Syndicate content

Researchers Discover First Gene Linked to Missing Spleen in Newborns

Researchers at Weill Cornell Medical College and Rockefeller University in New York City have identified the first gene to be linked to a rare condition in which babies are born without a spleen, putting those children at risk of dying from infections they cannot defend themselves against. The gene, Nkx2.5, was shown to regulate genesis of the spleen during early development in mice. The study, published online on May 3, 2012 in Developmental Cell, raises the hope that a simple genetic screening test for Nkx2.5 mutations can be developed that will alert parents that their developing child may be missing the organ, which could then be confirmed with a diagnostic scan. "The great news is that with the appropriate preventive antibiotic treatment these children will not succumb to fatal infections. This test could potentially save lives," says the study's lead investigator, Dr. Licia Selleri, an associate professor in the Department of Cell and Developmental Biology at Weill Cornell Medical College. Because defense against infections depends, in part, on the spleen, children known to be born without the organ require treatment with a regimen of antibiotic therapy throughout their lives. But most diagnoses of this condition, congenital asplenia, are made during an autopsy after a child dies, suddenly and unexpectedly, from a rapidly lethal infection, usually from bacteria that causes pneumonia or meningitis, Dr. Selleri says. "For those reasons, we believe this condition is not quite as rare as believed. Not every child who dies from an infection is given an autopsy." Patients with congenital asplenia usually lack a spleen as the sole abnormality, but sometimes have abnormalities of the heart and blood vessels.

Extra Gene Drove Instant Leap in Human Brain Evolution

A partial, duplicated copy of a gene appears to be responsible for the critical features of the human brain that distinguish us from our closest primate kin. The momentous gene duplication event occurred about two or three million years ago, at a critical transition in the evolution of the human lineage, according to a pair of studies published on May 3, 2012 in Cell. The studies are the first to explore the evolutionary history and function of any uniquely human gene duplicate. These "extra" genes are of special interest as they provide likely sources of raw material for adaptive evolutionary change. Until now, studying them has been a technical challenge because they are nearly indistinguishable from each other. "There are approximately 30 genes that were selectively duplicated in humans," said Dr. Franck Polleux, an expert in brain development at The Scripps Research Institute. "These are some of our most recent genomic innovations." Intriguingly, many of these genes appear to play some role in the developing brain. In two independent studies, Dr. Polleux and Dr. Evan Eichler, a genome scientist at the University of Washington, focused their expertise and attention on one of the genes known as SRGAP2. This gene has, in fact, been duplicated at least twice during the course of human evolution, first about 3.5 million years ago and then again about 2.5 million years ago. The new work shows that the second and relatively recent duplication event produced only a partial copy of the gene. This copy acts at exactly the same time and place as the original, allowing it to interact with and block the ancestral gene's function. "This innovation couldn't have happened without that incomplete duplication," Dr. Eichler said.

Beehive Extract Shows Potential As Prostate Cancer Treatment

An over-the-counter natural remedy derived from honeybee hives arrests the growth of prostate cancer cells and tumors in mice, according to a new paper from researchers at the University of Chicago Medicine. Caffeic acid phenethyl ester, or CAPE, is a compound isolated from honeybee hive propolis, the resin used by bees to patch up holes in hives. Propolis has been used for centuries as a natural remedy for conditions ranging from sore throats and allergies to burns and cancer. But the compound has not gained acceptance in the clinic due to scientific questions about its effect on cells. In a paper published in the May 1, 2012 issue of Cancer Prevention Research, researchers combined traditional cancer research methods with cutting-edge proteomics to find that CAPE arrests early-stage prostate cancer by shutting down the tumor cells' system for detecting sources of nutrition. "If you feed CAPE to mice daily, their tumors will stop growing. After several weeks, if you stop the treatment, the tumors will begin to grow again at their original pace," said Richard B. Jones, Ph.D., assistant professor in the Ben May Department for Cancer Research and Institute for Genomics and Systems Biology and senior author of the study. "So it doesn't kill the cancer, but it basically will indefinitely stop prostate cancer proliferation." Natural remedies isolated from plant and animal products are often marketed as cure-alls for a variety of maladies, usually based on vague antioxidant and anti-inflammatory claims. While substances such as ginseng or green tea have been occasionally tested in laboratories for their medicinal properties, scientific evidence is commonly lacking on the full biological effects of these over-the-counter compounds. "It's only recently that people have examined the mechanism by which some of these herbal remedies work," Dr. Jones said.

