305 results on '"Descombes P."'
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2. Sleep Treatment Education Program for Cancer Survivors: Protocol for an Efficacy Trial
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Briana L Bice, Alexis L Michaud, Katherine G McCormick, Eva M Miklos, Indiana D Descombes, Cheryl Medeiros-Nancarrow, Eric S Zhou, and Christopher J Recklitis
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Medicine ,Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
BackgroundCancer survivors are at increased risk for chronic insomnia, even years after treatment completion. As insomnia is associated with a variety of long-term health consequences, access to insomnia treatment is critically important for the survivor population. Cognitive behavioral therapy for insomnia (CBTI) is the recommended first-line treatment for insomnia but remains largely unavailable to survivors. Treatment barriers include geographic limitations, a shortage of trained providers, and demanding treatment regimens. Designed with these limitations in mind, the Sleep Treatment Education Program (STEP-1) delivers components of CBTI in a low-intensity educational intervention delivered online. ObjectiveThis is a phase II pilot randomized controlled trial. The primary aims are to test the efficacy of STEP-1 to improve (1) insomnia symptoms and (2) mood in cancer survivors compared to a control condition. The secondary aims will (1) explore participant factors associated with clinically significant response, (2) evaluate acceptability of the control intervention, (3) explore feasibility of delivering individualized coaching sessions for participants who do not have a significant response to STEP-1, and (4) describe participants’ satisfaction with STEP-1 and suggestions for improvement. MethodsThis 2-arm randomized controlled trial enrolled 70 off-treatment cancer survivors aged 40-89 years with clinically significant insomnia. Participants are randomized to receive either the STEP-1 intervention or control condition (relaxation education); interventions are delivered in one-on-one, synchronous, virtual videoconference sessions by trained interventionists. The STEP-1 intervention presents educational information on the development of insomnia after cancer and offers suggestions for improving insomnia symptoms based on the CBTI elements of sleep hygiene, stimulus control, and cognitive restructuring. With the interventionist, participants review the suggestions and develop a personalized sleep action plan for implementation. The relaxation education session provides information on the potential benefits of relaxation and how to independently access online relaxation exercises. The Insomnia Severity Index is used to measure insomnia symptoms, and the Profile of Mood States Short Form is used to measure mood at baseline and 4 and 8 weeks after intervention. The primary end point is change in the Insomnia Severity Index score at 8 weeks, and the secondary end point is change in mood symptoms (Profile of Mood States Short Form) at 8 weeks. ResultsThis trial was funded in July 2022. Enrollment and data collection began in February 2023 and concluded in October 2024, with 70 participants enrolled. The analysis will begin in fall 2024, and the results are expected in winter 2025. ConclusionsTrial results will determine if STEP-1 effects go beyond those that could be attributed to placebo and other nonspecific treatment factors. Should results support the efficacy of STEP-1 to improve mood and insomnia symptoms, we anticipate developing efficacy and implementation trials of STEP-1 in larger and more diverse samples. Trial RegistrationClinicalTrials.gov NCT05519982; https://clinicaltrials.gov/study/NCT05519982 International Registered Report Identifier (IRRID)DERR1-10.2196/60762
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- 2024
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3. The genome and population genomics of allopolyploid Coffea arabica reveal the diversification history of modern coffee cultivars
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Salojärvi, Jarkko, Rambani, Aditi, Yu, Zhe, Guyot, Romain, Strickler, Susan, Lepelley, Maud, Wang, Cui, Rajaraman, Sitaram, Rastas, Pasi, Zheng, Chunfang, Muñoz, Daniella Santos, Meidanis, João, Paschoal, Alexandre Rossi, Bawin, Yves, Krabbenhoft, Trevor J., Wang, Zhen Qin, Fleck, Steven J., Aussel, Rudy, Bellanger, Laurence, Charpagne, Aline, Fournier, Coralie, Kassam, Mohamed, Lefebvre, Gregory, Métairon, Sylviane, Moine, Déborah, Rigoreau, Michel, Stolte, Jens, Hamon, Perla, Couturon, Emmanuel, Tranchant-Dubreuil, Christine, Mukherjee, Minakshi, Lan, Tianying, Engelhardt, Jan, Stadler, Peter, Correia De Lemos, Samara Mireza, Suzuki, Suzana Ivamoto, Sumirat, Ucu, Wai, Ching Man, Dauchot, Nicolas, Orozco-Arias, Simon, Garavito, Andrea, Kiwuka, Catherine, Musoli, Pascal, Nalukenge, Anne, Guichoux, Erwan, Reinout, Havinga, Smit, Martin, Carretero-Paulet, Lorenzo, Filho, Oliveiro Guerreiro, Braghini, Masako Toma, Padilha, Lilian, Sera, Gustavo Hiroshi, Ruttink, Tom, Henry, Robert, Marraccini, Pierre, Van de Peer, Yves, Andrade, Alan, Domingues, Douglas, Giuliano, Giovanni, Mueller, Lukas, Pereira, Luiz Filipe, Plaisance, Stephane, Poncet, Valerie, Rombauts, Stephane, Sankoff, David, Albert, Victor A., Crouzillat, Dominique, de Kochko, Alexandre, and Descombes, Patrick
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- 2024
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4. Multispecies deep learning using citizen science data produces more informative plant community models
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Philipp Brun, Dirk N. Karger, Damaris Zurell, Patrice Descombes, Lucienne C. de Witte, Riccardo de Lutio, Jan Dirk Wegner, and Niklaus E. Zimmermann
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Science - Abstract
Abstract In the age of big data, scientific progress is fundamentally limited by our capacity to extract critical information. Here, we map fine-grained spatiotemporal distributions for thousands of species, using deep neural networks (DNNs) and ubiquitous citizen science data. Based on 6.7 M observations, we jointly model the distributions of 2477 plant species and species aggregates across Switzerland with an ensemble of DNNs built with different cost functions. We find that, compared to commonly-used approaches, multispecies DNNs predict species distributions and especially community composition more accurately. Moreover, their design allows investigation of understudied aspects of ecology. Including seasonal variations of observation probability explicitly allows approximating flowering phenology; reweighting predictions to mirror cover-abundance allows mapping potentially canopy-dominant tree species nationwide; and projecting DNNs into the future allows assessing how distributions, phenology, and dominance may change. Given their skill and their versatility, multispecies DNNs can refine our understanding of the distribution of plants and well-sampled taxa in general.
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- 2024
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5. BPS Dendroscopy on Local P2
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Bousseau, Pierrick, Descombes, Pierre, Le Floch, Bruno, and Pioline, Boris
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- 2024
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6. Adapting to change: Exploring the consequences of climate‐induced host plant shifts in two specialist Lepidoptera species
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Baptiste Bovay, Patrice Descombes, Yannick Chittaro, Gaëtan Glauser, Hanna Nomoto, and Sergio Rasmann
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elevation gradients ,global warming ,host plant shifts ,life‐history traits ,plant defences ,plant–herbivore interactions ,Ecology ,QH540-549.5 - Abstract
Abstract Asynchronous migration of insect herbivores and their host plants towards higher elevations following climate warming is expected to generate novel plant–insect interactions. While the disassociation of specialised interactions can challenge species' persistence, consequences for specialised low‐elevation insect herbivores encountering novel high‐elevation plants under climate change remain largely unknown. To explore the ability of two low‐elevation Lepidoptera species, Melitaea celadussa and Zygaena filipendulae, to undergo shifts from low‐ to high‐elevation host plants, we combined a translocation experiment performed at two elevations in the Swiss Alps with experiments conducted under controlled conditions. Specifically, we exposed M. celadussa and Z. filipendulae to current low‐ and congeneric high‐elevation host plants, to test how shifts in host plant use impact oviposition probability, number of eggs clutches laid, caterpillar feeding preference and growth, pupation rate and wing size. While our study shows that both M. celadussa and Z. filipendulae can oviposit and feed on novel high‐elevation host plants, we reveal strong preferences towards ovipositing and feeding on current low‐elevation host plants. In addition, shifts from current low‐ to novel high‐elevation host plants reduced pupation rates as well as wing size for M. celadussa, while caterpillar growth was unaffected by host plant identity for both species. Our study suggests that populations of M. celadussa and Z. filipendulae have the ability to undergo host plant shifts under climate change. However, these shifts may impact the ability of populations to respond to rapid climate change by altering developmental processes and morphology. Our study highlights the importance of considering altered biotic interactions when predicting consequences for natural populations facing novel abiotic and biotic environments.
