Chemical attenuation of pilus function and assembly in Gram-negative bacteria

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Highlights? The promise of receptor analogues and biogenesis inhibitors to curb adhesive pili. ? Mannoside-based type 1 pilus inhibitors are effective against UPEC in a murine model of UTI. ? Pilus adhesins contain specificity and affinity-determining regions. ? Bi-cyclic 2-pyridones inhibit curli and chaperone–usher pilus biogenesis.     

Information encoded in non-native States drives substrate-chaperone pairing

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Highlights? In vitro refolding intermediates are aptly targeted to specific chaperones ? Substrate-chaperone pairing depends on their relative affinity ? Structure of the intermediates play crucial role in precise chaperone targeting ? Substrates may be mistargeted due to large alterations in chaperone molar ratios     

Moonlighting by different stressors: crystal structure of the chaperone species of a 2-Cys peroxiredoxin

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Highlights? The Schistosoma mansoni peroxiredoxin I (SmPrxI) is a moonlighting protein ? SmPrxI switches from LMW peroxidase to HMW chaperone due to chemical stressors ? The three-dimensional structures of both LMW and HMW SmPrxI have been solved ? SmPrxI HMW is the structure of a Prx chaperone     

Substrate-Activated Conformational Switch on Chaperones Encodes a Targeting Signal in Type III Secretion

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Highlights? The targeting signal of TTS substrates to the ATPase was identified ? The ATPase engages the chaperone-substrate complex but not the free chaperone ? The ATPase recognizes a conformational change induced by the substrate to the chaperone ? Abrogation of the ternary complex results in secretion and infection defects     

The Myosin Chaperone UNC-45 Is Organized in Tandem Modules to Support Myofilament Formation in C. elegans

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Highlights? UNC-45 self-assembles a docking platform for multiple chaperone and client proteins ? Hsp70/90 and myosin bind to specific sites on the TPR and UCS domains of UNC-45 ? The UNC-45 multimer offers the proper spacing to couple myosin folding and assembly ? In vivo, UNC-45 chains support the formation of fully functional sarcomeric repeats     

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     

Conformational Dynamics of the Rpt6 ATPase in Proteasome Assembly and Rpn14 Binding

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Highlights? Proteasome ATPase Rpt6 undergoes helix-coil exchange in its C-terminal domain ? Rpt6 G^360,387A has a stabilized four-helix bundle and raised melting temperature ? Assembly chaperone Rpn14 binds selectively to the four-helix bundle Rpt6 conformer ? Rpt6 G^360,387A (rpt6AA) is synthetically defective with an rpn14 null mutation     

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     

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     

Perivascular Nitric Oxide Activates Notch Signaling and Promotes Stem-like Character in PDGF-Induced Glioma Cells

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Highlights? Perivascular niche nitric oxide activates Notch in PDGF-induced gliomas ? Notch signaling drives tumor stem-like characteristics and reduces survival ? Loss of eNOS activity decreases tumor stem-like characteristics ? Suppressing eNOS activity prolongs survival in glioma-bearing mice     

Comprehensive Analysis of Silencing Mutants Reveals Complex Regulation of the Arabidopsis Methylome

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Highlights? Genome-wide single-nucleotide resolution methylation maps in 86 silencing mutants ? Complex interplays between different DNA methylation pathways ? Identification of novel regulators of DNA methylation     

Protein model discrimination using mutational sensitivity derived from deep sequencing

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Highlights? Individual mutant phenotypes in a saturation library derived via deep sequencing ? Residue depth and active-site residue derivation from mutant phenotypes ? Mutant-phenotype-derived parameters used for protein model discrimination ? Derivation of sequence-structure-function relationships without protein isolation     

Spatial Restriction of FGF Signaling by a Matrix Metalloprotease Controls Branching Morphogenesis

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Highlights? Drosophila Matrix Metalloprotease (Mmp) inhibits FGF signaling ? An FGF – MMP feedback loop regulates branching morphogenesis ? Mmp2 spatially regulates FGF signaling in epithelia     

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     

Hypertrophy and unconventional cell division of hepatocytes underlie liver regeneration

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Highlights? Not all hepatocytes undergo cell division during liver regeneration ? Hypertrophy precedes proliferation in the regenerating liver ? Hepatocytes infrequently enter into M phase during liver regeneration ? Binuclear hepatocytes undergo cell division to generate mononuclear hepatocytes     

ESCs Require PRC2 to Direct the Successful Reprogramming of Differentiated Cells toward Pluripotency

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Highlights? Mouse pluripotent cells reprogram human B cells in heterokaryons ? ESCs lacking PRC1 or PRC2 cannot successfully reprogram ? Failure of PRC1/2-deficient ESCs to reprogram is functionally dominant ? PRC1/2 play a critical role in the chromatin reorganization required for reprogramming     

System-wide Rewiring Underlies Behavioral Differences in Predatory and Bacterial-Feeding Nematodes

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Highlights? Massive neural circuit rewiring between nematodes with divergent feeding behavior ? Striking patterns correlate with known functional differences ? Motor synapse differences indicate a substantial change in information flow ? Correlates of predatory feeding behavior are identified     

Tremor Suppression by Rhythmic Transcranial Current Stimulation

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Highlights? Phase-cancelling cortical stimulation attenuates Parkinsonian tremor ? Prolonged stimulation may invoke adaptive mechanisms ? Phase cancellation may provide a generic treatment approach to oscillopathies ? TACS provides a convenient probe of cortical circuit dynamics in humans