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Deadly Fungus Threatens Mass Extinction of Salamanders in North America, But Looming Crisis Is Preventable, San Francisco State University-Led Study Shows

A deadly fungus identified in 2013 could devastate native salamander populations in North America unless U.S. officials make an immediate effort to halt salamander importation, according to an urgent new report published in the July 31, 2015 issue of Science. The article is titled “Averting a North American Biodiversity Crisis.” San Francisco State University (SFSU) biologist Dr. Vance Vredenburg, his graduate student Tiffany Yap, and their colleagues at the University of California, Berkeley and the University of California, Los Angeles say the southeastern United States (particularly the southern extent of the Appalachian Mountain range and its southern neighboring region), the Pacific Northwest and the Sierra Nevada, and the central highlands of Mexico are at the highest risk for salamander declines and extinctions if the fatal Batrachochytrium salamandrivorans (Bsal) fungus makes its way into those regions. Salamanders are popular worldwide as pets, and frequently traded across borders. That has scientists worried that the fungus could spread from Asia, where it likely originated, to other parts of the globe. Dr. Vredenburg and his coauthors on the study are asking the U.S. Fish and Wildlife Service to place an immediate ban on live salamander imports to the U.S. until there is a plan in place to detect and prevent the spread of the Bsal fungus. Although the ban has been supported by key scientists for some time, including in a prominent op-ed in the New York Times last year, the government has been slow to act. "This is an imminent threat, and a place where policy could have a very positive effect," Dr. Vredenburg said. "We actually have a decent chance of preventing a major catastrophe."

Harvard Scientists Use Evolutionary Lineage of Adeno-Associated Viruses (AAVs) to Improve Vector Design for Gene Therapy, Particularly for Liver, Muscle, and Retina

Researchers have recreated the evolutionary lineage of adeno-associated viruses (AAVs) for the purpose of reconstructing an ancient viral particle that is highly effective at delivering gene therapies targeting the liver, muscle, and retina. This approach, published on July 30, 2015 in an open-access article in Cell Reports, could be used to design a new class of genetic drugs that are safer and more potent than those currently available. The article is titled “In Silico Reconstruction of the Viral Evolutionary Lineage Yields a Potent Gene Therapy Vector.” "Our novel methodology allows us to understand better the intricate structure of viruses and how different properties arose throughout evolution," says senior study author Dr. Luk H. Vandenberghe of Harvard Medical School. "We believe our findings will teach us how complex biological structures, such as AAVs, are built. From this knowledge, we hope to design next-generation viruses for use as vectors in gene therapy." Viruses need to efficiently transfer their genetic material into host cells in order to replicate and survive. Researchers have taken advantage of this natural property to develop viral vectors, or carriers, capable of shuttling therapeutic genes to the appropriate cells or tissues. Early-stage clinical trials have demonstrated the safety and effectiveness of this approach for treating inherited blindness and hemophilia. But so far, AAVs used for gene therapy have been chosen from naturally circulating viral strains, which patients may already have been exposed to, which means they would have natural immunity. Because natural immunization blocks the transfer of the therapeutic gene, these individuals are often ineligible for gene therapy.

July 29th

High Circulating Levels of Four Specific Proteins Seem to Offer Protection Against Type 1 Diabetes

Patients with type 1 diabetes have significantly lower blood levels of four proteins that help protect their tissue from attack by their immune system, scientists report. Conversely, the patients’ first-degree relatives, who share some of the high-risk genes but do not have the disease, have high levels of these proteins circulating in their blood, said Dr. Jin-Xiong She, Director of the Center for Biotechnology and Genomic Medicine at the Medical College of Georgia (MCG) at Georgia Regents University. Healthy individuals without the risky genes also have higher levels of the four proteins, IL8, IL-1Ra, MCP-1, and MIP-1β, according to the study published online on July 9, 2015 in the Journal of Clinical Endocrinology & Metabolism. The article is titled “Large-Scale Discovery and Validation Studies Demonstrate Significant Reductions in Circulating Levels of IL8, IL-1Ra, MCP-1, and MIP-1 in Type-1 Diabetes Patients.” The findings point toward a sort of protein cocktail that could help at-risk children avoid disease development, as well as new biomarkers in the blood that could aid disease diagnosis, prognosis, and management, said Dr. She, Georgia Research Alliance Eminent Scholar in Genomic Medicine and the study's corresponding author. The scientists looked at a total of 13 cytokines and chemokines, which are cell signaling molecules involved in regulating the immune response. They first looked at blood samples from 697 children with type 1 diabetes and from 681 individuals without antibodies to insulin-producing pancreatic beta cells, a hallmark of this generarally autoimmune disease. The scientists then analyzed the blood of a second and larger set of individuals, which included 1,553 children with type 1 diabetes and 1,493 individuals without any sign of anti-beta-cell antibodies.

Yet Another CRISPR/Cas9 Advance; UCSF & UC-Berkeley Scientists Modify Approach to Edit T-Cells to Disable CXCR4 Receptor for HIV and Also Manage to Knock Out PD-1 Protein That Inhibits T-Cell Attack on Cancers

In a project spearheaded by investigators at the University of California (UC) San Francisco (UCSF), scientists and collaborators have devised a new strategy to precisely modify human T cells using the genome-editing system known as CRISPR/Cas9. Because these immune-system cells play important roles in a wide range of diseases, from diabetes to AIDS to cancer, the achievement provides a versatile new tool for research on T cell function, as well as a path toward CRISPR/Cas9-based therapies for many serious health problems. Using their novel approach, the scientists were able to disable a protein on the T-cell surface called CXCR4, which can be exploited by HIV when the virus infects T cells and causes AIDS. The group also successfully shut down PD-1, a protein that has attracted intense interest in the burgeoning field of cancer immunotherapy, as scientists have shown that using drugs to block PD-1 coaxes T cells to attack tumors. The CRISPR/Cas9 system has captured the imagination of both scientists and the general public, because it makes it possible to easily and inexpensively edit genetic information in virtually any organism. T cells, which circulate in the blood, are an obvious candidate for medical applications of the technology, as these cells not only stand at the center of many disease processes, but could be easily gathered from patients, edited with CRISPR/Cas9, then returned to the body to exert therapeutic effects. But in practice, editing T cell genomes with CRISPR/Cas9 has proved surprisingly difficult, said Alexander Marson, Ph.D., a UCSF Sandler Fellow, and senior and co-corresponding author of the new study. "Genome editing in human T cells has been a notable challenge for the field," Dr. Marson said.

Major European Study Seeks to Reveal the Roles of Mammalian Genes in Disease; Analysis of 320 Mouse Genes Reported; 90% of Mouse Genome Shared with Humans

The role of over 300 mammalian genes (mouse) has been revealed by scientists across Europe in a major initiative to understand the part they play in disease and biology. The results have were published online on July 27, 2015 in Nature Genetics. The article is titled “Deciphering Mammalian Gene Function through Broad-Based Phenotypic Screens across a Consortium of Mouse Clinics.” Because mice share 90 percent of our genes, they play an important role in understanding human genetics. The European Mouse Disease Clinic (EUMODIC) brought together scientists from across Europe to investigate the functions of 320 genes in mice. Over half of these genes had no previously known role, and the remaining genes were poorly understood. In order to study gene function, the EUMODIC consortium produced mouse lines which each had a single gene removed. These mouse lines were then analyzed in mouse clinics, where each line was assessed by a series of tests and investigations, allowing researchers to establish the role of the missing genes. Over 80 percent of the mouse lines assessed had a characteristic that provided a clue to what the missing gene’s role might be. If the mouse fails a hearing test, for example, it suggests the missing gene has a role in hearing. In total, the researchers carried out over 150 different tests on each mouse line. EUMODIC represents the first step towards the creation of a database of all mouse gene functions, a vision now being realized by the International Mouse Phenotyping Consortium (IMPC). The IMPC incorporates 20 centers from across the globe with the aim, over the next ten years, of uncovering the role of all 20,000 genes in the mouse genome.

