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Author

Wang, Peng, Chiang, Fu-Kuo, Chai, Jiachun, Dugulan, A. Iulian, Dong, Juan, Chen, Wei, Broos, Robin J.P., Feng, Bo, Song, Yuanjun, Lv, Yijun, Lin, Quan, Wang, Rongming, Filot, Ivo A.W., Men, Zhuowu, Hensen, Emiel J.M., Wang, Peng, Chiang, Fu-Kuo, Chai, Jiachun, Dugulan, A. Iulian, Dong, Juan, Chen, Wei, Broos, Robin J.P., Feng, Bo, Song, Yuanjun, Lv, Yijun, Lin, Quan, Wang, Rongming, Filot, Ivo A.W., Men, Zhuowu, and Hensen, Emiel J.M.

Published
2024

3. Gebruikershandleiding BedrijfsWaterWijzer versie 2024.1.0.0 : Hulp voor werken met de Bedrijfswaterwijzer en toelichting over achtergronden

Author

Verloop, Koos, Holshof, Gertjan, Broos, Jan, Verloop, Koos, Holshof, Gertjan, and Broos, Jan

Abstract

Deze gebruikershandleiding van de BedrijfsWaterWijzer (BWW) bevat informatie over de functie en opzet van de BWW, versie 2024.1.0.0. De BWW is een gratis toegankelijke online tool voor mekveebedrijven. Het instrument brengt aandachtspunten voor het watermanagement in beeld alsmede mogelijke oplossingen. De thema’s waarvoor de BWW dit doet zijn erfafspoeling, droogte, wateroverlast, nitraatuitspoeling, N en P afspoeling, drinkwaterkwaliteit voor vee en slootbeheer. Om met de BWW te kunnen werken, moet de gebruiker een aantal stappen op het internet nemen. Het is namelijk nodig om Farmmaps voor te bereiden op het functioneren als digitaal platform voor de gebruiker. Deze handleiding geeft elke stap met een toelichting weer. Gegevens worden aangeroepen uit diverse databestanden. De gebruikershandleiding beschrijft wat de herkomst is van verschillende data en hoe deze in de BWW beschermd worden. Per thema in de BWW geeft de handleiding inzicht in de waar het thema precies over gaat, hoe risico’s worden bepaald en wat de concrete betekenis is van een risico-aanduiding. Bovendien beschrijft de handleiding welke factoren invloed hebben op het berekende risico. Deze inzichten kunnen gebruikt worden bij het kiezen van maatregelen om de risico’s met betrekking tot erfafspoeling, droogte, wateroverlast, nitraatuitspoeling, N en P afspoeling, drinkwaterkwaliteit voor vee en slootbeheer te verminderen. Het rapport bevat een begrippenlijst met uitleg over de betekenis van vaktermen.

Published
2024

4. Colonial sugar cultivation in Java and its long-term economic effects: a district-level perspective.

Author

Broos, Nafthali and Broos, Nafthali

Abstract

This thesis aims to study the long-term impact of extractive institutions structured around colonial sugar cultivation on economic development in Java. A spatial district-level model is used in combination with a panel data approach. Two different indicators of colonial sugar cultivation are analysed: one measuring the Cultivation System and one measuring the Liberal Period. The findings suggest that sugar cultivation had a beneficial effect in rural districts and resulted in mixed outcomes in urban districts. Further analysis suggests that the underlying mechanisms are likely structured around agricultural systems. The colonial accumulation of wealth and (unintended) investments are identified as a first potential channel of persistence. The second mechanism revolves around the persistence of inequality-reducing colonial land tenure systems into contemporary institutions. The results highlight the need for a re-evaluation of existing persistence frameworks and emphasize the importance for policymakers to also consider potential beneficial outcomes of extractive institutions.

Published
2024

5. Zuiverende werking van een erfsloot

Author

Dekker, N.J., Broos, J., Dekker, N.J., and Broos, J.

Abstract

Om te voldoen aan de Kaderrichtlijn Water (KRW) in 2027 zijn veldmaatregelen tegen de uit- en afspoeling van nutriënten van het land naar het oppervlaktewater alleen niet voldoende. Daarom is binnen het project Koeien & Kansen aandacht voor erfwater op het melkveebedrijf. Op het melkveebedrijf van Maurice en Ankie van Erp is in 2022 en 2023 op drie momenten het water van een filtersloot bemonsterd om te kijken in hoeverre deze in staat is om relatief schoon erfwater verder te zuiveren.

Published
2024

6. The Tarantula - Revealed by X-rays (T-ReX)

Author

Townsley, Leisa K., Broos, Patrick S., Povich, Matthew S., Townsley, Leisa K., Broos, Patrick S., and Povich, Matthew S.

Abstract

The Tarantula Nebula (30 Doradus) is the most important star-forming complex in the Local Group, offering a microscope on starburst astrophysics. At its heart lies the exceptionally rich young stellar cluster R136, containing the most massive stars known. Stellar winds and supernovae have carved 30 Dor into an amazing display of arcs, pillars, and bubbles. We present first results and advanced data processing products from the 2-Ms Chandra X-ray Visionary Project, "The Tarantula - Revealed by X-rays" (T-ReX). The 3615 point sources in the T-ReX catalog include massive stars, compact objects, binaries, bright pre-main-sequence stars and compact young stellar (sub)clusters in 30 Dor. After removing point sources and excluding the exceptionally bright supernova remnant N157B (30 Dor B), the global diffuse X-ray maps reveal hot plasma structures resolved at 1-10 pc scales, with an absorption-corrected total-band (0.5-7 keV) X-ray luminosity of $2.110\times 10^{37}$ erg s$^{-1}$. Spatially-resolved spectral modeling provides evidence for emission lines enhanced by charge-exchange processes at the interfaces. We identify a candidate for the oldest X-ray pulsar detected to date in 30 Dor, PSR J0538-6902, inside a newly-resolved arctuate X-ray wind nebula, the Manta Ray. The long time baseline of T-ReX monitored dozens of massive stars, several showing periodic variability tied to binary orbital periods, and captured strong flares from at least three low-mass Galactic foreground stars., Comment: 48 pages, 19 figures, accepted for publication in ApJS

Published
2024

7. Latest Evolution of the X-Ray Remnant of SN 1987A: Beyond the Inner Ring

Author

Ravi, Aravind P., Park, Sangwook, Zhekov, Svetozar A., Orlando, Salvatore, Miceli, Marco, Frank, Kari A., Broos, Patrick S., Burrows, David N., Ravi, Aravind P., Park, Sangwook, Zhekov, Svetozar A., Orlando, Salvatore, Miceli, Marco, Frank, Kari A., Broos, Patrick S., and Burrows, David N.

Abstract

Based on our Chandra imaging-spectroscopic observations, we present the latest evolution of the X-ray remnant of SN 1987A. Recent changes in the electron temperatures and volume emission measures suggest that the blast wave in SN 1987A is moving out of the dense inner ring structure, also called the equatorial ring (ER). The 0.5-2.0 keV X-ray light curve shows a linearly declining trend (by $\sim$4.5 % yr$^{-1}$) between 2016 and 2020, as the blast wave heats the hitherto unknown circumstellar medium (CSM) outside the ER. While the peak X-ray emission in the latest 0.3-8.0 keV image is still within the ER, the radial expansion rate in the 3.0-8.0 keV images suggests an increasing contribution of the X-ray emission from less dense CSM since 2012, at least partly from beyond the ER. It is remarkable that, since 2020, the declining soft X-ray flux has stabilized around $\sim$7 $\times$ 10$^{-12}$ erg s$^{-1}$ cm$^{-2}$, which may signal a contribution from the reverse-shocked outer layers of ejecta as predicted by the 3-D magneto-hydrodynamic (MHD) models. In the latest ACIS spectrum of supernova remnant (SNR) 1987A in 2022 we report a significant detection of the Fe K line at $\sim$6.7 keV, which may be due to changing thermal conditions of the X-ray emitting CSM and/or the onset of reverse shock interactions with the Fe-ejecta., Comment: 19 pages, 13 figures, resubmitted to ApJ after addressing referee's comments

Published
2024

8. Timescales in the Biosphere and Geosphere and Their Interactions:Importance in Establishing Earth System State

Author

Broos-Bavnbek, Bernhelm, Christensen, Jens Hesselbjerg, Richardson, Katherine, Codina, Oriol Vallès, Rosing, Minik, Broos-Bavnbek, Bernhelm, Christensen, Jens Hesselbjerg, Richardson, Katherine, Codina, Oriol Vallès, and Rosing, Minik

Abstract

The Earth is a complex system, and its overall condition (state) at any time is determined by Geosphere-Biosphere interactions. The state of the system as a whole changes over time, e.g., ice ages to interglacials. We, therefore, consider system state as a descriptor of, for example, climate. The timescales of the processes driving the interactions between the Geosphere and Biospheres vary. However, many of them are long, i.e., occurring over hundreds of thousands to millions of years. During periods of relative stability in the Earth system state, Geosphere-Biosphere interactions are in a kind of balance or “quasi-equilibrium.” Changes in system state tend to occur when this quasi equilibrium is disturbed through a change in timescales of one or more of these interactions. Examples here would include bolide impacts (an order of magnitude time-scale change in energy flow occurring within the Geosphere) and the evolution of photosynthesis (an order of magnitude change in element flow mediated by the Biosphere). The anthropogenic release of carbon to the atmosphere is occurring at a rate that is ~200 times faster than the rate of the geological transport of carbon back to the Earth’s mantle. This rapid change in element (carbon) flow thus represents a disruption in the balance between the interactions of the Earth system components that has characterized the Holocene and potentially can lead to a transition in the Earth system state. The turnover of C in the Biosphere is, however, also a rapid process. This means that the potential for stimulating biological carbon flow toward lowering the CO2 concentration in the atmosphere is realistic on timescales relevant for humanity.

Published
2024

9. Increased proportions of circulating PD-1+ CD4+ memory T cells and PD-1+ regulatory T cells associate with good response to prednisone in pulmonary sarcoidosis

Author

Miedema, Jelle R., de Jong, Lieke J., Kahlmann, Vivienne, Bergen, Ingrid M., Broos, Caroline E., Wijsenbeek, Marlies S., Hendriks, Rudi W., Corneth, Odilia B.J., Miedema, Jelle R., de Jong, Lieke J., Kahlmann, Vivienne, Bergen, Ingrid M., Broos, Caroline E., Wijsenbeek, Marlies S., Hendriks, Rudi W., and Corneth, Odilia B.J.

Abstract

Background: The treatment response to corticosteroids in patients with sarcoidosis is highly variable. CD4+ T cells are central in sarcoid pathogenesis and their phenotype in peripheral blood (PB) associates with disease course. We hypothesized that the phenotype of circulating T cells in patients with sarcoidosis may correlate with the response to prednisone treatment. Therefore, we aimed to correlate frequencies and phenotypes of circulating T cells at baseline with the pulmonary function response at 3 and 12 months during prednisone treatment in patients with pulmonary sarcoidosis. Methods:We used multi-color flow cytometry to quantify activation marker expression on PB T cell populations in 22 treatment-naïve patients and 21 healthy controls (HCs). Pulmonary function tests at baseline, 3 and 12 months were used to measure treatment effect. Results: Patients with sarcoidosis showed an absolute forced vital capacity (FVC) increase of 14.2% predicted (± 10.6, p < 0.0001) between baseline and 3 months. Good response to prednisone (defined as absolute FVC increase of ≥ 10% predicted) was observed in 12 patients. CD4+ memory T cells and regulatory T cells from patients with sarcoidosis displayed an aberrant phenotype at baseline, compared to HCs. Good responders at 3 months had significantly increased baseline proportions of PD-1+CD4+ memory T cells and PD-1+ regulatory T cells, compared to poor responders and HCs. Moreover, decreased fractions of CD25+ cells and increased fractions of PD-1+ cells within the CD4+ memory T cell population correlated with ≥ 10% FVC increase at 12 months. During treatment, the aberrantly activated phenotype of memory and regulatory T cells reversed. Conclusions: Increased proportions of circulating PD-1+CD4+ memory T cells and PD-1+ regu

Published
2024

11. Circulating T cells in sarcoidosis have an aberrantly activated phenotype that correlates with disease outcome

Author

Miedema, Jelle R., de Jong, Lieke J., van Uden, Denise, Bergen, Ingrid M., Kool, Mirjam, Broos, Caroline E., Kahlmann, Vivienne, Wijsenbeek, Marlies S., Hendriks, Rudi W., Corneth, Odilia B.J., Miedema, Jelle R., de Jong, Lieke J., van Uden, Denise, Bergen, Ingrid M., Kool, Mirjam, Broos, Caroline E., Kahlmann, Vivienne, Wijsenbeek, Marlies S., Hendriks, Rudi W., and Corneth, Odilia B.J.

Published
2023

12. Prognostic and predictive value of human equilibrative nucleoside transporter 1 (hENT1) in extrahepatic cholangiocarcinoma: a translational study

Author

Boyd, Lenka N.C., Nooijen, Lynn E., Ali, Mahsoem, Puik, Jisce R., Moustaquim, Jasmine, Fraga Rodrigues, Stephanie M., Broos, Robert, Belkouz, Ali, Meijer, Laura L., Le Large, Tessa Y.S., Erdmann, Joris I., Hooijer, Gerrit K.J., Heger, Michal, Van Laarhoven, Hanneke W.M., Roos, Eva, Kazemier, Geert, Giovannetti, Elisa, Verheij, Joanne, Klümpen, Heinz Josef, Boyd, Lenka N.C., Nooijen, Lynn E., Ali, Mahsoem, Puik, Jisce R., Moustaquim, Jasmine, Fraga Rodrigues, Stephanie M., Broos, Robert, Belkouz, Ali, Meijer, Laura L., Le Large, Tessa Y.S., Erdmann, Joris I., Hooijer, Gerrit K.J., Heger, Michal, Van Laarhoven, Hanneke W.M., Roos, Eva, Kazemier, Geert, Giovannetti, Elisa, Verheij, Joanne, and Klümpen, Heinz Josef

Abstract

Introduction: Effective (neo) adjuvant chemotherapy for cholangiocarcinoma is lacking due to chemoresistance and the absence of predictive biomarkers. Human equilibrative nucleoside transporter 1 (hENT1) has been described as a potential prognostic and predictive biomarker. In this study, the potential of rabbit-derived (SP120) and murine-derived (10D7G2) antibodies to detect hENT1 expression was compared in tissue samples of patients with extrahepatic cholangiocarcinoma (ECC), and the predictive value of hENT1 was investigated in three ECC cell lines. Methods: Tissues of 71 chemonaïve patients with histological confirmation of ECC were selected and stained with SP120 or 10D7G2 to assess the inter-observer variability for both antibodies and the correlation with overall survival. Concomitantly, gemcitabine sensitivity after hENT1 knockdown was assessed in the ECC cell lines EGI-1, TFK-1, and SK-ChA-1 using sulforhodamine B assays. Results: Scoring immunohistochemistry for hENT1 expression with the use of SP120 antibody resulted in the highest interobserver agreement but did not show a prognostic role of hENT1. However, 10D7G2 showed a prognostic role for hENT1, and a potential predictive role for gemcitabine sensitivity in hENT1 in SK-ChA-1 and TFK-1 cells was found. Discussion: These findings prompt further studies for both preclinical validation of the role of hENT1 and histochemical standardization in cholangiocarcinoma patients treated with gemcitabine-based chemotherapy.

