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Archive - Feb 2015

February 13th

Screening & Personalizing Nootropic Drugs & Cognitive Modulator Regimens in Silico

The Biogerontology Research Foundation (BGRF), a UK-based charity committed to the support of aging research to address the challenges of a rapidly aging population and to reduce the impact of disease on future generations, announces the publication of research into personalizing nootropic drugs using in silico prediction methods. The research, published online on Febuary 6, 2015 in an open-access article in Frontiers in Systems Neuroscience, uses gene expression data to evaluate activated or suppressed signaling pathways in tissues or neurons of the cognitively enhanced brain. The title of the article is. “Screening and Personalizing Nootropic Drugs and Cognitive Modulator Regimens in Silico.” [BioQuick Editor's Note: Nootropics, also referred to as smart drugs, memory enhancers, neuro enhancers, cognitive enhancers, and intelligence enhancers, are drugs, supplements, nutraceuticals, and functional foods that improve one or more aspects of mental function, such as working memory, motivation, and attention. The word nootropic was coined in 1972 by the Romanian Dr. Corneliu E. Giurgea,and is derived from the Greek words for "mind," and for "to bend" or "to turn."]. The scientists report that an algorithm maps expression data onto signaling pathways. The collective pathways, and their activation, form what is called a "signaling pathway cloud," a biological fingerprint of cognitive enhancement (or any other condition of interest). Drugs can then be screened and ranked based on their ability to minimize, mimic, or exaggerate pathway activation or suppression within that cloud.

Ground-Breaking Lung Cancer Breath Test Wil Be Evaluated in Clinical Trial

A clinical trial led by University of Leicester respiratory experts into a potentially ground-breaking “breath test” to detect lung cancer is set to get underway at the Glenfield Hospital in Leicester, UK. It is hoped that the LuCID (Lung Cancer Indicator Detection) program will lead to a non-invasive method of diagnosing lung cancer in the early stages. The company behind the device, Cambridge-based Owlstone Nanotech Ltd, carried out a health economic analysis and determined that detection of early-stage lung cancer could be increased from the current 14.5% to 25% by 2020. It is estimated this could save 10,000 lives and £250m of NHS money. Four publicly funded health care systems in the countries of the United Kingdom are referred to as the National Health Service (NHS). The “breath-test” device works by measuring volatile organic compounds (VOCs) at low concentrations in a patient’s breath and offers a cheaper and smaller alternative to existing detection technologies. Supported by the University of Leicester’s enterprise and business development team and Leicester’s Hospitals, Owlstone was awarded £1m by the NHS Small Business Research Initiative (SBRI) towards the second phase of the LuCID project – the clinical trials. The aim is to further evaluate Owlstone’s GC-FAIMS (Gas Chromatography – Field Asymmetric Ion Mobility Spectrometry) sensor in a rapid-access lung cancer clinic at Glenfield Hospital, Leicester, starting later this year. If successful, the project will pave the way to evaluate the technology in GPs’ surgeries and other hospitals.

Mechanical Tension Drives Cell Fusion; Myosin's "Mechanosensory" Response In Receiving Cell Is Key; Despite Chemical Signaling Having Been Disabled, Myosin “Swims” to the Membrane Fusion Site

