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September 4th, 2017

Study Suggests Simple Way to Predict Preterm Births: Test of Cervical Mucus May Reveal Pregnant Women’s Risk of Going into Labor Too Early

Up to 18 percent of babies born worldwide arrive before they are full-term, defined as 37 weeks of gestation. About 1 million of those babies do not survive, and those who do can face developmental problems such as impaired vision or hearing, defects in the heart or lungs, or cognitive impairments. Currently there is no reliable way to predict whether a woman with a normal pregnancy will go into labor before 37 weeks. However, a study from MIT offers a new approach to evaluating this risk, by analyzing the properties of cervical mucus. The researchers found that cervical mucus from women who delivered their babies before 37 weeks was very different from that of women who delivered later. This type of analysis could offer an easy way to calculate the risk of early labor, potentially allowing doctors to try to intervene earlier to prevent preterm births. “Our prediction is that we might be able to identify risk for preterm birth ahead of time, before labor sets in,” says Katharina Ribbeck (photo), PhD, an Associate Professor of Biological Engineering at MIT and the senior author of the study. “Diagnostic tools for this are missing.” Dr. Ribbeck worked on the study with Dr. Michael House, an Associate Professor at Tufts University School of Medicine. MIT postdoc Dr. Kathryn Smith-Dupont is the first author of the paper, which was published in the September 4, 2017 issue of Scientific Reports. The open-access article is titled “Probing the Potential of Mucus Permeability to Signify Preterm Birth Risk.” Dr. Ribbeck’s lab at MIT investigates the distinctive chemical and mechanical properties of mucus, and how those properties help mucus to perform many critical roles as part of the body’s first line of defense against infection. Several years ago, Dr.

Plant MicroRNAs in Larval Food Regulate Caste Development in Honey Bees

Bee larvae develop into workers, in part, because their diet of pollen and honey, called beebread, is rich in plant regulatory molecules called microRNAs, which delay development and keep their ovaries inactive. Xi Chen of Nanjing University in China, and colleagues, report these results online on August 31, 2017 in PLOS Genetics. The open-access article is titled “Plant microRNAs in Larval Food Regulate Honeybee Caste Development.” Researchers have long known that diet plays an important role in the complex process that determines whether a honeybee larva will become a worker or a queen. While the workers primarily consume beebread, the queens feast on royal jelly secreted by the glands of nurse bees. Beebread contains much higher levels of plant microRNAs than royal jelly, so researchers decided to investigate if these molecules, which regulate gene expression in plants, could also impact honeybee caste development. They found that honeybees raised in the lab on simulated beebread supplemented with plant microRNAs developed more slowly and had a smaller body and smaller ovaries than larvae raised without the supplements. The plant microRNAs also had a similar effect on fruit fly larvae, even though fruit flies are not social insects. Further experiments showed that one of the most common plant microRNAs in beebread targets the TOR gene in honeybees, which helps determine caste. The study shows that there is more to the story of honeybee caste formation than the traditional focus on royal jelly and identifies a previously unknown function of plant microRNAs in fine-tuning larval development. The work is a powerful example of the effects of cross-kingdom microRNAs and how these interactions can affect a species' development and evolution.

Liquid Biopsy Detects Tumor-Specific DNA and Protein Markers for Early-Stage Pancreatic Cancer, Hopkins Scientists Report

