Home
Google
 
Home-----History-----Bibliography-----Pregnancy Timeline-----Prescription Drugs in Pregnancy-----Pregnancy Calculator-----Female Reproductive System-----News Alerts-----Contact


Week Ending FRIDAY December 31, 2010---------News Archive

In Brain Cancer, Unique Genetic and “Epigenetic” Profile Means Better Odds

Brain cancers are deadly more often than not, but UCSF researchers have determined that a particular genetic signature is associated with longer survival.

Glial cellsThe discovery, reported online December 15 in the Journal of the National Cancer Institute, may lead to a better understanding of how certain cancers can arise and lead to better therapies for some of the deadliest brain cancers, for which there is no curative treatment.

Brain cancers cause 13,000 deaths in the US each year. A majority are advanced, grade-IV glioblastomas at the time of diagnosis. Even with surgery and radiation or chemotherapy, less than one in 20 individuals with a glioblastoma diagnosis remains alive after five years. Half die within one year.

Yet across all grades of brain tumors, including glioblastomas, the presence of an abnormally altered version of a gene called IDH is associated with improved survival, the UCSF researchers report.

The research was led by John Wiencke, PhD, and Margaret Wrensch, PhD, both professors in the Department of Neurological Surgery at UCSF and members of the UCSF Helen Diller Family Comprehensive Cancer Center, along with Karl Kelsey, MD, of Brown University. Their research group analyzed clinical data and brain tumor samples from the UCSF Brain Tumor Research Center’s Tissue Bank. The study included samples from 131 patients who had been treated by UCSF Department of Neurological Surgery physicians.

Brain Cancers with IDH Mutations are Distinctive

A patient with the IDH tumor mutation was four times more likely to survive longer than a patient with a similar tumor that lacked the mutation. The survival benefit was independent of the influence of other patient and tumor characteristics that are commonly charted in clinical pathology labs, such as age and tumor subtype.

Within the last few years the IDH mutation has been found to be associated with brain tumors and with a type of leukemia. Most strikingly, the UCSF team has found that the mutation is associated with a distinctive “epigenetic” fingerprint within tumors. It’s still early days when it comes to understanding what these fingerprints mean in cancers and how to use the information to battle tumors.

Changes in the epigenetic characteristics of DNA do not change the tumor’s genetic code – no substitutions are made in the alphabet building blocks that spell out a DNA sequence. But epigenetic changes do affect whether or not genes are active – whether a gene tells a cell to make its encoded protein, for instance. Methylation of DNA – the addition of a carbon-containing molecule – is one such epigenetic event that can affect whether the DNA is active.

In this way methylation patterns shape cell form, growth, function and identity. Changing methylation patterns guide the complex development of growing organisms. In humans the result is the generation of hundreds of different tissue types that work together to form the whole.

It is no surprise that abnormal tumor cells possess abnormal methylation patterns. Any collection of brain tumors typically displays a wide range of abnormal methylation patterns.

However, what was surprising to the UCSF researchers in their latest study is that DNA from almost all tumors with IDH mutations had the same distinctive methylation pattern. The degree of methylation throughout the genome was unusually high, and the same specific DNA was methylated.

“This one mutation is common to a whole subset of brain tumors,” Wrensch says. “It’s quite unique. It seems to dominate other mutations in the tumor and the epigenetic changes are very uniform.”

Metabolism Advantage for Tumors Suspected

The IDH mutation was present in less than 10 percent of brain cancers diagnosed as grade IV glioblastomas, but was detected in 80 percent of lower grade brain tumors. Although the cancers generally proved fatal in each type of brain cancer, the presence of the mutation was associated with longer survival compared to tumors of the same grade that lacked the mutation.

Because brain tumors with IDH mutations may arise by a common pathway, it may be possible to identify key biochemical events and molecules along this path to tumor formation. These molecules could be targeted for new drug development efforts aimed at tumors with this distinctive fingerprint, the UCSF researchers say.

The protein made according to the instructions encoded by the IDH gene is involved in sugar metabolism, a source of energy for cells. Tumors are believed to require more energy than normal tissue to fuel uncontrolled growth. The methylation pattern of DNA associated with the IDH mutation is associated with a ramping up of metabolic pathways. Wiencke speculates that the metabolic role of the IDH mutation may play a role in tumor formation.

The idea that glucose metabolism fuels cancer growth is a very old one, Wiencke says, dating back to the 1920s. It fell out of favor, but may be making a comeback. “How tumor cells get their energy is still mysterious,” he says.

“The fact that the same epigenetic pattern is in different types of brain cancers suggests that there is a common factor that drives the pattern — IDH mutation. Altered metabolism may be playing a role in these cancers.”

IDH Mutation Defines Methylation Class and Survival in Human Glioma

Brock C. Christensen, Ashley A. Smith, Shichun Zheng, Devin C. Koestler, E. Andres Houseman, Carmen J. Marsit, Joseph L. Wiemels, Heather H. Nelson, Margaret R. Karagas, Margaret R. Wrensch, Karl T. Kelsey, John K. Wiencke. JNCI, August, 15, 2010

Newborns Need For Vitamin D

Low levels may increase risk for respiratory infections.