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- 2024
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7. Improving CNNs classification with pathologist-based expertise: the renal cell carcinoma case study
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Francesco Ponzio, Xavier Descombes, and Damien Ambrosetti
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Medicine ,Science - Abstract
Abstract The prognosis of renal cell carcinoma (RCC) malignant neoplasms deeply relies on an accurate determination of the histological subtype, which currently involves the light microscopy visual analysis of histological slides, considering notably tumor architecture and cytology. RCC subtyping is therefore a time-consuming and tedious process, sometimes requiring expert review, with great impact on diagnosis, prognosis and treatment of RCC neoplasms. In this study, we investigate the automatic RCC subtyping classification of 91 patients, diagnosed with clear cell RCC, papillary RCC, chromophobe RCC, or renal oncocytoma, through deep learning based methodologies. We show how the classification performance of several state-of-the-art Convolutional Neural Networks (CNNs) are perfectible among the different RCC subtypes. Thus, we introduce a new classification model leveraging a combination of supervised deep learning models (specifically CNNs) and pathologist’s expertise, giving birth to a hybrid approach that we termed ExpertDeepTree (ExpertDT). Our findings prove ExpertDT’s superior capability in the RCC subtyping task, with respect to traditional CNNs, and suggest that introducing some expert-based knowledge into deep learning models may be a valuable solution for complex classification cases.
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- 2023
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8. Improving CNNs classification with pathologist-based expertise: the renal cell carcinoma case study
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Ponzio, Francesco, Descombes, Xavier, and Ambrosetti, Damien
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- 2023
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9. Global transcriptome profiling reveals differential regulatory, metabolic and hormonal networks during somatic embryogenesis in Coffea arabica
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Awada, Rayan, Lepelley, Maud, Breton, David, Charpagne, Aline, Campa, Claudine, Berry, Victoria, Georget, Frédéric, Breitler, Jean-Christophe, Léran, Sophie, Djerrab, Doâa, Martinez-Seidel, Federico, Descombes, Patrick, Crouzillat, Dominique, Bertrand, Benoît, and Etienne, Hervé
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- 2023
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10. Technical note: Improving the European air quality forecast of the Copernicus Atmosphere Monitoring Service using machine learning techniques
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J.-M. Bertrand, F. Meleux, A. Ung, G. Descombes, and A. Colette
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Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Model output statistics (MOS) approaches relying on machine learning algorithms were applied to downscale regional air quality forecasts produced by CAMS (Copernicus Atmosphere Monitoring Service) at hundreds of monitoring sites across Europe. Besides the CAMS forecast, the predictors in the MOS typically include meteorological variables but also ancillary data. We explored first a “local” approach where specific models are trained at each site. An alternative “global” approach where a single model is trained with data from the whole geographical domain was also investigated. In both cases, local predictors are used for a given station in predictive mode. Because of its global nature, the latter approach can capture a variety of meteorological situations within a very short training period and is thereby more suited to cope with operational constraints in relation to the training of the MOS (frequent upgrades of the modelling system, addition of new monitoring sites). Both approaches have been implemented using a variety of machine learning algorithms: random forest, gradient boosting, and standard and regularized multi-linear models. The quality of the MOS predictions is evaluated in this work for four key pollutants, namely particulate matter (PM10 and PM2.5), ozone (O3) and nitrogen dioxide (NO2), according to scores based on the predictive errors and on the detection of pollution peaks (exceedances of the regulatory thresholds). Both the local and the global approaches significantly improve the performances of the raw ensemble forecast. The most important result of this study is that the global approach competes with and can even outperform the local approach in some cases. This global approach gives the best RMSE scores when relying on a random forest model for the prediction of daily mean, daily max and hourly concentrations. By contrast, it is the gradient boosting model which is better suited for the detection of exceedances of the European Union regulated threshold values for O3 and PM10.
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- 2023
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11. Severe acute kidney injury in a patient with renal artery stenosis of a single-functioning kidney: A case report of rapid normalisation of the renal function after percutaneous transluminal angioplasty with stent placement
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Claire Seydoux, Ould Maouloud Hemett, Daniel Périard, and Eric Descombes
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Medicine (General) ,R5-920 - Abstract
Revascularisation of renal arterial stenosis in acute settings, such as uncontrolled arterial hypertension, flash pulmonary oedema and/or acute renal failure, has shown controversial results in observational and prospective studies. Current guidelines do not recommend revascularisation in the occurrence of renal failure as revascularisation and best medical treatment have shown similar long-term outcomes on renal function. We describe a case of acute degradation of the renal function (with oligo-anuria and a peak creatinine of 462 µmol/L) after the re-introduction of an angiotensin-II receptor blocker (irbesartan) in a 66-year-old Caucasian diabetic male patient with bilateral renal stenosis and a right-sided single-functioning kidney, with a rapid improvement of the renal function which normalized 5 days after percutaneous angioplasty and stenting of the right renal artery.
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- 2023
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12. Countrywide classification of permanent grassland habitats at high spatial resolution
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Nica Huber, Christian Ginzler, Robert Pazur, Patrice Descombes, Andri Baltensweiler, Klaus Ecker, Eliane Meier, and Bronwyn Price
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Bogs ,distribution models ,dry grasslands ,fens ,remote sensing ,Sentinel ,Technology ,Ecology ,QH540-549.5 - Abstract
Abstract European grasslands face strong declines in extent and quality. Many grassland types are priority habitats for national and European conservation strategies. Countrywide, high spatial resolution maps of their distribution are often lacking. Here, we modelled the spatial distribution of 20 permanent grassland habitats at the level of phytosociological alliances across Switzerland at 10x10 m resolution. First, we applied ensemble models to provide distribution maps of the individual habitat types, using training data from various sources. Copernicus Sentinel satellite imagery and variables describing climate, soil and topography were used as predictors. The performance of these models was assessed based on the true skill statistics with a split‐sampling of the data. Second, the individual maps were combined into countrywide maps of the most and second most likely habitat type, respectively, using an expert‐based weighting approach. The performance of the combined map for the most likely habitat type was assessed via an independent testing dataset and a comparison of the predicted habitat‐type proportions with extrapolations from field surveys. Most individual maps had useful to excellent predictive performance (TSS ≥ 0.6). For most grid cells in the combined maps, the most and second most likely habitat types were either ecologically closely related or representing two grassland types along a nutrient gradient. The same was true for omission errors. We found good agreement between the predicted and estimated proportions from field surveys. The area of raised bogs appears to be underestimated, while dry grasslands showed highest agreement. This work highlights the potential of earth observation data at fine spatial and temporal resolution to map habitats at broad scales, thereby providing the foundation for diverse conservation applications. A particular challenge remains in capturing the transition from nutrient‐poor to nutrient‐rich grasslands, which is highly important for biodiversity conservation.
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- 2023
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13. Global transcriptome profiling reveals differential regulatory, metabolic and hormonal networks during somatic embryogenesis in Coffea arabica
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Rayan Awada, Maud Lepelley, David Breton, Aline Charpagne, Claudine Campa, Victoria Berry, Frédéric Georget, Jean-Christophe Breitler, Sophie Léran, Doâa Djerrab, Federico Martinez-Seidel, Patrick Descombes, Dominique Crouzillat, Benoît Bertrand, and Hervé Etienne
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Cell fate ,Coffee ,Molecular markers ,Molecular networks ,Somatic embryogenesis ,Totipotency ,Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Background Somatic embryogenesis (SE) is one of the most promising processes for large-scale dissemination of elite varieties. However, for many plant species, optimizing SE protocols still relies on a trial and error approach. We report the first global scale transcriptome profiling performed at all developmental stages of SE in coffee to unravel the mechanisms that regulate cell fate and totipotency. Results RNA-seq of 48 samples (12 developmental stages × 4 biological replicates) generated 90 million high quality reads per sample, approximately 74% of which were uniquely mapped to the Arabica genome. First, the statistical analysis of transcript data clearly grouped SE developmental stages into seven important phases (Leaf, Dedifferentiation, Primary callus, Embryogenic callus, Embryogenic cell clusters, Redifferentiation and Embryo) enabling the identification of six key developmental phase switches, which are strategic for the overall biological efficiency of embryo regeneration. Differential gene expression and functional analysis showed that genes encoding transcription factors, stress-related genes, metabolism-related genes and hormone signaling-related genes were significantly enriched. Second, the standard environmental drivers used to control SE, i.e. light, growth regulators and cell density, were clearly perceived at the molecular level at different developmental stages. Third, expression profiles of auxin-related genes, transcription factor-related genes and secondary metabolism-related genes were analyzed during SE. Gene co-expression networks were also inferred. Auxin-related genes were upregulated during dedifferentiation and redifferentiation while transcription factor-related genes were switched on from the embryogenic callus and onward. Secondary metabolism-related genes were switched off during dedifferentiation and switched back on at the onset of redifferentiation. Secondary metabolites and endogenous IAA content were tightly linked with their respective gene expression. Lastly, comparing Arabica embryogenic and non-embryogenic cell transcriptomes enabled the identification of biological processes involved in the acquisition of embryogenic capacity. Conclusions The present analysis showed that transcript fingerprints are discriminating signatures of cell fate and are under the direct influence of environmental drivers. A total of 23 molecular candidates were successfully identified overall the 12 developmental stages and can be tested in many plant species to optimize SE protocols in a rational way.
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- 2023
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14. A descriptive study of routine laboratory testing in intensive care unit in nearly 140,000 patient stays
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Jérôme Allyn, Marjolaine Devineau, Matthieu Oliver, Guillaume Descombes, Nicolas Allou, and Cyril Ferdynus
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Medicine ,Science - Abstract
Abstract To describe the relationship between the use of laboratory tests and changes in laboratory parameters in ICU patients is necessary to help optimize routine laboratory testing. A retrospective, descriptive study was conducted on the large eICU-Collaborative Research Database. The relationship between the use of routine laboratory tests (chemistry and blood counts) and changes in ten common laboratory parameters was studied. Factors associated with laboratory tests were identified in a multivariate regression analysis using generalized estimating equation Poisson models. The study included 138,734 patient stays, with an ICU mortality of 8.97%. For all parameters, the proportion of patients with at least one test decreased from day 0 to day 1 and then gradually increased until the end of the ICU stay. Paradoxically, the results of almost all tests moved toward normal values, and the daily variation in the results of almost all tests decreased over time. The presence of an arterial catheter or teaching hospitals were independently associated with an increase in the number of laboratory tests performed. The paradox of routine laboratory testing should be further explored by assessing the factors that drive the decision to perform routine laboratory testing in ICU and the impact of such testing on patient.
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- 2022
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15. On the Existence of Scaling Multi-Centered Black Holes
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Descombes, Pierre and Pioline, Boris
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- 2022
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16. Bioprospecting of a Metschnikowia pulcherrima Indigenous Strain for Chasselas Winemaking in 2022 Vintage
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Federico Sizzano, Marie Blackford, Hélène Berthoud, Laurent Amiet, Sébastien Bailly, Frédéric Vuichard, Christine Monnard, Stefan Bieri, Jean-Laurent Spring, Yannick Barth, Corentin Descombes, François Lefort, Marilyn Cléroux, Scott Simonin, Charles Chappuis, Gilles Bourdin, and Benoît Bach
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non-Saccharomyces yeasts ,fermentation ,flow cytometry ,winemaking ,microbial communities ,Chemical technology ,TP1-1185 - Abstract
Interest in Metschnikowia (M.) pulcherrima is growing in the world of winemaking. M. pulcherrima is used both to protect musts from microbial spoilage and to modulate the aromatic profile of wines. Here, we describe the isolation, characterization, and use of an autochthonous strain of M. pulcherrima in the vinification of Chasselas musts from the 2022 vintage. M. pulcherrima was used in co-fermentation with Saccharomyces cerevisiae at both laboratory and experimental cellar scales. Our results showed that M. pulcherrima does not ferment sugars but has high metabolic activity, as detected by flow cytometry. Furthermore, sensory analysis showed that M. pulcherrima contributed slightly to the aromatic profile when compared to the control vinifications. The overall results suggest that our bioprospecting strategy can guide the selection of microorganisms that can be effectively used in the winemaking process.
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- 2023
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17. Cardiac dyspnea risk zones in the South of France identified by geo-pollution trends study
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Fanny Simões, Charles Bouveyron, Damien Piga, Damien Borel, Stéphane Descombes, Véronique Paquis-Flucklinger, Jaques Levraut, Pierre Gibelin, and Silvia Bottini
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Medicine ,Science - Abstract
Abstract The incidence of cardiac dyspnea (CD) and the distribution of pollution in the south of France suggests that environmental pollution may have a role in disease triggering. CD is a hallmark symptom of heart failure leading to reduced ability to function and engage in activities of daily living. To show the impact of short-term pollution exposure on the increment of CD emergency room visits, we collected pollutants and climate measurements on a daily basis and 43,400 events of CD in the Région Sud from 2013 to 2018. We used a distributed lag non-linear model (DLNM) to assess the association between air pollution and CD events. We divided the region in 357 zones to reconciliate environmental and emergency room visits data. We applied the DLNM on the entire region, on zones grouped by pollution trends and on singular zones. Each pollutant has a significant effect on triggering CD. Depending on the pollutant, we identified four shapes of exposure curves to describe the impact of pollution on CD events: early and late effect for NO2; U-shape and rainbow-shape (or inverted U) for O3; all the four shapes for PM10. In the biggest cities, O3 has the most significant association along with the PM10. In the west side, a delayed effect triggered by PM10 was found. Zones along the main highway are mostly affected by NO2 pollution with an increase of the association for a period up to 9 days after the pollution peak. Our results can be used by local authorities to set up specific prevention policies, public alerts that adapt to the different zones and support public health prediction-making. We developed a user-friendly web application called Health, Environment in PACA Region Tool (HEART) to collect our results. HEART will allow citizens, researchers and local authorities to monitor the impact of pollution trends on local public health.
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- 2022
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18. Cardiac dyspnea risk zones in the South of France identified by geo-pollution trends study
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Simões, Fanny, Bouveyron, Charles, Piga, Damien, Borel, Damien, Descombes, Stéphane, Paquis-Flucklinger, Véronique, Levraut, Jaques, Gibelin, Pierre, and Bottini, Silvia
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- 2022
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19. A descriptive study of routine laboratory testing in intensive care unit in nearly 140,000 patient stays
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Allyn, Jérôme, Devineau, Marjolaine, Oliver, Matthieu, Descombes, Guillaume, Allou, Nicolas, and Ferdynus, Cyril
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- 2022
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20. GenomeMixer and TRUST: Novel bioinformatics tools to improve reliability of Non-Invasive Prenatal Testing (NIPT) for fetal aneuploidies
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David Pratella, Véronique Duboc, Marco Milanesio, John Boudjarane, Stéphane Descombes, Véronique Paquis-Flucklinger, and Silvia Bottini
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Non-invasive prenatal testing ,Fetal fraction ,Aneuploidy detection ,Confidence intervals ,Semi-supervised method ,Biotechnology ,TP248.13-248.65 - Abstract
Non-invasive prenatal testing (NIPT) screens for common fetal chromosomal abnormalities through analysis of circulating cell-free DNA in maternal blood by massive parallel sequencing. NIPT reliability relies on both the estimation of the fetal fraction (ff) and on the sequencing depth (sd) but how these parameters are linked is unknown. Several bioinformatics tools have been developed to determine the ff but there is no universal ff threshold applicable across diagnostics laboratories. Thus, we developed two tools allowing the implementation of a strategy for NIPT results validation in clinical practice: GenomeMixer, a semi-supervised approach to create synthetic sequences and to estimate confidence intervals for NIPT validation and TRUST to estimate the reliability of NIPT results based on confidence intervals found in this study. We retrospectively validated these new tools on 2 cohorts for a total of 1439 samples with 31 confirmed aneuploidies. Through the analysis of the interrelationship between ff, sd and chromosomal aberration detection, we demonstrate that these parameters are profoundly connected and cannot be considered independently. Our tools take in account this critical relationship to improve NIPT reliability and facilitate cross laboratory standardization of this screening test.
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- 2022
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21. A spatial statistical framework for the parametric study of fiber networks: Application to fibronectin deposition by normal and activated fibroblasts
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Anca-Ioana Grapa, Georgios Efthymiou, Ellen Van Obberghen-Schilling, Laure Blanc-Féraud, and Xavier Descombes
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Extracellular matrix ,fibronectin ,graph networks ,oncofetal isoforms ,statistical parametric maps ,Biology (General) ,QH301-705.5 ,Medical technology ,R855-855.5 - Abstract
Due to the complex architectural diversity of biological networks, there is an increasing need to complement statistical analyses with a qualitative and local description of their spatial properties. One such network is the extracellular matrix (ECM), a biological scaffold for which changes in its spatial organization significantly impact tissue functions in health and disease. Quantifying variations in the fibrillar architecture of major ECM proteins should considerably advance our understanding of the link between tissue structure and function. Inspired by the analysis of functional magnetic resonance imaging (fMRI) images, we propose a novel statistical analysis approach embedded into a machine learning paradigm, to measure and detect local variations of meaningful ECM parameters. We show that parametric maps representing fiber length and pore directionality can be analyzed within the proposed framework to differentiate among various tissue states. The parametric maps are derived from graph-based representations that reflect the network architecture of fibronectin (FN) fibers in a normal, or disease-mimicking in vitro setting. Such tools can potentially lead to a better characterization of dynamic matrix networks within fibrotic tumor microenvironments and contribute to the development of better imaging modalities for monitoring their remodeling and normalization following therapeutic intervention.
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- 2023
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22. Identifying regions of interest in whole slide images of renal cell carcinoma
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Benomar, Mohammed Lamine, Settouti, Nesma, Debreuve, Eric, Descombes, Xavier, and Ambrosetti, Damien
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- 2021
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23. Isolation, Identification and Evaluation of the Effects of Native Entomopathogenic Fungi from Côte d’Ivoire on Galleria mellonella
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Fatoumatou Fofana, Corentin Descombes, Assiri Patrice Kouamé, and François Lefort
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Beauveria bassiana ,biological control ,Galleria mellonella ,fall armyworm ,Metarhizium anisopliae ,Spodoptera frugiperda ,Biology (General) ,QH301-705.5 - Abstract
The fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae), is a polyphagous pest highly damaging to maize and other food crops in Africa, particularly in Côte d’Ivoire. Chemical pesticides not only have often proved to be unsuccessful, but cause adverse effects on the environment and human health; therefore, entomopathogenic fungi could represent an alternative biocontrol solution. Against this background, fungi were isolated from soil samples collected in maize fields in three regions of Côte d’Ivoire, by the methods of soil dilution and baiting with Galleria mellonella. The resulting 86 fungal isolates were phenotypically and genetically identified. The pathogenicity of seven isolates of Metarhizium spp., three isolates of Beauveria bassiana and two isolates of Trichoderma sp. was evaluated on fifth instar larvae (L5) of G. mellonella. Larval mortality rates and the median lethal time (LT50) were determined seven days after inoculation for each of these selected isolates. The median lethal concentration (LC50) was determined for a selection of isolates. Beauveria bassiana isolate A214b was the most effective, causing 100% mortality, with an LT50 of 2.64 days and an LC50 of 1.12 × 104 conidia mL−1. Two other promising isolates, A211 and A214a, belonging to B. bassiana, caused 100% mortality with LT50 values of 3.44 and 4.04 days, respectively. Mortality caused by Metarhizium isolates varied from 65.38% to 100%, with Metarhizium anisopliae isolate T331 causing 100% mortality with an LT50 of 3.08 days at an LC50 of 3.33 × 104 conidia mL−1. Trichoderma sp. isolates were the least pathogenic ones. Beauveria bassiana and Metarhizium isolates showed to be virulent against the model Lepidopteran G. mellonella and will be tested on S. frugiperda.
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- 2023
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24. Contribution of genetic ancestry and polygenic risk score in meeting vitamin B12 needs in healthy Brazilian children and adolescents
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Carlos Alessandro Fuzo, Fábio da Veiga Ued, Sofia Moco, Ornella Cominetti, Sylviane Métairon, Solenn Pruvost, Aline Charpagne, Jerome Carayol, Raul Torrieri, Wilson Araujo Silva, Patrick Descombes, Jim Kaput, and Jacqueline Pontes Monteiro
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Medicine ,Science - Abstract
Abstract Polymorphisms in genes related to the metabolism of vitamin B12 haven’t been examined in a Brazilian population. To (a) determine the correlation between the local genetic ancestry components and vitamin B12 levels using ninety B12-related genes; (b) determine associations between these genes and their SNPs with vitamin B12 levels; (c) determine a polygenic risk score (PRS) using significant variants. This cross-sectional study included 168 children and adolescents, aged 9–13 years old. Total cobalamin was measured in plasma. Genotyping arrays and whole exome data were combined to yield ~ 7000 SNPs in 90 genes related to vitamin B12. The Efficient Local Ancestry Inference was used to estimate local ancestry for African (AFR), Native American, and European (EUR). The association between the genotypes and vitamin B12 levels were determined with generalized estimating equation. Vitamin B12 levels were driven by positive (EUR) and negative (AFR, AMR) correlations with genetic ancestry. A set of 36 variants were used to create a PRS that explained 42% of vitamin level variation. Vitamin B12 levels are influenced by genetic ancestry and a PRS explained almost 50% of the variation in plasma cobalamin in Brazilian children and adolescents.
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- 2021
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25. Attraction of Frankliniella occidentalis Females towards the Aggregation Pheromone Neryl (S)-2-Methylbutanoate and Kairomones in a Y-Olfactometer
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Charles J. F. Chappuis, Marilyn Cléroux, Corentin Descombes, Yannick Barth, and François Lefort
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western flower thrips ,pest management ,olfaction ,gas-phase concentration ,olfactometer ,Science - Abstract
An understanding of insect olfaction allows for more specific alternative methods of pest control. We evaluated the responses of the western flower thrips (WFT, Frankliniella occidentalis) in a Y-olfactometer to estimate gas-phase concentrations of the aggregation pheromone neryl (S)-2-methylbutanoate and known kairomones such as methyl isonicotinate, (S)-(-)-verbenone, and p-anisaldehyde. The gas-phase concentrations of these compounds were obtained from the release rates measured in dynamic headspace cells. The compounds were collected from the headspace using dried solid-phase extraction (SPE) cartridges and analyzed with a triple quadrupole GC-MS/MS. We observed that the aggregation pheromone significantly attracted WFT females at doses of 10 and 100 µg, whereas methyl isonicotinate and p-anisaldehyde significantly attracted WFT females at the highest dose. Verbenone did not produce any significant results. A completely different picture was obtained when the gas-phase concentrations were considered. The minimal gas-phase concentrations of the pheromone required to attract WFT females was 0.027 ng/mL, at least 100 times lower than that of the other two compounds. The relevance and implications of our results are discussed in light of the insect’s biology and pest management methods.