Johns Hopkins scientists and colleagues say they have developed a blood test that spots tumor-specific DNA and protein biomarkers for early-stage pancreatic cancer. The combined "liquid biopsy" identified the markers in the blood of 221 patients with the early-stage disease. The results, published online the week of Septtember 4, 2017 in PNAS, show that detection of markers from both DNA and protein products of DNA was twice as accurate at identifying the disease as detection of DNA alone. Such liquid biopsies aim to fish out DNA molecules specific for cancer amid a wide sea of normal DNA circulating in the blood. Tumors tend to shed their mutated DNA into the bloodstream, making it possible for scientists to use genomic sequencing tools to sift through the blood and find such cancer-linked DNA. Most early-stage pancreatic cancers are found incidentally during an imaging scan and generally cause no symptoms. But the disease is most often found late, when it's far advanced and resection, or surgery, is not the first treatment option, says Jin He, MD, Assistant Professor of Surgery at the Johns Hopkins University School of Medicine. "In the past 30 years, we haven't made much progress in identifying people with resectable cancers," says Dr. He. "If this test's performance is validated in larger studies, it could be used to identify patients with early, asymptomatic pancreatic cancer." While their test is not ready to be used outside of a research setting, the scientists say, mutated DNA of the type that is shed from tumors and found in blood is "exquisitely specific" for cancer.

Adipose Tissue May Affect Cancer Development in Multiple Ways, Review Concludes

In a comprehensive review, scientists report that adipose tissue, or fat, may influence the development of cancer in diverse ways, depending on the type of fat and the location in the body. The review was published in the September 2017 issue of Cancer Prevention Research, a journal of the American Association for Cancer Research (AACR). The article is titled “Signals from the Adipose Microenvironment and the Obesity-Cancer Link—A Systematic Review.” The senior author of the review is Cornelia M. Ulrich, PhD, Senior Director of Population Sciences at the Huntsman Cancer Institute at the University of Utah in Salt Lake City. "Obesity is increasing dramatically worldwide, and is now also recognized as one of the major risk factors for cancer, with 16 different types of cancer linked to obesity," Dr. Ulrich said. "We urgently need to identify the specific mechanisms that link obesity to cancer." Dr. Ulrich explained that previous research has shown several ways that fat contributes to carcinogenesis. For example, obesity increases the risk of inflammation, which has long been associated with cancer. Also, obesity is believed to affect cancer cell metabolism and immune clearance, all of which can contribute to the growth and spread of tumors, she said. The relationship between fat and carcinogenesis also depends upon "crosstalk," or the ways cells react when the same signal is shared by more than one signaling pathway in two different cell types, Dr. Ulrich explained. Identifying ways to interrupt the crosstalk could help researchers identify new cancer prevention strategies. In this study, Dr.

Alterations in Blood-Based miRNA Detected in Veterans Affected with Combat-Related PTSD

Individuals affected with PTSD (post-traumatic stress disorder) demonstrate changes in microRNA (miRNA) molecules associated with gene regulation. A controlled study, involving military personnel on deployment to a combat zone in Afghanistan, provided evidence for the role of blood-based miRNAs as candidate biomarkers for symptoms of PTSD. This may offer an approach towards screening for symptoms of PTSD, and holds promise for understanding other trauma-related psychiatric disorders. Limitations of the study are that it was a small pilot study, and the findings need to be validated, extended, and confirmed. First results were to be presented at the 30th Annual ECNP Conference in Paris (September 2-5). ECNP is the European College of Neuropsychopharmacology. PTSD is a psychiatric disorder that can manifest following exposure to a traumatic event, such as combat, assault, or natural disaster. Among individuals exposed to traumatic events, only a minority of individuals will develop PTSD, while others will show resiliency. Little is known of the mechanisms behind these different responses. The last few years have seen much attention given to whether the modification and expression of genes - epigenetic modifications - might be involved. But there are several practical and ethical challenges in designing a research study on humans undergoing such experiences, meaning that designing relevant study approaches is difficult. The research group from the Netherlands, worked with just over 1,000 Dutch soldiers and the Dutch Ministry of Defense to study changes in biology in relation to changes in presentations of symptoms of PTSD in soldiers who were deployed to combat zone in Afghanistan. In a longitudinal study, the researchers collected blood samples before deployment, as well as 6 months after deployment.

