within the bone marrow. The findings, reported in the January issue of Cell Stem Cell, may lead to improvements in the safety and efficiency of bone marrow transplants.
Specific bone marrow niches are critical for hematopoietic stem cell (HSC) function in both normal blood formation and in stem cell transplant therapy.

Bone marrow transplants are a type of stem cell therapy used to treat cancers such as lymphoma and leukemia and other blood-related diseases.

In a bone marrow transplant, the "active ingredients" are hematopoietic stem cells, which live in the bone marrow and give rise to all the different kinds of mature blood cells. The new study shows that hematopoietic stem cells use a molecule called Robo4 to anchor themselves in the bone marrow.

"Robo4 is a rare molecule that is found only in hematopoietic stem cells and in the endothelial cells of blood vessels," said Camilla Forsberg, an assistant professor of biomolecular engineering in the Baskin School of Engineering at UC Santa Cruz. After earlier work in her lab showed that Robo4 is specific for hematopoietic stem cells, Forsberg set out to discover how it functions.

The discovery that the cells need Robo4 to stay in the bone marrow has potential therapeutic value.

Bone marrow transplants require anesthesia for the bone marrow extraction, after which hematopoietic stem cells are harvested from the blood. Repeated injections of drugs are needed to get the stem cells to leave the bone marrow and enter the bloodstream so that they can be collected with a blood draw. A drug that blocks Robo4 could be a safer and more effective way to do this, Forsberg said.

"If we can get specific and efficient inhibition of Robo4, we might be able to mobilize the hematopoietic stem cells to the blood more efficiently," she said. "We're already working on that in the second phase of the project."

Robo4 acts as an adhesion molecule, interacting with other components of the bone marrow to bind the stem cells into their proper niche.

Forsberg's lab is trying to find out what molecules bind to Robo4, which could lead to a better understanding of that niche.

While other types of stem cells are routinely grown in petri dishes, hematopoietic stem cells are very difficult to grow in the lab. They seem to require the bone marrow environment to function properly, and Forsberg's research might enable researchers to recreate that environment in a petri dish.

Other molecules besides Robo4 are also known to be involved in guiding hematopoietic stem cells in the bone marrow. Forsberg's results indicate that one of these is called Cxcr4, which acts together with Robo4 to keep hematopoietic stem cells in the bone marrow.

But the two molecules appear to act through different mechanisms. Inhibiting both molecules may be the best way to efficiently mobilize hematopoietic stem cells, Forsberg said.

Stephanie Smith-Berdan, a research specialist in Forsberg's lab, is first author of the new paper. Coauthors include UCSC researchers Andrew Nguyen, Deena Hassanein, Matthew Zimmer, Fernando Ugarte, and Lindsay Hinck, professor of molecular, cell and developmental biology; Dean Li of the University of Utah; and Jesus Ciriza and Marcos Garcia-Ojeida of UC Merced. This work was funded by UCSC and the California Institute for Regenerative Medicine.















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