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- 2023
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26. The absence of the caffeine synthase gene is involved in the naturally decaffeinated status of Coffea humblotiana, a wild species from Comoro archipelago
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Nathalie Raharimalala, Stephane Rombauts, Andrew McCarthy, Andréa Garavito, Simon Orozco-Arias, Laurence Bellanger, Alexa Yadira Morales-Correa, Solène Froger, Stéphane Michaux, Victoria Berry, Sylviane Metairon, Coralie Fournier, Maud Lepelley, Lukas Mueller, Emmanuel Couturon, Perla Hamon, Jean-Jacques Rakotomalala, Patrick Descombes, Romain Guyot, and Dominique Crouzillat
- Subjects
Medicine ,Science - Abstract
Abstract Caffeine is the most consumed alkaloid stimulant in the world. It is synthesized through the activity of three known N-methyltransferase proteins. Here we are reporting on the 422-Mb chromosome-level assembly of the Coffea humblotiana genome, a wild and endangered, naturally caffeine-free, species from the Comoro archipelago. We predicted 32,874 genes and anchored 88.7% of the sequence onto the 11 chromosomes. Comparative analyses with the African Robusta coffee genome (C. canephora) revealed an extensive genome conservation, despite an estimated 11 million years of divergence and a broad diversity of genome sizes within the Coffea genus. In this genome, the absence of caffeine is likely due to the absence of the caffeine synthase gene which converts theobromine into caffeine through an illegitimate recombination mechanism. These findings pave the way for further characterization of caffeine-free species in the Coffea genus and will guide research towards naturally-decaffeinated coffee drinks for consumers.
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- 2021
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27. Altered synaptic ultrastructure in the prefrontal cortex of Shank3-deficient rats
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Sarah Jacot-Descombes, Neha U. Keshav, Dara L. Dickstein, Bridget Wicinski, William G. M. Janssen, Liam L. Hiester, Edward K. Sarfo, Tahia Warda, Matthew M. Fam, Hala Harony-Nicolas, Joseph D. Buxbaum, Patrick R. Hof, and Merina Varghese
- Subjects
Autism spectrum disorder ,Phelan–McDermid syndrome ,Synapse morphology ,Electron microscopy ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Deletion or mutations of SHANK3 lead to Phelan–McDermid syndrome and monogenic forms of autism spectrum disorder (ASD). SHANK3 encodes its eponymous scaffolding protein at excitatory glutamatergic synapses. Altered morphology of dendrites and spines in the hippocampus, cerebellum, and striatum have been associated with behavioral impairments in Shank3-deficient animal models. Given the attentional deficit in these animals, our study explored whether deficiency of Shank3 in a rat model alters neuron morphology and synaptic ultrastructure in the medial prefrontal cortex (mPFC). Methods We assessed dendrite and spine morphology and spine density in mPFC layer III neurons in Shank3-homozygous knockout (Shank3-KO), heterozygous (Shank3-Het), and wild-type (WT) rats. We used electron microscopy to determine the density of asymmetric synapses in mPFC layer III excitatory neurons in these rats. We measured postsynaptic density (PSD) length, PSD area, and head diameter (HD) of spines at these synapses. Results Basal dendritic morphology was similar among the three genotypes. Spine density and morphology were comparable, but more thin and mushroom spines had larger head volumes in Shank3-Het compared to WT and Shank3-KO. All three groups had comparable synapse density and PSD length. Spine HD of total and non-perforated synapses in Shank3-Het rats, but not Shank3-KO rats, was significantly larger than in WT rats. The total and non-perforated PSD area was significantly larger in Shank3-Het rats compared to Shank3-KO rats. These findings represent preliminary evidence for synaptic ultrastructural alterations in the mPFC of rats that lack one copy of Shank3 and mimic the heterozygous loss of SHANK3 in Phelan–McDermid syndrome. Limitations The Shank3 deletion in the rat model we used does not affect all isoforms of the protein and would only model the effect of mutations resulting in loss of the N-terminus of the protein. Given the higher prevalence of ASD in males, the ultrastructural study focused only on synaptic structure in male Shank3-deficient rats. Conclusions We observed increased HD and PSD area in Shank3-Het rats. These observations suggest the occurrence of altered synaptic ultrastructure in this animal model, further pointing to a key role of defective expression of the Shank3 protein in ASD and Phelan–McDermid syndrome.
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- 2020
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28. A landscape‐scale assessment of the relationship between grassland functioning, community diversity, and functional traits
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Hanneke van 'tVeen, Loïc Chalmandrier, Nadine Sandau, Michael P. Nobis, Patrice Descombes, Achilleas Psomas, Yann Hautier, and Loïc Pellissier
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BEF ,biodiversity ,drought ,ecosystem functioning ,ecosystem services ,grasslands ,Ecology ,QH540-549.5 - Abstract
Abstract Livestock farmers rely on a high and stable grassland productivity for fodder production to sustain their livelihoods. Future drought events related to climate change, however, threaten grassland functionality in many regions across the globe. The introduction of sustainable grassland management could buffer these negative effects. According to the biodiversity–productivity hypothesis, productivity positively associates with local biodiversity. The biodiversity–insurance hypothesis states that higher biodiversity enhances the temporal stability of productivity. To date, these hypotheses have mostly been tested through experimental studies under restricted environmental conditions, hereby neglecting climatic variations at a landscape‐scale. Here, we provide a landscape‐scale assessment of the contribution of species richness, functional composition, temperature, and precipitation on grassland productivity. We found that the variation in grassland productivity during the growing season was best explained by functional trait composition. The community mean of plant preference for nutrients explained 24.8% of the variation in productivity and the community mean of specific leaf area explained 18.6%, while species richness explained only 2.4%. Temperature and precipitation explained an additional 22.1% of the variation in productivity. Our results indicate that functional trait composition is an important predictor of landscape‐scale grassland productivity.
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- 2020
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29. Rhythmanalysis of Urban Events: Empirical Elements from the Montreux Jazz Festival
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Guillaume Drevon, Luca Pattaroni, Lucien Delley, Fabien Jacot-Descombes, and Nils Hamel
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eventful city ,gis ,hyper-place ,mobility ,montreux jazz festival ,rhythmanalysis ,rhythmic scales ,time machine ,visualisation ,City planning ,HT165.5-169.9 - Abstract
This article proposes an original approach to urban events mapping. At the theoretical level, the article is based on rhythmanalysis and recent research on urban rhythms. It contrasts with previous research by departing from everyday rhythms to tackle the specific rhythms of urban events. Drawing on this theoretical framework, the article proposes to analyse the rhythms of the Montreux Jazz Festival. The article proposes two main types of rhythmic scales, linked with the historical development of the Festival and its annual performance. The methodology is based on a mixed method of data collection and an original analysis framework. The analysis of the historical rhythm is carried out based on the analysis of the festival archives and interviews with experts. The analysis uses the Time Machine visualisation device that reveals three processes of urban resonance: the spread, which shows how the festival is integrated into the existing urban fabric; the openness, which shows accessibility; and the grip, which seeks to evaluate the urban sphere of influence of the event. These different visualisations are enriched by the addition of other data, including ticket scanning and commercial transactions that show the alternance between high and low-intensity periods. These allowed us to not only confirm the impact of programming on flows, but also the effects of the wider organisation of the leisure system. The results of the analysis show that the intertwining of the two rhythmic scales produces a hyper-place that resonates both internationally and locally.
