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  1. Book: Brown adipose tissue

    Guertin, David A. / Wolfrum, Christian

    methods and protocols

    (Methods in molecular biology ; 2448 ; Springer protocols)

    2022  

    Author's details edited by David A. Guertin, Christian Wolfrum
    Series title Methods in molecular biology ; 2448
    Springer protocols
    Collection
    Language English
    Size xiv, 309 Seiten, Illustrationen
    Publisher Humana Press
    Publishing place New York, NY
    Publishing country United States
    Document type Book
    HBZ-ID HT021264756
    ISBN 978-1-0716-2086-1 ; 9781071620878 ; 1-0716-2086-X ; 1071620878
    Database Catalogue ZB MED Medicine, Health

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    Shelf markLoan statusLocation
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  2. Article ; Online: Acetyl-CoA metabolism in cancer.

    Guertin, David A / Wellen, Kathryn E

    Nature reviews. Cancer

    2023  Volume 23, Issue 3, Page(s) 156–172

    Abstract: Few metabolites can claim a more central and versatile role in cell metabolism than acetyl coenzyme A (acetyl-CoA). Acetyl-CoA is produced during nutrient catabolism to fuel the tricarboxylic acid cycle and is the essential building block for fatty acid ... ...

    Abstract Few metabolites can claim a more central and versatile role in cell metabolism than acetyl coenzyme A (acetyl-CoA). Acetyl-CoA is produced during nutrient catabolism to fuel the tricarboxylic acid cycle and is the essential building block for fatty acid and isoprenoid biosynthesis. It also functions as a signalling metabolite as the substrate for lysine acetylation reactions, enabling the modulation of protein functions in response to acetyl-CoA availability. Recent years have seen exciting advances in our understanding of acetyl-CoA metabolism in normal physiology and in cancer, buoyed by new mouse models, in vivo stable-isotope tracing approaches and improved methods for measuring acetyl-CoA, including in specific subcellular compartments. Efforts to target acetyl-CoA metabolic enzymes are also advancing, with one therapeutic agent targeting acetyl-CoA synthesis receiving approval from the US Food and Drug Administration. In this Review, we give an overview of the regulation and cancer relevance of major metabolic pathways in which acetyl-CoA participates. We further discuss recent advances in understanding acetyl-CoA metabolism in normal tissues and tumours and the potential for targeting these pathways therapeutically. We conclude with a commentary on emerging nodes of acetyl-CoA metabolism that may impact cancer biology.
    MeSH term(s) Animals ; Humans ; Mice ; Acetyl Coenzyme A/metabolism ; Metabolic Networks and Pathways ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Disease Models, Animal
    Chemical Substances Acetyl Coenzyme A (72-89-9)
    Language English
    Publishing date 2023-01-19
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2062767-1
    ISSN 1474-1768 ; 1474-175X
    ISSN (online) 1474-1768
    ISSN 1474-175X
    DOI 10.1038/s41568-022-00543-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A new era of understanding in vivo metabolic flux in thermogenic adipocytes.

    Haley, John A / Jang, Cholsoon / Guertin, David A

    Current opinion in genetics & development

    2023  Volume 83, Page(s) 102112

    Abstract: Nonshivering thermogenesis by brown adipose tissue (BAT) is an adaptive mechanism for maintaining body temperature in cold environments. BAT is critical in rodents and human infants and has substantial influence on adult human metabolism. Stimulating BAT ...

    Abstract Nonshivering thermogenesis by brown adipose tissue (BAT) is an adaptive mechanism for maintaining body temperature in cold environments. BAT is critical in rodents and human infants and has substantial influence on adult human metabolism. Stimulating BAT therapeutically is also being investigated as a strategy against metabolic diseases because of its ability to function as a catabolic sink. Thus, understanding how brown adipocytes and the related brite/beige adipocytes use nutrients to fuel their demanding metabolism has both basic and translational implications. Recent advances in mass spectrometry and isotope tracing are improving the ability to study metabolic flux in vivo. Here, we review how such strategies are advancing our understanding of adipocyte thermogenesis and conclude with key future questions.
    MeSH term(s) Adult ; Humans ; Obesity/metabolism ; Adipose Tissue, Brown/metabolism ; Adipocytes, Brown/metabolism ; Thermogenesis/genetics
    Language English
    Publishing date 2023-09-11
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1077312-5
    ISSN 1879-0380 ; 0959-437X
    ISSN (online) 1879-0380
    ISSN 0959-437X
    DOI 10.1016/j.gde.2023.102112
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Unexpected cell population gives fat a brake.

    Guertin, David A

    Nature

    2018  Volume 559, Issue 7712, Page(s) 41–42

    MeSH term(s) Adipogenesis ; Animals ; Gastrointestinal Transit ; Stromal Cells
    Language English
    Publishing date 2018-06-26
    Publishing country England
    Document type News ; Comment
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/d41586-018-05120-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Oncogenic AKTivation by methylation.

