Convergent genetic and expression data implicate immunity in Alzheimer's disease

Background Late–onset Alzheimer's disease (AD) is heritable with 20 genes showing genome wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease we extended these genetic data in a pathway analysis. Methods The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (p = 3.27×10-12 after multiple testing correction for pathways), regulation of endocytosis (p = 1.31×10-11), cholesterol transport (p = 2.96 × 10-9) and proteasome-ubiquitin activity (p = 1.34×10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected p 0.002 – 0.05). Conclusions The immune response, regulation of endocytosis, cholesterol transport and protein ubiquitination represent prime targets for AD therapeutics

(Table 2) Vertical fluxes of organic carbon and sediment matter from the photic zone in the Arctic Basin

On the basis of analysis of satellite and field data collected in Russian Arctic Seas maps of distribution of primary production for different months of the vegetation period were compiled. These maps were used to estimate annual primary production of organic carbon: 55 million tons in the Barents Sea; about 20 million tons in the Kara Sea; 10-15 million tons in the Laptev Sea and in the East Siberian Sea, 42 million tons in the Chukchi Sea. In the central and eastern parts of the Barents Sea during the vegetation period values of primary production decreased by factor >5 (from >500 to <100 mg C/m**2/day). By reviewing results of studies with sediment traps vertical fluxes of organic carbon in different regions of the Arctic Basin were estimated. Significant temporal variability of Corg fluxes with maxima during phytoplankton blooms (by 830 mg C/m**2/day) was noted. Typical summer fluxes of Corg are 10-40 mg C/m**2/day in the southern Barents Sea, 1-10 mg C/m**2/day in the northern Barents Sea and in the Kara Sea, and up to 370 mg C/m**2/day in the zone of marginal filters of the Ob and Yenisey rivers

Estimating stress in online meetings by remote physiological signal and behavioral features

Abstract Work stress impacts people’s daily lives. Their well-being can be improved if the stress is monitored and addressed in time. Attaching physiological sensors are used for such stress monitoring and analysis. Such approach is feasible only when the person is physically presented. Due to the transfer of the life from offline to online, caused by the COVID-19 pandemic, remote stress measurement is of high importance. This study investigated the feasibility of estimating participants’ stress levels based on remote physiological signal features (rPPG) and behavioral features (facial expression and motion) obtained from facial videos recorded during online video meetings. Remote physiological signal features provided higher accuracy of stress estimation (78.75%) as compared to those based on motion (70.00%) and facial expression (73.75%) features. Moreover, the fusion of behavioral and remote physiological signal features increased the accuracy of stress estimation up to 82.50%

BK_Ca Activator NS1619 Improves the Structure and Function of Skeletal Muscle Mitochondria in Duchenne Dystrophy

Duchenne muscular dystrophy (DMD) is a progressive hereditary disease caused by the absence of the dystrophin protein. This is secondarily accompanied by a dysregulation of ion homeostasis, in which mitochondria play an important role. In the present work, we show that mitochondrial dysfunction in the skeletal muscles of dystrophin-deficient mdx mice is accompanied by a reduction in K+ transport and a decrease in its content in the matrix. This is associated with a decrease in the expression of the mitochondrial large-conductance calcium-activated potassium channel (mitoBKCa) in the muscles of mdx mice, which play an important role in cytoprotection. We observed that the BKCa activator NS1619 caused a normalization of mitoBKCa expression and potassium homeostasis in the muscle mitochondria of these animals, which was accompanied by an increase in the calcium retention capacity, mitigation of oxidative stress, and improvement in mitochondrial ultrastructure. This effect of NS1619 contributed to the reduction of degeneration/regeneration cycles and fibrosis in the skeletal muscles of mdx mice as well as a normalization of sarcomere size, but had no effect on the leakage of muscle enzymes and muscle strength loss. In the case of wild-type mice, we noted the negative effect of NS1619 manifested in the inhibition of the functional activity of mitochondria and disruption of their structure, which, however, did not significantly affect the state of the skeletal muscles of the animals. This article discusses the role of mitoBKCa in the development of DMD and the prospects of the approach associated with the correction of its function in treatments of this secondary channelopathy

Convergent genetic and expression data implicate immunity in Alzheimer's disease

International audienceBackground Late‐onset Alzheimer's disease (AD) is heritable with 20 genes showing genome‐wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response ( P = 3.27 × 10 −12 after multiple testing correction for pathways), regulation of endocytosis ( P = 1.31 × 10 −11 ), cholesterol transport ( P = 2.96 × 10 −9 ), and proteasome‐ubiquitin activity ( P = 1.34 × 10 −6 ). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002–.05). Conclusions The immune response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics

Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease

BACKGROUND: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.PRINCIPAL FINDINGS: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10-6) and 14 (IGHV1-67 p = 7.9×10-8) which indexed novel susceptibility loci.SIGNIFICANCE: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.</p