Previous studies found that children of women who took vitamin D supplements during pregnancy were less likely to develop wheezing during childhood. The current study was designed to examine the relationship between the actual blood levels of vitamin D of newborns and the risk of respiratory infection, wheezing and asthma.

The vitamin D levels of newborn babies appear to predict their risk of respiratory infections during infancy and the occurrence of wheezing during early childhood, but not the risk of developing asthma. Results of a study in the January 2011 issue of Pediatrics support the theory that widespread vitamin D deficiency contributes to risk of infections.

“Our data suggest that the association between vitamin D and wheezing, which can be a symptom of many respiratory diseases and not just asthma, is largely due to respiratory infections,” says Carlos Camargom of Harvard-affiliated Massachusetts General Hospital (MGH), who led the study. “Acute respiratory infections are a major health problem in children. For example, bronchiolitis — a viral illness that affects small airway passages in the lungs — is the leading cause of hospitalization in U.S. infants.”

Although vitamin D is commonly associated with its role in developing and maintaining strong bones, recent evidence suggests that it is also critical to the immune system. Vitamin D is produced by the body in response to sunlight, and achieving adequate levels in winter can be challenging, especially in regions with significant seasonal variation in sunlight. Previous studies by Camargo’s team found that children of women who took vitamin D supplements during pregnancy were less likely to develop wheezing during childhood. The current study was designed to examine the relationship between the actual blood levels of vitamin D of newborns and the risk of respiratory infection, wheezing and asthma.

The researchers analyzed data from the New Zealand Asthma and Allergy Cohort Study, which followed more than 1,000 children in the cities of Wellington and Christchurch. Midwives or study nurses gathered a range of measures, including samples of umbilical cord blood, from newborns whose mothers enrolled them in the study. The mothers subsequently answered questionnaires — which among other items asked about respiratory and other infectious diseases, the incidence of wheezing, and any diagnosis of asthma — 3 and 15 months later and then annually until the children were 5 years old. The cord blood samples were analyzed for levels of 25-hydroxyvitamin D (25OHD), considered to be the best measure of vitamin D status.

Cord blood samples were available from 922 newborns in the study cohort, and more than 20 percent of them had 25OHD levels less than 25 nmol/L, which is considered very low.

The average level of 44 nmol/L would still be considered deficient — some believe that the target level for most individuals should be as high as 100 nmol/L — and lower levels were more common among children born in winter, of lower socioeconomic status, and with familial histories of asthma and smoking.

By the age of 3 month, infants with 25OHD levels below 25 nmol/L were twice as like to have developed respiratory infections as those with levels of 75 nmol/L or higher.

Survey results covering the first five years of the participants’ lives showed that the lower the neonatal 25OHD level, the higher the cumulative risk of wheezing during that period.

But no significant association was seen between 25OHD levels and a physician diagnosis of asthma at age 5 years. Some previous studies had suggested that particularly high levels of vitamin D might increase the risk for allergies, but no such association was seen among study participants with the highest 25OHD levels. Camargo notes that very few children in this study took supplements; their vitamin D status was determined primarily by exposure to sunlight.

An associate professor of medicine at Harvard Medical School, Camargo said that the study results do not mean that vitamin D levels are unimportant for people with asthma.

“There’s a likely difference here between what causes asthma and what causes existing asthma to get worse. Since respiratory infections are the most common cause of asthma exacerbations, vitamin D supplements may help to prevent those events, particularly during the fall and winter when vitamin D levels decline and exacerbations are more common. That idea needs to be tested in a randomized clinical trial, which we hope to do next year.”


THURSDAY December 30, 2010---------News Archive

CF Protein Linked to Other Chronic Lung Diseases

A team of Johns Hopkins Children's Center researchers has discovered that a protein involved in cystic fibrosis (CF) also regulates inflammation and cell death in emphysema and may be responsible for other chronic lung diseases.

The findings, published online in the December issue of The Journal of Immunology, pave the way toward new treatments to prevent lung damage caused by infections or cigarette smoke in emphysema.

The protein, called CFTR (cystic fibrosis transmembrane conductance regulator), is already well known for its role in transporting chloride in and out of cells. In CF, the protein's chloride-carrying ability is absent due to genetic mutations, resulting in the buildup of thick sticky mucus in the lungs, which causes lung infections and breathing problems.

But the new Hopkins study indicates that CFTR is involved in immune regulation and immune response on a far wider scale. The research — conducted in mice and using lung tissue from people with and without emphysema — shows that those with lung damage from emphysema had less CFTR on the cell surface and that changes in the level of CFTR corresponded directly to disease severity. Decreases in CFTR also corresponded to increased buildup in the lung cells of a fatty molecule called ceramide, a well-known trigger of inflammation and cell death. Thus, the researchers say, by regulating ceramide's inflammation-causing activity, CFTR appears to be a watchdog for inflammation and cell death.

