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January 11th

Functional Inhibition of Dopaminergic Neurons by Astrocyte GABA Identified As Core Cause of Parkinson's Disease; Findings Suggest New Form of Treatment for Patients in Early Stages of PD

As many as 7 to 10 million people in the world are thought to live with Parkinson's disease (PD). Being the second most common neurodegenerative disease, PD severely affects patients' quality of life, not just brining movement abnormalities. Despite its prevalence and negative impact, current medical treatments for PD rely on alleviating PD symptoms with little effort to explore ways to reverse the symptoms. It has been firmly believed that abnormal movements of PD begin in the brain where the production of dopamine, a neurotransmitter for movement control, is irreversibly impaired, i.e., in a state of neuronal death. Currently, L-DOPA, a potent PD medication is mainly prescribed to replenish dopamine in the deprived brain. However, such a treatment is symptomatic therapy, rather than a disease-modifying therapy. Long-term use of L-DOPA is well-known to cause serious side effects such as involuntary, erratic, and writhing movements. Led by Dr. C. Justin Lee, along with Dr. Hoon Ryu and Dr. Sang Ryong Jeon, researchers at the Center for Cognition and Sociality within the Institute for Basic Science (IBS), the Korea Institute of Science and Technology (KIST), and the Asan Medical Center (AMC) have discovered a new mechanism for PD pathology. The researchers reported that the symptoms of PD begin when dopaminergic neurons are "non-functional", even before they die off. Though the neuronal death had been till now believed to be the obvious cause of PD, the study found that the movement abnormalities of PD begin in the earlier stage when dopaminergic neurons, though being alive, cannot synthesize dopamine (they are in a “dormant” state). "Everyone has been so trapped in the conventional idea of the neuronal death as the single cause of PD.

January 11th

Specific Insulin-Like Peptide (ILP) Regulates How Beetle “Weapons” Grow; Study Reveals How Larval Nutrition Leads to Differently Sized Mandibles in Broad-Horned Flour Beetles

A scientist from Tokyo Metropolitan University and co-workers have discovered that a specific insulin-like peptide called insulin-like peptide 2 (ILP2) regulates the size of "weapons" in Gnatocerus cornutus beetles in different nutritional environments. They found diminished mandible size when expression of the peptide was suppressed, and that it was specifically expressed in the "fat body,” where beetles store nutrients. This has important implications for understanding how striking growth occurs in different environments for different organisms. The findings were published online on November 27, 2019 in PLOS Biology. The open-access article is titled “A Specific Type of Insulin-Like Peptide Regulates the Conditional Growth of a Beetle Weapon.” From deer antlers to beetle horns, the animal kingdom is full of examples of exaggerated ornaments and weapons which derive from sexual selection. Their growth and size may vary significantly from one specimen to another and give rise to distinct mating tactics like fighting, sneaking, or dispersing to areas with less competition. This variation is often correlated with body size or "condition" in a relationship known as positive allometry. Despite the importance of condition-dependent growth of these features, the mechanism behind how the environment affects the complex development of these observable features remains poorly understood. Insulin-like peptides (ILPs) and growth factors (IGFs) are found in a wide range of both invertebrates and vertebrates, like humans, and are thought to play common roles related to growth and metabolism. Recent work into the genetics of insects has revealed a wide variety of ILPs playing different functional roles. Examples include fruit flies which have 8 ILPs, pea aphids with 10 ILPs, and silkworms with over 40 ILPs.

Speech-Disrupting Brain Disease (Primary Progressive Aphasia), Reflects Patients' Native Tongue, UCSF/San Raffaele Study Finds ; Dementia-Related Language Symptoms Differ in Italian and English Speakers

