Production of co-speech gestures in the right hemisphere: Evidence from individuals with complete or anterior callosotomy.

Introduction: A right-hand preference for co-speech gestures in right-handed neurotypical individuals as well as the co-occurrence of speech and gesture has induced neuropsychological research to primarily target the left hemisphere when investigating co-speech gesture production. However, the substantial number of spontaneous left-hand gestures in right-handed individuals has, thus far, been unexplained. Recent studies in individuals with complete callosotomy and exclusive left hemisphere speech production show a reliable left-hand preference for co-speech gestures, indicating a right hemispheric generation.

CARE frailty e-health scale: Association with incident adverse health outcomes and comparison with the Cardiovascular Health Study frailty scale in the NuAge cohort.

Background: This study examines and compares CARE and Cardiovascular Health Study (CHS) frailty states (i.e., robust, prefrail and frail) for their association with incident adverse health outcomes, including falls, depression, cognitive and functional decline, major neurocognitive disorders, hospitalization and mortality in community-dwelling older adults living in the province of Quebec (Canada).

Utility of In Vitro Mutagenesis of RPE65 Protein for Verification of Mutational Pathogenicity Before Gene Therapy.

Importance: Next-generation sequencing can detect variants of uncertain significance (VUSs), for some of which gene therapy would not be advantageous. Therefore, the pathogenicity of compound heterozygous or homozygous variants should be confirmed before bilateral vitrectomy and administration of voretigene neparvovec-rzyl.

Objective: To describe an in vitro mutagenesis assay for assessing the pathogenicity of variants in the RPE65 gene.

Regulating the transcriptomes that mediate the conversion of fibroblasts to various nervous system neural cell types.

Our understanding of the mechanism of cell fate transition during the direct reprogramming of fibroblasts into various central nervous system (CNS) neural cell types has been limited by the lack of a comprehensive analysis on generated cells, independently and in comparison with other CNS neural cell types. Here, we applied an integrative approach on 18 independent high throughput expression data sets to gain insight into the regulation of the transcriptome during the conversion of fibroblasts into induced neural stem cells, induced neurons (iNs), induced astrocytes, and induced oligodendrocyte progenitor cells (iOPCs). We found common down-regulated genes to be mostly related to fibroblast-specific functions, and suggest their potential as markers for screening of the silencing of the fibroblast-specific program.

Huwe1 Regulates the Establishment and Maintenance of Spermatogonia by Suppressing DNA Damage Response.

Spermatogenesis is sustained by a heterogeneous population of spermatogonia that includes the spermatogonial stem cells. However, the mechanisms underlying their establishment from gonocyte embryonic precursors and their maintenance thereafter remain largely unknown. In this study, we report that inactivation of the ubiquitin ligase Huwe1 in male germ cells in mice led to the degeneration of spermatogonia in neonates and resulted in a Sertoli cell-only phenotype in the adult.

H3.1 K36M mutation in a congenital-onset soft tissue neoplasm.

We describe a patient who presented with a congenital soft tissue lesion initially diagnosed as infantile fibromatosis at 15 days of age. Unusually, the mass demonstrated malignant progression leading to death at 20 months of age. Biological progression to malignancy is not known to occur in fibromatosis, and fibrosarcoma is not known to progress from a benign lesion.

MLL5 Orchestrates a Cancer Self-Renewal State by Repressing the Histone Variant H3.3 and Globally Reorganizing Chromatin.

Mutations in the histone 3 variant H3.3 have been identified in one-third of pediatric glioblastomas (GBMs), but not in adult tumors. Here we show that H3.

Nck1 deficiency improves pancreatic β cell survival to diabetes-relevant stresses by modulating PERK activation and signaling.

Increasing evidence strongly supports a critical role for PERK in regulating pancreatic β cell function. In agreement, we previously reported that enhancing PERK basal activity, by silencing the SH domain-containing adaptor protein Nck1 in pancreatic β cells, increased insulin content in a PERK-dependent manner. Here we report that Nck1-deficient MIN6 cells display normal overall morphology while as expected increased number of secretory granules.

USP19 deubiquitinating enzyme inhibits muscle cell differentiation by suppressing unfolded-protein response signaling.

The USP19 deubiquitinating enzyme modulates the expression of myogenin and myofibrillar proteins in L6 muscle cells. This raised the possibility that USP19 might regulate muscle cell differentiation. We therefore tested the effects of adenoviral-mediated overexpression or small interfering RNA (siRNA)-mediated silencing of either the cytoplasmic or endoplasmic reticulum (ER)-localized isoforms of USP19.

USP2 regulates the intracellular localization of PER1 and circadian gene expression.

Endogenous 24-h rhythms in physiology are driven by a network of circadian clocks located in most tissues. The molecular clock mechanism is based on feedback loops involving clock genes and their protein products. Posttranslational modifications, including ubiquitination, are important for regulating the clock feedback mechanism.

