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Artikel ; Online: Sorting through the extensive and confusing roles of sortilin in metabolic disease.

Mitok, Kelly A / Keller, Mark P / Attie, Alan D

2022 Band 63, Heft 8, Seite(n) 100243

Abstract: Sortilin is a post-Golgi trafficking receptor homologous to the yeast vacuolar protein sorting receptor 10 (VPS10). The VPS10 motif on sortilin is a 10-bladed β-propeller structure capable of binding more than 50 proteins, covering a wide range of ... ...

Abstract	Sortilin is a post-Golgi trafficking receptor homologous to the yeast vacuolar protein sorting receptor 10 (VPS10). The VPS10 motif on sortilin is a 10-bladed β-propeller structure capable of binding more than 50 proteins, covering a wide range of biological functions including lipid and lipoprotein metabolism, neuronal growth and death, inflammation, and lysosomal degradation. Sortilin has a complex cellular trafficking itinerary, where it functions as a receptor in the trans-Golgi network, endosomes, secretory vesicles, multivesicular bodies, and at the cell surface. In addition, sortilin is associated with hypercholesterolemia, Alzheimer's disease, prion diseases, Parkinson's disease, and inflammation syndromes. The 1p13.3 locus containing SORT1, the gene encoding sortilin, carries the strongest association with LDL-C of all loci in human genome-wide association studies. However, the mechanism by which sortilin influences LDL-C is unclear. Here, we review the role sortilin plays in cardiovascular and metabolic diseases and describe in detail the large and often contradictory literature on the role of sortilin in the regulation of LDL-C levels.
Mesh-Begriff(e)	Adaptor Proteins, Vesicular Transport ; Cholesterol, LDL ; Genome-Wide Association Study ; Humans ; Hypercholesterolemia ; Inflammation ; Protein Transport
Chemische Substanzen	Adaptor Proteins, Vesicular Transport ; Cholesterol, LDL ; sortilin (Z020Y8WIJ4)
Sprache	Englisch
Erscheinungsdatum	2022-06-18
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	80154-9
ISSN	1539-7262 ; 0022-2275
ISSN (online)	1539-7262
ISSN	0022-2275
DOI	10.1016/j.jlr.2022.100243
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Systems genetics approach uncovers associations between host amylase locus, gut microbiome and metabolic traits in hyperlipidemic mice.

Zhang, Qijun / Hutchison, Evan R / Pan, Calvin / Warren, Matthew F / Keller, Mark P / Attie, Alan D / Lusis, Aldons J / Rey, Federico E

bioRxiv : the preprint server for biology

2024

Abstract: The molecular basis for how host genetic variation impacts gut microbial community and bacterial metabolic niches remain largely unknown. We leveraged 90 inbred hyperlipidemic mouse strains from the Hybrid Mouse Diversity Panel (HMDP), previously studied ...

Abstract	The molecular basis for how host genetic variation impacts gut microbial community and bacterial metabolic niches remain largely unknown. We leveraged 90 inbred hyperlipidemic mouse strains from the Hybrid Mouse Diversity Panel (HMDP), previously studied for a variety of cardio-metabolic traits. Metagenomic analysis of cecal DNA followed by genome-wide association analysis identified genomic loci that were associated with microbial enterotypes in the gut. Among these we detected a genetic locus surrounding multiple amylase genes that was associated with abundances of Firmicutes (
Sprache	Englisch
Erscheinungsdatum	2024-03-03
Erscheinungsland	United States
Dokumenttyp	Preprint
DOI	10.1101/2024.02.28.582610
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: QTLViewer: an interactive webtool for genetic analysis in the Collaborative Cross and Diversity Outbred mouse populations.

Vincent, Matthew / Gerdes Gyuricza, Isabela / Keele, Gregory R / Gatti, Daniel M / Keller, Mark P / Broman, Karl W / Churchill, Gary A

G3 (Bethesda, Md.)

