Claudin1 plays a critical role in maintaining the epithelial barrier, and mucus hypersecretion induced by epidermal growth factor receptor (EGFR) activation is a pivotal pathological feature of asthma. The relationship between claudin1 expression and mucus hypersecretion and EGFR activation is still poorly understood. In this report, we showed that claudin1 expression correlated with asthma stage, in both patients with asthma and in the house dust mite (HDM)-induced mouse asthma model. Claudin1 knockdown induced MUC5AC overexpression both in 16HBE cells and in mouse airways. In addition, claudin1 expression negatively correlated with asthma severity as demonstrated by significantly higher MUC5AC expression, more severe airway inflammation, and increased airway hyperreactivity in mouse lungs with claudin1 knockdown following HDM challenge. EGFR activation reduced claudin1 expression and increased MUC5AC expression, both in vitro and in vivo. Erlotinib alleviated murine allergic airway inflammation, restored claudin1 expression and decreased MUC5AC expression. These results suggest that EGFR activation-induced decreases in claudin1 promote goblet-cell metaplasia, and restoring claudin1 to maintain barrier integrity by EGFR antagonism may provide a novel therapeutic strategy for asthma.Studies of marine benthic archaeal communities are updating our view of their taxonomic composition and metabolic versatility. However, large knowledge gaps remain with regard to community assembly processes and inter taxa associations. Here, using 16S rRNA gene amplicon sequencing and qPCR, we investigated the spatiotemporal dynamics, assembly processes, and co-occurrence relationships of the archaeal community in 58 surface sediment samples collected in both summer and winter from across ~1500 km of the eastern Chinese marginal seas. Clear patterns in spatiotemporal dynamics in the archaeal community structure were observed, with a more pronounced spatial rather than seasonal variation. Accompanying the geographic variation was a significant distance-decay pattern with varying contributions from different archaeal clades, determined by their relative abundance. In both seasons, dispersal limitation was the most important process, explaining ~40% of the community variation, followed by homogeneous selection and ecological drift, that made an approximately equal contribution (~30%). This meant that stochasticity rather than determinism had a greater impact on the archaeal community assembly. Furthermore, we observed seasonality in archaeal co-occurrence patterns closer inter-taxa connections in winter than in summer, and unmatched geographic patterns between community composition and co-occurrence relationship. These results demonstrate that the benthic archaeal community was assembled under a seasonal-consistent mechanism but the co-occurrence relationships changed over the seasons, indicating complex archaeal dynamic patterns in coastal sediments of the eastern Chinese marginal seas.CRISPR-Cas systems are considered as barriers to horizontal gene transfer (HGT). However, the influence of such systems on HGT within species is unclear. Also, little is known about the impact of CRISPR-Cas systems on bacterial evolution at the population level. Here, using Bacillus cereus sensu lato as model, we investigate the interplay between CRISPR-Cas systems and HGT at the population scale. We found that only a small fraction of the strains have CRISPR-Cas systems (13.9% of 1871), and most of such systems are defective based on their gene content analysis. Comparative genomic analysis revealed that the CRISPR-Cas systems are barriers to HGT within this group, since strains harboring active systems contain less mobile genetic elements (MGEs), have lower fraction of unique genes and also display limited environmental distributions than strains without active CRISPR-Cas systems. The introduction of a functional CRISPR-Cas system into a strain lacking the system resulted in reduced adaptability to various stresses and decreased pathogenicity of the transformant strain, indicating that B. cereus group strains could benefit from inactivating such systems. Our work provides a large-scale case to support that the CRISPR-Cas systems are barriers to HGT within species, and that in the B. cereus group the inactivation of CRISPR-Cas systems correlated with acquisition of MGEs that could result in better adaptation to diverse environments.An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Skeletal muscle represents the largest pool of body zinc, however, little is known about muscle zinc homeostasis or muscle-specific zinc functions.  https://www.selleckchem.com/products/ch-223191.html  Zip14 (Slc39a14) was the most highly expressed zinc transporter in skeletal muscle of mice in response to LPS-induced inflammation. We compared metabolic parameters of skeletal muscle from global Zip14 knockout (KO) and wild-type mice (WT). At basal steady state Zip14 KO mice exhibited a phenotype that included muscle wasting and metabolic endotoxemia. Microarray and qPCR analysis of gastrocnemius muscle RNA revealed that ablation of Zip14 produced increased muscle p-Mef2c, Hspb7 and miR-675-5p expression and increased p38 activation. ChIP assays showed enhanced binding of NF-[Formula see text] to the Mef2c promoter. In contrast, LPS-induced systemic inflammation enhanced Zip14-dependent zinc uptake by muscle, increased expression of Atrogin1 and MuRF1 and markedly reduced MyoD. These signatures of muscle atrophy and cachexia were not influenced by Zip14 ablation, however. LPS-induced miR-675-3p and -5p expression was Zip14-dependent. Collectively, these results with an integrative model are consistent with a Zip14 function in skeletal muscle at steady state that supports myogenesis through suppression of metabolic endotoxemia and that Zip14 ablation coincides with sustained activity of phosphorylated components of signaling pathways including p-Mef2c, which causes Hspb7-dependent muscle wasting.Motor control in the striatum is an orchestra played by various neuronal populations. Loss of harmony due to dopamine deficiency is considered the primary pathological cause of the symptoms of Parkinson's disease (PD). Recent progress in experimental approaches has enabled us to examine the striatal circuitry in a much more comprehensive manner, not only reshaping our understanding of striatal functions in movement regulation but also leading to new opportunities for the development of therapeutic strategies for treating PD. In addition to dopaminergic innervation, giant aspiny cholinergic interneurons (ChIs) within the striatum have long been recognized as a critical node for balancing dopamine signaling and regulating movement. With the roles of ChIs in motor control further uncovered and more specific manipulations available, striatal ChIs and their corresponding receptors are emerging as new promising therapeutic targets for PD. This review summarizes recent progress in functional studies of striatal circuitry and discusses the translational implications of these new findings for the treatment of PD.