Sphingosine 1-phosphate (S1P) induced interleukin-8 (IL-8) release is mediated by S1P receptor 2 and nuclear factor κB in BEAS-2B cells.

The airway epithelium may release pro-inflammatory cytokines and chemokines in the asthmatic airway. Sphingosine 1-phosphate (S1P) is a bioactive lipid, increased in the airways of asthmatics, that may trigger the release of the potent neutrophil chemoattractant Interleukin-8 (IL-8) by epithelial cells. S1P is a ligand for 5 G protein-coupled receptors, S1PR1-5.

Regulation of behavioral circadian rhythms and clock protein PER1 by the deubiquitinating enzyme USP2.

Endogenous 24-hour rhythms are generated by circadian clocks located in most tissues. The molecular clock mechanism is based on feedback loops involving clock genes and their protein products. Post-translational modifications, including ubiquitination, are important for regulating the clock feedback mechanism.

ICOS-expressing CD4 T cells induced via TLR4 in the nasal mucosa are capable of inhibiting experimental allergic asthma.

Modulation of adaptive immune responses via the innate immune pattern recognition receptors, such as the TLRs, is an emerging strategy for vaccine development. We investigated whether nasal rather than intrapulmonary application of Protollin, a mucosal adjuvant composed of TLR2 and TLR4 ligands, is sufficient to elicit protection against murine allergic lower airway disease. Wild-type, Tlr2(-/-), or Tlr4(-/-) BALB/c mice were sensitized to a birch pollen allergen extract (BPEx), then received either intranasal or intrapulmonary administrations of Protollin or Protollin admixed with BPEx, followed by consecutive daily BPEx challenges.

RAB-7 antagonizes LET-23 EGFR signaling during vulva development in Caenorhabditis elegans.

The Rab7 GTPase regulates late endosome trafficking of the Epidermal Growth Factor Receptor (EGFR) to the lysosome for degradation. However, less is known about how Rab7 activity, functioning late in the endocytic pathway, affects EGFR signaling. Here we used Caenorhabditis elegans vulva cell fate induction, a paradigm for genetic analysis of EGFR/Receptor Tyrosine Kinase (RTK) signaling, to assess the genetic requirements for rab-7.

Proteolysis in illness-associated skeletal muscle atrophy: from pathways to networks.

Improvements in health in the past decades have resulted in increased numbers of the elderly in both developed and developing regions of the world. Advances in therapy have also increased the prevalence of patients with chronic and degenerative diseases. Muscle wasting, a feature of most chronic diseases, is prominent in the elderly and contributes to both morbidity and mortality.

TBC-2 regulates RAB-5/RAB-7-mediated endosomal trafficking in Caenorhabditis elegans.

During endosome maturation the early endosomal Rab5 GTPase is replaced with the late endosomal Rab7 GTPase. It has been proposed that active Rab5 can recruit and activate Rab7, which in turn could inactivate and remove Rab5. However, many of the Rab5 and Rab7 regulators that mediate endosome maturation are not known.

Nitration of respiratory epithelial cells by myeloperoxidase depends on extracellular nitrite.

To investigate peroxidase induced 3'-nitrotyrosine (3NT) formation, neutrophil derived myeloperoxidase (MPO) (0.025 microM) was directly administered to A549 epithelial cells with or without H(2)O(2) (150 microM). Little evidence of 3NT was found.

Canadian Association of Neuroscience Review: Respiratory control and behavior in humans: lessons from imaging and experiments of nature.

The purpose of this review is to demonstrate that respiration is a complex behavior comprising both brainstem autonomic control and supramedullary influences, including volition. Whereas some fundamental mechanisms had to be established using animal models, this review focuses on clinical cases and physiological studies in humans to illustrate normal and abnormal respiratory behavior. To summarize, central respiratory drive is generated in the rostroventrolateral medulla, and transmitted to both the upper airway and to the main and accessory respiratory muscles.

Effects of age and clustered hypoxia on [(125)I] substance P binding to neurotachykinin-1 receptors in brainstem of developing swine.

This work focused on the postnatal development of substance P-bound neurotachykinin-1 (NK-1) receptors in the porcine brainstem using 2-3-, 6-11-, 16-18-, and 21-28-day-old piglets versus adult, and on alterations in these receptors after single and six-daily repeated clustered hypoxia using 6-11- and 21-28-day-old piglets. NK-1 receptor localization and densities were determined by quantitative autoradiography using mono-iodinated Bolton-Hunter substance P ([(125)I]BHSP). Slide-mounted brainstem sections, incubated in [(125)I]BHSP and then exposed to film, have shown [(125)I]BHSP binding throughout many brainstem nuclei and tracts, including the ambigual/periambigual (nAmb), dorsal motor vagal (dmnv), gigantocellular (nGC), hypoglossal (nHyp), medial parabrachial (nPBM), lateral reticular (nRL), raphe magnus (nRMg), raphe obscurus (nROb) and solitary tract (nTS) nuclei.