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Sweet Tooth May Be Achilles Heel of Salmonella

Scientists have shown that the Salmonella food poisoning bacterium requires glucose as a nutrient during infection, and that when it is unable to use this nutrient, infection is prevented. "This is the first time that anyone has identified the nutrients that sustain Salmonella while it is infecting a host's body," says Dr Arthur Thompson, the senior author of the report. Salmonella food poisoning causes infection in approximately 20 million people worldwide each year and is responsible for about 200,000 human deaths. It also infects farm animals and attaches to salad vegetables. During infection, Salmonella bacteria are engulfed by immune cells designed to kill them. Instead, however, the bacteria multiply. The scientists constructed Salmonella mutants unable to transport glucose into the immune cells they occupy and unable to use glucose as food. These mutant strains lost their ability to replicate within the immune cells, rendering them harmless. The mutant strains still stimulate the immune system, and the scientists have filed patents on these mutant strains which could be used to develop vaccines to protect people and animals against poisoning by fully virulent Salmonella. This work was published in the April 20 issue of Infection and Immunity. [Press release]

Atrial Fibrillation A Predictor for Alzheimer’s Disease

Patients under the age of 70 with atrial fibrillation are 130 percent more likely to develop Alzheimer’s disease than those without the heart disease, according to a recent study. "Previous studies have shown that patients with atrial fibrillation are at higher risk for some types of dementia, including vascular dementia. But to our knowledge, this is the first large-population study to clearly show that having atrial fibrillation puts patients at greater risk for developing Alzheimer's disease," said Dr. T. Jared Bunch, the study’s lead researcher. Atrial fibrillation is the most common heart rhythm problem, affecting about 2.2 million Americans. It occurs when the heart beats chaotically, leading blood to pool and possibly clot. If the clot leaves the heart, a stroke can result. "Now that we've established this link, our focus will be to see if early treatment of atrial fibrillation can prevent dementia or the development of Alzheimer's disease," said Dr. John Day, a co-author of the study. The work was presented on May 15 during the annual scientific sessions of the Heart Rhythm Society. [Press release]

Gateway to Brain in Bacterial Meningitis Is Discovered

Scientists have discovered a key common mechanism in the pathology of bacterial meningitis, a disease that can cause death within hours of the appearance of symptoms. The researchers have shown that the three bacteria most commonly associated with childhood bacterial meningitis—Streptococcus pneumoniae, Neisseria meningitides, and Haemophilus influenzae—all target the same receptor (the laminin receptor) in the special filtering system (the vascular endothelium) that helps form the blood-brain barrier. This interaction allows the bacteria to pass through the barrier and enter the brain. The researchers suggested that disruption or modulation of the interaction of bacterial adhesins with the barrier receptor might offer unexpectedly broad protection against bacterial meningitis and might provide a therapeutic target for the prevention and treatment of disease. This work was published on May 13 in the Journal of Clinical Investigation. [Press release] [Journal of Clinical Investigation article]

Coral Transcriptome Revealed

Using a new technique for cDNA preparation, combined with the latest sequencing methods, researchers have characterized the larval transcriptome of a reef-building coral (Acropora millepora). The research team identified approximately 11,000 genes on the basis of sequence similarity with known proteins, over 30,000 markers of genetic variation, and a number of novel candidate genes for stress-related processes. The characterization of the larval transcriptome for this widely studied coral will enable research into the biological processes underlying stress responses in corals and their evolutionary adaptation to global climate change. This work was published in BMC Genomics. [Press release] [BMC Genomics article]

Protective Gene Variant Identified for Lou Gehrig’s Disease

A gene variant that extends the survival time in amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, by as much as 50 percent has been identified by an international team of researchers. "This report is the first to describe genetic factors that determine rate of progression in ALS," said Dr. Robert Brown, one of the study leaders. The gene is KIFAP3 and researchers know that it is involved in a number of cellular processes, including the transport of essential molecules throughout the nerve cell. "The favorable gene variant decreases levels of a motor protein complex in nerves," said Dr. John Landers, also a leader of the study. "This complex transports substances through different parts of nerve cells. If we can understand the biological basis for the beneficial effect in ALS, it will potentially provide a target for the development of new ALS treatments.” Because survival with ALS is normally only three to five years, patients with the KIFAP3 gene variant experience a substantial improvement. In fact, the researchers suggested that impact of this genetic variant is comparable to the effect of the only drug (Riluzole) now approved for use in ALS in the United States. More importantly, this genetic variant may potentially point the way to future drug development efforts. This work is reported in PNAS. [Press release]

Novel Potassium Channel Implicated in Schizophrenia

Expression of a previously unknown, primate-specific, and brain-specific isoform (3.1) of a key potassium channel protein (KCNH2) that modulates neuronal firing was found to be 2.5-fold higher than normal in the hippocampus (brain memory hub) of people with schizophrenia, especially in those with schizophrenia risk-associated variations in the KCNH2 gene, according to a recent report. KCNH2-3.1 isoform levels were also found to be higher than normal in healthy individuals who carried the risk-associated KCNH2 gene variations, and these individuals were shown to exhibit some schizophrenia-like effects in brain circuitry and mental processing, even though they do not show psychotic behavior. "Our study goes further [than gene association studies], spanning discovery of a new gene variant, confirmation of its association with the illness, and multi-level probes into how it works--in human post-mortem brain tissue, the living human brain, and neurons," said Dr. Daniel Weinberger, director of the National Institute of Mental Health's Genes Cognition and Psychosis Program. An extensive series of experiments suggest that selectively inhibiting the KCNH2-3.1 isoform could help correct disorganized brain activity in schizophrenia, without risk of the cardiac side effects associated with some existing antipsychotic medications. This work was reported in the May issue of Nature Medicine. [NIH release] [Nature Medicine abstract]