2022 Band 12, Heft 8

Abstract: The Collaborative Cross and the Diversity Outbred mouse populations are related multiparental populations, derived from the same 8 isogenic founder strains. They carry >50 M known genetic variants, which makes them ideal tools for mapping genetic loci ... ...

Abstract	The Collaborative Cross and the Diversity Outbred mouse populations are related multiparental populations, derived from the same 8 isogenic founder strains. They carry >50 M known genetic variants, which makes them ideal tools for mapping genetic loci that regulate phenotypes, including physiological and molecular traits. Mapping quantitative trait loci requires statistical and computational training, which can present a barrier to access for some researchers. The QTLViewer software allows users to graphically explore Collaborative Cross and Diversity Outbred quantitative trait locus mapping and related analyses performed through the R/qtl2 package. Additionally, the QTLViewer website serves as a repository for published Collaborative Cross and Diversity Outbred studies, increasing the accessibility of these genetic resources to the broader scientific community.
Mesh-Begriff(e)	Animals ; Chromosome Mapping ; Collaborative Cross Mice/genetics ; Mice ; Phenotype ; Quantitative Trait Loci ; Software
Sprache	Englisch
Erscheinungsdatum	2022-05-19
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2629978-1
ISSN	2160-1836 ; 2160-1836
ISSN (online)	2160-1836
ISSN	2160-1836
DOI	10.1093/g3journal/jkac146
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Genetic Analysis of Obesity-Induced Diabetic Nephropathy in BTBR Mice.

Keller, Mark P / O'Connor, Chris / Bitzer, Markus / Schueler, Kathryn L / Stapleton, Donald S / Emfinger, Christopher H / Broman, Aimee Teo / Hodgin, Jeffrey B / Attie, Alan D

Diabetes

2023 Band 73, Heft 2, Seite(n) 312–317

Mesh-Begriff(e)	Humans ; Mice ; Animals ; Diabetic Nephropathies/genetics ; Diabetic Nephropathies/pathology ; Leptin ; Diabetes Mellitus, Type 2/genetics ; Mice, Inbred C57BL ; Disease Models, Animal ; Mice, Inbred Strains ; Obesity/complications ; Obesity/genetics ; Mice, Obese
Chemische Substanzen	Leptin
Sprache	Englisch
Erscheinungsdatum	2023-12-08
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	80085-5
ISSN	1939-327X ; 0012-1797
ISSN (online)	1939-327X
ISSN	0012-1797
DOI	10.2337/db23-0444
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: An Enhancer Within Abcb11 Regulates G6pc2 in C57BL/6 Mouse Pancreatic Islets.

Keller, Mark P / Hawes, Emily M / Schueler, Kathryn L / Stapleton, Donnie S / Mitok, Kelly A / Simonett, Shane P / Oeser, James K / Sampson, Leesa L / Attie, Alan D / Magnuson, Mark A / O'Brien, Richard M

Diabetes

2023 Band 72, Heft 11, Seite(n) 1621–1628

Mesh-Begriff(e)	Animals ; Humans ; Mice ; Blood Glucose/metabolism ; Glucose/metabolism ; Glucose-6-Phosphatase/genetics ; Insulin/metabolism ; Islets of Langerhans/metabolism ; Mice, Inbred C57BL
Chemische Substanzen	Blood Glucose ; G6pc2 protein, mouse (EC 3.1.3.9.) ; Glucose (IY9XDZ35W2) ; Glucose-6-Phosphatase (EC 3.1.3.9) ; Insulin ; Abcb11 protein, mouse
Sprache	Englisch
Erscheinungsdatum	2023-08-08
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	80085-5
ISSN	1939-327X ; 0012-1797
ISSN (online)	1939-327X
ISSN	0012-1797
DOI	10.2337/db23-0215
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Novel regulators of islet function identified from genetic variation in mouse islet Ca

Emfinger, Christopher H / Clark, Lauren E / Yandell, Brian / Schueler, Kathryn L / Simonett, Shane P / Stapleton, Donnie S / Mitok, Kelly A / Merrins, Matthew J / Keller, Mark P / Attie, Alan D

eLife

2023 Band 12

Abstract: Insufficient insulin secretion to meet metabolic demand results in diabetes. The intracellular flux of ... ...

