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Highlights? Identifying NPAC as a novel LSD2 cofactor stimulating H3K4 demethylation ? Structure determination of LSD2 alone or in complex with NPAC and histone H3 peptide ? Defining the key NPAC residues essential for its intrinsic LSD2 cofactor activity ? Establishing a molecular model for how a cofactor regulates histone demethylation  相似文献   

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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.  相似文献   

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Highlights? Fasting induces the plasticity of brain barriers in hypothalamic feeding regions ? Central neuroglucopenia triggers blood-hypothalamus barrier plasticity ? Fasting-induced brain barrier plasticity requires VEGF-A expression in tanycytes ? The tanycytic barrier modulates blood-borne signals access to CNS feeding circuits  相似文献   

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Highlights? Ogt forms a complex with Tet1 and Tet2 in the nucleus of embryonic stem cells ? Ogt preferentially associates with promoter regions in proximity of TSS ? Ogt shows >90% of colocalization with Tet1 at methylation-free CpG-rich elements ? Tet1 is required for global Ogt chromatin recruitment regulating its activity  相似文献   

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Highlights? Spp1 and histone H3K4 residue are important for meiotic DSB formation ? Spp1 physically interacts with the DSB protein Mer2 ? Spp1 in meiosis is not with RNA Pol II, but on chromosome axes in DSB-rich domains ? Spp1’s PHD finger tethers H3K4me3 regions to chromosome axes for DSB formation  相似文献   

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Highlights? Crystal structures of the cytokine-binding regions of OPG and RANK bound to RANKL ? High-affinity OPG engagement is associated with a distinct RANKL-binding cleft ? Structural basis of how the OPGF96L mutation promotes juvenile Paget’s disease  相似文献   

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Highlights? Structural changes in axonemal and cytoplasmic dynein motors seen by cryo-EM ? Movement is amplified by a hinge action within dynein's linker domain ? The linker is a stable structure that is actively remodeled by dynein's AAA+ modules ? Dynein's neck subdomain interacts with AAA4 and is an intrinsic site of flexibility  相似文献   

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Highlights? Structural features of 2OG oxygenases involved in substrate recognition are analyzed. ? Crystallographic studies reveal the versatility of the jelly roll fold in substrate binding. ? Defined structural regions that interact with substrate(s) are biased by fold topology. ? The utility of the enzyme–substrate structures for engineering and selective inhibition are discussed.  相似文献   

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Highlights? Structure of ABCA4 was determined by electron microscopy to a resolution of 18 Å ? Binding of ATP induced conformational changes in cytoplasmic and transmembrane regions ? Transport mechanism is proposed based on EM and hydrogen/deuterium exchange data  相似文献   

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Highlights? Y-family polymerases differ in fidelity and translesion synthesis specificity ? Polymerase fidelity and specificity are controlled by the interdomain linker ? Three amino acids in the interdomain linker are sufficient to determine conformation ? Differences in polymerase conformation determine differences in polymerase activity  相似文献   

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Highlights? Modified small-scale ChIP-seq method applicable to small number of cells ? Genome-wide maps of H3K4me3, H3K27me3, H3K27ac, and H2BK20ac of germ cells in vivo ? Identification of active and inactive regulatory elements in germ cells in vivo ? Germ cell H3K27me3 regions are enriched for retrotransposon repeats  相似文献   

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Highlights? Loss of mutant pVHL in VHL-associated tumors is due to rapid degradation ? Mutant pVHL maintains its intrinsic function as an E3 ligase ? HDACIs stabilize mutant pVHL and ameliorate tumor growth in vivo ? HDACIs represent a targeted therapy for VHL-associated tumors  相似文献   

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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  相似文献   

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Highlights? Protein and position-specific statistical potentials are more powerful ? Evolutionary information greatly boost performance of statistical potentials ? Observed probability is critical to energy potentials, in addition to reference state ? Observed probability can be estimated better using context-specific information  相似文献   

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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  相似文献   

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Highlights? RNA folding in miRNA target sites is distinct between animals ? There is a negative correlation between miRNA target-site structure and miRISC binding ? Conserved secondary structure features demarcate protein-coding regions of animal mRNAs ? There are conserved features of RNA secondary structure in animals  相似文献   

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