"Our findings suggest that CFTR is a multi-tasker protein that is not only involved in chloride transport but also in regulating cell death and inflammation by keeping in check the rampant and dangerous accumulation of ceramide," said principal investigator Neeraj Vij, Ph.D., a pulmonary researcher at Hopkins Children's and assistant professor at the Johns Hopkins University School of Medicine.

To elucidate the role played by cigarette smoking — the leading cause of emphysema — the researchers analyzed CFTR and ceramide levels in lung tissue obtained from non-smokers and from light and heavy former or current smokers. To further explore the link between cigarette smoke, CFTR and ceramide, the researchers compared lung tissue from mice with "virgin" lungs never exposed to smoke to tissue from the lungs of mice exposed to cigarette smoke for five hours a day over five days. The lungs of smoke-exposed mice had decreased CFTR expression and increased ceramide levels, thus confirming the role of cigarette smoke in lung damage. The heavier the smoking, the greater the lung damage, the lower the CFTR expression and the higher the ceramide accumulation, the researchers noted, clearly linking CFTR and ceramide levels to smoking history and disease severity.

Beyond clarifying the link between CFTR, ceramide and lung damage, the Hopkins team explained just how CFTR causes ceramide to trigger lung-damaging inflammation.

Analyzing lung cells from people and mice lacking CFTR in their cell membrane under a microscope and with a technique called flow cytometry (that captures changes in inflammatory and protein markers), the scientists noticed increased clustering of ceramide molecules on sections of the cell membrane called lipid rafts, known to be hot spots where inflammatory signaling proteins congregate.

This clustering leads to increased inflammatory signaling, greater inflammation and cell damage, but cells with normal CFTR had no such clustering. Apparently, when functioning properly CFTR keeps a lid on the signaling activity of inflammatory receptors by preventing them from clustering, thus warding off inflammation and lung damage.

"We anticipate that membrane CFTR and ceramide may turn out to be useful predictors of susceptibility to lung damage from smoking and infections and may be tailored for drug therapy to alter disease course," Vij said.

To further test their hypothesis, the researchers used two types of ceramide inhibitors to treat mice with lung damage caused by a bacterial infection. One of the inhibitors, FB1, successfully decreased ceramide buildup in mice with intact CFTR but failed to stop ceramide accumulation in mice with absent CFTR, as is the case in CF. However, the other type of inhibitor, AMT, curbed ceramide activity in the mice with the absent CFTR, while failing to do so in those with decreased CFTR.

"Each inhibitor appeared to be effective based on the levels of membrane CFTR and ceramide, suggesting two different therapies tailored to treat lung damage stemming from two distinct lung disorders — emphysema and CF," said co-investigator Manish Bodas, Ph.D., a post-doctoral fellow in Vij's lab at Hopkins Children's.

The research was funded by the National Institutes of Health and the Flight Attendant Medical Research Institute. Co-investigators in the study included Taehong Min and Steven Mazur, both of Hopkins.

PubMed Publication http://www.ncbi.nlm.nih.gov/pubmed/21135173

Founded in 1912 as the children's hospital of the Johns Hopkins Medical Institutions, the Johns Hopkins Children's Center offers one of the most comprehensive pediatric medical programs in the country, with more than 92,000 patient visits and nearly 9,000 admissions each year. Hopkins Children's is consistently ranked among the top children's hospitals in the nation. Hopkins Children's is Maryland's largest children's hospital and the only state-designated Trauma Service and Burn Unit for pediatric patients. It has recognized Centers of Excellence in dozens of pediatric subspecialties, including allergy, cardiology, cystic fibrosis, gastroenterology, nephrology, neurology, neurosurgery, oncology, pulmonary, and transplant. For more information, visit www.hopkinschildrens.org.

Nature's First Immune Systems Are In Bacteria

Studying how bacteria incorporate foreign DNA from invading viruses into their own regulatory processes, Thomas Wood, professor in the Artie McFerrin Department of Chemical Engineering at Texas A&M University, is uncovering the secrets of one of nature's most primitive immune systems.

His research has shed light on how bacteria have throughout the course of millions of years developed resistance to antibiotics by co-opting the DNA of their natural enemies—viruses.

Wood's findings appear in Nature Communications, a publication dedicated to research in all areas of the biological, physical and chemical sciences.

The battle between bacteria and bacteria-eating viruses, Wood explains, has been going on for millions of years, with viruses attempting to replicate themselves by – in one approach – invading bacteria cells and integrating themselves into the chromosomes of the bacteria. When this happens a bacterium makes a copy of its chromosome, which includes the virus particle. The virus then can choose at a later time to replicate itself, killing the bacterium—similar to a ticking time bomb, Wood says.

However, things can go radically wrong for the virus because of random but abundant mutations that occur within the chromosome of the bacterium. Having already integrated itself into the bacterium's chromosome, the virus is subject to mutation as well, and some of these mutations, Wood explains, render the virus unable to replicate and kill the bacterium.

With this new diverse blend of genetic material, Wood says, a bacterium not only overcomes the virus' lethal intentions but also flourishes at a greater rate than similar bacteria that have not incorporated viral DNA.

