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1.
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Highlights► The intestinal microbiome is recognized as an important determinant of health. ► Galacto-oligosaccharides are non-digestible carbohydrates. ► Galacto-oligosaccharides stimulate growth and activity of gut bacteria. ► Subtle differences in structure can result in significant differences in activity. ► Less abundant oligosaccharides from bovine milk are similar to those from human milk.  相似文献   

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Highlights? Lysosome-related organelles in intestinal cells are the major site of zinc storage ? The cation diffusion facilitator protein CDF-2 transports zinc into gut granules ? Gut granules adopt a bilobed morphology in high dietary zinc ? Zinc storage in gut granules promotes zinc detoxification and mobilization  相似文献   

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Highlights? Detailed analysis of diet-induced obesity in more than 100 inbred mouse strains ? Identification of 11 genetic loci associated with obesity and dietary responsiveness ? Significant overlap between mouse loci with human GWAS loci for obesity ? Strain-specific shifts in gut microbiota composition in response to dietary intervention  相似文献   

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Highlights? Production of soluble NIK kinase domain ? Structures of apo murine and human NIK possess active conformation ? Structure of mNIK bound to inhibitors reveals conformational flexibility ? Inhibitor potency varies against mNIK and hNIK due to substitution in the active site  相似文献   

5.
Highlights? Myosin-V alternates between active and passive actin-binding modes ? Myosin-V opposes kinesin-propelled cargo redistribution ? Myosin-V anchors kinesin-propelled cargo in actin-rich areas ? Myosin-V can drive medium-range directional transport at the cell periphery  相似文献   

6.
Highlights? The crystal structure of 12-lipoxygenase was solved at high resolution ? The position of an inhibitor identified the substrate binding/active site ? A channel providing access for oxygen to the active site was also discovered ? The structure accounts for virtually all features of catalysis and inhibition  相似文献   

7.
Highlights? Vault particles can be exploited in nanobiotechnology as drug delivery nanodevices. ? The structural information of vaults would serve as a guide for rational engineering. ? The dynamic structure of vaults may be controlled for manipulation of drug release. ? Engineered vaults allow specific cell targeting and controlled encapsulation.  相似文献   

8.
Highlights? Caspase activity is required for gut cell turnover ? Caspase is specifically activated in ECs of midgut after wounding ? Caspase activity in ECs is required for fly survival after wounding ? EC turnover is required for dampening the production of lethal factors after wounding  相似文献   

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Highlights? M. tuberculosis FadD13 is a peripheral membrane protein ? Mutagenesis reveals an arginine-rich patch as the site for membrane interaction ? A hydrophobic tunnel extends from the active site to the positively charged patch ? The architecture lets substrates reside partly in the membrane during catalysis  相似文献   

10.
Highlights? Antimycobacterial antibiotics activate autophagy in Mtb-infected host cells ? Autophagy activation depends on cellular and mitochondrial reactive oxygen species ? Host cell autophagy is essential for antimycobacterial drug action in infected macrophages and flies ? Antibiotic-induced autophagy dampened proinflammatory responses in infected macrophages  相似文献   

11.
Highlights? Satellite cells can differentiate into brown adipocytes ? MicroRNA-133 targets Prdm16 3′UTR and controls brown adipose determination ? MicroRNA-133 antagonism induces active brown adipocytes within regenerating muscle ? MicroRNA-133 antagonism impedes the development of obesity  相似文献   

12.
Highlights? Ell3 is preferentially found at active, poised, and inactive enhancers in ES cells ? Promoter-proximal Pol II occupancy at key developmental genes requires Ell3 ? Cohesin functions in Ell3-associated enhancer-promoter communication ? Recruitment of P-TEFb within SEC during differentiation is Ell3 dependent  相似文献   

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Highlights? LCMT-1 makes extensive contacts to PP2A active site for methylation of PP2A tail ? PP2A methylation is stimulated by phosphatase activation, hampered by inactivation ? LCMT-1 would facilitate efficient transition of activated PP2A to holoenzymes ? A high-affinity dnLCMT-1 mutant attenuates the cell cycle without causing cell death  相似文献   

15.
Highlights? Structures of the SAGA deubiquitinating module lacking the Sgf11 zinc finger domain ? The DUB module lacking the Sgf11 zinc finger forms a domain swapped complex dimer ? The conformational changes accompanying domain-swapping disrupt the active site ? Activating mutations in Ubp8 promote the compact form of the DUB module  相似文献   

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Highlights? Endodermal EpCAM cell autonomously modulates the Wnt2bb-induced hepatic development ? EpCAM directly binds to Kremen1 and disrupts the Kremen1-Dkk2 interaction ? EpCAM derepresses Lrp6 and allows Lrp6 clustering into active signalosomes ? EpCAM licenses and cooperatively activates Wnt2bb signaling in the endoderm  相似文献   

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Highlights? MO25 forms a stable complex with MST4 to enhance its kinase activity ? Association of MO25 activates MST4 by rotating its αC helix to active conformation ? Kinase-domain-mediated dimerization is required for MST4 trans-autophosphorylation ? MO25-stimulated activation of MST4 promotes apoptosis in HEK293T cells  相似文献   

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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  相似文献   

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Highlights? Endosome-proteins localize to centrosomes independent of membranes ? Rab11 and its modulators localize to mother centriole appendages ? Mother centriole appendages regulate membrane recycling through Rab11  相似文献   

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Highlights? Microbial genomes contain multiple clusters for biosynthesis of chemically diverse compounds. ? Most of such genes remain silent, preventing the respective compounds from being discovered. ? Silent gene clusters can be activated and/or heterologously expressed. ? New microbial hosts and tools are needed to make the abovementioned process efficient. ? Synthetic biology will play a major role in the genome-based drug discovery.  相似文献   

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