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Archive - Aug 2017


August 18th

Scientists Identify & Characterize Over 20 Odorant/Pherome Receptors in Ants

Queen ants spend most of their time having babies. To reign supreme in a colony, the queens exude a special scent, or pheromone, on the waxy surface of their body that suppresses ovary development in their sisters, rendering the latter reproductively inactive workers that find food, nurse the young, and protect the colony. Now, researchers at the University of California, Riverside (UCR) have begun to unravel the molecular mechanisms underlying how ants sense these pheromones and how they control reproduction regulation and other social activities in ant communities. The research, published on August 17, 2017 in Nature Communications, highlights how ants use olfactory receptors to distinguish between colony members so they can work together in a complex, hierarchical society. The open-access article is titled “Specialized Odorant Receptors in Social Insects That Detect Cuticular Hydrocarbon Cues and Candidate Pheromones.” The findings could help in the development of new pest management strategies. The research team, led by Dr. Anandasankar Ray, an Associate Professor in the Department of Molecular Cell Systems Biology at UCR, has identified and characterized more than 20 receptors found on the antennae of worker ants that play a role in the division of labor within colonies. Among these receptors is one that responds specifically to a pheromone produced by queen ants, an interaction that ultimately results in a physiological change to workers' ovaries. Ants are eusocial insects, meaning they live in cooperative groups where one female and several males are involved in reproduction, and non-breeding individuals play specialized roles, such as caring for the young, finding food, and warding off enemies.

H. pylori Bacteria Send Stomach Stem Cells into Overdrive; May Be Mechanism Underlying H. pylori-Caused Gastric Carcinoma

Gastric carcinoma is one of the most common causes of cancer-related deaths, primarily because most patients present at an advanced stage of the disease. The main cause of this cancer is the bacterium Helicobacter pylori, which chronically infects about half of all humans. However, unlike tumor viruses, bacteria do not deposit transforming genes in their host cells and how bacteria are able to cause cancer has so far remained a mystery. An interdisciplinary research team at the Max Planck Institute in Berlin, in collaboration with researchers at the Standord University School of Medicine, has now discovered that the bacterium sends stem cell renewal in the stomach into overdrive - and stem cell turnover has been suspected by many scientists to play a role in the development of cancer. By showing that the stomach contains two different stem cell types, which respond differently to the same driver signal, the scientists have uncovered a new mechanism of tissue plasticity. It allows tuning tissue renewal in response to bacterial infection. While it has long been recognized that certain viruses can cause cancer by inserting oncogenes into the host cell DNA, the fact that some bacteria can also cause cancer has been slower to emerge and much harder to prove. While it is now clear that most cases of stomach cancer are linked to chronic infections with H. pylori, the mechanism remains unknown. Dr. Thomas F. Meyer and his colleagues at the Max Planck Institute for Infection Biology in Berlin have spent many years investigating this bacterium and the changes it induces in the cells of the stomach epithelium. In particular, they were puzzled as to how malignancy could be induced in an environment in which cells are rapidly replaced.

August 18th

Mysteries in Development of Smallpox Vaccine—A Historical Investigation

Smallpox is an infectious disease caused by variola virus that has killed millions of people over the centuries. The disease is characterized by the growth of innumerable bumps that cover the entire body of the patient. The disease is fatal in 30% of cases, but this rate is much higher for hemorrhagic smallpox and flat-type smallpox. Vaccination against smallpox throughout the 19th and 20th centuries was successful and contributed to the eradication of the disease in 1977, after a successful worldwide campaign (1967-1977) coordinated by the World Health Organization. The vaccine was developed by British physician Edward Jenner in 1796 and the virus circulating in the vaccine was named as vaccinia virus. Cowpox virus, a cousin of variola virus, causes a mild smallpox-like disease in cows. The story goes that Jenner was told that milkers who acquired the "cow-version" of smallpox were immune to the human version of the disease. Thus, one day Jenner decided to perform a risky experiment. The researcher took pustular material from the lesion of a milker and used it to inoculate a young boy, the eight-year-old son of his gardener. If the hypothesis that previous cowpox infection protected humans from smallpox proved right, then the boy would not develop smallpox when later challenged with smallpox pustular material. Sure enough, the young boy remained immune to smallpox and the experiment was a milestone in the history of the smallpox vaccine (see additional information at Wikipedia link below). Following this success, vaccination (from the Latin vacca meaning cow) was adopted worldwide as the main strategy to prevent smallpox.