"Over millions of years, this virus becomes a normal part of the bacterium," Wood says. "It brings in new tricks, new genes, new proteins, new enzymes, new things that it can do. The bacterium learns how to do things from this.

"What we have found is that with this new viral DNA that has been trapped over millions of years in the chromosome, the cell has created a new immune system," Wood notes. "It has developed new proteins that have enabled it to resists antibiotics and other harmful things that attempt to oxidize cells, such as hydrogen peroxide. These cells that have the new viral set of tricks don't die or don't die as rapidly."

Understanding the significance of viral DNA to bacteria required Wood's research team to delete all of the viral DNA on the chromosome of a bacterium, in this case bacteria from a strain of E. coli.

Wood's team, led by postdoctoral researcher Xiaoxue Wang, used what in a sense could be described as "enzymatic scissors" to "cut out" the nine viral patches, which amounted to precisely removing 166,000 nucleotides. Once the viral patches were successfully removed, the team examined how the bacterium cell changed. What they found was a dramatically increased sensitivity to antibiotics by the bacterium.

While Wood studied this effect in E. coli bacteria, he says similar processes have taken place on a massive, widespread scale, noting that viral DNA can be found in nearly all bacteria, with some strains possessing as much as 20 percent viral DNA within their chromosome.

"To put this into perspective, for some bacteria, one-fifth of their chromosome came from their enemy, and until our study, people had largely neglected to study that 20 percent of the chromosome," Wood says. "This viral DNA had been believed to be silent and unimportant, not having much impact on the cell.

"Our study is the first to show that we need to look at all bacteria and look at their old viral particles to see how they are affecting the bacteria's current ability to withstand things like antibiotics. If we can figure out how the cells are more resistant to antibiotics because of this additional DNA, we can perhaps make new, effective antibiotics."

Contact: Lane Stephenson, News & Information Services at (979) 845-4662 or l-stephenson@tamu.edu; or Thomas Wood at (979) 862-1588 (office) or (979) 595-5539 (cell) or thomas.wood@che.tamu.edu.

For more news about Texas A&M University, go to http://tamunews.tamu.edu.


WEDNESDAY December 29, 2010---------News Archive

Learning To Read The Genome

The fruit-fly genome points the way to understanding the genomes of all organisms. In the past decade researchers have made astonishing progress in the sequencing of genomes from all realms of life. Yet the list of base pairs has gotten far ahead of understanding how the information they contain is functional. Even the best-understood genomes conceal mysteries.

Genetic information carried by DNA and RNA operates together with the patterns and physical organization of chromosomes to produce a working organism.

Major advances in understanding these complex relationships are published this week by the "model organism Encyclopedia of DNA Elements" (modENCODE) project, funded by the National Institutes of Health's National Human Genome Research Institute. These new insights into reading the genome apply not only to the two model organisms of the project, but will apply to human beings and many other organisms as well.

Susan Celniker and Gary Karpen of the Life Sciences Division at the U.S. Department of Energy's Lawrence Berkeley National Laboratory lead two of the principal research groups in the Drosophila (fruit fly) modENCODE Consortium. They are among the senior co-authors of the Consortium's report on integrating Drosophila functional elements and regulatory circuits, led by Manolis Kellis of the Massachusetts Institute of Technology, which appears in the December 24 issue of Science now online. Separate papers by the Celniker- and Karpen-led groups will appear in Nature in January and are now available online, and more papers by their groups will soon appear in an issue of Genome Research devoted to modENCODE studies.

"Drosophila may be the single most thoroughly studied model organism; it allowed us to discover, a century ago, that chromosomes are the carriers of genetic information," says Celniker, whose group studies the transcriptome - which is the totality of RNA forms that transmit genetic information to the cellular machinery by constructing functioning proteins, as well as the noncoding RNAs that regulate gene expression, splicing, RNA stability, and metabolism. Yet, says Celniker, "there's still a lot of undiscovered territory."

Celniker's group succeeded in exploring Drosophila RNAs at a level never achieved before. "From the RNAs we identified approximately one thousand new genes, both protein-coding and noncoding. These were previously missed because they are less well conserved, or were found in less-studied developmental stages and RNA populations. Thus they tend to be expressed at lower levels than known genes." She adds, "We also found an order-of-magnitude increase in the ways that genes are spliced and edited to produce alternate forms of known proteins, thus significantly increasing the complexity of the proteome." The proteome is the set of all proteins expressed by the genome.

Karpen's group studies chromatin, the combination of DNA and proteins that organize an organism's genome into chromosomes. In chromatin, the DNA is wound around structures called nucleosomes, made of histone proteins. They have produced the first comprehensive picture of how patterns of chromatin components are associated with chromosome functions, including the active transcription of genes. These mechanisms are called "epigenetic" because their influence on genome function is coded by the associated proteins rather than the DNA sequence.

The modENCODE transcriptome and chromatin groups, working with other groups that concentrate on small RNAs and DNA replication. The research groups carried out their studies on four different kinds of Drosophila cells maintained in laboratory cell cultures, not all of which had been extensively explored before. Additional studies with whole animals were carried out, especially in tracking developmental changes, from fly embryos through larvae and pupae to adult males and females.