English and Italian speakers with dementia-related language impairment experience distinct kinds of speech and reading difficulties based on features of their native languages, according to new research by scientists at the University of California SanFrancisco (UCSF) Memory and Aging Center (https://memory.ucsf.edu/) and colleagues at the Neuroimaging Research Unit and Neurology Unit at the San Raffaele Scientific Institute in Milan, Italy. Neurologists had long assumed that brain diseases that impact language abilities would manifest in essentially the same way in patients around the world. But recent discoveries have begun to challenge that assumption. For instance, Italian speakers with dyslexia tend to have less severe reading impairment than English or French speakers due to Italian's simpler and more phonetic spelling. "Clinical criteria for diagnosing disorders that affect behavior and language are still mainly based on studies of English speakers and Western cultures, which could lead to misdiagnosis if people who speak different languages or come from another cultural background express symptoms differently," said study senior author Maria Luisa Gorno-Tempini (photo), MD, PhD, a Professor of Neurology and Psychiatry and the Charles Schwab Distinguished Professor in Dyslexia and Neurodevelopment at the UCSF Memory and Aging Center.

January 10th

First-Ever Genome-Scale Study of Puberty Yields Insights into Development and Cancer; Study Includes First-Ever Genomic Analysis of the Testis of Adult Transfemales; May Also Offer Insights into Infertility, Cancer, and Other Diseases

In the first-ever genome-scale analysis of the puberty process in humans, researchers at the Huntsman Cancer Institute (HCI) at the University of Utah outline distinct and critical changes to stem cells in males during adolescence. The scientists further outline how testosterone, and the cells that produce testosterone, impact stem cells in male reproductive organs. The researchers believe this study adds dramatically to a foundation of knowledge that may yield insights into critical areas of human health, including infertility and cellular changes that lead to cancer and other diseases. The study, published online on January 9, 2020 in Cell Stem Cell, was led by Bradley Cairns, PhD, a cancer researcher at HCI and Professor and Chair of Oncological Sciences at the University of Utah, in collaboration with colleagues Jingtao Guo, PhD, a post-doctoral fellow in the Cairns lab at HCI, James Hotaling, MD, Associate Professor of Surgery at the University of Utah, and Anne Goriely, PhD, Associate Professor of Human Genetics at the University of Oxford. The article is titled “The Dynamic Transcriptional Cell Atlas of Testis Development During Human Puberty.” Puberty spurs numerous developmental changes in humans and other mammals. Hallmarks of puberty include physical characteristics easily visible to the naked eye, like rapid growth. These physical and hormonal changes signal the process of a maturing body preparing for reproductive years. In the testis, the male reproductive organ that makes and stores sperm and produces testosterone, puberty introduces monumental changes at a cellular and physiological level.

January 9th

San Francisco State Biology Professor Michael Goldman Receives Two Awards from California State University (CSU) System—One for Exceptional Faculty Service and One for Superb Leadership

BioQuick News has just learned that, on January 5, 2019, one of the publication’s Science & Medicine Advisors, San Francisco State University (SFSU) Professor of Biology and Former SFSU Dean of Biology Michael Goldman (see photo here and below), PhD, was recognized with two separate awards for his exemplary contributions to biotechnology programs in the California State University (CSU) system. Dr. Goldman was the sole recipient of the 2019 Andreoli Faculty Service Award, and he was also only the third recipient in the program’s long history of the CSUPERB Leadership Award, granted to him “in recognition of his dedication to and steady leadership of the CSUPERB community, ushering in an era of growth for the organization,” the selection committee wrote. CSUPERB is the CSU Program for Education & Research in Biotechnology (https://www2.calstate.edu/impact-of-the-csu/research/csuperb). Dr. Goldman has a long history with CSUPERB. Chosen to represent SFSU in the program’s Faculty Consensus Group in 2003, he was elected to the group’s Strategic Planning Council two years later and in 2010 became the chair, a position he held for eight years. He stepped down as chair in 2018, but that hasn’t stopped him from continuing to serve on the Strategic Planning Council. Asked what accomplishments he’s most proud of during his years leading the group, Dr. Goldman has a distinctly student-oriented focus. “We’ve been able to be pretty influential in pushing new ways of learning science such as active learning,” he said, as well as pushing an interdisciplinary focus by broadening representation in CSUPERB beyond biology and biochemistry departments.

