Sequence-based GWAS, network and pathway analyses reveal genes co-associated with milk cheese-making properties and milk composition in Montbéliarde cows

Background Milk quality in dairy cattle is routinely assessed via analysis of mid-infrared (MIR) spectra; this approach can also be used to predict the milk’s cheese-making properties (CMP) and composition. When this method of high-throughput phenotyping is combined with efficient imputations of whole-genome sequence data from cows’ genotyping data, it provides a unique and powerful framework with which to carry out genomic analyses. The goal of this study was to use this approach to identify genes and gene networks associated with milk CMP and composition in the Montbéliarde breed. Results Milk cheese yields, coagulation traits, milk pH and contents of proteins, fatty acids, minerals, citrate, and lactose were predicted from MIR spectra. Thirty-six phenotypes from primiparous Montbéliarde cows (1,442,371 test-day records from 189,817 cows) were adjusted for non-genetic effects and averaged per cow. 50 K genotypes, which were available for a subset of 19,586 cows, were imputed at the sequence level using Run6 of the 1000 Bull Genomes Project (comprising 2333 animals). The individual effects of 8.5 million variants were evaluated in a genome-wide association study (GWAS) which led to the detection of 59 QTL regions, most of which had highly significant effects on CMP and milk composition. The results of the GWAS were further subjected to an association weight matrix and the partial correlation and information theory approach and we identified a set of 736 co-associated genes. Among these, the well-known caseins, PAEP and DGAT1, together with dozens of other genes such as SLC37A1, ALPL, MGST1, SEL1L3, GPT, BRI3BP, SCD, GPAT4, FASN, and ANKH, explained from 12 to 30% of the phenotypic variance of CMP traits. We were further able to identify metabolic pathways (e.g., phosphate and phospholipid metabolism and inorganic anion transport) and key regulator genes, such as PPARA, ASXL3, and bta-mir-200c that are functionally linked to milk composition. Conclusions By using an approach that integrated GWAS with network and pathway analyses at the whole-genome sequence level, we propose candidate variants that explain a substantial proportion of the phenotypic variance of CMP traits and could thus be included in genomic evaluation models to improve milk CMP in Montbéliarde cows.info:eu-repo/semantics/publishedVersio

Sequence-based GWAS, network and pathway analyses reveal genes co-associated with milk cheese-making properties and milk composition in Montbéliarde cows

International audienceAbstractBackgroundMilk quality in dairy cattle is routinely assessed via analysis of mid-infrared (MIR) spectra; this approach can also be used to predict the milk’s cheese-making properties (CMP) and composition. When this method of high-throughput phenotyping is combined with efficient imputations of whole-genome sequence data from cows’ genotyping data, it provides a unique and powerful framework with which to carry out genomic analyses. The goal of this study was to use this approach to identify genes and gene networks associated with milk CMP and composition in the Montbéliarde breed.ResultsMilk cheese yields, coagulation traits, milk pH and contents of proteins, fatty acids, minerals, citrate, and lactose were predicted from MIR spectra. Thirty-six phenotypes from primiparous Montbéliarde cows (1,442,371 test-day records from 189,817 cows) were adjusted for non-genetic effects and averaged per cow. 50 K genotypes, which were available for a subset of 19,586 cows, were imputed at the sequence level using Run6 of the 1000 Bull Genomes Project (comprising 2333 animals). The individual effects of 8.5 million variants were evaluated in a genome-wide association study (GWAS) which led to the detection of 59 QTL regions, most of which had highly significant effects on CMP and milk composition. The results of the GWAS were further subjected to an association weight matrix and the partial correlation and information theory approach and we identified a set of 736 co-associated genes. Among these, the well-known caseins, PAEP and DGAT1, together with dozens of other genes such as SLC37A1, ALPL, MGST1, SEL1L3, GPT, BRI3BP, SCD, GPAT4, FASN, and ANKH, explained from 12 to 30% of the phenotypic variance of CMP traits. We were further able to identify metabolic pathways (e.g., phosphate and phospholipid metabolism and inorganic anion transport) and key regulator genes, such as PPARA, ASXL3, and bta-mir-200c that are functionally linked to milk composition.ConclusionsBy using an approach that integrated GWAS with network and pathway analyses at the whole-genome sequence level, we propose candidate variants that explain a substantial proportion of the phenotypic variance of CMP traits and could thus be included in genomic evaluation models to improve milk CMP in Montbéliarde cows

In situ targeted activation of an anticancer agent using ultrasound-triggered release of composite droplets

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COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Evaluation of kinematic and dynamic effects induced by foot orthotics during walking

La connaissance des effets biomécaniques induits par les orthèses plantaires représente un enjeu important afin de faire reconnaitre le rôle du podologue dans le traitement des pathologies ostéo-articulaires et musculo-tendineuses de l'appareil locomoteur. Ainsi, ce travail de thèse consiste à modéliser, par la biomécanique, l'appareil locomoteur afin d'évaluer les effets du port des orthèses plantaires durant la marche. Avant toute chose, une étude méthodologique a été menée afin de vérifier la reproductibilité des données biomécaniques de la marche. Les principaux résultats montrent que ces données biomécaniques peuvent présenter une variabilité importante, principalement causée par des erreurs de positionnement des capteurs sur le sujet, rendant parfois difficile l'interprétation clinique. Toutefois, la deuxième partie de cette étude a montré que l'utilisation d'une méthodologie de correction segmentaire à partir d'une position statique imposée permettait de réduire cette variabilité. Une étude clinique a donc été menée sur les répercussions de l'utilisation d'une orthèse plantaire de supination sur la correction instantanée du pied valgus. Les principales conclusions montrent que les données cinématiques et dynamiques, notamment du pied et de la cheville, sont impactées. Enfin, afin de démontrer l'intérêt d'utiliser la méthodologie de correction segmentaire pour l'interprétation des effets biomécaniques du traitement par orthèses plantaires à plus ou moins long terme, deux cas cliniques ont été analysés, l'un concernait un patient atteint d'un syndrome de loge de la jambe et l'autre d'une gonarthrose. Les principales conclusions indiquent que les orthèses plantaires ont une action sur des pathologies de la cheville et du genou mais que l'interprétation de cette action peut être erronée si la variabilité des données biomécaniques de la marche n'est pas prise en considérationThe knowledge of the biomechanical effects induced by foot orthotics is an important issue in order to recognize the role of the podiatrist in the treatment of osteoarticular and musculotendinous disorders of the musculoskeletal system. So, this work consists in modeling, by the biomechanics, the musculoskeletal system to assess the effects of wearing foot orthotics during walking. A first study was conducted to check the reproducibility of gait biomechanical data through two different sessions. The results show that these biomechanical data may show significant variability, mainly caused by errors in the positioning of sensors on the subject, making it difficult clinical interpretation. However, the second part of this study showed that the use of a methodology for segmental correction, from a static position imposed, allowed reducing this variability. Thus, a study was conducted on the impact of the use of supinated foot orthotics on immediate correction of valgus foot. The main findings show that the kinematic and dynamic data, notably the foot and ankle, are impacted. Before being able to estimate if this correction lasts over time, a second study was conducted. Thus, to demonstrate the benefits of using this methodology for the interpretation of the biomechanical effects of treatment with foot orthotic in the longer term, two clinical cases were analyzed, one involved a patient with compartment syndrome of the leg and the other with knee osteoarthritis. The main findings indicate that the insoles have an impact on diseases of the ankle and knee but that the interpretation of these actions may be wrong if the variability of gait biomechanical data is not considere

Évaluation des effets cinématiques et dynamiques induits par le port d’orthèses plantaires lors de la marche

The knowledge of the biomechanical effects induced by foot orthotics is an important issue in order to recognize the role of the podiatrist in the treatment of osteoarticular and musculotendinous disorders of the musculoskeletal system. So, this work consists in modeling, by the biomechanics, the musculoskeletal system to assess the effects of wearing foot orthotics during walking. A first study was conducted to check the reproducibility of gait biomechanical data through two different sessions. The results show that these biomechanical data may show significant variability, mainly caused by errors in the positioning of sensors on the subject, making it difficult clinical interpretation. However, the second part of this study showed that the use of a methodology for segmental correction, from a static position imposed, allowed reducing this variability. Thus, a study was conducted on the impact of the use of supinated foot orthotics on immediate correction of valgus foot. The main findings show that the kinematic and dynamic data, notably the foot and ankle, are impacted. Before being able to estimate if this correction lasts over time, a second study was conducted. Thus, to demonstrate the benefits of using this methodology for the interpretation of the biomechanical effects of treatment with foot orthotic in the longer term, two clinical cases were analyzed, one involved a patient with compartment syndrome of the leg and the other with knee osteoarthritis. The main findings indicate that the insoles have an impact on diseases of the ankle and knee but that the interpretation of these actions may be wrong if the variability of gait biomechanical data is not consideredLa connaissance des effets biomécaniques induits par les orthèses plantaires représente un enjeu important afin de faire reconnaitre le rôle du podologue dans le traitement des pathologies ostéo-articulaires et musculo-tendineuses de l'appareil locomoteur. Ainsi, ce travail de thèse consiste à modéliser, par la biomécanique, l'appareil locomoteur afin d'évaluer les effets du port des orthèses plantaires durant la marche. Avant toute chose, une étude méthodologique a été menée afin de vérifier la reproductibilité des données biomécaniques de la marche. Les principaux résultats montrent que ces données biomécaniques peuvent présenter une variabilité importante, principalement causée par des erreurs de positionnement des capteurs sur le sujet, rendant parfois difficile l'interprétation clinique. Toutefois, la deuxième partie de cette étude a montré que l'utilisation d'une méthodologie de correction segmentaire à partir d'une position statique imposée permettait de réduire cette variabilité. Une étude clinique a donc été menée sur les répercussions de l'utilisation d'une orthèse plantaire de supination sur la correction instantanée du pied valgus. Les principales conclusions montrent que les données cinématiques et dynamiques, notamment du pied et de la cheville, sont impactées. Enfin, afin de démontrer l'intérêt d'utiliser la méthodologie de correction segmentaire pour l'interprétation des effets biomécaniques du traitement par orthèses plantaires à plus ou moins long terme, deux cas cliniques ont été analysés, l'un concernait un patient atteint d'un syndrome de loge de la jambe et l'autre d'une gonarthrose. Les principales conclusions indiquent que les orthèses plantaires ont une action sur des pathologies de la cheville et du genou mais que l'interprétation de cette action peut être erronée si la variabilité des données biomécaniques de la marche n'est pas prise en considératio

Evaluation de l'envahissement carotidien dans les carcinomes des voies aérodigestives supérieures

Les carcinomes des voies aérodigestives supérieures representent 90 % des tumeurs cervicales malignes. Au cours de leurs développements ces lésions peuvent envahir la paroi carotidienne, impliquant une prise en charge thérapeutique et un pronostic différent. Cet événement concerne 14% des évidements radicaux. La circonférence carotidienne au contact des adénopathies et la qualité du liseré graisseux péricarotidien ont été mesurées au scanner et rapportées à l'envahissement carotidien. Il existe un lien significatif entre circonférence et envahissement. Plus la circonférence est importante, plus le risque d'envahissement est élevé. Un contact entre les adénopathies et l'axe artériel inférieur à 90 de circonférence ainsi que le respect du liseré graisseux sont 2 critères prédictifs de l'absence d'envahissement. L'encerclement du vaisseau et la disparition du liseré sont suspects sans que l'on puisse affirmer l'envahissement de façon formelle.NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Rôle des intégrines dans la fibrose cardiaque

International audienceCes vingt dernières années, l’intérêt pour les intégrines n’a cessé de grandir et les découvertes ont ouvert de nouvelles perspectives thérapeutiques, notamment dans le cadre de la fibrose, particulièrement pour les intégrines de la famille aV. Après les revers de la thérapie anti-angiogénique utilisée contre le cancer, de nouvelles molécules inhibitrices de ces intégrines se sont révélées intéressantes pour le traitement de la fibrose tissulaire de différents organes, notamment le cœur. La fibrose cardiaque conduit à terme à l’insuffisance cardiaque, une des premières causes de mortalité dans le monde. La compréhension des déterminants de la fibrose cardiaque et l’implication des intégrines dans son développement représentent un enjeu majeur de santé publique. Dans cette revue, nous présentons les différents types de fibrose cardiaque et leurs étiologies. Nous évoquons ensuite les premières applications de stratégies anti-fibrosantes reposant sur l’inhibition d’intégrines spécifiques, comme traitement futur contre le développement de la fibrose cardiaque

Looking for prosodic patterns in LSF and coverbal gestures. What about (de)synchronization?”

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Looking for prosodic patterns in LSF and coverbal gestures. What about (de)synchronization?”

International audienc