CNPY2 Is Key Initiator of a Pathway of Unfolded Protein Response (UPR); May Be Potential Therapeutic Target in UPR-Related Diseases Such As Metabolic Disorders, Inflammation, and Cancer

The cell's response to unfolded or misfolded proteins could be a cause, rather than a consequence, of metabolic disorders, report researchers at the Medical University of South Carolina (MUSC) in an article published online on September 4, 2017 in Nature Structural & Molecular Biology. The researchers identified a little-known molecule as the trigger for this response. The article is titled “CNPY2 Is a Key Initiator of the PERK–CHOP Pathway of the Unfolded Protein Response.” There are links between protein-folding problems at the cellular level and a range of metabolic disorders, though it is unclear if those problems are causes or manifestations of such disorders. This study provides evidence that problems with protein folding contribute to certain metabolic disorders, according to Zihai Li, MD, PhD, Chair of the Department of Microbiology and Immunology at the MUSC Hollings Cancer Center and principal investigator on the project. Feng Hong, MD, PhD, in the Department of Microbiology and Immunology, is lead author on the paper. "The unfolded protein response in the cell plays important roles in aging and in many diseases, such as cancer, diabetes, and neurodegenerative disease," says Dr. Li. "Our study has uncovered a novel mechanism that triggers this response." When improperly folded molecules are encountered in cells, the unfolded protein response (UPR) is activated within the endoplasmic reticulum (ER). The ER is in charge of molecular quality control, making sure proteins, lipids, and other molecules are folded properly before the cell attempts to use them for metabolic processes. Here, a master protein called grp78 is in contact with three main signaling hubs that make up the control center of the UPR.

New Study in Mice Reveals Biological Origins of a Core Symptom (Memory Deficits) of Schizophrenia

A team of Columbia scientists has found that disruptions to the brain's center for spatial navigation -- its internal GPS -- result in some of the severe memory deficits seen in schizophrenia. The new study in mouse models of the disorder marks the first time that schizophrenia's effects have been observed in the behavior of living animals -- and at the level of individual brain cells -- with such high-resolution, precision and clarity. The findings offer a promising entry point for attacking a near-universal and debilitating symptom of schizophrenia, memory deficits, which has thus far withstood all forms of treatment. The results of this study were published online on September 4, 2017 in Nature Neuroscience. The article is titled “Impaired Hippocampal Place Cell Dynamics in a Mouse Model of 22q11.2 Deletion.” "An almost intractably complex disorder, schizophrenia is nearly impossible to fully treat -- in large part because it acts as two disorders in one," said Joseph Gogos, MD, PhD, a principal investigator at Columbia's Mortimer B. Zuckerman Mind Brain Behavior Institute and the paper's co-senior author. "On one hand, you have paranoia, hallucinations, and delusions; while on the other, you have severe memory deficits. Antipsychotic drugs, which treat the first class of symptoms, are entirely ineffective when dealing with the second. The reasons for this are simple: we do not yet understand what happens in the brains of schizophrenia patients.” Cracking schizophrenia's code must therefore start with deciphering its biological origins, says Dr. Gogos, who is also Professor of Physiology, Cellular Biophysics and Neuroscience at Columbia University Medical Center (CUMC). This has led to a recent focus on the memory impairments that are so common among schizophrenia patients.

September 2nd

Scientists Engineer Mutant Ants That Shed Light on Evolution of Social Behavior

Ants run a tight ship. They organize themselves into groups with very specific tasks: foraging for food, defending against predators, building tunnels, etc. An enormous amount of coordination and communication is required to accomplish this. To explore the evolutionary roots of the remarkable system, researchers at The Rockefeller University have created the first genetically altered ants, modifying a gene essential for sensing the pheromones that ants use to communicate. The result, severe deficiencies in the ants’ social behaviors and their ability to survive within a colony, both sheds light on a key facet of social evolution and demonstrates the feasibility and utility of genome editing in ants. “It was well known that ant language is produced through pheromones, but now we understand a lot more about how pheromones are perceived,” says Dr. Daniel Kronauer, Head of the Laboratory of Social Evolution and Behavior. “The way ants interact is fundamentally different from how solitary organisms interact, and with these findings we know a bit more about the genetic evolution that enabled ants to create structured societies.” The most important class of pheromones in ant communication is that of hydrocarbons, which can communicate species, colony, and caste identity, as well as reproductive status. These pheromone signals are detected by porous sensory hairs on the ants’ antennae that contain what are called odorant receptors—proteins that recognize specific chemicals and pass the signal up to the brain. Work in the Kronauer lab, led by graduate student Sean McKenzie and published in PNAS in late 2016, has shown that a group of odorant receptor genes, known as 9-exon-alpha ORs, are responsible for sensing hydrocarbons in the clonal raider ant species Ooceraea biroi.

