Neural Cell News 13.28 July 24, 2019 | |
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TOP STORYMultiple Sclerosis Attacks Brain’s ‘Projection Neurons’ Brain damage associated with multiple sclerosis specifically targets a common class of brain cells called projection neurons, according to a new international study by scientists at UC San Francisco, Cambridge University, and the University of Heidelberg. [Press release from University of California San Francisco discussing online prepublication in Nature] Press Release | Abstract | Editorial | |
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PUBLICATIONS(Ranked by impact factor of the journal)CAR-T Cells Secreting BiTEs Circumvent Antigen Escape without Detectable Toxicity Investigators developed a bicistronic construct to drive expression of a CAR specific for EGFRvIII, a glioblastoma-specific tumor antigen, and a bispecific T-cell engager (BiTE) against EGFR, an antigen frequently overexpressed in glioblastoma but also expressed in normal tissues. [Nat Biotechnol] Abstract | Editorial An Integrative Model of Cellular States, Plasticity, and Genetics for Glioblastoma Researchers found that malignant cells in glioblastoma exist in four main cellular states that recapitulated distinct neural cell types, were influenced by the tumor microenvironment, and exhibited plasticity. The relative frequency of cells in each state varied between glioblastoma samples and was influenced by copy number amplifications of the CDK4, EGFR, and PDGFRA loci and by mutations in the NF1 locus, which each favored a defined state. [Cell] Abstract | Press Release | Graphical Abstract Nox2 Contributes to Age-Related Oxidative Damage to Neurons and the Cerebral Vasculature Aging WT brains had high levels of angiotensin II (Ang II) and ROS production; activation of ERK1/2, p53, and γH2AX; and losses of capillaries and neurons. However, these abnormalities were markedly reduced in aging Nox2-knockout brains. [J Clin Invest] Full Article | Graphical Abstract Investigators observed that inactivation of DNMT1 in human neural progenitor cells resulted in viable, proliferating cells despite a global loss of DNA CpG-methylation. DNA demethylation led to specific transcriptional activation and chromatin remodeling of evolutionarily young, hominoid-specific LINE-1 elements (L1s), while older L1s and other classes of transposable elements remained silent. [Nat Commun] Full Article | Press Release Live Cell Imaging Reveals 3′-UTR Dependent mRNA Sorting to Synapses Researchers used Rgs4 mRNA to investigate 3′-UTR-dependent transport by MS2 live-cell imaging. The majority of observed RNA granules displayed 3′-UTR independent bidirectional transport in dendrites. Importantly, the Rgs4 3′-UTR caused an anterograde transport bias, which required the Staufen2 protein. [Nat Commun] Full Article | Press Release An Autocrine ActivinB Mechanism Drives TGFβ/Activin Signaling in Group 3 Medulloblastoma The authors demonstrated that an ActivinB autocrine stimulation was responsible for pathway activation in a subset of Group 3 medulloblastoma (MB) characterized by high PMEPA1 levels. Importantly, galunisertib, a kinase inhibitor of the cognate receptors currently tested in clinical trials for glioblastoma patients, showed efficacy on orthotopically grafted MB-PDX. [EMBO Mol Med] Full Article | Press Release | Graphical Abstract Exosomes Regulate Neurogenesis and Circuit Assembly Scientists compared the protein cargo and signaling bioactivity of exosomes released by human induced pluripotent stem cell-derived neural cultures lacking MECP2, a model of the neurodevelopmental disorder Rett syndrome, with exosomes released by isogenic rescue control neural cultures. Quantitative proteomic analysis indicated that control exosomes contained multiple functional signaling networks known to be important for neuronal circuit development. [Proc Natl Acad Sci USA] Full Article | Press Release PI31 Is an Adaptor Protein for Proteasome Transport in Axons and Required for Synaptic Development Inactivation of PI31 inhibited proteasome motility in axons and disrupted synaptic proteostasis, structure, and function. Moreover, phosphorylation of PI31 by p38 MAPK enhanced binding to DYNLL1/2 and promoted the directional movement of proteasomes in axons, suggesting a mechanism to regulate loading of proteasomes onto motors. [Dev Cell] Full Article | Graphical Abstract Proteostasis Is Essential during Cochlear Development for Neuron Survival and Hair Cell Polarity Researchers showed that altered proteostasis consequent to elongator complex deficiency impacted the proper development of the cochlea and resulted in deafness. In the absence of the catalytic subunit Elp3, differentiating spiral ganglion neurons displayed large aggresome-like structures and underwent apoptosis before birth. [EMBO Rep] Abstract | Graphical Abstract FMRP Modulates Neural Differentiation through m6A-Dependent mRNA Nuclear Export Fragile X mental retardation 1 (Fmr1) knockout (KO) mice showed delayed neural progenitor cell cycle progression and extended maintenance of proliferating neural progenitors into postnatal stages, phenocopying methyltransferase Mettl14 conditional KO mice that had no N6-methyladenosine (m6A) modification. [Cell Rep] Full Article | Press Release | Graphical Abstract Synaptogenesis Stimulates a Proteasome-Mediated Ribosome Reduction in Axons Scientists observed in vitro that different synaptogenic inducers triggered an overall decrease of ribosomal proteins and rRNA in the axons of spinal motor neurons. They further observed that this process was dependent on the ubiquitin-proteasome system but not on autophagy. [Cell Rep] Full Article | Graphical Abstract Subscribe to one of our other 19 science newsletters such as Cancer Stem Cell News & ESC & iPSC News. | |
