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Archive - Nov 2013

November 20th

Ancient Siberian Genome Reveals Genetic Origins of Native Americans

The genome sequence of a 24,000-year-old Siberian individual has provided a key piece of the puzzle in the quest for Native American origins. The ancient Siberian demonstrates genomic signatures that are basal to present-day western Eurasians and close to modern Native Americans. The breakthrough was reported online on November 20, 2013 in Nature by an international team of scientists, led by researchers from the University of Copenhagen. The search for Native American ancestors has been focused in northeastern Eurasia. In late 2009, researchers sampled, at the Hermitage Museum, St. Petersburg, the remains of a juvenile individual (MA-1) from the Upper Palaeolithic site of Mal’ta in south-central Siberia. The MA-1 individual dated to approximately 24,000 years ago. Now, the team reports genomic results from the MA-1 individual which unravel the origins of the First Americans – ancestors of modern-day Native Americans. “Representing the oldest anatomically modern human genome reported thus far, the MA-1 individual has provided us with a unique window into the genetic landscape of Siberia some 24,000 years ago,” says Dr. Maanasa Raghavan from the Centre for GeoGenetics and one of the lead authors of the study. “Interestingly, the MA-1 individual shows little to no genetic affinity to modern populations from the region from where he originated - south Siberia.” Instead, both the mitochondrial and nuclear genomes of MA-1 indicate that he was related to modern-day western Eurasians. This result paints a picture of Eurasia 24,000 years ago which is quite different from the present-day context. The genome of MA-1 indicates that prehistoric populations related to modern western Eurasians occupied a wider geographical range into northeast Eurasia than they do today.

NCI Awards Labcyte $1 Million for Development of High-Throughput Cancer Biomarker Detection Process

In a November 20, 2013 press release, Labcyte Inc., the acoustic dispensing company, announced that it has been awarded $1 million to create an innovative process to detect cancer-related proteins in samples, with initial work in breast cancer detection. The unsurpassed precision and accuracy of Labcyte acoustic liquid handling enables biomarker detection by measuring multiple proteins with a MALDI mass spectrometer. Recent work with the Canary Center at Stanford, also supported by the National Cancer Institute, showed the ability to achieve the sensitivity required for quantifying very small amounts of proteins associated with ovarian cancer. Measuring the amount of multiple proteins, and at lower cost, is an essential step in developing new diagnostic tools for disease treatment and monitoring. This cutting-edge process encompasses stable standards and capture of biomarkers with antibodies and expects to achieve greater throughput than traditional liquid chromatography-mass spectrometric approaches. The utility of this technique will be tested by simultaneously analyzing 16 different biomarkers, run in quadruplicate, to simulate the analysis of 64 unique biomarkers. The process has the potential to expand to a greater number of biomarkers as well. It may enable significant advances in diagnostics and discovery. "I am particularly enthusiastic about participating with Labcyte on the further development of their protein multiplexed biomarker detection platform,” said Dr. Mark Stolowitz, Director of the Proteomics Core Facility at the Canary Center at Stanford for Cancer Early Detection. “This novel immunoaffinity mass spectrometry-based approach exploits MALDI-TOF-MS for detection of proteotypic peptides.

November 19th

mTOR: A Key Brain Signaling Mechanism for Rapidly Acting Antidepressants

Two years ago, mammalian target of rapamycin or mTOR, a signaling protein, was identified as a key mediator of the antidepressant effects of ketamine, the first rapidly acting antidepressant medication to be identified. Later, a group at the National Institutes of Mental Health Intramural Program reported that scopolamine (image), a muscarinic acetylcholine receptor antagonist, also produced rapidly appearing antidepressant effects, similar to the actions of ketamine. Together these findings represent one of the most significant advances in the field of depression in recent years. Now, new results reported in the November 15, 2013 issue of Biological Psychiatry by researchers at the Yale University School of Medicine demonstrate that scopolamine causes rapid activation of mTOR signaling and increased number of synaptic connections in the prefrontal cortex. The prefrontal cortex is an important brain region, involved in executive and cognitive functioning, decision-making, planning, and the expression of personality. It is also implicated in the pathophysiology and treatment of depression. "These effects are similar to the actions of ketamine, showing that two drugs with completely different receptor blocking profiles have common downstream actions linked to rapid antidepressant responses," said Dr. Ronald Duman, senior author on the project. "Moreover, the increase in synaptic connections reverses the deficit caused by stress and depression and thereby reinstates the normal control of mood and emotion." "It would be very important to know if all of the new generation of rapidly acting antidepressant medications acted through a final common signaling pathway within neurons.

