Peroxiredoxin stabilization of DE-cadherin promotes primordial germ cell adhesion

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Highlights? The peroxiredoxin, Jafrac1, controls primordial germ cell adhesion during gastrulation ? H₂O₂ treatment of Drosophila embryos reduces DE-cadherin and β-catenin levels ? Increasing DE-cadherin levels is sufficient to rescue the Jafrac1 phenotype ? Jafrac1 stabilizes the level of adherens junction components in Drosophila embryos     

Crystal Structure of the O2-Tolerant Membrane-Bound Hydrogenase 1 from Escherichia coli in Complex with Its Cognate Cytochrome b

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Highlights? The structure of a membrane-bound [NiFe]-hydrogenase/cytochrome b complex ? One active hydrogenase is able to “jumpstart” its O₂-inactivated counterpart ? E. coli hydrogenase 1 has a central protective role against O₂-induced cell damage ? The structure defines the hydrogenase/cytochrome b active-interacting surface     

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     

SOD1 Integrates Signals from Oxygen and Glucose to Repress Respiration

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Highlights? Glucose and O₂ signal through Cu/Zn SOD1 to repress respiration ? SOD1 binds to and prevents turnover of a casein kinase CK1γ for respiration control ? Superoxide from aerobic glucose metabolism feeds the SOD1 reaction to stabilize CK1γ ? Both human and yeast CK1γ stability are regulated by SOD1     

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     

Targeting the Cell Wall of Mycobacterium tuberculosis: Structure and Mechanism of L,D-Transpeptidase 2

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Highlights? The structure of Mtb Ldt_Mt2 shows the binding of a peptidoglycan fragment ? The structure of the complex maps the interaction between acyl donor and enzyme ? Ldts show a conserved C-terminal ykuD domain with a divergent N-terminal domain ? Based on the structure of this complex, a reaction mechanism is proposed     

Probing H2O2-mediated Structural Dynamics of the Human 26S Proteasome Using Quantitative Cross-linking Mass Spectrometry (QXL-MS)

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Highlights

• •Two-step cross-linking coupled with affinity purification to facilitate structural analysis of protein complexes.
• •Integrated QXL-MS workflow for studying condition-dependent structural changes of protein complexes.
• •Mechanistic insights on in vivo H₂O₂-induced conformational dynamics of proteasome complexes.

     

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

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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     

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     

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     

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     

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     

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

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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     

Structural Determinants of RGS-RhoGEF Signaling Critical to Entamoeba histolytica Pathogenesis

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Highlights? E. histolytica expresses a convergently evolved RGS-RhoGEF protein ? EhRGS-RhoGEF possesses a conventional nine-helix RGS domain ? Activated EhRGS-RhoGEF induces S2 cell spreading through Rac1/2 ? EhRGS-RhoGEF modulates amoebic migration and host cell killing     

Genetic Correction of a LRRK2 Mutation in Human iPSCs Links Parkinsonian Neurodegeneration to ERK-Dependent Changes in Gene Expression

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Highlights? hiPSC-derived neurons with LRRK2 G2019S exhibit Parkinsonian neurodegeneration ? Genetic correction of the LRRK2 mutation rescued neurodegenerative phenotypes ? Comparative analysis links LRRK2 G2019S, gene dysregulation, and ERK activation ? ERK-dependent gene dysregulation by LRRK2 G2019S contributes to neurodegeneration     

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

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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     

DAD2 Is an α/β Hydrolase Likely to Be Involved in the Perception of the Plant Branching Hormone,Strigolactone

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Highlights? DAD2 gene, identified by transposon tagging, encodes an α/β hydrolase fold protein ? DAD2 acts in the shoot; mutants are insensitive to strigolactones ? DAD2 crystal structure shows an internal cavity capable of binding strigolactones ? DAD2 can hydrolyze the strigolactone GR24     

The bacterial stressosome: a modular system that has been adapted to control secondary messenger signaling

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Highlights? Regulation of cyclic di-GMP biosynthesis in Moorella thermoacetica ? Stressosome signal transduction and resetting ? X-ray crystal structure of type 2C phosphatase MtX ? X-ray crystal structures of phosphorylated MtS and the N-terminal domain of MtR     

Deletion of Iron Regulatory Protein 1 Causes Polycythemia and Pulmonary Hypertension in Mice through Translational Derepression of HIF2α

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Highlights? Irp1 deficiency causes polycythemia and pulmonary hypertension ? Irp1 regulates HIF2α translation and expression of EPO and endothelin 1 ? Irp1 represses erythropoiesis to protect tissue iron levels during iron deficiency ? A low-iron diet worsens polycythemia and causes sudden death in Irp1?/? animals     

A Pan-BCL2 Inhibitor Renders Bone-Marrow-Resident Human Leukemia Stem Cells Sensitive to Tyrosine Kinase Inhibition

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Highlights? Splice-isoform switching favors prosurvival BCL2 family expression in human BC ? BC LSCs are quiescent and TKI-resistant in the marrow niche ? Sabutoclax, a pan-BCL2 inhibitor, enhances TKI sensitivity of bone marrow BC LSCs