Construction of a potato consensus map and QTL meta-analysis offer new insights into the genetic architecture of late blight resistance and plant maturity traits

<p>Abstract</p> <p>Background</p> <p>Integrating QTL results from independent experiments performed on related species helps to survey the genetic diversity of loci/alleles underlying complex traits, and to highlight potential targets for breeding or QTL cloning. Potato (<it>Solanum tuberosum </it>L.) late blight resistance has been thoroughly studied, generating mapping data for many Rpi-genes (R-genes to <it>Phytophthora infestans</it>) and QTLs (quantitative trait loci). Moreover, late blight resistance was often associated with plant maturity. To get insight into the genomic organization of late blight resistance loci as compared to maturity QTLs, a QTL meta-analysis was performed for both traits.</p> <p>Results</p> <p>Nineteen QTL publications for late blight resistance were considered, seven of them reported maturity QTLs. Twenty-one QTL maps and eight reference maps were compiled to construct a 2,141-marker consensus map on which QTLs were projected and clustered into meta-QTLs. The whole-genome QTL meta-analysis reduced by six-fold late blight resistance QTLs (by clustering 144 QTLs into 24 meta-QTLs), by <it>ca</it>. five-fold maturity QTLs (by clustering 42 QTLs into eight meta-QTLs), and by <it>ca</it>. two-fold QTL confidence interval mean. Late blight resistance meta-QTLs were observed on every chromosome and maturity meta-QTLs on only six chromosomes.</p> <p>Conclusions</p> <p>Meta-analysis helped to refine the genomic regions of interest frequently described, and provided the closest flanking markers. Meta-QTLs of late blight resistance and maturity juxtaposed along chromosomes IV, V and VIII, and overlapped on chromosomes VI and XI. The distribution of late blight resistance meta-QTLs is significantly independent from those of Rpi-genes, resistance gene analogs and defence-related loci. The anchorage of meta-QTLs to the potato genome sequence, recently publicly released, will especially improve the candidate gene selection to determine the genes underlying meta-QTLs. All mapping data are available from the Sol Genomics Network (SGN) database.</p

Le rôle de l’attachement amoureux dans l’ajustement et le traitement des femmes souffrant de douleur génito-pelvienne : une approche dyadique et longitudinale

Thèse de doctorat présenté en vue de l'obtention du doctorat en psychologie - recherche intervention, option psychologie clinique (Ph.D)L’une des causes la plus fréquente de douleur génito-pelvienne est la vestibulodynie provoquée (VP), qui affecterait 8% à 12% des femmes de la population générale (Harlow et al., 2014). Elle se caractérise par une douleur à l’entrée du vestibule vulvaire provoquée par l’application d’une pression, principalement lors des relations sexuelles. La VP a de nombreuses conséquences négatives sur la vie sexuelle, relationnelle et psychologique des femmes et de leurs partenaires amoureux (Bergeron et al., 2015). Des études ont démontré que certains facteurs interpersonnels affectent l’intensité de la douleur et l’ajustement des couples à la VP (Rosen & Bergeron, 2019). Bien qu’associée à des niveaux plus élevés de douleur chez les femmes et à une plus faible fonction et satisfaction sexuelles chez les couples avec la VP, l’insécurité d’attachement (i.e., anxiété d’abandon et/ou évitement de l’intimité) a été peu étudiée dans cette population (Granot et al., 2010; Leclerc et al., 2015). Ainsi, on note une absence d’études utilisant une perspective longitudinale ou dyadique, malgré le contexte très intime dans lequel la douleur survient. De plus, aucune étude n’a examiné ses associations avec des facteurs proximaux pouvant influencer la douleur ou encore en contexte de traitement. Ainsi, l’objectif général de la thèse était de mieux comprendre les mécanismes liés à l’attachement qui sous-tendent l’ajustement des femmes et de leur partenaire à la VP. Le premier article examinait les associations longitudinales entre l’attachement, le sentiment d’auto-efficacité dans la gestion de la douleur et l’intensité de la douleur chez les couples avec la VP. Deux-cent-treize couples avec la VP ont complété des questionnaires auto-rapportés lors de deux temps de mesures, espacés de deux ans. Les résultats ont démontré qu’une plus grande anxiété d’abandon prédisait un plus faible sentiment d’auto-efficacité dans la gestion de la douleur, qui en retour prédisait une plus grande intensité de la douleur chez les femmes deux ans plus tard. Plus d’évitement de l’intimité chez les femmes avec la VP était également un prédicteur d’une plus grande intensité de la douleur deux ans plus tard. Le second article de la thèse examinait les associations entre l’attachement, les réponses des partenaires et l’ajustement sexuel et relationnel chez 125 couples avec la VP. Des effets acteurs et partenaires ont été trouvés dans les associations entre l’insécurité d’attachement et plus de réponses négatives et moins de réponses facilitatrices pour les deux membres du couple, qui en retour était associé à un plus faible bien-être sexuel et relationnel. Le troisième article a examiné l’attachement et la maltraitance à l’enfance comme modérateurs de l’efficacité thérapeutique en comparant un traitement médical – la lidocaïne topique – à une thérapie cognitive comportementale de couple (TCCC) pour la VP développée par notre équipe. Un essai clinique randomisé impliquant 108 femmes avec la VP a trouvé que les femmes avec des niveaux élevés d’évitement de l’intimité ou de maltraitance à l’enfance bénéficiaient davantage de la lidocaïne que de la TCCC dans l’amélioration de leur satisfaction, leur fonction et leur détresse sexuelles à la fin du traitement ou six mois plus tard. Les implications et les contributions théoriques, cliniques et méthodologiques de ces résultats sont discutées.One of the most common causes of genito-pelvic pain is provoked vestibulodynia (PVD), affecting approximately 8% to 12% of women in population-based samples (Harlow et al., 2014). PVD is characterized by pressure provoked pain at the entrance of the vulvar vestibule, occurring mostly during sexual intercourse. PVD has deleterious effects on women and partners’ psychological, sexual and relational wellbeing (Bergeron et al., 2015), Studies show that proximal and distal interpersonal factors are associated with pain intensity and couples’ adjustment to PVD (Rosen & Bergeron, 2019). Although associated with greater pain intensity and poorer sexual satisfaction and function in couples with PVD, attachment insecurity (i.e., abandonment anxiety and/or avoidance of intimacy) has been scantily studied in this population (Granot et al., 2010; Leclerc et al., 2015). In fact, very few studies have examined the impact of attachment on couples’ adjustment while using longitudinal or dyadic methodologies, despite the very intimate nature of the context in which pain arises. Also, no study to date has examined attachment in relation to proximal variables affecting the pain experience or in a treatment setting. Therefore, the overarching goal of this thesis was to better understand how attachment affects couples’ adjustment to PVD. The first article of the thesis examined the longitudinal associations between attachment, pain self-efficacy and pain intensity in women and their partners. Two-hundred and thirteen couples completed self-report questionnaires on two occasions, spaced out over two years. Results showed that greater attachment anxiety predicted lower pain self-efficacy in women with PVD, which in turn predicted higher pain intensity two years later. Greater attachment avoidance in women with PVD also predicted higher pain intensity over two years. The second article tested the associations between attachment, partner responses to pain and relationship and sexual adjustment in 125 couples with PVD. Actor and partner effects were found between attachment insecurity and greater negative and fewer facilitative partner responses for both members of the couple, which in turn was associated with poorer relational and sexual wellbeing. The third article examined attachment and childhood maltreatment as moderators of treatment efficacy while comparing a first line medical treatment – topical lidocaine – to cognitive-behavioral couples therapy (CBCT) for PVD developed by our team. In a randomized clinical trial implicating 108 women with PVD, higher levels of attachment avoidance or childhood maltreatment were associated with poorer outcomes in CBCT compared to topical lidocaine on women’s sexual satisfaction and function at either post-treatment or 6-month follow-up. Implications of the results, along with theoretical, clinical, and methodological contributions of the thesis are discussed

Sox5 and Sox6 are needed to develop and maintain source, columnar, and hypertrophic chondrocytes in the cartilage growth plate

Sox5 and Sox6 encode Sry-related transcription factors that redundantly promote early chondroblast differentiation. Using mouse embryos with three or four null alleles of Sox5 and Sox6, we show that they are also essential and redundant in major steps of growth plate chondrocyte differentiation. Sox5 and Sox6 promote the development of a highly proliferating pool of chondroblasts between the epiphyses and metaphyses of future long bones. This pool is the likely cellular source of growth plates. Sox5 and Sox6 permit formation of growth plate columnar zones by keeping chondroblasts proliferating and by delaying chondrocyte prehypertrophy. They allow induction of chondrocyte hypertrophy and permit formation of prehypertrophic and hypertrophic zones by delaying chondrocyte terminal differentiation induced by ossification fronts. They act, at least in part, by down-regulating Ihh signaling, Fgfr3, and Runx2 and by up-regulating Bmp6. In conclusion, Sox5 and Sox6 are needed for the establishment of multilayered growth plates, and thereby for proper and timely development of endochondral bones

De Novo SOX6 Variants Cause a Neurodevelopmental Syndrome Associated with ADHD, Craniosynostosis, and Osteochondromas

Introduction: The SOX gene family consists of twenty transcription factors that play a pivotal role in cell fate and differentiation during the development of many organ systems. Within these SRY-related (SOX) genes is a highly conserved high mobility group (HMG) domain that has been shown to be critical for DNA binding and bending, nuclear trafficking, and protein-protein interactions. Mutations within this transcription factor family have been associated with rare congenital disorders, known as SOXopathies. These mutations are commonly de novo, heterozygous and inactivating, and exhibit gene haploinsufficiency. Of these twenty transcription factors, SOX6 is known to be involved in chondrocyte differentiation and development of the central nervous system. Although there have been reports of SOX6 variants causing adult pathological conditions, there has yet to be a well-established association between SOX6 variants and a developmental syndrome. Objectives: The objective of this study was to use clinical and genetic data to examine SOX6 mutations found in 19 individuals demonstrating developmental delay and to test the transcriptional activity of the 4 missense variants in vitro to determine if SOX6 haploinsufficiency leads to a neurodevelopmental SOXopathy. Methods: Nineteen individuals were identified as carriers of SOX6 variants, confirmed by molecular karyotyping, whole-exome sequencing, or whole-genome sequencing. Clinical pathogenicity was predicted and assessed in silico and in vitro. Expression plasmids for SOX6 missense variants were generated by PCR mutagenesis. The four missense variants generated were: p.Trp161Cys, p.Met605Thr, p.Trp639Arg, and p.Ser746Leu, with p.Met605Thr and p.Trp639Arg located within the HMG domain. For reporter assays, HEK293 cells were transfected in triplicate cultures with 3.5 µL ViaFect Transfection Reagent and a total of 1000ng of DNA. SOX6 intracellular localization was tested by transfecting either HEK293 or COS-1 cells and cytoplasmic and nuclear extracts were prepared for Western Blot analysis. Whole cell extracts transfected with respective WT-SOX6 or variant plasmid were also prepared for a dimerization assay. SOX6’s ability to bind DNA was also tested in an electrophoretic mobility shift assay (EMSA). Results: Study cohort consisted of 19 individuals from 17 unrelated families originating in Belgium, Canada, France, Germany, the Netherlands, Slovenia, the UK, and the US. These individuals shared milestone delays and intellectual disability, and exhibited abnormalities including mild dysmorphism, craniosynostosis, and osteochondromas. Immunoblots of nuclear and cytoplasmic extracts showed all variants were efficiently expressed however p.Met605Thr and p.Trp639Arg were not translocated or retained into the nucleus as efficiently as WT-SOX6 and the other two missense variants. The EMSA showed that proteins outside of the HMG domain behaved like WT-SOX6, but p.Met605Thr and p.Trp639Arg failed to bind the DNA probe. Reporter assay activity showed that the two variants outside of the HMG domain p.Trp161Cys and p.Ser746Leu displayed similar or slightly higher activity compared to WT-SOX6 while the two variants p.Met605Thr and p.Trp639Arg showed diminished reporter activity. Conclusions: These findings provide evidence that SOX6 variants cause a SOXopathy, which has been designated in Online Mendelian Inheritance in Man (OMIM) as #618971 Tolchin-Le Caignec syndrome (TOLCAS)

Why us? Perceived injustice is associated with more sexual and psychological distress in couples coping with genito-pelvic pain

Introduction Provoked vestibulodynia (PVD) is the most frequent cause of genito-pelvic pain/penetration disorder (GPPPD) and is associated with negative psychological and sexual consequences for affected women and their partners. PVD is often misdiagnosed or ignored and many couples may experience a sense of injustice, due to the loss of their ability to have a normal sexual life. Perceiving injustice has been documented to have important consequences in individuals with chronic pain. However, no quantitative research has investigated the experience of injustice in this population. Aim The aim of this study was to investigate the associations between perceived injustice and pain, sexual satisfaction, sexual distress, and depression among women with PVD and their partners. Methods Women diagnosed with PVD (N = 50) and their partners completed questionnaires of perceived injustice, pain, sexual satisfaction, sexual distress, and depression. Main Outcome Measures (1) Global Measure of Sexual Satisfaction Scale; (2) Female Sexual Distress Scale; (3) Beck Depression Inventory-II; and (4) McGill-Melzack Pain Questionnaire. Results After controlling for partners' age, women's higher level of perceived injustice was associated with their own greater sexual distress, and the same pattern was found for partners. Women's higher level of perceived injustice was associated with their own greater depression, and the same pattern was found for partners. Women's higher perceived injustice was not associated with their own lower sexual satisfaction but partners' higher perceived injustice was associated with their own lower sexual satisfaction. Perceived injustice was not associated with women's pain intensity. Conclusion Results suggest that perceiving injustice may have negative consequences for the couple's sexual and psychological outcomes. However, the effects of perceived injustice appear to be intra-individual. Targeting perceived injustice could enhance the efficacy of psychological interventions for women with PVD and their partners