Using a variety of techniques, the researchers developed 700 new data sets of information on different aspects of the fly genome. The transcriptome group identified 17,000 genes, both coding and noncoding, of which 1,938 were new.

But DNA is surprisingly versatile – coding sequences, known as exons, can be spliced together in different ways to produce more than one form of a protein. The researchers found almost 53,000 new or modified exons and almost 23,000 new splicing junctions, with 14,000 alternative ways of transcribing the genetic information. Despite the scrutiny to which the Drosophila genome has been subjected, the researchers found new or altered exons or splice forms in almost three-quarters of Drosophila's previously annotated genes.

Like all eukaryotes (organisms whose cell nuclei are enclosed within a membrane) Drosophila's genome is divided among euchromatin, which contains many active genes, and heterochromatin, which – although it amounts to about a third of the genome – contains relatively few active genes. The Drosophila chromatin group was surprised to discover some regions of heterochromatin are almost as active in expression as euchromatin.

The mark of an active or silent chromatin region is the chemical state of its nucleosomes, specifically whether the histones, on which the DNA is wrapped, permit or prevent the RNA-constructing enzyme - RNA polymerase - to bind to the DNA for transcription. Acetylated histones generally promote transcription, while many methylated histones can repress transcription.

The Drosophila chromatin group found that in some regions, what controlled gene expression could not be identified from the DNA sequence, yet these regions were marked by specific histone modifications and other epigenetic factors. They also found active regions of euchromatin that carried marks characteristic of heterochromatin, patterns that were a combination of both "active" and "silent" marks.

By identifying the patterns of 18 different histone modifications, and analyzing their associations with gene expression and other functions, the group developed a model of chromatin states working in concert, and how these vary among different cell lines. Their model identified novel chromatin signatures associated with regulation of gene activity and other functions, as well as many previously unidentified genes and promoters.

Of the modENCODE project, Celniker says, "The goal is not only to map every base in the genome but to discover the function of every base." Adds Karpen, "Discovering function starts with mapping all the components that affect it."

From the genomes of model organisms like the fruit fly and the roundworm, says Celniker, "We would like to crack the genomic code and discover the rules required to read a genome – any genome. Knowing which signals control gene expression in the fruit fly and the roundworm, including how chromatin affects gene expression, will be applicable to understanding how to read the human genome."

"Identification of Functional Elements and Regulatory Circuits by Drosophila modENCODE," by the Drosophila modENCODE Consortium, appears in the 24 December 2010 issue of Science and is now online. The Consortium's transcriptome group, led by Berkeley Lab's Susan Celniker, includes research teams led by Brenton Graveley of the University of Connecticut Health Center, Peter Cherbas of Indiana University Bloomington, Tom Gingeras of Cold Spring Harbor Laboratory, Norbert Perrimon of Harvard Medical School, Michael Brent of Washington University in Saint Louis, and Steven Brenner of the University of California at Berkeley. The chromatin group, led by Gary Karpen of Berkeley Lab and UC Berkeley, includes teams led by Sarah Elgin of Washington University in Saint Louis, Mitzi Kuroda of Harvard Medical School, Peter Park of Harvard Medical School, and Vince Pirrotta of Rutgers University.

"The developmental transcriptome of Drosophila melanogaster," by members of the transcriptome group, and "Comprehensive analysis of the chromatin landscape in Drosophila melanogaster," by members of the chromatin group, now appears in advance online publication of Nature.

Forthcoming papers on promoter architecture, by Celniker and first author Roger Hoskins of her team at Berkeley Lab; on transcriptional profiling of Drosophila cell lines, by Lucy and Peter Cherbas of the Celniker group; and on chromatin organization of heterochromatin by the Karpen group, including co-first author Aki Minoda of Berkeley Lab, will appear in a forthcoming issue of Genome Research devoted to modENCODE studies.

Measuring DNA of Basque Diaspora

Making good use of the extensive network of Euskal Etxeak (Basque social centres abroad), researchers have obtained samples of saliva from hundreds of persons of Basque origin in Argentina and in the United States (California, Nevada and Idaho) for comparison of environmental affects on Basque DNA.

In the United States, two groups have already been identified. One being the Basque who married within the Basque community. The second, those who mixed with non Basques.

The BIOMICs Group, based at the Lucio Lascaray building in the Álava/Araba campus of the University of the Basque Country (UPV/EHU), is known for overseeing the SGIker DNA Bank, and for generating gene research.

Led by Dr. Marian Martínez de Pancorbo, BIOMICs has numerous areas of genetic research including neurodegenerative, cancer, and forensics. Dr. de Pancorbo works jointly with Basque hospitals and universities worldwide to identify disease markers. The BIOMICs team recently published a study on Alzheimer’s in Nature Genetics. “We studied the stage prior to Alzheimer [diagnosis]. If we manage to detect genes that can indicate a greater risk, palliative therapies can be tried earlier,” explained Dr. de Pancorbo.

Another line of research on breast cancer undertaken by researcher Naiara Bediaga, was published in the prestigious journal Breast Cancer Research: “If one looks at the DNA of a tumour and that of healthy tissue, the sequence of bases is the same. But when one looks inside the tumour, the DNA bases of the tumour have methyl groups which modify the DNA.” This could be a key for earlier detection of cancer.

Cancer, Alzheimer, Parkinson, prionopathy (fatal familiar insomnia), archaeogenetics, and more are being targeted through DNA research. However, one of their strongest interests involves traditional curiosity – the genetics of human populations and evolution. Therefore, the team is now focused on the Basque community living on the other side of the Atlantic.

“We have these genetically similar populations (from the Basque Country) living in other environments. We wanted to see how these [environments] influenced the Basque populations, ... [we are able to follow] a Basque who immigrates [ from a] very small region, thanks to their surname,” explained Dr. M. de Pancorbo: “We believe that it can contribute a lot to knowing how mixtures of populations are going to be influenced, above all, from the viewpoint of health and of illness.”

Knowing the genetic heritage of the Basques, Dr. de Pancorbo states: “we are now beginning to carry out studies regarding obesity and we also wish to investigate related illnesses.”

The research team is preparing an expedition to take place within the next two years, to explore when the Basque whalers first appeared on the North American continent.

“Here the surnames have not been kept, but the Y chromosome enables us to follow the trail of the Basques, as the Y chromosome of the Native American Indians is different. We want to see what percentage there is of certain genes, what percentage of others and how this is correlated with the state of health and illnesses of the Native American peoples who interelated with our population,” explains the Director of BIOMICs.


TUESDAY December 28, 2010---------News Archive

Quails’ Social Stress Affects Their Young

A recent study has revealed that the social environment of mother quails has a direct influence on the growth and the behaviour of their young.

The phrase “nature versus nurture” was coined in the mid-19th century by the English scientist Francis Galton symbolizing the debate over the importance of inherited factors compared to environmental factors (or upbringing) in determining the behaviour of offspring.

This issue has become even more complicated today with the discovery that “epigenetic” factors, passed on by mothers in particular, can alter the genetic material of our children.

A new twist is provided by these findings - that female birds affect their chicks by adding varying amounts of hormones to their eggs.

It may come as a surprise to many that quails are able to distinguish one another, let alone form close relationships with other quails.

Nevertheless, it has long been known that disruption of quails’ social environment causes them stress. A research group at the CNRS-Université de Rennes 1 in France has been studying the influence of adult quails on the behavioural development of their offspring.

Together with scientists in Austria, they have now shown that changing the composition of groups of quails housed together causes the birds to behave more aggressively towards one another. And, that the level of steroid hormones (corticosterone) in their blood increases when their group composition is disrupted.

Intriguingly, eggs laid by socially disrupted groups of quail were found to have significantly higher levels of testosterone. These results are consistent with previous findings, which showed that House sparrows, American coots and Common starlings lay eggs with more testosterone when they breed in dense colonies, rather than when they nest in isolation.

But the new work from the French-Austrian collaboration goes further, to show that the eggs of female quails under social stress hatch later with the chicks growing more slowly in the first three weeks. Chicks’ also behave differently: they are more cautious and seem more vunerable to disturbances. They tend to move around more, which can be interpreted as increased attempts to escape from threats or, perhaps, as seeking more social support.

The results support that growth and behaviour in chicks is influenced by the concentration of steroid hormones in the eggs from which they hatch.

As Erich Möstl of the Uiversity of Veterinary Medicine, Vienna, says, “We know that stress on female mammals influences the development of their young, which takes place in the womb, but it was a big surprise that social stress causes such changes in the level of hormones in the yolks of birds’ eggs.”

The social environment of mother quails thus has a direct effect on the growth and the behaviour of their offspring. It ssuggests that pre-natal nurture is extremely important in birds as well as in mammals and this finding is sure to add fresh fuel to the century-old nature versus nurture debate.

The work was performed by Floriane Guibert and Cécilia Houdelier at the CNRS-Université de Rennes 1 in France, together with researchers at the INRA in Nouzilly, France and with Austrian scientists including Erich Möstl of the University of Veterinary Medicine, Vienna. Research results were published in November by PloS ONE (10.1371/journal.pone.0014069).

The paper Social Instability in Laying Quail: Consequences on Yolk Steroids and Offspring's Phenotype by Floriane Guibert, Marie-Annick Richard-Yris, Sophie Lumineau, Kurt Kotrschal, Daniel Guémené, Aline Bertin, Erich Möstl and Cécilia Houdelier was published in November by PloS ONE (10.1371/journal.pone.0014069).

The University of Veterinary Medicine, Vienna is the only academic and research institution in Austria that focusses on the veterinary sciences. About 1000 employees and 2300 students work on the campus in the north of Vienna, which also houses the animal hospital and various spin-off-companies.

Not All Infant Formulas Are Alike

New findings from the Monell Center reveal that weight gain of formula-fed infants is influenced by the type of formula the infant is consuming.

