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Article
Interaction between the gut microbiota and colonic enteroendocrine cells regulates host metabolism
Nutrient handling is an essential function of the gastrointestinal tract. Hormonal responses of small intestinal enteroendocrine cells (EECs) have been extensively studied but much less is known about the role...
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Article
Structural organization of the retriever–CCC endosomal recycling complex
The recycling of membrane proteins from endosomes to the cell surface is vital for cell signaling and survival. Retriever, a trimeric complex of vacuolar protein-sorting-associated protein (VPS)35L, VPS26C and...
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Article
Open AccessRORγt-Raftlin1 complex regulates the pathogenicity of Th17 cells and colonic inflammation
Th17 cells that produce Interleukin IL-17 are pathogenic in many human diseases, including inflammatory bowel disease, but are, paradoxically, essential for maintaining the integrity of the intestinal barrier ...
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Article
Open AccessSCGN deficiency is a risk factor for autism spectrum disorder
Autism spectrum disorder (ASD) affects 1–2% of all children and poses a great social and economic challenge for the globe. As a highly heterogeneous neurodevelopmental disorder, the development of its treatmen...
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Article
Open AccessGMPPB-congenital disorders of glycosylation associate with decreased enzymatic activity of GMPPB
The congenital disorders of glycosylation (CDG) are a family of metabolic diseases in which glycosylation of proteins or lipids is deficient. GDP-mannose pyrophosphorylase B (GMPPB) mutations lead to CDG, char...
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Article
Immune Dysfunction in Mendelian Disorders of POLA1 Deficiency
POLA1 encodes the catalytic unit of DNA polymerase α, which together with the Primase complex launches the DNA replication process. While complete deficiency of this essential gene is presumed to be lethal, at le...
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Article
Open AccessJAK Inhibition in a Patient with X-Linked Reticulate Pigmentary Disorder
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Article
Open AccessEndosomal PI(3)P regulation by the COMMD/CCDC22/CCDC93 (CCC) complex controls membrane protein recycling
Protein recycling through the endolysosomal system relies on molecular assemblies that interact with cargo proteins, membranes, and effector molecules. Among them, the COMMD/CCDC22/CCDC93 (CCC) complex plays a...
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Article
Precision editing of the gut microbiota ameliorates colitis
Tungstate inhibits molybdenum-cofactor-dependent microbial respiratory pathways and shows potential as a selective treatment for microbial imbalances that occur during inflammation of the gastrointestinal tract.
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Article
Retriever is a multiprotein complex for retromer-independent endosomal cargo recycling
Following endocytosis into the endosomal network, integral membrane proteins undergo sorting for lysosomal degradation or are retrieved and recycled back to the cell surface. Here we describe the discovery of...
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Article
Open AccessStructural and mechanistic insights into regulation of the retromer coat by TBC1d5
Retromer is a membrane coat complex that is recruited to endosomes by the small GTPase Rab7 and sorting nexin 3. The timing of this interaction and consequent endosomal dynamics are thought to be regulated by ...
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Article
Open AccessInhibiting cancer cell hallmark features through nuclear export inhibition
Treating cancer through inhibition of nuclear export is one of the best examples of basic research translation into clinical application. Nuclear export factor chromosomal region maintenance 1 (CRM1; Xpo1 and ...
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Article
DNA polymerase-α regulates the activation of type I interferons through cytosolic RNA:DNA synthesis
The causative mechanism for the immunodeficiency and autoinflammatory disease XLPDR is unknown. Burstein and colleagues show that XLPDR is caused by disruption of POLA1, which encodes a DNA polymerase subunit; th...
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Article
Open AccessCCC- and WASH-mediated endosomal sorting of LDLR is required for normal clearance of circulating LDL
The low-density lipoprotein receptor (LDLR) plays a pivotal role in clearing atherogenic circulating low-density lipoprotein (LDL) cholesterol. Here we show that the COMMD/CCDC22/CCDC93 (CCC) and the Wiskott–A...
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Article
Obesity in Inflammatory Bowel Disease: A Marker of Less Severe Disease
Both obesity and inflammatory bowel disease (IBD) are highly prevalent in Western societies. IBD, including Crohn’s disease (CD) and ulcerative colitis (UC), has been historically associated with cachexia and ...
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Protocol
Detection of IκB Degradation Dynamics and IκB-α Ubiquitination
The NF-κB signaling pathway is a primary regulator of inflammation that has been implicated in the pathogenesis of immune disorders and cancer. This signaling network is strictly regulated; in a nonactivated s...
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Protocol
Methodology to Study NF-κB/RelA Ubiquitination In Vivo
Nuclear factor-kappa B (NF-κB) is a family of transcription factors that regulate immune responses, cell proliferation, differentiation, and survival. Activity of the NF-κΒ pathway on a cellular level is tight...
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Protocol
Bimolecular Affinity Purification: A Variation of TAP with Multiple Applications
The identification of true interacting partners of any given bait can be plagued by the nonspecific purification of irrelevant proteins. To avoid this problem, Tandem Affinity Purification (TAP) is a widely us...
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Article
Paraneoplastic diarrhea in a patient with lung adenocarcinoma
We present a case of newly diagnosed lung adenocarcinoma and a five-month history of diarrhea. The patient was found to have elevated chromogranin A serum levels and the tumor displayed histologic and immunohi...
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Article
A bimolecular affinity purification method under denaturing conditions for rapid isolation of a ubiquitinated protein for mass spectrometry analysis
Ubiquitination can have profound effects on the stability and function of cellular proteins. Mass spectrometry (MS) can be used to map the specific amino acid residues that are conjugated to ubiquitin in a tar...