September 1st

Study Establishes Fish As Experimental Platform for Studying How Ancient Genetic Information Controls Development and Dysfunction of Human Intestine

Scientists have discovered a network of genes and genetic regulatory elements in the lining of the intestines that has stayed remarkably the same from fishes to humans. Many of these genes are linked to human illnesses, such as inflammatory bowel diseases, diabetes, and obesity. The findings, which were published online on August 29, 2017 in PLOS Biology, establish the fish as an experimental platform for studying how this ancient genetic information -- distilled over 420 million years of evolution -- controls the development and dysfunction of the intestine. "Our research has uncovered aspects of intestinal biology that have been well-conserved during vertebrate evolution, suggesting they are of central importance to intestinal health," said John F. Rawls, PhD, senior author of the study and Associate Professor of Molecular Genetics and Microbiology at Duke University School of Medicine. "By doing so, we have built a foundation for mechanistic studies of intestinal biology in non-human model systems like fish and mice that would be impossible to perform in humans alone." The open-access PLOS Biology article is titled “"Genomic Dissection of Conserved Transcriptional Regulation in Intestinal Epithelial Cells." The intestine serves a variety of important functions that are common to all vertebrates. It takes up nutrients, stimulates the immune system, processes toxins and drugs, and provides a critical barrier to microorganisms. Defects in the intestinal epithelial cells lining the intestine have been implicated in a growing number of ailments, including inflammatory bowel diseases, colorectal cancer, food allergy, diabetes, obesity, malnutrition, and infectious diarrheas.

September 1st

Asthma Drug Targeting Beta2-Adrenoreceptor May Be Effective in Reducing Parkinson’s Disease by Turning Down Production of Alpha-Synclein

Lewy bodies - abnormal clumps of alpha-synuclein protein that accumulate in the brain - are a hallmark of Parkinson's disease (PD). Traditional drug development approaches for PD have focused on clearing alpha-synuclein from the brain or on preventing its downstream effects. But researchers from Brigham and Women's Hospital (BWH) in Boston want to prevent alpha-synuclein from accumulating in the first place. To do so, the team searched for drugs that turn down alpha-synuclein production. They then tested the drugs in mice and stem cells and studied the health records of millions of people living in Norway. The results of their efforts, which point to a new drug development path for PD, were published in the September 1, 2017 issue of Science. The article is titled “Beta2-Adrenoreceptor Is a Regulator of the alpha-Synuclein Gene Driving Risk of Parkinson's.” "Our study suggests a potential new pathway to target PD," said corresponding author Clemens Scherzer, MD, a neurologist and principal investigator at the Ann Romney Center for Neurologic Diseases at BWH and Harvard Medical School. The research team screened more 1,100 drugs already approved for treating diseases other than PD, looking for compounds that could be repurposed for lowering alpha-synuclein production in neuronal cells. They narrowed in on promising candidates, members of a class of drugs known as beta2-adrenergic agonists. The team studied the effects of this class of drugs in mice, finding that it could significantly reduce alpha-synuclein levels. Working with collaborators from the University of Bergen in Norway, the team combed through data from the health records of more than 4 million Norwegians, pulling out information on patients who had been taking salbutamol, a beta2-adrenergic agonist commonly used to treat of asthma.