Abstract	Insufficient insulin secretion to meet metabolic demand results in diabetes. The intracellular flux of Ca
Mesh-Begriff(e)	Mice ; Humans ; Animals ; Islets of Langerhans/metabolism ; Genome-Wide Association Study ; Insulin/metabolism ; Glucose/metabolism ; Genetic Variation ; Amino Acids/metabolism
Chemische Substanzen	Insulin ; Glucose (IY9XDZ35W2) ; Amino Acids
Sprache	Englisch
Erscheinungsdatum	2023-10-03
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.88189
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: D2H2: diabetes data and hypothesis hub.

Marino, Giacomo B / Ahmed, Nasheath / Xie, Zhuorui / Jagodnik, Kathleen M / Han, Jason / Clarke, Daniel J B / Lachmann, Alexander / Keller, Mark P / Attie, Alan D / Ma'ayan, Avi

Bioinformatics advances

2023 Band 3, Heft 1, Seite(n) vbad178

Abstract: Motivation: There is a rapid growth in the production of omics datasets collected by the diabetes research community. However, such published data are underutilized for knowledge discovery. To make bioinformatics tools and published omics datasets from ... ...

Abstract	Motivation: There is a rapid growth in the production of omics datasets collected by the diabetes research community. However, such published data are underutilized for knowledge discovery. To make bioinformatics tools and published omics datasets from the diabetes field more accessible to biomedical researchers, we developed the Diabetes Data and Hypothesis Hub (D2H2). Results: D2H2 contains hundreds of high-quality curated transcriptomics datasets relevant to diabetes, accessible via a user-friendly web-based portal. The collected and processed datasets are curated from the Gene Expression Omnibus (GEO). Each curated study has a dedicated page that provides data visualization, differential gene expression analysis, and single-gene queries. To enable the investigation of these curated datasets and to provide easy access to bioinformatics tools that serve gene and gene set-related knowledge, we developed the D2H2 chatbot. Utilizing GPT, we prompt users to enter free text about their data analysis needs. Parsing the user prompt, together with specifying information about all D2H2 available tools and workflows, we answer user queries by invoking the most relevant tools via the tools' API. D2H2 also has a hypotheses generation module where gene sets are randomly selected from the bulk RNA-seq precomputed signatures. We then find highly overlapping gene sets extracted from publications listed in PubMed Central with abstract dissimilarity. With the help of GPT, we speculate about a possible explanation of the high overlap between the gene sets. Overall, D2H2 is a platform that provides a suite of bioinformatics tools and curated transcriptomics datasets for hypothesis generation. Availability and implementation: D2H2 is available at: https://d2h2.maayanlab.cloud/ and the source code is available from GitHub at https://github.com/MaayanLab/D2H2-site under the CC BY-NC 4.0 license.
Sprache	Englisch
Erscheinungsdatum	2023-12-04
Erscheinungsland	England
Dokumenttyp	Journal Article
ISSN	2635-0041
ISSN (online)	2635-0041
DOI	10.1093/bioadv/vbad178
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Pptc7 maintains mitochondrial protein content by suppressing receptor-mediated mitophagy.

Niemi, Natalie M / Serrano, Lia R / Muehlbauer, Laura K / Balnis, Catie / Kozul, Keri-Lyn / Rashan, Edrees H / Shishkova, Evgenia / Schueler, Kathryn L / Keller, Mark P / Attie, Alan D / Pagan, Julia / Coon, Joshua J / Pagliarini, David J

bioRxiv : the preprint server for biology

2023

Abstract: Pptc7 is a resident mitochondrial phosphatase essential for maintaining proper mitochondrial content and function. Newborn mice ... ...