Published
2023

13. Safety of mRNA-based COVID-19 vaccination in paediatric patients with a PEG-asparaginase allergy

Author

Arts-assistenten Kinderen, Cluster A, DT Panda, MS Dermatologie/Allergologie, Infection & Immunity, PMC Medisch specialisten, Broos, Nancy, Brigitha, Leiah J., Schuurhof, Annemieke, Röckmann-Helmbach, Heike, Tissing, Wim J.E., Pieters, Rob, van der Sluis, Inge M., Stadermann, Marike B., Arts-assistenten Kinderen, Cluster A, DT Panda, MS Dermatologie/Allergologie, Infection & Immunity, PMC Medisch specialisten, Broos, Nancy, Brigitha, Leiah J., Schuurhof, Annemieke, Röckmann-Helmbach, Heike, Tissing, Wim J.E., Pieters, Rob, van der Sluis, Inge M., and Stadermann, Marike B.

Published
2023

14. Cost Effectiveness of Rectal Culture-based Antibiotic Prophylaxis in Transrectal Prostate Biopsy: The Results from a Randomized, Nonblinded, Multicenter Trial.

Author

Tops, S.C.M., Kolwijck, E., Koldewijn, E.L., Somford, D.M., Delaere, F.J.M., Leeuwen, Maarten van, Breeuwsma, A.J., Vocht, T.F. de, Broos, H.J., Schipper, R.A., Steffens, M.G., Wegdam-Blans, M.C., Brauwer, E. de, Bijllaardt, W. van den, Leenders, A.C., Sedelaar, J.P.M., Wertheim, H.F.L., Adang, E.M.M., Tops, S.C.M., Kolwijck, E., Koldewijn, E.L., Somford, D.M., Delaere, F.J.M., Leeuwen, Maarten van, Breeuwsma, A.J., Vocht, T.F. de, Broos, H.J., Schipper, R.A., Steffens, M.G., Wegdam-Blans, M.C., Brauwer, E. de, Bijllaardt, W. van den, Leenders, A.C., Sedelaar, J.P.M., Wertheim, H.F.L., and Adang, E.M.M.

Abstract

01 april 2023, Item does not contain fulltext, BACKGROUND: Culture-based antibiotic prophylaxis is a plausible strategy to reduce infections after transrectal prostate biopsy (PB) related to fluoroquinolone-resistant pathogens. OBJECTIVE: To assess the cost effectiveness of rectal culture-based prophylaxis compared with empirical ciprofloxacin prophylaxis. DESIGN SETTING AND PARTICIPANTS: The study was performed alongside a trial in 11 Dutch hospitals investigating the effectiveness of culture-based prophylaxis in transrectal PB between April 2018 and July 2021 (trial registration number: NCT03228108). INTERVENTION: Patients were 1:1 randomized for empirical ciprofloxacin prophylaxis (oral) or culture-based prophylaxis. Costs for both prophylactic strategies were determined for two scenarios: (1) all infectious complications within 7 d after biopsy and (2) culture-proven Gram-negative infections within 30 d after biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Differences in costs and effects (quality-adjusted life-years [QALYs]) were analyzed from a healthcare and societal perspective (including productivity losses, and travel and parking costs) using a bootstrap procedure presenting uncertainty surrounding the incremental cost-effectiveness ratio in a cost-effectiveness plane and acceptability curve. RESULTS AND LIMITATIONS: For the 7-d follow-up period, culture-based prophylaxis (n = 636) was €51.57 (95% confidence interval [CI] 6.52-96.63) more expensive from a healthcare perspective and €16.95 (95% CI -54.29 to 88.18) from a societal perspective than empirical ciprofloxacin prophylaxis (n = 652). Ciprofloxacin-resistant bacteria were detected in 15.4%. Extrapolating our data, from a healthcare perspective, 40% ciprofloxacin resistance would lead to equal cost for both strategies. Results were similar for the 30-d follow-up period. No significant differences in QALYs were observed. CONCLUSIONS: Our results should be interpreted in the context of local ciprofloxacin resistance rates. In our setting, fr

Published
2023

15. Prognostic and predictive value of human equilibrative nucleoside transporter 1 (hENT1) in extrahepatic cholangiocarcinoma: a translational study

Author

Sub Membrane Biochemistry & Biophysics, Afd Pharmaceutics, Pharmaceutics, Boyd, Lenka N.C., Nooijen, Lynn E., Ali, Mahsoem, Puik, Jisce R., Moustaquim, Jasmine, Fraga Rodrigues, Stephanie M., Broos, Robert, Belkouz, Ali, Meijer, Laura L., Le Large, Tessa Y.S., Erdmann, Joris I., Hooijer, Gerrit K.J., Heger, Michal, Van Laarhoven, Hanneke W.M., Roos, Eva, Kazemier, Geert, Giovannetti, Elisa, Verheij, Joanne, Klümpen, Heinz Josef, Sub Membrane Biochemistry & Biophysics, Afd Pharmaceutics, Pharmaceutics, Boyd, Lenka N.C., Nooijen, Lynn E., Ali, Mahsoem, Puik, Jisce R., Moustaquim, Jasmine, Fraga Rodrigues, Stephanie M., Broos, Robert, Belkouz, Ali, Meijer, Laura L., Le Large, Tessa Y.S., Erdmann, Joris I., Hooijer, Gerrit K.J., Heger, Michal, Van Laarhoven, Hanneke W.M., Roos, Eva, Kazemier, Geert, Giovannetti, Elisa, Verheij, Joanne, and Klümpen, Heinz Josef

Published
2023

16. Prognostic and predictive value of human equilibrative nucleoside transporter 1 (hENT1) in extrahepatic cholangiocarcinoma:a translational study

Author

Boyd, LNC, Nooijen, LE, Ali, M, Puik, JR, Moustaquim, J, Rodrigues, SMF, Broos, R, Belkouz, A, Meijer, LL, Le Large, TYS, Erdmann, JI, Hooijer, GKJ, Heger, M, Van Laarhoven, HWM, Roos, E, Kazemier, G, Giovannetti, E, Verheij, J, Kluempen, HJ, Boyd, LNC, Nooijen, LE, Ali, M, Puik, JR, Moustaquim, J, Rodrigues, SMF, Broos, R, Belkouz, A, Meijer, LL, Le Large, TYS, Erdmann, JI, Hooijer, GKJ, Heger, M, Van Laarhoven, HWM, Roos, E, Kazemier, G, Giovannetti, E, Verheij, J, and Kluempen, HJ

Abstract

Introduction: Effective (neo) adjuvant chemotherapy for cholangiocarcinoma is lacking due to chemoresistance and the absence of predictive biomarkers. Human equilibrative nucleoside transporter 1 (hENT1) has been described as a potential prognostic and predictive biomarker. In this study, the potential of rabbit-derived (SP120) and murine-derived (10D7G2) antibodies to detect hENT1 expression was compared in tissue samples of patients with extrahepatic cholangiocarcinoma (ECC), and the predictive value of hENT1 was investigated in three ECC cell lines. Methods: Tissues of 71 chemonaïve patients with histological confirmation of ECC were selected and stained with SP120 or 10D7G2 to assess the inter-observer variability for both antibodies and the correlation with overall survival. Concomitantly, gemcitabine sensitivity after hENT1 knockdown was assessed in the ECC cell lines EGI-1, TFK-1, and SK-ChA-1 using sulforhodamine B assays. Results: Scoring immunohistochemistry for hENT1 expression with the use of SP120 antibody resulted in the highest interobserver agreement but did not show a prognostic role of hENT1. However, 10D7G2 showed a prognostic role for hENT1, and a potential predictive role for gemcitabine sensitivity in hENT1 in SK-ChA-1 and TFK-1 cells was found. Discussion: These findings prompt further studies for both preclinical validation of the role of hENT1 and histochemical standardization in cholangiocarcinoma patients treated with gemcitabine-based chemotherapy.

Published
2023

18. Project ElectriFly: Electric Commuter Aircraft with Mid-Flight Recharging Capability

Author

Dadoo, Vani (author), Jadhavrao, Vishwa (author), Vale de Almeida Norte, Marta (author), Aversa, Alberto (author), Fabrykiewicz, Ada (author), van der Spek, Bas (author), Broos, Sam (author), Savelberg, Thijs (author), Gniadek, Gosia (author), Dissel, Luca (author), Dadoo, Vani (author), Jadhavrao, Vishwa (author), Vale de Almeida Norte, Marta (author), Aversa, Alberto (author), Fabrykiewicz, Ada (author), van der Spek, Bas (author), Broos, Sam (author), Savelberg, Thijs (author), Gniadek, Gosia (author), and Dissel, Luca (author)

Abstract

Bachelor Thesis: Design Synthesis Exercise 2023 Group 13: Electric General Aircraft in collaboration with Group 10: Mid-Flight Recharging System Addressing the pressing need for sustainability amid climate change, the aviation sector is under pressure to mitigate its significant carbon emissions. As aviation accounts for over 2% of global emissions, achieving zero-emissions aviation by 2050 is crucial. The challenge lies in finding alternatives to jet fuel. One option is battery-powered electric aviation, but limitations such as range constraints and emissions during production and disposal must be considered. This report proposes a solution to extend the range of all-electric passenger aircraft. The ElectriFly aircraft can currently fly 600km at 110m/s before requiring recharging. To achieve perpetual flight capability, a mid-flight recharging system is introduced using a drogue and probe system, similar to military refueling technologies. This approach not only increases range but also reduces turn around time at airports. Powered by four parallel-connected solid-state batteries with an energy density of 600kWh/kg, the ElectriFly aircraft features 14 propellers using distributed propulsion and potential plasma actuators. This setup improves aerodynamic performance, reduces noise, and allows for regenerative braking, easing the burden on the recharging drone. Real-time data sensors enable predictive maintenance, minimizing downtime and providing pilots with crucial flight anomaly information. This research presents a promising solution for electric aircraft limitations through mid-flight recharging. The proposed ElectriFly aircraft offers extended range capabilities and improved operational efficiency, supporting the goal of sustainable aviation., AE3200 - Design Synthesis Exercise, Aerospace Engineering

Published
2023

19. Cesin, a short natural variant of nisin, displays potent antimicrobial activity against major pathogens despite lacking two C-terminal macrocycles

Author

Wang, Hui, Wang, H ( Hui ), Guo, Longcheng; https://orcid.org/0000-0003-4409-7935, Wambui, Joseph; https://orcid.org/0000-0002-6071-5505, Wang, Chenhui, Muchaamba, Francis; https://orcid.org/0000-0003-2266-3318, Fernandez-Cantos, Maria Victoria, Broos, Jaap, Tasara, Taurai; https://orcid.org/0000-0003-3377-8858, Kuipers, Oscar P; https://orcid.org/0000-0001-5596-7735, Stephan, Roger; https://orcid.org/0000-0003-1002-4762, Wang, Hui, Wang, H ( Hui ), Guo, Longcheng; https://orcid.org/0000-0003-4409-7935, Wambui, Joseph; https://orcid.org/0000-0002-6071-5505, Wang, Chenhui, Muchaamba, Francis; https://orcid.org/0000-0003-2266-3318, Fernandez-Cantos, Maria Victoria, Broos, Jaap, Tasara, Taurai; https://orcid.org/0000-0003-3377-8858, Kuipers, Oscar P; https://orcid.org/0000-0001-5596-7735, and Stephan, Roger; https://orcid.org/0000-0003-1002-4762

Abstract

Nisin is a widely used lantibiotic owing to its potent antimicrobial activity and its food-grade status. Its mode of action includes cell wall synthesis inhibition and pore formation, which are attributed to the lipid II binding and pore-forming domains, respectively. We discovered cesin, a short natural variant of nisin, produced by the psychrophilic anaerobe Clostridium estertheticum. Unlike other natural nisin variants, cesin lacks the two terminal macrocycles constituting the pore-forming domain. The current study aimed at heterologous expression and characterization of the antimicrobial activity and physicochemical properties of cesin. Following the successful heterologous expression of cesin in Lactococcus lactis, the lantibiotic demonstrated a broad and potent antimicrobial profile comparable to that of nisin. Determination of its mode of action using lipid II and lipoteichoic acid binding assays linked the potent antimicrobial activity to lipid II binding and electrostatic interactions with teichoic acids. Fluorescence microscopy showed that cesin lacks pore-forming ability in its natural form. Stability tests have shown the lantibiotic is highly stable at different pH values and temperature conditions, but that it can be degraded by trypsin. However, a bioengineered analog, cesin R15G, overcame the trypsin degradation, while keeping full antimicrobial activity. This study shows that cesin is a novel (small) nisin variant that efficiently kills target bacteria by inhibiting cell wall synthesis without pore formation. IMPORTANCE The current increase in antibiotic-resistant pathogens necessitates the discovery and application of novel antimicrobials. In this regard, we recently discovered cesin, which is a short natural variant of nisin produced by the psychrophilic Clostridium estertheticum. However, its suitability as an antimicrobial compound was in doubt due to its structural resemblance to nisin(1-22), a bioengineered short variant of nisin with low antim

Published
2023

21. Parathyroid gland detection in hyperparathyroidism with 18F-fluorocholine PET/CT

Author

Broos, Wouter Adrianus Maria, Broos, Wouter Adrianus Maria, Broos, Wouter Adrianus Maria, and Broos, Wouter Adrianus Maria

Abstract

Accurate preoperative localization of hyperfunctioning parathyroid glands is important in patients with hyperparathyroidism who are planned for parathyroidectomy, especially since minimally invasive surgical procedures are regularly used nowadays. An upcoming imaging technique to localize hyperfunctioning parathyroid glands is PET/CT with 18F-fluorocholine (18F-FCH). In this thesis, several both technical as well as clinical aspects of this relatively new imaging method were studied. The current scientific literature related to 18F-FCH PET/CT was reviewed, which showed favorable results for this technique. Different scan acquisition protocols such as dual-time-point scanning and dynamic scanning were studied, which contributed to further optimalization of acquisition protocols. Furthermore, the incidence and relevance of incidental findings on 18F-FCH PET/CT were studied, and in a retrospective cohort study it was concluded that 18F-FCH PET/CT is an excellent imaging technique to detect hyperfunctioning parathyroid glands, not only in case conventional imaging methods are inconclusive, but also as a first-line imaging modality.

