Neural Cell News Volume 12.22 | Jun 6 2018

TOP STORY

Meet Three New Genes That May Have Influenced Human Brain Size

Three brain development genes are found only in humans and may have helped drive the rapid expansion of the brain starting roughly three million years ago. [Press release from the Howard Hughes Medical Institute discussing online prepublication in Cell] Press Release 1 | Press Release 2 | Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

Human-Specific NOTCH2NL Genes Expand Cortical Neurogenesis through Delta/Notch Regulation

NOTCH2NL promoted the clonal expansion of human cortical progenitors, ultimately leading to higher neuronal output. At the molecular level, NOTCH2NL function by activating the Notch pathway through inhibition of cis Delta/Notch interactions. [Cell] Full Article | Graphical Abstract

A First-in-Human, Phase I Study of Neural Stem Cell Transplantation for Chronic Spinal Cord Injury

Four subjects with T2-T12 spinal cord injury received treatment consisting of removal of spinal instrumentation, laminectomy, and durotomy, followed by six midline bilateral stereotactic injections of human-spinal-cord-derived neural stem cells. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract

Acute and Chronic Neurological Consequences of Early-Life Zika Virus Infection in Mice

Scientists evaluated short- and long-term neuropathological and behavioral consequences of neonatal Zika virus (ZIKV) infection in mice. ZIKV showed brain tropism, causing postnatal-onset microcephaly and several behavioral deficits in adulthood. [Sci Transl Med] Abstract | Press Release

APOE4 Causes Widespread Molecular and Cellular Alterations Associated with Alzheimer’s Disease Phenotypes in Human iPSC-Derived Brain Cell Types

Apolipoprotein E4 (APOE4) neurons exhibited increased synapse number and elevated Aβ42 secretion relative to isogenic APOE3 cells while APOE4 astrocytes displayed impaired Aβ uptake and cholesterol accumulation. Notably, APOE4 microglia-like cells exhibited altered morphologies, which correlated with reduced Aβ phagocytosis. [Neuron] Abstract | Graphical Abstract

Precise Temporal Regulation of Alternative Splicing during Neural Development

Investigators systematically analyzed the temporal regulation of alternative splicing (AS) in a large number of transcriptome profiles of developing mouse cortices, in vivo purified neuronal subtypes, and neurons differentiated in vitro. [Nat Commun] Full Article

Mitochondrial Aging Defects Emerge in Directly Reprogrammed Human Neurons Due To Their Metabolic Profile

Researchers analyzed mitochondrial features in induced neurons (iNs) from individuals of different ages. iNs from old donors displayed decreased oxidative phosphorylation-related gene expression, impaired axonal mitochondrial morphologies, lower mitochondrial membrane potentials, reduced energy production, and increased oxidized proteins levels. [Cell Rep] Full Article | Press Release | Graphical Abstract

The NAD⁺ Precursor Nicotinamide Riboside Rescues Mitochondrial Defects and Neuronal Loss in iPSC and Fly Models of Parkinson’s Disease

Scientists report that increasing NAD⁺ via the NAD⁺ precursor nicotinamide riboside significantly ameliorated mitochondrial function in patient neurons. Human neurons required nicotinamide phosphoribosyltransferase to maintain the NAD⁺ pool and utilized NRK1 to synthesize NAD⁺ from NAD⁺ precursors. [Cell Rep] Full Article | Graphical Abstract

Cross Talk between One-Carbon Metabolism, Eph Signaling, and Histone Methylation Promotes Neural Stem Cell Differentiation

Investigators report a link between the Eph:ephrin cell-cell communication pathway and one-carbon metabolism in controlling neural stem cell differentiation. [Cell Rep] Full Article | Graphical Abstract

The Impact of APP on Alzheimer-Like Pathogenesis and Gene Expression in Down Syndrome iPSC-Derived Neurons

Early-onset Alzheimer disease-like pathology in Down syndrome is commonly attributed to an increased dosage of the amyloid precursor protein (APP) gene. To test this in an isogenic human model, scientists deleted the supernumerary copy of the APP gene in trisomic Down syndrome induced pluripotent stem cells or upregulated APP expression in euploid human pluripotent stem cells using CRISPRa. [Stem Cell Reports] Full Article | Graphical Abstract

Convergent Pathways in Idiopathic Autism Revealed by Time Course Transcriptomic Analysis of Patient-Derived Neurons

Researchers examined the transcriptional differences between induced pluripotent stem cell-derived cortical neurons from patients with idiopathic autism spectrum disorder (ASD) and unaffected controls over a 135-day course of neuronal differentiation. Their data showed ASD-specific misregulation of genes involved in neuronal differentiation, axon guidance, cell migration, DNA and RNA metabolism, and neural region patterning. [Sci Rep] Full Article

Defined Geldrop Cultures Maintain Neural Precursor Cells

By reconstituting selected environmental propertiess in geldrop cultures, scientists showed that neural precursor cells can be maintained stably at high density over an extended period of time. [Sci Rep] Full Article

