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Highlights? PPARγ full agonists induce a brown fat phenotype in subcutaneous WAT ? PRDM16 is required for the development of PPARγ agonist-inducible brow adipocytes ? PRDM16 and PPARγ agonists synergistically activate the brown fat gene program ? Browning effect is mediated through the enhanced stability of the PRDM16 protein  相似文献   

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Highlights? Domains from PLCγ regulatory region show structural and functional integration ? Only cSH2 domain interacts with the PLC-core forming a high affinity surface ? Activation involves removal of autoinhibition and dissociation from the receptor ? Disease-linked mutations map to the autoinhibitory interface  相似文献   

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Highlights? Ebf2 is selectively expressed in brown relative to white adipocytes and binds to chromatin at brown fat-specific target sites of Pparγ ? Ebf2 expression in white fat or muscle precursor cells recruits Pparγ to its brown fat-specific gene targets and drives a complete program of brown adipocyte differentiation ? Brown adipose cells and tissue from Ebf2-deficient mice display a complete loss of thermogenic characteristics while gaining molecular attributes of white adipose  相似文献   

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Highlights? PI3Kγ inhibits βAR resensitization by regulating PP2A activity ? PI3Kγ inhibits PP2A activity by phosphorylating I2PP2A on Serine 9 and 93 ? Phosphorylation of I2PP2A leads to its agonist-mediated interaction with PP2A ? siRNA-targeted depletion of I2PP2A results in βAR resensitization  相似文献   

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Highlights? Activated CaMKII recruits CK2 to form a trimolecular complex (GluN2B/CaMKII/CK2) ? GluN2B/CaMKII binding controls CK2 phosphorylation of the GluN2B PDZ ligand (S1480) ? Disruption of GluN2B/CaMKII binding increases GluN2B surface expression ? GluN2B/CaMKII binding drives synaptic GluN2B clearance  相似文献   

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Highlights? Human cancers harbor frequent mutations in Gq-linked GPCRs and Gαq subunits ? A genome-wide RNAi screen revealed that Trio is essential for activating AP-1 via Gαq ? A network of Trio-regulated Rho GTPases and MAPKs links Gq to the nucleus ? A hard-wired Gq-Trio signaling axis promotes the growth of many human malignancies  相似文献   

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Highlights? 1.1/1.37 Å polysaccharide monooxygenases structures have active-site dioxygen species ? The structures reveal a large variance in substrate binding surfaces ? Proposed electron transport pathways in polysaccharide monooxygenases are conserved ? Polysaccharide monooxygenases and CBM33 enzymes likely bind substrates differently  相似文献   

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Highlights► Microbes can efficiently reduce CO2 to organic commodities with electrical energy. ► Direct electrode-to-microbe electron transfer can support anaerobic CO2 respiration. ► Electrochemically generated H2 can support anaerobic or aerobic CO2 reduction. ► Anaerobic CO2 respiration yields high recovery of electrons in organic commodities. ► If scalable, electrobiocommodities could revolutionize biocommodity production.  相似文献   

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Highlights? Improved models by DEN refinement at 7 Å ? Best method is DEN refinement with initial segmented rigid-body refinement ? Rfree has predictive power at 7 Å  相似文献   

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Highlights? Two structures of inactivated RNRs show two concatenated α4β4 rings in the crystal ? Solution scattering shows rings interlock in the presence of crystallization solution ? Electron microscopy shows open and incomplete states of ring formation ? Mechanism of protein ring concatenation by ring opening and closing is proposed  相似文献   

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Highlights? Two conformations of yeast V-ATPase EGChead peripheral stalk complex were solved ? The EG heterodimer of the eukaryotic V-ATPase forms a noncanonical coiled coil ? Subunit G contains a conserved random coiled bulge that interrupts the coiled coil ? The EGChead interaction represents an important target for therapeutic development  相似文献   

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Highlights? Global levels of histone acetylation change in response to pHi alterations ? Histone deacetylation and acetate transport through H+-coupled MCTs regulates pHi ? Proliferation of T cells results in increases in pHi and global histone acetylation ? HDAC and MCT inhibitors decrease pHi  相似文献   

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Highlights? Small, sneaky squid males produce spermatozoa that swarm to CO2 ? Sneaker, but not consort, sperm acidify their intracellular pH due to extracellular acidification by carbonic anhydrase ? Recovery from intracellular acidosis evokes Ca2+-dependent chemotactic swarming ? Swarming by sneaker sperm might be an evolutionary adaptation to mating tactics  相似文献   

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Highlights? The peroxiredoxin, Jafrac1, controls primordial germ cell adhesion during gastrulation ? H2O2 treatment of Drosophila embryos reduces DE-cadherin and β-catenin levels ? Increasing DE-cadherin levels is sufficient to rescue the Jafrac1 phenotype ? Jafrac1 stabilizes the level of adherens junction components in Drosophila embryos  相似文献   

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Highlights? The structure of Mtb LdtMt2 shows the binding of a peptidoglycan fragment ? The structure of the complex maps the interaction between acyl donor and enzyme ? Ldts show a conserved C-terminal ykuD domain with a divergent N-terminal domain ? Based on the structure of this complex, a reaction mechanism is proposed  相似文献   

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Highlights? Crystal structure of the DNA polymerase IIIα in complex with τc and a DNA substrate ? τc interacts with the C-terminal domain of PolIIIα through its C-terminal helix and the loop that follows it ? PolIIIα in complex with τc and DNA displays an open form ? The structure of this complex suggests an atomic model of the bacterial replisome  相似文献   

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