January 8th

Relaxin Hormone Reverses Maladaptive Remodeling of Aged Heart by Activating Canonical Wnt Signaling; Discovery May Point to Ways of Treating or Preventing Cardiovascular Disease

As a healthy heart ages, it becomes more susceptible to cardiovascular diseases. Though researchers have discovered that relaxin, an insulin-like hormone, suppresses atrial fibrillation (AF), inflammation, and fibrosis in aged rats, the underlying mechanisms of these benefits are still unknown. In an open-access Scientific Reports article published online on December 6, 2019,, University of Pittsburgh (Pitt) graduate student Brian Martin discusses how relaxin interacts with the body's signaling processes to produce a fundamental mechanism that may have great therapeutic potential. The study, titled "Relaxin Reverses Maladaptive Remodeling of the Aged Heart Through Wnt-Signaling" was led by Guy Salama, PhD, Professor of Medicine at Pitt, and Martin, a graduate student researcher from Swanson School of Engineering's Department of Bioengineering at Pitt. "Relaxin is a reproductive hormone discovered in the early 20th century that has been shown to suppress cardiovascular disease symptoms," said Martin. "In this paper, we show that relaxin treatment reverses electrical remodeling in animal models by activating canonical Wnt signaling, a discovery that reveals a fundamental underlying mechanism behind relaxin's benefits." A better understanding of how relaxin interacts with the body may improve its efficacy as a therapy to treat cardiovascular disease in humans. As the U.S. population ages, the rates of these age-associated diseases are expected to rise, requiring better treatment for this leading cause of death. According to a report (https://healthmetrics.heart.org/wp-content/uploads/2017/10/Cardiovascula... ) from the American Heart Association, the total direct medical costs of cardiovascular disease are projected to increase to $749 billion in 2035.

January 7th

Study of 200,000 Vets Identifies Six Gene Variants Linked to Anxiety and One Is Found Only in African Americans; Study Highlights Advantages of Scale & Diversity in Association Studies; Evidence Also Found for Frequent Co-Morbidity of Anxiety & Depression

A massive genome-wide analysis of approximately 200,000 military veterans has identified six genetic variants linked to anxiety, researchers from Yale and colleagues at other institutions report in an article published online on January 7, 2020, in the American Journal of Psychiatry (https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2019.19030256). The article is titled “Reproducible Genetic Risk Loci for Anxiety: Results from ∼200,000 Participants in the Million Veteran Program.” Some of the variants associated with anxiety had previously been implicated as risk factors for bipolar disorder, post-traumatic stress disorder (PTSD), and schizophrenia. The new study further contributes the first convincing molecular explanation for why anxiety and depression often coexist. "This is the richest set of results for the genetic basis of anxiety to date," said co-lead author Joel Gelernter, MD, the Foundations Fund Professor of Psychiatry, Professor of Genetics and of Neuroscience at Yale. "There has been no explanation for the comorbidity of anxiety and depression and other mental health disorders, but here we have found specific, shared genetic risks." Finding the genetic underpinnings of mental health disorders is the primary goal of the Million Veteran Program (MVP), a compilation of health and genetic data on U.S. military veterans run by the U.S. Veterans Administration. The research team analyzed the program's data and zeroed in on six variants linked to anxiety. Five were found in European Americans and one was found only in African Americans. The findings for the African American participants are especially important, says Dr. Dan Levey, PhD, of the VA Connecticut Healthcare Center and Yale University, and a co-lead author of the study.

ERS Genomics Announces Agreement with New England Biolabs to Commercialize CRISPR Gene Editing Tools and Reagents; License Expands New England Biolabs’ Rights to Use and Sell CRISPR/Cas9 Reagents and Tools

On January 7, 2019, ERS Genomics Limited (Dublin, Ireland), which was formed to provide broad access to the foundational CRISPR/Cas9 intellectual property (IP) co-owned by Dr. Emmanuelle Charpentier, announced it has signed an agreement with New England Biolabs (NEB®) (Ipswich, Massachusetts), a global leader in the discovery and production of enzymes for molecular biology applications, granting NEB rights to sell CRISPR/Cas9 tools and reagents. NEB offers the largest selection of recombinant and native enzymes for genomic research, and continues to expand its product offerings into new areas of research, including genome editing. As a provider of CRISPR/Cas9 reagents and tools, NEB’s license from ERS Genomics expands the Company’s rights to use and sell these technologies. ERS Genomics holds an exclusive worldwide license from Dr. Charpentier to the foundational IP covering CRISPR/Cas9. Companies can obtain licenses to this technology for internal research and commercialization of research tools, kits, reagents and genetically modified cell lines and organisms. “New England Biolabs is a recognized world leader in the discovery and production of enzymes for molecular biology applications,“ stated Eric Rhodes, CEO of ERS Genomics. “Adding CRISPR/Cas9 to the company’s portfolio ensures it can continue to support its customers in the latest areas of technology advancement.

