Zyxin is a novel interacting partner for SIRT1

<p>Abstract</p> <p>Background</p> <p>SIRT1 is a mammalian homologue of NAD+-dependent deacetylase sirtuin family. It regulates longevity in several model organisms and is involved with cell survival, differentiation, metabolism among other processes in mammalian cells. SIRT1 modulates functions of various key targets via deacetylation. Recent studies have revealed SIRT1 protects neurons from axonal degeneration or neurodegeneration. Further, SIRT1 null mice exhibit growth retardation and developmental defects, suggesting its critical roles in neurons and development.</p> <p>Results</p> <p>To identify novel binding partners for SIRT1 in the central nervous system, we performed yeast two-hybrid screening on human fetal brain cDNA library and found that zyxin is a possible binding partner. SIRT1 and zyxin transcript were both preferentially expressed in developmental mouse brain. Zyxin accumulates in the nucleus where it is co-localized with SIRT1 after treatment with leptomycin B in COS-7 cells. Furthermore, SIRT1 deacetylates zyxin, suggesting SIRT1 could interact with nuclear-accumulated zyxin and modulate its function through deacetylation.</p> <p>Conclusion</p> <p>Zyxin could be a novel interacting partner of SIRT1. Zyxin is an adaptor protein at focal adhesion plaque, regulating cytoskeletal dynamics and signal transduction to convey signal from the ECM (extracellular matrix) to the nucleus. Our results raise the possibility that SIRT1 regulates signal transmission from ECM to the nucleus by modulating the functions of zyxin via deacetylation.</p

Clustering and Classification in Fisheries

This goal of this research is to investigate associations between presences of fish species, space, and time in a selected set of areas in New Zealand waters. In particular we use fish abundance indices on the Chatham Rise from scientific surveys in 2002, 2011, 2012, and 2013. The data are collected in annual bottom trawl surveys carried out by the National Institute of Water and Atmospheric Research (NIWA). This research applies clustering via finite mixture models that gives a likelihood-based foundation for the analysis. We use the methods developed by Pledger and Arnold (2014) to cluster species into common groups, conditional on the measured covariates (body size, depth, and water temperature). The project for the first time applies these methods incorporating covariates, and we use simple binary presence/absence data rather than abundances. The models are fitted using the Expectation-Maximization (EM) algorithm. The performance of the models is evaluated by a simulation study. We discuss the advantages and the disadvantages of the EM algorithm. We then introduce a newly developed function clustglm (Pledger et al., 2015) in R, which implements this clustering methodology, and perform our analysis using this function on the real-life presence/absence data. The results are analysed and interpreted from a biological point of view. We present a variety of visualisations of the models to assist in their interpretation. We found that depth is the most important factor to explain the data

細胞内微視領域での時間分解蛍光分光を目指した低温顕微鏡システムの展開

Tohoku University叶深課

Sirtuins in Neuroendocrine Regulation and Neurological Diseases

Silent information regulator 1 (SIRT1) is a mammalian homolog of the nicotinamide adenine dinucleotide (NAD)-dependent deacetylase sirtuin family. Sirtuin was originally studied as the lifespan-extending gene, silent information regulator 2 (SIRT2) in budding yeast. There are seven mammalian homologs of sirtuin (SIRT1–7), and SIRT1 is the closest homolog to SIRT2. SIRT1 modulates various key targets via deacetylation. In addition to histones, these targets include transcription factors, such as forkhead box O (FOXO), Ku70, p53, NF-κB, PPAR-gamma co-activator 1-alpha (PGC-1α), and peroxisome proliferator-activated receptor γ (PPARγ). SIRT1 has many biological functions, including aging, cell survival, differentiation, and metabolism. Genetic and physiological analyses in animal models have shown beneficial roles for SIRT1 in the brain during both development and adulthood. Evidence from in vivo and in vitro studies have revealed that SIRT1 regulates the cellular fate of neural progenitors, axon elongation, dendritic branching, synaptic plasticity, and endocrine function. In addition to its importance in physiological processes, SIRT1 has also been implicated in protection of neurons from degeneration in models of neurological diseases, such as traumatic brain injury and Alzheimer’s disease. In this review, we focus on the role of SIRT1 in the neuroendocrine system and neurodegenerative diseases. We also discuss the potential therapeutic implications of targeting the sirtuin pathway

KCNJ13 Gene Deletion Impairs Cell Alignment and Phagocytosis in Retinal Pigment Epithelium Derived from Human-Induced Pluripotent Stem Cells

Purpose: The purpose of this study was to establish and analyze a cell model of Leber congenital amaurosis type 16 (LCA16), which is caused by mutations in the KCNJ13 gene encoding Kir7.1, an inward-rectifying potassium ion channel. Methods: The two guide RNAs specific to the target sites in the KCNJ13 gene were designed and KCNJ13 knock-out (KO) human-induced pluripotent stem cells (hiPSCs) were generated using the CRISPR/Cas9 system. The KCNJ13-KO hiPSCs were differentiated into retinal pigment epithelial cells (hiPSC-RPEs). The KCNJ13-KO in hiPSC-RPEs was confirmed by immunostaining. Phagocytic activity of hiPSC-RPEs was assessed using the uptake of fluorescently labeled porcine photoreceptor outer segments (POSs). Phagocytosis-related genes in RPE cells were assessed by quantitative polymerase chain reaction. Results: Most of the translated region of the KCNJ13 gene was deleted in the KCNJ13-KO hiPSCs by the CRISPR/Cas9 system, and this confirmed that the Kir7.1 protein was not present in RPE cells induced from the hiPSCs. Expression of RPE marker genes such as BEST1 and CRALBP was retained in the wild-type (WT) and in the KCNJ13-KO hiPSC-RPE cells. However, phagocytic activity and expression of phagocytosis-related genes in the KCNJ13-null hiPSC-RPE cells were significantly reduced compared to those of WT. Conclusions: We succeeded in generating an RPE model of LCA16 using hiPSCs. We suggest that Kir7.1 is required for phagocytosis of POSs by RPE cells and that impaired phagocytosis in the absence of Kir7.1 would be involved in the retinal degeneration found in LCA16

Selective Transfer of Si Thin-Film Microchips by SiO₂ Terraces on Host Chips for Fluidic Self-Assembly

Fluidic self-assembly is a versatile on-chip integration method. In this scheme, a large number of semiconductor microchips are spontaneously deposited onto a host chip. The host chip typically comprises a Si substrate with an array of pockets at the designated microchip placement sites. In this study, we installed an SiO₂ layer on the terrace region between the pockets of the host chip, to reduce the attraction with the Si microchips. By the SiO₂-topped terrace scheme, we demonstrated a significant enhancement in the deposition selectivity of the Si microchips to the pocket sites, relative to the case of the conventional Si-only host chip. We theoretically explained the deposition selectivity enhancement in terms of the van der Waals interaction. Furthermore, our quantitative analysis implicated a potential applicability of the commonly used interlayer dielectrics, such as HfO₂, silsesquioxanes, and allyl ethers, directly as the terrace component