CRISPR/Cas9 Directed Reprogramming of iPSC for Accelerated Motor Neuron Differentiation Leads to Dysregulation of Neuronal Fate Patterning and Function.

Neurodegeneration causes a significant disease burden and there are few therapeutic interventions available for reversing or slowing the disease progression. Induced pluripotent stem cells (iPSCs) hold significant potential since they are sourced from adult tissue and have the capacity to be differentiated into numerous cell lineages, including motor neurons. This differentiation process traditionally relies on cell lineage patterning factors to be supplied in the differentiation media.

Warning Signs of Potential Black Swan Outbreaks in Infectious Disease.

Black swan events in infectious disease describe rare but devastatingly large outbreaks. While experts are skeptical that such events are predictable, it might be possible to identify the warning signs of a black swan event. Specifically, the initiation of an outbreak, key differentiating features could serve as alerts.

Optimization of Application-Driven Development of Neuromuscular Junction Models.

Neuromuscular junctions (NMJs) are specialized synapses responsible for signal transduction between motor neurons (MNs) and skeletal muscle tissue. Malfunction at this site can result from developmental disorders, toxic environmental exposures, and neurodegenerative diseases leading to severe neurological dysfunction. Exploring these conditions in human or animal subjects is restricted by ethical concerns and confounding environmental factors.

Global transcriptome profile of the developmental principles of in vitro iPSC-to-motor neuron differentiation.

Background: Human induced pluripotent stem cells (iPSC) have opened new avenues for regenerative medicine. Consequently, iPSC-derived motor neurons have emerged as potentially viable therapies for spinal cord injuries and neurodegenerative disorders including Amyotrophic Lateral Sclerosis. However, direct clinical application of iPSC bears in itself the risk of tumorigenesis and other unforeseeable genetic or epigenetic abnormalities.

Resources to Discover and Use Short Linear Motifs in Viral Proteins.

Viral proteins evade host immune function by molecular mimicry, often achieved by short linear motifs (SLiMs) of three to ten consecutive amino acids (AAs). Motif mimicry tolerates mutations, evolves quickly to modify interactions with the host, and enables modular interactions with protein complexes. Host cells cannot easily coordinate changes to conserved motif recognition and binding interfaces under selective pressure to maintain critical signaling pathways.

Fetal regional brain protein signature in FASD rat model.

Fetal alcohol spectrum disorders (FASD) describe neurodevelopmental deficits in children exposed to alcohol in utero. We hypothesized that gestational alcohol significantly alters fetal brain regional protein signature. Pregnant rats were binge-treated with alcohol or pair-fed and nutritionally-controlled.

Mechanisms Underlying Chronic Binge Alcohol Exposure-Induced Uterine Artery Dysfunction in Pregnant Rat.

Background: A cardinal feature of fetal alcohol syndrome is growth restriction. Maternal uterine artery adaptations to pregnancy correlate with birthweight and survival. We hypothesized that gestational binge alcohol exposure impairs maternal uterine vascular function, affecting endothelial nitric oxide (NO)-mediated vasodilation.

Regional dysregulation of taurine and related amino acids in the fetal rat brain following gestational alcohol exposure.

The fetal brain exhibits exquisite alcohol-induced regional neuronal vulnerability. A candidate mechanism for alcohol-mediated brain deficits is disruption of amino acid (AA) bioavailability. AAs are vitally important for proper neurodevelopment, as they comprise the most abundant neurotransmitters in the brain and act as neurotransmitter precursors, nitric oxide donors, antioxidants, and neurotrophic factors, which induce synaptogenesis, neuronal proliferation, and migration.

Placental Proteomics Reveal Insights into Fetal Alcohol Spectrum Disorders.

Background: Fetal alcohol spectrum disorders (FASD) describe many of the well-known neurodevelopmental deficits afflicting children exposed to alcohol in utero. The effects of alcohol on the maternal-fetal interface, especially the placenta, have been less explored. We herein hypothesized that chronic binge alcohol exposure during pregnancy significantly alters the placental protein profile in a rat FASD model.

Chronic binge alcohol consumption during pregnancy alters rat maternal uterine artery pressure response.

We aimed to investigate pressure-dependent maternal uterine artery responses and vessel remodeling following gestational binge alcohol exposure. Two groups of pregnant rats were used: the alcohol group (28.5% wt/v, 6.