Neural Cell News Volume 11.22 | Jun 7 2017

TOP STORY

Building Better Brains: A Bioengineered Upgrade for Organoids

For the first time, scientists combined organoids with bioengineering. Using small microfilaments, they showed improved tissue architecture that mimicked human brain development more accurately and allowed more targeted studies of brain development and its malfunctions. [Press release from the Institute of Molecular Biotechnology of the Austrian Academy of Sciences discussing online prepublication in Nature Biotechnology] Press Release | Abstract

(Ranked by impact factor of the journal)

Neurodevelopmental Protein Musashi 1 Interacts with the Zika Genome and Promotes Viral Replication

Investigators report that the neural RNA-binding protein Musashi 1 (MSI1) interacts with the Zika genome and enables viral replication. They showed that MSI1 was highly expressed in neural progenitors of the human embryonic brain, and was mutated in individuals with autosomal recessive primary microcephaly. [Science] Full Article | Press Release

Mitochondrial Dynamics Mediated by Mitofusin 1 Is Required for POMC Neuron Glucose-Sensing and Insulin Release Control

Researchers showed that mitochondrial dynamics mediated by Mitofusin 1 (MFN1) in proopiomelanocortin (POMC) neurons couple nutrient sensing with systemic glucose metabolism. Mice lacking MFN1 in POMC neurons exhibited defective mitochondrial architecture remodeling and attenuated hypothalamic gene expression programs during the fast-to-fed transition. [Cell Metab] Abstract | Press Release | Graphical Abstract

Cancer-Induced Anorexia and Malaise Are Mediated by CGRP Neurons in the Parabrachial Nucleus

The authors investigated the contribution to cancer anorexia made by calcitonin gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN) that transmit anorexic signals. They showed that CGRP^PBN neurons were activated in mice implanted with Lewis lung carcinoma cells. Inactivation of CGRP^PBN neurons before tumor implantation prevented anorexia and loss of lean mass, and their inhibition after symptom onset reversed anorexia. [Nat Neurosci] Abstract

Tumor-Associated Macrophages Secrete Pleiotrophin to Promote PTPRZ1 Signaling in Glioblastoma Stem Cells for Tumor Growth

Scientists report that tumor-associated macrophages secrete abundant pleiotrophin (PTN) to stimulate glioma stem cells through its receptor PTPRZ1 thus promoting glioblastoma malignant growth through PTN–PTPRZ1 paracrine signaling. [Nat Commun] Full Article

Loss of Function CHCHD10 Mutations in Cytoplasmic TDP-43 Accumulation and Synaptic Integrity

Researchers made a series of observations utilizing Caenorhabditis elegans models, mammalian cell lines, primary neurons and mouse brains, which demonstrated that CHCHD10 normally exerts a protective role in mitochondrial and synaptic integrity as well as in the retention of nuclear TDP-43, whereas frontotemporal dementia–amyotrophic lateral sclerosis-associated mutations exhibit loss of function phenotypes in C. elegans genetic complementation assays and dominant negative activities in mammalian systems, resulting in mitochondrial/synaptic damage and cytoplasmic TDP-43 accumulation. [Nat Commun] Full Article

Neurog2 and Ascl1 Together Regulate a Postmitotic Derepression Circuit to Govern Laminar Fate Specification in the Murine Neocortex

The proneural genes Neurog2 and Ascl1 cooperate in progenitors to control the temporal switch from neurogenesis to gliogenesis. The authors asked whether these proneural genes also regulate laminar fate transitions. Several defects were observed in the derepression circuit in Neurog2^-/-;Ascl1^-/- mutants: an inability to repress expression of Tbr1 during upper-layer neurogenesis, a loss of Fezf2⁺/Ctip2⁺ layer V neurons, and precocious differentiation of normally late-born, Satb2⁺ layer II-IV neurons. [Proc Natl Acad Sci USA] Full Article

The Alzheimer’s Disease γ-Secretase Generates Higher 42:40 Ratios for β-Amyloid than for p3 Peptides

Sequential cleavage of amyloid precursor protein (APP) by β- and γ-secretases gives rise to full-length β-amyloid (Aβ) and N-terminally truncated Aβ′ whereas cleavage by α- and γ-secretases leads to the shorter p3 peptides. Scientists uncovered significantly higher ratios of 42- versus 40-ending variants for Aβ and Aβ′ than for p3 secreted by mouse neurons and human induced pluripotent stem cell-derived neurons or produced in a cell-free γ-secretase assay with recombinant APP-CTFs. The 42:40 ratio was highest for Aβ′, followed by Aβ and then p3. [Cell Rep] Full Article | Graphical Abstract

Progressive Motor Neuron Pathology and the Role of Astrocytes in a Human Stem Cell Model of VCP-Related ALS

Researchers optimized directed differentiation of induced pluripotent stem cells into highly enriched functional populations of spinal cord motor neurons (MNs) and astrocytes. They identified significantly increased cytoplasmic TDP-43 and ER stress as primary pathogenic events in patient-specific valosin-containing protein (VCP)-mutant MNs, with secondary mitochondrial dysfunction and oxidative stress. [Cell Rep] Full Article | Graphical Abstract

Hypoxia Epigenetically Confers Astrocytic Differentiation Potential on Human Pluripotent Cell-Derived Neural Precursor Cells

Investigators showed that hypoxia confers astrocytic differentiation potential on human neural precursor cells through epigenetic gene regulation. This was achieved by cooperation between hypoxia-inducible factor 1α and Notch signaling, accompanied by a reduction of DNA methylation level in the promoter region of a typical astrocyte-specific gene, glial fibrillary acidic protein. [Stem Cell Reports] Full Article | Graphical Abstract

