Lack of association of methylenetetrahydrofolate reductase 677C\u3eT mutation with coronary artery disease in a Pakistani population

Pakistanis belong to the South Asian population which has the highest known rate of coronary artery disease. Folic acid deficiency also appears to be highly prevalent in this population. Methylenetetrahydrofolate reductase (MTHFR) 677C\u3eT polymorphism decreases the activity of this enzyme and can be associated with mild to moderate hyperhomocysteinemia in homozygotes, particularly when there is folic acid deficiency, as well as with coronary artery disease. To assess the value of genotyping the MTHFR 677C\u3eT dimorphism, we carried out a case-control study of dimorphism 677C\u3eT for putative association with myocardial infarction (MI) among Pakistani nationals. We investigated a sample population of 622 Pakistanis consisting of 225 controls and 397 patients with clinical diagnosis of acute MI (AMI). MTHFR C677T alleles were determined by assays based on polymerase chain reaction and restriction endonuclease analysis. Frequencies of C alleles were 0.87 among controls and 0.86 among AMI patients. The MTHFR 677C\u3eT dimorphism showed no association with MI (chi(2) = 0.25, 1df, P=0.62), serum levels of folate and vitamin B12 and plasma level of vitamin B6. A significant association, however, was found between homozygous 677T genotype and plasma levels of homocysteine. Multivariate analysis of the data showed that in case of log homocysteine, age and MTHFR genotypes were significantly different (PT polymorphism, though associated with homocysteine levels, confers no significant risk of coronary artery disease in the Pakistani population investigated here. We suggest that the higher incidence of AMI in South Asia occurs through mechanisms other than the MTHFR related pathways

Bilan et perspectives des deux écoles techniques « notions et techniques en écologie » organisées par le Département EFPA

La création du Département «Écologie des Forêts, Prairies et milieux Aquatiques» a suscité de la part des personnels techniques concernés une volonté d’intégration collective sous le concept fédérateur de l’écologie. Pour cela deux écoles techniques ont été organisées sur des notions et méthodes d’écologie par un Comité de pilotage composé de techniciens et de scientifiques. L’objectif visait à familiariser les techniciens aux concepts de l’écologie et à les aider à se situer dans les thématiques de recherche du Département EFPA. Enfin, il s’agissait d’instaurer une communauté de pratique autour de l’écologie. Ces écoles ont rassemblé 79 personnes, en proposant visites sur le terrain et séances en salle. Deux animations ont particulièrement été appréciées, l’une sous forme d’un jeu en préambule, l’autre sous forme de présentations par des binômes techniciens/chercheurs. Les participants sont plutôt convaincus d’avoir progressé sur les notions en écologie et ils ont la volonté d’aller plus loin avec la création d’un Réseau de Technicien en Ecologie (RTE), la mise en place d’une liste de diffusion et l’organisation régulière de rencontres entre membres du réseau

Metagenomics of the Deep Mediterranean, a Warm Bathypelagic Habitat

BACKGROUND: Metagenomics is emerging as a powerful method to study the function and physiology of the unexplored microbial biosphere, and is causing us to re-evaluate basic precepts of microbial ecology and evolution. Most marine metagenomic analyses have been nearly exclusively devoted to photic waters. METHODOLOGY/PRINCIPAL FINDINGS: We constructed a metagenomic fosmid library from 3,000 m-deep Mediterranean plankton, which is much warmer (approximately 14 degrees C) than waters of similar depth in open oceans (approximately 2 degrees C). We analyzed the library both by phylogenetic screening based on 16S rRNA gene amplification from clone pools and by sequencing both insert extremities of ca. 5,000 fosmids. Genome recruitment strategies showed that the majority of high scoring pairs corresponded to genomes from Rhizobiales within the Alphaproteobacteria, Cenarchaeum symbiosum, Planctomycetes, Acidobacteria, Chloroflexi and Gammaproteobacteria. We have found a community structure similar to that found in the aphotic zone of the Pacific. However, the similarities were significantly higher to the mesopelagic (500-700 m deep) in the Pacific than to the single 4000 m deep sample studied at this location. Metabolic genes were mostly related to catabolism, transport and degradation of complex organic molecules, in agreement with a prevalent heterotrophic lifestyle for deep-sea microbes. However, we observed a high percentage of genes encoding dehydrogenases and, among them, cox genes, suggesting that aerobic carbon monoxide oxidation may be important in the deep ocean as an additional energy source. CONCLUSIONS/SIGNIFICANCE: The comparison of metagenomic libraries from the deep Mediterranean and the Pacific ALOHA water column showed that bathypelagic Mediterranean communities resemble more mesopelagic communities in the Pacific, and suggests that, in the absence of light, temperature is a major stratifying factor in the oceanic water column, overriding pressure at least over 4000 m deep. Several chemolithotrophic metabolic pathways could supplement organic matter degradation in this most depleted habitat

Characterization of greater middle eastern genetic variation for enhanced disease gene discovery

The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia1-3, has resulted in an elevated burden of recessive disease4. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Greenhouse gas emissions after application of landfilled paper mill sludge for land reclamation of a nonacidic mine tailings site

Large areas of mine tailings are reclaimed by applying organic amendments such as paper mill sludge (PMS). Although mining industries can use PMS freshly generated by paper mills, operational constraints on paper industries make temporary landfilling of this material an unavoidable alternative for the paper industries, creating the most prominent PMS source for mining industries. This study aimed to quantify soil greenhouse gas (GHG) emissions (N2O, CO2, and CH4) after application of landfilled PMS (LPMS; i.e., excavated from a landfill site at a paper mill) and LPMS combined with a seeding treatment of white clover (Trifolium repens L.) on nonacidic mine tailings site prior to reforestation. Soil N2O, CO2, and CH4 fluxes were measured after applications of 50 and 100 Mg dry LPMS ha−1 during two consecutive snowfree seasons on two adjacent sites; LPMS was applied once in the first season. The LPMS application increased N2O emissions (7.6 to 34.7 kg N2O-N ha−1, comprising 1.04 to 2.43% of applied N) compared with the unamended control during the first season; these emissions were negligible during the second season. The LPMS application increased CO2 emissions (~5800 to 11,400 kg CO2–C ha−1, comprising 7 to 27% of applied C) compared with the unamended control on both sites and in both seasons. Fluxes of CH4 were negligible. White clover combined with LPMS treatments did not affect soil GHG emissions. These new GHG emission factors should be integrated into life-cycle analyses to evaluate the C footprint of potential symbioses between the mining and paper industries. Future research should focus on the effect of PMS applications on soil GHG emissions from a variety of mine tailings under various management practices and climatic conditions to plan responsible and sustainable land reclamation

Développement de méthodes alternatives à l'expérimentation animale pour la détection du potentiel de sensibilisation de contact

L'allergie de contact est une hypersensibilité retardée à médiation cellulaire, initialisée au niveau de la peau par la cellule de Langerhans, cellule dendritique spécialisée, au contact des haptènes. Actuellement, seuls des tests in vivo réglementaire sont disponibles pour la détermination du potentiel sensibilisant des produits chimiques.L'objectif de ce travail a été de développer deux nouvelles méthodes : le LLNA-IL-2 dérivé de la méthode in vivo réglementaire LLNA (Local Lymph Node Assay), et la lignée myéloïde cellulaire MUTZ-3 comme modèle in vitro.La première approche a consisté en l'amélioration du LLNA par la mesure de la production ex-vivo d'IL-2 par les cellules ganglionnaires. Après comparaison de diverses techniques de dosages et optimisation du protocole, les performances de cette méthode baptisée LLNA-IL-2 ont été évaluées à l'aide d'un panel de sensibilisants et irritants prototypiques. Les résultats obtenus sont comparables qualitativement et quantitativement à ceux du LLNA radioactif (P. Azam et al.. 2004 Toxicology. Sous presse).Le développement d'un test prédictif in-vitro, réalisé sur la lignée cellulaire myéloïde humaine. Cytoline dépendante et CD34 positive, MUTZ- constituait la deuxième partie du projet. Après caractérisation du phénotype monocytaire de la lignée, une évaluation de sa capacité de réponse à un panel d'irritants et de sensibilisants faibles, modérés ou forts, a été effectuée par cytométrie en flux sur l'expression d'une série de marqueurs d'activation (HLA-DR, CD54, CD86, CD40, B7-H1, B7-H2, B7-DC). En particulier avec CD86, l'ensemble des sensibilisants testés induisant une réponse positive spécifique.D'autres part, dans des expériences préliminaires, la lignée MUTZ-3 a présenté des capacités uniques de différenciation en cellules de types dendritiques.Ces données suggèrent la possibilité du développement d'un modèle in-vitro de criblage (MUTZ-3 non différenciées), d'un modèle in-vitro hautement différencié (MUTZ-3 différenciées) et de comparer leurs performances avec les tests in-vivo (LLNA) ou en cours de développement (PBMC).MONTPELLIER-BU Pharmacie (341722105) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF