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Archive - 2012

April 15th

Blood Type A May Predispose to Some Rotavirus Infections

Whether you become infected by some strains of rotavirus may depend on your blood type. Some strains of rotavirus find their way into the cells of the gastrointestinal tract by recognizing antigens associated with the type A blood group, a finding that represents a new paradigm in understanding how this gut pathogen infects humans, said Baylor College of Medicine (BCM) researchers in an online report published on April 15, 2012 in the journal Nature. Rotavirus is a major intestinal pathogen that is the leading cause of severe dehydration and diarrhea in infants around the world. An estimated 500,000 people worldwide die from the infection annually. The structure of a key part of a strain of the virus known as P[14] provides a clue to how the virus infects human cells, said Dr. B. V. Venkataram Prasad, professor of biochemistry and molecular biology at BCM and the report's corresponding author. In strains of rotavirus that infect animals, the top of a spike on the virus attaches to the cell via a glycan (one of many sugars linked together to form complex branched-chain structures) with a terminal molecule of sialic acid. The same did not appear to be true of virus strains that infect humans, and scientists believed the human rotavirus strains were bound to glycans with an internal sialic acid molecule, but they did not know how this occurs. "We wondered how this genotype of rotavirus recognized a cellular glycan," said Dr. Prasad. "With colleagues at Emory (University School of Medicine), we did a glycan array analysis to see which glycans interacted with the top of the virus spike (called VP8*)." The only type of glycan that interacted with VP8* was type A histo-blood group antigen, he said. "That was surprising," he said.

Pac Bio Sequencing Technology ID’s FLT3 Gene As Therapeutic Target in AML

Through a groundbreaking new gene sequencing technology, researchers have demonstrated that the gene FLT3 is a valid therapeutic target in acute myeloid leukemia, AML, one of the most common types of leukemia. The technique, developed by Pacific Biosciences, allows for the rapid and comprehensive detection of gene mutations in patients with AML. The findings, published online on April 15, 2012 in Nature, are a result of collaboration among scientists at the University of California, San Francisco, Pacific Biosciences, Mount Sinai School of Medicine, and other institutions. The discovery may help lead to the development of new drugs to treat AML. "By sequencing the FLT3 gene in AML patients who have relapsed on therapy targeted against FLT3, we have determined that FLT3 is a valid therapeutic target, and this will certainly help us better understand the physiology of this type of leukemia in order to help us develop new therapies in the future," said Andrew Kasarskis, Ph.D., who performed the research with colleagues at Pacific Biosciences prior to becoming Vice Chair of the Department of Genetics and Genomic Sciences at Mount Sinai School of Medicine. "In addition, sequencing hundreds of single molecules of FLT3 allowed us to see drug resistance mutations at low frequency. This increased ability to see resistance will let us identify the problem of the resistance sooner in a patient's clinical course and help us take steps to address it." Historically, DNA sequencing of individual molecules in a mixture has been difficult and time-consuming to achieve. However, Pacific Biosciences' single-molecule real-time sequencer, the PacBio® RS, identified mutations in the sequence reads obtained in a single run even at low levels, on the order of 1 to 3 percent of total sequence reads.

April 14th

New Blood Test Links Strains of Toxoplasma gondii to Severe Illness in Newborns

Scientists have identified which strains of the Toxoplasma gondii parasite, the cause of toxoplasmosis, are most strongly associated with premature births and severe birth defects in the United States. The researchers used a new blood test developed by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, to pinpoint T. gondii strains that children acquire from their acutely infected mothers while in the womb. Pregnant women can become infected with T. gondii through contact with cat feces that contain infectious forms of the parasite or by eating undercooked meat. Women who become infected while pregnant may miscarry, give birth prematurely, or have babies with eye or brain damage. “If undetected or untreated, congenital toxoplasmosis can have serious consequences for a child’s quality of life,” noted NIAID Director Anthony S. Fauci, M.D. “The findings from this study support the value of screening for toxoplasmosis to identify patients who could benefit from treatment.” Currently available blood tests can determine whether a person has ever been infected with any strain of Toxoplasma parasite. The experimental test developed at NIAID improves upon the older tests because it can detect the presence of strain-specific antibodies that distinguish infecting strains from one another. The test was developed by Michael Grigg, Ph.D., of NIAID’s Laboratory of Parasitic Diseases, and his colleagues. It was applied to blood samples collected between 1981 and 2009 as part of the National Collaborative Chicago-Based Congenital Toxoplasmosis Study. The study of congenitally infected children was initiated by NIAID grantee Rima McLeod, M.D., of the University of Chicago, who is the first author of the new study, published online on April 11, 2012 in Clinical Infectious Diseases.

