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     

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     

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     

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     

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     

Generation of Rejuvenated Antigen-Specific T Cells by Reprogramming to Pluripotency and Redifferentiation

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Highlights? Reprogramming of antigen-specific T cells to generate iPSCs (T-iPSCs) ? Redifferentiation of CD8⁺ T cells, with original antigen specificity, from T-iPSCs ? Newly differentiated T cells show high proliferation and elongated telomeres ? T cell antigen-specific cytotoxicity is maintained     

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     

Retinoic acid production by endocardium and epicardium is an injury response essential for zebrafish heart regeneration

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Highlights? Cardiac injury induces structural and molecular changes in zebrafish endocardium ? Endocardial and epicardial cells at the site of injury synthesize retinoic acid (RA) ? The extent of this injury response correlates with a species' regenerative capacity ? Regenerative cardiomyocyte proliferation in zebrafish requires retinoic acid signaling     

FGF9 and FGF20 maintain the stemness of nephron progenitors in mice and man

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Highlights? FGF20 and FGF9 are the niche ligands for developing metanephric kidney progenitors ? FGF9 is expressed in duct epithelia; both ligands are expressed by progenitor cells ? FGF20 loss in humans, or FGF9/20 loss in mice, results in kidney agenesis ? FGF9/20 can maintain competence of sorted, pure progenitor cell populations in vitro     

Development and Regeneration of Sox2+ Endoderm Progenitors Are Regulated by a HDAC1/2-Bmp4/Rb1 Regulatory Pathway

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Highlights? Hdac1/2 regulate development of Sox2+ endoderm progenitors ? Bmp4, Rb1, p21, and p16 are direct targets of Hdac1/2 in lung endoderm ? Increased Bmp4 suppresses Sox2 expression in lung endoderm ? Hdac1/2 are required for lung secretory epithelial regeneration     

Liver-Primed Memory T Cells Generated under Noninflammatory Conditions Provide Anti-infectious Immunity

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Highlights? Memory-like CD8⁺ T cells are generated in the liver in the absence of inflammation ? An alternative pathway of T cell priming is facilitated by nonimmune cells ? Liver-primed T cells are rescued from deletion for anti-infectious immunity ? T cell priming in the liver complements conventional memory T cell generation     

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     

Histone Acetylation Regulates Intracellular pH

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Highlights? Global levels of histone acetylation change in response to pH_i alterations ? Histone deacetylation and acetate transport through H⁺-coupled MCTs regulates pH_i ? Proliferation of T cells results in increases in pH_i and global histone acetylation ? HDAC and MCT inhibitors decrease pH_i     

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     

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     

Induced Pluripotent Stem Cell-Derived Neural Cells Survive and Mature in the Nonhuman Primate Brain

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Highlights? Autologous iPSC-derived neural progenitors survive in the monkey brain for 6 months ? Grafted cells differentiate into neurons, astrocytes, and oligodendrocytes ? Autologous transplantation elicits minimal immune and glial response     

Saturated fatty acid and TLR signaling link β cell dysfunction and islet inflammation

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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     

Quiescent and Active Hippocampal Neural Stem Cells with Distinct Morphologies Respond Selectively to Physiological and Pathological Stimuli and Aging

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Highlights? Notch signaling defines morphologically distinct hippocampal stem cell populations ? Radial and horizontal hippocampal stem cells depend on canonical Notch signaling ? Different neural stem cell subpopulations respond selectively to neurogenic stimuli ? Aging results in a reversible transition of stem cells to a quiescent state     

β-Catenin-Driven Binary Fate Specification Segregates Germ Layers in Ascidian Embryos

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Highlights? β-catenin nuclear asymmetry after animal-vegetal-oriented cell divisions ? β-catenin nuclear asymmetry drives binary cell fate choices ? Combinatorial codes of nuclear β-catenin activation segregate ascidian germ layers ? Nuclear β-catenin ON-to-OFF activity is required for marginal mesoderm formation