Just as human relationships are a two-way street, fusion between cells requires two active partners: one to send protrusions into its neighbor, and one to hold its ground and help complete the process. Researchers have now found that one way the receiving cell plays its role is by having a key structural protein come running in response to pressure on the cell membrane, rather than waiting for chemical signals to tell it that it's needed. The study, which helps open the curtain on a process relevant to muscle formation and regeneration, fertilization, and immune response, was published online on February 12, 2016 in journal Developmental Cell. "We knew that in cell fusion, one cell attacks its fusion partner, but we didn't know what the other cell was doing," says Elizabeth Chen, Ph.D., an Associate Professor of Molecular Biology and Genetics at the Johns Hopkins University School of Medicine. "Now we know that the other cell is putting up some resistance." The merging of two cells, which is crucial to conception, development, and physiology of complex organisms, was long thought to be a symmetrical process, where two cells contribute equally. But two years ago, Dr. Chen's research group showed that, in fact, one of the fusion partners initiates the process by extending fingerlike protrusions into the other partner. For the current study, Dr. Chen's group and collaborators focused on the receiving partner. Using fruit fly embryos and lab-grown fly cells that were induced to fuse, they saw that in the areas where the attacking cells drilled in, the receiving cells quickly fortified their cellular skeletons, effectively pushing back. "We think that by stiffening its skeleton in this way, the receiving cell avoids moving away from the attacking cell, in which case fusion couldn't occur," Dr. Chen says.

Oyster Disease (Dermo), Caused by Parasite, Thrives in Nightly Oxygen Dead Zones in Shallow Waters

In shallow waters around the world, where nutrient pollution runs high, oxygen levels can plummet to nearly zero at night. Oysters living in these zones are far more likely to pick up the lethal Dermo disease, a team of scientists from the Smithsonian Environmental Research Center has discovered. Their findings were published online on Wednesday February 11, 2015 in the open-access journal PLOS ONE. Oxygen loss in the shallows is a global phenomenon, but it is not nearly as well known as the dead zones of the deep. Unlike deep-water dead zones, which can persist for months, oxygen in shallow waters swings in day-night cycles, called diel-cycling hypoxia. When algae photosynthesize during the day, they release oxygen into the water. But at night, when photosynthesis stops, plants and animals continue to respire and take oxygen from the water, causing dissolved oxygen to drop. Lack of oxygen can cripple the oysters' ability to fight off the parasite Perkinsus marinus that causes Dermo disease and slowly takes over the oysters’ bodies. "We usually think of shallow-water habitats as highly productive refuges from deep-water dead zones," says Denise Breitburg, marine ecologist at SERC and lead author of the study. "But if low oxygen makes even these shallow waters inhospitable for fish and shellfish, the whole system may suffer." In a field experiment, Dr. Breitburg and her colleagues suspended hundreds of eastern oysters (Crassostrea virginica) in underwater cages at each of 14 sites around Chesapeake Bay. Some oysters that were only a year old and did not show signs of being infected were used to test the vulnerability of new populations, especially where oyster restoration is concerned. Others that were older and had already been infected were used to test whether low-oxygen made the disease more severe.

Gold Nanotubules: First Demonstrated Biomedical Use in Mouse Model of Human Cancer

Scientists have shown that gold nanotubes have many applications in fighting cancer: internal nanoprobes for high-resolution imaging; drug delivery vehicles; and agents for destroying cancer cells. The study, published February 13, 2015 in the journal Advanced Functional Materials, details the first successful demonstration of the biomedical use of gold nanotubes in a mouse model of human cancer. The article is titled, “'Engineering Gold Nanotubes with Controlled Length and Near-Infrared Absorption for Theranostic Applications.” Study lead author Dr. Sunjie Ye, who is based in both the School of Physics and Astronomy and the Leeds Institute for Biomedical and Clinical Sciences at the University of Leeds, said: "High recurrence rates of tumors after surgical removal remain a formidable challenge in cancer therapy. Chemo- or radiotherapy is often given following surgery to prevent this, but these treatments cause serious side effects. Gold nanotubes--that is, gold nanoparticles with tubular structures that resemble tiny drinking straws-- have the potential to enhance the efficacy of these conventional treatments by integrating diagnosis and therapy in one single system." The researchers say that a new technique to control the length of nanotubes underpins the research. By controlling the length, the researchers were able to produce gold nanotubes with the right dimensions to absorb a type of light called “near infrared.” The study's corresponding author Professor Steve Evans, from the School of Physics and Astronomy at the University of Leeds, said: "Human tissue is transparent for certain frequencies of light--in the red/infrared region. This is why parts of your hand appear red when a torch is shone through it."