November 18th

New Study Suggests “Anti-Ketamine” Might Also Treat Depression

Thirteen years ago, an article in Biological Psychiatry first reported that the anesthetic medication, ketamine, showed evidence of producing rapid antidepressant effects in depressed patients who had not responded to prior treatments. Ketamine works by blocking one of the targets for the neurotransmitter glutamate in the brain, the N-methyl-D-aspartate (NMDA) glutamate receptor. Now, a new study printed in the November 15, 2013 issue of Biological Psychiatry reports that enhancing, instead of blocking, that same target – the NMDA glutamate receptor – also causes antidepressant-like effects. Scientists theorize that NMDA receptor activity plays an important role in the pathophysiology of depression, and that normalizing its functioning can, potentially, restore mood to normal levels. Prior studies have already shown that the underlying biology is quite complex, indicating that both hyperfunction and hypofunction of the NMDA receptor is somehow involved. But, most studies have focused on antagonizing, or blocking, the receptor, and until now, studies investigating NMDA enhancement have been in the early phases. Sarcosine is one such compound that acts by enhancing NMDA function. Collaborators from China Medical University Hospital in Taiwan and the University of California in Los Angeles studied sarcosine in an animal model of depression and, separately, in a clinical trial of depressed patients. “We found that enhancing NMDA function can improve depression-like behaviors in rodent models and in human depression,” said Dr. Hsien-Yuan Lane, the corresponding author on the article. In the clinical portion of the study, they conducted a 6-week trial where 40 depressed patients were randomly assigned to receive sarcosine or citalopram (Celexa), an antidepressant already on the market that was used as a comparison drug.

November 15th

Wind Turbines Killed 600,000 Bats in U.S. Last Year by Conservative Estimates

More than 600,000 bats were killed by wind energy turbines in 2012, a serious blow to creatures who pollinate crops and help control flying insects, according to a new study from the University of Colorado (CU) Denver, described in a November 15, 2013 press release from the University. "The development and expansion of wind energy facilities is a key threat to bat populations in North America," said study author Mark Hayes, Ph.D., research associate in integrated biology at CU Denver. "Dead bats are being found underneath wind turbines across North America. The estimate of bat fatalities is probably conservative." The study, which analyzed data on the number of dead bats found at wind turbine sites, will be published next week in the journal BioScience. Dr. Hayes said areas near the Appalachian Mountains like Buffalo, Tennessee, and Mountaineer, West Virginia had the highest bat fatality rates. Little information is available on bat deaths at wind turbine facilities in the Rocky Mountain West or the Sierra Nevadas. The bats are killed when they fly into the towering turbines which spin at up to 179 mph with blades that can stretch 130 feet. Earlier estimates of bat deaths ranged from 33,000 to 880,000. Dr. Hayes said his estimates are likely conservative for two reasons. First, when a range of fatality estimates were reported at a wind facility, he chose the minimum estimate. Secondly, the number of deaths was estimated for just migratory periods, not the entire year, likely leaving out many other fatalities. "The number could be as high as 900,000 dead," he said. There are 45 known bat species in the contiguous U.S., many of which have important economic impacts. Not only do they control flying insects like mosquitoes, they also pollinate commercial crops, flowers, and various cacti.

New Mutations in P. vivax Malaria Parasite May Increase Human Susceptibility

Researchers at Case Western Reserve University and Cleveland Clinic Lerner Research Institute have discovered recent genetic mutations in a parasite that causes over 100 million cases of malaria annually—changes that may render tens of millions of Africans who had been considered resistant, susceptible to infection. Dr. Peter A. Zimmerman, professor of international health, biology, and genetics at the Case Western Reserve School of Medicine, and Dr. David Serre, a scientific staff member of the Genomic Medicine Institute at Lerner and assistant professor of genomics at Case Western Reserve, report their findings at the American Society of Tropical Medicine and Hygiene annual meeting today, Friday, November 15, 2013. They and fellow researchers describe the changes in the Plasmodium vivax genome in papers scheduled to be published in the journal PLoS Neglected Tropical Disease on November 21 and December 5, 2013. To learn the functions of the mutations, and whether the parasite is evolving around a natural defense, Drs. Zimmerman and Serre have received a $3.5 million grant from the National Institute of Allergy and Infectious Disease at the National Institutes of Health. They will begin their field study in early 2014. "We've found a duplication of a gene known to enable the parasite to infect red blood cells and two possible additional components to a more complex red cell invasion mechanism," Dr. Zimmerman said. Researchers have long thought that P. vivax infects a person one way: a protein on the parasite, called the Duffy binding protein, latches onto a Duffy receptor on the surface of the person's red blood cell and works itself through the membrane. People who lack the receptor are called Duffy-negative and are resistant to infection.

Ash Fungus Might Have Mechanism to Define Territory and Combat Viruses

The fungus which causes Chalara dieback of ash trees has the potential to defend itself against virus attacks, research by British scientists has shown. Plant pathologists Dr. Joan Webber, from Forest Research, the research agency of the Forestry Commission, and Professor Clive Brasier found that the defense mechanisms which the Chalara fraxinea (C. fraxinea) fungus uses to defend its territory could make it more resistant to virus-based control methods. Their research findings will be published in the December 2013 issue of Fungal Ecology and are available online now. Professor Brasier and Dr. Webber studied C. fraxinea’s genetic recognition system, called a vegetative compatibility (vc) system, in samples of the fungus from three different UK sites. Their results suggest that for most of these UK samples the fungal colonies are likely to be vegetatively incompatible with each other. This has implications for studying the biology of the fungus and for controlling its spread. Vegetative compatibility (vc) systems are a fungal equivalent of the tissue rejection systems in humans, enabling the fungus to distinguish between self and non-self. Fungal colonies of the same vc-type can fuse to form a single individual, but those of a different vc-type cannot. Vc systems are central to the ecology and survival of a fungus, enabling it to define its territory, to resist viral attack and to promote outbreeding. Initial results show that the vc system of C. fraxinea generates a reaction between incompatible colonies which makes their filaments (the mycelium) collapse, creating a zone between the two colonies where growth is inhibited.

