Detection of quantitative trait loci for carcass composition traits in pigs

A quantitative trait locus (QTL) analysis of carcass composition data from a three-generation experimental cross between Meishan (MS) and Large White (LW) pig breeds is presented. A total of 488 F2 males issued from six F1 boars and 23 F1 sows, the progeny of six LW boars and six MS sows, were slaughtered at approximately 80 kg live weight and were submitted to a standardised cutting of the carcass. Fifteen traits, i.e. dressing percentage, loin, ham, shoulder, belly, backfat, leaf fat, feet and head weights, two backfat thickness and one muscle depth measurements, ham + loin and back + leaf fat percentages and estimated carcass lean content were analysed. Animals were typed for a total of 137 markers covering the entire porcine genome. Analyses were performed using a line-cross (LC) regression method where founder lines were assumed to be fixed for different QTL alleles and a half/full sib (HFS) maximum likelihood method where allele substitution effects were estimated within each half-/full-sib family. Additional analyses were performed to search for multiple linked QTL and imprinting effects. Significant gene effects were evidenced for both leanness and fatness traits in the telomeric regions of SSC 1q and SSC 2p, on SSC 4, SSC 7 and SSC X. Additional significant QTL were identified for ham weight on SSC 5, for head weight on SSC 1 and SSC 7, for feet weight on SSC 7 and for dressing percentage on SSC X. LW alleles were associated with a higher lean content and a lower fat content of the carcass, except for the fatness trait on SSC 7. Suggestive evidence of linked QTL on SSC 7 and of imprinting effects on SSC 6, SSC 7, SSC 9 and SSC 17 were also obtained

La médiation humaniste, pour ‘faire société’ dans la prise en charge des différends

This paper is the work of a collective, and contains multidisciplinary reflexions on a humanistic practice of mediation that was pioneered in France in 1984, and refined over 30 years of practical experience and thousands of completed mediations. This kind of mediation focuses its efforts less on the specific area of dispute, and more on the transformation of human and social relationships, thereby justifying the qualifier ‘humanistic’. The exchanges established between the mediants, made possible and facilitated by the mediator, have the core objective of rebuilding a lasting and peaceable relationship.Humanistic mediation is shown to be a tool for personal, ontological transformation – a way of supporting the deep aspirations and values which everyone needs in order to live. In social interaction it enables common ground (‘commons’) to emerge which forms the basis of a new mode of sharing; it introduces a process that is humanizing and mutually nurturing while still respecting differences. Humanistic mediation is rooted in the trans-modern beginnings of our ongoing societal transformation. By reintroducing a sense of existential solidarity which is founded more on sharing than on exchange, it offers itself as an educational tool for peace, using a civilizing pedagogy to create a humanism for our times.The process is laid out in three sequential phases, which take into account the emotions of the mediants. With often spectacular results, the process leads to a pivotal moment that allows the energy of the conflict to be redirected. The role and attitude of the mediator are precisely defined. The relationship between mediation and institutions such as justice and education is discussed. Humanistic mediation takes its place in the evolution of a justice that both repairs and restores.Cet article est la réflexion pluridisciplinaire d’un collectif sur une pratique humaniste de la médiation, introduite de façon pionnière en 1984 et affinée au cours de 30 ans d’expérience et de milliers de médiations réalisées. Ce type de médiation concentre ses efforts moins sur le différend que sur la transformation des rapports humains et sociaux, justifiant ainsi le qualificatif humaniste. Les échanges instaurés entre les médiants, rendus possibles et facilités par le médiateur, ont pour objectif essentiel de reconstruire une relation pacifiée et durable.La médiation humaniste se révèle un outil ontologique de transformation personnelle prenant appui sur les aspirations profondes et les valeurs dont chacun a besoin pour vivre. Socialement, elle permet l’émergence de communs sur lesquels fonder un nouveau mode de partage, introduisant un processus de fécondation mutuelle et d’humanisation réciproque, dans le respect des différences. La médiation humaniste s’inscrit dans les prémices trans-modernes de la transformation sociétale en cours. Réintroduisant le sens d’une solidarité existentielle, fondée plus sur le partage que sur l’échange, elle se présente comme un outil d’éducation à la paix, pédagogique et civilisateur, pour un humanisme de notre temps.Le déroulement en est explicité en trois phases successives prenant en compte les émotions des médiants et aboutissant à un retournement souvent spectaculaire qui permet de réorienter l’énergie du conflit. Le rôle et la posture du médiateur sont précisés.Le rapport aux institutions Justice et Education est discuté. La médiation humaniste s’inscrit dans une démarche de justice réparatrice et restauratrice