The findings have implications related to the infant's risk for the development of obesity, diabetes and other diseases later in life.

"Events early in life have long-term consequences on health and one of the most significant influences is early growth rate," said study lead author Julie Mennella, Ph.D., a developmental psychobiologist at Monell. "We already know that formula-fed babies gain more weight than breast-fed babies. But we didn't know whether this was true for all types of formula."

While most infant formulas are cow's milk-based, other choices include soy-based and protein hydrolysate-based formulas. Protein hydrolysate formulas contain pre-digested proteins and typically are fed to infants who cannot tolerate the intact proteins in other formulas.

In adults, pre-digested proteins are believed to act in the intestine to initiate the end of a meal, thus leading to smaller meals and intake of fewer calories. Based on this, researchers hypothesized that infants who were feeding protein hydrolysate formulas would eat less and have an altered growth pattern relative to infants feeding cow's milk-based formula.

In the study, published online in the journal Pediatrics, infants whose parents had already decided to bottle-feed were randomly assigned at two weeks of age to feed either a cow's milk-based formula (35 infants) or a protein hydrolysate formula (24 infants) for seven months.

Both formulas contained the same amount of calories, but the hydrolysate formula had more protein, including greater amounts of small peptides and free amino acids.

Infants were weighed once each month in the laboratory, where they also were videotaped consuming a meal of the assigned formula. The meal continued until the infant signaled that s/he was full.

Over the seven months of the study, the protein hydrolysate infants gained weight at a slower rate than infants fed cow milk formula. Linear growth, or length, did not differ between the two groups, demonstrating that the differences in growth were specifically attributable to weight.

"All formulas are not alike," said Mennella. "These two formulas have the same amount of calories, but differ considerably in terms of how they influence infant growth."

When the data were compared to national norms for breast-fed infants, the rate of weight gain of protein hydrolysate infants was comparable to the breast milk standards; in contrast, infants fed cow's milk formula gained weight at a greater rate than the same breast milk standards.

Analysis of the laboratory meal revealed the infants fed the protein hydrolysate formula consumed less formula during the meal.

"One of the reasons the protein hydrolysate infants had similar growth patterns to breast-fed infants, who are the gold standard, is that they consumed less formula during a feed as compared to infants fed cow's milk formula" said Mennella. "The next question to ask is: Why do infants on cow's milk formula overfeed?"

The findings highlight the need to understand the long-term influences of infant formula composition on feeding behavior, growth, and metabolic health. Future studies will utilize measures of energy metabolism and expenditure to examine how the individual formulas influence growth, and how each differs from breastfeeding.

Also contributing to the study, which was funded by the National Institute of Child Health and Human Development, were Monell scientists Gary Beauchamp and Alison Ventura.

The Monell Chemical Senses Center is an independent nonprofit basic research institute based in Philadelphia, Pennsylvania. Monell advances scientific understanding of the mechanisms and functions of taste and smell to benefit human health and well-being. Using an interdisciplinary approach, scientists collaborate in the programmatic areas of sensation and perception; neuroscience and molecular biology; environmental and occupational health; nutrition and appetite; health and well-being; development, aging and regeneration; and chemical ecology and communication. For more information about Monell, visit www.monell.org.


MONDAY December 27, 2010---------News Archive

Low Vitamin D in Babies = Risk For Lung Infections

The vitamin D levels of newborn babies appear to predict their risk of respiratory infections during infancy and the occurrence of wheezing during early childhood, but not the risk of developing asthma.

Results of a study in the January 2011 issue of Pediatrics support the theory that widespread vitamin D deficiency contributes to risk of infections.

"Our data suggest that the association between vitamin D and wheezing, which can be a symptom of many respiratory diseases and not just asthma, is largely due to respiratory infections," says Carlos Camargo, MD, DrPH, of the Massachusetts General Hospital (MGH), who led the study.

"Acute respiratory infections are a major health problem in children. For example, bronchiolitis – a viral illness that affects small airway passages in the lungs – is the leading cause of hospitalization in U.S. infants."

Although vitamin D is commonly associated with its role in developing and maintaining strong bones, recent evidence suggests that it is also critical to the immune system.

Vitamin D is produced by the body in response to sunlight, and achieving adequate levels in winter can be challenging, especially in regions with significant seasonal variation in sunlight. Previous studies by Camargo's team found that children of women who took vitamin D supplements during pregnancy were less likely to develop wheezing during childhood. The current study was designed to examine the relationship between the actual blood levels of vitamin D of newborns and the risk of respiratory infection, wheezing and asthma.

The researchers analyzed data from the New Zealand Asthma and Allergy Cohort Study, which followed more than 1,000 children in the cities of Wellington and Christchurch.

Midwives or study nurses gathered a range of measures, including samples of umbilical cord blood, from newborns whose mothers enrolled them in the study. The mothers subsequently answered questionnaires – which among other items asked about respiratory and other infectious diseases, the incidence of wheezing, and any diagnosis of asthma – 3 and 15 months later and then annually until the children were 5 years old. The cord blood samples were analyzed for levels of 25-hydroxyvitamin D (25OHD) – considered to be the best measure of vitamin D status.