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REVIEWSNeuroinflammation in Frontotemporal Dementia The authors discuss specific evidence of neuroinflammatory mechanisms in frontotemporal dementia (FTD) and describe how advances in the understanding of these mechanisms, in FTD as well as in other neurodegenerative diseases, might facilitate the development and implementation of diagnostic tools and disease-modifying treatments for FTD. [Nat Rev Neurol] Abstract Improving CNS Delivery to Brain Metastases by Blood-Tumor Barrier Disruption Investigators review blood-brain barrier (BBB) physiology and blood-tumor barrier (BTB) pathophysiology. Additionally, they review the limitations of routinely practiced therapies and three current methods being explored for BBB/BTB disruption for improved delivery of chemotherapy to brain tumors. [Trends Cancer] Abstract Visit our reviews page to see a complete list of reviews in the neural cell research field. | |
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INDUSTRY NEWSDiffusion Pharmaceuticals Inc. reported that based on favorable safety data in a 19-patient dose-escalation run-in study, the Data Safety Monitoring Board has recommended the continuation of the company’s Phase III clinical trial with trans sodium crocetinate in inoperable glioblastoma multiforme patients. [Diffusion Pharmaceuticals Inc.] Press Release Orphazyme A/S announced that it has completed enrollment in its Phase III trial evaluating arimoclomol for the treatment of Amyotrophic Lateral Sclerosis ahead of schedule. Headline results from the full analysis remain on track for the first half of 2021. [Orphazyme A/S] Press Release BioXcel Therapeutics, Inc. announced positive top-line results from the adaptive Phase Ib, randomized, double-blind, placebo-controlled, multi-center, US trial, evaluating multiple doses of BXCL501 for acute treatment of agitation in 135 patients with schizophrenia. [BioXcel Therapeutics, Inc.] Press Release Kazia to Test GDC-0084 with Radiotherapy in Phase I Clinical Trial at Leading US Cancer Center Kazia Therapeutics Limited announced that Memorial Sloan Kettering Cancer Center in New York, will investigate the potential use of Kazia’s investigational new drug, GDC-0084, in combination with radiotherapy in a Phase I clinical trial for cancer that has spread to the brain. [Kazia Therapeutics Limited] Press Release Samus Therapeutics Launches PU-AD Clinical Program in Alzheimer’s Disease Samus Therapeutics, Inc. announced the initiation of its clinical program for PU-AD, an oral, brain permeable inhibitor of epichaperomes in Alzheimer’s Disease following clearance of its Investigational New Drug application by the FDA. [Samus Therapeutics, Inc.] Press Release Apic Bio, Inc. announced that the FDA has granted orphan drug designation to APB-102, a gene therapy soon to be in clinical development for the treatment of genetic SOD1 amyotrophic lateral sclerosis. [Apic Bio, Inc. (Business Wire, Inc.)] Press Release The First 3D Models of Parkinson’s, MS Are Headed into Space A group of brain organoids are set to blast off to the International Space Station, the first to model Parkinson’s disease and MS in microgravity. A team of researchers from across the country believes the models could shed light on how brain cells behave in these diseases and uncover new approaches to treat them. [FierceBiotech] Press Release | |
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POLICY NEWSIndonesia’s Strict New Biopiracy Rules Could Stifle International Research Indonesia’s rich biodiversity and complex geology have lured scientists from abroad for centuries. But a law adopted by Indonesia’s parliament may convince some to go elsewhere. The legislation includes strict requirements on foreign scientists doing research in Indonesia, including the need to recruit local collaborators and a near-ban on exporting specimens, along with stiff sanctions, including jail time, for violators. [ScienceInsider] Editorial Mexico’s New President Shocks Scientists with Budget Cuts and Disparaging Remarks A package of harsh austerity measures implemented, has had a deep impact on federally funded laboratories and institutes; it includes a 30% cut to fuel for vehicles and office supplies and a 50% cut to international travel funds and payments to contract workers. Scientists say the cuts are a serious threat to the future of Mexican research. [ScienceInsider] Editorial
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EVENTSNEW Neuroscience 2019 Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Scientific Communications Coordinator (STEMCELL Technologies Inc.) Tenure-Track Assistant Professor – Cognitive Neuroscience (Lawrene University of Wisconsin) Early Stage Researchers – Multiple Sclerosis Research (National University of Ireland Galway) Postdoctoral Fellowship – Neurogenesis & Neural Cell Aging (Lund University) Postdoctoral Fellowship – Bioinformatics & Neurogenesis (Lund University) Postdoctoral Fellowship – Reprogramming Glioblastoma (Lund University) Postdoctoral Scientist – Glioma Organoids (Rutgers Cancer Institute of New Jersey) Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California) Postdoctoral Researcher – Retinal Stem Cell Biology (NIH National Eye Institute) Postdoctoral Research Fellow – Molecular Neuroscience (Fred Hutchinson Cancer Research Center) Postdoctoral Researcher – Brain Cancer Research (University of Alabama at Birmingham) Postdoctoral Position – Neuropsychiatric Disorders (Stanford University) Postdoctoral Position – Retinal Stem Cell Biology (Johns Hopkins University) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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