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Archive - 2016

December 26th

Fat May Fuel the Road to Cancer Cell Metastasis Through Lymphatics

Cancer cells spread to other sites in the body through promoting the growth of new “roads” to travel on. In a study published online on December 26, 2016 in Nature, an international and multidisciplinary team of researchers, led by Professor Dr. Peter Carmeliet (VIB-KU Leuven), discovered how a shift to increased fat utilization is required for the development and growth of these “roads,” termed lymphatic vessels - a special kind of blood vessels. This discovery paves the way towards developing therapeutics to limit lymphatic vessel growth in cancer by targeting fat utilization. The spread of cancer, termed metastasis, is one of the most important and life-threatening complications of cancer today. Current chemotherapy and radiotherapy can effectively treat many cancers, however, the spread of cancer cells to multiple sites within the body results in the majority of deaths associated with cancer. In order for cancer cells to spread, they must find a pre-existing “road,” or build a new “road” to travel on. Lymphatic vessels, a specialized kind of vessels transporting lymph fluid rather than blood, are a primary route of cancer cell spread, and the formation of new lymphatic vessels, termed lymphangiogenesis, is a poorly understood process, which currently lacks clinically approved drugs to prevent their growth during disease. The new article is titled “Fat Fuels the Road To Cancer Cell Spread.” Expanding upon recent work in the laboratory published in top journals such as Cell and Nature, a team consisting of Drs. Brian Wong, Xingwu Wang, and Annalisa Zecchin, guided by Professor Carmeliet, sought to investigate the nutrient utilization (metabolism) of lymphatic vessels. The study began with a simple observation: lymphatics use more fat (fatty acids) compared to blood vessels.

Genome Sequence May Aid Effort to Thwart Dieback Disease in European Ash Trees (Article 1)

Researchers at the University of York (UK) have identified genetic markers for disease tolerance that suggest UK ash trees may have a fighting chance against a fungal infection, which has the potential to wipe out 90% of the European ash tree population. The disease, called ash dieback, was first identified in Poland, where it devastated the native ash tree population. It rapidly spread across northern Europe, and was discovered in the UK in 2012. Results from the latest study, a collaboration between the University of York and Queen Mary University of London (QMUL), could contribute to breeding new varieties of ash that are tolerant to the disease. The disease is aggressive, spreads quickly through the population, and has no cure, other than individual natural tolerance to the infection. The disease is spread on the wind or via the transfer of infected saplings between areas. Symptoms include loss of leaves and lesions, which are a useful way to diagnose fungal ash dieback, as they leave a characteristic diamond shape scar on the bark. Professor Ian Bancroft, plant biologist at the University of York, said: "This disease has spread across Europe in less than 10 years so there is some urgency to understand how we can better support breeding programs for the species. Ash trees can be found in home gardens, parks, and roadsides and are an important woodland species that supports a number of insects and fungi. It is not known exactly how the loss of this tree species will impact the eco-system, but from past examples, we know that the extinction of any species can fundamentally alter the environment." The York team had previously tested a genetic screening process on Danish trees.

Genome Sequence of European Ash Tree May Reveal Ways to Combat Deadly Ash Dieback Disease (Article 2)

Tens of millions of ash trees across Europe are dying from the Hymenoscyphus fraxinea fungus - the most visible signs that a tree is infected with ash dieback fungus are cankers on the bark and dying leaves. Project leader Dr. Richard Buggs from Queen Mary University of London”s (QMUL's) School of Biological and Chemical Sciences said: "This ash tree genome sequence lays the foundations for accelerated breeding of ash trees with resistance to ash dieback." A small percentage of ash trees in Denmark show some resistance to the fungus and the reference genome is the first step towards identifying the genes that confer this resistance. The ash tree genome also contains some surprises. Up to quarter of its genes are unique to ash. Known as orphan genes, they were not found in ten other plants whose genomes have been sequenced. Dr. Buggs added: "Orphan genes present a fascinating evolutionary conundrum as we have no idea how they evolved." The research was published online on December 26, 2016 in Nature. The article is titled “Genome Sequence and Genetic Diversity of European Ash Trees.” The work involved a collaboration among scientists at: QMUL, the Earlham Institute, Royal Botanic Gardens Kew, University of York, University of Exeter, University of Warwick, Earth Trust, University of Oxford, Forest Research, Teagasc, John Innes Centre, and National Institute of Agricultural Botany. The reference genome from QMUL was used by scientists at York University who discovered genes that are associated with greater resistance to ash dieback. They have used these to predict the occurrence of more resistant trees in parts of the UK not yet affected by the disease, which is spreading rapidly. The genome sequence will also help efforts to combat the beetle Emerald Ash Borer, which has killed hundreds of millions of ash trees in North America.

Distinctive Brain Pattern May Underlie Dyslexia; Study Suggests Reduced Plasticity Could Account for Reading Difficulties

A distinctive neural signature found in the brains of people with dyslexia may explain why these individuals have difficulty learning to read, according to a new study from MIT neuroscientists. The researchers discovered that in people with dyslexia, the brain has a diminished ability to acclimate to a repeated input — a trait known as neural adaptation. For example, when dyslexic students see the same word repeatedly, brain regions involved in reading do not show the same adaptation seen in typical readers. This suggests that the brain’s plasticity, which underpins its ability to learn new things, is reduced, says John Gabrieli, Ph.D., the Grover M. Hermann Professor in Health Sciences and Technology, a Professor of Brain and Cognitive Sciences, and a member of MIT’s McGovern Institute for Brain Research. “It’s a difference in the brain that’s not about reading per se, but it’s a difference in perceptual learning that’s pretty broad,” says Dr. Gabrieli, who is the study’s senior author. “This is a path by which a brain difference could influence learning to read, which involves so many demands on plasticity.” Former MIT graduate student Tyler Perrachione, Ph.D., who is now an Assistant Professor at Boston University, is the lead author of the study, which was pubished in the December 21, 2016 issue of Neuron. The open-access article is titled “Dysfunction of Rapid Neural Adaptation in Dyslexia” The MIT team used magnetic resonance imaging (MRI) to scan the brains of young adults with and without reading difficulties as they performed a variety of tasks. In the first experiment, the subjects listened to a series of words read by either four different speakers or a single speaker.

December 24th

Cryo-EM Work Reveals Structure of BK Potassium Channel

New research from Dr. Roderick MacKinnon’s Laboratory of Molecular Neurobiology and Biophysics at The Rockefeller University has determined, for the first time, the complete structure of an ion channel that plays an important role in cellular electrical signaling by sending potassium ions out of the cell at an extremely rapid rate. By revealing new insights into how the molecule works, this research leads to a deeper understanding of the link between the membrane and processes inside the cell, including calcium regulation of electrical signals, which is central to muscle contraction and neural activity. The results are described in two papers “Cryo-EM structure of the Open High-Conductance Ca2+-Activated K+ Channel” and “Structural Basis for Gating the High-Conductance Ca2+-Activated K+ Channel”) published online in Nature on December 14, 2016. Potassium channels both regulate the occurrence of electrical impulses and terminate the impulses once they are generated. One such potassium channel, known as the BK or “big potassium” channel, conducts ions up to a level 20 times that of other potassium channels. To do so, BK responds to two separate triggers—electrical activity on the cell membrane and levels of calcium—that it ties together. When BK malfunctions, cells can become too active because they can’t turn off their electrical impulses. This contributes to diseases such as hypertension, a hereditary form of asthma, and overactive bladder, in which smooth muscles in the vascular system, airway, or bladder are overactive. Dr. MacKinnon began trying to work out the structure of this channel, including the tunnel-like pore through which the ions travel, about 15 years ago; but new imaging technology has only just now made this effort feasible.

Genetic Cause Identified for Previously Unrecognized Developmental Disorder

An international team of scientists has identified variants of the gene EBF3 causing a developmental disorder with features in common with autism. Identification of these gene variants leads to a better understanding of these complex conditions and opens the possibility of diagnosing other previously undiagnosed patients with similar clinical disorders. The study was published online on December 22, 2016 in the American Journal of Human Genetics. The article is titled “A Syndromic Neurodevelopmental Disorder Caused by De Novo Variants in EBF3.” “We investigate the genetic causes of complex neurological conditions of various types, such as autism spectrum disorders and intellectual disability," said first author Dr. Hsiao-Tuan Chao, Postdoctoral Research Fellow of Pediatric-Neurology at Baylor College of Medicine. "Such conditions are long-lasting, manifest very early in life and range from mild to severe. They can affect different neurological functions; however, sometimes they have overlapping similarities. For many of these conditions there is no definite diagnosis, treatments are limited, and there is no cure." Dr. Chao and colleagues have taken a step toward better understanding some of these conditions. They discovered new mutations of the gene EBF3 in three patients presenting with a newly described syndrome. "The patients' main features include developmental delay, coordination problems, limited facial expressions at an early age, and abnormal verbal communication and social behaviors. They can also present with repetitive motor movements, high threshold to pain, and cognitive impairments," said Dr. Chao.

NIAID Research Aids Discovery of Genetic Immune Disorder; CD70 Deficiency Increases Patients' Risk Of Epstein-Barr Virus Infection and EBV-Related Cancer

Investigators at the National Institutes of Health (NIH) and international colleagues have identified a genetic immune disorder characterized by increased susceptibility and poor immune control of Epstein-Barr virus (EBV) and, in some cases, an EBV-associated cancer called Hodgkin's lymphoma. The researchers studied two unrelated sets of siblings with similar immune problems and determined their symptoms were likely caused by a lack of CD70, a protein found on the surface of several types of immune cells. Scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH, conducted the research with an international team of collaborators. Both sets of siblings had evidence of uncontrolled infection with EBV, a common and usually mild virus, which resulted in the development of Hodgkin's lymphoma in three of these children. Each child also had other immune symptoms, such as reduced activity of pathogen-fighting T cells, low production of antibodies, and poor activation of antibody-producing B cells. The researchers analyzed the genomes of all four children and found that each had two mutated copies of the CD70 gene, resulting in nonfunctioning or nonexistent CD70 proteins. All four parents, who had healthy immune systems, had only one copy of the mutation--indicating that CD70 deficiency follows an autosomal recessive pattern of inheritance. This means affected individuals receive a flawed gene from each parent in order to have symptoms. While no specific treatment for CD70 deficiency currently exists, each of the four children has recovered from Hodgkin's lymphoma and is receiving antibody infusions to help bolster the immune system. This work also offers insight into the normal role of CD70.

“Ant-Like” Bees Among New Desert Species Identified by Utah State University Entomologist; Solitary Bees Appear to Be Important Pollinators of Native Crinklemat Plants

Though declines in bee populations have heightened awareness of the importance of pollinating insects to the world's food supply, numerous bee species remain undescribed or poorly understood. Utah State University entomologist Zach Portman studies a diverse group of solitary, desert bees that aren't major pollinators of agricultural crops, but fill an important role in natural ecosystems of the American Southwest, including the sizzling sand dunes of California's Death Valley. With Terry Griswold, Ph.D., of the USDA-ARS Pollinating Insects Research Unit at Utah State and John Neff, Ph.D., of the Central Texas Melittological Institute in Austin, Portman reports nine, newly identified species of the genus Perdita in the December 23, 2016, issue of Zootaxa. The articled is titled “Taxonomic Revision of Perdita Subgenus Heteroperdita Timberlake (Hymenoptera: Andrenidae), with Descriptions of Two Ant-Like Males.” Unexpected finds include the curious ant-like males of two of the species, which are completely different in appearance from their mates. "It's unclear why these males have this unique form, but it could indicate they spend a lot of time in the nest," Portman says. "We may find more information as we learn more about their nesting biology." Some of these bees, found exclusively in North America, sport scientific names inspired by Shakespearean characters, such as Perdita titania, named for the fairy queen from A Night's Dream. Elusive and tiny, Portman tracks the bees by watching for their buzzing shadows in the blinding, midday sunlight the diminutive insects tend to favor.

December 23rd

Fungus-Infecting Virus Could Help Track Spread of White-Nose Syndrome in Bats

A newly discovered virus infecting the fungus that causes white-nose syndrome in bats could help scientists and wildlife agencies track the spread of the disease that is decimating bat populations in the United States, a new study suggests. Regional variations in this virus could provide clues that would help researchers better understand the epidemiology of white-nose syndrome, according to Marilyn Roossinck, Professor of Plant Pathology and Environmental Microbiology, College of Agricultural Sciences, Penn State. White-nose syndrome is a particularly lethal wildlife disease, killing an estimated 6 million bats in North America since it was identified in 2006. The disease, caused by the fungus Pseudogymnoascus destructans, was first found in New York and now has spread to 29 states and four Canadian provinces. Although several species of bats have been affected, some of the most prevalent species in the Northeast -- such as little brown bats -- have suffered estimated mortality as high as 99 percent. These losses have serious ecological implications. For instance, bats have a voracious appetite for insects and are credited with helping to control populations of mosquitoes and some agricultural pests. The researchers examined 62 isolates of the fungus, including 35 from the United States, 10 from Canada, and 17 from Europe, with the virus infection found only in North American samples. P. destructans is clonal, meaning it is essentially identical everywhere it has been found in North America, making it difficult to determine how it is moving, said Dr. Roossinck, who is also affiliated with Penn State's Center for Infectious Disease Dynamics. "But the virus it harbors has quite a bit of variation," she said. "For example, in all the fungal isolates from Pennsylvania we analyzed, the viruses are similar.

Genomic Sequencing Illuminates Recent Shigella Outbreaks in California; Researchers ID Genes Associated With Toxin Production and Antibiotic Resistance

In a study that could have significant impact on how disease outbreaks are managed, researchers at UC Davis and the California Department of Public Health (CDPH) have sequenced and analyzed genomes from Shigella sonnei (S. sonnei) bacteria associated with major shigellosis outbreaks in California in 2014 and 2015. The results offer new insights into how the bacteria acquired virulence and antibiotic resistance genes, as well as the California strains' relationships to other strains around the world. This was the first major, whole-genome study of S. sonnei strains found in North America. The research was published in online on December 21, 2016 in the journal mSphere. The open-access article is titled “Recent Outbreaks of Shigellosis in California Caused by Two Distinct Populations of Shigella sonnei with Either Increased Virulence or Fluoroquinolone Resistance.” "If you have an outbreak and you want to know what is causing a particular problem, like antibiotic resistance, sequencing the genome can identify the genes involved," said Dr. Jonathan Eisen, Professor with appointments in the Department of Medical Microbiology and Immunology and the Department of Evolution and Ecology at UC Davis and a collaborator on the study. "Eventually, we should be able to sequence whole genomes of bacteria to support patient care," he said.