Abstract	Pptc7 is a resident mitochondrial phosphatase essential for maintaining proper mitochondrial content and function. Newborn mice lacking
Sprache	Englisch
Erscheinungsdatum	2023-03-01
Erscheinungsland	United States
Dokumenttyp	Preprint
DOI	10.1101/2023.02.28.530351
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Lipidomic QTL in Diversity Outbred mice identifies a novel function for α/β hydrolase domain 2 (

Price, Tara R / Stapleton, Donnie S / Schueler, Kathryn L / Norris, Marie K / Parks, Brian W / Yandell, Brian S / Churchill, Gary A / Holland, William L / Keller, Mark P / Attie, Alan D

bioRxiv : the preprint server for biology

2023

Abstract: We and others have previously shown that genetic association can be used to make causal connections between gene loci and small molecules measured by mass spectrometry in the bloodstream and in tissues. We identified a locus on mouse chromosome 7 where ... ...

Abstract	We and others have previously shown that genetic association can be used to make causal connections between gene loci and small molecules measured by mass spectrometry in the bloodstream and in tissues. We identified a locus on mouse chromosome 7 where several phospholipids in liver showed strong genetic association to distinct gene loci. In this study, we integrated gene expression data with genetic association data to identify a single gene at the chromosome 7 locus as the driver of the phospholipid phenotypes. The gene encodes α/β-hydrolase domain 2 (
Sprache	Englisch
Erscheinungsdatum	2023-03-24
Erscheinungsland	United States
Dokumenttyp	Preprint
DOI	10.1101/2023.03.23.533902
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Lipidomic QTL in Diversity Outbred mice identifies a novel function for α/β hydrolase domain 2 (Abhd2) as an enzyme that metabolizes phosphatidylcholine and cardiolipin.

Price, Tara R / Stapleton, Donnie S / Schueler, Kathryn L / Norris, Marie K / Parks, Brian W / Yandell, Brian S / Churchill, Gary A / Holland, William L / Keller, Mark P / Attie, Alan D

PLoS genetics

2023 Band 19, Heft 7, Seite(n) e1010713

Abstract	We and others have previously shown that genetic association can be used to make causal connections between gene loci and small molecules measured by mass spectrometry in the bloodstream and in tissues. We identified a locus on mouse chromosome 7 where several phospholipids in liver showed strong genetic association to distinct gene loci. In this study, we integrated gene expression data with genetic association data to identify a single gene at the chromosome 7 locus as the driver of the phospholipid phenotypes. The gene encodes α/β-hydrolase domain 2 (Abhd2), one of 23 members of the ABHD gene family. We validated this observation by measuring lipids in a mouse with a whole-body deletion of Abhd2. The Abhd2KO mice had a significant increase in liver levels of phosphatidylcholine and phosphatidylethanolamine. Unexpectedly, we also found a decrease in two key mitochondrial lipids, cardiolipin and phosphatidylglycerol, in male Abhd2KO mice. These data suggest that Abhd2 plays a role in the synthesis, turnover, or remodeling of liver phospholipids.
Mesh-Begriff(e)	Animals ; Male ; Mice ; Cardiolipins/genetics ; Cardiolipins/metabolism ; Collaborative Cross Mice/metabolism ; Hydrolases/genetics ; Hydrolases/metabolism ; Lipidomics ; Phosphatidylcholines/genetics ; Phospholipids/genetics ; Phospholipids/metabolism
Chemische Substanzen	Cardiolipins ; Hydrolases (EC 3.-) ; Phosphatidylcholines ; Phospholipids ; Abhd2 protein, mouse (EC 3.1.1.-)
Sprache	Englisch
Erscheinungsdatum	2023-07-31
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	2186725-2
ISSN	1553-7404 ; 1553-7390
ISSN (online)	1553-7404
ISSN	1553-7390
DOI	10.1371/journal.pgen.1010713
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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