GAPDH is emerging as a key player in T cell development and function. To investigate the role of GAPDH in T cells, we generated a transgenic mouse model overexpressing GAPDH in the T cell lineage. ...Aged mice developed a peripheral Tfh-like lymphoma that recapitulated key molecular, pathological, and immunophenotypic features of human angioimmunoblastic T cell lymphoma (AITL). GAPDH induced non-canonical NF-κB pathway activation in mouse T cells, which was strongly activated in human AITL. We developed a NIK inhibitor to reveal that targeting the NF-κB pathway prolonged AITL-bearing mouse survival alone and in combination with anti-PD-1. These findings suggest the therapeutic potential of targeting NF-κB signaling in AITL and provide a model for future AITL therapeutic investigations.
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•Overexpression of GAPDH in T cell lineage in a mouse model recapitulates AITL disease•AITL tumors are characterized by a GAPDH induction of the NF-κB pathway•plck-GAPDH mice allow to model AITL disease for testing of new therapeutic strategies
Mondragón et al. find that transgenic mice overexpressing GAPDH in T cells develop lymphoma that recapitulates key features of human angioimmunoblastic T cell lymphoma (AITL), including activation of the non-canonical NF-κB pathway. Blocking NF-κB activity with an NIK inhibitor reduces human and mouse AITL growth.
En cette ère d’inclusion, force est d’admettre que les directions d’établissement scolaire, qui baignent ou non dans un contexte de diversité ethnoculturelle, linguistique et religieuse, ont intérêt ...à développer leur compétence interculturelle. Or, comment conscientiser les directions et savoir si elles ont développé une telle compétence ? Compte tenu d’un tel enjeu, l’objectif de cet article est de présenter le processus d’élaboration d’un questionnaire d’autoévaluation de la compétence interculturelle des directions d’établissement scolaire de langue française au Québec et au Nouveau-Brunswick, qui comprend 1) la recension de questionnaires portant sur cette compétence, 2) la construction d’une banque d’items, 3) le recueil de preuves basées sur le contenu, 4) l’élaboration de la version préliminaire du questionnaire d’autoévaluation, 5) le prétest et 6) l’accumulation de preuves basées sur la structure interne. Finalement, un questionnaire d’autoévaluation préliminaire de 43 items est proposé. Les limites de la recherche et les retombées de ce questionnaire d’autoévaluation préliminaire sont mentionnées en conclusion.
•A method for assessing wood density on large increment cores sampling is described.•The method based on X-ray CT scanning is fast (3000 samples/h) and semi-automatic.•The method was found to be ...accurate and unbiased for 5 mm diameter cores.•The software outputs radial profiles of density.•Correct mean density taking into account radial variations can be computed.•The method is yet applied by the French forest inventory on thousands of cores.
Increment cores are often used in wood science for measuring wood density of trees non destructively and at large scale, for instance with the objective to assess the available biomass in a forest resource. This paper presents a software allowing to measure by X-ray computed tomography (CT) the wood density of thousands increment cores. The software is able to process 3000 cores per hour semi-automatically. Manual intervention may be required to control and eventually adjust the positioning of the cores. The software was tested on 30 trees from 13 temperate species. Two increment cores were taken from each tree: one 5 mm diameter core and one 4 mm diameter core. The obtained CT density of the cores was compared to reference data obtained by volume and mass measurement on the 5 mm cores. The reference data were used for tuning the software settings by leave-one-out cross validation method. The obtained root mean square error was below 10 kg/m3 (1.7%) for the 5 mm cores. For the 4 mm cores, the root mean square difference with the reference density of the 5 mm cores was 25 kg/m3 (4.2%).
The incidence of oropharyngeal cancers (OPC) is increasing in the world. Among OPC, those induced by human papillomaviruses have a better prognosis than non-HPV-associated OPC. The objective of this ...study was to highlight the relevance of HPV16 load, HPV16 DNA integration and HPV16-L1 serology on progression-free survival and overall survival of OPC patients. The PAPILLOPHAR cohort consists of 362 patients with oropharyngeal squamous cell carcinomas prospectively followed up for 5 years after treatment. Tumor biopsies and sera were collected at inclusion to investigate tumor HPV DNA/RNA characteristics and HPV16 L1 serology, respectively. Twenty-seven percent of tumor biopsies were HPV DNA- and RNA-positive and HPV16 represented 93% of HPV-positive cases. Among them, neither HPV16 viral load nor HPV16 DNA integration was associated with overall survival (OS) or progression-free survival (PFS). In contrast, high anti-HPV16 L1 antibody titers were significantly associated with a better OS and PFS. This study reveals that HPV16 load and integration are not relevant prognosis biomarkers in OPC patients.
Clinical Relevance: High levels of HPV16 L1 antibodies may be useful to predict OPC patient outcome following treatment.
ClinicalTrials.gov Identifier: NCT00918710, May 2017.
Purpose
This study examined patient-related outcome measures (PROMs) after repair of ventral primary or incisional hernias using Symbotex™ composite mesh (SCM), a novel three-dimensional ...collagen-coated monofilament polyester textile.
Methods
Pre-operative, peri-operative, and post-operative data were obtained from the French “Club Hernie” registry with 12- and 24-month follow-up.
Results
One-hundred consecutive patients (mean age 62.0 ± 13.7; 51% female) underwent repair of 105 hernias: primary (39/105, 37.1%, defect area 5.2 ± 5.6 cm
2
) and incisional (66/105, 62.9%, 31.9 ± 38.7.8 cm
2
). The mean BMI was 29.7 (± 5.6 kg/m
2
). American Society of Anesthesiologists classifications were I 39.4%, II 37.4% and III 23.2%. 75% had risk factors for healing and/or dissection. Of 38 primary repairs, 37 were completed laparoscopically (combined approach
n
= 1), and of 62 incisional hernia repairs, 40 were completed laparoscopically, and 20 by open repair (combined approach
n
= 2). Laparoscopic was quicker than open repair (36.2 ± 23.5 min vs. 67.4 ± 25.8,
p
< 0001). Before surgery, 86.3% of hernias were reported to cause discomfort/pain or dysesthesia. At 24 months (93 of 100 patients), 91 (97.8%) reported no lump and 81 (87.1%) no pain or discomfort. Of 91 patients, 86 (94.5%) rated their repair “good” or “excellent.” There were nine non-serious, surgeon-detected adverse events (ileus,
n
= 3; seroma,
n
= 6) and one hernia recurrence (6–12 months).
Conclusions
Compared to baseline, open and laparoscopic surgery improved PROMs 24 months after primary and incisional hernia repair. Minimal complications and recurrence support the long-term efficacy of SCM.
High-risk human papillomavirus (hrHPVs), particularly HPV16 and HPV18, are the etiologic factors of ano-genital cancers and some head and neck squamous cell carcinomas (HNSCCs). Viral E6 and E7 ...oncoproteins, controlled at both transcriptional and post-transcriptional levels, drive hrHPVs-induced carcinogenesis. In the present study, we investigated the implication of the DEAD-box helicase eukaryotic translation initiation factor 4A3 (eIF4A3,) an Exon Junction Complex factor, in the regulation of HPV16 gene expression. Our data revealed that the depletion of the factor eIF4A3 up-regulated E7 oncoprotein levels. We also showed that the inhibition of the nonsense-mediated RNA decay (NMD) pathway, resulted in the up-regulation of E7 at both RNA and protein levels. We therefore proposed that HPV16 transcripts might present different susceptibilities to NMD and that this pathway could play a key role in the levels of expression of these viral oncoproteins during the development of HPV-related cancers.
Sex pheromones are intraspecific olfactory signals emitted by one sex to attract a potential mating partner. Behavioural responses to sex pheromones are generally highly stereotyped. However, they ...can be modulated by experience, as male moths previously exposed to female sex pheromone respond with a lower threshold upon further detection, even after long delays. Here, we address the question of the neural mechanisms underlying such long-term modulation. As previous work has shown increased responses to pheromone in central olfactory neurons, we asked whether brief exposure to the pheromone increases input activity from olfactory receptor neurons. Males pre-exposed to sex pheromone exhibited increased peripheral sensitivity to the main pheromone component. Among nine antennal genes targeted as putatively involved in pheromone reception, one encoding a pheromone-binding protein showed significant upregulation upon exposure. In the primary olfactory centre (antennal lobe), the neural compartment processing the main pheromone component was enlarged after a brief pheromone exposure, thus suggesting enduring structural changes. We hypothesise that higher peripheral sensitivity following pre-exposure leads to increased input to the antennal lobe, thus contributing to the structural and functional reorganization underlying a stable change in behaviour.
Field pea (Pisum sativum L.) is an attractive crop for human and livestock nutrition and an important contributor to low-input farming systems. Multiple environmental challenges face field pea ...production and penalize yield regularity. The work-package 1 of the French National ANR project PeaMUST aims at identifying efficient gene combinations for yield stability in low-input cropping systems through genomic selection. Genomic selection is a new breeding method that uses increasingly abundant genomic information and statistical modelling to select superior genotypes based on genomic estimated breeding values (GEBVs). The main goals are: 1- to build a genomic selection prediction equation for yield stability in low-input cropping systems, 2- to implement a genomic selection program and, 3- to evaluate the genetic progress obtained after one and two genomic selection cycles.
Dans un contexte de diversité ethnoculturelle, linguistique et religieuse, plusieurs recherches mentionnent que les directions d’établissement scolaire doivent posséder une compétence interculturelle ...de même que promouvoir l’équité et la justice sociale pour assurer la réussite éducative des élèves (Potvin, 2014; Shields, 2018). Or, comment les directions d’établissement scolaire peuvent-elles évaluer le plus objectivement possible le développement de leur compétence interculturelle? Pour répondre à cette question, une première étude a présenté un modèle de compétence interculturelle pour les directions d’établissement scolaire (Gélinas-Proulx, Labelle & Jacquin, 2017). Bien que cette étude ait offert un cadre théorique et conceptuel exhaustif, la présente recherche vise à aller plus loin et valide un questionnaire d’autoévaluation de la compétence interculturelle spécifiquement conçu pour les directions d’établissement scolaire. Cette validation fut effectuée auprès des directions d’établissements scolaires de langue française du Québec et du Nouveau-Brunswick. Le processus de validation du questionnaire a comporté les étapes suivantes : 1) la recension de questionnaires portant sur la compétence interculturelle, 2) la rédaction d’une banque d’items, 3) la validation de contenu, 4) l’élaboration du questionnaire, 5) le prétest et 6) la validation de construit. Au final, un questionnaire d’autoévaluation de 20 items est proposé afin que les directions d’établissement scolaire puissent mieux évaluer leurs connaissances, leurs attitudes et leurs habiletés en matière de compétence interculturelle.
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