The MurG glycosyltransferase provides an oligomeric scaffold for the cytoplasmic steps of peptidoglycan biosynthesis in the human pathogen Bordetella pertussis

Peptidoglycan is a major component of the bacterial cell wall and thus a major determinant of cell shape. Its biosynthesis is initiated by several sequential reactions catalyzed by cytoplasmic Mur enzymes. Mur ligases (MurC, -D, -E, and -F) are essential for bacteria, metabolize molecules not present in eukaryotes, and are structurally and biochemically tractable. However, although many Mur inhibitors have been developed, few have shown promising antibacterial activity, prompting the hypothesis that within the cytoplasm, Mur enzymes could exist as a complex whose architecture limits access of small molecules to their active sites. This suggestion is supported by the observation that in many bacteria, mur genes are present in a single operon, and pairs of these genes often are fused to generate a single polypeptide. Here, we explored this genetic arrangement in the human pathogen Bordetella pertussis and show that MurE and MurF are expressed as a single, bifunctional protein. EM, small angle X-ray scattering (SAXS), and analytical centrifugation (AUC) revealed that the MurE-MurF fusion displays an elongated, flexible structure that can dimerize. Moreover, MurE-MurF interacted with the peripheral glycosyltransferase MurG, which formed discrete oligomers resembling 4- or 5-armed stars in EM images. The oligomeric structure of MurG may allow it to play a bona fide scaffolding role for a potential Mur complex, facilitating the efficient conveyance of peptidoglycan-building blocks toward the inner membrane leaflet. Our findings shed light on the structural determinants of a peptidoglycan formation complex involving Mur enzymes in bacterial cell wall formation9FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP11/52067-6; 2017/12436-9; 2013/02451-0FRISBI [ANR-10-INSB-05-02]; GRAL within the Grenoble Partnership for Structural Biology (PSB) [ANR-10-LABX-49-01]; Rhone-Alpes RegionRegion Auvergne-Rhone-Alpes; Fondation pour la Recherche Medicale (FRM)Fondation pour la Recherche Medicale; fonds FEDER; Centre National de la Recherche Scientifique (CNRS)Centre National de la Recherche Scientifique (CNRS); Commissariat a l'Energie Atomique et aux Energies Alternatives (CEA)French Atomic Energy Commission; University of Grenoble Alpes; EMBL; GIS-Infrastructures en Biologie Sante et Agronomie (IBISA); Laboratoire International Associe BACWALL (CNRS); FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [11/52067-6, 2017/12436-9]; Agence Nationale de la RechercheFrench National Research Agency (ANR) [ANR-13-BSV8-0015-01]; ANRFrench National Research Agency (ANR); Fondation pour la Recherche Medicale (FRM)Fondation pour la Recherche Medicale [FDT20160435484]; FAPESPFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2013/02451-0

Neogene and Pleistocene geodynamics: the paleoseismic evolution of Armorica (Western France)