New Model Suggests Low Oxygen Levels, Not Mutations, Drive Cancer Growth

Low oxygen levels in cells may be a primary cause of uncontrollable tumor growth in some cancers, according to a new University of Georgia study. The authors' findings run counter to widely accepted beliefs that genetic mutations are responsible for cancer growth. If hypoxia, or low oxygen levels in cells, is proven to be a key driver of certain types of cancer, treatment plans for curing the malignant growth could change in significant ways, said Dr. Ying Xu, Regents-Georgia Research Alliance Eminent Scholar and professor of bioinformatics and computational biology in the Franklin College of Arts and Sciences. The research team analyzed samples of messenger RNA data—also called transcriptomic data—from seven different cancer types in a publicly available database. They found that long-term lack of oxygen in cells may be a key driver of cancer growth. The study was published on April 20, 2012 in the early online edition of the Journal of Molecular Cell Biology. Previous studies have linked low oxygen levels in cells as a contributing factor in cancer development, but not as the driving force for cancer growth. High incidence rates of cancer around the world cannot be explained by chance genetic mutations alone, Dr. Xu said. He added that bioinformatics, which melds biology and computational science, has allowed researchers to see cancer in a new light. Gene-level mutations may give cancer cells a competitive edge over healthy cells, but the proposed new cancer growth model does not require the presence of common malfunctions such as a sudden proliferation of oncogenes, precursors to cancer cells. "Cancer drugs try to get to the root—at the molecular level—of a particular mutation, but the cancer often bypasses it," Dr. Xu said.

Scientists Analyze “Junk DNA” to Find Colorectal Cancer Clues

Two researchers at the Geisel School of Medicine at Dartmouth have helped to identify switches that can turn on or off genes associated with colorectal cancer. The finding offers clues about the development of colorectal cancer and could—potentially—provide targets for new therapies. Dr. Jason Moore, Third Century Professor of genetics and the director of the Institute for Quantitative Biomedical Sciences, and Richard Cowper-Sal.lari, a graduate student in Dr. Moore's lab, were part of a team that included researchers from Case Western Reserve University and the Cleveland Clinic. The team published its findings in Science Express, the online prepublication site for the journal Science, on April 12, 2012. Many studies of cancer and other diseases have looked for genetic variations that lead to disease. But for this study, Dr. Moore, Cowper-Sal.lari, and their colleagues examined sections of DNA that do not code for proteins—sections that have sometimes been referred to as "junk DNA." Long overlooked, junk DNA has gained more attention of late as it has become clear that it can regulate the expression of genes. "We're now starting to assign function to what historically has been known as the junk DNA—stuff in between genes that we weren't really sure what it did, if it did anything at all," Dr. Moore says. Proteins that bind to noncoding sections far away from a gene, Dr. Moore explains, can help turn that gene on or off. The researchers looked at specific sections of noncoding DNA in nine colorectal cancer samples and three samples of healthy colon tissue. They found patterns in the sections of noncoding DNA that differed depending on whether the tissue was cancerous or healthy. They refer to these sections as variant enhancer loci (VELs).

Bacteria Discovery Could Lead to Alternatives to Antibiotics

Scientists have discovered an Achilles heel within our cells that some bacteria are able to exploit to cause and spread infection. The researchers say their findings could lead to the development of new anti-infective drugs as alternatives to antibiotics whose overuse has led to resistance. University of Manchester researchers studied Listeria – a potentially deadly group of bacteria that can cause listeriosis in humans when digested – and found they are able to spread infection by hitching a ride on a naturally occurring protein called calpain. "Bacteria produce a number of chemicals that allow them to invade a host and to establish an infection," said lead researcher Dr. David Brough, who is based in Manchester's Faculty of Life Sciences. "The chemicals produced depend upon many factors, such as the species of bacteria, the type of host, and also whether the infection grows inside or outside a cell. We have investigated the growth of Listeria, a pathogenic bacterium that grows inside cells. An essential step for its growth, and thus the infection, is the bacteria's ability to move from within one compartment in a cell to another. We discovered that in order for this particular type of bacteria to move and to grow some of the host cells biology is exploited, a protein called calpain. Without calpain the bacteria cannot move within the cell and so do not grow. This discovery highlights the possibility of using drugs against these host proteins to block infections, potentially reducing the need to use antibiotics." The study, funded by the Wellcome Trust, was published April 26, 2012 in PLoS ONE. [Press release] [PLoS ONE article]

Cohesin SA1 Has Functions Relevant to Cancer and Cornelia de Lange Syndrome

Cohesin is a ring-shaped protein complex involved in the spatial organization of the genome and in mitotic chromosome structure. Vertebrate somatic cells have two versions of cohesin that contain either SA1 or SA2, but their functional specificity has been largely ignored. Researchers of the Spanish National Cancer Research Centre (CNIO) under the direction of Dr. Ana Losada have identified new functions of cohesin SA1 that are relevant for two human diseases, cancer and Cornelia de Lange Syndrome (CdLS). These results are published in two papers that appeared back-to-back in the March 13, 2012 issue of the EMBO Journal. The first study shows that SA1 is required for efficient duplication of chromosome ends, the telomeres. In its absence, aberrant telomere structures hinder chromosome segregation during cell division and aneuploid cells (i.e., those with an incorrect number of chromosomes) are generated. This aneuploidy likely contributes to accelerating the onset of tumorigenesis in SA1-deficient mice. The appearance of certain types of pancreatic tumours, extremely rare in mice, is particularly striking. This mouse model may turn out to be a very useful tool for the study of pancreatic cancer. The second study reports for the first time a precise map of the distribution of cohesin SA1 and cohesin SA2 along the mouse genome. Moreover, it uncovers an essential role of cohesin SA1 in the regulation of gene expression during embryonic development. Lack of cohesin SA1 alters the transcription of genes involved in biological processes related to CdLS. This developmental disorder affects 1:30,000 newborns and is characterized by growth and mental retardation and multiple organ abnormalities. The study offers new clues to understanding the origin of the pathologies observed in CdLS patients.

