Widespread Regulation of Translation by Elongation Pausing in Heat Shock

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Highlights? Global translation elongation pause at 5′ end of ORFs in severe heat shock ? Modulation of Hsp70 levels/activity affects elongation pausing ? Pausing is associated with hydrophobic N termini ? Hsp70 shows reduced ribosome association and altered interactions in heat stress     

Short Telomeres in ESCs Lead to Unstable Differentiation

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Highlights? ESCs with short telomeres do not stably differentiate and can resume proliferation ? Critically short telomeres impair Nanog regulation during ESC differentiation ? Short telomeres elicit genome-wide DNA hypomethylation and altered H3K27me3 levels ? Impaired DNA methylation and differentiation are rescued by Dnmt3b or telomere elongation     

Neuronal ER Stress Impedes Myeloid-Cell-Induced Vascular Regeneration through IRE1α Degradation of Netrin-1

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Highlights? Canonical ER stress pathways are activated in central neurons during hypoxia/ischemia ? The ER stress endoribonuclease IRE1α degrades the neurovascular guidance cue netrin-1 ? Neuronal-derived netrin-1 activates a reparative proangiogenic program in microglial cells ? Neuronal ER stress prevents reparative angiogenesis in the ischemic neural retina     

p58IPK-Mediated Attenuation of the Proapoptotic PERK-CHOP Pathway Allows Malignant Progression upon Low Glucose

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Highlights? Transformation-associated glucose shortage triggers ER stress ? The ER stress acts as barrier to malignancy by triggering UPR-dependent apoptosis ? p58^IPK expression removes the UPR barrier by attenuating its PERK-CHOP branch ? This adaptive mechanism enables implementation of UPR cytoprotective features     

The Impact of Aminoglycosides on the Dynamics of Translation Elongation

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Highlights? Combined single-molecule, structural, and biochemical studies on aminoglycoside action ? Aminoglycosides disrupt translation through inhibiting the dynamics of elongation ? Apramycin blocks translocation in translation elongation ? Paromomycin and gentamicin disrupt ribosomal rotation and translocation     

Metabolic Stress Controls mTORC1 Lysosomal Localization and Dimerization by Regulating the TTT-RUVBL1/2 Complex

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Highlights? Glucose and glutamine feed back to promote mTORC1 signaling through ATP production ? Energetic stress prevents mTOR lysosomal localization independently of AMPK and Rag ? ATP-dependent TTT-RUVBL complex is disassembled and repressed by energetic stress ? TTT-RUVBL is required for mTORC1 functional assembly and lysosomal localization     

Kinetic Competition between RNA Polymerase II and Sen1-Dependent Transcription Termination

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Highlights? Fast Pol II elongation rate leads to Sen1-dependent termination defects ? Deletion of Rrp6 reveals a noncoding RNA termination window sensitive to Pol II rate ? Slow Pol II rate promotes earlier Sen1 termination events, rescues sen1 defects ? Fast Pol II rate promotes later Sen1 termination events, worsens sen1 defects     

p38 MAPK controls prothrombin expression by regulated RNA 3' end processing

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Highlights? External signals regulate 3′ end mRNA processing through p38 MAPK activation ? The mechanism is controlled by a competitive mRNP formation in the 3′UTR ? The mechanism is activated by acute phase stress and inflammation ? The prototypic thrombin links the mechanism to blood coagulation and tumor spread     

Differential Regulation of Distinct Vps34 Complexes by AMPK in Nutrient Stress and Autophagy

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Highlights? Different Vps34 complexes are distinctly regulated upon energy stress ? AMPK activates the proautophagy Vps34 complex by phosphorylating Beclin1 ? AMPK inhibits the nonautophagic Vps34 complex by phosphorylating Vps34 ? ATG14L determines whether the Vps34 complex is activated or inhibited by AMPK     

Asymmetric mode of Ca²⁺-S100A4 interaction with nonmuscle myosin IIA generates nanomolar affinity required for filament remodeling

