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February 23rd, 2010

Pesky Aphid Thrives Despite Weak Immune System

Pea aphids, expert survivors of the insect world, appear to lack major biological defenses, according to the first genetic analysis of their immune system. "It's surprising," said Emory University biologist Dr. Nicole Gerardo, who led the study."Aphids have some components of an immune system, but they are missing the genes that we thought were critical to insect immunity." One hypothesis is that aphids may compensate for their lack of immune defenses by focusing on reproduction. From birth, a parthenogenic female aphid contains embryos that also contain embryos. This is called "telescoping of generations." "She is born carrying her granddaughters," Dr. Gerardo said. "In a lab, a female aphid can produce up to 20 copies of herself per day. About 10 days later, those babies will start producing their own offspring." Over 50 million years, aphids have evolved complex relationships with beneficial bacteria that supply them with nutrients or protect them from predators and pathogens. It's possible that the weak immune response in aphids developed as a way to keep from killing off these beneficial microbes, Dr. Gerardo noted. "A key question is whether these microbes could have changed the aphid genome, or changed how the aphid uses its genes." Further study of how the aphid immune system interacts with microbes could yield better methods for controlling them in agriculture. Pea aphids are major agricultural pests and also important biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and genetic plasticity. These resilient insects thrive despite a host of enemies, including parasitic wasps, lady bugs, fungal pathogens, and frustrated farmers and gardeners the world over.

Gene Identified for Atrial Fibrillation

By analyzing data from multiple genome-wide association studies (GWAS), scientists have identified common variants in the KCNN3 gene that are associated with a form of irregular heartbeat known as “lone atrial fibrillation” (lone AF). This is a type of AF seen in younger individuals with no other signs of heart disease. The finding may open the way to the development of innovative treatments not only for lone AF in specific, but for AF in general. The KCNN3 gene, located on chromosome 1, codes for a potassium channel protein that carries signals across cell membranes in organs including the brain and the heart. While the exact cardiac role of the protein is unknown, it may play a part in resetting the electrical activity of the atria, a process that goes awry in AF. Animal studies have suggested that a related protein, KCNN2, may help control signals originating in the atria and in the pulmonary veins, areas known to be involved in lone AF. The researchers replicated the association of KCNN3 variants with lone AF in data from two additional GWAS involving another 1,000 lone AF patients and 3,500 controls. "The genetic location we have identified could be a new drug target for the treatment of AF," said cardiologist Dr. Patrick Ellinor of the Massachusetts General Hospital Cardiovascular Research Center and Cardiac Arrhythmia Service and an assistant professor of medicine at Harvard Medical School, the first author of the report. "We also will be investigating whether these variants can help us predict patients' clinical outcomes or their response to the various treatments for AF."

Cancer Stem Cells Created from Normal Prostate Stem Cells

Researchers reported that they have been able to break apart normal human prostate tissue, extract the stem cells in that tissue, and alter those cells genetically so that they spur cancer. This effort should provide a model for studying so-called “cancer stem cells,” i.e., cancer cells that develop from stem cells in the body and that are believed to be the origin of many cancers. This model may prove useful in understanding how cancers grow--and provide a new opportunity to test and identify novel cancer drugs. Many tissues contain pools of normal stem cells that replenish the tissue when it's damaged or when changes take place. For instance, stem cells in the skin produce new cells to replace those irreparably damaged by the sun, and stem cells in the breast create milk-producing cells when a woman is pregnant. The hallmark of these stem cells is that they self-renew. This means that in addition to making cells with a specific function, they also make many new stem cells. Mounting evidence suggests that these self-renewing cells are also tied to cancer. They tend to collect mutations, said Dr. Owen Witte, a Howard Hughes Medical Institute (HHMI) Investigator at UCLA, who was scheduled to present his group’s data on February 20, 2010, at the annual meeting of the American Association for the Advancement of Science (AAAS) in San Diego; and not much separates tumor cells, with their capacity for unchecked growth, from healthy, tissue-forming stem cells. "These cells have a huge capacity for self-renewal, and when the pathways that control self-renewal are augmented or changed, they can form tumors," Dr. Witte said.