Ocean Channel in Bahamas Marks Genetic Divide in Brazilian Free-Tailed Bats

Brazilian free-tailed bats are expert flyers, capable of migrating hundreds of miles and regularly traveling more than 30 miles a night. But they pull up short at a narrow ocean channel that cuts across the Bahamas, dividing bat populations that last shared an ancestor hundreds of thousands of years ago. A new study, published online on August 17, 2017, in Ecology and Evolution, uncovers a dramatic and unexpected genetic rift between populations of Tadarida brasiliensis on either side of the Northwest and Northeast Providence Channels, about 35 miles across at their most narrow point. Genetic analysis of the populations suggests that bats from Florida colonized the northern Bahamian islands while bats from other parts of the Caribbean likely colonized the southern Bahamas. The open-access article is titled “Population Structure of a Widespread Bat (Tadarida Brasiliensis) in an Island System.” Why the bats balk at crossing a channel so narrow they can likely see land on the other side while in flight remains a mystery, said Kelly Speer, the study's lead author who completed the research while a master's student at the Florida Museum of Natural History. "Based on their mainland population behavior, we know they're able to disperse much farther than the distances between islands in the Caribbean," said Speer, now a doctoral student at the American Museum of Natural History. "It doesn't seem like distance is the factor, and there's no association with wind direction. We don't have any idea why they don't cross this channel." Because they can fly, bats are good models for studying mammal movement in fragmented habitats, Speer said.

How Cilia Beat in One Direction to Promote Fluid flow in the Brain

Researchers at Nagoya University in Japan have identified a molecule that enables cell appendages called cilia to beat in a coordinated way to drive the flow of fluid around the brain; this prevents the accumulation of this fluid, which otherwise leads to swelling of the head as found in the condition hydrocephalus. Some cells in the body contain long thin structures called cilia on their surfaces, which exhibit a whip-like motion that promotes the flow of fluid past the cell. Although these cilia are known to play vital roles in the body, much remains to be understood about their molecular components and the mechanisms by which they work. This is especially true for the cilia on cells that line the ventricles of the brain, which contain cerebrospinal fluid (CSF) that has various functions including cushioning the brain against potentially damaging impacts. A team at Nagoya University has shed light on this issue by revealing that a molecule called Daple is essential for cilia to adopt an arrangement by which they can beat in one direction at the same time, thereby creating a flow of fluid past the cell exterior. This arrangement on cell surfaces all along the lining of ventricles in the brain ensures the correct flow of CSF, which in turn prevents its accumulation associated with brain swelling known as hydrocephalus. The work was published in the July 25, 2017 issue of Cell Reports. The title of the open-access article is “Daple Coordinates Planar Polarized Microtubule Dynamics in Ependymal Cells and Contributes to Hydrocephalus.” The team revealed the importance of Daple by creating mutant mice that did not express the Daple protein. By approximately 20 days after birth, these mice had enlarged heads, similar to those seen in human hydrocephalus cases.

Solving ME/CFS Initiative (SMCI) Announces New Research Program at Brigham & Women’s Hospital to Study Myalgic Encephalomyelitis/Chronic Fatigue Syndrome(ME/CFS)

On August 16, 2017, the Solve ME/CFS Initiative (SMCI) announced that the SMCI and its partners are initiating a new ME/CFS Research Fund at Brigham and Women’s Hospital (BWH) in Boston, Massachusetts. The establishment of this fund supports the continuation of BWH’s Dr. David Systrom’s ME/CFS research. This work will further understanding of the autonomic, peripheral neuropathy, and cardiovascular features of ME/CFS. In other words, this research focuses on the involuntary nervous system, nerve pain in the hands and feet, and the heart and blood vessels. Specifically, the work aims to characterize the connection between small fiber polyneuropathy (nerve damage) and exertional intolerance during the course of cardiopulmonary (relating to the heart and the lungs) testing. Future study directions will include a continued focus on exertion intolerance with particular attention to the development of therapeutic interventions. Under Dr. Zaher Nahle, Chief Scientific Officer at SMCI’s leadership, the SMCI is committed to creating and advancing stand-alone ME/CFS programs, like this one, at major research universities and medical centers. The SMCI is extremely pleased to facilitate this work at the prestigious BWH. Notably, this was made possible by a donation from a visionary patient through the recently established “patient scientist” program, designed to facilitate patient participation in research through partnerships between patients, SMCI, and selected medical programs.

August 16th

How Genome Sets Its Functional Micro-Architecture

The genes that are involved in the development of the fetus are activated in different tissues and at different times. Their expression is carefully regulated by so-called "enhancer sequences,” which are often located far from their target genes, and this expression requires the DNA molecule to loop around and bring the enhancer sequences in close proximity to their target genes. Such 3D changes of the DNA are in turn controlled by other sequences called topologically associating domains (TADs). École Polytechnique Fédérale de Lausanne (EPFL) scientists have now studied the TADs involved in digit development in the fetus and have gained insights regarding some of the important questions surrounding them. The work was published online on August 7, 2017 in Genome Biology. The open-access article is titled “Large Scale Genomic Reorganization of Topological Domains at The Hoxd Locus.” TADs are portions of the DNA molecule that divide the entire genome of an organism into manageable chunks, like districts in a city. Inside the cell, the vast amount of DNA is packaged into chromatin and chromatin is packaged into the familiar chromosomes. Inside every TAD, there exist genes as well as the elements that regulate them, all packaged together and insulated from genes and regulators in neighboring TADs, like channels or walls that separate city districts. Breaking down the boundaries set by TADs leads to a number of disorders such as colon, esophagus, brain, and blood cancers. But despite their importance, we know little about these boundaries, which confer to a TAD its structure. This raises the question: Is the information coming from the inner parts of a TAD or due to boundaries.