    Luciano, Amelia K / Guertin, David A

    Nature cell biology

    2019  Volume 21, Issue 2, Page(s) 114–115

    MeSH term(s) Carcinogenesis/genetics ; Histone-Lysine N-Methyltransferase ; Humans ; Methylation ; Oncogenes ; Protein Methyltransferases ; Proto-Oncogene Proteins c-akt/genetics
    Chemical Substances Protein Methyltransferases (EC 2.1.1.-) ; Histone-Lysine N-Methyltransferase (EC 2.1.1.43) ; SETDB1 protein, human (EC 2.1.1.43) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
    Language English
    Publishing date 2019-02-27
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 1474722-4
    ISSN 1476-4679 ; 1465-7392
    ISSN (online) 1476-4679
    ISSN 1465-7392
    DOI 10.1038/s41556-019-0275-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: De Novo Lipogenesis as a Source of Second Messengers in Adipocytes.

    Hsiao, Wen-Yu / Guertin, David A

    Current diabetes reports

    2019  Volume 19, Issue 11, Page(s) 138

    Abstract: Purpose of review: Obesity is a major risk factor for type 2 diabetes. Although adipose tissue allows storage of excess calories in periods of overnutrition, in obesity, adipose tissue metabolism becomes dysregulated and can promote metabolic diseases. ... ...

    Abstract Purpose of review: Obesity is a major risk factor for type 2 diabetes. Although adipose tissue allows storage of excess calories in periods of overnutrition, in obesity, adipose tissue metabolism becomes dysregulated and can promote metabolic diseases. This review discusses recent advances in understandings how adipocyte metabolism impacts metabolic homeostasis.
    Recent findings: The ability of adipocytes to synthesize lipids from glucose is a marker of metabolic fitness, e.g., low de novo lipogenesis (DNL) in adipocytes correlates with insulin resistance in obesity. Adipocyte DNL may promote synthesis of special "insulin sensitizing" signaling lipids that act hormonally. However, each metabolic intermediate in the DNL pathway (i.e., citrate, acetyl-CoA, malonyl-CoA, and palmitate) also has second messenger functions. Mounting evidence suggests these signaling functions may also be important for maintaining healthy adipocytes. While adipocyte DNL contributes to lipid storage, lipid precursors may have additional second messenger functions critical for maintaining adipocyte health, and thus systemic metabolic homeostasis.
    MeSH term(s) Adipocytes/physiology ; Diabetes Mellitus, Type 2 ; Humans ; Insulin Resistance ; Lipogenesis ; Obesity/complications ; Second Messenger Systems
    Language English
    Publishing date 2019-11-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2065167-3
    ISSN 1539-0829 ; 1534-4827
    ISSN (online) 1539-0829
    ISSN 1534-4827
    DOI 10.1007/s11892-019-1264-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Insulin PACS a Punch in SIRT1 Activity.

    Jung, Su Myung / Guertin, David A

    Molecular cell

    2018  Volume 72, Issue 6, Page(s) 917–919

    Abstract: In this issue of Molecular Cell, Krzysiak et al. (2018) describe a mechanism by which insulin signaling represses the ... ...

    Abstract In this issue of Molecular Cell, Krzysiak et al. (2018) describe a mechanism by which insulin signaling represses the NAD
    MeSH term(s) Insulin ; Signal Transduction ; Sirtuin 1
    Chemical Substances Insulin ; Sirtuin 1 (EC 3.5.1.-)
    Language English
    Publishing date 2018-12-21
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2018.12.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Modeling hydrologic responses using multi-site and single-site rainfall generators in a semi-arid watershed

    Zhao, Ying / Nearing, Mark A. / Guertin, David Phillip

    International Research and Training Center on Erosion and Sedimentation, China Water and Power Press, and China Institute of Water Resources and Hydropower Research International soil and water conservation research. 2022 June, v. 10, no. 2

    2022  

    Abstract: Hydrologic response in a watershed is driven by precipitation. Multi-site rainfall generators can be used to model watersheds using spatially varied rainfall inputs to better analyze how the rainfall variability affects runoff generation. This study ... ...

