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Autism spectrum disorder (ASD) is a neurodevelopmental disorder caused by genetic and environmental factors. Among the environmental factors, maternal infection is known as one of the principal risk factors for ASD. On the other hand, postmortem studies suggested the relationship of oxidative stress with ASD etiology. However, the role of oxidative stress in the development of ASD remains unclear. Here, we report the involvement of NOX1/NADPH oxidase, an enzyme generating reactive oxygen species (ROS), in behavioral and anatomical abnormalities in a maternal immune activation (MIA) model. In the MIA model of gestational polyinosinic-polycytidylic acid (poly(IC)) exposure, increased serum levels of IL-6 were observed in both wild-type (WT) and Nox1-deficient mice (Nox1KO). Following the comparable induction of MIA in the two genotypes, impairment of social preference and defects in motor coordination were observed in WT offspring but not in offspring deficient in Nox1. MIA up-regulated NOX1 mRNA in the cerebral cortex and cerebellum of the fetus but not in the adult offspring. Although the development of cortical neurons was unaffected by MIA in either genotype, the dropout of Purkinje cells in lobule VII of MIA-affected offspring was significantly ameliorated in Nox1KO. Taken together, these results suggested that NOX1/NADPH oxidase plays an essential role in some behavioral phenotypes observed in ASD, possibly by promoting the loss of Purkinje cells in the cerebellum.Upregulation of C-terminal tensin-like (CTEN) is induced by the activation of epidermal growth factor receptor (EGFR) signaling and mainly contributes to cancer cell migration and invasion. CTEN is known as a downstream target of the EGFR-RAF-MEK-ERK pathway but the regulatory mechanism underlying EGFR signaling regulates the increased expression of CTEN is still incompletely understood. In this study, we investigated the epigenetic regulation of CTEN gene transcription upon EGFR activation. Analyses of chromatin accessibility revealed that the structure of CTEN promoter became more loosed and the acetylation state of the histone tails within the core promoter region was increased after EGF treatment. Moreover, activation of EGFR signaling facilitates histone acetyltransferase p300 to be recruited to CTEN promoter through MEK-ERK pathway. MEK-ERK activation also induces the phosphorylation of p300, thereby enhancing the levels of histone acetylation within CTEN promoter, which in turn upregulates CTEN gene expression. Our work provides new insights into the actions of EGFR signaling to upregulate CTEN, which may lead to the rational design of novel therapeutic approaches.HU, a DNA-binding protein, has a helical N-terminal region (NTR) of ∼44 residues and a beta strand- and IDR-rich C-terminal region (CTR) of ∼46 residues. CTR binds to DNA through (i) a clasp (two arginine/lysine-rich, IDR-rich beta hairpins that bind to phosphate groups in the minor groove), (ii) a flat surface (comprising four antiparallel beta strands that abut the major groove), and (iii) a charge cluster (two lysine residues upon a short C-terminal helix). HU forms a dimer displaying extensive inter-subunit CTR-CTR contacts. selleck kinase inhibitor A single-chain simulacrum of these contacts (HU-Simul) incorporating all DNA-binding elements was created by fusing together the CTRs of Escherichia coli HU-A and Thermus thermophilus HU. HU-Simul is monomeric, binds to dsDNA and cruciform DNA, but not to ssDNA.Single-stranded DNA-binding proteins (SSBs) are essential to cells because they participate in DNA metabolic processes, such as DNA replication, repair, and recombination. Some bacteria possess more than one paralogous SSB. Three similar SSBs, namely, SsbA, SsbB, and SsbC, are found in Staphylococcus aureus. Whether the FDA-approved clinical drug 5-fluorouracil (5-FU) that is used to target the enzyme thymidylate synthase for anticancer therapy can also bind to SSBs remains unknown. In this study, we found that 5-FU could form a stable complex with S. aureus SsbB (SaSsbB). We cocrystallized 5-FU with SaSsbB and solved complex structures to assess binding modes. Two complex forms of the structures were determined, namely, the individual asymmetric unit (two SaSsbB monomers) containing one (PDB entry 7D8J) or two 5-FU molecules (PDB entry 7DEP). The locations of 5-FU in these two SaSsbB complexes were similar regardless of the binding ratio. The structures revealed that residues T12, K13, T30, F48, and N50 of SaSsbB were involved in 5-FU binding. The mutations of T12, K13, and F48 caused the low 5-FU binding activity of SaSsbB, a result consistent with the structural analysis results. Taken together, the complexed structure and the binding mode analysis of SaSsbB extended the anticancer drug 5-FU interactome to include the oligonucleotide/oligosaccharide-binding fold protein.Abnormal crosstalk between gut immune and the liver was involved in nonalcoholic steatohepatitis (NASH). Mice with methionine choline-deficient (MCD) diet-induced NASH presented an imbalance of pro-(IL-6 and IFN-γ) and anti-inflammatory cytokines (IL-10) in the intestine. We also clarified that the ratio of CD4+ T cells and found that the NASH mesenteric lymph node (MLN) presents decreased numbers of CD4+Th17 cells but increased numbers of CD4+CD8+FoxP3+ regulatory T cells (Tregs). Furthermore, the intestinal immune imbalance in NASH was attributed to impaired gut chemokine receptor 9 (CCR9)/chemokine ligand 25 (CCL25) signalling, which is a crucial pathway for immune cell homing in the gut. We also demonstrated that CD4+CCR9+ T cell homing was dependent on CCL25 and that the numbers and migration abilities of CD4+CCR9+ T cells were reduced in NASH. Interestingly, the analysis of dendritic cell (DC) subsets showed that the numbers and retinal dehydrogenase (RALDH) activity of CD103+CD11b+ DCs were decreased and that the