Legionella pneumophila Effector RomA Uniquely Modifies Host Chromatin to Repress Gene Expression and Promote Intracellular Bacterial Replication

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Highlights? Upon infection, L. pneumophila secretes RomA, a SET domain-containing methyltransferase ? RomA triggers H3K14 trimethylation, causing a switch from gene activation to repression ? ChIP-seq identified 4,870 H3K14 methylated promoter regions, including innate immune genes ? RomA SET domain is required for efficient intracellular replication of L. pneumophila     

Uncovering a Region of Heat Shock Protein 90 Important for Client Binding in E. coli and Chaperone Function in Yeast

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Highlights? Using a genetic screen, we selected for defective mutants of E. coli Hsp90 ? The mutants are impaired in ATP-dependent chaperone activity ? The mutations define a client-binding region of E. coli Hsp90 ? Mutation of homologous residues in yeast Hsp90 causes in vivo and in vitro defects     

Structural Determinants of RGS-RhoGEF Signaling Critical to Entamoeba histolytica Pathogenesis

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Highlights? E. histolytica expresses a convergently evolved RGS-RhoGEF protein ? EhRGS-RhoGEF possesses a conventional nine-helix RGS domain ? Activated EhRGS-RhoGEF induces S2 cell spreading through Rac1/2 ? EhRGS-RhoGEF modulates amoebic migration and host cell killing     

Distinct States of Methionyl-tRNA Synthetase Indicate Inhibitor Binding by Conformational Selection

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Highlights? Complexes of MetRS from T. brucei with its substrate, intermediate, and inhibitors ? In crystals, substrate-bound MetRS undergoes extensive changes with inhibitor binding ? The inhibitor-bound conformation is surprisingly similar to the ligand-free state ? This indicates inhibitor binding occurs via conformational selection not by induced fit     

An Autoinhibited State in the Structure of Thermotoga maritima NusG

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Highlights? Thermotoga maritima NusG shows a dynamic intramolecular NTD-CTD interaction ? The NTD-CTD interaction hides the binding surfaces for RNA polymerase, S10, and Rho ? Domain interaction contributes to thermostability ? Thermotoga maritima NusG does not complement a NusG-deficient E. coli strain     

Fertility and Germline Stem Cell Maintenance under Different Diets Requires nhr-114/HNF4 in C. elegans

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Highlights? C. elegans fertility on different diets requires nuclear receptor nhr-114 activity ? Somatic NHR-114 is necessary to maintain germline stem cells under different diets ? NHR-114 might mediate a detoxification response that preserves the germline ? Bacterial tryptophan metabolites may underlie diet-sensitive nhr-114(?) sterility     

HRG1 Is Essential for Heme Transport from the Phagolysosome of Macrophages during Erythrophagocytosis

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Highlights? Humans have about 25 trillion RBCs, each containing over a billion heme moieties ? Five million senescent RBCs are recycled per second by erythrophagocytosis in macrophages to make new RBCs ? HRG1, the mammalian homolog of C. elegans heme transporter, recycles heme-iron from the macrophage phagolysosome ? Missense polymorphisms in human HRG1 may be genetic modifiers of iron metabolism     

The Binding of Antibiotics in OmpF Porin

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Highlights? OmpF porin binds antibiotics in the extracellular and periplasmic pore vestibules ? MD simulations show that ionic current through OmpF is blocked by bound ampicillin ? Carbenicillin binding alters ion selectivity of OmpF but not total ionic current ? Disruption of binding increases the susceptibility of E. coli for antibiotics     

Inflammatory Chemokines Direct and Restrict Leukocyte Migration within Live Tissues as Glycan-Bound Gradients

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Highlights? Chemokines form tissue-bound gradients in vivo through heparan sulfate proteoglycans ? Chemokines guide neutrophils in vivo as haptotactic gradients ? Chemokines guide neutrophils toward infection loci by triggering orthotaxis ? Chemokines locally restrict neutrophil motility at sites of infection     

Cdc42 Explores the Cell Periphery for Mate Selection in Fission Yeast

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Highlights? Active Cdc42 forms dynamic zones at the periphery of mating S. pombe cells ? This defines a novel exploratory phase, without cell wall synthase exocytosis or growth ? Zone dynamics occur upon exposure to low- but not high-level pheromone ? Mating partner choice is compromised in absence of low-level pheromone signaling     

Mesenchymal stem cells as therapeutic agents of inflammatory and autoimmune diseases

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Highlights? Immunomodulatory properties of MSCs in vitro and in vivo are discussed. ? Safety and efficacy of treatments with allogeneic MSCs are discussed. ? Future directions to improve efficacy of MSC treatments are proposed.     