August 16th

Study of Exosome miRNA in Canine Mitral Valve Disease & Congestive Heart Failure Provides Clues to Target Therapies in Dogs and Human Mitral Valve Prolapse

esearchers at the Cummings School of Veterinary Medicine at Tufts University have discovered important biomarkers in extracellular vesicles in dogs with myxomatous mitral valve disease and congestive heart failure. This is the first biomarker discovery based on extracellular vesicles in a veterinary disease. The genomic material (microRNA, or miRNA) was isolated from small extracellular vesicles called exosomes, which are released from cells and can circulate in blood. These findings could provide important insight into the molecular basis, diagnosis, and therapies for myxomatous mitral valve disease in dogs, as well as mitral valve prolapse, a similar disease in humans. The results were published online on July 12, 2017 in the Journal of Extracellular Vesicles. The open-access article is titled “Circulating Exosome MicroRNA Associated With Heart Failure Secondary to Myxomatous Mitral Valve Disease in a Naturally Occurring Canine Model.” In their analysis of circulating exosome miRNA (Ex-miRNA), researchers found that the expressions not only change with disease progression and development of heart failure in dogs with myxomatous mitral valve disease but also exhibit changes solely on the basis of aging in dogs. Additionally, they found that Ex-miRNA expression level changes appear to be more specific to disease states than the measure of miRNA from plasma without attention to the isolation of Ex-miRNA. This suggests that Ex-miRNA may offer a novel approach that improves upon current established methods of monitoring patients with heart disease and other diseases, yet relies on readily available samples such as blood and urine.

Scientists Develop Blood Test That Spots Tumor-Derived DNA in People with Early-Stage Cancers; Hopkins-Developed Test Targets 58 Cancer-Associated Genes Using Deep Sequencing Technology

In a bid to detect cancers early and in a noninvasive way, scientists at the Johns Hopkins Kimmel Cancer Center, and colleagues, report they have developed a test that spots tiny amounts of cancer-specific DNA in blood and have used it to accurately identify more than half of 138 people with relatively early-stage colorectal, breast, lung, and ovarian cancers. The test, the scientists say, is novel in that it can distinguish between DNA shed from tumors and other altered DNA that can be mistaken for cancer biomarkers. A report on the research, performed on blood and tumor tissue samples from 200 people with all stages of cancer in the U.S., Denmark, and the Netherlands, appears in the August 16, 2017 issue of Science Translational Medicine. The open-access article is titled “Direct Detection of Early-Stage Cancers Using Circulating Tumor DNA.” "This study shows that identifying cancer early using DNA changes in the blood is feasible and that our high-accuracy sequencing method is a promising approach to achieve this goal," says Victor Velculescu (photo), MD, PhD, Professor of Oncology at the Johns Hopkins Kimmel Cancer Center. Blood tests for cancer are a growing part of clinical oncology, but they remain in the early stages of development. To find small bits of cancer-derived DNA in the blood of cancer patients, scientists have frequently relied on DNA alterations found in patients' biopsied tumor samples as guideposts for the genetic mistakes they should be looking for among the masses of DNA circulating in those patients' blood samples. To develop a cancer screening test that could be used to screen seemingly healthy people, scientists had to find novel ways to spot DNA alterations that could be lurking in a person's blood but had not been previously identified.

Micromotors Deliver Drugs to Treat Bacterial Infection in Stomach; New Results in Animals Open Door to Use of Synthetic Motors As Active Delivery Platforms for In Vivo Treatment of Diseases

Nanoengineers at the University of California San Diego have demonstrated, for the first time, the use of micromotors to treat a bacterial infection in the stomach. These tiny vehicles, each about half the width of a human hair, move rapidly throughout the stomach while neutralizing gastric acid, and then release their cargo of antibiotics at the desired pH. The researchers published their findings on August 16, 2017 in Nature Communications. The open-access article is titled “Micromotor-Enabled Active Drug Delivery for In Vivo Treatment of Stomach Infection.” This micromotor-enabled delivery approach is a promising new method for treating stomach and gastrointestinal tract diseases with acid-sensitive drugs, researchers said. The effort is a collaboration between the research groups of nanoengineering professors Joseph Wang (photo) and Liangfang Zhang at the UC San Diego Jacobs School of Engineering. Dr. Wang and Dr. Zhang pioneered research on the in vivo operation of micromotors and this study represents the first example of drug-delivering micromotors for treating bacterial infection. Gastric acid can be destructive to orally administered drugs such as antibiotics and protein-based pharmaceuticals. Drugs used to treat bacterial infections, ulcers, and other diseases in the stomach are normally taken with additional substances, called proton pump inhibitors, to suppress gastric acid production. But when taken over longer periods or in high doses, proton pump inhibitors can cause adverse side effects including headaches, diarrhea, and fatigue. In more serious cases, they can cause anxiety or depression.