The IRP1-HIF-2α Axis Coordinates Iron and Oxygen Sensing with Erythropoiesis and Iron Absorption

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Highlights? Derepression of HIF-2α mRNA in Irp1^?/? mice causes age-dependent polycythemia ? HIF-2α hyperactivity is observed in multiple tissues of Irp1^?/? mice ? The mRNA regulons of IRP1 and IRP2 are separable in vivo ? The IRP1-HIF-2α axis is a therapeutic target for hematologic or oncologic disorders     

AMPK Is a Negative Regulator of the Warburg Effect and Suppresses Tumor Growth In Vivo

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Highlights? Loss of AMPKα1 cooperates with the Myc oncogene to accelerate lymphomagenesis ? AMPKα dysfunction enhances aerobic glycolysis (Warburg effect) ? Inhibiting HIF-1α reverses the metabolic effects of AMPKα loss ? HIF-1α mediates the growth advantage of tumors with reduced AMPK signaling     

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     

Identification of Distinct Ligands for the C-type Lectin Receptors Mincle and Dectin-2 in the Pathogenic Fungus Malassezia

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Highlights? Mincle and Dectin-2 cooperatively recognize Malassezia through distinct ligands ? The Mincle ligands in Malassezia are glucosyl- and mannosylglycolipids ? The Dectin-2 ligand in Malassezia is an O-linked mannobiose-rich glycoprotein ? Cytokine response to the respective ligands was impaired in Mincle^?/? and Dectin-2^?/? DCs     

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     

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     

Strong immunogenicity and cross-reactivity of Mycobacterium tuberculosis ESX-5 type VII secretion: encoded PE-PPE proteins predicts vaccine potential

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Highlights? Mtb ESX-5-associated and -nonassociated PE/PPE proteins are highly immunogenic ? ESX-5 core component eccD₅ modulates the mycobacterial antigenic repertoire ? ESX-5 PE/PPE deleted Δppe25-pe19 Mtb strain is avirulent, yet strongly immunogenic ? Δppe25-pe19 strain protects mice against Mtb infection and represents a vaccine candidate     

A Molecular Motor,KIF13A,Controls Anxiety by Transporting the Serotonin Type 1A Receptor

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Highlights? Kif13a^?/? mice show elevated-anxiety-like behavioral defects ? 5HT_1A receptors are not properly transported in Kif13a^?/? neurons ? The forkhead-associated domain of KIF13A associates directly with 5HT_1A receptors ? KIF13A can translocate 5HT_1A receptors in vivo and in vitro     

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     

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     

Inactivation of BAD by IKK Inhibits TNFα-Induced Apoptosis Independently of NF-κB Activation

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Highlights? IKK can inhibit TNFα-induced apoptosis independently of NF-κB activation ? Inhibition of BAD constitutes the NF-κB-independent antiapoptotic axis of IKK ? IKK phosphorylates BAD at Ser26 and primes it for inactivation ? BAD inactivation coordinates with NF-κB activation to suppress TNFα-induced apoptosis     

Conformational Dynamics of the Rpt6 ATPase in Proteasome Assembly and Rpn14 Binding

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Highlights? Proteasome ATPase Rpt6 undergoes helix-coil exchange in its C-terminal domain ? Rpt6 G^360,387A has a stabilized four-helix bundle and raised melting temperature ? Assembly chaperone Rpn14 binds selectively to the four-helix bundle Rpt6 conformer ? Rpt6 G^360,387A (rpt6AA) is synthetically defective with an rpn14 null mutation     

Stalled fork rescue via dormant replication origins in unchallenged S phase promotes proper chromosome segregation and tumor suppression

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Highlights? An unstable MCM2-7 complex results in a loss of dormant origins in Mcm4^Chaos3 cells ? A loss of dormant origins impairs stalled fork recovery in unchallenged S phase ? A loss of dormant origins increases replication intermediates in prophase ? Replication intermediates in M phase are a likely cause of chromosome instability     

A Genome-wide RNAi Screen Reveals a Trio-Regulated Rho GTPase Circuitry Transducing Mitogenic Signals Initiated by G Protein-Coupled Receptors

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Highlights? Human cancers harbor frequent mutations in Gq-linked GPCRs and Gα_q subunits ? A genome-wide RNAi screen revealed that Trio is essential for activating AP-1 via Gα_q ? A network of Trio-regulated Rho GTPases and MAPKs links Gq to the nucleus ? A hard-wired Gq-Trio signaling axis promotes the growth of many human malignancies     

Monitoring Tumorigenesis and Senescence In Vivo with a p16INK4a-Luciferase Model

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Highlights? Activation of cellular senescence with aging does not predict cancer mortality ? p16^LUC detects emerging tumors in 14 genetically distinct tumor models ? p16^LUC provides a detection advantage over other in vivo cancer monitoring systems ? Both the tumor and stroma of emerging neoplasms express high levels of p16^INK4a     

Structure of a bacteriophytochrome and light-stimulated protomer swapping with a gene repressor

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Highlights? Bacteriophytochrome structure containing photosensory and output transducing domain ? RpBphP1 binds to the cognate repressor RpPpsR2 on illumination with far-red light ? HOS domain is distantly related to Dhp and is essential for binding to the repressor ? Light-induced protomer swapping mechanism between dimers     

Snx3 Regulates Recycling of the Transferrin Receptor and Iron Assimilation

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Highlights? Snx3 is highly expressed in vertebrate hematopoietic tissues ? Silencing of Snx3 results in anemia and hemoglobin defects in vertebrates ? Snx3 and Vps35 physically interact with Tfrc ? Snx3 is required for endosomal recycling of Tf-Tfrc complex     

Variable lymphocyte receptor recognition of the immunodominant glycoprotein of Bacillus anthracis spores

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Highlights? VLRBs use their C-terminal LRRs and the LRRCT-loop to interact with antigen ? Sequence-related VLRBs exhibit differential recognition of their BclA epitopes ? VLR4 binds a conserved protein epitope, yet is specific for B. anthracis spores