Brain Circuitry Associated with Addictive, Depressive Behaviors Identified

Scientists at the Gladstone Institutes in San Francisco, California, have determined how specific circuitry in the brain controls not only body movement, but also motivation and learning, providing new insight into neurodegenerative disorders such as Parkinson's disease—and psychiatric disorders such as addiction and depression. [Referential website: California rehab centers http://www.allaboutcounseling.com/dir/drug-rehab-programs/california/ Previously, researchers in the laboratory of Gladstone Investigator Anatol Kreitzer, Ph.D., discovered how an imbalance in the activity of a specific category of brain cells is linked to Parkinson's. Now, in a paper published online on April 29, 2012 in Nature Neuroscience, Dr. Kreitzer and his team used animal models to demonstrate that this imbalance may also contribute to psychiatric disorders. These findings also help explain the wide range of Parkinson's symptoms—and mark an important step in finding new treatments for those who suffer from addiction or depression. “The physical symptoms that affect people with Parkinson's—including tremors and rigidity of movement—are caused by an imbalance between two types of medium spiny neurons in the brain,” said Dr. Kreitzer, whose lab studies how Parkinson's disease affects brain functions. “In this paper, we showed that psychiatric disorders—specifically addiction and depression—might be caused by this same neural imbalance.” Normally, two types of medium spiny neurons, or MSNs, coordinate body movements. One type, called direct pathway MSNs (dMSNs), acts like a gas pedal. The other type, known as indirect pathway MSNs (iMSNs), acts as a brake.

Black Pepper's Secrets As a Fat Fighter

A new study provides a long-sought explanation for the beneficial fat-fighting effects of black pepper. The research, published online on April 2, 2012 in the ACS Journal of Agricultural and Food Chemistry, pinpoints piperine — the pungent-tasting substance that gives black pepper its characteristic taste, concluding that piperine also can block the formation of new fat cells. Dr. Soo-Jong Um, Dr. Ji-Cheon Jeong, and colleagues describe previous studies indicating that piperine reduces fat levels in the bloodstream and has other beneficial health effects. Black pepper and the black pepper plant, they note, have been used for centuries in traditional Eastern medicine to treat gastrointestinal distress, pain, inflammation, and other disorders. Despite that long medicinal history, scientists know little about how piperine works on the innermost molecular level. The scientists set out to get that information about piperine's anti-fat effects. Their laboratory studies and computer models found that piperine interferes with the activity of genes that control the formation of new fat cells. In doing so, piperine may also set off a metabolic chain reaction that helps keep fat in check in other ways. The group suggests that the finding may lead to wider use of piperine or black-pepper extracts in fighting obesity and related diseases. [Press release] [Journal of Agricultural and Food Chemistry abstract]

Huge Study Finds Brain Networks Connected to Drug Abuse by Teenagers

Why do some teenagers start smoking or experimenting with drugs—while others don't? In the largest imaging study of the human brain ever conducted—involving 1,896 14-year-olds—scientists have discovered a number of previously unknown networks that go a long way toward an answer. Dr. Robert Whelan and Dr. Hugh Garavan of the University of Vermont, along with a large group of international colleagues, report that differences in these networks provide strong evidence that some teenagers are at higher risk for drug and alcohol experimentation—simply because their brains work differently, making them more impulsive. Their findings were published online on April 29, 2012 in Nature Neuroscience. This discovery helps answer a long-standing chicken-or-egg question about whether certain brain patterns come before drug use—or are caused by it. "The differences in these networks seem to precede drug use," says Dr. Garavan, Dr. Whelan's colleague in the University of Vermont’s psychiatry department, who also served as the principal investigator of the Irish component of a large European research project, called IMAGEN, that gathered the data about the teens in the new study. In a key finding, diminished activity in a network involving the "orbitofrontal cortex" is associated with experimentation with alcohol, cigarettes, and illegal drugs in early adolescence. (Referential web site: 60-day treatment http://www.rehabs.com/about/60-days-two-months-program/) "These networks are not working as well for some kids as for others," says Dr. Whelan, making them more impulsive. Faced with a choice about smoking or drinking, the 14-year-old with a less functional impulse-regulating network will be more likely to say, "yeah, gimme, gimme, gimme!" says Dr.

Syndicate content