The Integrated Stress Response and Phosphorylated Eukaryotic Initiation Factor 2α in Neurodegeneration.

The proposed molecular mechanisms underlying neurodegenerative pathogenesis are varied, precluding the development of effective therapies for these increasingly prevalent disorders. One of the most consistent observations across neurodegenerative diseases is the phosphorylation of eukaryotic initiation factor 2α (eIF2α). eIF2α is a translation initiation factor, involved in cap-dependent protein translation, which when phosphorylated causes global translation attenuation.

Is It Anxiety or Arousal That Can Facilitate Musical Performance?

Is it anxiety or arousal that can facilitate musical performance? This is a complicated question that begs for clarification. This letter is an attempt to dig into the issue by framing some of the core questions that will hopefully lead to a greater understanding.

BACE1 Mediates HIV-Associated and Excitotoxic Neuronal Damage Through an APP-Dependent Mechanism.

HIV-associated neurocognitive disorders (HANDs) share common symptoms with Alzheimer's disease (AD), which is characterized by amyloid-β (Aβ) plaques. Plaques are formed by aggregation of Aβ oligomers, which may be the toxic species in AD pathogenesis, and oligomers are generated by cleavage of amyloid precursor protein (APP) by β-site amyloid precursor protein cleaving enzyme 1 (BACE1). BACE1 inhibitors reverse neuronal loss and cognitive decline in animal models of AD.

HIV Protease Inhibitors Alter Amyloid Precursor Protein Processing via β-Site Amyloid Precursor Protein Cleaving Enzyme-1 Translational Up-Regulation.

Mounting evidence implicates antiretroviral (ARV) drugs as potential contributors to the persistence and evolution of clinical and pathological presentation of HIV-associated neurocognitive disorders in the post-ARV era. Based on their ability to induce endoplasmic reticulum (ER) stress in various cell types, we hypothesized that ARV-mediated ER stress in the central nervous system resulted in chronic dysregulation of the unfolded protein response and altered amyloid precursor protein (APP) processing. We used in vitro and in vivo models to show that HIV protease inhibitor (PI) class ARVs induced neuronal damage and ER stress, leading to PKR-like ER kinase-dependent phosphorylation of the eukaryotic translation initiation factor 2α and enhanced translation of β-site APP cleaving enzyme-1 (BACE1).

Altered Oligodendrocyte Maturation and Myelin Maintenance: The Role of Antiretrovirals in HIV-Associated Neurocognitive Disorders.

Despite effective viral suppression through combined antiretroviral therapy (cART), approximately half of HIV-positive individuals have HIV-associated neurocognitive disorders (HAND). Studies of antiretroviral-treated patients have revealed persistent white matter abnormalities including diffuse myelin pallor, diminished white matter tracts, and decreased myelin protein mRNAs. Loss of myelin can contribute to neurocognitive dysfunction because the myelin membrane generated by oligodendrocytes is essential for rapid signal transduction and axonal maintenance.

Two N-terminal acetyltransferases antagonistically regulate the stability of a nod-like receptor in Arabidopsis.

Nod-like receptors (NLRs) serve as immune receptors in plants and animals. The stability of NLRs is tightly regulated, though its mechanism is not well understood. Here, we show the crucial impact of N-terminal acetylation on the turnover of one plant NLR, Suppressor of NPR1, Constitutive 1 (SNC1), in Arabidopsis thaliana.

Orientation of actin filaments in teleost retinal pigment epithelial cells, and the effect of the lectin, Concanavalin A, on melanosome motility.

Retinal pigment epithelial cells of teleosts contain numerous melanosomes (pigment granules) that exhibit light-dependent motility. In light, melanosomes disperse out of the retinal pigment epithelium (RPE) cell body (CB) into long apical projections that interdigitate with rod photoreceptors, thus shielding the photoreceptors from bleaching. In darkness, melanosomes aggregate through the apical projections back into the CB.

Antiretroviral drugs induce oxidative stress and neuronal damage in the central nervous system.

