CYP2E1 genotype and isoniazid-induced hepatotoxicity in patients treated for latent tuberculosis

Objective: To determine whether pharmacogenetic tests such as N-acetyltransferase 2 (NAT2) and cytochrome P4502E1 (CYP2E1) genotyping are useful in identifying patients prone to antituberculosis drug-induced hepatotoxicity in a cosmopolite population. Methods: In a prospective study we genotyped 89 patients treated with isoniazid (INH) for latent tuberculosis. INH-induced hepatitis (INH-H) or elevated liver enzymes including hepatitis (INH-ELE) was diagnosed based on the clinical diagnostic scale (CDS) designed for routine clinical practice. NAT2 genotypes were assessed by fluorescence resonance energy transfer probe after PCR analysis, and CYP2E1 genotypes were determined by PCR with restriction fragment length polymorphism analysis. Results: Twenty-six patients (29%) had INH-ELE, while eight (9%) presented with INH-H leading to INH treatment interruption. We report no significant influence of NAT2 polymorphism, but we did find a significant association between the CYP2E1 *1A/*1A genotype and INH-ELE (OR: 3.4; 95% CI:1.1-12; p=0.02) and a non significant trend for INH-H (OR: 5.9; 95% CI: 0.69-270; p=0.13) compared with other CYP2E1 genotypes. This test for predicting INH-ELE had a positive predictive value (PPV) of 39% (95% CI: 26-54%) and a negative predictive value (NPV) of 84% (95% CI: 69-94%). Conclusion: The genotyping of CYP2E1 polymorphisms may be a useful predictive tool in the common setting of a highly heterogeneous population for predicting isoniazid-induced hepatic toxicity. Larger prospective randomized trials are needed to confirm these result

Anti-apolipoprotein A-1 IgG as an independent cardiovascular prognostic marker affecting basal heart rate in myocardial infarction

Aims To assess the prognostic value of anti-apolipoprotein A-1 (anti-apoA-1) IgG after myocardial infarction (MI) and its association with major cardiovascular events (MACEs) at 12 months and to determine their association with resting heart rate (RHR), a well-established prognostic feature after MI. Anti-apoA-1 IgG have been reported in MI without autoimmune disease, but their clinical significance remains undetermined. Methods and results A total of 221 consecutive patients with MI were prospectively included, and all completed a 12-month follow-up. Major cardiovascular events consisted in death, MI, stroke, or hospitalization either for an acute coronary syndrome or heart failure. Resting heart rate was obtained on Holter the day before discharge under the same medical treatment. Neonate rat ventricular cardiomyocytes (NRVC) were used in vitro to assess the direct anti-apoA-1 IgG effect on RHR. During follow-up, 13% of patients presented a MACE. Anti-apoA-1 IgG positivity was 9% and was associated with a higher RHR (P = 0.0005) and higher MACE rate (adjusted OR, 4.3; 95% CI, 1.46-12.6; P = 0.007). Survival models confirmed the significant nature of this association. Patients with MACE had higher median anti-apoA-1 IgG values at admission than patients without (P = 0.007). On NRVC, plasma from MI patients and monoclonal anti-apoA-1 IgG induced an aldosterone and dose-dependent positive chronotropic effect, abrogated by apoA-1 and therapeutic immunoglobulin (IVIG) pre-incubation. Conclusions In MI patients, anti-apoA-1 IgG is independently associated with MACE at 1-year, interfering with a currently unknown aldosterone-dependent RHR determinant. Knowing whether anti-apoA-1 IgG assessment could be of interest to identify an MI patient subset susceptible to benefit from apoA-1/IVIG therapy remains to be demonstrate

Electron and Cooper-pair transport across a single magnetic molecule explored with a scanning tunneling microscope

A scanning tunneling microscope is used to explore the evolution of electron and Cooper-pair transport across single Mn-phthalocyanine molecules adsorbed on Pb(111) from tunneling to contact ranges. Normal-metal as well as superconducting tips give rise to a gradual transition of the Bardeen-Cooper-Schrieffer energy gap in the tunneling range into a zero-energy resonance close to and at contact. Supporting transport calculations show that in the normal-metal–superconductor junctions this resonance reflects the merging of in-gap Yu-Shiba-Rusinov states as well as the onset of Andreev reflection. For the superconductor-superconductor contacts, the zero-energy resonance is rationalized in terms of a finite Josephson current that is carried by phase-dependent Andreev and Yu-Shiba-Rusinov levels.Financial support by the Deutsche Forschungsgemeinschaft through Grant No. KR 2912/10-1, the FCT (Projects No. PTDC/FIS-NAN/4662/2014 and No. P2020-PTDC/FISNAN/3668/2014), and the MINECO-Spain (MAT2016-78625-C2) is acknowledged. J.L.L. acknowledges financial support from the ETH Zurich Postdoctoral Fellowship program

Spatial variability of soil phosphorus in the Fribourg canton, Switzerland

Phosphorus (P) is the second essential nutrient for plant growth but can become an ecological and economical concern in case of over-fertilization. Soil P dynamic is influenced by many parameters like soil physical-chemical properties and farming practices. A better understanding of the factors controlling its distribution is required to achieve best P crops management. In Switzerland, the FRIBO network was launched in 1987 and comprises of 250 sites covering a wide diversity of soils and three different land uses (croplands, grasslands and mountain pastures) across the Fribourg canton. A spatial investigation of the different P forms for the FRIBO network led to the following main conclusions: i) The P status in agricultural soils was significantly different among the three land uses encountered, with the highest mean values of available P found in croplands (from 2.12 to 81.3 mg.kg-1 according to the indicator used), whereas total P was more abundant in permanent grasslands (1186.2 mg.kg-1), followed by mountain pastures (1039.0 mg.kg-1) and croplands (935.0 mg.kg-1). A full characterization of the soil P status provides necessary data on P distribution related to soil properties and land use, and should help to develop more accurate estimation procedures and fertilization strategies in a near future; ii) Environmental variables derived from digital elevation model (DEM) only explained a small part of the spatial variation of the different P forms (20 to 25%). Thus, the geostatistic analyses revealed that land use play a major role in soil P distribution. However, this pattern was less visible for total P than for available P. Future studies should include more data points as well as additional variables such as parent material and soil type to accurately estimate the role of soil parameters on the distribution of P-related forms

Spatial variability of potassium in agricultural soils of the canton of Fribourg, Switzerland

Potassium (K) is a crucial element for plant nutrition and its availability and spatial distribution in agricultural soils is influenced by many agro-environmental factors. In Switzerland, a soil monitoring network (FRIBO) was established in 1987 with 250 sites distributed over the whole of the canton of Fribourg (representing 4% of the surface area of Switzerland), whose territory is shared between the Swiss Midlands and the Western Alp foothills. In this study area, diverse geological deposits (sandstone, marlstone, silts and calcareous rocks), soil types (Cambisols, Gleysols, Rendzinas, Luvisols and Fluvisols) and land uses (cropland, permanent grassland and mountain pasture) are present, making the network interesting for assessing the relative contribution of environmental variables and land use management on soil properties. The aims of the present study were to (i) characterize the soil K status in the Fribourg canton according to four different extraction methods; (ii) analyse the spatial variability of soil K in relation to land use, soil type, soil parent material and topography; (iii) evaluate the spatial predictability of K at the canton level; and (iv) analyse the implications for K fertilization management. The overall amount of soil total K averaged 13.6 g.kg-1 with significant variations across the sites (5.1-22.1 g.kg-1). The spatial distribution of total K was particularly influenced by soil parent materials, as suggested by a significant global spatial autocorrelation measure (Moran’s I10km = 0.43) and significant differences observed among soil types and soil parent materials. On the other hand, available mean K forms were significantly different among land uses, with the highest mean values of available K encountered in permanent grasslands, from 46.3 mg.kg-1 (water extraction) to 198 mg.kg-1 (acetate ammonium + EDTA extraction). All K forms showed similar spatial regional patterns for all spatial interpolation methods, with areas dominated by permanent grassland and crops presenting higher values. However, these trends were less pronounced for the available K forms due to the prevalence of on-farm management practices for these K forms and their high temporal variability. This hypothesis was supported by spatial clustering of low and/or high K fertility status that could be related to local particular farming practices. Grasslands require particular attention with regard to overall high K fertility status

The inositol Inpp5k 5-phosphatase affects osmoregulation through the vasopressin-aquaporin 2 pathway in the collecting system