IgE-Bearing B-Cells Undergo Apoptosis to Forestall Allergy

Scientists from the CNRS, INSERM, and the Université de Limoges, working in the Laboratoire Contrôle de la Réponse Immune B et Lymphoproliférations (CNRS/Université de Limoges) have demonstrated that the production of type E immunoglobulins (IgE) by B-lymphocytes induces a loss in their mobility and the initiation of cell death mechanisms. These antibodies, present in small quantities, are the most powerful "weapons" in the immune system and can trigger extremely violent immune reactions or immediate allergies (asthma, urticaria, allergic shock) as soon as their levels rise, even slightly. These findings, published online in Cell Reports on February 12, 2015, elucidate how our bodies restrict the production of IgE in order to prevent an allergic reaction. The title of the article is “Self-Restrained B Cells Arise Following Membrane IgE Expression.” Immunity is based on cells, B lymphocytes, which carry or secrete antibacterial or antiviral "weapons," the immunoglobulins (IgG, IgM, IgA, IgE) or antibodies. Although these weapons of immunity offer protection, they can also sometimes turn on us. This is the case for the most effective of antibodies, IgE, where even infinitesimal traces (these IgE are 100,000 times less abundant than other antibodies) can trigger extremely violent allergic reactions. The lymphocytes that produce IgM, IgG or IgA are numerous, easily identifiable, and persistent (as "memory cells"). For hitherto unexplained reasons, the cells that produce IgE are rare and have thus been the subject of very little study. In order to understand the mechanisms controlling IgE, the scientists first of all used genetic engineering to force cells to produce these antibodies in large numbers. They then succeeded in demonstrating two principal control mechanisms.

Dogs Can Discriminate Emotional Expressions of Human Faces

Dogs can tell the difference between happy and angry human faces, according to a new study published in Current Biology on February 12, 2015. The article was titled, “Dogs Can Discriminate Emotional Expressions of Human Faces." The discovery represents the first solid evidence that an animal other than humans can discriminate between emotional expressions in another species, the researchers say. "We think the dogs in our study could have solved the task only by applying their knowledge of emotional expressions in humans to the unfamiliar pictures we presented to them," says Dr. Corsin Müller of the University of Veterinary Medicine Vienna. Previous attempts had been made to test whether dogs could discriminate between human emotional expressions, but none of them had been completely convincing. In the new study, the researchers trained dogs to discriminate between images of the same person making either a happy or an angry face. In every case, the dogs were shown only the upper or the lower half of the face. After training on 15 picture pairs, the dogs' discriminatory abilities were tested in four types of trials, including (1) the same half of the faces as in the training but of novel faces, (2) the other half of the faces used in training, (3) the other half of novel faces, and (4) the left half of the faces used in training. The dogs were able to select the angry or happy face more often than would be expected by random chance in every case, the study found.

February 11th

Evolution of Darwin’s Finches and Their Beaks Revealed by Genome Sequencing

Researchers from Princeton University in the United States and Uppsala University in Sweden have identified a gene in the Galápagos finches studied by English naturalist Charles Darwin that influences beak shape and that played a role in the birds' evolution from a common ancestor more than 1 million years ago. The study illustrates the genetic foundation of evolution, including how genes can flow from one species to another, and how different versions of a gene within a species can contribute to the formation of entirely new species, the researchers report in Nature, in an article that was published online on February 11, 2015 one day before birthday anniversary of Darwin, who studied the finches during the 1835 voyage that would lead him to publish the seminal work on evolution, "On the Origin of Species," in 1859. The article was entitled "Evolution of Darwin's Finches and Their Beaks Revealed by Genome Sequencing," "We now know more about the genetic basis for our evolutionary studies, and this is a highly satisfactory, very exciting discovery after all these years," said Dr. Peter Grant, Princeton's Class of 1877 Professor of Zoology, Emeritus, and a Professor of Ecology and Evolutionary Biology, Emeritus. Together with co-author and wife Dr. B. Rosemary Grant, a senior biologist in ecology and evolutionary biology at Princeton, Dr. Peter Grant has studied the finches for 40 years on the arid, rocky islands of Daphne Major and Genovesa in the Galápagos archipelago. The latest study reveals how evolution occurs in halting and disordered steps, with many opportunities for genes to spread in different species and create new lineages. Given the right conditions, such as isolation from the original population and an accumulation of genetic differences, these lineages can eventually evolve into entirely new species.

