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05). Age, on the other hand, influenced the prebiotic effect on Cyp2a4 expression (P  less then  0.01). CONCLUSION The expression of hepatic genes implicated in drug metabolism and transport displays sensitivity to the microbiome, microbiome-derived metabolites and a microbial-targeted intervention. Our study may provide the impetus to explore microbiota-targeted interventions in normalising host metabolic activity and reducing inter-individual variability in drug pharmacokinetics. © 2020 Royal Pharmaceutical Society.Cataglyphis ants are known for their outstanding navigational abilities. They return to their inconspicuous nest after far-reaching foraging trips using path integration, and whenever available, learn and memorize visual features of panoramic sceneries. To achieve this, the ants combine directional visual information from celestial cues and panoramic scenes with distance information from an intrinsic odometer. The largely vision-based navigation in Cataglyphis requires sophisticated neuronal networks to process the broad repertoire of visual stimuli. Although Cataglyphis ants have been subject to many neuroethological studies, little is known about the general neuronal organization of their central brain and the visual pathways beyond major circuits. Here, we provide a comprehensive, three-dimensional neuronal map of synapse-rich neuropils in the brain of Cataglyphis nodus including major connecting fiber systems. In addition, we examined neuronal tracts underlying the processing of visual information in more detail. This study revealed a total of 33 brain neuropils and 30 neuronal fiber tracts including six distinct tracts between the optic lobes and the cerebrum. We also discuss the importance of comparative studies on insect brain architecture for a profound understanding of neuronal networks and their function. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.TDP-43 is the major pathogenic protein of amyotrophic lateral sclerosis (ALS). Previously, we identified that TDP-43 interacts with G-quadruplex (G4)-containing RNA and is involved in their long-distance transport in neurons. For the molecular dissection of the TDP-43 and G4-RNA interaction, we analyzed it here in vitro and in cultured cells using a set of ten mutant TDP-43 proteins from familial and sporadic ALS patients as well as using the TDP-43 C-terminal Gly-rich domain alone. Our results altogether indicate the involvement of the Gly-rich region of TDP-43 in the initial recognition and binding of G4-RNA, which then induces tight binding of TDP-43 with target RNAs, supposedly in conjunction with its RNA recognition motifs (RRMs). This article is protected by copyright. All rights reserved.BACKGROUND AND PURPOSE Pulmonary arterial hypertension (PAH, type 1 pulmonary hypertension) has a 3-year survival of ~50% and is in need of new, effective therapies. In PAH, remodeling of the pulmonary artery (PA) increases pulmonary vascular resistance and can result in right heart dysfunction and failure. Genetic mutations can cause PAH but it can also be idiopathic (IPAH). Enhanced contractility and proliferation of PA smooth muscle cells (PASMCs) are key contributors to the pathophysiology of PAH, but the underlying mechanisms are not well understood. EXPERIMENTAL APPROACH We conducted an exploratory study utilizing RNA-sequencing (RNA-seq) of IPAH and control patient-derived PASMCs as an unbiased approach to define differentially expressed (DE) genes that may identify new biology and potential therapeutic targets. KEY RESULTS Overall gene expression was consistent among replicates (n=4/group). Analysis of DE genes for shared gene pathways revealed increases in genes involved in cell proliferation and mitosis and decreases in a variety of gene sets, including response to cytokine signaling. ADGRG6/GPR126, an adhesion GPCR, was increased in IPAH-PASMCs compared to control-PASMCs. Increased expression of this receptor in control-PASMCs decreased their proliferation; siRNA knockdown of ADGRG6/GPR126 in IPAH-PASMCs increased proliferation. CONCLUSION AND IMPLICATIONS The data provide insights regarding the expression of current and experimental PAH drug targets, G protein-coupled receptors (GPCRs) and GPCR-related genes as potentially new therapeutic targets in PAH-PASMCs. Overall, the findings identify genes and pathways that may contribute to IPAH-PASMC function and suggest that ADGRG6/GPR126 is a novel therapeutic target for IPAH. Results from this pilot study provide a basis for further studies to confirm and validate ADGRG6/GPR126 and other potential therapeutic targets for IPAH. This article is protected by copyright. LY294002 in vivo All rights reserved.We used a field experiment to test the effects of population density on the growth rate and survival of Austrolebias bellottii, a Neotropical annual killifish. Effects differed between the sexes; males at high densities achieved a smaller final size and experienced higher mortality while no such effects were observed in females. This sex-specific effect could be an indirect consequence of mate competition. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.BACKGROUND According to the Global Burden of Disease Study 2015, lower respiratory tract infection is the leading cause of infectious disease death, and the fifth most common cause of death overall. Vitamin C has a role in modulating resistance to infectious agents, therefore vitamin C supplementation may be important in preventing and treating pneumonia. OBJECTIVES To assess the impact of vitamin C supplementation to prevent and treat pneumonia in children and adults. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, PubMed, CINAHL, LILACS, Web of Science, and two trials registers to 4 March 2020. We also checked references to identify additional studies. We did not apply any publication status or language filters. SELECTION CRITERIA We included randomised controlled trials (RCTs) and quasi-RCTs (studies using allocation methods that are not random, e.g. date of birth, medical record number) assessing the role of vitamin C supplementation in the prevention and treatment of pneumonia in children and adultsn C supplementation group and 7.75 days in the control group; another study reported a lower mean duration of hospital stay in the vitamin C supplementation group compared to the control group (109.55 hours ± 27.89 versus 130.64 hours ± 41.76). AUTHORS' CONCLUSIONS Due to the small number of included studies and very low quality of the existing evidence, we are uncertain of the effect of vitamin C supplementation for the prevention and treatment of pneumonia. Further good-quality studies are required to assess the role of vitamin C supplementation in the prevention and treatment of pneumonia. Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.This perspective provides a vision for creating digital patient-centric regulatory platforms to share reliable, relevant, and current information while minimizing environmental impact. Current technologies provide opportunities for healthcare providers (HCPs) and patients to obtain approved product information in a personalized manner to meet individual needs. Electronic labels serve as a foundation for truly advanced information communication and telemedicine allowing HCPs and patients to make informed decisions based on easily accessible, relevant, and current information. This article is protected by copyright. All rights reserved.Protein phosphorylation regulates a large variety of biological processes in all living cells. In pathogenic bacteria, the study of serine, threonine and tyrosine (Ser/Thr/Tyr) phosphorylation has shed light on the course of infectious diseases, from adherence to host cells to pathogen virulence, replication and persistence. Mass spectrometry (MS)-based phosphoproteomics has provided global maps of Ser/Thr/Tyr phosphosites in bacterial pathogens. Despite recent developments, a quantitative and dynamic view of phosphorylation events that occur during bacterial pathogenesis is currently lacking. Temporal, spatial and sub-population resolution of phosphorylation data is required to identify key regulatory nodes underlying bacterial pathogenesis. Herein we discuss how technological improvements in sample handling, MS instrumentation, data processing and machine learning should improve bacterial phosphoproteomic datasets and the information extracted from them. Such information is expected to significantly extend the current knowledge of Ser/Thr/Tyr phosphorylation in pathogenic bacteria and should ultimately contribute to the design of novel strategies to combat bacterial infections. This article is protected by copyright. All rights reserved.Formation of clathrin-coated vesicles (CCVs) in receptor-mediated endocytosis is a mechanistically well-established process, in which clathrin, the adaptor protein complex AP-2, and the large GTPase dynamin play crucial roles. In order to obtain more mechanistic insight into this process, here we established a giant unilamellar vesicle-(GUV)-based in vitro CCV reconstitution system with chemically defined components and the full-length recombinant proteins clathrin, AP-2, epsin-1 and dynamin-2. Our results support the predominant model in which hydrolysis of GTP by dynamin is a prerequisite to generate CCVs. Strikingly, in this system at near physiological concentrations of reagents, epsin-1 alone does not have the propensity for scission but is required for bud formation, whereas AP-2 and clathrin are not sufficient. Thus, our study reveals that epsin-1 rather than AP2 induces the curvature of endocytic CCVs. This article is protected by copyright. All rights reserved.The original version of this article unfortunately contained one mistake. The institutions of the authors are wrong. The corrected institutions are given below.Zhi-cai DU1, 2, Li-xin ZHU11Department of Spinal Surgery, Orthopaedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China 2Department of Minimally Invasive Spinal Surgery, The Second Affiliated Hospital of Inner Mon-golia Medical University, Hohhot 010030, China.The article "Protein Phosphatase 2A as a Drug Target in the Treatment of Cancer and Alzheimer's Disease", written by Hui WEI, Hui-liang ZHANG, Jia-zhao XIE, Dong-li MENG, Xiao-chuan WANG, Dan KE, Ji ZENG, Rong LIU, was originally published electronically on the publisher's internet portal on 13 March 2020 without open access. With the author(s)' decision to opt for Open Choice the copyright of the article changed to © The Author(s) 2020 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License (https//creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The original article has been corrected.Corresponding authors Dan KE, E-mail kedan@hust.edu.cn; Ji ZENG, E-mail whzjmicro@163.com.