Axon Regrowth during Development and Regeneration Following Injury Share Molecular Mechanisms

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Highlights? Initial axon outgrowth and regrowth during remodeling are mechanistically distinct ? The nuclear receptor UNF is necessary for axon regrowth but not for initial growth ? TOR is also required for developmental regrowth but not for initial axon outgrowth ? UNF promotes axon regrowth via the TOR pathway and guidance via unknown mechanisms     

The Tripartite Motif Protein MADD-2 Functions with the Receptor UNC-40 (DCC) in Netrin-Mediated Axon Attraction and Branching

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Highlights? UNC-6 (Netrin), its receptor UNC-40 (DCC), and the TRIM protein MADD-2 promote axon branching ? MADD-2 and UNC-40 proteins are localized to the affected axon branch ? MADD-2 stimulates axon attraction to Netrin by acting as an UNC-40 cofactor ? MADD-2 enables UNC-40 to recruit MIG-10, an actin-binding effector protein     

Conversion of a Signal into Forces for Axon Outgrowth through Pak1-Mediated Shootin1 Phosphorylation

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Highlights? An attractive guidance cue, netrin-1, induces Pak1-mediated shootin1 phosphorylation ? Pak1-mediated shootin1 phosphorylation enhances clutch engagement at growth cones ? Pak1-mediated shootin1 phosphorylation promotes formation of traction forces ? Pak1-mediated shootin1 phosphorylation promotes axon outgrowth     

Spikes in Mammalian Bipolar Cells Support Temporal Layering of the Inner Retina

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Highlights? Light-driven calcium changes were recorded in mouse bipolar cell axon terminals ? Bipolar cells cluster into ≥eight functional types, which match anatomical types ? Fast and slow bipolar cells project to the inner retina in an organized manner ? The fastest bipolar cells generate clear all-or-nothing spikes     

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     

Cotranslational Response to Proteotoxic Stress by Elongation Pausing of Ribosomes

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Highlights? Proteotoxic stress reduces global protein synthesis by influencing elongation ? Proteotoxic stress induces ribosome pausing on mRNAs in the first 50 codons ? Molecular chaperones facilitate translation elongation by binding to nascent chains ? Ribosomes fine tune elongation rate in response to proteotoxic stress     

Spatial restriction of bone morphogenetic protein signaling in mouse gastrula through the mVam2-dependent endocytic pathway

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Highlights? mVam2 mediates endocytic transport from late endosomes to lysosomes ? mVam2 is essential for assembly of large apical vacuoles in visceral endoderm ? Loss of mVam2 results in hyperactivation of BMP signaling ? The mVam2-dependent BMP attenuation contributes to patterning in gastrulation     

Protein Secondary Structure Determination by Constrained Single-Particle Cryo-Electron Tomography

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Highlights? Efficient extraction of high-resolution information from cryo-EM tilt series ? Successful CTF correction strategy despite low-contrast and quality of tilted images ? Use of geometric constraints in refinement improves orientational accuracy of images ? Enforcement of tomographic constraints reduces model bias and overfitting artifacts     

LRP6 Enhances Glucose Metabolism by Promoting TCF7L2-Dependent Insulin Receptor Expression and IGF Receptor Stabilization in Humans

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Highlights? Nondiabetic LRP6 mutation carriers are hyperinsulinemic and insulin resistant ? IR expression is reduced in skeletal muscles of the LRP6 mutation carriers ? Wnt/LRP6 regulate the insulin receptor and IGFR expression ? The LRP6 mutation reduces TCF7L2-dependent IR expression and enhances mTOR activity     

Malaria Parasites Co-opt Human Factor H to Prevent Complement-Mediated Lysis in the Mosquito Midgut

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Highlights? Malaria gametes evade human complement by binding factor H ? The plasmodial protein PfGAP50 binds to factor H on the gamete surface ? Binding of factor H results in inactivation of the complement protein C3b ? Functional inhibition of factor H or PfGAP50 reduces parasite transmission to the mosquito     

Kinetic,Energetic, and Mechanical Differences between Dark-State Rhodopsin and Opsin

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Highlights? Mapping the stability of opsin from the rod outer segment of the mouse eye ? Compared to dark-state rhodopsin opsin increases mechanical stability and rigidity ? Compared to dark-state rhodopsin opsin reduces lifetime and free energy ? Compared to dark-state rhodopsin opsin is pliable and adopts alternate conformations     

Adipose Vascular Endothelial Growth Factor Regulates Metabolic Homeostasis through Angiogenesis

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Highlights? Two-way modulations of adipose VEGF were generated with aP2-Cre transgene ? Adipose VEGF KO reduces vasculature, increases hypoxia and inflammation in fat ? Adipose VEGF KO accelerates the development of metabolic disease in high-fat diet ? Induced adipose VEGF has opposite effect on fat and restores metabolic homeostasis     

Efficient Retrograde Transport of Pseudorabies Virus within Neurons Requires Local Protein Synthesis in Axons

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Highlights? Pseudorabies virus (PRV) infection stimulates local protein synthesis in axons ? Infection induces the synthesis of LIS1, peripherin, and annexin A2 in axons ? Axonal inhibition of protein synthesis retards retrograde PRV capsid transport ? Prior damage in axons significantly reduces retrograde PRV capsid transport     

Reactive Glia in the Injured Brain Acquire Stem Cell Properties in Response to Sonic Hedgehog

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Highlights? Stab wound injury and MCAo elicit a profound stem cell response ? Noninvasive brain injury fails to elicit a stem cell response ? SHH is upregulated and required in lesion conditions with a stem cell response ? SHH transducer deletion in astrocytes reduces their proliferative response to injury     

Lactocepin secreted by Lactobacillus exerts anti-inflammatory effects by selectively degrading proinflammatory chemokines

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Highlights? PrtP-encoded lactocepin degrades proinflammatory chemokines, notably IP-10 ? Lactocepin reduces lymphocyte infiltration in an ileitis model ? Lactocepin lowers IP-10 levels and cecal inflammation in a colitis model ? Lactocepin-based therapy may be a treatment option for chemokine-mediated diseases     

Leishmania donovani Targets Dicer1 to Downregulate miR-122, Lower Serum Cholesterol,and Facilitate Murine Liver Infection

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Highlights? Leishmania infection reduces liver miR-122 and lowers serum cholesterol ? Leishmania metalloprotease gp63 is required for inhibition of hepatic miR-122 activity ? gp63 cleaves DICER1 to downregulate miRNP-122 formation in hepatocytes ? Restoration of miR-122 elevates serum cholesterol to reduce liver parasite load     

Unfolded phosphopolypeptides enable soft and hard tissues to coexist in the same organism with relative ease

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Highlights? Some unfolded phosphoproteins form stable complexes with amorphous calcium phosphate. ? Stable complexes require ≥3 phosphorylated residues within a short sub-sequence. ? Soft and hard tissues can co-exist in the same organism because of these complexes.     

Decision Making during the Psychological Refractory Period

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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     

HIV Nef,Paxillin, and Pak1/2 Regulate Activation and Secretion of TACE/ADAM10 Proteases

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Highlights? HIV-Nef translocates activated TACE/ADAM17 into extracellular vesicles (EVs) ? The mechanism is initiated by interaction of Eed and paxillin with TACE ? Translocation of TACE into EVs is regulated by Pak2 ? Melanoma cells activate the same mechanism to upload activated ADAM10 into EVs