Glioblastoma Spread Slowed in Mouse Model by Cutting Off Communication Mechanism of Cancer Cells; Gap Junction Targeting May Be Effective Approach to Treatment

The rapid spread of a common and deadly brain tumor has been slowed down significantly in a mouse model by cutting off the way some cancer cells communicate, according to a team of researchers that includes University of Florida (UF) Health faculty. The technique improved survival time by 50 percent when tested in a mouse model, said Loic P. Deleyrolle, Ph.D., a Research Assistant Professor of Neurosurgery in the UF College of Medicine. Researchers focused on disrupting the cell-to-cell communication that allows cancer stem cells to spread. To do that, they targeted a channel that cancer cells use to transfer molecules. By cutting off their communications pathway, it is possible to keep the deadly cells in check, Dr. Deleyrolle said. Eight UF Health researchers took part in the study, which was co-authored by Dr. Deleyrolle and published in an open-access article in the May 19, 2015 issue of Cell Reports. The article is titled “Differential Connexin Function Enhances Self-Renewal in Glioblastoma.” The UF scientists collaborated with researchers at the Cleveland Clinic and the University of California, Berkeley in this research effort. Glioblastoma is the most common brain tumor in adults and there is no effective long-term treatment. Patients usually live for just 12 to 15 months after diagnosis, according to the National Cancer Institute. Glioblastoma tumors, which are highly malignant, typically start in the largest part of the brain and can spread rapidly. The current research focused on connexin 46, a protein that is an essential component of cancer stem cells. Connexin 46 is part of intercellular channels known as a gap junctions. Those intercellular channels, which allow cells to exchange molecules and ions, are crucial to the growth of a glioblastoma tumor, researchers found.

July 28th

Research Shows Different Growth Rates in Two Pygmy Populations Despite Similar Adult Heights; Different Mechanisms at Work; Scientists Conclude That Human Growth Rates Can Change and Evolve Rapidly

While the stature of pygmies is well-suited to tropical rainforests, the mechanisms underlying their growth remain poorly understood. In order to decipher these mechanisms, a team of scientists from the CNRS (Laboratoire Dynamique de l'Evolution Humaine), IRD (Laboratoire Patrimoines Locaux et Gouvernance) and UPMC1 (Centre de Recherche Saint-Antoine) studied a group of Baka pygmies in Cameroon. Their findings revealed that the Baka pygmy growth rate differed completely from that of another pygmy cluster, despite a similar adult height, which implies that small stature appeared independently in the two clusters. This work was published online on July 28, 2015 in an open-accerss article in Nature Communications. The article is titled “Growth Pattern from Birth to Adulthood in African Pygmies of Known Age.” The stature of pygmies has intrigued Westerners since their first encounter with them in 1865. This population is, in fact, made up of several ethnic groups, which belong to two main clusters. One is spread across Equatorial West Africa (Congo, Cameroon, Gabon, Central African Republic, and Western DRC) while the other is found in East Africa, in Eastern DRC and Rwanda. They all live in forested regions, linked with Bantu farmers. Although genetic factors are responsible for the small stature of pygmies, until now, scientists were unable to produce reliable data on their age in order to analyze their growth patterns. Thanks to the registers of the Catholic mission in Moange-le-Bosquet, Cameroon, it was possible, in the current research, to study 500 members of the Baka ethnic group for eight years in order to establish the first growth curves for pygmies. The scientists were thus able to show that although the body size at birth of the Baka was within normal limits, their growth rate then slowed significantly until the age of three years.

July 27th

Much of Polar Bear Y-Chromosome Sequence Is Identified; Study Shows That Two Male Lineages Diverged Over 100,000 Years Ago