Safety and Efficacy of Human Embryonic Stem Cell-Derived Astrocytes following Intrathecal Transplantation in SOD1^G93A and NSG Animal Models

Intrathecal injections of the human embryonic stem cell-AS into transgenic hSOD1G93A mice and rats significantly delayed disease onset and improved motor performance compared to sham-injected animals. [Stem Cell Res Ther] Full Article | Press Release

A Proposed Mechanism for Neurodegeneration in Movement Disorders Characterized by Metal Dyshomeostasis and Oxidative Stress

The absence of superoxide dismutase 1 (SOD1) mutations in Parkinson disease highlights mounting evidence that SOD1 mutations are not the sole cause of SOD1 protein misfolding occasioning oligomerization and toxicity, reinforcing the importance of non-genetic factors, including protein metallation and post-translational modification in determining SOD1 stability and function. [Cell Chem Biol] Abstract | Graphical Abstract

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

Interim Results from Clinical Trial of Immunotherapy for Glioblastoma Show Significant Clinical Benefit

Collaborators from organizations including Roswell Park Comprehensive Cancer Center, the Cleveland Clinic and MimiVax LLC share data from their Phase II study of SurVaxM as part of a combination treatment for patients with glioblastoma. [Press release from Roswell Park Comprehensive Cancer Center discussing research presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

FUJIFILM Cellular Dynamics Announces Agreement with University of California, Irvine to Commercialize iPSC-Derived Microglia and Media Formulation

FUJIFILM Cellular Dynamics, Inc. announced that it has entered into an exclusive patent license agreement with the University of California, Irvine (UCI) through its offices at UCI Applied Innovation to license and commercialize UCI’s technologies for derivation of microglia in the commercial research field and also a non-exclusive patent license agreement to commercialize microglia media formulation. [FUJIFILM Cellular Dynamics, Inc.] Press Release

Immunotherapy Clinical Trial Reveals Brain Tumor Shrinkage, Continues with Phase III Study

Following successful Phase I clinical trials, the Toca regimen – a new immunotherapy for patients with recurrent brain cancer – has advanced to a Phase III study, which is currently underway. [Atlantic Health System (Newswise, Inc)] Press Release

Phase II Clinical Study of Elenbecestat Demonstrates Safety and Tolerability in MCI and Mild to Moderate Alzheimer’s Disease at 18-Months

Eisai Co., Ltd. and Biogen Inc. announced that elenbecestat was generally safe and well tolerated in a Phase II clinical study of the oral BACE inhibitor elenbecestat conducted in the United States, and the results demonstrated a statistically significant difference in amyloid beta levels in the brain measured by amyloid-PET. [Eisai Co., Ltd.] Press Release

Scientists Fare Poorly in Super Tuesday Primary Vote

Science-minded candidates seeking seats in the next U.S. Congress took a drubbing from their Democratic opponents in a raft of primary elections across the country. [ScienceInsider] Editorial

Chile, Keen to Become a Knowledge Society, Creates a Ministry of Science

Scientists in Chile have welcomed a decision by Congress to create a science ministry. Many researchers hope that a dedicated ministry will give science more prominence and better-coordinated policies—provided the ministry’s budget matches the government’s ambitions to “bring Chile towards an information and knowledge society,” as Gonzalo Blumel, the country’s minister secretary-general of the presidency, put it in a statement issued after the 31 May vote. [ScienceInsider] Editorial

Europe’s Top Science Funder Shows High-Risk Research Pays Off

A popular and unusual self-review carried out by Europe’s most prestigious science funder is back. The annual assessment, now in its third year, found that nearly one in five projects by the European Research Council led to a scientific breakthrough. [Nature News] Editorial

NEW Gordon Research Conferences: Cell Biology of the Neuron
June 24-29, 2018
Waterville Valley, New Hampshire, United States

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

NEW Postdoctoral Research Scientist – Psychiatric Disorders (Columbia University)

Research Associate – Neural Research (STEMCELL Technologies Inc.)

Project Leader/Director – Neurodegenerative Research (Servier Group)

Postdoctoral Fellows – Neuroscience (Louisiana State University)

Research Associate/Postdoctoral Position – Neurodegenerative Diseases (TU Dresden)

Postdoctoral Fellow – Glioma Genetics/Epigenetics (Heidelberg University)

Research Technician – Neuroscience (Howard Hughes Medical Institute)

Research Fellow/Associate – Neuroscience and Diabetes (Rutgers University)

Postdoctoral Position – Bacterial Virulence Factors (University of California, Irvine)

Postdoctoral Position – Cancer, Immunotherapy, and Fibrosis (University of Alabama at Birmingham)

Postdoctoral Associate – hiPSC-Based Brain Organoids (Rutgers University)

Postdoctoral Position – Pain in Mouse Models of Spinal Cord Injury (Indiana University)

Postdoctoral Position – Spinal Cord Injury (Nanyang Technological University)

Multiple Faculty Positions – Neuroscience and Neuroengineering (Tsinghua University)

Faculty Members – Neuroscience (Mercer University)

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