Methyl gallate (MG) is an effective microbicide with great potential application in the integrated management of plant diseases and an important potential drug for clinical application. However, its target remains unknown. This study conducted a transposon sequencing (Tn-seq) under MG treatment in plant pathogenic bacterium Ralstonia solanacearum. Tn-seq identified that the mutation of caseinolytic protease proteolytic subunit gene clpP significantly increased the resistance of R. solanacearum to MG, which was validated by the in-frame gene deletion. iTRAQ (isobaric tags for relative and absolute quantitation) proteomics analysis revealed that chemotaxis and flagella associated proteins were the major substrates degraded by ClpP under the tested condition. Moreover, sulfur metabolism-associated proteins were potential substrates of ClpP and were upregulated by MG treatment in wild-type R. RG7388 cost solanacearum but not in clpP mutant. Furthermore, molecular docking confirmed the possible interaction between MG and ClpP. Collectively, this study revealed that MG might target bacterial ClpP, inhibit the activity of ClpP, and consequently disturb bacterial proteostasis, providing a theoretical basis for the application of MG.Objective This study describes the types of Human astroviruses detected in stool samples collected from a birth cohort of children in Nepal. Methods Using a commercial kit (ProSpecT), a total of 5,224 diarrheal and non-diarrheal stool samples were screened for Human astrovirus by ELISA. RT-PCR was performed on ELISA positive samples (2.8%) for further confirmation. The primary RT-PCR assay used targets the ORF2 region and detects human astrovirus type 1-8. Samples that were negative in this assay were further analyzed using primers that target the ORF1b region of human astrovirus which detect both classical type (HAstV 1-8) and novel types (MLB1-5, VA 1-5). PCR positive samples were analyzed by Sanger sequencing to determine the genotype. Results A total of 148 available ELISA positive stool samples were analyzed by RT-PCR and further genotyped. RT-PCR analysis of these samples using the ORF2 and ORF1b assay revealed that 124 (84%) were positive for classical human types (HAstV 1-8). Seven different classical HAstV genotypes based on ORF2 and ORF1a were identified (HAstV 1- HAstV 8) with the greatest prevalence of HAstV 5 genotype (42.2%), followed by HAstV 1 (34.7%), HAstV 2 and HAstV 8 (7.4%), HAstV 4 (4.1%), HAstV 3 (3.3%), and HAstV 6 (0.8%). Non-classical types were not detected in our study. Conclusion A high diversity of circulating Astrovirus strains were detected in young children, both with and without symptoms of gastroenteritis. HAstV 5 and HAstV 1 were the most common genotypes in young children in Nepal.The recruitment and activation of polymorphonuclear neutrophils (PMNs) are of central importance for the elimination of pathogens in bacterial infections. We investigated the Streptococcus pneumoniae-dependent induction of the transcription factor Krüppel-like factor (KLF) 4 in PMNs as a potential regulator of PMN activation. We found that KLF4 expression is induced in human blood-derived PMNs in a time- and dose-dependent manner by wild-type S. pneumoniae and capsule knockout mutants. Unencapsulated knockout mutants induced stronger KLF4 expression than encapsulated wild types. The presence of autolysin LytA-competent (thus viable) pneumococci and LytA-mediated bacterial autolysis were required for KLF4 induction in human and murine PMNs. LyzMcre-mediated knockdown of KLF4 in murine blood-derived PMNs revealed that KLF4 influences pneumococci killing and increases the release of the proinflammatory cytokines tumor necrosis factor α and keratinocyte chemoattractant and decreases the release of the anti-inflammatory cytokine interleukin-10. Thus, S. pneumoniae induces KLF4 expression in PMNs, which contributes to PMN activation in S. pneumoniae infection.Viral infection induces dynamic changes in transcriptional profiles. Virus-induced and antiviral responses are intertwined during the infection. Epstein-Barr virus (EBV) is a human gammaherpesvirus that provides a model of herpesvirus latency. To measure the transcriptome changes during the establishment of EBV latency, we infected EBV-negative Akata cells with EBV-EGFP and performed transcriptome sequencing (RNA-seq) at 0, 2, 4, 7, 10, and 14 days after infection. We found transient downregulation of mitotic division-related genes, reflecting reprogramming of cell growth by EBV, and a burst of viral lytic gene expression in the early phase of infection. Experimental and mathematical investigations demonstrate that infectious virions were not produced in the pre-latent phase, suggesting the presence of an abortive lytic infection. Fate mapping using recombinant EBV provided direct evidence that the abortive lytic infection in the pre-latent phase converges to latent infection during EBV infection of B-cells, shedding light on novel roles of viral lytic gene(s) in establishing latency. Furthermore, we find that the BZLF1 protein, which is a key regulator of reactivation, was dispensable for abortive lytic infection in the pre-latent phase, suggesting the divergent regulation of viral gene expressions from a productive lytic infection.Glucagon (GCG) plays a stimulatory role in pituitary hormone regulation, although previous studies have not defined the molecular mechanism whereby GCG affects pituitary hormone secretion. To this end, we identified two distinct proglucagons, Gcga and Gcgb, as well as GCG receptors, Gcgra and Gcgrb, in Nile tilapia (Oreochromis niloticus). Using the cAMP response element (CRE)-luciferase reporter system, tilapia GCGa and GCGb could reciprocally activate the two GCG receptors expressed in human embryonic kidney 293 (HEK293) cells. Quantitative real-time PCR analysis revealed that differential expression of the Gcga and Gcgb and their cognate receptors Gcgra and Gcgrb was found in the various tissues of tilapia. In particular, the Gcgrb is abundantly expressed in the neurointermediate lobe (NIL) of the pituitary gland. In primary cultures of tilapia NIL cells, GCGb effectively stimulated SL release, with parallel rises in the mRNA levels, and co-incubation with the GCG antagonist prevented GCGb-stimulated SL release.