Vellingkramer5480

BACKGROUND Isolated REM behaviour disorder (iRBD) is a parasomnia, recently recognized as a risk factor for progression to Parkinson's disease, dementia with Lewy Body (DLB) and multiple system atrophy. Biomarker studies in iRBD are relevant due to lack of evidence in this condition. The identification of biomarkers able to predict progression to synucleinopathy diseases is critical for iRBD. FDG-PET imaging might provide information about ongoing neurodegenerative processes. In the present study, we tested for presence of brain hypometabolism patterns, as biomarkers of neurodegeneration in single iRBD individuals. METHODS We recruited 37 polysomnography-confirmed iRBD subjects, with neuropsychological assessment and available FDG-PET scan. Images were analysed with a validated statistical parametric mapping (SPM) procedure, providing individual hypometabolism maps. RESULTS According to the neuropsychological evaluation, 22 iRBD subjects had normal cognition and 15 subjects showed impairments, particularly in visuo-perceptive/visuospatial and memory domains. One/fifth of the cases was impaired at the qualitative scoring of pentagon test. In 32 iRBD, FDG-PET SPM maps revealed significant cerebral hypometabolism and namely, in the occipital lobes (N=5), occipital and cerebellar regions (N=13), occipito-parietal regions (N=13) and a selective cerebellar hypometabolism (N=1). Five cases had normal FDG-PET scans. CONCLUSIONS These imaging findings indicate that brain neurodegenerative processes are present and already detectable in iRBD. The different hypometabolism patterns in the single individuals may reflect specific early pathophysiological events due to the underlying synucleinopathy, with a specific neural vulnerability for the occipital cortex that might predate a risk of progression towards DLB. This article is protected by copyright. All rights reserved.Expression of particular genes in hypothami of ewes was measured across the natural pubertal transition by in situ hybridization. The ewes were allocated to three groups (n = 4); prepubertal, postpubertal and postpubertally gonadectomized (GDX). Prepubertal sheep were euthanized at 20 weeks of age and postpubertal animals at 32 weeks. GDX sheep were also euthanized at 32 weeks, 1 week after surgery. Expression of KISS1, TAC3, PDYN in the arcuate nucleus (ARC), RFRP in the dorsomedial hypothalamus and GNRH1 in the preoptic area was quantified on a cellular basis. KISS1R expression by GNRH1 cells was quantified by double-label in situ hybridization. Across puberty, detectable KISS1 cell number increased in the caudal ARC and whilst PDYN cell numbers were low, numbers increased in the rostral ARC. TAC3 expression did not change but RFRP expression/cell was reduced across puberty. There was no change across puberty in the number of GNRH1 cells that expressed the kisspeptin receptor (KISS1R). GDX shortly after puberty did not increase expression of any of the genes of interest. We conclude that KISS1 expression in the ARC increases during puberty in ewes and this may be a causative factor in the pubertal activation of the reproductive axis. A reduction in expression of RFRP may be a factor in the onset of puberty, removing negative tone on GNRH1 cells. The lack of changes in expression of genes following GDX suggest that the effects of gonadal hormones may differ in young and mature animals. © 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.Dairy records from the Dairy Recording Service of Kenya were classified into low, medium and high production systems based on mean 305-day milk yield using the K-means clustering method. Milk and fertility records were then analysed to develop genetic evaluation systems accounting for genotype-by-environment interaction between the production systems. Data comprised 26,638 lactation yield, 3,505 fat yield, 9,235 age at first calving and 17,870 calving interval records from 12,631 cows which were descendants of 2,554 sires and 8,433 dams. An animal model was used to estimate variance components, genetic correlations and breeding values for the production systems. Variance components increased with production means, apart from genetic group variances, which decreased from the low to the high production system. Moderate heritabilities were estimated for milk traits (0.21-0.27) and fat traits (0.11-0.38). Low heritabilities were estimated for lactation length (0.04-0.10) and calving interval (0.03-0.06). Moderate.BACKGROUND Lipid peroxidation plays a very important role in sickle cell pathophysiology. The formation of malondialdehyde (MDA) in patients with sickle cell disease (SCD) may lead to endothelial dysfunction. Nitric oxide (NO) is a known vasodilator which plays a role in endothelial function. The current study determined the association between MDA and NO metabolites (NOx), trace elements, and antioxidant enzymes (SOD and CAT) in patients with SCD. The ratio of MDA/NOx was also determined as an index of oxidative stress in the study groups. METHODS This was a cross-sectional study involving 90 patients with SCD and 50 "healthy" controls. Blood samples (n = 140) were collected from the study groups. U0126 purchase The plasma, sera, and red cells were kept at -20°C for biochemical analyses. Hemoglobin (Hb) and NOx levels were determined in the plasma using Labsystem Multiskan MS and Griess reagent system, respectively. Super oxide dismutase (SOD) and catalase (CAT) levels were determined in the red cells using assay kits fromnical Laboratory Analysis published by Wiley Periodicals, Inc.Microtubule (MT)-associated proteins regulate the dynamic behavior of MTs during cellular processes. MT severing enzymes are the associated proteins which destabilize MTs by removing subunits from the lattice. One model for how severing enzymes remove tubulin dimers from the MT lattice is by unfolding its subunits through pulling on the carboxy-terminal tails of tubulin dimers. This model stems from the fact that severing enzymes are AAA+ unfoldases. To test this mechanism, we apply pulling forces on the carboxy-terminal regions of MT subunits using coarse grained molecular simulations. In our simulations, we used different MT lattices and concentrations of severing enzymes. We compare our simulation results with data from in vitro severing assays and find that the experimental data is best fit by a model of cooperative removal of protofilament fragments by severing enzymes, which depends on the severing enzyme concentration and placement on the MT lattice. © 2020 Wiley Periodicals, Inc.