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Highlights? S100A4 dimer binds single-myosin IIA molecule in an asymmetrical mode ? Synergy between Ca-dependent sites in S100A4 leads to high-affinity interaction ? Electron microscopy shows that two S100A4 dimers bind to the myosin coiled coil ? S100A4 has direct effect on formation of stress fibers and cell migration     

Modeling Alzheimer’s Disease with iPSCs Reveals Stress Phenotypes Associated with Intracellular Aβ and Differential Drug Responsiveness

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Highlights? Familial and sporadic Alzheimer’s patient iPSC-derived neural cells were analyzed ? Intracellular Aβ oligomers accumulate in lines from some patients ? Aβ oligomer accumulation is associated with ER and oxidative stress ? DHA-alleviated ER and oxidative stresses improve cell viability     

A three-state model of telomere control over human proliferative boundaries

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Highlights? Human telomeres are protected from the DDR by a higher-order structure. ? Intermediate-state telomeres are susceptible to a DDR and regulate senescence. ? Uncapped-state telomeres are susceptible to fusions and induce crisis. ? Intermediate-state telomeres regulate the prolonged mitosis checkpoint. ? Telomeres may serve as epigenetic sensors of cellular stress.     

A comprehensive genomic binding map of gene and chromatin regulatory proteins in Saccharomyces

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Highlights? Genomic maps of 200 yeast regulators in normal and stress conditions provide a compendium for discovery ? SAGA assembly pathway is associated with more regulation than the TFIID pathway ? SAGA-linked regulators are distal, and TFIID-linked regulators are proximal to the promoter ? During heat shock, SAGA- and TFIID-linked regulators displayed distinct mobilization patterns     

Xenobiotics Shape the Physiology and Gene Expression of the Active Human Gut Microbiome

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Highlights? The gut microbiome is highly active, similar to nutrient-rich productive systems ? Firmicutes dominate the active and damaged subsets of the gut microbiome ? Both antibiotics and host-targeted drugs rapidly alter the active gut microbiome ? Xenobiotics induce genes for drug metabolism, drug resistance, and stress response     

Macrophage autophagy plays a protective role in advanced atherosclerosis

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Highlights? Proapoptotic oxidative stress induces autophagy in macrophages (M?s) ? Inhibition of autophagy enhances oxidative stress and apoptosis in M?s ? Atheromata of M?-Atg5^?/?Ldlr^?/? mice have increased apoptosis and plaque necrosis ? Apoptotic Atg5^?/? M?s are poorly recognized by phagocytes in vitro and in atheromata     

Two Deubiquitylases Act on Mitofusin and Regulate Mitochondrial Fusion along Independent Pathways

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Highlights? Mitochondrial fusion is regulated by independent ubiquitylation pathways ? The deubiquitylase Ubp2 promotes fusion, whereas Ubp12 inhibits fusion events ? Self-assembly and ubiquitylation cooperatively enable mitochondrial fusion ? Yeast mitofusin is sequentially ubiquitylated     

Solution Conformations of Prototype Foamy Virus Integrase and Its Stable Synaptic Complex with U5 Viral DNA

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Highlights? Missing domains in PFV intasome revealed by SAXS/SANS ? PFV IN undergoes dramatic changes in conformation and oligomerization upon binding DNA ? Strand transfer inhibitors do not alter quaternary structure of PFV intasome     

SIP1 Mediates Cell-Fate Decisions between Neuroectoderm and Mesendoderm in Human Pluripotent Stem Cells

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Highlights? Smad-interacting protein 1 (SIP1) regulates hESC differentiation ? SIP1 upregulation promotes neuroectodermal differentiation ? SIP1 inhibits mesendodermal and endodermal differentiation ? SMAD2/3 and NANOG/OCT4/SOX2 cooperatively regulate SIP1 expression     

Keeping cell identity in Arabidopsis requires PRC1 RING-finger homologs that catalyze H2A monoubiquitination

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Highlights? AtBMI1A/B proteins prevent misexpression of embryonic traits in somatic cells ? PRC2 and AtBMI1A/B proteins maintain cells in their differentiated state ? AtBMI1A/B proteins mediate H2A monoubiquitination