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  • 1
    Online Resource
    Online Resource
    Measuring the Exercise Component of Energy Availability during Arduous Training in Women
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Medicine & Science in Sports & Exercise Vol. 53, No. 4 ( 2021-4), p. 860-868
    Details
    In: Medicine & Science in Sports & Exercise, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 4 ( 2021-4), p. 860-868
    Abstract: Low energy availability (EA) may impede adaptation to exercise, suppressing reproductive function and bone turnover. Exercise energy expenditure (EEE) measurements lack definition and consistency. This study aimed to compare EA measured from moderate and vigorous physical activity from accelerometry (EEE mpva ) with EA from total physical activity (EEE tpa ) from doubly labeled water in women. The secondary aim was to determine the relationship of EA with physical fitness, body composition by dual-energy x-ray absorptiometry, heart rate variability (HRV), and eating behavior (Brief Eating Disorder in Athletes Questionnaire [BEDA-Q]). Methods This was a prospective, repeated-measures study, assessing EA measures and training adaptation during 11-month basic military training. Forty-seven women (23.9 ± 2.6 yr) completed three consecutive 10-d assessments of EEE mvpa , EEE tpa , and energy intake (EI). EA measures were compared using linear regression and Bland–Altman analyses; relationships of EA with fat mass, HRV, 1.5-mile run times, and BEDA-Q were evaluated using partial correlations. Results EA from EEE mvpa demonstrated strong agreement with EA from EEE tpa across the measurement range ( R 2 = 0.76, r = 0.87, P 〈 0.001) and was higher by 10 kcal·kg −1 FFM·d −1 . However, EA was low in absolute terms because of underreported EI. Higher EA was associated with improved 1.5-mile run time ( r = 0.28, P 〈 0.001), fat mass loss ( r = 0.38, P 〈 0.001), and lower BEDA-Q score ( r = −0.37, P 〈 0.001) but not HRV (all P 〉 0.10). Conclusion Accelerometry-based EEE demonstrated validity against doubly labeled water during multistressor training, the difference representing 10 kcal·kg −1 FFM·d −1 EEE from nonexercise activity. Beneficial physical but not autonomic adaptations were associated with higher EA. EA mvpa and BEDA-Q warrant consideration for low EA assessment and screening.
    Type of Medium: Online Resource
    ISSN: 1530-0315 , 0195-9131
    URL: Article
    DOI: 10.1249/MSS.0000000000002527
    RVK:
    ZX 1000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2031167-9
    SSG: 31
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  • 2
    Online Resource
    Online Resource
    Disease Modeling on Tumor Organoids Implicates AURKA as a Therapeutic Target in Liver Metastatic Colorectal Cancer
    Elsevier BV ; 2022
    In:  Cellular and Molecular Gastroenterology and Hepatology Vol. 13, No. 2 ( 2022), p. 517-540
    Details
    In: Cellular and Molecular Gastroenterology and Hepatology, Elsevier BV, Vol. 13, No. 2 ( 2022), p. 517-540
    Type of Medium: Online Resource
    ISSN: 2352-345X
    URL: Article
    DOI: 10.1016/j.jcmgh.2021.10.008
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2819778-1
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  • 3
    Online Resource
    Online Resource
    Wnt/LARGE2/α-DG axis reveals possible target for colorectal cancer therapy
    Springer Science and Business Media LLC ; 2020
    In:  Cell Communication and Signaling Vol. 18, No. 1 ( 2020-12)
    Details
    In: Cell Communication and Signaling, Springer Science and Business Media LLC, Vol. 18, No. 1 ( 2020-12)
    Abstract: Wnt signaling drives epithelial self-renewal and disease progression in human colonic epithelium and colorectal cancer (CRC). Characterization of Wnt effector pathways is key for our understanding of these processes and for developing therapeutic strategies that aim to preserve tissue homeostasis. O-glycosylated cell surface proteins, such as α-dystroglycan (α-DG), mediate cellular adhesion to extracellular matrix components. We revealed a Wnt/LARGE2/α-DG signaling pathway which triggers this mode of colonic epithelial cell-to-matrix interaction in health and disease. Methods Next generation sequencing upon shRNA-mediated silencing of adenomatous polyposis coli (APC), and quantitative chromatin immunoprecipitation (qChIP) combined with CRISPR/Cas9-mediated transcription factor binding site targeting characterized LARGE2 as a Wnt target gene. Quantitative mass spectrometry analysis on size-fractionated, glycoprotein-enriched samples revealed functional O-glycosylation of α-DG by LARGE2 in CRC. The biology of Wnt/LARGE2/α-DG signaling was assessed by affinity-based glycoprotein enrichment, laminin overlay, CRC-to-endothelial cell adhesion, and transwell migration assays. Experiments on primary tissue, human colonic (tumor) organoids, and bioinformatic analysis of CRC cohort data confirmed the biological relevance of our findings. Results Next generation sequencing identified the LARGE2 O-glycosyltransferase encoding gene as differentially expressed upon Wnt activation in CRC. Silencing of APC, conditional expression of oncogenic β-catenin and endogenous β-catenin-sequestration affected LARGE2 expression. The first intron of LARGE2 contained a CTTTGATC motif essential for Wnt-driven LARGE2 expression, showed occupation by the Wnt transcription factor TCF7L2, and Wnt activation triggered LARGE2-dependent α-DG O-glycosylation and laminin-adhesion in CRC cells. Colonic crypts and organoids expressed LARGE2 mainly in stem cell-enriched subpopulations. In human adenoma organoids, activity of the LARGE2/α-DG axis was Wnt-dose dependent. LARGE2 expression was elevated in CRC and correlated with the Wnt-driven molecular subtype and intestinal stem cell features. O-glycosylated α-DG represented a Wnt/LARGE2-dependent feature in CRC cell lines and patient-derived tumor organoids. Modulation of LARGE2/α-DG signaling affected CRC cell migration through laminin-coated membranes and adhesion to endothelial cells. Conclusions We conclude that the LARGE2 O-glycosyltransferase-encoding gene represents a direct target of canonical Wnt signaling and mediates functional O-glycosylation of α-dystroglycan (α-DG) in human colonic stem/progenitor cells and Wnt-driven CRC. Our work implies that aberrant Wnt activation augments CRC cell-matrix adhesion by increasing LARGE/α-DG-mediated laminin-adhesiveness. Graphical abstract
    Type of Medium: Online Resource
    ISSN: 1478-811X
    URL: Article
    URL: Article
    DOI: 10.1186/s12964-020-00561-6
    DOI: 10.21203/rs.3.rs-100958/v1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2126315-2
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Antibodies against endogenous retroviruses promote lung cancer immunotherapy
    Springer Science and Business Media LLC ; 2023
    In:  Nature Vol. 616, No. 7957 ( 2023-04-20), p. 563-573
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 616, No. 7957 ( 2023-04-20), p. 563-573
    Abstract: B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS) 1,2 . Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive 1,2 . Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma 3 . We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response.
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/s41586-023-05771-9
    RVK:
    TA 1000
    RVK:
    UA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
    SSG: 11
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