Inositol Inpp5k (or Pps, SKIP) is a member of the inositol polyphosphate 5-phosphatases family with a poorly characterized function in vivo. In this study, we explored the function of this inositol 5-phosphatase in mice and cells overexpressing the 42-kDa mouse Inpp5k protein. Inpp5k transgenic mice present defects in water metabolism characterized by a reduced plasma osmolality at baseline, a delayed urinary water excretion following a water load, and an increased acute response to vasopressin. These defects are associated with the expression of the Inpp5k transgene in renal collecting ducts and with alterations in the arginine vasopressin/aquaporin-2 signalling pathway in this tubular segment. Analysis in a mouse collecting duct mCCD cell line revealed that Inpp5k overexpression leads to increased expression of the arginine vasopressin receptor type 2 and increased cAMP response to arginine vasopressin, providing a basis for increased aquaporin-2 expression and plasma membrane localization with increased osmotically induced water transport. Altogether, our results indicate that Inpp5k 5-phosphatase is important for the control of the arginine vasopressin/aquaporin-2 signalling pathway and water transport in kidney collecting duct

Convergent consequences of parthenogenesis on stick insect genomes

International audienceThe shift from sexual reproduction to parthenogenesis has occurred repeatedly in animals, but how the loss of sex affects genome evolution remains poorly understood. We generated reference genomes for five independently evolved parthenogenetic species in the stick insect genus Timema and their closest sexual relatives. Using these references and population genomic data, we show that parthenogenesis results in an extreme reduction of heterozygosity and often leads to genetically uniform populations. We also find evidence for less effective positive selection in parthenogenetic species, suggesting that sex is ubiquitous in natural populations because it facilitates fast rates of adaptation. Parthenogenetic species did not show increased transposable element (TE) accumulation, likely because there is little TE activity in the genus. By using replicated sexual-parthenogenetic comparisons, our study reveals how the absence of sex affects genome evolution in natural populations, providing empirical support for the negative consequences of parthenogenesis as predicted by theory

The beginning of a new era

With this editorial, the Swiss Psychological Society (SPS) is relaunching its journal under the new name Swiss Psychology Open (SPO), published by UbiquityPress. Originally founded by Jean Piaget in 1942 as the Schweizerische Zeitschrift für Psychologie und ihre Anwendungen [engl. Swiss Journal of Psychology and its Applications], SPO will continue to serve its original mission – in an open and accessible way

Vers une typologie des dispositifs hybrides de formation en enseignement supérieur

International audienceAssessing the effects of hybrid system requires a descriptive framework to understand and differentiate their effects. In this perspective, this article proposes a typology of hybrid system from their educational, organizational and material characteristics (modalities of articulation of presential and distant phases, teaching approaches, human support, forms of media and mediation related to the use of a techno-environment, degree of openness).L'évaluation des effets des dispositifs hybrides de formation en enseignement supérieur nécessite un cadre descriptif pour en comprendre les effets différenciés. Dans cette perspective, le présent article propose d'établir une typologie des dispositifs hybrides de formation à partir de leurs caractéristiques pédagogiques, organisationnelles et matérielles (modalités d'articulation des phases présentielles et distantes, accompagnement humain, formes de médiatisation et médiation liées à l'utilisation d'un environnement technopédagogique, degré d'ouverture). Il rend également compte, d'un point de vue méthodologique, de la manière dont les chercheurs investis dans le projet européen HySup (2009-12) ont progressivement élaboré ce cadre et en ont fait une première expérimentation

Arbovirus-Derived piRNAs Exhibit a Ping-Pong Signature in Mosquito Cells

The siRNA pathway is an essential antiviral mechanism in insects. Whether other RNA interference pathways are involved in antiviral defense remains unclear. Here, we report in cells derived from the two main vectors for arboviruses, Aedes albopictus and Aedes aegypti, the production of viral small RNAs that exhibit the hallmarks of ping-pong derived piwi-associated RNAs (piRNAs) after infection with positive or negative sense RNA viruses. Furthermore, these cells produce endogenous piRNAs that mapped to transposable elements. Our results show that these mosquito cells can initiate de novo piRNA production and recapitulate the ping-pong dependent piRNA pathway upon viral infection. The mechanism of viral-piRNA production is discussed