Cord blood samples available from 922 newborns in the study cohort, showed more than 20 percent of them had 25OHD levels less than 25 nmol/L, which is considered very low.

The average level of 44 nmol/L would still be considered deficient – some believe that the target level for most individuals should be as high as 100 nmol/L – and lower levels were more common among children born in winter, of lower socioeconomic status and with familial histories of asthma and smoking.

By the age of 3 month, infants with 25OHD levels below 25 nmol/L were twice as like to have developed respiratory infections as those with levels of 75 nmol/L or higher.

Survey results covering the first five years of the participants' lives showed that, the lower the neonatal 25OHD level, the higher the cumulative risk of wheezing during that period. But no significant association was seen between 25OHD levels and a physician diagnosis of asthma at age 5 years. Some previous studies had suggested that particularly high levels of vitamin D might increase the risk for allergies, but no such association was seen among study participants with the highest 25OHD levels.

Camargo notes that very few children in this study took supplements; their vitamin D status was determined primarily by exposure to sunlight.

An associate professor of Medicine at Harvard Medical School, Camargo notes that the study results do not mean that vitamin D levels are unimportant for people with asthma.

"There's a likely difference here between what causes asthma and what causes existing asthma to get worse. Since respiratory infections are the most common cause of asthma exacerbations, vitamin D supplements may help to prevent those events, particularly during the fall and winter when vitamin D levels decline and exacerbations are more common. That idea needs to be tested in a randomized clinical trial, which we hope to do next year."

Co-authors of the Pediatrics paper are Ravi Thadhani, MD, and Janice Espinola, MPH, from MGH; Tristram Ingham, MBChB, Kristin Wickens, PhD, and Julian Crane, FRACP, from University of Otaga, Wellington, New Zealand; Karen Silvers, PhD, Michael Epton, PhD, FRACP, and Philip Pattemore, MD, FRACP, from University of Otago, Christchurch, NZ; and Ian Town, DM, from University of Canterbury, Christchurch, NZ. The study was supported by grants from the Health Research Council of New Zealand, the David and Cassie Anderson Bequest and the MGH Center for D-receptor Activation Research.

Amygdala Contributes to Rich, Varied Social Life

Scientists have discovered that the amygdala, a small almond shaped structure deep within the temporal lobe, is important to a rich and varied social life among humans.

Published this week in Nature Neuro-science, the results are similar to previous findings which compared size and complexity of social groups across primate species.

"We know that primates who live in larger social groups have a larger amygdala, even when controlling for overall brain size and body size," says Lisa Feldman Barrett, PhD, of the Massachusetts General Hospital (MGH) Psychiatric Neuroimaging Research Program and a Distinguished Professor of Psychology at Northeastern University, who led the study.

"We considered a single primate species, humans, and found that the amygdala volume positively correlated with the size and complexity of social networks in adult humans."

The researchers also performed an exploratory analysis of all the subcortical structures within the brain and found no compelling evidence of a similar relationship between any other subcortical structure and the social life of humans. The volume of the amygdala was not related to other social variables in the life of humans such as life support or social satisfaction.

"This link between amygdala size and social network size and complexity was observed for both older and younger individuals and for both men and women," says Bradford C. Dickerson, MD, of the MGH Department of Neurology and the Martinos Center for Biomedical Research.

"This link was specific to the amygdala, because social network size and complexity were not associated with the size of other brain structures." Dickerson is an associate professor of Neurology at Harvard Medical School, and co-led the study with Dr. Barrett.

The researchers asked 58 participants to report information about the size and the complexity of their social networks by completing standard questionnaires that measured the total number of regular social contacts that each participant maintained, as well the number of different groups to which these contacts belonged.

Participants, ranging in age from 19 to 83 years, also received a magnetic resonance imaging brain scan to gather information about the structure of various brain structures, including the volume of the amygdala.

A member of the the Martinos Center at MGH, Barrett also notes that the results of the study were consistent with the "social brain hypothesis," which suggests that the human amygdala might have evolved partially to deal with an increasingly complex social life.

"Further research is in progress to try to understand more about how the amygdala and other brain regions are involved in social behavior in humans," she says. "We and other researchers are also trying to understand how abnormalities in these brain regions may impair social behavior in neurologic and psychiatric disorders."

Co-Authors of the Nature Neuroscience paper are Kevin C. Bickart, Boston University School of Medicine; and Christopher I. Wright, MD, PhD, and Rebecca J. Dautoff of the MGH Psychiatric Neuroimaging Research Program and the Martinos Center. The study was supported by grants from the US National Institutes of Health and the US National Institute on Aging.

Celebrating the 200th anniversary of its founding in 1811, Massachusetts General Hospital is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $600 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.















Care.com





Home---History- --Bibliography- -Pregnancy Timeline---Prescription Drugs in Pregnancy--- Pregnancy Calculator----Female Reproductive System---News Alerts---Contact-
Creative Commons LicenseContent protected under a Creative Commons License. No dirivative works may be made or used for commercial purposes.