    Abstract Hydrologic response in a watershed is driven by precipitation. Multi-site rainfall generators can be used to model watersheds using spatially varied rainfall inputs to better analyze how the rainfall variability affects runoff generation. This study adopted both a single-site rainfall generator (CLIGEN) and a multi-site rainfall generator to generate two rainfall data sequences, which were then used to drive the Soil and Water Assessment Tool (SWAT) for runoff simulation. The 148-km² Walnut Gulch Experimental Watershed and its two sub-watersheds were selected to evaluate the hydrologic response. Runoff calibration was done against measured runoff in the watershed. Statistics showed that the single-site and multi-site rainfall generators gave similar results regarding annual precipitation. However, the multi-site generator performed much better than the single-site generator in both mean summer flow and for the different return period flows. The runoff derived from the single-site generator was significantly over-estimated in all three watersheds. As for the multi-site generator, the derived runoff was satisfactorily predicted in the smaller watersheds but only overestimated in the largest watershed. This indicated that in small to medium sized watersheds, the spatial variability of rainfall could play an important role for hydrologic response because of the heterogeneity of convective rainfall in this semi-arid region, which makes the application of multi-site rainfall generator a better option than the single-site generator.
    Keywords Soil and Water Assessment Tool model ; meteorological data ; rain ; research ; runoff ; semiarid zones ; soil ; statistics ; subwatersheds ; summer ; water conservation
    Language English
    Dates of publication 2022-06
    Size p. 177-187.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 2835330-4
    ISSN 2095-6339
    ISSN 2095-6339
    DOI 10.1016/j.iswcr.2021.09.003
    Database NAL-Catalogue (AGRICOLA)

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  9. Article: Molecular test of Paget's disease of bone in families not linked to

    You, Yang / Simonyan, David / Bureau, Alexandre / Gagnon, Edith / Albert, Caroline / Guertin, Jason R / Tarride, Jean-Eric / Brown, Jacques P / Michou, Laëtitia

    Bone reports

    2023  Volume 18, Page(s) 101670

    Abstract: Purpose: Paget's disease of bone (PDB) is a focal metabolic bone disorder characterized by an increased bone remodeling. Fifteen to 40 % of PDB patients have a familial form with an autosomal dominant inheritance. Disease-causing mutations of the : ... ...

    Abstract Purpose: Paget's disease of bone (PDB) is a focal metabolic bone disorder characterized by an increased bone remodeling. Fifteen to 40 % of PDB patients have a familial form with an autosomal dominant inheritance. Disease-causing mutations of the
    Objective: This study aimed at estimating the performance of our previous test of PDB, in families not linked to
    Methods: We genotyped the five SNPs cited above, and measured calcium corrected for albumin and P1NP in 181 relatives, with PDB or not, from 19 PDB families not linked to
    Results: Logistic regression estimates of our previous molecular test gave rise to a high sensitivity of 78 %, 97 % and 88 % for the genetic, biochemical, and combined test but the specificity was very low, 35 %, 11 % and 21 %, respectively. This poor specificity persisted even when the cut-off point was changed. We then generated in these families, new logistic regression estimates but on the same parameters as mentioned above, giving rise to an AUC of 0.65 (0.55; 0.75) for the genetic test, of 0.84 (0.74; 0.94) for the biochemical test, and 0.89 (0.82; 0.96) for the combination test, the latter having a sensitivity of 96 % and specificity of 57 %. By comparison serum P1NP alone gave rise to an AUC of 0.84 (0.73; 0.94), with a sensitivity of 71 % and a specificity of 79 %.
    Conclusion: In PDB families not linked to
    Language English
    Publishing date 2023-02-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2821774-3
    ISSN 2352-1872
    ISSN 2352-1872
    DOI 10.1016/j.bonr.2023.101670
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Functional genomic screens with death rate analyses reveal mechanisms of drug action.

    Honeywell, Megan E / Isidor, Marie S / Harper, Nicholas W / Fontana, Rachel E / Birdsall, Gavin A / Cruz-Gordillo, Peter / Porto, Sydney A / Jerome, Madison / Fraser, Cameron S / Sarosiek, Kristopher A / Guertin, David A / Spinelli, Jessica B / Lee, Michael J

    Nature chemical biology

    2024  

    Abstract: A common approach for understanding how drugs induce their therapeutic effects is to identify the genetic determinants of drug sensitivity. Because 'chemo-genetic profiles' are performed in a pooled format, inference of gene function is subject to ... ...

    Abstract A common approach for understanding how drugs induce their therapeutic effects is to identify the genetic determinants of drug sensitivity. Because 'chemo-genetic profiles' are performed in a pooled format, inference of gene function is subject to several confounding influences related to variation in growth rates between clones. In this study, we developed Method for Evaluating Death Using a Simulation-assisted Approach (MEDUSA), which uses time-resolved measurements, along with model-driven constraints, to reveal the combination of growth and death rates that generated the observed drug response. MEDUSA is uniquely effective at identifying death regulatory genes. We apply MEDUSA to characterize DNA damage-induced lethality in the presence and absence of p53. Loss of p53 switches the mechanism of DNA damage-induced death from apoptosis to a non-apoptotic death that requires high respiration. These findings demonstrate the utility of MEDUSA both for determining the genetic dependencies of lethality and for revealing opportunities to potentiate chemo-efficacy in a cancer-specific manner.
    Language English
    Publishing date 2024-03-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2202962-X
    ISSN 1552-4469 ; 1552-4450
    ISSN (online) 1552-4469
    ISSN 1552-4450
    DOI 10.1038/s41589-024-01584-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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