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- 2020
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30. Genomic history of the Italian population recapitulates key evolutionary dynamics of both Continental and Southern Europeans
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Marco Sazzini, Paolo Abondio, Stefania Sarno, Guido Alberto Gnecchi-Ruscone, Matteo Ragno, Cristina Giuliani, Sara De Fanti, Claudia Ojeda-Granados, Alessio Boattini, Julien Marquis, Armand Valsesia, Jerome Carayol, Frederic Raymond, Chiara Pirazzini, Elena Marasco, Alberto Ferrarini, Luciano Xumerle, Sebastiano Collino, Daniela Mari, Beatrice Arosio, Daniela Monti, Giuseppe Passarino, Patrizia D’Aquila, Davide Pettener, Donata Luiselli, Gastone Castellani, Massimo Delledonne, Patrick Descombes, Claudio Franceschi, and Paolo Garagnani
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Italian population ,Whole-genome sequences ,Demographic inference ,Polygenic adaptation ,Evolutionary medicine ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background The cline of human genetic diversity observable across Europe is recapitulated at a micro-geographic scale by variation within the Italian population. Besides resulting from extensive gene flow, this might be ascribable also to local adaptations to diverse ecological contexts evolved by people who anciently spread along the Italian Peninsula. Dissecting the evolutionary history of the ancestors of present-day Italians may thus improve the understanding of demographic and biological processes that contributed to shape the gene pool of European populations. However, previous SNP array-based studies failed to investigate the full spectrum of Italian variation, generally neglecting low-frequency genetic variants and examining a limited set of small effect size alleles, which may represent important determinants of population structure and complex adaptive traits. To overcome these issues, we analyzed 38 high-coverage whole-genome sequences representative of population clusters at the opposite ends of the cline of Italian variation, along with a large panel of modern and ancient Euro-Mediterranean genomes. Results We provided evidence for the early divergence of Italian groups dating back to the Late Glacial and for Neolithic and distinct Bronze Age migrations having further differentiated their gene pools. We inferred adaptive evolution at insulin-related loci in people from Italian regions with a temperate climate, while possible adaptations to pathogens and ultraviolet radiation were observed in Mediterranean Italians. Some of these adaptive events may also have secondarily modulated population disease or longevity predisposition. Conclusions We disentangled the contribution of multiple migratory and adaptive events in shaping the heterogeneous Italian genomic background, which exemplify population dynamics and gene-environment interactions that played significant roles also in the formation of the Continental and Southern European genomic landscapes.
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- 2020
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31. In vivo transcriptomic profiling using cell encapsulation identifies effector pathways of systemic aging
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Omid Mashinchian, Xiaotong Hong, Joris Michaud, Eugenia Migliavacca, Gregory Lefebvre, Christophe Boss, Filippo De Franceschi, Emmeran Le Moal, Jasmin Collerette-Tremblay, Joan Isern, Sylviane Metairon, Frederic Raymond, Patrick Descombes, Nicolas Bouche, Pura Muñoz-Cánoves, Jerome N Feige, and C Florian Bentzinger
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aging ,cell encapsulation ,transcriptomics ,myogenic progenitors ,MuSCs ,satellite cells ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Sustained exposure to a young systemic environment rejuvenates aged organisms and promotes cellular function. However, due to the intrinsic complexity of tissues it remains challenging to pinpoint niche-independent effects of circulating factors on specific cell populations. Here, we describe a method for the encapsulation of human and mouse skeletal muscle progenitors in diffusible polyethersulfone hollow fiber capsules that can be used to profile systemic aging in vivo independent of heterogeneous short-range tissue interactions. We observed that circulating long-range signaling factors in the old systemic environment lead to an activation of Myc and E2F transcription factors, induce senescence, and suppress myogenic differentiation. Importantly, in vitro profiling using young and old serum in 2D culture does not capture all pathways deregulated in encapsulated cells in aged mice. Thus, in vivo transcriptomic profiling using cell encapsulation allows for the characterization of effector pathways of systemic aging with unparalleled accuracy.
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- 2022
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32. Contrasting responses of above- and below-ground herbivore communities along elevation
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Pitteloud, Camille, Descombes, Patrice, Sànchez-Moreno, Sara, Kergunteuil, Alan, Ibanez, Sébastien, Rasmann, Sergio, and Pellissier, Loïc
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- 2020
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33. Comment on: “Post-Dialysis Parenteral Antimicrobial Therapy in Patients Receiving Intermittent High-Flux Haemodialysis”
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Descombes, Eric, Hemett, Ould Maouloud, Erard, Véronique, and Chuard, Christian
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- 2021
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34. The absence of the caffeine synthase gene is involved in the naturally decaffeinated status of Coffea humblotiana, a wild species from Comoro archipelago
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Raharimalala, Nathalie, Rombauts, Stephane, McCarthy, Andrew, Garavito, Andréa, Orozco-Arias, Simon, Bellanger, Laurence, Morales-Correa, Alexa Yadira, Froger, Solène, Michaux, Stéphane, Berry, Victoria, Metairon, Sylviane, Fournier, Coralie, Lepelley, Maud, Mueller, Lukas, Couturon, Emmanuel, Hamon, Perla, Rakotomalala, Jean-Jacques, Descombes, Patrick, Guyot, Romain, and Crouzillat, Dominique
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- 2021
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35. Contribution of genetic ancestry and polygenic risk score in meeting vitamin B12 needs in healthy Brazilian children and adolescents
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Fuzo, Carlos Alessandro, da Veiga Ued, Fábio, Moco, Sofia, Cominetti, Ornella, Métairon, Sylviane, Pruvost, Solenn, Charpagne, Aline, Carayol, Jerome, Torrieri, Raul, Silva, Jr, Wilson Araujo, Descombes, Patrick, Kaput, Jim, and Monteiro, Jacqueline Pontes
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- 2021
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36. Compound- and fiber type-selective requirement of AMPKγ3 for insulin-independent glucose uptake in skeletal muscle
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Philipp Rhein, Eric M. Desjardins, Ping Rong, Danial Ahwazi, Nicolas Bonhoure, Jens Stolte, Matthieu D. Santos, Ashley J. Ovens, Amy M. Ehrlich, José L. Sanchez Garcia, Qian Ouyang, Julian M. Yabut, Mads Kjolby, Mathieu Membrez, Niels Jessen, Jonathan S. Oakhill, Jonas T. Treebak, Pascal Maire, John W. Scott, Matthew J. Sanders, Patrick Descombes, Shuai Chen, Gregory R. Steinberg, and Kei Sakamoto
- Subjects
AMP-activated protein kinase ,5-aminoimidazole-4-carboxamide riboside ,MK-8722 ,TBC1D1 ,Brown adipose tissue ,Beige adipose tissue ,Internal medicine ,RC31-1245 - Abstract
Objective: The metabolic master-switch AMP-activated protein kinase (AMPK) mediates insulin-independent glucose uptake in muscle and regulates the metabolic activity of brown and beige adipose tissue (BAT). The regulatory AMPKγ3 isoform is uniquely expressed in skeletal muscle and potentially in BAT. Herein, we investigated the role that AMPKγ3 plays in mediating skeletal muscle glucose uptake and whole-body glucose clearance in response to small-molecule activators that act on AMPK via distinct mechanisms. We also assessed whether γ3 plays a role in adipose thermogenesis and browning. Methods: Global AMPKγ3 knockout (KO) mice were generated. A systematic whole-body, tissue, and molecular phenotyping linked to glucose homeostasis was performed in γ3 KO and wild-type (WT) mice. Glucose uptake in glycolytic and oxidative skeletal muscle ex vivo as well as blood glucose clearance in response to small molecule AMPK activators that target the nucleotide-binding domain of the γ subunit (AICAR) and allosteric drug and metabolite (ADaM) site located at the interface of the α and β subunit (991, MK-8722) were assessed. Oxygen consumption, thermography, and molecular phenotyping with a β3-adrenergic receptor agonist (CL-316,243) treatment were performed to assess BAT thermogenesis, characteristics, and function. Results: Genetic ablation of γ3 did not affect body weight, body composition, physical activity, and parameters associated with glucose homeostasis under chow or high-fat diet. γ3 deficiency had no effect on fiber-type composition, mitochondrial content and components, or insulin-stimulated glucose uptake in skeletal muscle. Glycolytic muscles in γ3 KO mice showed a partial loss of AMPKα2 activity, which was associated with reduced levels of AMPKα2 and β2 subunit isoforms. Notably, γ3 deficiency resulted in a selective loss of AICAR-, but not MK-8722-induced blood glucose-lowering in vivo and glucose uptake specifically in glycolytic muscle ex vivo. We detected γ3 in BAT and found that it preferentially interacts with α2 and β2. We observed no differences in oxygen consumption, thermogenesis, morphology of BAT and inguinal white adipose tissue (iWAT), or markers of BAT activity between WT and γ3 KO mice. Conclusions: These results demonstrate that γ3 plays a key role in mediating AICAR- but not ADaM site binding drug-stimulated blood glucose clearance and glucose uptake specifically in glycolytic skeletal muscle. We also showed that γ3 is dispensable for β3-adrenergic receptor agonist-induced thermogenesis and browning of iWAT.
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- 2021
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37. Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities
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Eugenia Migliavacca, Stacey K. H. Tay, Harnish P. Patel, Tanja Sonntag, Gabriele Civiletto, Craig McFarlane, Terence Forrester, Sheila J. Barton, Melvin K. Leow, Elie Antoun, Aline Charpagne, Yap Seng Chong, Patrick Descombes, Lei Feng, Patrice Francis-Emmanuel, Emma S. Garratt, Maria Pilar Giner, Curtis O. Green, Sonia Karaz, Narasimhan Kothandaraman, Julien Marquis, Sylviane Metairon, Sofia Moco, Gail Nelson, Sherry Ngo, Tony Pleasants, Frederic Raymond, Avan A. Sayer, Chu Ming Sim, Jo Slater-Jefferies, Holly E. Syddall, Pei Fang Tan, Philip Titcombe, Candida Vaz, Leo D. Westbury, Gerard Wong, Wu Yonghui, Cyrus Cooper, Allan Sheppard, Keith M. Godfrey, Karen A. Lillycrop, Neerja Karnani, and Jerome N. Feige
- Subjects
Science - Abstract
Sarcopenia is the loss of muscle mass and strength associated with physical disability during ageing. Here, the authors analyse muscle biopsies from 119 patients with sarcopenia and age-matched controls of different ethnic groups and find transcriptional signatures indicating mitochondrial dysfunction, associated with reduced mitochondria numbers and lower NAD+ levels in older individuals with sarcopenia.
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- 2019
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38. Macroencapsulated Human iPSC-Derived Pancreatic Progenitors Protect against STZ-Induced Hyperglycemia in Mice
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Corinne Haller, Julie Piccand, Filippo De Franceschi, Yuki Ohi, Anindita Bhoumik, Christophe Boss, Umberto De Marchi, Guillaume Jacot, Sylviane Metairon, Patrick Descombes, Andreas Wiederkehr, Alessio Palini, Nicolas Bouche, Pascal Steiner, Olivia G. Kelly, and Marine R.-C. Kraus
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Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Summary: In type 1 diabetes, a renewable source of human pancreatic β cells, in particular from human induced pluripotent stem cell (hiPSC) origin, would greatly benefit cell therapy. Earlier work showed that pancreatic progenitors differentiated from human embryonic stem cells in vitro can further mature to become glucose responsive following macroencapsulation and transplantation in mice. Here we took a similar approach optimizing the generation of pancreatic progenitors from hiPSCs. This work demonstrates that hiPSCs differentiated to pancreatic endoderm in vitro can be efficiently and robustly generated under large-scale conditions. The hiPSC-derived pancreatic endoderm cells (HiPECs) can further differentiate into glucose-responsive islet-like cells following macroencapsulation and in vivo implantation. The HiPECs can protect mice from streptozotocin-induced hyperglycemia and maintain normal glucose homeostasis and equilibrated plasma glucose concentrations at levels similar to the human set point. These results further validate the potential use of hiPSC-derived islet cells for application in clinical settings. : In this article, Kraus and colleagues show that human induced pluripotent stem cells can robustly and efficiently be differentiated to pancreatic endoderm in a large-scale setup. Moreover, after macroencapsulation and further in vivo maturation, hiPSC-derived pancreatic endoderm cells can give rise to glucose-responsive β cells, which protect mice from STZ-induced hyperglycemia. Keywords: β cell, diabetes mellitus, differentiation, human, stem cell, iPSC, encapsulation, therapy
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- 2019
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39. Genome-wide gene-based analyses of weight loss interventions identify a potential role for NKX6.3 in metabolism
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Armand Valsesia, Qiao-Ping Wang, Nele Gheldof, Jérôme Carayol, Hélène Ruffieux, Teleri Clark, Victoria Shenton, Lisa J. Oyston, Gregory Lefebvre, Sylviane Metairon, Christian Chabert, Ondine Walter, Polina Mironova, Paulina Lau, Patrick Descombes, Nathalie Viguerie, Dominique Langin, Mary-Ellen Harper, Arne Astrup, Wim H. Saris, Robert Dent, Greg G. Neely, and Jörg Hager
- Subjects
Science - Abstract
Individuals show large variability in their capacity to lose weight and maintain this weight. Here, the authors perform GWAS in two weight loss intervention cohorts and identify two genetic loci associated with weight loss that are taken forward for Bayesian fine-mapping and functional assessment in flies.
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- 2019
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40. Whole-genome sequencing analysis of semi-supercentenarians
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Paolo Garagnani, Julien Marquis, Massimo Delledonne, Chiara Pirazzini, Elena Marasco, Katarzyna Malgorzata Kwiatkowska, Vincenzo Iannuzzi, Maria Giulia Bacalini, Armand Valsesia, Jerome Carayol, Frederic Raymond, Alberto Ferrarini, Luciano Xumerle, Sebastiano Collino, Daniela Mari, Beatrice Arosio, Martina Casati, Evelyn Ferri, Daniela Monti, Benedetta Nacmias, Sandro Sorbi, Donata Luiselli, Davide Pettener, Gastone Castellani, Claudia Sala, Giuseppe Passarino, Francesco De Rango, Patrizia D'Aquila, Luca Bertamini, Nicola Martinelli, Domenico Girelli, Oliviero Olivieri, Cristina Giuliani, Patrick Descombes, and Claudio Franceschi
- Subjects
longevity ,ageing ,clonal hematopoiesis ,sequencing ,geroscience ,semi-supercentenarians ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Extreme longevity is the paradigm of healthy aging as individuals who reached the extreme decades of human life avoided or largely postponed all major age-related diseases. In this study, we sequenced at high coverage (90X) the whole genome of 81 semi-supercentenarians and supercentenarians [105+/110+] (mean age: 106.6 ± 1.6) and of 36 healthy unrelated geographically matched controls (mean age 68.0 ± 5.9) recruited in Italy. The results showed that 105+/110+ are characterized by a peculiar genetic background associated with efficient DNA repair mechanisms, as evidenced by both germline data (common and rare variants) and somatic mutations patterns (lower mutation load if compared to younger healthy controls). Results were replicated in a second independent cohort of 333 Italian centenarians and 358 geographically matched controls. The genetics of 105+/110+ identified DNA repair and clonal haematopoiesis as crucial players for healthy aging and for the protection from cardiovascular events.
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- 2021
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41. Prevalence of fosfomycin resistance among ESBL-producing Escherichia coli isolates in the community, Switzerland
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Mueller, Linda, Cimen, Cansu, Poirel, Laurent, Descombes, Marie-Christine, and Nordmann, Patrice
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- 2019
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42. COFRET’14 special issue of IJEEE
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Descombes, G., Podevin, P., Fazelpour, Farivar, Feidt, M., and Morozuk, T.