The \u3cem\u3eSOX9\u3c/em\u3e upstream region prone to chromosomal aberrations causing campomelic dysplasia contains multiple cartilage enhancers

Two decades after the discovery that heterozygous mutations within and around SOX9 cause campomelic dysplasia, a generalized skeleton malformation syndrome, it is well established that SOX9 is a master transcription factor in chondrocytes. In contrast, the mechanisms whereby translocations in the –350/–50-kb region 5 of SOX9 cause severe disease and whereby SOX9 expression is specified in chondrocytes remain scarcely known. We here screen this upstream region and uncover multiple enhancers that activate Sox9-promoter transgenes in the SOX9 expression domain. Three of them are primarily active in chondrocytes. E250 (located at – 250 kb) confines its activity to condensed prechondrocytes, E195 mainly targets proliferating chondrocytes, and E84 is potent in all differentiated chondrocytes. E84 and E195 synergize with E70, previously shown to be active in most Sox9-expressing somatic tissues, including cartilage. While SOX9 protein powerfully activates E70, it does not control E250. It requires its SOX5/SOX6 chondrogenic partners to robustly activate E195 and additional factors to activate E84. Altogether, these results indicate that SOX9 expression in chondrocytes relies on widely spread transcriptional modules whose synergistic and overlapping activities are driven by SOX9, SOX5/SOX6 and other factors. They help elucidate mechanisms underlying campomelic dysplasia and will likely help uncover other disease mechanisms

Synthesis and characterization of bimetallic Fe/Mn oxides for chemical looping combustion

Fe-Mn mixed oxides have been prepared by different routes, characterized, and tested with TGA for application as oxygen carriers in the CLC process. These mixed oxides exhibit a lower oxygen transfer capacity than Ni based materials which is also dependant on synthesis method. In-situ XRD analysis was performed with one sample and allowed to clearly demonstrate the reaction pathway, reduction and oxidation reactions occurring stepwise, with little phase coexistence. SEM-EDS analysis on reduced and re-oxidized samples show atom migration occurs on a rather long distance, forming Fe0 and MnO particles during reduction which are oxidized back to (Fe,Mn)2O3

Using landscape history to predict biodiversity patterns in fragmented landscapes

Landscape ecology plays a vital role in understanding the impacts of land-use change on biodiversity, but it is not a predictive discipline, lacking theoretical models that quantitatively predict biodiversity patterns from first principles. Here, we draw heavily on ideas from phylogenetics to fill this gap, basing our approach on the insight that habitat fragments have a shared history. We develop a landscape ‘terrageny’, which represents the historical spatial separation of habitat fragments in the same way that a phylogeny represents evolutionary divergence among species. Combining a random sampling model with a terrageny generates numerical predictions about the expected proportion of species shared between any two fragments, the locations of locally endemic species, and the number of species that have been driven locally extinct. The model predicts that community similarity declines with terragenetic distance, and that local endemics are more likely to be found in terragenetically distinctive fragments than in large fragments. We derive equations to quantify the variance around predictions, and show that ignoring the spatial structure of fragmented landscapes leads to over-estimates of local extinction rates at the landscape scale. We argue that ignoring the shared history of habitat fragments limits our ability to understand biodiversity changes in human-modified landscape

Minocycline-induced hypersensitivity syndrome presenting with meningitis and brain edema: a case report

<p/> <p>Background</p> <p>Hypersentivity Syndrome (HS) may be a life-threatening condition. It frequently presents with fever, rash, eosinophilia and systemic manifestations. Mortality can be as high as 10% and is primarily due to hepatic failure. We describe what we believe to be the first case of minocycline-induced HS with accompanying lymphocytic meningitis and cerebral edema reported in the literature.</p> <p>Case presentation</p> <p>A 31-year-old HIV-positive female of African origin presented with acute fever, lymphocytic meningitis, brain edema, rash, eosinophilia, and cytolytic hepatitis. She had been started on minocycline for inflammatory acne 21 days prior to the onset of symptoms. HS was diagnosed clinically and after exclusion of infectious causes. Minocycline was withdrawn and steroids were administered from the second day after presentation because of the severity of the symptoms. All signs resolved by the seventh day and steroids were tailed off over a period of 8 months.</p> <p>Conclusion</p> <p>Clinicians should maintain a high index of suspicion for serious adverse reactions to minocycline including lymphocytic meningitis and cerebral edema among HIV-positive patients, especially if they are of African origin. Safer alternatives should be considered for treatment of acne vulgaris. Early recognition of the symptoms and prompt withdrawal of the drug are important to improve the outcome.</p