Published
2021

23. Evolution of X-ray Activity in <25 Myr Old Pre-Main Sequence Stars

Author

Getman, Konstantin V., Feigelson, Eric D., Garmire, Gordon P., Broos, Patrick S., Kuhn, Michael A., Preibisch, Thomas, Airapetian, Vladimir S., Getman, Konstantin V., Feigelson, Eric D., Garmire, Gordon P., Broos, Patrick S., Kuhn, Michael A., Preibisch, Thomas, and Airapetian, Vladimir S.

Abstract

Measuring the evolution of X-ray emission from pre-main sequence (PMS) stars gives insight into two issues: the response of magnetic dynamo processes to changes in interior structure and the effects of high-energy radiation on protoplanetary disks and primordial planetary atmospheres. We present a sample of 6,003 stars with ages 7-25Myr in ten nearby open clusters from Chandra X-ray and Gaia-EDR3 surveys. Combined with previous results in large samples of younger (<5Myr) stars in MYStIX and SFiNCs star forming regions, mass-stratified activity-age relations are derived for early phases of stellar evolution. X-ray luminosity (Lx) is constant during the first few Myr, possibly due to the presence of extended X-ray coronas insensitive to temporal changes in stellar size. Lx then decays during the 7-25Myr period, more rapidly as stellar mass increases. This decay is interpreted as decreasing efficiency of the alpha^2 dynamo as radiative cores grow and a solar-type alpha-Omega dynamo emerges. For more massive 3.5-7Mo fully radiative stars, the X-ray emission plummets indicating lack of an effective magnetic dynamo. The findings provide improved measurements of high energy radiation effects on circumstellar material, first the protoplanetary disk and then the atmospheres of young planets. The observed X-ray luminosities can be so high that an inner Earth-mass rocky, unmagnetized planet around a solar-mass PMS star might lose its primary and secondary atmospheres within a few-several million years. PMS X-ray emission may thus have a significant impact on evolution of early planetary atmospheres and the conditions promoting the rise of habitability., Comment: 39 pages, 12 figures, 8 tables. Accepted for publication in The Astrophysical Journal, June 10, 2022

Published
2022
Full Text
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24. The Effect of Molecular Cloud Properties on the Kinematics of Stars Formed in the Trifid Region

Author

Kuhn, Michael A., Hillenbrand, Lynne A., Feigelson, Eric D., Fowler, Ian, Getman, Konstantin V., Broos, Patrick S., Povich, Matthew S., Gromadzki, Mariusz, Kuhn, Michael A., Hillenbrand, Lynne A., Feigelson, Eric D., Fowler, Ian, Getman, Konstantin V., Broos, Patrick S., Povich, Matthew S., and Gromadzki, Mariusz

Abstract

The dynamical states of molecular clouds may affect the properties of the stars they form. In the vicinity of the Trifid Nebula ($d=1180\pm25$ pc), the main star cluster (Trifid Main) lies within an expanding section of the molecular cloud; however, ~0.3 deg to the north (Trifid North), the cloud's velocity structure is more tranquil. We acquired a Chandra X-ray observation to identify pre-main-sequence stars in Trifid North, complementing a previous observation of Trifid Main. In Trifid North, we identified 51 candidate pre-main-sequence stars, of which 13 are high-confidence Trifid members based on Gaia EDR3 parallaxes and proper motions. We also re-analyzed membership of Trifid Main and separated out multiple background stellar associations. Trifid North represents a stellar population ~10% as rich as Trifid Main that formed in a separate part of the cloud. The 1D stellar velocity dispersion in Trifid North ($0.6\pm0.2$ km/s) is three times lower than in Trifid Main ($1.9\pm0.2$ km/s). Furthermore, in Trifid Main, proper motions indicate that the portion of the star cluster superimposed on the optical nebula is expanding. Expansion of the HII region around the O-star HD 164492A, and the resulting gas expulsion, can explain both the motions of the stars and gas in Trifid Main. Contrary to previous studies, we find no evidence that a cloud-cloud collision triggered star formation in the region., Comment: 27 pages, 18 figures, and 4 tables. Accepted for publication in ApJ

Published
2022

25. Evolution of X-ray Activity in <25 Myr Old Pre-Main Sequence Stars

Author

Getman, Konstantin V., Feigelson, Eric D., Garmire, Gordon P., Broos, Patrick S., Kuhn, Michael A., Preibisch, Thomas, Airapetian, Vladimir S., Getman, Konstantin V., Feigelson, Eric D., Garmire, Gordon P., Broos, Patrick S., Kuhn, Michael A., Preibisch, Thomas, and Airapetian, Vladimir S.

Abstract

Measuring the evolution of X-ray emission from pre-main sequence (PMS) stars gives insight into two issues: the response of magnetic dynamo processes to changes in interior structure and the effects of high-energy radiation on protoplanetary disks and primordial planetary atmospheres. We present a sample of 6,003 stars with ages [7-25] Myr in ten nearby open clusters from Chandra X-ray and Gaia-EDR3 surveys. Combined with previous results in large samples of younger (<5 Myr) stars in MYStIX and SFiNCs star forming regions, mass-stratified activity-age relations are derived for early phases of stellar evolution. X-ray luminosity (Lx) is constant during the first few Myr, possibly due to the presence of extended X-ray coronas insensitive to temporal changes in stellar size. Lx then decays during the [7-25] Myr period, more rapidly as stellar mass increases. This decay is interpreted as decreasing efficiency of the alpha^2 dynamo as radiative cores grow and a solar-type alpha-Omega dynamo emerges. For more massive [2-7] Msun fully radiative stars, the X-ray emission plummets indicating lack of an effective magnetic dynamos. The findings provide improved measurements of high energy radiation effects on circumstellar material, first the protoplanetary disk and then the atmospheres of young planets. The observed X-ray luminosities can be so high that an inner Earth-mass rocky, unmagnetized planet around a solar-mass PMS star might lose its primary and secondary atmospheres within a few-several million years. PMS X-ray emission may thus have a significant impact on evolution of early planetary atmospheres and the conditions promoting the rise of habitability., Comment: 31 pages, 10 figures, 7 tables. Submitted for publication in The Astrophysical Journal, March 03, 2022

Published
2022

26. Evolution of X-ray Activity in <25 Myr Old Pre-Main Sequence Stars

Author

Getman, Konstantin V., Feigelson, Eric D., Garmire, Gordon P., Broos, Patrick S., Kuhn, Michael A., Preibisch, Thomas, Airapetian, Vladimir S., Getman, Konstantin V., Feigelson, Eric D., Garmire, Gordon P., Broos, Patrick S., Kuhn, Michael A., Preibisch, Thomas, and Airapetian, Vladimir S.

Abstract

Measuring the evolution of X-ray emission from pre-main sequence (PMS) stars gives insight into two issues: the response of magnetic dynamo processes to changes in interior structure and the effects of high-energy radiation on protoplanetary disks and primordial planetary atmospheres. We present a sample of 6,003 stars with ages 7-25Myr in ten nearby open clusters from Chandra X-ray and Gaia-EDR3 surveys. Combined with previous results in large samples of younger (<5Myr) stars in MYStIX and SFiNCs star forming regions, mass-stratified activity-age relations are derived for early phases of stellar evolution. X-ray luminosity (Lx) is constant during the first few Myr, possibly due to the presence of extended X-ray coronas insensitive to temporal changes in stellar size. Lx then decays during the 7-25Myr period, more rapidly as stellar mass increases. This decay is interpreted as decreasing efficiency of the alpha^2 dynamo as radiative cores grow and a solar-type alpha-Omega dynamo emerges. For more massive 3.5-7Mo fully radiative stars, the X-ray emission plummets indicating lack of an effective magnetic dynamo. The findings provide improved measurements of high energy radiation effects on circumstellar material, first the protoplanetary disk and then the atmospheres of young planets. The observed X-ray luminosities can be so high that an inner Earth-mass rocky, unmagnetized planet around a solar-mass PMS star might lose its primary and secondary atmospheres within a few-several million years. PMS X-ray emission may thus have a significant impact on evolution of early planetary atmospheres and the conditions promoting the rise of habitability., Comment: 39 pages, 12 figures, 8 tables. Accepted for publication in The Astrophysical Journal, June 10, 2022

Published
2022

27. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Author

Wang, Zhe, Emmerich, A., Pillon, N.J., Moore, T., Hemerich, D., Cornelis, M.C., Mazzaferro, E., Broos, S., Ahluwalia, T.S., Bartz, T.M., Bentley, A.R., Bielak, L.F., Chong, M., Chu, A.Y., Berry, D., Dorajoo, R., Dueker, N.D., Kasbohm, E., Feenstra, B., Feitosa, M.F., Gieger, C., Graff, M, Hall, L.M., Haller, T., Hartwig, F.P., Hillis, D.A., Huikari, V., Heard-Costa, N., Holzapfel, C., Jackson, A.U., Johansson, Å., Jørgensen, A.M., Kaakinen, M.A., Karlsson, R., Kerr, K.F., Kim, Boram, Koolhaas, C.M., Kutalik, Z., Lagou, V., Lind, P.A., Lorentzon, M., Lyytikäinen, L.P., Mangino, M., Metzendorf, C., Monroe, K.R., Pacolet, A., Pérusse, L., Pool, R., Richmond, R.C., Rivera, N.V., Robiou-du-Pont, S., Schraut, K.E., Schulz, C.A., Stringham, H.M., Tanaka, T., Teumer, A., Turman, C., Most, P.J. van der, Vanmunster, M., Rooij, F.J. van, Vliet-Ostaptchouk, J.V. Van, Zhang, Xiaoshuai, Zhao, J.H., Zhao, W, Balkhiyarova, Z., Balslev-Harder, M.N., Baumeister, S.E., Beilby, J., Blangero, J., Boomsma, D.I., Brage, S., Braund, P.S., Brody, J.A., Bruinenberg, M., Ekelund, U., Liu, C.T., Cole, J.W., Collins, F.S., Cupples, L.A., Esko, T., Enroth, S., Faul, J.D., Fernandez-Rhodes, L., Fohner, A.E., Franco, O.H., Galesloot, T.E., Gordon, S.D.S., Grarup, N., Hartman, C.A., Heiss, G., Hui, J., Illig, T., Jago, R., James, A., Joshi, P.K., Jung, T., Kähönen, M., Kilpeläinen, T.O., Koh, W.P., Kolcic, I., Kiemeney, L.A.L.M., Loos, R.J.F., Hoed, Marcel Den, Wang, Zhe, Emmerich, A., Pillon, N.J., Moore, T., Hemerich, D., Cornelis, M.C., Mazzaferro, E., Broos, S., Ahluwalia, T.S., Bartz, T.M., Bentley, A.R., Bielak, L.F., Chong, M., Chu, A.Y., Berry, D., Dorajoo, R., Dueker, N.D., Kasbohm, E., Feenstra, B., Feitosa, M.F., Gieger, C., Graff, M, Hall, L.M., Haller, T., Hartwig, F.P., Hillis, D.A., Huikari, V., Heard-Costa, N., Holzapfel, C., Jackson, A.U., Johansson, Å., Jørgensen, A.M., Kaakinen, M.A., Karlsson, R., Kerr, K.F., Kim, Boram, Koolhaas, C.M., Kutalik, Z., Lagou, V., Lind, P.A., Lorentzon, M., Lyytikäinen, L.P., Mangino, M., Metzendorf, C., Monroe, K.R., Pacolet, A., Pérusse, L., Pool, R., Richmond, R.C., Rivera, N.V., Robiou-du-Pont, S., Schraut, K.E., Schulz, C.A., Stringham, H.M., Tanaka, T., Teumer, A., Turman, C., Most, P.J. van der, Vanmunster, M., Rooij, F.J. van, Vliet-Ostaptchouk, J.V. Van, Zhang, Xiaoshuai, Zhao, J.H., Zhao, W, Balkhiyarova, Z., Balslev-Harder, M.N., Baumeister, S.E., Beilby, J., Blangero, J., Boomsma, D.I., Brage, S., Braund, P.S., Brody, J.A., Bruinenberg, M., Ekelund, U., Liu, C.T., Cole, J.W., Collins, F.S., Cupples, L.A., Esko, T., Enroth, S., Faul, J.D., Fernandez-Rhodes, L., Fohner, A.E., Franco, O.H., Galesloot, T.E., Gordon, S.D.S., Grarup, N., Hartman, C.A., Heiss, G., Hui, J., Illig, T., Jago, R., James, A., Joshi, P.K., Jung, T., Kähönen, M., Kilpeläinen, T.O., Koh, W.P., Kolcic, I., Kiemeney, L.A.L.M., Loos, R.J.F., and Hoed, Marcel Den

Abstract

Contains fulltext : 282313.pdf (Publisher’s version ) (Open Access), Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type II(A) muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.

Published
2022

28. The Effect of Molecular Cloud Properties on the Kinematics of Stars Formed in the Trifid Region

Author

Kuhns, Michael A., Hillenbrand, Lynne A., Feigelson, Eric D., Fowler, Ian, Getman, Konstantin V., Broos, Patrick S., Povich, Matthew S., Gromadzki, Mariusz, Kuhns, Michael A., Hillenbrand, Lynne A., Feigelson, Eric D., Fowler, Ian, Getman, Konstantin V., Broos, Patrick S., Povich, Matthew S., and Gromadzki, Mariusz

Abstract

The dynamical states of molecular clouds may affect the properties of the stars they form. In the vicinity of the Trifid Nebula (d = 1180 ± 25 pc), the main star cluster (Trifid Main) lies within an expanding section of the molecular cloud; however, ~0.3 deg to the north (Trifid North), the cloud's velocity structure is more tranquil. We acquired a Chandra X-ray observation to identify pre-main-sequence stars in Trifid North, complementing a previous observation of Trifid Main. In Trifid North, we identified 51 candidate pre-main-sequence stars, of which 13 are high-confidence Trifid members based on Gaia EDR3 parallaxes and proper motions. We also re-analyzed membership of Trifid Main and separated out multiple background stellar associations. Trifid North represents a stellar population ~10% as rich as Trifid Main that formed in a separate part of the cloud. The 1D stellar velocity dispersion in Trifid North (0.6 ± 0.2 km/s) is three times lower than in Trifid Main (1.9 ± 0.2 km/s). Furthermore, in Trifid Main, proper motions indicate that the portion of the star cluster superimposed on the optical nebula is expanding. Expansion of the HII region around the O-star HD 164492A, and the resulting gas expulsion, can explain both the motions of the stars and gas in Trifid Main. Contrary to previous studies, we find no evidence that a cloud-cloud collision triggered star formation in the region.

