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

1. Download : Download high-res image (158KB)
2. Download : Download full-size image

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     

Macrophage autophagy plays a protective role in advanced atherosclerosis

1. Download : Download high-res image (147KB)
2. Download : Download full-size image

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     

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

1. Download : Download high-res image (150KB)
2. Download : Download full-size image

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     

Regulation of Glycolysis by Pdk Functions as a Metabolic Checkpoint for Cell Cycle Quiescence in Hematopoietic Stem Cells

1. Download : Download high-res image (269KB)
2. Download : Download full-size image

Highlights? LT-HSCs activate glycolysis and generate ATP in a HIF-1α-dependent manner ? Pdk overexpression in HIF-1α^Δ/Δ HSCs restored glycolysis and stem cell capacity ? Pdk2^?/?: Pdk4^?/? LT-HSCs show defective glycolysis and cell cycle quiescence ? Pdk mimetic promotes the survival and transplantation capacity of LT-HSCs     

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

1. Download : Download high-res image (169KB)
2. Download : Download full-size image

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     

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

1. Download : Download full-size image

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     

Tmem64 Modulates Calcium Signaling during RANKL-Mediated Osteoclast Differentiation

1. Download : Download high-res image (172KB)
2. Download : Download full-size image

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     

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

1. Download : Download high-res image (164KB)
2. Download : Download full-size image

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     

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

1. Download : Download high-res image (239KB)
2. Download : Download full-size image

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     

Endothelial Cells Are Essential for the Self-Renewal and Repopulation of Notch-Dependent Hematopoietic Stem Cells

1. Download : Download high-res image (363KB)
2. Download : Download full-size image

Highlights? Coculture with endothelial cells promotes HSC expansion and self-renewal ? Endothelial cell effect on HSCs mediated by Notch signaling ? In vivo, sinusoidal endothelial cells (SECs) express Notch ligands ? Blocking vessel remodeling impairs hematopoietic recovery after irradiation     

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

1. Download : Download high-res image (289KB)
2. Download : Download full-size image

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

1. Download : Download high-res image (121KB)
2. Download : Download full-size image

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     

Interplay between the Dividing Cell and Its Neighbors Regulates Adherens Junction Formation during Cytokinesis in Epithelial Tissue

1. Download : Download high-res image (261KB)
2. Download : Download full-size image

Highlights? During cytokinesis, neighboring cells accumulate MyoII at the edges of the furrow ? MyoII nonautonomously sets the initial geometry of the daughter cell interface ? Neighboring membranes impede adherens junction (AJ) formation until a midbody forms ? Arp2/3-dependent actin accumulation in the dividing cell maintains AJ geometry     

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

1. Download : Download high-res image (156KB)
2. Download : Download full-size image

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     

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

1. Download : Download high-res image (451KB)
2. Download : Download full-size image

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     

HSF-1 regulators DDL-1/2 link insulin-like signaling to heat-shock responses and modulation of longevity

1. Download : Download high-res image (260KB)
2. Download : Download full-size image

Highlights? C. elegans DAF-2 insulin-like signaling negatively regulates HSF-1 activity ? DDL-1 and DDL-2 are negative regulators of HSF-1 ? Formation of a complex containing DDL-1/2 and HSF-1 inhibits HSF-1 activity ? DAF-2 signaling promotes DHIC formation by inhibiting DDL-1 phosphorylation     

Snx3 Regulates Recycling of the Transferrin Receptor and Iron Assimilation

1. Download : Download high-res image (201KB)
2. Download : Download full-size image

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     

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

1. Download : Download high-res image (98KB)
2. Download : Download full-size image

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     

ASH2L Regulates Ubiquitylation Signaling to MLL: trans-Regulation of H3 K4 Methylation in Higher Eukaryotes

1. Download : Download high-res image (146KB)
2. Download : Download full-size image

Highlights? ASH2L WH motif is important for trans-regulation of H3 K4 methylation by H2Bub ? Ub stimulates MLL activity in trans, in contrast to DOT1L regulation by H2Bub ? H2Bub enhances MLL, but not MLL3, methyltransferase activity ? H2Aub directly represses MLL methyltransferase activity