A microRNA miR-34a-Regulated Bimodal Switch Targets Notch in Colon Cancer Stem Cells

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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     

Differential Regulation of Distinct Vps34 Complexes by AMPK in Nutrient Stress and Autophagy

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Highlights? Different Vps34 complexes are distinctly regulated upon energy stress ? AMPK activates the proautophagy Vps34 complex by phosphorylating Beclin1 ? AMPK inhibits the nonautophagic Vps34 complex by phosphorylating Vps34 ? ATG14L determines whether the Vps34 complex is activated or inhibited by AMPK     

Dynamic Interaction between Sigma-1 Receptor and Kv1.2 Shapes Neuronal and Behavioral Responses to Cocaine

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Highlights? Sig-1R activity enhances sensitivity to cocaine by decreasing accumbal firing ? Cocaine decreases accumbal firing via Sig-1R-dependent increase of Kv1.2 current ? The Sig-1R forms a complex with Kv1.2 channel in the nucleus accumbens shell ? Cocaine triggers a long-lasting upregulation of the Sig-1R-Kv1.2 channel complex     

Keeping cell identity in Arabidopsis requires PRC1 RING-finger homologs that catalyze H2A monoubiquitination

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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     

SIP1 Mediates Cell-Fate Decisions between Neuroectoderm and Mesendoderm in Human Pluripotent Stem Cells

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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     

Perivascular Nitric Oxide Activates Notch Signaling and Promotes Stem-like Character in PDGF-Induced Glioma Cells

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Highlights? Perivascular niche nitric oxide activates Notch in PDGF-induced gliomas ? Notch signaling drives tumor stem-like characteristics and reduces survival ? Loss of eNOS activity decreases tumor stem-like characteristics ? Suppressing eNOS activity prolongs survival in glioma-bearing mice     

Comprehensive Analysis of Silencing Mutants Reveals Complex Regulation of the Arabidopsis Methylome

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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     

Protein model discrimination using mutational sensitivity derived from deep sequencing

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Highlights? Individual mutant phenotypes in a saturation library derived via deep sequencing ? Residue depth and active-site residue derivation from mutant phenotypes ? Mutant-phenotype-derived parameters used for protein model discrimination ? Derivation of sequence-structure-function relationships without protein isolation     

Visualizing the Determinants of Viral RNA Recognition by Innate Immune Sensor RIG-I

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Highlights? Crystallographic structure of RIG-I with 5′ triphosphorylated RNA duplex and ADP ? Solution biophysical analysis of ATP-dependent RIG-I conformational change ? The structural basis for ATP-stimulated RIG-I activation     

The Centrosome Regulates the Rab11- Dependent Recycling Endosome Pathway at Appendages of the Mother Centriole

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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     

Sculpting of DNA at Abasic Sites by DNA Glycosylase Homolog Mag2

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Highlights? Unflipped AP site stabilized by helix-hairpin-helix DNA glycosylase homolog Mag2 ? Nonenzymatic AP site recognition and DNA sculpting ? Sculpting of DNA conformation enhances substrate transfer between proteins     

Spatial Restriction of FGF Signaling by a Matrix Metalloprotease Controls Branching Morphogenesis

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Highlights? Drosophila Matrix Metalloprotease (Mmp) inhibits FGF signaling ? An FGF – MMP feedback loop regulates branching morphogenesis ? Mmp2 spatially regulates FGF signaling in epithelia     

System-wide Rewiring Underlies Behavioral Differences in Predatory and Bacterial-Feeding Nematodes

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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     

Tremor Suppression by Rhythmic Transcranial Current Stimulation

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Highlights? Phase-cancelling cortical stimulation attenuates Parkinsonian tremor ? Prolonged stimulation may invoke adaptive mechanisms ? Phase cancellation may provide a generic treatment approach to oscillopathies ? TACS provides a convenient probe of cortical circuit dynamics in humans     

Solution Conformations of Prototype Foamy Virus Integrase and Its Stable Synaptic Complex with U5 Viral DNA

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Highlights? Missing domains in PFV intasome revealed by SAXS/SANS ? PFV IN undergoes dramatic changes in conformation and oligomerization upon binding DNA ? Strand transfer inhibitors do not alter quaternary structure of PFV intasome     

Evidence for Geomagnetic Imprinting as a Homing Mechanism in Pacific Salmon

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Highlights? Sockeye salmon use geomagnetic imprinting as a homing mechanism ? The homing route of salmon is predicted by magnetic field drift (secular variation)     

Hypertrophy and unconventional cell division of hepatocytes underlie liver regeneration

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Highlights? Not all hepatocytes undergo cell division during liver regeneration ? Hypertrophy precedes proliferation in the regenerating liver ? Hepatocytes infrequently enter into M phase during liver regeneration ? Binuclear hepatocytes undergo cell division to generate mononuclear hepatocytes     

Two Deubiquitylases Act on Mitofusin and Regulate Mitochondrial Fusion along Independent Pathways

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Highlights? Mitochondrial fusion is regulated by independent ubiquitylation pathways ? The deubiquitylase Ubp2 promotes fusion, whereas Ubp12 inhibits fusion events ? Self-assembly and ubiquitylation cooperatively enable mitochondrial fusion ? Yeast mitofusin is sequentially ubiquitylated     

MTR1 encodes a secretory fasciclin glycoprotein required for male reproductive development in rice

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Highlights? The fasciclin glycoprotein MTR1 regulates male reproductive development in rice ? Rice male reproductive cells secrete MTR1 to control somatic tapetum development