HIV-associated neurocognitive disorder (HAND), characterized by a wide spectrum of behavioral, cognitive, and motor dysfunctions, continues to affect approximately 50 % of HIV(+) patients despite the success of combination antiretroviral drug therapy (cART) in the periphery. Of note, potential toxicity of antiretroviral drugs in the central nervous system (CNS) remains remarkably underexplored and may contribute to the persistence of HAND in the cART era. Previous studies have shown antiretrovirals (ARVs) to be neurotoxic in the peripheral nervous system in vivo and in peripheral neurons in vitro.

Transportin-SR is required for proper splicing of resistance genes and plant immunity.

Transportin-SR (TRN-SR) is a member of the importin-β super-family that functions as the nuclear import receptor for serine-arginine rich (SR) proteins, which play diverse roles in RNA metabolism. Here we report the identification and cloning of mos14 (modifier of snc1-1, 14), a mutation that suppresses the immune responses conditioned by the auto-activated Resistance (R) protein snc1 (suppressor of npr1-1, constitutive 1). MOS14 encodes a nuclear protein with high similarity to previously characterized TRN-SR proteins in animals.

Current understanding of HIV-associated neurocognitive disorders pathogenesis.

Purpose Of Review: The present review discusses current concepts of HIV-associated neurocognitive disorders (HAND) in the era of antiretroviral therapy (ART). As the HIV epidemic enters its fourth decade (the second decade of ART), research must address evolving factors in HAND pathogenesis. These include persistent systemic and central nervous system (CNS) inflammation, aging in the HIV-infected brain, HIV subtype (clade) distribution, concomitant use of drugs of abuse, and potential neurotoxicity of ART drugs.

MOS11: a new component in the mRNA export pathway.

Nucleocytoplasmic trafficking is emerging as an important aspect of plant immunity. The three related pathways affecting plant immunity include Nuclear Localization Signal (NLS)-mediated nuclear protein import, Nuclear Export Signal (NES)-dependent nuclear protein export, and mRNA export relying on MOS3, a nucleoporin belonging to the Nup107-160 complex. Here we report the characterization, identification, and detailed analysis of Arabidopsis modifier of snc1, 11 (mos11).

Arabidopsis snc2-1D activates receptor-like protein-mediated immunity transduced through WRKY70.

Plant immune receptors belonging to the receptor-like protein (RLP) family contain extracellular leucine-rich repeats (LRRs) and a short cytoplasmic tail linked by a single transmembrane motif. Here, we report the identification of snc2-1D (for suppressor of npr1-1, constitutive 2), a semidominant Arabidopsis thaliana mutant with constitutively activated defense responses. Map-based cloning of snc2-1D showed that it encodes an RLP.

Odor identification ability and self-reported upper respiratory symptoms in workers at the post-9/11 World Trade Center site.

Unlabelled: Following the World Trade Center (WTC) collapse on September 11, 2001, more than 40,000 people were exposed to a complex mixture of inhalable nanoparticles and toxic chemicals. While many developed chronic respiratory symptoms, to what degree olfaction was compromised is unclear. A previous WTC Medical Monitoring and Treatment Program study found that olfactory and nasal trigeminal thresholds were altered by the toxic exposure, but not scores on a 20-odor smell identification test.

Distinct region-specific alpha-synuclein oligomers in A53T transgenic mice: implications for neurodegeneration.

Aggregation of alpha-synuclein (alpha-syn), a process that generates oligomeric intermediates, is a common pathological feature of several neurodegenerative disorders. Despite the potential importance of the oligomeric alpha-syn intermediates in neuron function, their biochemical properties and pathobiological functions in vivo remain vastly unknown. Here we used two-dimensional analytical separation and an array of biochemical and cell-based assays to characterize alpha-syn oligomers that are present in the nervous system of A53T alpha-syn transgenic mice.

RFC3 regulates cell proliferation and pathogen resistance in Arabidopsis.

Replication factor C subunit 3 (RFC3) is one of the small subunits of the RFC complex originally purified from the HeLa cells that is essential for the in vitro replication of Simian virus 40 (SV40). Although RFC has been reported to be involved in DNA replication, DNA repair and check-point control of cell cycle progression in yeast, little is known about the precise function of each subunit of the RFC in plants. We recently reported the identification of , which carries a point mutation leading to plants with enhanced expression of () genes and resistance against the virulent oomycete () Noco2.

Symbolic gestures and spoken language are processed by a common neural system.

Symbolic gestures, such as pantomimes that signify actions (e.g., threading a needle) or emblems that facilitate social transactions (e.

CNS activation and regional connectivity during pantomime observation: no engagement of the mirror neuron system for deaf signers.

Deaf signers have extensive experience using their hands to communicate. Using fMRI, we examined the neural systems engaged during the perception of manual communication in 14 deaf signers and 14 hearing non-signers. Participants passively viewed blocked video clips of pantomimes (e.

Leftward interhemispheric asymmetry of macaque monkey temporal lobe language area homolog is evident at the cytoarchitectural, but not gross anatomic level.

The most marked leftward interhemispheric asymmetry of the human and great ape brain is present in a multisensory association area of the superior temporal gyrus. This cortical region, the planum temporale (part of Brodmann's area 22), has a cytoarchitectural homolog, area Tpt, in Old World monkeys. Reports in non-human primates vary widely in descriptions of area Tpt-associated indices of asymmetry at the gross anatomic level, but such asymmetry has not yet been considered at the cellular level.

Planum parietale of chimpanzees and orangutans: a comparative resonance of human-like planum temporale asymmetry.

We have previously demonstrated that leftward asymmetry of the planum temporale (PT), a brain language area, was not unique to humans since a similar condition is present in great apes. Here we report on a related area in great apes, the planum parietale (PP). PP in humans has a rightward asymmetry with no correlation to the L>R PT, which indicates functional independence.

Communicating bioastronautics research to students, families and the nation.

The National Space Biomedical Research Institute (NSBRI) is supporting the National Aeronautics and Space Administration's (NASA) education mission through a comprehensive Education and Public Outreach Program (EPOP) that communicates the excitement and significance of space biology to schools, families, and lay audiences. The EPOP is comprised of eight academic institutions: Baylor College of Medicine, Massachusetts Institute of Technology, Morehouse School of Medicine, Mount Sinai School of Medicine, Texas A&M University, University of Texas Medical Branch Galveston, Rice University, and the University of Washington. This paper describes the programs and products created by the EPOP to promote space life science education in schools and among the general public.

Evolution of the brainstem orofacial motor system in primates: a comparative study of trigeminal, facial, and hypoglossal nuclei.

The trigeminal motor (Vmo), facial (VII), and hypoglossal (XII) nuclei of the brainstem comprise the final common output for neural control of most orofacial muscles. Hence, these cranial motor nuclei are involved in the production of adaptive behaviors such as feeding, facial expression, and vocalization. We measured the volume and Grey Level Index (GLI) of Vmo, VII, and XII in 47 species of primates and examined these nuclei for scaling patterns and phylogenetic specializations.

Microvascular transplantation of tracheal allografts model in the canine.

The inability to reconstruct extensive and often life-threatening tracheal defects is a clinical dilemma. The objective of this study was to achieve microvascular revascularization and transplantation of long-segment circumferential tracheal allografts in a canine model. Fifteen mongrel dogs were randomly assigned to 5 treatment groups.

Variability of Broca's area homologue in African great apes: implications for language evolution.

The cortical circuits subserving neural processing of human language are localized to the inferior frontal operculum and the posterior perisylvian region. Functional language dominance has been related to anatomical asymmetry of Broca's area and the planum temporale. The evolutionary history of these asymmetric patterns, however, remains obscure.

Microvascular transfer of long tracheal autograft segments in the canine model.

Objective: The reconstruction of long segment tracheal defects represents an unsolved clinical dilemma. Prior attempts to directly revascularize tracheal segments have been unsuccessful. The objective of this study was to evaluate orthotopic autotransplantation of revascularized long tracheal segments in the canine model.