Possible Explanation for Late Onset of Huntington Disease

Researchers have identified a molecular pathway that may play a role in delaying the onset of symptoms in Huntington disease (HD). The findings could possibly lead to the development of effective treatments for HD. The new data indicate that group I mGluR-mediated signaling pathways are altered in HD and that these cell signaling adaptations could be important for the survival of striatal neurons, neurons that are lost in the course of HD. The researchers used a genetically-modified mouse model of HD to look at the effects of the causative mutated huntingtin protein (mutant Htt) on the brain. "We found there was some kind of compensation going on early in the life of these mice that was helping to protect them from the development of the disease," said Dr. Stephen Ferguson, senior author of the paper and director of the Molecular Brain Research Group at the Robarts Research Institute at The University of Western Ontario in Canada, and also a professor in the Department of Physiology & Pharmacology at Western’s Schulich School of Medicine and Dentistry. "As they age, they lose this compensation and the associated protective effects, which could explain the late onset of the disease.” Dr. Ferguson added that the metabotropic glutamate receptors (mGluRs), which are responsible for communication between brain cells, play an important role in these protective effects. By interacting with the mutant Htt protein, mGluRs change the way the brain signals in the early stages of HD in an attempt to offset the disease, and save the brain from cell death. As a result, mGluRs could offer a drug target for HD treatment. HD is a dominant hereditary condition that leads to severe physical and mental deterioration, psychiatric problems, and eventually, death. Currently, there are no treatments to slow down or stop the disease.

February 22nd

It’s Not Magic—Merlin Works in Nucleus

According to previous models, the tumor suppressor protein Merlin, encoded by the neurofibromatosis type 2 (NF2) gene, inhibits mitotic signaling at or near the cell membrane. However, in the cover story of the February 19, 2010 issue of Cell, researchers present evidence supporting the proposal that Merlin actually suppresses tumorigenesis by translocating to the nucleus where it binds to the E3 ubiquitin ligase CRL4DCAF1 and inhibits its ability to ubiquitylate target proteins. The researchers stated that multiple converging lines of evidence now indicate that Merlin's inhibition of CRL4DCAF1 activity is required to induce growth arrest and suppress tumorigenesis. Notably, the scientists showed that the tumor-derived mutations in NF2 that they examined invariably disrupted Merlin’s ability to interact with or inhibit CRL4DCAF1. This represents a new mechanism for the production of certain tumors in the brain. These tumors occur in a range of cell types, including Schwann cells. Schwann cells produce the sheaths that surround and insulate neurons. The tumors most often occur spontaneously, but can also occur in significant numbers as part of the inherited disease NF2. In NF2, the sheer number of tumors can overwhelm a patient, often leading to severe disability and eventually death. Patients can suffer from 20 to 30 tumors at any one time, and the condition typically affects older children and young adults. No therapy, other than invasive (radio) surgery which is aimed at a single tumor and which may not eradicate the full extent of the tumors, exists. NF2 is estimated to affect one in every 2,500 people worldwide. It can affect any family, regardless of past history, through gene mutation, and currently there is no cure. Dr.

Calcineurin Critical to Healthy Heart Function

Researchers have reported the first-ever data to show that the enzyme calcineurin is critical to controlling normal development and function of heart cells, and that loss of the protein leads to heart problems and death in genetically modified mice. The near total absence of calcineurin in these experimental mice led to heart arrhythmia, failure, and death, according to the research team. This report was selected as the paper of the week for the February 26, 2010 issue of the Journal of Biological Chemistry and was published online on February 19. Calcineurin is a protein phosphatase that is uniquely regulated by sustained increases in intracellular calcium ions following signal transduction events. Calcineurin is known to control cellular proliferation, differentiation, apoptosis, and inducible gene expression following stress and neuroendocrine stimulation. In the adult heart, calcineurin has earlier been shown to regulate hypertrophic growth of cardiomyocytes in response to pathologic insults that are associated with altered Ca2+ handling. It was previously known that calcineurin is important to heart function, but the extent of its role had not been defined prior to the current study. Although the current research involved mice, it nevertheless offers important insights for future studies that could lead to new approaches in diagnosis and treatment of heart patients, said Dr. Marjorie Maillet, the study's lead author and a researcher in the laboratory of senior author Dr. Jeffery Molkentin, at the Cincinnati Children’s Hospital Medical Center. In their work, the researches determined that calcineurin signaling is directly linked to the proper control of cardiac contractility, rhythm, and the expression of Ca2+-handling genes in the heart.