Published
2022

29. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Author

Wang, Zhe, Emmerich, A., Pillon, N.J., Moore, T., Hemerich, D., Cornelis, M.C., Mazzaferro, E., Broos, S., Ahluwalia, T.S., Bartz, T.M., Bentley, A.R., Bielak, L.F., Chong, M., Chu, A.Y., Berry, D., Dorajoo, R., Dueker, N.D., Kasbohm, E., Feenstra, B., Feitosa, M.F., Gieger, C., Graff, M, Hall, L.M., Haller, T., Hartwig, F.P., Hillis, D.A., Huikari, V., Heard-Costa, N., Holzapfel, C., Jackson, A.U., Johansson, Å., Jørgensen, A.M., Kaakinen, M.A., Karlsson, R., Kerr, K.F., Kim, Boram, Koolhaas, C.M., Kutalik, Z., Lagou, V., Lind, P.A., Lorentzon, M., Lyytikäinen, L.P., Mangino, M., Metzendorf, C., Monroe, K.R., Pacolet, A., Pérusse, L., Pool, R., Richmond, R.C., Rivera, N.V., Robiou-du-Pont, S., Schraut, K.E., Schulz, C.A., Stringham, H.M., Tanaka, T., Teumer, A., Turman, C., Most, P.J. van der, Vanmunster, M., Rooij, F.J. van, Vliet-Ostaptchouk, J.V. Van, Zhang, Xiaoshuai, Zhao, J.H., Zhao, W, Balkhiyarova, Z., Balslev-Harder, M.N., Baumeister, S.E., Beilby, J., Blangero, J., Boomsma, D.I., Brage, S., Braund, P.S., Brody, J.A., Bruinenberg, M., Ekelund, U., Liu, C.T., Cole, J.W., Collins, F.S., Cupples, L.A., Esko, T., Enroth, S., Faul, J.D., Fernandez-Rhodes, L., Fohner, A.E., Franco, O.H., Galesloot, T.E., Gordon, S.D.S., Grarup, N., Hartman, C.A., Heiss, G., Hui, J., Illig, T., Jago, R., James, A., Joshi, P.K., Jung, T., Kähönen, M., Kilpeläinen, T.O., Koh, W.P., Kolcic, I., Kiemeney, L.A.L.M., Loos, R.J.F., Hoed, Marcel Den, Wang, Zhe, Emmerich, A., Pillon, N.J., Moore, T., Hemerich, D., Cornelis, M.C., Mazzaferro, E., Broos, S., Ahluwalia, T.S., Bartz, T.M., Bentley, A.R., Bielak, L.F., Chong, M., Chu, A.Y., Berry, D., Dorajoo, R., Dueker, N.D., Kasbohm, E., Feenstra, B., Feitosa, M.F., Gieger, C., Graff, M, Hall, L.M., Haller, T., Hartwig, F.P., Hillis, D.A., Huikari, V., Heard-Costa, N., Holzapfel, C., Jackson, A.U., Johansson, Å., Jørgensen, A.M., Kaakinen, M.A., Karlsson, R., Kerr, K.F., Kim, Boram, Koolhaas, C.M., Kutalik, Z., Lagou, V., Lind, P.A., Lorentzon, M., Lyytikäinen, L.P., Mangino, M., Metzendorf, C., Monroe, K.R., Pacolet, A., Pérusse, L., Pool, R., Richmond, R.C., Rivera, N.V., Robiou-du-Pont, S., Schraut, K.E., Schulz, C.A., Stringham, H.M., Tanaka, T., Teumer, A., Turman, C., Most, P.J. van der, Vanmunster, M., Rooij, F.J. van, Vliet-Ostaptchouk, J.V. Van, Zhang, Xiaoshuai, Zhao, J.H., Zhao, W, Balkhiyarova, Z., Balslev-Harder, M.N., Baumeister, S.E., Beilby, J., Blangero, J., Boomsma, D.I., Brage, S., Braund, P.S., Brody, J.A., Bruinenberg, M., Ekelund, U., Liu, C.T., Cole, J.W., Collins, F.S., Cupples, L.A., Esko, T., Enroth, S., Faul, J.D., Fernandez-Rhodes, L., Fohner, A.E., Franco, O.H., Galesloot, T.E., Gordon, S.D.S., Grarup, N., Hartman, C.A., Heiss, G., Hui, J., Illig, T., Jago, R., James, A., Joshi, P.K., Jung, T., Kähönen, M., Kilpeläinen, T.O., Koh, W.P., Kolcic, I., Kiemeney, L.A.L.M., Loos, R.J.F., and Hoed, Marcel Den

Abstract

Contains fulltext : 282313.pdf (Publisher’s version ) (Open Access), Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type II(A) muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.

Published
2022

30. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Author

Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J, Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C, Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S, Bartz, Traci M, Bentley, Amy R, Bielak, Lawrence F, Chong, Mike, Chu, Audrey Y, Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D, Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F, Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M, Haller, Toomas, Hartwig, Fernando P, Hillis, David A, Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U, Johansson, Åsa, Jørgensen, Anja Moltke, Kaakinen, Marika A, Karlsson, Robert, Kerr, Kathleen F, Kim, Boram, Koolhaas, Chantal M, Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope A, Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine R, Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca C, Rivera, Natalia V, Robiou-du-Pont, Sebastien, Schraut, Katharina E, Schulz, Christina-Alexandra, Stringham, Heather M, Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter J, Vanmunster, Mathias, van Rooij, Frank J A, van Vliet-Ostaptchouk, Jana V, Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie N, Baumeister, Sebastian E, Beilby, John, Blangero, John, Boomsma, Dorret I, Brage, Soren, Braund, Peter S, Brody, Jennifer A, Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John W, Collins, Francis S, Cupples, L Adrienne, Esko, Tõnu, Enroth, Stefan, Faul, Jessica D, Fernandez-Rhodes, Lindsay, Fohner, Alison E, Franco, Oscar H, Galesloot, Tessel E, Gordon, Scott D, Grarup, Niels, Hartman, Catharina A, Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter K, Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas O, Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter P, Kuusisto, Johanna, Launer, Lenore J, Li, Aihua, Linneberg, Allan, Luan, Jian'an, Vidal, Pedro Marques, Medland, Sarah E, Milaneschi, Yuri, Moscati, Arden, Musk, Bill, Nelson, Christopher P, Nolte, Ilja M, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Power, Christine, Raitakari, Olli T, Reedik, Mägi, Reiner, Alex P, Ridker, Paul M, Rudan, Igor, Ryan, Kathy, Sarzynski, Mark A, Scott, Laura J, Scott, Robert A, Sidney, Stephen, Siggeirsdottir, Kristin, Smith, Albert V, Smith, Jennifer A, Sonestedt, Emily, Strøm, Marin, Tai, E Shyong, Teo, Koon K, Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Uitterlinden, Andre G, Vangipurapu, Jagadish, van Schoor, Natasja, Völker, Uwe, Willemsen, Gonneke, Williams, Kayleen, Wong, Quenna, Xu, Huichun, Young, Kristin L, Yuan, Jian Min, Zillikens, M Carola, Zonderman, Alan B, Ameur, Adam, Bandinelli, Stefania, Bis, Joshua C, Boehnke, Michael, Bouchard, Claude, Chasman, Daniel I, Smith, George Davey, de Geus, Eco J C, Deldicque, Louise, Dörr, Marcus, Evans, Michele K, Ferrucci, Luigi, Fornage, Myriam, Fox, Caroline, Garland, Theodore, Gudnason, Vilmundur, Gyllensten, Ulf, Hansen, Torben, Hayward, Caroline, Horta, Bernardo L, Hyppönen, Elina, Jarvelin, Marjo-Riitta, Johnson, W Craig, Kardia, Sharon L R, Kiemeney, Lambertus A, Laakso, Markku, Langenberg, Claudia, Lehtimäki, Terho, Marchand, Loic Le, Magnusson, Patrik K E, Martin, Nicholas G, Melbye, Mads, Metspalu, Andres, Meyre, David, North, Kari E, Ohlsson, Claes, Oldehinkel, Albertine J, Orho-Melander, Marju, Pare, Guillaume, Park, Taesung, Pedersen, Oluf, Penninx, Brenda W J H, Pers, Tune H, Polasek, Ozren, Prokopenko, Inga, Rotimi, Charles N, Samani, Nilesh J, Sim, Xueling, Snieder, Harold, Sørensen, Thorkild I A, Spector, Tim D, Timpson, Nicholas J, van Dam, Rob M, van der Velde, Nathalie, van Duijn, Cornelia M, Vollenweider, Peter, Völzke, Henry, Voortman, Trudy, Waeber, Gérard, Wareham, Nicholas J, Weir, David R, Wichmann, Heinz-Erich, Wilson, James F, Hevener, Andrea L, Krook, Anna, Zierath, Juleen R, Thomis, Martine A I, Loos, Ruth J F, den Hoed, Marcel, Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J, Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C, Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S, Bartz, Traci M, Bentley, Amy R, Bielak, Lawrence F, Chong, Mike, Chu, Audrey Y, Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D, Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F, Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M, Haller, Toomas, Hartwig, Fernando P, Hillis, David A, Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U, Johansson, Åsa, Jørgensen, Anja Moltke, Kaakinen, Marika A, Karlsson, Robert, Kerr, Kathleen F, Kim, Boram, Koolhaas, Chantal M, Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope A, Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine R, Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca C, Rivera, Natalia V, Robiou-du-Pont, Sebastien, Schraut, Katharina E, Schulz, Christina-Alexandra, Stringham, Heather M, Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter J, Vanmunster, Mathias, van Rooij, Frank J A, van Vliet-Ostaptchouk, Jana V, Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie N, Baumeister, Sebastian E, Beilby, John, Blangero, John, Boomsma, Dorret I, Brage, Soren, Braund, Peter S, Brody, Jennifer A, Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John W, Collins, Francis S, Cupples, L Adrienne, Esko, Tõnu, Enroth, Stefan, Faul, Jessica D, Fernandez-Rhodes, Lindsay, Fohner, Alison E, Franco, Oscar H, Galesloot, Tessel E, Gordon, Scott D, Grarup, Niels, Hartman, Catharina A, Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter K, Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas O, Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter P, Kuusisto, Johanna, Launer, Lenore J, Li, Aihua, Linneberg, Allan, Luan, Jian'an, Vidal, Pedro Marques, Medland, Sarah E, Milaneschi, Yuri, Moscati, Arden, Musk, Bill, Nelson, Christopher P, Nolte, Ilja M, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Power, Christine, Raitakari, Olli T, Reedik, Mägi, Reiner, Alex P, Ridker, Paul M, Rudan, Igor, Ryan, Kathy, Sarzynski, Mark A, Scott, Laura J, Scott, Robert A, Sidney, Stephen, Siggeirsdottir, Kristin, Smith, Albert V, Smith, Jennifer A, Sonestedt, Emily, Strøm, Marin, Tai, E Shyong, Teo, Koon K, Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Uitterlinden, Andre G, Vangipurapu, Jagadish, van Schoor, Natasja, Völker, Uwe, Willemsen, Gonneke, Williams, Kayleen, Wong, Quenna, Xu, Huichun, Young, Kristin L, Yuan, Jian Min, Zillikens, M Carola, Zonderman, Alan B, Ameur, Adam, Bandinelli, Stefania, Bis, Joshua C, Boehnke, Michael, Bouchard, Claude, Chasman, Daniel I, Smith, George Davey, de Geus, Eco J C, Deldicque, Louise, Dörr, Marcus, Evans, Michele K, Ferrucci, Luigi, Fornage, Myriam, Fox, Caroline, Garland, Theodore, Gudnason, Vilmundur, Gyllensten, Ulf, Hansen, Torben, Hayward, Caroline, Horta, Bernardo L, Hyppönen, Elina, Jarvelin, Marjo-Riitta, Johnson, W Craig, Kardia, Sharon L R, Kiemeney, Lambertus A, Laakso, Markku, Langenberg, Claudia, Lehtimäki, Terho, Marchand, Loic Le, Magnusson, Patrik K E, Martin, Nicholas G, Melbye, Mads, Metspalu, Andres, Meyre, David, North, Kari E, Ohlsson, Claes, Oldehinkel, Albertine J, Orho-Melander, Marju, Pare, Guillaume, Park, Taesung, Pedersen, Oluf, Penninx, Brenda W J H, Pers, Tune H, Polasek, Ozren, Prokopenko, Inga, Rotimi, Charles N, Samani, Nilesh J, Sim, Xueling, Snieder, Harold, Sørensen, Thorkild I A, Spector, Tim D, Timpson, Nicholas J, van Dam, Rob M, van der Velde, Nathalie, van Duijn, Cornelia M, Vollenweider, Peter, Völzke, Henry, Voortman, Trudy, Waeber, Gérard, Wareham, Nicholas J, Weir, David R, Wichmann, Heinz-Erich, Wilson, James F, Hevener, Andrea L, Krook, Anna, Zierath, Juleen R, Thomis, Martine A I, Loos, Ruth J F, and den Hoed, Marcel

Abstract

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.

