The vital role of actin and the intermediate filaments in the maintenance of cellular architecture

The cytoskeleton is a system of structural protein primarily involved in the cellular architectural maintenance, intracellular transport, cell division and movement. The classical major components of the cytoskeleton are microtubules, intermediate filaments and microfilaments. Traditionally the microtubules are involved in intracellular transport and organelle structural support. Intermediate filaments provide a rigid structural support to the cell while the microfilaments maintain the cellular surface architectureand support movement and contraction. Emerging evidences however are challenging this classical view of cytoskeleton functions which calls for further investigation. The present study investigates the structural role of the three classical cytoskeletal elements in the maintenance of cell shape and architecture. The study exploits the high resolving power of the confocal microscopy in displaying subcellular components of intact cells, coupled with differential interference imaging. The use of monoclonal antibodies in immunocytochemical staining increases the detection efficiency of the structural details of the cytoskeleton. The present study has empirically demonstrated that actin filaments provide a crucialmechanical support and maintain its contents in space. Intermediate filaments, while they contribute to the cell architectural support theytypically sustain the nucleus and associated structures in spatial proximity inside the cell. Microtubule filaments exhibit no apparent involvement in cellular architecture maintenance. This study has highlighted the specificstructural functions of the classical cytoskeletal elements in which actin filaments play the most important role. These results are important in such areas as cancer research and in pathogen entry and internalization into the cell.Key words: actin, intermediate filaments, microtubules, cell architecture, confocal microscop

Precision Modulation of Neurodegenerative Disease-Related Gene Expression in Human iPSC-Derived Neurons

The ability to reprogram adult somatic cells into induced pluripotent stem cells (iPSCs) and the subsequent development of protocols for their differentiation into disease-relevant cell types have enabled in-depth molecular analyses of multiple disease states as hitherto impossible. Neurons differentiated from patient-specific iPSCs provide a means to recapitulate molecular phenotypes of neurodegenerative diseases in vitro. However, it remains challenging to conduct precise manipulations of gene expression in iPSC-derived neurons towards modeling complex human neurological diseases. The application of CRISPR/Cas9 to mammalian systems is revolutionizing the utilization of genome editing technologies in the study of molecular contributors to the pathogenesis of numerous diseases. Here, we demonstrate that CRISPRa and CRISPRi can be used to exert precise modulations of endogenous gene expression in fate-committed iPSC-derived neurons. This highlights CRISPRa/i as a major technical advancement in accessible tools for evaluating the specific contributions of critical neurodegenerative disease-related genes to neuropathogenesis

Effects of probiotics and paraprobiotics on subjective and objective sleep metrics: A systematic review and meta-analysis

Khalesi, S ORCiD: 0000-0002-8208-2518Inadequate sleep (i.e., duration and/or quality) is becoming increasingly recognized as a global public health issue. Interaction via the gut-brain axis suggests that modification of the gut microbial environment via supplementation with live microorganisms (probiotics) or nonviable microorganisms/microbial cell fractions (paraprobiotics) may improve sleep health. This systematic review and meta-analysis aimed to clarify the effect of consuming probiotics/paraprobiotics on subjective and objective sleep metrics. Online databases were searched from 1980 to October 2019 for studies involving adults who consumed probiotics or paraprobiotics in controlled trials, during which, changes in subjective and/or objective sleep parameters were examined. A total of 14 studies (20 trials) were included in meta-analysis. Random effects meta-analyses indicated that probiotics/paraprobiotics supplementation significantly reduced Pittsburgh Sleep Quality Index (PSQI) score (i.e., improved sleep quality) relative to baseline (−0.78-points, 95% confidence interval: 0.395–1.166; p < 0.001). No significant effect was found for changes on other subjective sleep scales, nor objective parameters of sleep (efficiency/latency) measured using polysomnography or actigraphy. Subgroup analysis for PSQI data suggested that the magnitude of the effect was greater (although not statistically) in healthy participants than those with a medical condition, when treatment contained a single (rather than multiple) strain of probiotic bacteria, and when the duration of treatment was ≥8 weeks. Probiotics/paraprobiotics supplementation may have some efficacy in improving perceived sleep health, measured using the PSQI. While current evidence does not support a benefit of consuming probiotics/paraprobiotics when measured by other subjective sleep scales, nor objective measures of sleep; more studies using well-controlled, within-subject experimental designs are needed. © 2020, The Author(s), under exclusive licence to Springer Nature Limited