Most Common Protein in Urine Associated with Altered Kidney Disease Risk

An international research team has shown that a common genetic variant of the gene (UMOD) for the most common protein in normal human urine is associated with a lowered risk of chronic kidney disease. This protein is the Tamm-Horsfall protein and, although it has been known for almost 60 years, its functions are not well understood and its relationship to chronic kidney disease risk was not known previously. "Previous research showed that rare mutations in the UMOD gene cause hereditary forms of severe kidney disease. Our research indicates that a common genetic variant with a frequency of 18 percent in populations of European ancestry is associated with about 25 percent lower risk of chronic kidney disease," said the lead author of the study, Dr. Anna Köttgen, a researcher in the Johns Hopkins Bloomberg School of Public Health. In their genome-wide association studies, the researchers also identified two additional genes (SHROOM3 and STC1) that were associated with altered risk for reduced kidney function and chronic kidney disease. The study was published in the May 10 online edition of Nature Genetics. [Johns Hopkins release] [Nature Genetics abstract]

Blocking Single Target May Prevent Lethal Aneurysms

Researchers have shown that removal of a single key protein can prevent early damage in blood vessels from triggering a later-stage, frequently lethal complication of atherosclerosis. By eliminating the gene for a signaling protein called cyclophilin A (CypA) from a strain of mice, the team was able to provide complete protection against abdominal aortic aneurysm (AAA). AAA leads to 15,000 deaths a year, mostly in aging men, when aneurysms rupture to spill blood into the abdomen, a fatal event in 90 percent of cases. When study mice were engineered to remove their CypA gene, none from that group developed AAA in the face of the hypertension and high cholesterol known to accelerate it. In contrast, 78 percent of mice with "normal" amounts of CypA developed AAA under the same conditions, 35 percent with a fatal rupture. The researchers also found high CypA levels in the rupture-prone vessels of humans with AAA, and that major drugs like statins reduce CypA levels, which may partly explain their benefit. “It is extremely unusual for the removal of one protein to provide absolute protection, but it makes perfect sense because cyclophilin A promotes three of the most destructive forces in blood vessels: oxidative stress, inflammation, and matrix degradation," said Dr. Bradford C. Berk, of the Aab Cardiovascular Research Institute at the University of Rochester Medical Center, and senior author of the study. "We are working to design anti-CypA drugs that will diminish the disease processes underlying AAA, atherosclerosis and hypertension." This study was published in the May 10 online edition of Nature Medicine. [Press release] [Nature Medicine abstract]

Alcohol Flushing Response May Indicate Cancer Risk

The alcohol flushing response, seen in approximately 36% of East Asians (Japanese, Chinese, and Koreans), may be an indictor of a much increased risk of esophageal cancer from alcohol consumption in these individuals, according to a recent article in PLoS Medicine. This is particularly unfortunate as esophageal cancer is one of the deadliest cancers worldwide, with five-year survival rates of 15.6% in the United States, 12.3% in Europe, and 31.6% in Japan, the authors noted. The flushing response is predominantly due to an inherited deficiency in the enzyme alcohol dehydrogenase 2 (ALDH2), and there is accumulating evidence that individuals deficient in ALDH2 are at a much higher risk of esophageal cancer than are those with normal levels of ALDH2. The authors advised that doctors should counsel their ALDH2-deficient patients to limit alcohol consumption and thereby reduce the risk of developing esophageal cancer. Clinicians can determine ALDH2 deficiency simply by asking about previous episodes of alcohol-induced flushing. As a result, ALDH2-deficient patients can then be counseled to reduce alcohol consumption, and high-risk patients can be assessed for endoscopic cancer screening. In view of the approximately 540 million ALDH2-deficient individuals in the world, many of whom now live in Western societies, even a small percent reduction in esophageal cancers due to a reduction in alcohol drinking would translate into a substantial number of lives saved, the authors asserted. [PLoS Medicine article]

Gecko’s Night Vision May Be Basis for Better Cameras, Contact Lenses

The key to the exceptional night vision of the nocturnal helmeted gecko is a series of distinct concentric zones of different refractive powers, according to a study published in the online Journal of Vision. Nocturnal geckos are among the very few living creatures able to see colors at night. "We were interested in the geckos because they, and other lizards, differ from most other vertebrates in having only cones in their retina," said project leader Dr. Lina Roth of Lund University in Sweden. "With the knowledge from the gecko eyes, we might be able to develop more effective cameras and maybe even useful multifocal contact lenses." The nocturnal gecko’s multifocal optical system is comprised of large cones, which the researchers calculated to be more than 350 times more sensitive than human cone vision at the human color vision threshold. The nocturnal gecko’s optical system gives them an advantage because light of different ranges of wavelengths can be focused simultaneously on the retina. Another possible advantage is that their eyes allow them to focus on objects at different distances. Therefore, the multifocal eye would generate a sharp image for at least two different depths. Geckos that are active during the day do not possess the distinct concentric zones and are considered monofocal, the researchers said. [Press release] [Journal of Vision abstract]

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