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1.
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   

2.
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   

3.
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   

4.
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   

5.
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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   

6.
EMT and dissemination precede pancreatic tumor formation   总被引:2,自引:0,他引:2  
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   

7.
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   

8.
Highlights? miR-34a regulates colon cancer stem cell asymmetric division ? miR-34a generates a sharp threshold response ? miR-34a converts Notch signaling into a toggle switch ? Binary Notch levels specify self-renewal versus differentiation  相似文献   

9.
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   

10.
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   

11.
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   

12.
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   

13.
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   

14.
15.
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   

16.
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   

17.
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   

18.
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   

19.
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  相似文献   

20.
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