Direct Transfer of Chloroplast Genes into Cell Nucleus

Chloroplasts, the plant cell’s green solar power generators, were once living beings in their own right. This changed about one billion years ago, when they were swallowed up, but not digested, by larger cells. Since then, they have lost much of their autonomy. As time went on, most of their genetic information found its way into the cell nucleus; today, chloroplasts would no longer be able to live outside their host cell. Scientists on Dr. Ralph Bock’s team at the Max Planck Institute of Molecular Plant Physiology in Germany have discovered that chloroplast genes take a direct route to the cell nucleus, where they can be correctly read in spite of their architectural differences. Their results were published online on April 12, 2012 in Current Biology. Cyanobacteria are among the oldest life forms, and appear to be the forerunners of green chloroplasts in plant cells. They do not possess a true cell nucleus, but their genetic substance is made up of the same four building blocks as that of humans, plants, and animals. Therefore, the genes encoded in the chloroplast DNA can also be read in the cell nucleus; indeed, many genes that were still found in the cell organelles during early evolution are now located exclusively in the genome of the nucleus. How they made their way there has previously been unclear. Two mechanisms appeared likely: either direct transport in the form of DNA fragments from the chloroplasts to the nucleus or transport in the form of mRNA, which is then transcribed back into DNA. The direct transfer of DNA appears to predominate in the chloroplasts, but this pathway raises two problems. The first problem lies in the promoters, the DNA sequences which ensure that genes are recognized as such.

April 13th

Epigenetic Changes May Underlie Preeclampsia

Virginia Commonwealth University (VCU) School of Medicine researchers have discovered that epigenetic-based changes in the gene expression of a key enzyme may contribute to high blood pressure and increase susceptibility to forming blood clots in pregnant women with preeclampsia. These findings could provide clues to the best treatment approaches for high blood pressure and the formation of blood clots that can block blood flow to a pregnant woman’s internal organs and lead to organ failure. Researchers have been working to determine the root cause of preeclampsia on the molecular level and have now determined that epigenetic mechanisms may be at play. Epigenetics refers to changes in gene expression that are mediated through mechanisms other than changes in the DNA sequence. In a study published online on April 9, 2012 in Hypertension, a journal of the American Heart Association, the VCU team reported that thromboxane synthase – an important inflammatory enzyme – is increased in the blood vessels of expectant mothers with preeclampsia. The thromboxane synthase gene codes for this enzyme, which is involved in several processes, including cardiovascular disease and stroke. This enzyme results in the synthesis of thromboxane, which increases blood pressure and causes blood clots. “The present work is unique because it opens up a new concept as to the cause and subsequent consequences of preeclampsia relating to epigenetics,” said corresponding author Scott W. Walsh, Ph.D., professor in the VCU Department of Obstetrics and Gynecology. “It is the first study to show that epigenetic alterations in the blood vessels of the mother are related to preeclampsia.” According to Dr. Walsh, one of the main epigenetic mechanisms is methylation of the DNA, which controls the expression of genes.

How Worms “Speak” to Each Other

All animals seem to have ways of exchanging information—monkeys vocalize complex messages, ants create scent trails to food, and fireflies light up their bellies to attract mates. Yet, despite the fact that nematodes, or roundworms, are among the most abundant animals on the planet, little is known about the way they network. Now, research led by California Institute of Technology (Caltech) biologists has shown that a wide range of nematodes communicate using a recently discovered class of chemical cues. A paper outlining their studies—which were a collaborative effort with the laboratory of Dr. Frank C. Schroeder, assistant scientist at the Boyce Thompson Institute for Plant Research (BTI) of Cornell University—was published online on April 12, 2012 in the journal Current Biology. Previous research by several members of this team had recently shown that a much-studied nematode, Caenorhabditis elegans, uses certain chemical signals to trade data. What was unknown was whether other worms of the same phylum "talk" to one another in similar ways. But when the researchers looked at a variety of nematodes, they found the very same types of chemicals being combined and used for communication, says Dr. Paul Sternberg, the Thomas Hunt Morgan Professor of Biology at Caltech and senior author on the study. "It really does look like we've stumbled upon the letters or words of a universal nematode language, the syntax of which we don't yet fully understand," he says. Nematodes are wide-ranging creatures; they have been found in hot springs, arctic ice, and deep-sea sediments. Many types of nematodes are harmless, or even beneficial, but others cause damage to plants and harm to humans and animals.

April 12th

Genetic Adaptation of Fat Metabolism Key to Development of Human Brain

About 300,000 years ago, humans adapted genetically to be able to produce larger amounts of omega-3 and omega-6 fatty acids. This adaptation may have been crucial to the development of the unique brain capacity in modern humans. In today's life situation, this genetic adaptation contributes instead to a higher risk of developing disorders like cardiovascular disease. The human nervous system and brain contain large amounts of polyunsaturated fatty acids, and these are essential for the development and function of the brain. These omega-3 and omega-6 fatty acids occur in high quantities in just a few foods, such as fat fish. Our bodies can also produce these important fatty acids themselves from certain vegetable oils. In a new study led by researchers at Uppsala University in Sweden and published April 12, 2012 in The American Journal of Human Genetics, scientists have investigated the genes for the two key enzymes that are needed to produce omega-3 and omega-6 fatty acids from vegetable oils. They have found that humans have a unique genetic variant that leads to increased production. This genetic adaptation for high production of omega-3 and omega-6 fatty acids is found only in humans, and not in our living primate relatives chimpanzees, gorillas, and rhesus monkeys. Neanderthals or Denisovans, another type of extinct hominin species, also did not have this genetic variant. It appeared some 300,000 years ago in the evolutionary line that led to modern humans. This genetic adaptation for more efficient omega-3 and omega-6 production from vegetable oils developed in Africa and has probably been an important factor for human survival in environments with limited dietary access to fatty acids.

