STIM1 Juxtaposes ER to Phagosomes,Generating Ca2+ Hotspots that Boost Phagocytosis

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Highlights? STIM1 drives store-operated recruitment of ER cisternae to phagosomes ? STIM1 is required for Ca²⁺-dependent, high-efficiency phagocytosis ? STIM1 gates phagosomal Ca²⁺ channels, generating periphagosomal Ca²⁺ microdomains     

ALKBH5 Is a Mammalian RNA Demethylase that Impacts RNA Metabolism and Mouse Fertility

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Highlights? ALKBH5 is a mammalian m⁶A RNA demethylase ? RNA demethylation affects mRNA export and RNA metabolism ? RNA demethylation is important for mouse fertility ? Reversible mammalian messenger RNA methylation affects gene expression     

Bone marrow-derived cell therapy stimulates endogenous cardiomyocyte progenitors and promotes cardiac repair

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Highlights? c-kit⁺ cell therapy stimulates endogenous cardiomyocyte progenitors ? Nkx2.5- and Gata4-expressing progenitors increase in the infarct border zone ? c-kit⁺ cell therapy leads to improved cardiac function ? No evidence for cardiomyocyte transdifferentiation by bone marrow progenitors     

p58IPK-Mediated Attenuation of the Proapoptotic PERK-CHOP Pathway Allows Malignant Progression upon Low Glucose

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Highlights? Transformation-associated glucose shortage triggers ER stress ? The ER stress acts as barrier to malignancy by triggering UPR-dependent apoptosis ? p58^IPK expression removes the UPR barrier by attenuating its PERK-CHOP branch ? This adaptive mechanism enables implementation of UPR cytoprotective features     

ADF/cofilin regulates secretory cargo sorting at the TGN via the Ca2+ ATPase SPCA1

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Highlights? ADF/cofilin localizes to the TGN and binds SPCA1 in an actin-dependent manner ? Dynamic actin regulates the activity of the Ca²⁺ pump SPCA1 ? ADF/cofilin facilitates secretory cargo sorting in a Ca²⁺-dependent manner     

Cap-assisted internal initiation of translation of histone H4

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Highlights? Two structural elements of histone H4 mRNA drive translation initiation ? Ribosome is tethered by an eIF4E-binding site located in the coding region ? A RNA three-way helix junction element positions ribosome on the start codon ? The m⁷G cap-binding pocket formed by the mRNA controls histone translation     

Characterization and In Vivo Pharmacological Rescue of a Wnt2-Gata6 Pathway Required for Cardiac Inflow Tract Development

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Highlights? Wnt2 is required for atrial and inflow tract morphogenesis ? Wnt2 regulates expansion of secondary heart field progenitors ? Defects in Wnt2^?/? mutants can be rescued using Wnt signaling agonists ? Wnt2 cooperates with Gata6 to regulate cardiac inflow tract development     

Proton-Coupled Dynamics in Lactose Permease

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Highlights? Deprotonation of Glu325 brings H⁺ translocation and sugar-binding sites together ? Deprotonation of Glu325 closes the internal water-filled cytoplasmic cavity ? Deprotonated LacY inserted into DMPC lipids shows no structural rearrangements ? The structural changes show remarkable similarities to experimental observations     

A master switch couples Mg²⁺-assisted catalysis to domain motion in B. stearothermophilus tryptophanyl-tRNA Synthetase

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Highlights? Combinatorial mutagenesis at four remote sites shifts reaction coordinate stabilities ? Cooperative action of all four sites accounts for the entire catalytic role of Mg2⁺ ? Catalysis of ATP utilization by Mg2⁺ occurs if, and only if, the conformation changes ? This type of allosteric effect may explain vectorial coupling in transducing NTPases     

Long-Term Space Flight Simulation Reveals Infradian Rhythmicity in Human Na+ Balance

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Highlights? Increased salt intake lowers urinary aldosterone but increases cortisol excretion ? At constant salt intake, urinary Na⁺ excretion exhibits a circaseptan pattern ? Total body Na⁺ exhibits a far-longer infradian rhythm, not related to body water ? Na⁺ can be stored in the body independent of water or blood pressure     

Structural Basis of Selective Ubiquitination of TRF1 by SCFFbx4

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Highlights? SCF ubiquitin ligase subunit Fbx4 binds TRF1 using an atypical small GTPase fold ? Fbx4 recognizes a globular domain of TRF1, not just short phosphorylated degrons ? Telomere shelterin component TIN2 competes with Fbx4 for TRF1 binding ? TIN2 and SCF^Fbx4 thus control TRF1 ubiquitination and degradation     