Published
2022
Full Text
View/download PDF

31. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Author

Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J, Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C, Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S, Bartz, Traci M, Bentley, Amy R, Bielak, Lawrence F, Chong, Mike, Chu, Audrey Y, Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D, Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F, Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M, Haller, Toomas, Hartwig, Fernando P, Hillis, David A, Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U, Johansson, Åsa, Jørgensen, Anja Moltke, Kaakinen, Marika A, Karlsson, Robert, Kerr, Kathleen F, Kim, Boram, Koolhaas, Chantal M, Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope A, Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine R, Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca C, Rivera, Natalia V, Robiou-du-Pont, Sebastien, Schraut, Katharina E, Schulz, Christina-Alexandra, Stringham, Heather M, Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter J, Vanmunster, Mathias, van Rooij, Frank J A, van Vliet-Ostaptchouk, Jana V, Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie N, Baumeister, Sebastian E, Beilby, John, Blangero, John, Boomsma, Dorret I, Brage, Soren, Braund, Peter S, Brody, Jennifer A, Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John W, Collins, Francis S, Cupples, L Adrienne, Esko, Tõnu, Enroth, Stefan, Faul, Jessica D, Fernandez-Rhodes, Lindsay, Fohner, Alison E, Franco, Oscar H, Galesloot, Tessel E, Gordon, Scott D, Grarup, Niels, Hartman, Catharina A, Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter K, Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas O, Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter P, Kuusisto, Johanna, Launer, Lenore J, Li, Aihua, Linneberg, Allan, Luan, Jian'an, Vidal, Pedro Marques, Medland, Sarah E, Milaneschi, Yuri, Moscati, Arden, Musk, Bill, Nelson, Christopher P, Nolte, Ilja M, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Power, Christine, Raitakari, Olli T, Reedik, Mägi, Reiner, Alex P, Ridker, Paul M, Rudan, Igor, Ryan, Kathy, Sarzynski, Mark A, Scott, Laura J, Scott, Robert A, Sidney, Stephen, Siggeirsdottir, Kristin, Smith, Albert V, Smith, Jennifer A, Sonestedt, Emily, Strøm, Marin, Tai, E Shyong, Teo, Koon K, Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Uitterlinden, Andre G, Vangipurapu, Jagadish, van Schoor, Natasja, Völker, Uwe, Willemsen, Gonneke, Williams, Kayleen, Wong, Quenna, Xu, Huichun, Young, Kristin L, Yuan, Jian Min, Zillikens, M Carola, Zonderman, Alan B, Ameur, Adam, Bandinelli, Stefania, Bis, Joshua C, Boehnke, Michael, Bouchard, Claude, Chasman, Daniel I, Smith, George Davey, de Geus, Eco J C, Deldicque, Louise, Dörr, Marcus, Evans, Michele K, Ferrucci, Luigi, Fornage, Myriam, Fox, Caroline, Garland, Theodore, Gudnason, Vilmundur, Gyllensten, Ulf, Hansen, Torben, Hayward, Caroline, Horta, Bernardo L, Hyppönen, Elina, Jarvelin, Marjo-Riitta, Johnson, W Craig, Kardia, Sharon L R, Kiemeney, Lambertus A, Laakso, Markku, Langenberg, Claudia, Lehtimäki, Terho, Marchand, Loic Le, Magnusson, Patrik K E, Martin, Nicholas G, Melbye, Mads, Metspalu, Andres, Meyre, David, North, Kari E, Ohlsson, Claes, Oldehinkel, Albertine J, Orho-Melander, Marju, Pare, Guillaume, Park, Taesung, Pedersen, Oluf, Penninx, Brenda W J H, Pers, Tune H, Polasek, Ozren, Prokopenko, Inga, Rotimi, Charles N, Samani, Nilesh J, Sim, Xueling, Snieder, Harold, Sørensen, Thorkild I A, Spector, Tim D, Timpson, Nicholas J, van Dam, Rob M, van der Velde, Nathalie, van Duijn, Cornelia M, Vollenweider, Peter, Völzke, Henry, Voortman, Trudy, Waeber, Gérard, Wareham, Nicholas J, Weir, David R, Wichmann, Heinz-Erich, Wilson, James F, Hevener, Andrea L, Krook, Anna, Zierath, Juleen R, Thomis, Martine A I, Loos, Ruth J F, den Hoed, Marcel, Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J, Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C, Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S, Bartz, Traci M, Bentley, Amy R, Bielak, Lawrence F, Chong, Mike, Chu, Audrey Y, Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D, Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F, Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M, Haller, Toomas, Hartwig, Fernando P, Hillis, David A, Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U, Johansson, Åsa, Jørgensen, Anja Moltke, Kaakinen, Marika A, Karlsson, Robert, Kerr, Kathleen F, Kim, Boram, Koolhaas, Chantal M, Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope A, Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine R, Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca C, Rivera, Natalia V, Robiou-du-Pont, Sebastien, Schraut, Katharina E, Schulz, Christina-Alexandra, Stringham, Heather M, Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter J, Vanmunster, Mathias, van Rooij, Frank J A, van Vliet-Ostaptchouk, Jana V, Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie N, Baumeister, Sebastian E, Beilby, John, Blangero, John, Boomsma, Dorret I, Brage, Soren, Braund, Peter S, Brody, Jennifer A, Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John W, Collins, Francis S, Cupples, L Adrienne, Esko, Tõnu, Enroth, Stefan, Faul, Jessica D, Fernandez-Rhodes, Lindsay, Fohner, Alison E, Franco, Oscar H, Galesloot, Tessel E, Gordon, Scott D, Grarup, Niels, Hartman, Catharina A, Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter K, Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas O, Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter P, Kuusisto, Johanna, Launer, Lenore J, Li, Aihua, Linneberg, Allan, Luan, Jian'an, Vidal, Pedro Marques, Medland, Sarah E, Milaneschi, Yuri, Moscati, Arden, Musk, Bill, Nelson, Christopher P, Nolte, Ilja M, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Power, Christine, Raitakari, Olli T, Reedik, Mägi, Reiner, Alex P, Ridker, Paul M, Rudan, Igor, Ryan, Kathy, Sarzynski, Mark A, Scott, Laura J, Scott, Robert A, Sidney, Stephen, Siggeirsdottir, Kristin, Smith, Albert V, Smith, Jennifer A, Sonestedt, Emily, Strøm, Marin, Tai, E Shyong, Teo, Koon K, Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Uitterlinden, Andre G, Vangipurapu, Jagadish, van Schoor, Natasja, Völker, Uwe, Willemsen, Gonneke, Williams, Kayleen, Wong, Quenna, Xu, Huichun, Young, Kristin L, Yuan, Jian Min, Zillikens, M Carola, Zonderman, Alan B, Ameur, Adam, Bandinelli, Stefania, Bis, Joshua C, Boehnke, Michael, Bouchard, Claude, Chasman, Daniel I, Smith, George Davey, de Geus, Eco J C, Deldicque, Louise, Dörr, Marcus, Evans, Michele K, Ferrucci, Luigi, Fornage, Myriam, Fox, Caroline, Garland, Theodore, Gudnason, Vilmundur, Gyllensten, Ulf, Hansen, Torben, Hayward, Caroline, Horta, Bernardo L, Hyppönen, Elina, Jarvelin, Marjo-Riitta, Johnson, W Craig, Kardia, Sharon L R, Kiemeney, Lambertus A, Laakso, Markku, Langenberg, Claudia, Lehtimäki, Terho, Marchand, Loic Le, Magnusson, Patrik K E, Martin, Nicholas G, Melbye, Mads, Metspalu, Andres, Meyre, David, North, Kari E, Ohlsson, Claes, Oldehinkel, Albertine J, Orho-Melander, Marju, Pare, Guillaume, Park, Taesung, Pedersen, Oluf, Penninx, Brenda W J H, Pers, Tune H, Polasek, Ozren, Prokopenko, Inga, Rotimi, Charles N, Samani, Nilesh J, Sim, Xueling, Snieder, Harold, Sørensen, Thorkild I A, Spector, Tim D, Timpson, Nicholas J, van Dam, Rob M, van der Velde, Nathalie, van Duijn, Cornelia M, Vollenweider, Peter, Völzke, Henry, Voortman, Trudy, Waeber, Gérard, Wareham, Nicholas J, Weir, David R, Wichmann, Heinz-Erich, Wilson, James F, Hevener, Andrea L, Krook, Anna, Zierath, Juleen R, Thomis, Martine A I, Loos, Ruth J F, and den Hoed, Marcel

Abstract

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.

Published
2022
Full Text
View/download PDF

32. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Author

Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J, Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C, Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S, Bartz, Traci M, Bentley, Amy R, Bielak, Lawrence F, Chong, Mike, Chu, Audrey Y, Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D, Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F, Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M, Haller, Toomas, Hartwig, Fernando P, Hillis, David A, Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U, Johansson, Åsa, Jørgensen, Anja Moltke, Kaakinen, Marika A, Karlsson, Robert, Kerr, Kathleen F, Kim, Boram, Koolhaas, Chantal M, Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope A, Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine R, Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca C, Rivera, Natalia V, Robiou-du-Pont, Sebastien, Schraut, Katharina E, Schulz, Christina-Alexandra, Stringham, Heather M, Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter J, Vanmunster, Mathias, van Rooij, Frank J A, van Vliet-Ostaptchouk, Jana V, Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie N, Baumeister, Sebastian E, Beilby, John, Blangero, John, Boomsma, Dorret I, Brage, Soren, Braund, Peter S, Brody, Jennifer A, Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John W, Collins, Francis S, Cupples, L Adrienne, Esko, Tõnu, Enroth, Stefan, Faul, Jessica D, Fernandez-Rhodes, Lindsay, Fohner, Alison E, Franco, Oscar H, Galesloot, Tessel E, Gordon, Scott D, Grarup, Niels, Hartman, Catharina A, Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter K, Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas O, Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter P, Kuusisto, Johanna, Launer, Lenore J, Li, Aihua, Linneberg, Allan, Luan, Jian'an, Vidal, Pedro Marques, Medland, Sarah E, Milaneschi, Yuri, Moscati, Arden, Musk, Bill, Nelson, Christopher P, Nolte, Ilja M, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Power, Christine, Raitakari, Olli T, Reedik, Mägi, Reiner, Alex P, Ridker, Paul M, Rudan, Igor, Ryan, Kathy, Sarzynski, Mark A, Scott, Laura J, Scott, Robert A, Sidney, Stephen, Siggeirsdottir, Kristin, Smith, Albert V, Smith, Jennifer A, Sonestedt, Emily, Strøm, Marin, Tai, E Shyong, Teo, Koon K, Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Uitterlinden, Andre G, Vangipurapu, Jagadish, van Schoor, Natasja, Völker, Uwe, Willemsen, Gonneke, Williams, Kayleen, Wong, Quenna, Xu, Huichun, Young, Kristin L, Yuan, Jian Min, Zillikens, M Carola, Zonderman, Alan B, Ameur, Adam, Bandinelli, Stefania, Bis, Joshua C, Boehnke, Michael, Bouchard, Claude, Chasman, Daniel I, Smith, George Davey, de Geus, Eco J C, Deldicque, Louise, Dörr, Marcus, Evans, Michele K, Ferrucci, Luigi, Fornage, Myriam, Fox, Caroline, Garland, Theodore, Gudnason, Vilmundur, Gyllensten, Ulf, Hansen, Torben, Hayward, Caroline, Horta, Bernardo L, Hyppönen, Elina, Jarvelin, Marjo-Riitta, Johnson, W Craig, Kardia, Sharon L R, Kiemeney, Lambertus A, Laakso, Markku, Langenberg, Claudia, Lehtimäki, Terho, Marchand, Loic Le, Magnusson, Patrik K E, Martin, Nicholas G, Melbye, Mads, Metspalu, Andres, Meyre, David, North, Kari E, Ohlsson, Claes, Oldehinkel, Albertine J, Orho-Melander, Marju, Pare, Guillaume, Park, Taesung, Pedersen, Oluf, Penninx, Brenda W J H, Pers, Tune H, Polasek, Ozren, Prokopenko, Inga, Rotimi, Charles N, Samani, Nilesh J, Sim, Xueling, Snieder, Harold, Sørensen, Thorkild I A, Spector, Tim D, Timpson, Nicholas J, van Dam, Rob M, van der Velde, Nathalie, van Duijn, Cornelia M, Vollenweider, Peter, Völzke, Henry, Voortman, Trudy, Waeber, Gérard, Wareham, Nicholas J, Weir, David R, Wichmann, Heinz-Erich, Wilson, James F, Hevener, Andrea L, Krook, Anna, Zierath, Juleen R, Thomis, Martine A I, Loos, Ruth J F, den Hoed, Marcel, Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J, Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C, Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S, Bartz, Traci M, Bentley, Amy R, Bielak, Lawrence F, Chong, Mike, Chu, Audrey Y, Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D, Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F, Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M, Haller, Toomas, Hartwig, Fernando P, Hillis, David A, Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U, Johansson, Åsa, Jørgensen, Anja Moltke, Kaakinen, Marika A, Karlsson, Robert, Kerr, Kathleen F, Kim, Boram, Koolhaas, Chantal M, Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope A, Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine R, Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca C, Rivera, Natalia V, Robiou-du-Pont, Sebastien, Schraut, Katharina E, Schulz, Christina-Alexandra, Stringham, Heather M, Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter J, Vanmunster, Mathias, van Rooij, Frank J A, van Vliet-Ostaptchouk, Jana V, Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie N, Baumeister, Sebastian E, Beilby, John, Blangero, John, Boomsma, Dorret I, Brage, Soren, Braund, Peter S, Brody, Jennifer A, Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John W, Collins, Francis S, Cupples, L Adrienne, Esko, Tõnu, Enroth, Stefan, Faul, Jessica D, Fernandez-Rhodes, Lindsay, Fohner, Alison E, Franco, Oscar H, Galesloot, Tessel E, Gordon, Scott D, Grarup, Niels, Hartman, Catharina A, Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter K, Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas O, Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter P, Kuusisto, Johanna, Launer, Lenore J, Li, Aihua, Linneberg, Allan, Luan, Jian'an, Vidal, Pedro Marques, Medland, Sarah E, Milaneschi, Yuri, Moscati, Arden, Musk, Bill, Nelson, Christopher P, Nolte, Ilja M, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Power, Christine, Raitakari, Olli T, Reedik, Mägi, Reiner, Alex P, Ridker, Paul M, Rudan, Igor, Ryan, Kathy, Sarzynski, Mark A, Scott, Laura J, Scott, Robert A, Sidney, Stephen, Siggeirsdottir, Kristin, Smith, Albert V, Smith, Jennifer A, Sonestedt, Emily, Strøm, Marin, Tai, E Shyong, Teo, Koon K, Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Uitterlinden, Andre G, Vangipurapu, Jagadish, van Schoor, Natasja, Völker, Uwe, Willemsen, Gonneke, Williams, Kayleen, Wong, Quenna, Xu, Huichun, Young, Kristin L, Yuan, Jian Min, Zillikens, M Carola, Zonderman, Alan B, Ameur, Adam, Bandinelli, Stefania, Bis, Joshua C, Boehnke, Michael, Bouchard, Claude, Chasman, Daniel I, Smith, George Davey, de Geus, Eco J C, Deldicque, Louise, Dörr, Marcus, Evans, Michele K, Ferrucci, Luigi, Fornage, Myriam, Fox, Caroline, Garland, Theodore, Gudnason, Vilmundur, Gyllensten, Ulf, Hansen, Torben, Hayward, Caroline, Horta, Bernardo L, Hyppönen, Elina, Jarvelin, Marjo-Riitta, Johnson, W Craig, Kardia, Sharon L R, Kiemeney, Lambertus A, Laakso, Markku, Langenberg, Claudia, Lehtimäki, Terho, Marchand, Loic Le, Magnusson, Patrik K E, Martin, Nicholas G, Melbye, Mads, Metspalu, Andres, Meyre, David, North, Kari E, Ohlsson, Claes, Oldehinkel, Albertine J, Orho-Melander, Marju, Pare, Guillaume, Park, Taesung, Pedersen, Oluf, Penninx, Brenda W J H, Pers, Tune H, Polasek, Ozren, Prokopenko, Inga, Rotimi, Charles N, Samani, Nilesh J, Sim, Xueling, Snieder, Harold, Sørensen, Thorkild I A, Spector, Tim D, Timpson, Nicholas J, van Dam, Rob M, van der Velde, Nathalie, van Duijn, Cornelia M, Vollenweider, Peter, Völzke, Henry, Voortman, Trudy, Waeber, Gérard, Wareham, Nicholas J, Weir, David R, Wichmann, Heinz-Erich, Wilson, James F, Hevener, Andrea L, Krook, Anna, Zierath, Juleen R, Thomis, Martine A I, Loos, Ruth J F, and den Hoed, Marcel

Abstract

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.

