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Meldgaard Moos posted an update 1 week, 2 days ago
Mercury (Hg) pollution poses global human health and environmental risks. However, still knowledge gaps exist on both exposures and health effects. Here, we combined transcriptome sequencing technique to further investigate the specific mechanisms of inorganic Hg toxicity in the kidney. Strikingly, transcriptomic analysis revealed that 4174 unigenes (including 2646 upregulated and 1528 downregulated unigenes) were differentially expressed under acute HgCl2 (5 mg/kg) exposure in the kidney. Additionally, we observed that HgCl2 selectively induced tumor necrosis factor superfamily (TNFSF) to participate in renal damage, which was consistent with the high-throughput sequencing data. The phenomenon is accompanied by NLRP3 inflammasome and NF-κB signal activation in the kidney. Simultaneously, ELISA results shown that TNF-α, IL-1β and IL-6 concentrations in the kidney were significant increased. KEGG enrichment analysis showed that peroxisome proliferators-activated receptors (PPAR) signaling pathway might be vital toxic mechanism of Hg in the kidney. Then, our data showed that PPARγ agonist (GW 1929) attenuated HgCl2 (15 μg/ml)-induced apoptosis and NLRP3 inflammasome activation via decreasing translocation of NF-κB and increasing Bcl2 levels in vitro. Along with this, we demonstrated that PPARγ antagonists (GW9662) effectively aggravated HgCl2-induced nephrotoxicity. Overall, our results suggested that PPARγ signaling pathway is considered to be a protective mechanism to combat against HgCl2-triggered NLRP3 inflammasome activation and apoptosis.Exposure to manganese (Mn) can cause male reproductive damage and lead to abnormal secretion of sex hormones. Gonadotropin-releasing hormone (GnRH) plays an important role in the neuromodulation of vertebrate reproduction. Astrocytes can indirectly regulate the secretion of GnRH by binding paracrine prostaglandin E2 (PGE2) specifically to the EP1 and EP2 receptors on GnRH neurons. Prior studies assessed the abnormal secretion of GnRH caused by Mn exposure, but the specific mechanism has not been reported in detail. This study investigated the effects of Mn exposure on the reproductive system of male mice to clarify the role of PGE2 in the abnormal secretion of GnRH in the hypothalamus caused by exposure to Mn. Our data demonstrate that antagonizing the EP1 and EP2 receptors of PGE2 can restore abnormal levels of GnRH caused by Mn exposure. Mn exposure causes reduced sperm count and sperm shape deformities. These findings suggest that EP1 and EP2, the receptors of PGE2, may be the key to abnormal GnRH secretion caused by Mn exposure. Selleckchem Samotolisib Antagonizing the PGE2 receptors may reduce reproductive damage caused by Mn exposure.Recent advances in imaging technology and fluorescent probes have made it possible to gain information about the dynamics of subcellular processes at unprecedented spatiotemporal scales. Unfortunately, a lack of automated tools to efficiently process the resulting imaging data encoding fine details of the biological processes remains a major bottleneck in utilizing the full potential of these powerful experimental techniques. Here we present a computational tool, called PunctaSpecks, that can characterize fluorescence signals arising from a wide range of biological molecules under normal and pathological conditions. Among other things, the program can calculate the number, areas, life-times, and amplitudes of fluorescence signals arising from multiple sources, track diffusing fluorescence sources like moving mitochondria, and determine the overlap probability of two processes or organelles imaged using indicator dyes of different colors. We have tested PunctaSpecks on synthetic time-lapse movies containing mobile fluorescence objects of various sizes, mimicking the activity of biomolecules. The robustness of the software is tested by varying the level of noise along with random but known pattern of appearing, disappearing, and movement of these objects. Next, we use PunctaSpecks to characterize protein-protein interaction involved in store-operated Ca2+ entry through the formation and activation of plasma membrane-bound ORAI1 channel and endoplasmic reticulum membrane-bound stromal interaction molecule (STIM), the evolution of inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ signals from sub-micrometer size local events into global waves in human cortical neurons, and the activity of Alzheimer’s disease-associated β amyloid pores in the plasma membrane. The tool can also be used to study other dynamical processes imaged through fluorescence molecules. The open source algorithm allows for extending the program to analyze more than two types of biomolecules visualized using markers of different colors.Performing in a social context can result in negative feelings when our actions harm another person, but it can also lead to positive feelings when observing an opponent fail. The extent to which individuals scoring high on psychopathic traits, often characterized as self-centered with reduced concern for others’ welfare, are sensitive to own and others’ success and failure is yet unknown. However, knowledge about these processes is crucial for comprehending how these traits are involved in understanding ourselves and others during social interactions. In this functional magnetic resonance imaging (fMRI) study, healthy females scoring low or high on psychopathic traits performed a cannon-shooting game in non-social, cooperative, and competitive contexts. We hypothesized group differences regarding (1) monitoring of own actions in a non-social context (errors that only negatively affect oneself) versus cooperative context (errors that also harm others), (2) successfully performing with either positive (shared t of interventions aimed at normalizing reduced concern for others.Coronavirus disease (COVID-19) is caused by SARS-COV2 and has resulted in more than four million cases globally and the death cases exceeded 300,000. Normally, a range of surviving and propagating host factors must be employed for the completion of the infectious process including RPs. Viral protein biosynthesis involves the interaction of numerous RPs with viral mRNA, proteins which are necessary for viruses replication regulation and infection inside the host cells. Most of these interactions are crucial for virus activation and accumulation. However, only small percentage of these proteins is specifically responsible for host cells protection by triggering the immune pathway against virus. This research proposes RPs extracted from bacillus sp. and yeast as new forum for the advancement of antiviral therapy. Hitherto, antiviral therapy with RPs-involving viral infection has not been widely investigated as critical targets. Also, exploring antiviral strategy based on RPs could be a promising guide for more potential therapeutics.