Cryopreservation Maintains Functionality of Human iPSC Dopamine Neurons and Rescues Parkinsonian Phenotypes In Vivo

Scientists derived midbrain dopamine neurons from human induced pluripotent stem cells (iPSC-mDA) and cryopreserved them in large production lots for biochemical and transplantation studies. Cryopreserved, post-mitotic iPSC-mDA neurons retained high viability with gene, protein, and electrophysiological signatures consistent with midbrain floor-plate lineage. [Stem Cell Reports] Full Article

Modeling Neurodegenerative Diseases with Patient-Derived Induced Pluripotent Cells: Possibilities and Challenges

The authors review findings from induced pluripotent stem cell (iPSC)-based modeling of selected neurodegenerative diseases, including Alzheimer’s disease, frontotemporal dementia and spinocerebellar ataxia. They discuss the possibilities of generating three-dimensional models using the iPSC-derived cells and compare their advantages and disadvantages to conventional two-dimensional models. [N Biotechnol] Abstract

Visit our reviews page to see a complete list of reviews in the neural cell research field.

AFFiRiS Announces Top Line Results of First-in-Human Clinical Study Using AFFITOPE^® PD03A, Confirming Immunogenicity and Safety Profile in Parkinson’s Disease Patients

AFFiRiS AG announced top line results of their pilot Phase I randomized, placebo-controlled, parallel group, patient-blinded, bi-center study, assessing tolerability and safety of repeated subcutaneous administration of two doses of AFFITOPE^® PD03A formulated with adjuvant to patients with early Parkinson’s disease. [Press release from AFFiRiS AG (PR Newswire Association LLC.) discussing research presented at the 21^st International Congress of Parkinson´s Disease and Movement Disorders, Vancouver] Press Release

vTv Therapeutics Completes Enrollment of Part B of Pivotal Phase III STEADFAST Trial Evaluating Azeliragon for the Treatment of Patients with Mild Alzheimer’s Disease

vTv Therapeutics Inc. announced the completion of enrollment for vTv’s Phase III placebo-controlled trial, Single Trial Evaluating Alzheimer’s Disease Following Addition to Symptomatic Therapy (STEADFAST). STEADFAST is evaluating the efficacy and safety of azeliragon, an oral antagonist of the receptor for advanced glycation endproducts, for treatment of mild Alzheimer’s disease. [vTv Therapeutics Inc.] Press Release

Yale School of Medicine Expands Partnership to Promote Clinical Trials and Training in Puerto Rico

An expanded partnership between the Yale School of Medicine and research institutions in Puerto Rico is set to foster collaborative clinical research and training opportunities in both countries. The partnership’s goal is to improve the health of Latino people through clinical research and trials, and to train Latinos in Puerto Rico and the United States to become clinical scientists and health services researchers. [Yale University] Press Release

Trump Retains Collins as NIH Director

President Donald Trump announced that he is keeping Francis Collins as director of the National Institutes of Health (NIH). Collins, who was appointed by former President Barack Obama in 2009, was asked to stay on temporarily after the election. The decision comes despite a recent call from some conservative members of Congress to fire Collins because he supports embryonic stem cell research. Collins has said he would return to full-time research if Trump asked him to step down. [ScienceInsider] Editorial

Romania’s Science Reforms Prompt Boycott

Researchers in Romania are stepping up protests against controversial government science reforms. Hundreds of scientists at leading research institutions say they will refuse to sit on national panels that assess and award grants, after the Romanian researchers’ association Ad Astra called for the boycott. But not all scientists in the country support the move. [Nature News] Editorial

NIH Plan to Reduce Overhead Payments Draws Fire

President Donald Trump’s administration has brought a long-simmering debate over how the U.S. government supports university research back to a boil. In its 2018 budget proposal, the White House proposes cutting so-called indirect cost payments that the National Institutes of Health (NIH) makes to universities, hospitals, and research institutes by about two-thirds, to 10% of each grant. The administration says the change would allow it to redirect about $4.6 billion now spent each year on overhead—including maintaining labs and complying with regulations—to research. [ScienceInsider] Editorial

NEW Growth Hormone/Prolactin Family in Biology and Disease
July 23-28, 2017
Steamboat Springs, Colorado, United States

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Fellow – Neuroscience (State University of New York)

NEW PhD Position – Molecular Biology (Institute of Molecular Biology Mainz)

Postdoctoral Fellow – Applied Neural Interfaces (Florida International University)

Postdoctoral Position – Neuroscience-Neural Engineering (University of California, Los Angeles)

Postdoctoral Scientist – Neural Stem Cell Biology (Institute for Neuroscience of Montpellier)

Faculty Position(s) – Pain Medicine (Southern University of Science and Technology)

Senior/Principle Research Associate – Cell and Molecular Biology (Editas Medicine)

Postdoctoral Fellow – Neuroendocrine Biology of Metabolism (The Scripps Research Institute)

Research Fellow – Neuroscience and Behavioral Disorders (Duke-NUS Medical School)

Postdoctoral Position – Molecular Biology (KU Leuven)

Postdoctoral Researcher – Neuroscience and Imaging (Howard Hughes Medical Institute)

Director – BrainHub (Carnegie Mellon University)

Postdoctoral Researcher – Stem Cell Differentiation (University of Oklahoma)

Postdoctoral Positions – Stem Cell Technology/Neuroscience/Drug Discovery (University of California Davis)

Neuroscientist – Precision Neurotherapeutics (University of California Davis)

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