Diabetes Drug Proglitazone Can Stimulate Production of ROS from Mitochonria of WBCs, Meliorating Chronic Granulomatous Disease in Mouse Model

Pioglitazone, a medication approved for treatment of type 2 diabetes, can help bypass genetic defects in chronic granulomatous disease (CJD) to help white blood cells fight bacterial infections, according to researchers at National Jewish Health. Patients with CGD, a rare inherited disorder, lack a functional enzyme, known as NADPH oxidase, which impairs their ability to produce a variety of oxidant molecules, known as reactive oxygen species (ROS), in response to bacterial infection. Normally, ROS destroy bacteria by chemically reacting with their cell walls and other components. As a result of genetic mutation, CGD patients lack this early immune response and suffer ongoing and severe infections, especially of the lungs, liver, skin, and lymph nodes. Pioglitazone, an agonist of the signaling molecule PPAR-gamma, has broad effects on cellular metabolism, which include mimicry of insulin and anti-inflammatory activities. The medication is approved for treatment of type 2 diabetes and is being investigated for use in a variety of other disorders, primarily for its anti-inflammatory properties. Recent findings have suggested that it may also boost the production of ROS. National Jewish Health Professor of Pediatrics, Donna Bratton, M.D., and her colleagues reported in the February 2015 Journal of Allergy and Clinical Immunology that pioglitazone does indeed boost production of ROS in white blood cells by about 30 percent in a mouse model of CGD and in white blood cells from CGD patients. They also found that pioglitazone enhanced the ability of the cells from the CGD mouse model to kill Staphylococcus aureus and Burkholdia cepacia, two pathogens that are difficult to treat and common in CGD.

Morpholino Targeted at VP24 Protein Protects 75% of Rhesus Monkeys Against Ebola

Scientists protected 75 percent of rhesus monkeys infected with Ebola virus that were treated with a compound targeting the expression of VP24, a single Ebola virus protein--suggesting that VP24 may hold the key to developing effective therapies for the deadly disease. The study, which appears on February 10, 2015 in mBio, the online journal of the American Society for Microbiology, was conducted by the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), in collaboration with the biotechnology firm Sarepta Therapeutics, Inc. For over a decade, USAMRIID and Sarepta have been collaborating to develop and test a class of antisense compounds known as phosphorodiamidate morpholino oligomers (or PMOs), according to principal investigator and first author Travis K. Warren, Ph.D., of USAMRIID. "Antisense drugs are designed to enter cells and eliminate viruses by preventing their replication," Dr. Warren said. The drugs act by blocking the translation of critical viral genetic sequences, preventing the xxx protein from being made, and giving the infected host time to mount an immune response and clear the virus, he explained. In work previously published in Nature Medicine, the team demonstrated that a combination PMO called AVI-6002, a product targeting genes that code for two proteins, VP24 and VP35, prevented Ebola virus infection in rhesus monkeys. The current study compared the activity of the individual components against that of the combination treatment. In this experiment, animals were treated with AVI-7537, which targets VP24 alone; AVI-7539, which targets VP35 alone; or AVI-6002, which targets both proteins. A fourth group served as the untreated control. Animals were treated once a day for up to 14 days beginning approximately one hour after virus exposure.