Published
2022
Full Text
View/download PDF

33. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Author

Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J, Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C, Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S, Bartz, Traci M, Bentley, Amy R, Bielak, Lawrence F, Chong, Mike, Chu, Audrey Y, Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D, Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F, Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M, Haller, Toomas, Hartwig, Fernando P, Hillis, David A, Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U, Johansson, Åsa, Jørgensen, Anja Moltke, Kaakinen, Marika A, Karlsson, Robert, Kerr, Kathleen F, Kim, Boram, Koolhaas, Chantal M, Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope A, Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine R, Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca C, Rivera, Natalia V, Robiou-du-Pont, Sebastien, Schraut, Katharina E, Schulz, Christina-Alexandra, Stringham, Heather M, Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter J, Vanmunster, Mathias, van Rooij, Frank J A, van Vliet-Ostaptchouk, Jana V, Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie N, Baumeister, Sebastian E, Beilby, John, Blangero, John, Boomsma, Dorret I, Brage, Soren, Braund, Peter S, Brody, Jennifer A, Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John W, Collins, Francis S, Cupples, L Adrienne, Esko, Tõnu, Enroth, Stefan, Faul, Jessica D, Fernandez-Rhodes, Lindsay, Fohner, Alison E, Franco, Oscar H, Galesloot, Tessel E, Gordon, Scott D, Grarup, Niels, Hartman, Catharina A, Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter K, Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas O, Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter P, Kuusisto, Johanna, Launer, Lenore J, Li, Aihua, Linneberg, Allan, Luan, Jian'an, Vidal, Pedro Marques, Medland, Sarah E, Milaneschi, Yuri, Moscati, Arden, Musk, Bill, Nelson, Christopher P, Nolte, Ilja M, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Power, Christine, Raitakari, Olli T, Reedik, Mägi, Reiner, Alex P, Ridker, Paul M, Rudan, Igor, Ryan, Kathy, Sarzynski, Mark A, Scott, Laura J, Scott, Robert A, Sidney, Stephen, Siggeirsdottir, Kristin, Smith, Albert V, Smith, Jennifer A, Sonestedt, Emily, Strøm, Marin, Tai, E Shyong, Teo, Koon K, Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Uitterlinden, Andre G, Vangipurapu, Jagadish, van Schoor, Natasja, Völker, Uwe, Willemsen, Gonneke, Williams, Kayleen, Wong, Quenna, Xu, Huichun, Young, Kristin L, Yuan, Jian Min, Zillikens, M Carola, Zonderman, Alan B, Ameur, Adam, Bandinelli, Stefania, Bis, Joshua C, Boehnke, Michael, Bouchard, Claude, Chasman, Daniel I, Smith, George Davey, de Geus, Eco J C, Deldicque, Louise, Dörr, Marcus, Evans, Michele K, Ferrucci, Luigi, Fornage, Myriam, Fox, Caroline, Garland, Theodore, Gudnason, Vilmundur, Gyllensten, Ulf, Hansen, Torben, Hayward, Caroline, Horta, Bernardo L, Hyppönen, Elina, Jarvelin, Marjo-Riitta, Johnson, W Craig, Kardia, Sharon L R, Kiemeney, Lambertus A, Laakso, Markku, Langenberg, Claudia, Lehtimäki, Terho, Marchand, Loic Le, Magnusson, Patrik K E, Martin, Nicholas G, Melbye, Mads, Metspalu, Andres, Meyre, David, North, Kari E, Ohlsson, Claes, Oldehinkel, Albertine J, Orho-Melander, Marju, Pare, Guillaume, Park, Taesung, Pedersen, Oluf, Penninx, Brenda W J H, Pers, Tune H, Polasek, Ozren, Prokopenko, Inga, Rotimi, Charles N, Samani, Nilesh J, Sim, Xueling, Snieder, Harold, Sørensen, Thorkild I A, Spector, Tim D, Timpson, Nicholas J, van Dam, Rob M, van der Velde, Nathalie, van Duijn, Cornelia M, Vollenweider, Peter, Völzke, Henry, Voortman, Trudy, Waeber, Gérard, Wareham, Nicholas J, Weir, David R, Wichmann, Heinz-Erich, Wilson, James F, Hevener, Andrea L, Krook, Anna, Zierath, Juleen R, Thomis, Martine A I, Loos, Ruth J F, den Hoed, Marcel, Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J, Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C, Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S, Bartz, Traci M, Bentley, Amy R, Bielak, Lawrence F, Chong, Mike, Chu, Audrey Y, Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D, Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F, Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M, Haller, Toomas, Hartwig, Fernando P, Hillis, David A, Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U, Johansson, Åsa, Jørgensen, Anja Moltke, Kaakinen, Marika A, Karlsson, Robert, Kerr, Kathleen F, Kim, Boram, Koolhaas, Chantal M, Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope A, Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine R, Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca C, Rivera, Natalia V, Robiou-du-Pont, Sebastien, Schraut, Katharina E, Schulz, Christina-Alexandra, Stringham, Heather M, Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter J, Vanmunster, Mathias, van Rooij, Frank J A, van Vliet-Ostaptchouk, Jana V, Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie N, Baumeister, Sebastian E, Beilby, John, Blangero, John, Boomsma, Dorret I, Brage, Soren, Braund, Peter S, Brody, Jennifer A, Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John W, Collins, Francis S, Cupples, L Adrienne, Esko, Tõnu, Enroth, Stefan, Faul, Jessica D, Fernandez-Rhodes, Lindsay, Fohner, Alison E, Franco, Oscar H, Galesloot, Tessel E, Gordon, Scott D, Grarup, Niels, Hartman, Catharina A, Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter K, Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas O, Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter P, Kuusisto, Johanna, Launer, Lenore J, Li, Aihua, Linneberg, Allan, Luan, Jian'an, Vidal, Pedro Marques, Medland, Sarah E, Milaneschi, Yuri, Moscati, Arden, Musk, Bill, Nelson, Christopher P, Nolte, Ilja M, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Power, Christine, Raitakari, Olli T, Reedik, Mägi, Reiner, Alex P, Ridker, Paul M, Rudan, Igor, Ryan, Kathy, Sarzynski, Mark A, Scott, Laura J, Scott, Robert A, Sidney, Stephen, Siggeirsdottir, Kristin, Smith, Albert V, Smith, Jennifer A, Sonestedt, Emily, Strøm, Marin, Tai, E Shyong, Teo, Koon K, Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Uitterlinden, Andre G, Vangipurapu, Jagadish, van Schoor, Natasja, Völker, Uwe, Willemsen, Gonneke, Williams, Kayleen, Wong, Quenna, Xu, Huichun, Young, Kristin L, Yuan, Jian Min, Zillikens, M Carola, Zonderman, Alan B, Ameur, Adam, Bandinelli, Stefania, Bis, Joshua C, Boehnke, Michael, Bouchard, Claude, Chasman, Daniel I, Smith, George Davey, de Geus, Eco J C, Deldicque, Louise, Dörr, Marcus, Evans, Michele K, Ferrucci, Luigi, Fornage, Myriam, Fox, Caroline, Garland, Theodore, Gudnason, Vilmundur, Gyllensten, Ulf, Hansen, Torben, Hayward, Caroline, Horta, Bernardo L, Hyppönen, Elina, Jarvelin, Marjo-Riitta, Johnson, W Craig, Kardia, Sharon L R, Kiemeney, Lambertus A, Laakso, Markku, Langenberg, Claudia, Lehtimäki, Terho, Marchand, Loic Le, Magnusson, Patrik K E, Martin, Nicholas G, Melbye, Mads, Metspalu, Andres, Meyre, David, North, Kari E, Ohlsson, Claes, Oldehinkel, Albertine J, Orho-Melander, Marju, Pare, Guillaume, Park, Taesung, Pedersen, Oluf, Penninx, Brenda W J H, Pers, Tune H, Polasek, Ozren, Prokopenko, Inga, Rotimi, Charles N, Samani, Nilesh J, Sim, Xueling, Snieder, Harold, Sørensen, Thorkild I A, Spector, Tim D, Timpson, Nicholas J, van Dam, Rob M, van der Velde, Nathalie, van Duijn, Cornelia M, Vollenweider, Peter, Völzke, Henry, Voortman, Trudy, Waeber, Gérard, Wareham, Nicholas J, Weir, David R, Wichmann, Heinz-Erich, Wilson, James F, Hevener, Andrea L, Krook, Anna, Zierath, Juleen R, Thomis, Martine A I, Loos, Ruth J F, and den Hoed, Marcel

Abstract

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.

Published
2022
Full Text
View/download PDF

34. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention.

Author

Wang, Zhe, Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas, Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn, Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer, Bartz, Traci, Bentley, Amy, Bielak, Lawrence, Chong, Mike, Chu, Audrey, Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole, Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary, Gieger, Christian, Graff, Mariaelisa, Hall, Leanne, Haller, Toomas, Hartwig, Fernando, Hillis, David, Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne, Johansson, Åsa, Jørgensen, Anja, Kaakinen, Marika, Karlsson, Robert, Kerr, Kathleen, Kim, Boram, Koolhaas, Chantal, Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope, Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine, Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca, Rivera, Natalia, Robiou-du-Pont, Sebastien, Schraut, Katharina, Schulz, Christina-Alexandra, Stringham, Heather, Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter, Vanmunster, Mathias, van Rooij, Frank, van Vliet-Ostaptchouk, Jana, Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie, Baumeister, Sebastian, Beilby, John, Blangero, John, Boomsma, Dorret, Brage, Soren, Braund, Peter, Brody, Jennifer, Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John, Collins, Francis, Cupples, L, Esko, Tõnu, Enroth, Stefan, Faul, Jessica, Fernandez-Rhodes, Lindsay, Fohner, Alison, Franco, Oscar, Galesloot, Tessel, Gordon, Scott, Grarup, Niels, Hartman, Catharina, Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter, Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas, Koh, Woon-Puay, Kolcic, Ivana, Wang, Zhe, Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas, Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn, Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer, Bartz, Traci, Bentley, Amy, Bielak, Lawrence, Chong, Mike, Chu, Audrey, Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole, Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary, Gieger, Christian, Graff, Mariaelisa, Hall, Leanne, Haller, Toomas, Hartwig, Fernando, Hillis, David, Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne, Johansson, Åsa, Jørgensen, Anja, Kaakinen, Marika, Karlsson, Robert, Kerr, Kathleen, Kim, Boram, Koolhaas, Chantal, Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope, Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine, Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca, Rivera, Natalia, Robiou-du-Pont, Sebastien, Schraut, Katharina, Schulz, Christina-Alexandra, Stringham, Heather, Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter, Vanmunster, Mathias, van Rooij, Frank, van Vliet-Ostaptchouk, Jana, Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie, Baumeister, Sebastian, Beilby, John, Blangero, John, Boomsma, Dorret, Brage, Soren, Braund, Peter, Brody, Jennifer, Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John, Collins, Francis, Cupples, L, Esko, Tõnu, Enroth, Stefan, Faul, Jessica, Fernandez-Rhodes, Lindsay, Fohner, Alison, Franco, Oscar, Galesloot, Tessel, Gordon, Scott, Grarup, Niels, Hartman, Catharina, Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter, Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas, Koh, Woon-Puay, and Kolcic, Ivana

Abstract

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.

Published
2022

35. The SOFIA FEEDBACK Legacy Survey Dynamics and Mass Ejection in the Bipolar H ii Region RCW 36

Author

Bonne, L., Schneider, N., Garcia, P., Bij, A., Broos, P., Fissel, L., Guesten, R., Jackson, J., Simon, R., Townsley, L., Zavagno, A., Aladro, R., Buchbender, C., Guevara, C., Higgins, R., Jacob, A. M., Kabanovic, S., Karim, R., Soam, A., Stutzki, J., Tiwari, M., Wyrowski, F., Tielens, A. G. G. M., Bonne, L., Schneider, N., Garcia, P., Bij, A., Broos, P., Fissel, L., Guesten, R., Jackson, J., Simon, R., Townsley, L., Zavagno, A., Aladro, R., Buchbender, C., Guevara, C., Higgins, R., Jacob, A. M., Kabanovic, S., Karim, R., Soam, A., Stutzki, J., Tiwari, M., Wyrowski, F., and Tielens, A. G. G. M.

Abstract

We present [C ii] 158 mu m and [O i] 63 mu m observations of the bipolar H ii region RCW 36 in the Vela C molecular cloud, obtained within the SOFIA legacy project FEEDBACK, which is complemented with APEX (CO)-C-12/13 (3-2) and Chandra X-ray (0.5-7 keV) data. This shows that the molecular ring, forming the waist of the bipolar nebula, expands with a velocity of 1-1.9 km s(-1). We also observe an increased line width in the ring, indicating that turbulence is driven by energy injection from the stellar feedback. The bipolar cavity hosts blueshifted expanding [C ii] shells at 5.2 +/- 0.5 +/- 0.5 km s(-1) (statistical and systematic uncertainty), which indicates that expansion out of the dense gas happens nonuniformly and that the observed bipolar phase might be relatively short (similar to 0.2 Myr). The X-ray observations show diffuse emission that traces a hot plasma, created by stellar winds, in and around RCW 36. At least 50% of the stellar wind energy is missing in RCW 36. This is likely due to leakage that is clearing even larger cavities around the bipolar RCW 36 region. Lastly, the cavities host high-velocity wings in [C ii], which indicates relatively high mass ejection rates (similar to 5 x 10(-4) M (circle dot) yr(-1)). This could be driven by stellar winds and/or radiation but remains difficult to constrain. This local mass ejection, which can remove all mass within 1 pc of RCW 36 in 1-2 Myr, and the large-scale clearing of ambient gas in the Vela C cloud indicate that stellar feedback plays a significant role in suppressing the star formation efficiency.