November 14th

Blood Test Shows Promise for Early Detection of Breast Cancer

What could someday be the first blood test for the early detection of breast cancer was shown in preliminary studies to successfully identify the presence of breast cancer cells from serum biomarkers, say the Houston Methodist Research Institute scientists who are developing the technology. With a New York University Cancer Institute colleague, the researchers reported online on October 21, 2013 in Clinical Chemistry that the mixture of free-floating blood proteins created by the enzyme carboxypeptidase N (CPN) accurately predicted the presence of early-stage breast cancer tissue in mice and in a small population of human patients. "In this paper we link the catalytic activity of carboxypeptidase N to tumor progression in clinical samples from breast cancer patients and a breast cancer animal model," said biomedical engineer Tony Hu, Ph.D., who led the project. "Our results indicate that circulating peptides generated by CPN can serve as clear signatures of early disease onset and progression." The technology is not yet available to the public, and may not be for years. More extensive clinical tests are needed, and those tests are expected to begin in early 2014. There are currently no inexpensive laboratory tests for the early detection of breast cancer, providing the impetus for researchers around the world to invent them. "What we are trying to create is a non-invasive test that profiles what's going on at a tissue site without having to do a biopsy or costly imaging," Dr. Hu said. "We think this could be better for patients and -- if we are successful -- a lot cheaper than the technology that exists.

Penguin Is Model for New Propulsion System

Back in 1991, Nature published a picture from the IMAX movie Antarctica, along with the caption: "Emperor penguins may be waddling jokes on land, but underwater they can turn into regular rockets…accelerating from 0 to 7 m/s in less than a second." That's all it took to inspire Flavio Noca, who at the time was a graduate student in Caltech's Aeronautics Department, and now teaches aerodynamics at the University of Applied Sciences Western Switzerland (hepia) and the Swiss Federal Institute of Technology (EPFL), to explore leveraging penguins' "rocket" properties to create new propulsion technologies with high maneuverability and improved hydrodynamic efficiency. At the American Physical Society's (APS) Division of Fluid Dynamics meeting, November 24 – 26, in Pittsburgh, Pennsylvania, Noca will present a penguin-inspired propulsion system that uses a novel spherical joint mechanism developed and manufactured by Bassem Sudki, a research assistant within Noca's aerodynamics group, under the supervision of Professor Michel Lauria who leads hepia's Robotics Laboratory. Based on a penguin's shoulder-and-wing system, the mechanism features a spherical joint that enables three degrees of freedom and a fixed center of rotation. "Unlike an animal shoulder joint, however, this spherical joint enables unlimited rotational range about the main shaft axis like a propeller," Noca said. To achieve this, they needed to overcome the technical challenges of spherical joints, such as the lack of rigidity and the inability to generate high torques. To understand the challenge involved, just try lifting a 10-pound weight on your hand with your arm extended. The researchers maneuvered around these challenges by choosing a parallel robotic architecture for this type of mechanism, because it enables rigidity as well as high actuation frequencies and amplitudes.

Annexin A5 Is Possible New Treatment for Sepsis

Sepsis is the leading cause of in-hospital death and there is no specific treatment for it. Now, research led by Dr. Qingping Feng of Western University (London, Canada) suggests a protein called recombinant human annexin A5 may have therapeutic potential for the treatment of this disease. The paper has been published in advance, online in Critical Care Medicine. Sepsis is caused by an overwhelming immune response to an existing infection. It's estimated there are 18 million cases annually worldwide. The mortality rate is 30 to 40 per cent for severe sepsis and 40 to 80 per cent for septic shock. Dr. Feng, a professor in the Departments of Physiology and Pharmacology, and Medicine at Western's Schulich School of Medicine & Dentistry and a scientist at Lawson Health Research Institute is particularly interested in how sepsis causes cardiac dysfunction. Annexin A5 is a lipid-binding protein produced by cells. Using mice with induced sepsis, Dr. Feng, Dr. Xiangru Lu, and Paul Arnold, M.Sc., studied the effects of annexin A5 on cardiac function and animal survival. "We treated the septic animals and to our surprise we found a dramatic, significant effect in improving cardiac function during sepsis and improved survival rates in the mice," says Dr. Feng. "We also found it helped even if administered hours after the septic infection. This is important because the delayed treatment simulates what usually happens in a clinical setting. The patient often has had sepsis for several hours, or a few days when they seek treatment." Annexin A5 is not currently used as a therapeutic agent, but its safety has been tested in humans. It's currently used in imaging studies to identify cells undergoing apoptosis (cell death). While this study looked at the heart, Dr.