ability of these cells to upregulate CD4+ T cell CCR9 expression was damaged in NASH. Taken together, impaired intestinal CCR9/CCL25 signalling induced by CD103+CD11b+ DC dysfunction contributes to the gut immune imbalance observed in NASH.Protein labeling with a functional molecule is a technique widely used for protein research. The covalent reaction of self-labeling peptide tags with synthetic probe-modified small molecules enables tag-fused protein labeling with chemically diverse molecules, including fluorescent probes. We report the discovery, by in vitro directed evolution, of a novel 23-mer dibenzocyclooctyne (DBCO)-reactive peptide (DRP) tag using Systematic Evolution of Ligands by EXponential enrichment (SELEX) with a combination of a reconstituted cell-free translation system (PURE system) and cDNA display. The N- and C-terminal DRP truncations created a shorter 16-mer DBCO-reactive peptide (sDRP) tag without significant reactivity reduction. By fusing the sDRP tag to a model protein, we showed the chemical labeling and in-gel fluorescence imaging of the sDRP-fused protein using a fluorescent DBCO probe. Results showed that sDRP tag-mediated protein labeling has potential for use as a basic molecular tool in a variety of applications for protein research.The tumor suppressor p53 utilizes a facilitated diffusion mechanism to search for and bind to target DNA sequences. Sub-millisecond single-molecule fluorescence tracking demonstrated that p53 forms a short-lived encounter complex to DNA then converts to the long-lived complex that can move and jump along DNA during the target search. To reveal the role of each DNA-binding domain of p53 in these processes, we investigated two p53 mutants lacking either of two DNA-binding domains; structured core and disordered C-terminal domains, using sub-millisecond single-molecule fluorescence microscopy. We found that the C-terminal domain is required for the encounter complex formation and conversion to the long-lived complex. The long-lived complex is stabilized by the core domain as well as the C-terminal domain. Furthermore, only the C-terminal domain participates in the jump of p53 along DNA at a high salt concentration. We propose that the flexible C-terminal domain of p53 is twined around DNA, which can form the encounter complex, convert to the long-lived complex, and enable p53 to land on DNA after the jump.Bone represents the most common site for breast cancer metastasis. Bone is a highly dynamic organ that is constantly adapting to its biophysical environment, orchestrated largely by the resident osteocyte network. Osteocytes subjected to physiologically relevant biophysical conditions may therefore represent a source of key factors mediating breast cancer cell metastasis to bone. Therefore, we investigated the potential proliferative and migratory capacity of soluble factors released by mechanically stimulated osteocytes on breast cancer cell behaviour. Interestingly the secretome of mechanically stimulated osteocytes enhanced both the proliferation and migration of cancer cells when compared to the secretome of statically cultured osteocytes, demonstrating that mechanical stimuli is an important physiological stimulus that should be considered when identifying potential targets. Using a cytokine array, we further identified a group of mechanically activated cytokines in the osteocyte secretome, which potentially drive breast cancer metastasis. In particular, CXCL1 and CXCL2 cytokines are highly expressed, mechanically regulated, and are known to interact with one another. Lastly, we demonstrate that these specific factors enhance breast cancer cell migration independently and in a synergistic manner, identifying potential osteocyte derived factors mediating breast cancer metastasis to bone.Chemoresistance has doubled the effort needed to reach an effective treatment for cancer. Now, scientists should consider molecular pathways and mechanisms involved in chemoresistance to overcome cancer. Autophagy is a "self-digestion" mechanism in which potentially toxic and aged organelles and macromolecules are degraded. Increasing evidence has shown that autophagy possesses dual role in cancer cells (onco-suppressor or oncogene). So, it is vital to identify its role in cancer progression and malignancy. MicroRNAs (miRs) are epigenetic factors capable of modulation of autophagy in cancer cells. In the current review, we emphasize on the relationship between miRs and autophagy in cancer chemotherapy. Besides, we discuss upstream mediators of miR/autophagy axis in cancer chemotherapy including long non-coding RNAs, circular RNAs, Nrf2 c-Myc, and HIF-1α. At the final section, we provide a discussion about how anti-tumor compounds affect miR/autophagy axis in ensuring chemosensitivity. These topics are described in this review to show how autophagy inhibition/induction can lead to chemosensitivity/chemoresistance, and miRs are considered as key players in these discussions.

To review the virology, immunology, epidemiology, clinical manifestations, and treatment of the following 3 major zoonotic coronavirus epidemics severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19).

Published literature obtained through PubMed database searches and reports from national and international public health agencies.

Studies relevant to the basic science, epidemiology, clinical characteristics, and treatment of SARS, MERS, and COVID-19, with a focus on patients with asthma, allergy, and primary immunodeficiency.

Although SARS and MERS each caused less than a thousand deaths, COVID-19 has caused a worldwide pandemic with nearly 1 million deaths. Diagnosing COVID-19 relies on nucleic acid amplification tests, and infection has broad clinical manifestations that can affect almost every organ system. Asthma and atopy do not seem to predispose patients to COVID-19 infection, but their effects on COVID-19 clinical outcomes remain mixed and inconclusive.