Published
2022

36. Evaluating HEmopatch (R) in Reducing Seroma-Related Complications following Axillary Lymph Node DIssection: A Pilot Study (HEIDI)

Author

Spiekerman van Weezelenburg, Merel A, de Rooij, Lisa, Aldenhoven, Loeki, Broos, Pieter P H L, van Kuijk, Sander M J, van Haaren, Elisabeth R M, Janssen, Alfred, Vissers, Yvonne L J, Beets, Geerard L, van Bastelaar, James, Spiekerman van Weezelenburg, Merel A, de Rooij, Lisa, Aldenhoven, Loeki, Broos, Pieter P H L, van Kuijk, Sander M J, van Haaren, Elisabeth R M, Janssen, Alfred, Vissers, Yvonne L J, Beets, Geerard L, and van Bastelaar, James

Abstract

PURPOSE: Axillary lymph node dissection (ALND) is performed to treat locoregional metastatic disease in breast cancer and melanoma patients. However, it is notorious for its complications, most commonly seroma formation and its sequelae. Ample research has been done to evaluate seroma formation after ALND; these results, however, have not been conclusive. Hence, this pilot study aimed to evaluate a readily available haemostatic patch, Hemopatch®, to assess its effect on seroma formation following ALND.METHODS: In this pilot study, a prospective cohort of 20 patients receiving Hemopatch® following ALND was compared to a retrospective cohort of patients who underwent ALND between 2014 and 2019. The primary outcome measure was the number of patients developing clinically significant seroma (CSS) after ALND. Additionally, the number of wound complications, subsequent interventions, additional outpatient clinic visits, and drain output was assessed. Differences between groups were deemed clinically relevant if the proportions differed >50% between groups.RESULTS: In total, 20 prospective and 42 retrospective patients were included. In the Hemopatch® group, 30% of the patients developed CSS, compared to 43% in the control group. Three patients in both groups developed a surgical site infection. Thirty-five percent of patients in the Hemopatch® group required additional unscheduled visits versus 62% of patients in the control group.CONCLUSION: The application of Hemopatch® after ALND did not lead to a clinically relevant reduction of CSS and wound complications. However, fewer Hemopatch® patients required additional outpatient clinic visits. Due to the limited amount of participants, the true value of Hemopatch® in ALND remains unclear.

Published
2022

37. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Author

Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J., Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C., Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S., Bartz, Traci M., Bentley, Amy R., Bielak, Lawrence F., Chong, Mike, Chu, Audrey Y., Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D., Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F., Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M., Haller, Toomas, Hartwig, Fernando P., Hillis, David A., Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U., Johansson, Asa, Jorgensen, Anja Moltke, Kaakinen, Marika A., Karlsson, Robert, Kerr, Kathleen F., Kim, Boram, Koolhaas, Chantal M., Kutalik, Zoltan, Pacolet, Alexander, Zhao, Jing-Hua, Balslev-Harder, Marie N., Grarup, Niels, Linneberg, Allan, Hansen, Torben, Melbye, Mads, Pedersen, Oluf, Pers, Tune H., Sorensen, Thorkild I. A., Zierath, Juleen R., Oskari Kilpeläinen, Tuomas, Loos, Ruth J. F., Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J., Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C., Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S., Bartz, Traci M., Bentley, Amy R., Bielak, Lawrence F., Chong, Mike, Chu, Audrey Y., Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D., Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F., Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M., Haller, Toomas, Hartwig, Fernando P., Hillis, David A., Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U., Johansson, Asa, Jorgensen, Anja Moltke, Kaakinen, Marika A., Karlsson, Robert, Kerr, Kathleen F., Kim, Boram, Koolhaas, Chantal M., Kutalik, Zoltan, Pacolet, Alexander, Zhao, Jing-Hua, Balslev-Harder, Marie N., Grarup, Niels, Linneberg, Allan, Hansen, Torben, Melbye, Mads, Pedersen, Oluf, Pers, Tune H., Sorensen, Thorkild I. A., Zierath, Juleen R., Oskari Kilpeläinen, Tuomas, and Loos, Ruth J. F.

Abstract

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.

Published
2022

38. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Author

Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J, Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C, Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S, Bartz, Traci M, Bentley, Amy R, Bielak, Lawrence F, Chong, Mike, Chu, Audrey Y, Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D, Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F, Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M, Haller, Toomas, Hartwig, Fernando P, Hillis, David A, Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U, Johansson, Åsa, Jørgensen, Anja Moltke, Kaakinen, Marika A, Karlsson, Robert, Kerr, Kathleen F, Kim, Boram, Koolhaas, Chantal M, Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope A, Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine R, Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca C, Rivera, Natalia V, Robiou-du-Pont, Sebastien, Schraut, Katharina E, Schulz, Christina-Alexandra, Stringham, Heather M, Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter J, Vanmunster, Mathias, van Rooij, Frank J A, van Vliet-Ostaptchouk, Jana V, Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie N, Baumeister, Sebastian E, Beilby, John, Blangero, John, Boomsma, Dorret I, Brage, Soren, Braund, Peter S, Brody, Jennifer A, Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John W, Collins, Francis S, Cupples, L Adrienne, Esko, Tõnu, Enroth, Stefan, Faul, Jessica D, Fernandez-Rhodes, Lindsay, Fohner, Alison E, Franco, Oscar H, Galesloot, Tessel E, Gordon, Scott D, Grarup, Niels, Hartman, Catharina A, Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter K, Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas O, Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter P, Kuusisto, Johanna, Launer, Lenore J, Li, Aihua, Linneberg, Allan, Luan, Jian'an, Vidal, Pedro Marques, Medland, Sarah E, Milaneschi, Yuri, Moscati, Arden, Musk, Bill, Nelson, Christopher P, Nolte, Ilja M, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Power, Christine, Raitakari, Olli T, Reedik, Mägi, Reiner, Alex P, Ridker, Paul M, Rudan, Igor, Ryan, Kathy, Sarzynski, Mark A, Scott, Laura J, Scott, Robert A, Sidney, Stephen, Siggeirsdottir, Kristin, Smith, Albert V, Smith, Jennifer A, Sonestedt, Emily, Strøm, Marin, Tai, E Shyong, Teo, Koon K, Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Uitterlinden, Andre G, Vangipurapu, Jagadish, van Schoor, Natasja, Völker, Uwe, Willemsen, Gonneke, Williams, Kayleen, Wong, Quenna, Xu, Huichun, Young, Kristin L, Yuan, Jian Min, Zillikens, M Carola, Zonderman, Alan B, Ameur, Adam, Bandinelli, Stefania, Bis, Joshua C, Boehnke, Michael, Bouchard, Claude, Chasman, Daniel I, Smith, George Davey, de Geus, Eco J C, Deldicque, Louise, Dörr, Marcus, Evans, Michele K, Ferrucci, Luigi, Fornage, Myriam, Fox, Caroline, Garland, Theodore, Gudnason, Vilmundur, Gyllensten, Ulf, Hansen, Torben, Hayward, Caroline, Horta, Bernardo L, Hyppönen, Elina, Jarvelin, Marjo-Riitta, Johnson, W Craig, Kardia, Sharon L R, Kiemeney, Lambertus A, Laakso, Markku, Langenberg, Claudia, Lehtimäki, Terho, Marchand, Loic Le, Magnusson, Patrik K E, Martin, Nicholas G, Melbye, Mads, Metspalu, Andres, Meyre, David, North, Kari E, Ohlsson, Claes, Oldehinkel, Albertine J, Orho-Melander, Marju, Pare, Guillaume, Park, Taesung, Pedersen, Oluf, Penninx, Brenda W J H, Pers, Tune H, Polasek, Ozren, Prokopenko, Inga, Rotimi, Charles N, Samani, Nilesh J, Sim, Xueling, Snieder, Harold, Sørensen, Thorkild I A, Spector, Tim D, Timpson, Nicholas J, van Dam, Rob M, van der Velde, Nathalie, van Duijn, Cornelia M, Vollenweider, Peter, Völzke, Henry, Voortman, Trudy, Waeber, Gérard, Wareham, Nicholas J, Weir, David R, Wichmann, Heinz-Erich, Wilson, James F, Hevener, Andrea L, Krook, Anna, Zierath, Juleen R, Thomis, Martine A I, Loos, Ruth J F, den Hoed, Marcel, Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J, Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C, Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S, Bartz, Traci M, Bentley, Amy R, Bielak, Lawrence F, Chong, Mike, Chu, Audrey Y, Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D, Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F, Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M, Haller, Toomas, Hartwig, Fernando P, Hillis, David A, Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U, Johansson, Åsa, Jørgensen, Anja Moltke, Kaakinen, Marika A, Karlsson, Robert, Kerr, Kathleen F, Kim, Boram, Koolhaas, Chantal M, Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope A, Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine R, Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca C, Rivera, Natalia V, Robiou-du-Pont, Sebastien, Schraut, Katharina E, Schulz, Christina-Alexandra, Stringham, Heather M, Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter J, Vanmunster, Mathias, van Rooij, Frank J A, van Vliet-Ostaptchouk, Jana V, Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie N, Baumeister, Sebastian E, Beilby, John, Blangero, John, Boomsma, Dorret I, Brage, Soren, Braund, Peter S, Brody, Jennifer A, Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John W, Collins, Francis S, Cupples, L Adrienne, Esko, Tõnu, Enroth, Stefan, Faul, Jessica D, Fernandez-Rhodes, Lindsay, Fohner, Alison E, Franco, Oscar H, Galesloot, Tessel E, Gordon, Scott D, Grarup, Niels, Hartman, Catharina A, Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter K, Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas O, Koh, Woon-Puay, Kolcic, Ivana, Kraft, Peter P, Kuusisto, Johanna, Launer, Lenore J, Li, Aihua, Linneberg, Allan, Luan, Jian'an, Vidal, Pedro Marques, Medland, Sarah E, Milaneschi, Yuri, Moscati, Arden, Musk, Bill, Nelson, Christopher P, Nolte, Ilja M, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Power, Christine, Raitakari, Olli T, Reedik, Mägi, Reiner, Alex P, Ridker, Paul M, Rudan, Igor, Ryan, Kathy, Sarzynski, Mark A, Scott, Laura J, Scott, Robert A, Sidney, Stephen, Siggeirsdottir, Kristin, Smith, Albert V, Smith, Jennifer A, Sonestedt, Emily, Strøm, Marin, Tai, E Shyong, Teo, Koon K, Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Uitterlinden, Andre G, Vangipurapu, Jagadish, van Schoor, Natasja, Völker, Uwe, Willemsen, Gonneke, Williams, Kayleen, Wong, Quenna, Xu, Huichun, Young, Kristin L, Yuan, Jian Min, Zillikens, M Carola, Zonderman, Alan B, Ameur, Adam, Bandinelli, Stefania, Bis, Joshua C, Boehnke, Michael, Bouchard, Claude, Chasman, Daniel I, Smith, George Davey, de Geus, Eco J C, Deldicque, Louise, Dörr, Marcus, Evans, Michele K, Ferrucci, Luigi, Fornage, Myriam, Fox, Caroline, Garland, Theodore, Gudnason, Vilmundur, Gyllensten, Ulf, Hansen, Torben, Hayward, Caroline, Horta, Bernardo L, Hyppönen, Elina, Jarvelin, Marjo-Riitta, Johnson, W Craig, Kardia, Sharon L R, Kiemeney, Lambertus A, Laakso, Markku, Langenberg, Claudia, Lehtimäki, Terho, Marchand, Loic Le, Magnusson, Patrik K E, Martin, Nicholas G, Melbye, Mads, Metspalu, Andres, Meyre, David, North, Kari E, Ohlsson, Claes, Oldehinkel, Albertine J, Orho-Melander, Marju, Pare, Guillaume, Park, Taesung, Pedersen, Oluf, Penninx, Brenda W J H, Pers, Tune H, Polasek, Ozren, Prokopenko, Inga, Rotimi, Charles N, Samani, Nilesh J, Sim, Xueling, Snieder, Harold, Sørensen, Thorkild I A, Spector, Tim D, Timpson, Nicholas J, van Dam, Rob M, van der Velde, Nathalie, van Duijn, Cornelia M, Vollenweider, Peter, Völzke, Henry, Voortman, Trudy, Waeber, Gérard, Wareham, Nicholas J, Weir, David R, Wichmann, Heinz-Erich, Wilson, James F, Hevener, Andrea L, Krook, Anna, Zierath, Juleen R, Thomis, Martine A I, Loos, Ruth J F, and den Hoed, Marcel

Abstract

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.

Published
2022
Full Text
View/download PDF

39. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Author

Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J., Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C., Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S., Bartz, Traci M., Bentley, Amy R., Bielak, Lawrence F., Chong, Mike, Chu, Audrey Y., Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D., Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F., Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M., Haller, Toomas, Hartwig, Fernando P., Hillis, David A., Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U., Johansson, Asa, Jorgensen, Anja Moltke, Kaakinen, Marika A., Karlsson, Robert, Kerr, Kathleen F., Kim, Boram, Koolhaas, Chantal M., Kutalik, Zoltan, Pacolet, Alexander, Zhao, Jing-Hua, Balslev-Harder, Marie N., Grarup, Niels, Linneberg, Allan, Hansen, Torben, Melbye, Mads, Pedersen, Oluf, Pers, Tune H., Sorensen, Thorkild I. A., Zierath, Juleen R., Oskari Kilpeläinen, Tuomas, Loos, Ruth J. F., Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J., Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C., Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S., Bartz, Traci M., Bentley, Amy R., Bielak, Lawrence F., Chong, Mike, Chu, Audrey Y., Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D., Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F., Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M., Haller, Toomas, Hartwig, Fernando P., Hillis, David A., Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U., Johansson, Asa, Jorgensen, Anja Moltke, Kaakinen, Marika A., Karlsson, Robert, Kerr, Kathleen F., Kim, Boram, Koolhaas, Chantal M., Kutalik, Zoltan, Pacolet, Alexander, Zhao, Jing-Hua, Balslev-Harder, Marie N., Grarup, Niels, Linneberg, Allan, Hansen, Torben, Melbye, Mads, Pedersen, Oluf, Pers, Tune H., Sorensen, Thorkild I. A., Zierath, Juleen R., Oskari Kilpeläinen, Tuomas, and Loos, Ruth J. F.

Abstract

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.

Published
2022

40. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Author

Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J., Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C., Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S., Bartz, Traci M., Bentley, Amy R., Bielak, Lawrence F., Chong, Mike, Chu, Audrey Y., Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D., Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F., Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M., Haller, Toomas, Hartwig, Fernando P., Hillis, David A., Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U., Johansson, Åsa, Jørgensen, Anja Moltke, Kaakinen, Marika A., Karlsson, Robert, Kerr, Kathleen F., Kim, Boram, Koolhaas, Chantal M., Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope A., Richmond, Rebecca C., Teumer, Alexander, Zhao, Jing Hua, Zhao, Wei, Uitterlinden, Andre G., Zillikens, M. Carola, Hansen, Torben, van der Velde, Nathalie, van Duijn, Cornelia M., Voortman, Trudy, van Rooij, FJA, Franco Duran, Oscar, Loos, Ruth J.F., den Hoed, M, Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas J., Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn C., Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer S., Bartz, Traci M., Bentley, Amy R., Bielak, Lawrence F., Chong, Mike, Chu, Audrey Y., Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole D., Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary F., Gieger, Christian, Graff, Mariaelisa, Hall, Leanne M., Haller, Toomas, Hartwig, Fernando P., Hillis, David A., Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne U., Johansson, Åsa, Jørgensen, Anja Moltke, Kaakinen, Marika A., Karlsson, Robert, Kerr, Kathleen F., Kim, Boram, Koolhaas, Chantal M., Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope A., Richmond, Rebecca C., Teumer, Alexander, Zhao, Jing Hua, Zhao, Wei, Uitterlinden, Andre G., Zillikens, M. Carola, Hansen, Torben, van der Velde, Nathalie, van Duijn, Cornelia M., Voortman, Trudy, van Rooij, FJA, Franco Duran, Oscar, Loos, Ruth J.F., and den Hoed, M

Abstract

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.