Biomarker Family Found for Chemo-Resistant Breast Cancers

Biomarkers that could help predict resistance to chemotherapy in breast cancer patients have been identified by researchers from the University of Hull, UK. The researchers found a family of proteins to be twice as prevalent in clinical samples obtained from breast cancer patients who were resistant to chemotherapy than in samples from patients who were successfully treated. Chemotherapy resistance is a major problem for some types of breast cancer and many patients undergo treatment that does not work, delaying other more suitable treatments and subjecting the patient to adverse side effects in the process. Published online on April 3, 2012 in the Journal of Proteomics, the Hull research identifies a number of potential biomarkers associated with resistance to common chemotherapy drugs, including epirubicin and docetaxel. Lead researcher Dr. Lynn Cawkwell says, "A major goal in cancer research is to be able to predict the response of a patient to chemotherapy. Unfortunately, a reliable test has not yet been developed to achieve this. We hope our work can help to bring us a step closer. Most of my work uses clinical samples instead of cell lines, thanks to the links I have with oncologists and surgeons at Castle Hill Hospital in Hull. Studying clinical samples gives a more accurate representation of what is relevant in real-life diseases." The project used two high-throughput processes to screen clinical samples of breast tumour tissue. One screening method using antibodies identified 38 proteins that were twice as prevalent in samples from patients who were resistant to chemotherapy than in samples from those who were successfully treated. The other screening method used mass spectrometry and uncovered 57 potential biomarkers, of which 5 belong to the 14-3-3 protein family.

April 11th

Chromosomes Organize into “Yarns”

Chromosomes, the molecular basis of genetic heredity, remain enigmatic 130 years after their discovery in 1882 by Dr. Walther Flemming. New research published online on April 11, 2012 in Nature by the team of Edith Heard, Ph.D., from the Curie Institute and Job Dekker, Ph.D., from the University of Massachusetts Medical School (UMMS), reveals a new layer in the complex organization of chromosomes. The scientists have shown that chromosomes fold in a series of contiguous "yarns" that harbor groups of genes and regulatory elements, bringing them in contact with each other and allowing them to work in a coordinated manner during development. Chromosomes are relatively large molecules that, when spread out, can measure up to the length of an entire human arm. Despite their size, however, they are actually confined within the small space of the cell nucleus which is just a few micrometers in size. Furthermore, within each cell nucleus are multiple chromosomes. In humans, for example, there are 23 pairs of chromosomes. In order to fit all this material into this small area, chromosomes are folded, compacted, and mingled in the three-dimensional space of the nucleus. So do chromosomes fill the nucleus just like spaghetti fills a plate? "Not quite," said Elphege Nora, PhD, a post-doctoral fellow on the team of Dr. Heard, head of the Genetics and Developmental Biology Lab at the Curie Institute. "Chromosome folding follows a pattern, and this actually turns out to be important for ensuring their proper function." "We have known for decades that the DNA of individual genes is wrapped around nucleosomes to form the classical 'beads-on-a-string' structure," said Dr. Dekker, co-director of the Program in Systems Biology at UMMS.

Genes Identified for Common Childhood Obesity

Genetics researchers have identified at least two new gene variants that increase the risk of common childhood obesity. "This is the largest-ever genome-wide study of common childhood obesity, in contrast to previous studies that have focused on more extreme forms of obesity primarily connected with rare disease syndromes," said lead investigator Struan F.A. Grant, Ph.D., associate director of the Center for Applied Genomics at The Children's Hospital of Philadelphia. "As a consequence, we have definitively identified and characterized a genetic predisposition to common childhood obesity." The study, by an international collaborative group, the Early Growth Genetics (EGG) Consortium, appeared online on April 8, 2012 in Nature Genetics. As one of the major health issues affecting modern societies, obesity has increasingly received public attention, especially given a rising prevalence of the condition among children. Research indicates that obese adolescents tend to have higher risk of mortality as adults. Although environmental factors, such as food choices and sedentary habits, contribute to the increasing rates of obesity in childhood, twin studies and other family-based evidence have suggested a genetic component to the disease as well. Previous studies have identified gene variants contributing to obesity in adults and in children with extreme obesity, but relatively little is known about genes implicated in regular childhood obesity. "The Center for Applied Genomics at the Children's Hospital of Philadelphia has recruited and genotyped the world's largest collection of DNA from children with common obesity," said Dr. Grant.