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     

PRDM14 Ensures Naive Pluripotency through Dual Regulation of Signaling and Epigenetic Pathways in Mouse Embryonic Stem Cells

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Highlights? Prdm14 expression is important for maintenance of naive pluripotency ? PRDM14 antagonizes FGFR signaling and activates Akt-mTORC1 signaling ? PRDM14 represses de novo DNA methyltransferase expression ? This regulatory input is mediated through recruitment of PRC2     

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     

Trachea-Derived Dpp Controls Adult Midgut Homeostasis in Drosophila

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Highlights? Trachea-derived Dpp/Bmp is required for midgut homeostasis ? Dpp expressed in tracheal cells reach intestinal cells through visceral muscles ? Dpp signaling is activated in enterocytes (ECs) in the Drosophila adult midgut ? Dpp signaling stabilizes ECs to restrict intestinal stem cell proliferation     

Viral-mediated noisy gene expression reveals biphasic E2f1 response to MYC

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Highlights? Gene expression noise is an efficient means to probe dose responses ? Variability in MYC reveals biphasic E2f1 dose response ? Modeling predicts serum attenuates E2F repression by MYC ? Biphasic expression underlies discrimination of aberrant levels of growth signaling     

Spatial Restriction of FGF Signaling by a Matrix Metalloprotease Controls Branching Morphogenesis

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Highlights? Drosophila Matrix Metalloprotease (Mmp) inhibits FGF signaling ? An FGF – MMP feedback loop regulates branching morphogenesis ? Mmp2 spatially regulates FGF signaling in epithelia     

The Ciliary G-Protein-Coupled Receptor Gpr161 Negatively Regulates the Sonic Hedgehog Pathway via cAMP Signaling

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Highlights? The GPCR Gpr161 localizes to primary cilia in a Tulp3/IFT-A-dependent manner ? Complete loss of Gpr161 increases Shh signaling in the mouse neural tube ? Gpr161 couples protein kinase A activation to Shh signaling via cAMP signaling ? Shh signaling internalizes Gpr161 from the cilia, preventing its activity     

A novel aux/IAA28 signaling cascade activates GATA23-dependent specification of lateral root founder cell identity

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Highlights? GATA23 is involved in lateral root founder cell specification ? A coordinated migration of pericycle nuclei precedes the first asymmetric division ? An Aux/IAA28-dependent auxin signaling cascade controls GATA23 expression     

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     

Mycobacterium tuberculosis activates the DNA-dependent cytosolic surveillance pathway within macrophages

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Highlights? M. tuberculosis permeabilizes phagosomes and activates cytosolic signaling pathways ? Host cytoplasmic DNA receptors sense M. tuberculosis extracellular DNA ? DNA recognition activates the STING/TBK1/IRF3 pathway ? Cytosolic sensing promotes M. tuberculosis infection     

bantam miRNA Promotes Systemic Growth by Connecting Insulin Signaling and Ecdysone Production

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Highlights? bantam is required in ecdysone-producing cells to promote body growth ? bantam inhibits ecdysone biosynthesis ? Insulin signaling regulates ecdysone production by repressing bantam activity ? Both the systemic and tissue-autonomous activities of bantam promote organ growth     

An ERK-p38 Subnetwork Coordinates Host Cell Apoptosis and Necrosis during Coxsackievirus B3 Infection

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Highlights? Intracellular signaling predicts the fate of coxsackievirus B3 (CVB3)-infected cells ? p38 and ERK signaling pathways are tightly interconnected during CVB3 infection ? CVB3-induced apoptosis of cardiomyocytes is inhibited by ERK5 and ERK1/2 pathways ? CVB3 induces necrosis of cardiomyocytes via p38 activation     

Robustness and Epistasis in the C. elegans Vulval Signaling Network Revealed by Pathway Dosage Modulation

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Highlights? A phase map of cell fate patterns is built as a function of signaling pathway dose ? The vulva system can buffer a 4-fold variation in mean lin-3/egf mRNA number ? The major role of LIN-12/Notch in the vulva is to promote the 2° fate ? Inhibition of 1° fate by LIN-12 is important when lin-3 dose is mildly increased     

The Helicobacter pylori virulence effector CagA abrogates human β-defensin 3 expression via inactivation of EGFR signaling

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Highlights? H. pylori is highly susceptible to the bactericidal activity of hBD3 ? hBD3 is initially induced by H. pylori via activation of EGFR/MAPK/JAK signaling ? H. pylori evades killing by downregulating hBD3 via CagA-mediated SHP-2 activation ? CagA virulence factor is a potent inhibitor of an immune effector mechanism     

Dopamine controls neurogenesis in the adult salamander midbrain in homeostasis and during regeneration of dopamine neurons

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Highlights? Regeneration of midbrain dopamine neurons depends on decreased dopamine signaling ? L-dopa inhibits ependymoglia cell proliferation during dopamine neuron regeneration ? Proliferation of ependymoglia cells is constantly suppressed by dopamine signaling ? Inhibition of dopamine signaling evokes neurogenesis by quiescent ependymoglia cells     

Rspo3 binds syndecan 4 and induces Wnt/PCP signaling via clathrin-mediated endocytosis to promote morphogenesis

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Highlights? Discovery that Rspo3 binds syndecan 4 ? Rspo3/Sdc4 induce Wnt/PCP signaling via clathrin-mediated endocytosis ? Rspo3/PCP signaling is essential for gastrulation and cartilage morphogenesis     

Cofactors required for TLR7- and TLR9-dependent innate immune responses

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Highlights? RNAi and systems-based analysis identified 190 TLR7/9 signaling cofactors ? Pathway crossprofiling enabled mapping cofactors to specific NFκB signaling modules ? HRS is a mediator of ubiquitin-dependent nondegradative endosomal TLR sorting     

MicroRNA-92a Upholds Bmp Signaling by Targeting noggin3 during Pharyngeal Cartilage Formation

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Highlights? mir92a inactivation leads to loss of pharyngeal cartilages in zebrafish embryos ? mir92a is required for chondrogenic progenitor proliferation and survival ? Bmp signaling is positively regulated by mir92a in the pharyngeal region ? nog3 mRNA is degraded by mir92a to maintain Bmp activity