Highlights? Top-down and bottom-up approaches to genome streamlining. ? Computational support for constructing and refactoring streamlined genomes. ? From genome engineering to metabolic reprogramming. ? Perspectives in applied genome engineering. 相似文献
Highlights? Many domains are erased along every lineage thus depriving genomes of building blocks. ? Novel domains are rare but spread rapidly in genomes and confer a high adaptive value. ? Novel domains arise in their own ORFs, by exonisation or extending ORFs. ? Rearrangements of proteins are evolutionary fast and drive molecular biodiversity. ? Rearrangements entail subtle but important adaptations, triggering gene family growth. 相似文献
Highlights? Structure of dimeric apoA-IV solved to 2.4 Å by X-ray crystallography ? Structure confirmed through biochemical and mutational analysis ? Understanding of apoA-IV dimerization allowed us to create a monomeric mutant ? Structural features in the dimer offer clues to the genesis of apoA-IV lipoproteins 相似文献
Highlights? The Sensor assay reliably identifies potent single-copy shRNAs ? Potent shRNAs are rare and generally not predicted by existing algorithms ? Analyses of ~20,000 shRNAs reveal insights into shRNA biogenesis and function ? Sensor-based rules provide a criteria framework for rational shRNA design 相似文献
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
Highlights? Invading cells exhibit EMT in an autochthonous model of pancreatic cancer ? Mutant cells enter the circulation before cancer is found on histology ? Circulating pancreatic cells (CPCs) express cancer stem cell-associated markers ? Inflammation is necessary and sufficient for EMT, invasion, and dissemination 相似文献
Highlights? Amino acid changes near the central pore of XPD confer defective excision repair ? These mutants retain DNA helicase activity when tested in an archaeal framework ? The mutants are unable to sense lesions during their ATP-driven tracking movement ? The mutants are unable to build a stable demarcation complex at DNA lesion sites 相似文献
Highlights? Palmitate induces β cell dysfunction by activating inflammatory processes in islets ? β cells sense palmitate via the TLR4 pathway and recruit M1 macrophages to islets ? M1 macrophages play a pivotal role in palmitate-induced β cell dysfunction ? M1 macrophages and inflammation also play a role in β cell dysfunction in T2D models 相似文献
Highlights? The PRP interferes with decision making and routing to the motor response ? Sensory evidence accumulation can occur for multiple decisions at the same time ? A large fraction of the PRP occurs after the commitment to a choice ? Evidence accumulation and sensory-motor mapping are distinct processes 相似文献
Highlights? MS quantifies 1,578 mitochondrial acetyl sites altered during CR and loss of SIRT3 ? SIRT3 functions as a prominent regulator in CR adaptation ? CR and SIRT3 regulate previously unrecognized processes in mitochondria ? We provide an acetylation atlas for understanding mitochondrial regulation in CR 相似文献
Highlights? Nature is equipped with solutions to use light to drive essential metabolic processes. ? Delivery of foreign genes enables light sensitivity to otherwise insensitive cells. ? Cells are engineered to transform light energy into desired biological functions. ? Light-regulated control has led to great advances in biomedical research. 相似文献
Highlights? Contrary to previous predictions FAM3B PANDER exhibits a new non-cytokine-like fold ? The new fold is also conserved in FAM3C ILEI and involved in cancer and tumor formation ? FAM3 is a new class of signaling molecules different from currently known cytokines 相似文献
Highlights? A high-content chemical screen identifies modulators of intracellular mycobacteria ? Three compounds that kill bacteria by altering host processes were validated ? Multiparametric chemical and genetic data sets integrated to identify mode of action ? Modulation of autophagy and endosomal trafficking identified as mode of action 相似文献
Highlights? K48 and K63 linkages in branched and unbranched tri-Ub retain their structural features ? Linkage-selective receptors recognize K48 and K63 linkages in the branched tri-Ub ? Linkage-specific deubiquitinases cleave their cognate Ub-Ub linkages in the mixed-linkage chains ? The 26S proteasome recognizes and processes branched K48- and K63-linked tri-Ub 相似文献
Highlights? Sox2+ve basal stem/progenitor cells self-renew and differentiate in vitro and in vivo ? Conditional Sox2 overexpression promotes the expansion of basal progenitor cells ? Sox2 cooperates with an inflammatory microenvironment to induce squamous cancer ? Sox2 and Stat3 together transform mouse and human esophageal progenitor cells 相似文献
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