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- 2022
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43. Linking Human Milk Oligosaccharides, Infant Fecal Community Types, and Later Risk To Require Antibiotics
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Bernard Berger, Nadine Porta, Francis Foata, Dominik Grathwohl, Michèle Delley, Deborah Moine, Aline Charpagne, Léa Siegwald, Patrick Descombes, Philippe Alliet, Giuseppe Puccio, Philippe Steenhout, Annick Mercenier, and Norbert Sprenger
- Subjects
human milk oligosaccharides ,2′FL ,LNnT ,infant ,formula ,microbiota ,Microbiology ,QR1-502 - Abstract
ABSTRACT Human milk oligosaccharides (HMOs) may provide health benefits to infants partly by shaping the development of the early-life intestinal microbiota. In a randomized double-blinded controlled multicentric clinical trial, healthy term infants received either infant formula (control) or the same formula with two HMOs (2′-fucosyllactose and lacto-N-neotetraose; test) from enrollment (0 to 14 days) to 6 months. Then, all infants received the same follow-up formula without HMOs until 12 months of age. Breastfed infants (BF) served as a reference group. Stool microbiota at 3 and 12 months, analyzed by 16S rRNA gene sequencing, clustered into seven fecal community types (FCTs) with marked differences in total microbial abundances. Three of the four 12-month FCTs were likely precursors of the adult enterotypes. At 3 months, microbiota composition in the test group (n = 58) appeared closer to that of BF (n = 35) than control (n = 63) by microbiota alpha (within group) and beta (between groups) diversity analyses and distribution of FCTs. While bifidobacteriaceae dominated two FCTs, its abundance was significantly higher in one (FCT BiH for Bifidobacteriaceae at high abundance) than in the other (FCT Bi for Bifidobacteriaceae). HMO supplementation increased the number of infants with FCT BiH (predominant in BF) at the expense of FCT Bi (predominant in control). We explored the association of the FCTs with reported morbidities and medication use up to 12 months. Formula-fed infants with FCT BiH at 3 months were significantly less likely to require antibiotics during the first year than those with FCT Bi. Previously reported lower rates of infection-related medication use with HMOs may therefore be linked to gut microbiota community types. (This study has been registered at ClinicalTrials.gov under registration number NCT01715246.) IMPORTANCE Human milk is the sole and recommended nutrition for the newborn infant and contains one of the largest constituents of diverse oligosaccharides, dubbed human milk oligosaccharides (HMOs). Preclinical and clinical association studies indicate that HMOs have multiple physiological functions largely mediated through the establishment of the gut microbiome. Until recently, HMOs were not available to investigate their role in randomized controlled intervention trials. To our knowledge, this is the first report on the effects of 2 HMOs on establishing microbiota in newborn infants. We provide a detailed description of the microbiota changes observed upon feeding a formula with 2 HMOs in comparison to breastfed reference infants' microbiota. Then, we associate the microbiota to long-term health as assessed by prescribed antibiotic use.
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- 2020
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44. Logic of the Egotistical Sentence: A Reading of Descartes
- Author
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Vincent Descombes
- Subjects
descartes ,reflexivity ,egotism ,egology ,cogito ,Philosophy (General) ,B1-5802 - Abstract
This text is a translation of two extracts from Vincent Descombes' 2014 book Le parler de soi. The majority of the translation consists of the chapter (I.3) that Descombes dedicates to discussing Descartes extensively. In this text, Descombes analyzes “egotistical sentences,” or I-statements, beginning with the infamous example from Descartes (cogito ergo sum). From here, he develops a substantial meditation on the nature of the self and its inherent philosophical paradoxes. The “radical question” guiding Descombes is whether or not an egotistical sentence has or implies a subject in the metaphysical sense. The conclusion, ultimately supported in part by Anscombe’s work on “I-thoughts,” explains how it could be that a subject is not implied by an egotistical sentence.
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- 2018
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45. Quantifying errors in surface ozone predictions associated with clouds over the CONUS: a WRF-Chem modeling study using satellite cloud retrievals
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Y.-H. Ryu, A. Hodzic, J. Barre, G. Descombes, and P. Minnis
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Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Clouds play a key role in radiation and hence O3 photochemistry by modulating photolysis rates and light-dependent emissions of biogenic volatile organic compounds (BVOCs). It is not well known, however, how much error in O3 predictions can be directly attributed to error in cloud predictions. This study applies the Weather Research and Forecasting with Chemistry (WRF-Chem) model at 12 km horizontal resolution with the Morrison microphysics and Grell 3-D cumulus parameterization to quantify uncertainties in summertime surface O3 predictions associated with cloudiness over the contiguous United States (CONUS). All model simulations are driven by reanalysis of atmospheric data and reinitialized every 2 days. In sensitivity simulations, cloud fields used for photochemistry are corrected based on satellite cloud retrievals. The results show that WRF-Chem predicts about 55 % of clouds in the right locations and generally underpredicts cloud optical depths. These errors in cloud predictions can lead to up to 60 ppb of overestimation in hourly surface O3 concentrations on some days. The average difference in summertime surface O3 concentrations derived from the modeled clouds and satellite clouds ranges from 1 to 5 ppb for maximum daily 8 h average O3 (MDA8 O3) over the CONUS. This represents up to ∼ 40 % of the total MDA8 O3 bias under cloudy conditions in the tested model version. Surface O3 concentrations are sensitive to cloud errors mainly through the calculation of photolysis rates (for ∼ 80 %), and to a lesser extent to light-dependent BVOC emissions. The sensitivity of surface O3 concentrations to satellite-based cloud corrections is about 2 times larger in VOC-limited than NOx-limited regimes. Our results suggest that the benefits of accurate predictions of cloudiness would be significant in VOC-limited regions, which are typical of urban areas.
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- 2018
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46. Similarity of the dog and human gut microbiomes in gene content and response to diet
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Luis Pedro Coelho, Jens Roat Kultima, Paul Igor Costea, Coralie Fournier, Yuanlong Pan, Gail Czarnecki-Maulden, Matthew Robert Hayward, Sofia K. Forslund, Thomas Sebastian Benedikt Schmidt, Patrick Descombes, Janet R. Jackson, Qinghong Li, and Peer Bork
- Subjects
Microbiome ,Diet ,Metagenomics ,Dog microbiome ,Human microbiome ,Mouse microbiome ,Microbial ecology ,QR100-130 - Abstract
Abstract Background Gut microbes influence their hosts in many ways, in particular by modulating the impact of diet. These effects have been studied most extensively in humans and mice. In this work, we used whole genome metagenomics to investigate the relationship between the gut metagenomes of dogs, humans, mice, and pigs. Results We present a dog gut microbiome gene catalog containing 1,247,405 genes (based on 129 metagenomes and a total of 1.9 terabasepairs of sequencing data). Based on this catalog and taxonomic abundance profiling, we show that the dog microbiome is closer to the human microbiome than the microbiome of either pigs or mice. To investigate this similarity in terms of response to dietary changes, we report on a randomized intervention with two diets (high-protein/low-carbohydrate vs. lower protein/higher carbohydrate). We show that diet has a large and reproducible effect on the dog microbiome, independent of breed or sex. Moreover, the responses were in agreement with those observed in previous human studies. Conclusions We conclude that findings in dogs may be predictive of human microbiome results. In particular, a novel finding is that overweight or obese dogs experience larger compositional shifts than lean dogs in response to a high-protein diet.
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- 2018
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47. Altered synaptic ultrastructure in the prefrontal cortex of Shank3-deficient rats
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Jacot-Descombes, Sarah, Keshav, Neha U., Dickstein, Dara L., Wicinski, Bridget, Janssen, William G. M., Hiester, Liam L., Sarfo, Edward K., Warda, Tahia, Fam, Matthew M., Harony-Nicolas, Hala, Buxbaum, Joseph D., Hof, Patrick R., and Varghese, Merina
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- 2020
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48. DNA methylation during human adipogenesis and the impact of fructose
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Tini, Giulia, Varma, Vijayalakshmi, Lombardo, Rosario, Nolen, Greg T., Lefebvre, Gregory, Descombes, Patrick, Métairon, Sylviane, Priami, Corrado, Kaput, Jim, and Scott-Boyer, Marie-Pier
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- 2020
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49. Genomic history of the Italian population recapitulates key evolutionary dynamics of both Continental and Southern Europeans
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Sazzini, Marco, Abondio, Paolo, Sarno, Stefania, Gnecchi-Ruscone, Guido Alberto, Ragno, Matteo, Giuliani, Cristina, De Fanti, Sara, Ojeda-Granados, Claudia, Boattini, Alessio, Marquis, Julien, Valsesia, Armand, Carayol, Jerome, Raymond, Frederic, Pirazzini, Chiara, Marasco, Elena, Ferrarini, Alberto, Xumerle, Luciano, Collino, Sebastiano, Mari, Daniela, Arosio, Beatrice, Monti, Daniela, Passarino, Giuseppe, D’Aquila, Patrizia, Pettener, Davide, Luiselli, Donata, Castellani, Gastone, Delledonne, Massimo, Descombes, Patrick, Franceschi, Claudio, and Garagnani, Paolo
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- 2020
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50. Plant physical and chemical defence variation along elevation gradients: a functional trait-based approach
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Kergunteuil, Alan, Descombes, Patrice, Glauser, Gaetan, Pellissier, Loïc, and Rasmann, Sergio
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- 2018
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