The evolution of the passive Armorican margin (Western France) during the Neogene and Quaternary was analyzed using field data. The morphology of the margin attests to a late Hercynian shaping, further deformation during the Mesozoic mid-Atlantic opening, during the Alpine Orogeny, and ultimately, a Late Cenozoic uplift, mostly related to an onshore isostatic accommodation in response to erosion and limited tectonic activity. A very limited strike–slip dynamic, with very low seismicity, accommodated the Neogene–Pleistocene N170 strains around the rigid Armorican terrane. The South Armorican domain and English Channel floor include shear zones that adjusted the Alpine convergence, facilitating its transpressive slip to the west. The Permo-Triassic N150 faults were reactivated during the inversion phases that began after the Bartonian under the distal control of the Alpine convergence and the decrease in the Atlantic spreading rate after 34 Ma. The Armorican marine platforms were stable after the late Eocene and slightly subsident, experiencing pulsed episodes of transient lithospheric doming during the Neogene and Quaternary. Co-seismic activity onshore without surface rupture was recorded around ∼5.3 Ma, ∼3.7 Ma, ∼2.4–1.2 Ma, and ∼400–250 ka, in tandem with an inland exhumation driven by isostatic adjustment due to an intensification of periglacial erosion at the onset of the early interstadials or by agriculture. Low-magnitude and ubiquitous shallow seismic activities seem to be related today to an isostatic uplifted old brittle–ductile transition due to the accumulation of shearing strain

Detection of quantitative trait loci for growth and fatness in pigs

A quantitative trait locus (QTL) analysis of growth and fatness data from a three-generation experimental cross between Meishan (MS) and Large White (LW) pig breeds is presented. Six boars and 23 F1 sows, the progeny of six LW boars and six MS sows, produced 530 F2 males and 573 F2 females. Nine growth traits, i.e. body weight at birth and at 3, 10, 13, 17 and 22 weeks of age, average daily gain from birth to 3 weeks, from 3 to 10 weeks and from 10 to 22 weeks of age, as well as backfat thickness at 13, 17 and 22 weeks of age and at 40 and 60 kg live weight were analysed. Animals were typed for a total of 137 markers covering the entire porcine genome. Analyses were performed using two interval mapping methods: a line-cross (LC) regression method where founder lines were assumed to be fixed for different QTL alleles and a half-/full-sib (HFS) maximum likelihood method where allele substitution effects were estimated within each half-/full-sib family. Both methods revealed highly significant gene effects for growth on chromosomes 1, 4 and 7 and for backfat thickness on chromosomes 1, 4, 5, 7 and X, and significant gene effects on chromosome 6 for growth and backfat thickness. Suggestive QTLs were also revealed by both methods on chromosomes 2 and 3 for growth and 2 for backfat thickness. Significant gene effects were detected for growth on chromosomes 11, 13, 14, 16 and 18 and for backfat thickness on chromosome 8, 10, 13 and 14. LW alleles were associated with high growth rate and low backfat thickness, except for those of chromosome 7 and to a lesser extent early-growth alleles on chromosomes 1 and 2 and backfat thickness alleles on chromosome 6

Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism

Objectives Gut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome\u27s functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation. Design We performed metagenomic analyses in 1545 subjects from the MetaCardis cohorts and different murine experiments, including germ-free and antibiotic treated animals, faecal microbiota transfer, bariatric surgery and supplementation with biotin and prebiotics in mice. Results Severe obesity is associated with an absolute deficiency in bacterial biotin producers and transporters, whose abundances correlate with host metabolic and inflammatory phenotypes. We found suboptimal circulating biotin levels in severe obesity and altered expression of biotin-associated genes in human adipose tissue. In mice, the absence or depletion of gut microbiota by antibiotics confirmed the microbial contribution to host biotin levels. Bariatric surgery, which improves metabolism and inflammation, associates with increased bacterial biotin producers and improved host systemic biotin in humans and mice. Finally, supplementing high-fat diet-fed mice with fructo-oligosaccharides and biotin improves not only the microbiome diversity, but also the potential of bacterial production of biotin and B vitamins, while limiting weight gain and glycaemic deterioration. Conclusion Strategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN