SIP1 Mediates Cell-Fate Decisions between Neuroectoderm and Mesendoderm in Human Pluripotent Stem Cells

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Highlights? Smad-interacting protein 1 (SIP1) regulates hESC differentiation ? SIP1 upregulation promotes neuroectodermal differentiation ? SIP1 inhibits mesendodermal and endodermal differentiation ? SMAD2/3 and NANOG/OCT4/SOX2 cooperatively regulate SIP1 expression     

MicroRNA-9 Coordinates Proliferation and Migration of Human Embryonic Stem Cell-Derived Neural Progenitors

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Highlights? miR-9 is expressed in hESC-derived early hNPCs and their progeny ? Loss of miR-9 inhibits early hNPC proliferation and delays maturation ? miR-9 knockdown promotes hNPC migration in vitro and in vivo ? Stathmin is a target of miR-9 and mediates its effects in early hNPCs     

A microRNA miR-34a-Regulated Bimodal Switch Targets Notch in Colon Cancer Stem Cells

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Highlights? miR-34a regulates colon cancer stem cell asymmetric division ? miR-34a generates a sharp threshold response ? miR-34a converts Notch signaling into a toggle switch ? Binary Notch levels specify self-renewal versus differentiation     

Leishmania donovani Targets Dicer1 to Downregulate miR-122, Lower Serum Cholesterol,and Facilitate Murine Liver Infection

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Highlights? Leishmania infection reduces liver miR-122 and lowers serum cholesterol ? Leishmania metalloprotease gp63 is required for inhibition of hepatic miR-122 activity ? gp63 cleaves DICER1 to downregulate miRNP-122 formation in hepatocytes ? Restoration of miR-122 elevates serum cholesterol to reduce liver parasite load     

Chromosome Engineering Allows the Efficient Isolation of Vertebrate Neocentromeres

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Highlights? Chromosome engineering efficiently generates neocentromeres in chicken DT40 cells ? CENP-A reproducibly occupies an ～40 kb genomic region at each neocentromere ? Nonkinetochore CENP-A appears to function as a seed for neocentromere assembly     

Structure and Intrinsic Disorder in Protein Autoinhibition

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Highlights? Autoinhibitory regions in proteins are enriched in intrinsic disorder ? Modulation of intrinsic disorder contributes to the fine-tuning of autoinhibition ? Disordered autoinhibitory regions are more often phosphorylated and change structure ? Intrinsic disorder in inhibitory regions is exploited to fine-tune inhibition     

Derepression of a Neuronal Inhibitor due to miRNA Dysregulation in a Schizophrenia-Related Microdeletion

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Highlights? A mouse model of a hemizygous 22q11.2 deletion shows over 50% reduction of miR-185 ? Mirta22 is a miR-185 target and a major effector of the 22q11.2 miRNA dysregulation ? Mirta22 is a prenatally biased neuronal inhibitor located in the Golgi apparatus ? Altered levels of miR-185 and Mirta22 affect dendrite and spine development     

LRP6 Enhances Glucose Metabolism by Promoting TCF7L2-Dependent Insulin Receptor Expression and IGF Receptor Stabilization in Humans

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Highlights? Nondiabetic LRP6 mutation carriers are hyperinsulinemic and insulin resistant ? IR expression is reduced in skeletal muscles of the LRP6 mutation carriers ? Wnt/LRP6 regulate the insulin receptor and IGFR expression ? The LRP6 mutation reduces TCF7L2-dependent IR expression and enhances mTOR activity     

ZNF750 is a p63 target gene that induces KLF4 to drive terminal epidermal differentiation

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Highlights? Induction of ZNF750 expression is necessary for terminal epidermal differentiation ? The C2H2 domain of ZNF750 is necessary for its prodifferentiation function ? p63 is necessary for the induction of ZNF750 expression during differentiation ? ZNF750 activates the expression of KLF4 to drive differentiation gene expression     

Repression of the Long Noncoding RNA-LET by Histone Deacetylase 3 Contributes to Hypoxia-Mediated Metastasis

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Highlights? There is low expression of lncRNA-LET in various tumor tissues ? Hypoxia-induced low expression of lncRNA-LET occurred through histone deacetylase 3 ? The lncRNA-LET is bound to NF90, which increases NF90 degradation by the proteasome ? Low lncRNA-LET expression contributes to hypoxia-induced cell invasion     

Pou5f1-Dependent EGF Expression Controls E-Cadherin Endocytosis,Cell Adhesion,and Zebrafish Epiboly Movements

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Highlights? Pou5f1 regulates EGF expression during oogenesis ? EGFR signaling controls E-cadherin trafficking at blastula and gastrula stages ? E-cadherin subcellular trafficking controls adhesion and cell migration ? Dynamics of E-cadherin adhesion is essential for effective cell migration     

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     

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     

Sirt3 promotes the urea cycle and fatty acid oxidation during dietary restriction

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Highlights? High-throughput analyses identify potential targets of Sirt3 ? Sirt3 deacetylates and stimulates ornithine transcarbamoylase ? Caloric restriction induces Sirt3 expression and stimulation of the urea cycle ? Sirt3 regulates amino acid catabolism and β-oxidation during caloric restriction     

Tanycytic VEGF-A Boosts Blood-Hypothalamus Barrier Plasticity and Access of Metabolic Signals to the Arcuate Nucleus in Response to Fasting

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Highlights? Fasting induces the plasticity of brain barriers in hypothalamic feeding regions ? Central neuroglucopenia triggers blood-hypothalamus barrier plasticity ? Fasting-induced brain barrier plasticity requires VEGF-A expression in tanycytes ? The tanycytic barrier modulates blood-borne signals access to CNS feeding circuits     

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