A balanced transcription between telomerase and the telomeric DNA-binding proteins TRF1, TRF2 and Pot1 in resting, activated, HTLV-1-transformed and Tax-expressing human T lymphocytes

BACKGROUND: The functional state of human telomeres is controlled by telomerase and by a protein complex named shelterin, including the telomeric DNA-binding proteins TRF1, TRF2 and Pot1 involved in telomere capping functions. The expression of hTERT, encoding the catalytic subunit of telomerase, plays a crucial role in the control of lymphocyte proliferation by maintaining telomere homeostasis. It has been previously found that hTERT activity is down-regulated by the human T cell leukaemia virus type 1 (HTLV-1) Tax protein in HTLV-1 transformed T lymphocytes. In this study, we have examined the effects of Tax expression on the transcriptional profile of telomerase and of shelterin in human T lymphocytes. RESULTS: We first provide evidence that the up-regulation of hTERT transcription in activated CD4+ T lymphocytes is associated with a down-regulation of that of TERF1, TERF2 and POT1 genes. Next, the down-regulation of hTERT transcription by Tax in HTLV-1 transformed or in Tax-expressing T lymphocytes is found to correlate with a significant increase of TRF2 and/or Pot1 mRNAs. Finally, ectopic expression of hTERT in one HTLV-1 T cell line induces a marked decrease in the transcription of the POT1 gene. Collectively, these observations predict that the increased transcriptional expression of shelterin genes is minimizing the impact on telomere instability induced by the down-regulation of hTERT by Tax. CONCLUSION: These findings support the notion that Tax, telomerase and shelterin play a critical role in the proliferation of HTLV-1 transformed T lymphocytes

Randomised pharmacokinetic trial of rifabutin with lopinavir/ritonavir-antiretroviral therapy in patients with HIV-associated tuberculosis in Vietnam.

BACKGROUND: Rifampicin and protease inhibitors are difficult to use concomitantly in patients with HIV-associated tuberculosis because of drug-drug interactions. Rifabutin has been proposed as an alternative rifamycin, but there is concern that the current recommended dose is suboptimal. The principal aim of this study was to compare bioavailability of two doses of rifabutin (150 mg three times per week and 150 mg daily) in patients with HIV-associated tuberculosis who initiated lopinavir/ritonavir-based antiretroviral therapy in Vietnam. Concentrations of lopinavir/ritonavir were also measured. METHODS: This was a randomized, open-label, multi-dose, two-arm, cross-over trial, conducted in Vietnamese adults with HIV-associated tuberculosis in Ho Chi Minh City (Clinical trial registry number NCT00651066). Rifabutin pharmacokinetics were evaluated before and after the introduction of lopinavir/ritonavir -based antiretroviral therapy using patient randomization lists. Serial rifabutin and 25-O-desacetyl rifabutin concentrations were measured during a dose interval after 2 weeks of rifabutin 300 mg daily, after 3 weeks of rifabutin 150 mg daily with lopinavir/ritonavir and after 3 weeks of rifabutin 150 mg three times per week with lopinavir/ritonavir. RESULTS: Sixteen and seventeen patients were respectively randomized to the two arms, and pharmacokinetic analysis carried out in 12 and 13 respectively. Rifabutin 150 mg daily with lopinavir/ritonavir was associated with a 32% mean increase in rifabutin average steady state concentration compared with rifabutin 300 mg alone. In contrast, the rifabutin average steady state concentration decreased by 44% when rifabutin was given at 150 mg three times per week with lopinavir/ritonavir. With both dosing regimens, 2 - 5 fold increases of the 25-O-desacetyl- rifabutin metabolite were observed when rifabutin was given with lopinavir/ritonavir compared with rifabutin alone. The different doses of rifabutin had no significant effect on lopinavir/ritonavir plasma concentrations. CONCLUSIONS: Based on these findings, rifabutin 150 mg daily may be preferred when co-administered with lopinavir/ritonavir in patients with HIV-associated tuberculosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00651066

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

One health, une seule santé

One Health, « Une seule santé », est une stratégie mondiale visant à développer les collaborations interdisciplinaires pour la santé humaine, animale et environnementale. Elle promeut une approche intégrée, systémique et unifiée de la santé aux échelles locale, nationale et mondiale, afin de mieux affronter les maladies émergentes à risque pandémique, mais aussi s'adapter aux impacts environnementaux présents et futurs. Bien que ce mouvement s’étende, la littérature en français reste rare. Traduit de l’anglais, coordonné par d’éminents épidémiologistes et s'appuyant sur un large panel d' approches scientifiques rarement réunies autour de la santé, cet ouvrage retrace les origines du concept et présente un contenu pratique sur les outils méthodologiques, la collecte de données, les techniques de surveillance et les plans d’étude. Il combine recherche et pratique en un seul volume et constitue un ouvrage de référence unique pour la santé mondiale

Comparaison du retrait dans les marnes carbonatées et les sols argileux traités à la chaux

Le retrait-gonflement des sols argileux est à l’origine de nombreuses pathologies à cause des tassements différentiels engendrés par leurs variations de teneur en eau. Le développement d’un essai de retrait volumique automatisé a permis d’observer que les sols argileux ont une amplitude de déformation en retrait plus importante que les marnes, dont la microstructure doit jouer un rôle majeur en empêchant les déformations. Le retrait sur une marne décarbonatée ou une argile carbonatée confirme cette hypothèse alors qu’un essai de retrait en présence de gypse montre le rôle particulier des ions CO32-. Par comparaison, la structure acquise par un sol argileux traité à la chaux modifie la forme de la courbe de retrait et empêche pratiquement toute déformation. Enfin, si la quantité de carbonates créant un squelette rigide et le traitement à la chaux semblent contrôler la courbe de retrait du sol, d’autres paramètres comme leur répartition, leur granulométrie ou bien la densité du sol ont également une influence

Role of carbonate on the swelling/shrinkage of clayey soils

In the past decades, the succession of several periods of drought caused damages on individual constructions in France. After the summer heat in 2003, an increasing number of pathologies with cracks appeared consequently to soil deformation under foundations because of the presence of sensitive clay. Indeed, smectites may swell and shrink when the soil water content varies. So characterize the swelling/shrinkage potential of soils after identifying the presence of clay represents a real challenge to reduce expensive reparations on damaged constructions and prevent new buildings to sinister. Experiments were conducted on the two major clayey materials as named Romainville’s green clay and Argenteuil’s blue marl and at the origin of the pathologies encountered near to Paris. After the geotechnical, physico-chemical and mineralogical characterization of materials extracted from a gypsum carrier, mechanical tests were applied to better understand the relation between microstructural characteristics of soils and macroscopic behaviour. An automatised instrumented apparatus developed in LCPC to measure the volumetric shrinkage were uses as well as the free swell test (Makki, 2008). Several parameters impacting to the soil behaviour were identified as the soil density, the numbers of humidification/desiccation cycles, the sample structure (intact or compacted after destructurated soil sample) and the presence of carbonates. This last parameter appears as determining as it can modify the soil sensitivity, compared to the same soils with similar clay. Between aggregates, the carbonates may form cementation submitted to alteration under dry/wet cycles. This cementation, we tried to put in evidence from observations by scanning electron and optical microscopies completed by porosimetric measurement by mercury intrusion, reduce the soil deformation. So, such parameters must be considered in the classification of soil sensitivity to swelling-shrinkage

Les légumineuses écrivent l'avenir

BAPGEAPSIDijon : les légumineuses écrivent l’avenir. Dans le cadre de ses 70 ans, l’Institut National de la Recherche Agronomique (INRA) tient aujourd’hui, sur le parvis de la gare de Dijon, un stand consacré aux légumineuses. Question à 1 000 € : de quoi 2016 est-elle l’année internationale ? La courtoisie au volant ? La politesse avec ses voisins ? Les Pokémon ? Raté. 2016 n’est rien de moins que l’année internationale des légumineuses. L’INRA est de la partie grâce à un pôle spécifique intégré à l’Unité Mixte de Recherche Agroécologie. Son nom de code : Génétiques et environnementaux de l’adaptation des plantes à des systèmes de culture innovants (Geapsi). Il cherche, notamment, à comprendre ce que les légumineuses peuvent apporter à l’agriculture et à l’alimentation de demain. L’équipe du pôle Geapsi participe, ainsi, à la création de nouvelles variétés de légumineuses, grâce au croisement de différentes plantes, sur des critères de rendement ou encore de résistance au stress hydrique. Sur un stand, ce mercredi, sur le parvis de la gare et lors des journées portes ouvertes, ce week-end, l’Inra rappellera qu’« aux côtés des instituts techniques et des acteurs privés, il s’engage dans les orientations stratégiques de la France pour le développement de protéines durables en alimentation animale et humaine, notamment en faisant connaître les atouts nutritionnels et environnementaux des légumineuses à graines ». Les légumineuses ont, en effet, de nombreux atouts : elles permettent de fixer l’azote atmosphérique et donc de limiter l’utilisation de pesticides, qui peuvent être synonymes de pollution. Elles permettent, aussi, la diminution des émissions de gaz à effet de serre. Les légumineuses sont, par ailleurs, très riches en protéines, ce qui est très intéressant pour l’alimentation animale, particulièrement pour la volaille, les porcs ou l’aquaculture. Du côté de la santé, la consommation régulière de légumineuses pourrait, aussi, aider à prévenir les maladies cardio-vasculaires et le diabète. Enfin, l’utilisation de graines entières des légumineuses ou de farine pourrait permettre de développer des produits alimentaires riches en protéines, équilibrés et adaptés aux régimes sans gluten ou végétariens (pâtes avec légumineuses, steaks végétaux…). Les légumineuses représentent finalement un fort potentiel d’innovation pour les industriels de l’alimentation ou même les grands chefs. Pas mal, dans un contexte où Dijon va bientôt se doter d’une Cité de la gastronomie

Direct One-Step Seedless Hydrothermal Growth of ZnO Nanostructures on Zinc: Primary Study for Photocatalytic Roof Development for Rainwater Purification

To shift towards the greener city, photocatalytic urban infrastructures have emerged as a promising solution for pollution remediation. To reach this goal, the large bandgap semiconductors, such as nontoxic Zinc Oxide (ZnO), already proved their excellent photocatalytic performances. However, integrating and developing cost-effective and greener photocatalytic surfaces with an easily scaled-up synthesis method and without energy and chemical product overconsumption is still challenging. Therefore, this work proposes to develop a depolluting Zinc (Zn) roof covered by ZnO nanostructures (NSs) using a one-step seedless hydrothermal growth method in 2 h. The feasibility of this synthesis was firstly studied on small areas of Zn (1.25 cm2) before being scaled up to medium-sized areas (25 cm2). The efficiency of this functionalization route for ZnO NSs grown without seed layer was attributed to the presence of Zn2+ sites and the native oxide film on the Zn surface. Their photocatalytic efficiency was demonstrated by removing in less than 3 h the Methylene Blue (MB) and Acid Red 14 (AR14) in both DI water and rainwater under UV-light. Promising results were also recorded under solar light. Therefore, the photocatalytic Zn roof functionalized by ZnO NSs is a promising route for rainwater purification by photocatalysis