February 21st

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Parasitic Wasps May Aid Pest Control Efforts

Parasitoid wasps kill pest insects, but their existence is largely unknown to the public. Now, scientists have sequenced the genomes of three parasitoid wasp species, revealing many features that could be useful in pest control and medicine, and in the enhancement of our understanding of genetics and evolution. "Parasitic wasps attack and kill pest insects, but many of them are smaller than the head of a pin, so people don't even notice them or know of their important role in keeping pest numbers down," said Dr. John Werren, from the University of Rochester, a co-leader of the study along with Dr. Stephen Richards of the Baylor College of Medicine. "There are over 600,000 species of these amazing critters, and we owe them a lot. If it weren't for parasitoids and other natural enemies, we would be knee-deep in pest insects.” Parasitoid wasp females are like "smart bombs" that seek out and kill only specific kinds of insects, said Dr. Werren. "Therefore, if we can harness their full potential, they would be vastly preferable to chemical pesticides, which broadly kill or poison many organisms in the environment, including us." Parasitoid wasps are four times smaller than the common fruit fly. The females seek out specific insect, tick, or mite hosts, inject venom and lay their eggs, with the wasp young emerging to devour the host insect; traits that make the wasps valuable assets as agents for biological control. Although their size is insignificant, the importance of parasitoid wasps in the control of populations of agricultural pests is crucial. Thanks to these insects billions of dollars’ worth of crops is saved each year.

Carnivorous Plants May Yield Anti-Fungal Compounds

The sticky liquid-filled pitchers of carnivorous plants contain anti-fungal compounds that may prove useful for combating fungal diseases in humans, according to research being carried out at Tel Aviv University in Israel. "To avoid sharing precious food resources with other micro-organisms such as fungi, the carnivorous plant has developed a host of agents that act as natural anti-fungal agents," said Dr. Aviah Zilberstein, an author of the report. "In the natural habitat of the tropics, competition for food is fierce, and the hot, moist environment is perfect for fungi, which would also love to eat the plant's insect meal.” In a study conducted together with Dr. Haviva Eilenberg, Dr.Esther Segal, and Dr. Shmuel Carmeli; Dr. Zilberstein and her colleagues found that unusual secondary metabolites from the pitchers of the carnivorous Nepenthes khasiana plant (originally found in India) were effective against pathogens responsible for widespread fungal infections of people in hospitals. "The pitcher of the carnivorous plant produces these compounds in a gland," said Dr. Zilberstein. Until now, no one has published or discussed the anti-fungal metabolites found in the trap liquid of this plant, she said. Currently there is a need for additional, broadly effective anti-fungal drugs. Even mildly severe forms of athlete's foot or other skin fungal infections lack effective treatments. The problem becomes more severe at hospitals, where thousands of Americans die each year from secondary fungal infections they acquire during their stays as patients.

February 19th

Gene Variations Associated with Endurance Running Ability

Scientists have shown that elite endurance runners are more likely to have particular variations (SNPs) of the NRF2 (nuclear respiratory factor 2) gene than are elite sprinters. Non-elite endurance runners were also more likely to have these NRF2 variations compared to sprinters, although the difference was not as pronounced. “These findings suggest that harboring this specific genotype might increase the probability of being an endurance athlete,” said lead author Dr. Nir Eynon of the Wingate Institute in Israel. The authors said that their data supports the notion that these specific gene variants might belong to a growing group of SNPs that are associated with endurance performance. The researchers investigated the NRF2 gene because previous studies had shown that it might play a role in endurance performance as it helps produce new mitochondria, a key cellular structure that produces energy. Earlier studies had also shown that the NRF2 gene can reduce the harmful effects of oxidation and inflammation, which increase during exercise. The researchers noted that their study shows an association between the gene variations and endurance, but does not establish a cause-effect relationship. Future studies are needed to unravel exactly what role the NRF2 gene plays in athletic performance. The current study is part of a larger body of research that is exploring the human genome and which aims to understand the genetic underpinnings of athletic performance. The results were published online in Physiological Genomics on December 22, 2009. The Sports Illustrated photo shows American marathon runner Bill Rodgers in 1979. [Press release] [Physiological Genomics abstract]