Published
2022

41. The SOFIA FEEDBACK Legacy Survey: Dynamics and mass ejection in the bipolar HII region RCW 36

Author

Bonne, L., Schneider, N., García, P., Bij, A., Broos, P., Fissel, L., Guesten, R., Jackson, J., Simon, R., Townsley, L., Zavagno, A., Aladro, R., Buchbender, C., Guevara, C., Higgins, R., Jacob, A. M., Kabanovic, S., Karim, R., Soam, A., Stutzki, J., Tiwari, M., Wyrowski, F., Tielens, A. G. G. M., Bonne, L., Schneider, N., García, P., Bij, A., Broos, P., Fissel, L., Guesten, R., Jackson, J., Simon, R., Townsley, L., Zavagno, A., Aladro, R., Buchbender, C., Guevara, C., Higgins, R., Jacob, A. M., Kabanovic, S., Karim, R., Soam, A., Stutzki, J., Tiwari, M., Wyrowski, F., and Tielens, A. G. G. M.

Abstract

We present [CII] 158 $\mu$m and [OI] 63 $\mu$m observations of the bipolar HII region RCW 36 in the Vela C molecular cloud, obtained within the SOFIA legacy project FEEDBACK, which is complemented with APEX $^{12/13}$CO(3-2) and Chandra X-ray (0.5-7 keV) data. This shows that the molecular ring, forming the waist of the bipolar nebula, expands with a velocity of 1 - 1.9 km s$^{-1}$. We also observe an increased linewidth in the ring indicating that turbulence is driven by energy injection from the stellar feedback. The bipolar cavity hosts blue-shifted expanding [CII] shells at 5.2$\pm$0.5$\pm$0.5 km s$^{-1}$ (statistical and systematic uncertainty) which indicates that expansion out of the dense gas happens non-uniformly and that the observed bipolar phase might be relatively short ($\sim$0.2 Myr). The X-ray observations show diffuse emission that traces a hot plasma, created by stellar winds, in and around RCW 36. At least 50 \% of the stellar wind energy is missing in RCW 36. This is likely due to leakage which is clearing even larger cavities around the bipolar RCW 36 region. Lastly, the cavities host high-velocity wings in [CII] which indicates relatively high mass ejection rates ($\sim$5$\times$10$^{-4}$ M$_{\odot}$ yr$^{-1}$). This could be driven by stellar winds and/or radiation pressure, but remains difficult to constrain. This local mass ejection, which can remove all mass within 1 pc of RCW 36 in 1-2 Myr, and the large-scale clearing of ambient gas in the Vela C cloud indicates that stellar feedback plays a significant role in suppressing the star formation efficiency (SFE)., Comment: 38 pages, 27 figures, 8 tables, accepted in ApJ

Published
2022
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42. X-ray properties of early-type stars in the Tarantula Nebula from T-ReX

Author

Crowther, Paul A, Broos, Patrick S, Townsley, Leisa K, Pollock, Andy M T, Tehrani, Katie A, Gagne, Marc, Crowther, Paul A, Broos, Patrick S, Townsley, Leisa K, Pollock, Andy M T, Tehrani, Katie A, and Gagne, Marc

Abstract

We reassess the historical $L_{X}/L_{Bol}$ relation for early-type stars from a comparison between T-ReX, the Chandra ACIS X-ray survey of the Tarantula Nebula in the LMC, and contemporary spectroscopic analysis of massive stars obtained primarily from VLT/FLAMES, VLT/MUSE and HST/STIS surveys. For 107 sources in common (some host to multiple stars), the majority of which are bolometrically luminous (40% exceed $10^6 L_{\odot}$), we find an average $\log L_{X} /L_{Bol} = -6.90 \pm 0.65$. Excluding extreme systems Mk 34 (WN5h+WN5h), R140a (WC4+WN6+) and VFTS 399 (O9 IIIn+?), plus four WR sources with anomalously hard X-ray components (R130, R134, R135, Mk 53) and 10 multiple sources within the spatially crowded core of R136a, $\log L_{X}/L_{Bol} = -7.00 \pm 0.49$, in good agreement with Galactic OB stars. No difference is found between single and binary systems, nor between O, Of/WN and WR stars, although there does appear to be a trend towards harder X-ray emission from O dwarfs, through O (super)giants, Of/WN stars and WR stars. The majority of known OB stars in the Tarantula are not detected in the T-ReX point source catalogue, so we have derived upper limits for all undetected OB stars for which log $L_{Bol}/L_{\odot} \geq 5.0$. A survival analysis using detected and upper-limit log $L_{X}/L_{Bol}$ values indicates no significant difference between luminous O stars in the LMC and the Carina Nebula. This analysis suggests that metallicity does not strongly influence $L_{X}/L_{Bol}$. Plasma temperatures for single, luminous O stars in the Tarantula ($\overline{kT_{m}}=1.0$ keV) are higher than counterparts in Carina ($\overline{kT_{m}}=0.5$ keV)., Comment: 14 pages, 8 figures, accepted for MNRAS plus Appendices providing X-ray plasma fits (A1), properties of early-type stars (A2), LMC baseline abundances (B1), plus X-ray upper limits for other luminous early-type stars (S1)

Published
2022
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43. The Effect of Molecular Cloud Properties on the Kinematics of Stars Formed in the Trifid Region

Author

Kuhn, Michael A., Hillenbrand, Lynne A., Feigelson, Eric D., Fowler, Ian, Getman, Konstantin V., Broos, Patrick S., Povich, Matthew S., Gromadzki, Mariusz, Kuhn, Michael A., Hillenbrand, Lynne A., Feigelson, Eric D., Fowler, Ian, Getman, Konstantin V., Broos, Patrick S., Povich, Matthew S., and Gromadzki, Mariusz

Abstract

The dynamical states of molecular clouds may affect the properties of the stars they form. In the vicinity of the Trifid Nebula ($d=1180\pm25$ pc), the main star cluster (Trifid Main) lies within an expanding section of the molecular cloud; however, ~0.3 deg to the north (Trifid North), the cloud's velocity structure is more tranquil. We acquired a Chandra X-ray observation to identify pre-main-sequence stars in Trifid North, complementing a previous observation of Trifid Main. In Trifid North, we identified 51 candidate pre-main-sequence stars, of which 13 are high-confidence Trifid members based on Gaia EDR3 parallaxes and proper motions. We also re-analyzed membership of Trifid Main and separated out multiple background stellar associations. Trifid North represents a stellar population ~10% as rich as Trifid Main that formed in a separate part of the cloud. The 1D stellar velocity dispersion in Trifid North ($0.6\pm0.2$ km/s) is three times lower than in Trifid Main ($1.9\pm0.2$ km/s). Furthermore, in Trifid Main, proper motions indicate that the portion of the star cluster superimposed on the optical nebula is expanding. Expansion of the HII region around the O-star HD 164492A, and the resulting gas expulsion, can explain both the motions of the stars and gas in Trifid Main. Contrary to previous studies, we find no evidence that a cloud-cloud collision triggered star formation in the region., Comment: Accepted for publication in ApJ. 26 pages, 18 figures, and 4 tables. Minor style changes have been applied to match the published version

Published
2022
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44. Evolution of X-ray Activity in <25 Myr Old Pre-Main Sequence Stars

Author

Getman, Konstantin V., Feigelson, Eric D., Garmire, Gordon P., Broos, Patrick S., Kuhn, Michael A., Preibisch, Thomas, Airapetian, Vladimir S., Getman, Konstantin V., Feigelson, Eric D., Garmire, Gordon P., Broos, Patrick S., Kuhn, Michael A., Preibisch, Thomas, and Airapetian, Vladimir S.

Abstract

Measuring the evolution of X-ray emission from pre-main sequence (PMS) stars gives insight into two issues: the response of magnetic dynamo processes to changes in interior structure and the effects of high-energy radiation on protoplanetary disks and primordial planetary atmospheres. We present a sample of 6,003 stars with ages 7-25Myr in ten nearby open clusters from Chandra X-ray and Gaia-EDR3 surveys. Combined with previous results in large samples of younger (<5Myr) stars in MYStIX and SFiNCs star forming regions, mass-stratified activity-age relations are derived for early phases of stellar evolution. X-ray luminosity (Lx) is constant during the first few Myr, possibly due to the presence of extended X-ray coronas insensitive to temporal changes in stellar size. Lx then decays during the 7-25Myr period, more rapidly as stellar mass increases. This decay is interpreted as decreasing efficiency of the alpha^2 dynamo as radiative cores grow and a solar-type alpha-Omega dynamo emerges. For more massive 3.5-7Mo fully radiative stars, the X-ray emission plummets indicating lack of an effective magnetic dynamo. The findings provide improved measurements of high energy radiation effects on circumstellar material, first the protoplanetary disk and then the atmospheres of young planets. The observed X-ray luminosities can be so high that an inner Earth-mass rocky, unmagnetized planet around a solar-mass PMS star might lose its primary and secondary atmospheres within a few-several million years. PMS X-ray emission may thus have a significant impact on evolution of early planetary atmospheres and the conditions promoting the rise of habitability., Comment: 39 pages, 12 figures, 8 tables. Accepted for publication in The Astrophysical Journal, June 10, 2022

Published
2022
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45. Mijn mooiste monster

Author

E. Stegeman - Broos and E. Stegeman - Broos

Abstract

A nice small pool with many desmids is described

Published
2022

50. The impact of viral mutations on recognition by SARS-CoV-2 specific T cells

Author

de Silva, Thushan I, de Silva, Thushan I, Liu, Guihai, Lindsey, Benjamin B, Dong, Danning, Moore, Shona C, Hsu, Nienyun Sharon, Shah, Dhruv, Wellington, Dannielle, Mentzer, Alexander J, Angyal, Adrienn, Brown, Rebecca, Parker, Matthew D, Ying, Zixi, Yao, Xuan, Turtle, Lance, Dunachie, Susanna, Aanensen, David M, Abudahab, Khalil, Adams, Helen, Adams, Alexander, Afifi, Safiah, Aggarwal, Dinesh, Ahmad, Shazaad SY, Aigrain, Louise, Alcolea-Medina, Adela, Alikhan, Nabil-Fareed, Allara, Elias, Amato, Roberto, Annett, Tara, Aplin, Stephen, Ariani, Cristina V, Asad, Hibo, Ash, Amy, Ashfield, Paula, Ashford, Fiona, Atkinson, Laura, Attwood, Stephen W, Auckland, Cressida, Aydin, Alp, Baker, David J, Baker, Paul, Balcazar, Carlos E, Ball, Jonathan, Barrett, Jeffrey C, Barrow, Magdalena, Barton, Edward, Bashton, Matthew, Bassett, Andrew R, Batra, Rahul, Baxter, Chris, Bayzid, Nadua, Beaver, Charlotte, Beckett, Angela H, Beckwith, Shaun M, Bedford, Luke, Beer, Robert, Beggs, Andrew, Bellis, Katherine L, Berry, Louise, Bertolusso, Beatrice, Best, Angus, Betteridge, Emma, Bibby, David, Bicknell, Kelly, Binns, Debbie, Birchley, Alec, Bird, Paul W, Bishop, Chloe, Blacow, Rachel, Blakey, Victoria, Blane, Beth, Bolt, Frances, Bonfield, James, Bonner, Stephen, Bonsall, David, Boswell, Tim, Bosworth, Andrew, Bourgeois, Yann, Boyd, Olivia, Bradley, Declan T, Breen, Cassie, Bresner, Catherine, Breuer, Judith, Bridgett, Stephen, Bronner, Iraad F, Brooks, Ellena, Broos, Alice, Brown, Julianne R, Bucca, Giselda, Buchan, Sarah L, Buck, David, Bull, Matthew, Burns, Phillipa J, Burton-Fanning, Shirelle, Byaruhanga, Timothy, Byott, Matthew, Campbell, Sharon, Carabelli, Alessandro M, Cargill, James S, Carlile, Matthew, de Silva, Thushan I, de Silva, Thushan I, Liu, Guihai, Lindsey, Benjamin B, Dong, Danning, Moore, Shona C, Hsu, Nienyun Sharon, Shah, Dhruv, Wellington, Dannielle, Mentzer, Alexander J, Angyal, Adrienn, Brown, Rebecca, Parker, Matthew D, Ying, Zixi, Yao, Xuan, Turtle, Lance, Dunachie, Susanna, Aanensen, David M, Abudahab, Khalil, Adams, Helen, Adams, Alexander, Afifi, Safiah, Aggarwal, Dinesh, Ahmad, Shazaad SY, Aigrain, Louise, Alcolea-Medina, Adela, Alikhan, Nabil-Fareed, Allara, Elias, Amato, Roberto, Annett, Tara, Aplin, Stephen, Ariani, Cristina V, Asad, Hibo, Ash, Amy, Ashfield, Paula, Ashford, Fiona, Atkinson, Laura, Attwood, Stephen W, Auckland, Cressida, Aydin, Alp, Baker, David J, Baker, Paul, Balcazar, Carlos E, Ball, Jonathan, Barrett, Jeffrey C, Barrow, Magdalena, Barton, Edward, Bashton, Matthew, Bassett, Andrew R, Batra, Rahul, Baxter, Chris, Bayzid, Nadua, Beaver, Charlotte, Beckett, Angela H, Beckwith, Shaun M, Bedford, Luke, Beer, Robert, Beggs, Andrew, Bellis, Katherine L, Berry, Louise, Bertolusso, Beatrice, Best, Angus, Betteridge, Emma, Bibby, David, Bicknell, Kelly, Binns, Debbie, Birchley, Alec, Bird, Paul W, Bishop, Chloe, Blacow, Rachel, Blakey, Victoria, Blane, Beth, Bolt, Frances, Bonfield, James, Bonner, Stephen, Bonsall, David, Boswell, Tim, Bosworth, Andrew, Bourgeois, Yann, Boyd, Olivia, Bradley, Declan T, Breen, Cassie, Bresner, Catherine, Breuer, Judith, Bridgett, Stephen, Bronner, Iraad F, Brooks, Ellena, Broos, Alice, Brown, Julianne R, Bucca, Giselda, Buchan, Sarah L, Buck, David, Bull, Matthew, Burns, Phillipa J, Burton-Fanning, Shirelle, Byaruhanga, Timothy, Byott, Matthew, Campbell, Sharon, Carabelli, Alessandro M, Cargill, James S, and Carlile, Matthew

Published
2021

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