Crystal Structure of the O2-Tolerant Membrane-Bound Hydrogenase 1 from Escherichia coli in Complex with Its Cognate Cytochrome b

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Highlights? The structure of a membrane-bound [NiFe]-hydrogenase/cytochrome b complex ? One active hydrogenase is able to “jumpstart” its O₂-inactivated counterpart ? E. coli hydrogenase 1 has a central protective role against O₂-induced cell damage ? The structure defines the hydrogenase/cytochrome b active-interacting surface     

Deuterostomic Development in the Protostome Priapulus caudatus

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Highlights? In the protostome P. caudatus, the blastopore forms the anus (deuterostomy) ? The hindgut markers brachyury and cdx are expressed in the blastopore and in the anus ? The foregut markers foxA and gsc are detected in the mouth, but not in the blastopore ? Results favor deuterostomy in ecdysozoan, protostome, and bilaterian ancestors     

Ubiquitin C-Terminal Hydrolase-L1 Potentiates Cancer Chemosensitivity by Stabilizing NOXA

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Highlights? Proteasomal degradation of NOXA is enhanced in chemoresistant tumor samples ? UCH-L1 is the specific deubiquitylating enzyme of NOXA ? Lack of UCH-L1 results in inefficient DNA damage-induced apoptosis in cancer ? Knockdown of UCH-L1 homolog in C. elegans results in reduced apoptosis     

The IRP1-HIF-2α Axis Coordinates Iron and Oxygen Sensing with Erythropoiesis and Iron Absorption

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Highlights? Derepression of HIF-2α mRNA in Irp1^?/? mice causes age-dependent polycythemia ? HIF-2α hyperactivity is observed in multiple tissues of Irp1^?/? mice ? The mRNA regulons of IRP1 and IRP2 are separable in vivo ? The IRP1-HIF-2α axis is a therapeutic target for hematologic or oncologic disorders     

Estimating the Microtubule GTP Cap Size In Vivo

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Highlights? The microtubule (MT) GTP cap is ～750 tubulin subunits in vivo and extends over 1 μm ? EGFP brightness can be calibrated in vivo using GFP-tubulin signals from MTs ? The presence of GTP-tubulin in the MT lattice influences MT shortening and rescue ? MT tip trackers, like EB1, can be highly concentrated at the MT plus end (～100 μM)     

Specificity and Function of Archaeal DNA Replication Initiator Proteins

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Highlights? The S. islandicus chromosome has three origins, each with its own initiator ? Two origins are Orc dependent, and one requires a Cdt1 homolog ? The ATP-bound form of Orc1 is proficient at MCM loading ? ATP binding remodels the protein structure, not that of the DNA template     

Foxg1 Coordinates the Switch from Nonradially to Radially Migrating Glutamatergic Subtypes in the Neocortex through Spatiotemporal Repression

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Highlights? Foxg1 directs projection neuron production onset in the neocortex ? Foxg1 acts cell autonomously to switch mammalian cortical subtypes ? Progenitors retain a prolonged competence to initiate corticogenesis in vivo ? Ebf2/3, Dmrta1, and Eya2 are mammalian-specific repression targets of Foxg1     

MicroRNA-9 Coordinates Proliferation and Migration of Human Embryonic Stem Cell-Derived Neural Progenitors

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Highlights? miR-9 is expressed in hESC-derived early hNPCs and their progeny ? Loss of miR-9 inhibits early hNPC proliferation and delays maturation ? miR-9 knockdown promotes hNPC migration in vitro and in vivo ? Stathmin is a target of miR-9 and mediates its effects in early hNPCs