For the first time, a team of scientists, led by Professor Axel Janke of the Senckenberg Research Center for Biodiversity and Climate in Franfurt, Germany, has reconstructed part of the male chromosome in polar bears (Ursus maritimus). The scientists were able to assign 1.9 million base pairs specifically to the polar bear Y chromosome. In their study, published online on May 27, 2015 in an open-access article in “Genome Biology and Evolution,” they show that more than 100,000 years ago, the male polar bear lineages split and developed in two separate genetic groups. The article is titled “Genome-Wide Search Identifies 1.9 Megabases from the Polar Bear Y Chromosome for Evolutionary Analyses.” The polar bear is the world’s largest land-dwelling predator and is hard to miss. Nevertheless, it is difficult to study the evolution of this Arctic resident. Polar bears live and die on the frozen sea, and their remains are seldom found. “In order to gain insights into the evolutionary development of Ursus maritimus, we use genetics instead of fossils,” explains Professor Janke. For the first time, the evolutionary geneticist and his Ph.D. student Tobias Bidon, have reconstructed large parts of the polar bear Y chromosome. “In this age of biological revolution, it is possible to sequence the entire genome of an organism rather quickly and cost-effectively,” says Dr. Janke. However, to date, such comprehensive genome projects have mostly been limited to female animals, neglecting the males’ special chromosome – the Y chromosome. Mr. Bidon commented that “this is quite surprising, because the Y chromosome is an important part of the mammalian genome. It is the only genetic material that is passed on from male to male, thereby offering unique insights into the evolutionary history and population dynamics.”

July 26th

DNA Studies Show That Inbreeding Is Likely Not the Cause of Decline in Bighorn Sheep Population in Colorado’s Rocky Mountain National Park

The health of Colorado's bighorn sheep population remains as precarious as the steep alpine terrain the animals inhabit, but a new study led by researchers at the University of Colorado Boulder (CU-Boulder) has found that inbreeding--a common hypothesis for a recent population decline--likely is not to blame. Bighorn herds tend to be small and isolated in their mountain ecosystems, putting the animals at high risk for a genetic "bottleneck," said Catherine Driscoll, a graduate student in the Department of Ecology and Evolutionary Biology at CU-Boulder and lead author of the study. Previous research has shown that inbreeding can weaken a population's immunity to disease across subsequent generations. However, after using mitochondrial DNA data to analyze a diverse set of hereditary markers, researchers found that all five native herds in Colorado’s Rocky Mountain National Park (RMNP) are maintaining healthy levels of genetic variation compared to other bighorn populations across the western United States. "There's been enough gene flow between the herds, primarily due to high ram migration, that the population has been genetically rescued," Ms. Driscoll said. The new findings, which were published in the July 2015 issue of the Journal of Wildlife Management, suggest that other factors, such as nutritional deficiencies, habitat fragmentation, and competition from encroaching mountain goats may play a more significant role in depressing bighorn population growth. The article is titled “A Tale of Two Markers: Population Genetics of Colorado Rocky Mountain Bighorn Sheep Estimated from Microsatellite and Mitochondrial Data.” The researchers used DNA testing to examine genetic diversity across five separate RMNP herds.

Researchers Unravel How TOPLESS Co-Repressor in Plants Interacts with Other Molecules to Turn Genes Off; Work Provides a General Model for Type of Gene Silencing

Scientists at Van Andel Research Institute (VARI), in Grand Rapids, Michigan, have revealed an important molecular mechanism in plants that has significant similarities to certain signaling mechanisms in humans, which are closely linked to early embryonic development and to diseases such as cancer. In plants, as in animals and humans, intricate molecular networks regulate key biological functions, such as development and stress responses. The system can be likened to a massive switchboard--when the wrong switches are flipped, genes can be inappropriately turned on or off, leading to the onset of diseases. Now, VARI scientists have unraveled how an important plant protein, known as TOPLESS, interacts with other molecules responsible for turning genes off. The findings in plants provide a general model across species for this type of gene silencing, which is linked to several vital biological functions in humans. The discovery was published in the July 3, 2015 issue of Science Advances. The article is titled "Structural Basis for Recognition of Diverse Transcriptional Repressors by the TOPLESS Family of Corepressors." This is really a fundamental discovery--our structure shows the co-repressor TOPLESS interacting with key repressor motifs, which constitutes a major component of gene silencing in plants," said Van Andel Research Institute's Karsten Melcher, Ph.D., one of the study's corresponding authors. "Understanding this interaction in plants gives us unique insight into similar pathways in humans that involve these proteins, which are notoriously tough to investigate." Using X-ray crystallography, the team determined the three-dimensional structure of TOPLESS, both on its own and when linked with other molecules responsible for turning genes off, thereby regulating gene expression.