Structure of Phosphorylated SF1 Bound to U2AF65 in an Essential Splicing Factor Complex

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Highlights? Splicing factor SF1 phosphorylation on a conserved SPSP motif is required in vivo ? SPSP phosphorylation (P) induces local folding within an SF1/U2AF⁶⁵ interface ? Phosphorylation promotes an acutely bent (P)SF1/U2AF⁶⁵/RNA conformation     

Sprouty1 Regulates Reversible Quiescence of a Self-Renewing Adult Muscle Stem Cell Pool during Regeneration

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Highlights? Pax7⁺ skeletal satellite cells regenerate muscle in their endogenous environment ? Quiescent satellite cells express the RTK inhibitor Spry1 ? Spry1 is needed for satellite cells to return to quiescence after muscle injury ? Deletion of Spry1 in satellite cells depletes the muscle stem cell pool     

Na+ Regulation in the Malaria Parasite Plasmodium falciparum Involves the Cation ATPase PfATP4 and Is a Target of the Spiroindolone Antimalarials

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Highlights? The intraerythrocytic malaria parasite extrudes Na⁺ via a Na⁺-ATPase ? Parasite Na⁺ homeostasis is disrupted by the antimalarial spiroindolones ? Mutations in PfATP4 confer resistance to Na⁺ disruption by the spiroindolones ? PfATP4 is postulated to be a Na⁺ efflux ATPase and a target of the spiroindolones     

Imbalance between Neutrophil Elastase and its Inhibitor α1-Antitrypsin in Obesity Alters Insulin Sensitivity,Inflammation, and Energy Expenditure

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Highlights? Obese men and mice have decreased serum A1AT levels and increased NE activity ? Neutrophil infiltration and NE deposition occur in adipose tissue from HFD-fed mice ? NE^?/? and A1AT Tg mice have reduced HFD-induced insulin resistance and inflammation ? NE deletion increases AMPK signaling and fatty acid oxidation in liver and BAT     

Tmem64 Modulates Calcium Signaling during RANKL-Mediated Osteoclast Differentiation

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Highlights? Tmem64-deficient mice show increased bone volume ? Tmem64 deficiency reduces [Ca²⁺]_i oscillation in response to RANKL stimulation ? Tmem64 interacts with SERCA2 ? Tmem64 positively regulates osteoclast formation via SERCA2/Ca²⁺ signaling     

A subpopulation of adult skeletal muscle stem cells retains all template DNA strands after cell division

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Highlights? Pax7^Hi quiescent stem cells constitute a metabolically low “dormant” subpopulation ? Both Pax7^Hi and Pax7^Lo quiescent stem cells are serially transplantable ? Only proliferating Pax7^Hi cells segregate old DNA strands to the renewing stem cell ? CO-FISH demonstrates that template DNA strand cosegregation engages all chromosomes     

Polycomb Associates Genome-wide with a Specific RNA Polymerase II Variant,and Regulates Metabolic Genes in ESCs

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Highlights? A unique RNAPII variant (S5p⁺S7p^?S2p^?) binds PRC targets genome-wide in ESCs ? RNAPII-S5p and PRC coincide in time and localization, and show proportional abundance ? Novel, active PRC-target genes identified in ESCs include metabolic genes ? Active PRC targets switch between on/off (active/PRC) states in the ESC population     

Sperm from Sneaker Male Squids Exhibit Chemotactic Swarming to CO2

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Highlights? Small, sneaky squid males produce spermatozoa that swarm to CO₂ ? Sneaker, but not consort, sperm acidify their intracellular pH due to extracellular acidification by carbonic anhydrase ? Recovery from intracellular acidosis evokes Ca²⁺-dependent chemotactic swarming ? Swarming by sneaker sperm might be an evolutionary adaptation to mating tactics     

Macrophage autophagy plays a protective role in advanced atherosclerosis

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Highlights? Proapoptotic oxidative stress induces autophagy in macrophages (M?s) ? Inhibition of autophagy enhances oxidative stress and apoptosis in M?s ? Atheromata of M?-Atg5^?/?Ldlr^?/? mice have increased apoptosis and plaque necrosis ? Apoptotic Atg5^?/? M?s are poorly recognized by phagocytes in vitro and in atheromata