January 6th

European Commission Approves Roche’s Kadcyla for the Adjuvant Treatment of People with HER2-Positive Early Breast Cancer with Residual Invasive Disease After Neoadjuvant Treatment

On December 19, 2019, Roche (SIX: RO, ROG; OTCQX: RHHBY) announced that the European Commission has approved Kadcyla® (trastuzumab emtansine) for the adjuvant (after surgery) treatment of adult patients with HER2-positive early breast cancer (eBC) who have residual invasive disease in the breast and/or lymph nodes after neoadjuvant (before surgery) taxane-based and HER2-targeted therapy. “Optimal treatment is vital for every patient with early-stage breast cancer, a setting where cures are possible,” said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development. “This approval of Kadcyla will allow many more women with HER2-positive early breast cancer to be given a transformative treatment that may cut the risk of their disease returning or progressing." The goal of neoadjuvant treatment is to shrink tumors in order to help improve surgical outcomes. Adjuvant treatment aims to eliminate any remaining cancer cells in the body to help reduce the risk of the cancer returning. People who have residual disease after neoadjuvant treatment have a worse prognosis than those with no detectable disease. The approval of Kadcyla in Europe is based on results from the phase III KATHERINE study, which showed that Kadcyla significantly reduced the risk of invasive breast cancer recurrence or death from any cause (invasive disease-free survival; iDFS) by 50% (HR=0.50, 95% CI 0.39-0.64, p<0.001) compared to Herceptin® (trastuzumab) as an adjuvant treatment in people with HER2-positive eBC who have residual invasive disease after neoadjuvant taxane and Herceptin-based treatment. At three years, 88.3% of people treated with Kadcyla did not have their breast cancer return compared to 77.0% treated with Herceptin, an absolute improvement of 11.3%.

January 5th

NIH Researchers Discover Rare Autoinflammatory Disease (CRIA Syndrome) and Determine Its Biological Cause: Mutations in the RIPK1 Gene; Immunosuppressive Drug (Tocilizumab) Is Effective Treatment in Some Cases

Over the last 20 years, three families have been unsuspectingly linked by an unknown illness. Researchers at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, and other organizations have now identified the cause of the illness, a new disease called CRIA syndrome. The results were published online on December 11, 2019 in Nature. The article is titled “Mutations That Prevent Caspase Cleavage of RIPK1 Cause Autoinflammatory Disease.” NHGRI Scientific Director Daniel Kastner (photo), MD, PhD, a pioneer in the field of autoinflammatory diseases, and his team discovered CRIA, which has symptoms including fevers, swollen lymph nodes, severe abdominal pain, gastrointestinal problems, headaches, and, in some cases, abnormally enlarged spleen and liver. The disorder has characteristics typical of an autoinflammatory disease, where the immune system appears to be activated without any apparent trigger. Although the condition is not life-threatening, patients have persistent fever and swollen lymph nodes from childhood to old age, as well as other symptoms that can lead to lifelong pain and disability. When confronted by the symptoms of patients, who were first seen at the NIH Clinical Center, researchers looked for infections and cancer as the cause. After those were ruled out, they sought answers in the genome, a person’s complete set of DNA. Dr. Kastner and his team sequenced gene regions across the genome and discovered only one gene — RIPK1 — to be consistently different in all patients. The image here depicts the kinase domain of the RIPK1 protein. Researchers identified a specific type of variation in the patients: a single DNA letter at a specific location incorrectly changed. This change can alter the corresponding amino acid added to the encoded protein.