-
Wolfe Topp posted an update 11 hours, 48 minutes ago
This novel chronic myocarditis mouse model may allow the identification of the central pathophysiological and immunological processes involved in the progression to DCM.Biological membranes are not only essential barriers that separate cellular and subcellular structures, but also perform other critical functions such as the initiation and propagation of intra- and intercellular signals. Each membrane-delineated organelle has a tightly regulated and custom-made membrane lipid composition that is critical for its normal function. The endoplasmic reticulum (ER) consists of a dynamic membrane network that is required for the synthesis and modification of proteins and lipids. The accumulation of unfolded proteins in the ER lumen activates an adaptive stress response known as the unfolded protein response (UPR-ER). buy JNJ-7706621 Interestingly, recent findings show that lipid perturbation is also a direct activator of the UPR-ER, independent of protein misfolding. Here, we review proteostasis-independent UPR-ER activation in the genetically tractable model organism Caenorhabditis elegans. We review the current knowledge on the membrane lipid composition of the ER, its impact on organelle function and UPR-ER activation, and its potential role in human metabolic diseases. Further, we summarize the bi-directional interplay between lipid metabolism and the UPR-ER. We discuss recent progress identifying the different respective mechanisms by which disturbed proteostasis and lipid bilayer stress activate the UPR-ER. Finally, we consider how genetic and metabolic disturbances may disrupt ER homeostasis and activate the UPR and discuss how using -omics-type analyses will lead to more comprehensive insights into these processes.Carboxylation of bis(pyrazol-1-yl)alkanes by oxalyl chloride was studied. It was found that 4,4′-dicarboxylic derivatives of substrates with electron-donating methyl groups and short linkers (from one to three methylene groups) can be prepared using this method. Longer linkers lead to significantly lower product yields, which is probably due to instability of the intermediate acid chlorides that are initially formed in the reaction with oxalyl chloride. Thus, bis(pyrazol-1-yl)methane gave only monocarboxylic derivative even with a large excess of oxalyl chloride and prolonged reaction duration. An alternative approach involves the reaction of ethyl 4-pyrazolecarboxylates with dibromoalkanes in a superbasic medium (potassium hydroxide-dimethyl sulfoxide) and is suitable for the preparation of bis(4-carboxypyrazol-1-yl)alkanes with both short and long linkers independent of substitution in positions 3 and 5 of pyrazole rings. The obtained dicarboxylic acids are interesting as potential building blocks for metal-organic frameworks.Ammonia detection in ambient air is critical, given its implication on the environment and human health. In this work, an optical fiber tapered to a 20 µm diameter and coated with graphene oxide was developed for absorbance response monitoring of ammonia at visible (500-700 nm) and near-infrared wavelength regions (700-900 nm). The morphology, surface characteristics, and chemical composition of the graphene oxide samples were confirmed by a field emission scanning electron microscope, an atomic force microscope, X-ray diffraction, and an energy dispersion X-ray. The sensing performance of the graphene oxide-coated optical microfiber sensor towards ammonia at room temperature revealed better absorbance response at the near-infrared wavelength region compared to the visible region. The sensitivity, response and recovery times at the near-infrared wavelength region were 61.78 AU/%, 385 s, and 288 s, respectively. The sensitivity, response and recovery times at the visible wavelength region were 26.99 AU/%, 497 s, and 192 s, respectively. The selectivity of the sensor towards ammonia was affirmed with no response towards other gases.Fog computing is an emerging technology. It has the potential of enabling various wireless networks to offer computational services based on certain requirements given by the user. Typically, the users give their computing tasks to the network manager that has the responsibility of allocating needed fog nodes optimally for conducting the computation effectively. The optimal allocation of nodes with respect to various metrics is essential for fast execution and stable, energy-efficient, balanced, and cost-effective allocation. This article aims to optimize multiple objectives using fog computing by developing multi-objective optimization with high exploitive searching. The developed algorithm is an evolutionary genetic type designated as Hyper Angle Exploitative Searching (HAES). It uses hyper angle along with crowding distance for prioritizing solutions within the same rank and selecting the highest priority solutions. The approach was evaluated on multi-objective mathematical problems and its superiority was revealed by comparing its performance with benchmark approaches. A framework of multi-criteria optimization for fog computing was proposed, the Fog Computing Closed Loop Model (FCCL). Results have shown that HAES outperforms other relevant benchmarks in terms of non-domination and optimality metrics with over 70% confidence of the t-test for rejecting the null-hypothesis of non-superiority in terms of the domination metric set coverage.DEAD-box protein 6 (DDX6) is a member of the DDX RNA helicase family that exists in all eukaryotes. It has been extensively studied in yeast and mammals and has been shown to be involved in messenger ribonucleoprotein assembly, mRNA storage, and decay, as well as in miRNA-mediated gene silencing. DDX6 participates in many developmental processes but the biological function of DDX6 in insects has not yet been adequately addressed. Herein, we characterized the LmDDX6 gene that encodes the LmDDX6 protein in Locusta migratoria, a global, destructive pest. LmDDX6 possesses five motifs unique to the DDX6 subfamily. In the phylogenetic tree, LmDDX6 was closely related to its orthologs in Apis dorsata and Zootermopsis nevadensis. RT-qPCR data revealed high expression of LmDDX6 in the ovary, muscle, and fat body, with a declining trend in the ovary after adult ecdysis. LmDDX6 knockdown downregulated the expression levels of the juvenile hormone receptor Met, and genes encoding Met downstream targeted Grp78-1 and Grp78-2, reduced LmVg expression, and impaired ovary development and oocyte maturation.