topIb, a phylogenetic hallmark gene of Thaumarchaeota encodes a functional eukaryote-like topoisomerase IB

International audienceType IB DNA topoisomerases can eliminate torsional stresses produced during replication and transcription. These enzymes are found in all eukaryotes and a short version is present in some bacteria and viruses. Among prokaryotes, the long eukaryotic version is only observed in archaea of the phylum Thau-marchaeota. However, the activities and the roles of these topoisomerases have remained an open question. Here, we demonstrate that all available thaumar-chaeal genomes contain a topoisomerase IB gene that defines a monophyletic group closely related to the eukaryotic enzymes. We show that the topIB gene is expressed in the model thaumarchaeon Ni-trososphaera viennensis and we purified the recom-binant enzyme from the uncultivated thaumarchaeon Candidatus Caldiarchaeum subterraneum. This enzyme is active in vitro at high temperature, making it the first thermophilic topoisomerase IB characterized so far. We have compared this archaeal type IB enzyme to its human mitochondrial and nuclear counterparts. The archaeal enzyme relaxes both negatively and positively supercoiled DNA like the eukaryotic enzymes. However, its pattern of DNA cleavage specificity is different and it is resistant to camptothecins (CPTs) and non-CPT Top1 inhibitors, LMP744 and lamellarin D. This newly described ther-mostable topoisomerases IB should be a promising new model for evolutionary, mechanistic and structural studies

C5b9 Deposition in Glomerular Capillaries Is Associated With Poor Kidney Allograft Survival in Antibody-Mediated Rejection

C4d deposition in peritubular capillaries (PTC) reflects complement activation in antibody-mediated rejection (ABMR) of kidney allograft. However, its association with allograft survival is controversial. We hypothesized that capillary deposition of C5b9—indicative of complement-mediated injury—is a severity marker of ABMR. This pilot study aimed to determine the frequency, location and prognostic impact of these deposits in ABMR. We retrospectively selected patients diagnosed with ABMR in two French transplantation centers from January 2005 to December 2014 and performed C4d and C5b9 staining by immunohistochemistry. Fifty-four patients were included. Median follow-up was 52.5 (34.25–73.5) months. Thirteen patients (24%) had C5b9 deposits along glomerular capillaries (GC). Among these, seven (54%) had a global and diffuse staining pattern. Twelve of the C5b9+ patients also had deposition of C4d in GC and PTC. C4d deposits along GC and PTC were not associated with death-censored allograft survival (p = 0.42 and 0.69, respectively). However, death-censored allograft survival was significantly lower in patients with global and diffuse deposition of C5b9 in GC than those with a segmental pattern or no deposition (median survival after ABMR diagnosis, 6 months, 40.5 months and 44 months, respectively; p = 0.015). Double contour of glomerular basement membrane was diagnosed earlier after transplantation in C5b9+ ABMR than in C5b9– ABMR (median time after transplantation, 28 vs. 85 months; p = 0.058). In conclusion, we identified a new pattern of C5b9+ ABMR, associated with early onset of glomerular basement membrane duplication and poor allograft survival. Complement inhibitors might be a therapeutic option for this subgroup of patients

Evolution de la qualité de vie et du profil émotionnel chez des patients anxieux, avant et après la prise en charge en hôpital de jour

POITIERS-BU Médecine pharmacie (861942103) / SudocSudocFranceF

Advances in Human B19 Erythrovirus Biology▿

Since its discovery, human parvovirus B19 (B19V), now termed erythrovirus, has been associated with many clinical situations (neurological and myocardium infections, persistent B19V DNAemia) in addition to the prototype clinical manifestations, i.e., erythema infectiosum and erythroblastopenia crisis. In 2002, the use of new molecular tools led to the characterization of three different genotypes of human B19 erythrovirus. Although the genomic organization is conserved, the geographic distribution of the different genotypes varies worldwide, and the nucleotidic divergences can impact the molecular diagnosis of B19 virus infection. The cell cycle of the virus remains partially unresolved; however, recent studies have shed light on the mechanism of cell entry and the interactions of B19V proteins with apoptosis pathways

Influenza virus nucleoprotein: structure, RNA binding, oligomerization and antiviral drug target.

International audienceThe nucleoprotein (NP) of influenza virus covers the viral RNA entirely and it is this NP-RNA complex that is the template for transcription and replication by the viral polymerase. Purified NP forms a dynamic equilibrium between monomers and small oligomers, but only the monomers can oligomerize onto RNA. Therefore, drugs that stabilize the monomers or that induce abnormal oligomerization may have an antiviral effect, as would drugs that interfere with RNA binding. Crystal structures have been produced for monomeric and dimeric mutants, and for trimers and tetramers; high-resolution electron microscopy structures have also been calculated for the viral NP-RNA complex. We explain how these structures and the dynamic oligomerization equilibrium of NP can be and have been used for anti-influenza drug development

Prevalence and Risk Factors of Noncontrolled and Resistant Arterial Hypertension in Renal Transplant Recipients

International audienceBACKGROUND:Arterial hypertension (HT) is common in renal transplant recipients (RTRs). Control of HT is not optimal in this high-risk population despite recommendations for target blood pressure levels under 130/80 mm Hg.METHODS:We performed a cross-sectional analysis of the prevalence of uncontrolled HT, and using a Cox regression model, we identified the risk factors associated with resistant HT.RESULTS:Eight hundred eleven RTRs (>1 year after transplantation) were included. A total of 10.5% were normotensive (<130/80 mm Hg without treatment), 41% had controlled HT, 32.5% uncontrolled HT, and 16% resistant HT. In univariate analysis, compared to controlled HT, the RH group had significantly higher body mass index and older donors, delayed graft function, prevalence of metabolic syndrome (69.2 vs. 51.9%), fast glycemia and glycated hemoglobin, albuminuria, triglycerides and uric acid levels, and worse measured glomerular filtration rate (mGFR). In multivariate analysis, recipient age (P < 0,001), mGFR (P = 0.037), albuminuria (P < 0.001), and metabolic syndrome (P = 0.007) were significantly associated with RH. Association of metabolic syndrome with RH was much stronger than each of its components.CONCLUSION:Our data show that despite the recommendations issued by scientific societies, blood pressure control in RTRs is far from the recommended targets. At least a third of our patients (uncontrolled HT) did not receive optimal treatment and suffered therapeutic inertia. Decreased mGFR, metabolic syndrome, and urinary albumin excretion emerged as strong predictors of poor HT control. Whether prevention and management of the metabolic syndrome and reduction of albuminuria could help to more consistently reach the blood pressure recommended targets deserves further investigation

Reinforcement learning with formal performance metrics for quadcopter attitude control under non-nominal contexts

International audienceWe explore the reinforcement learning approach to designing controllers by extensively discussing the case of a quadcopter attitude controller. We provide all details allowing to reproduce our approach, starting with a model of the dynamics of a crazyflie 2.0 under various nominal and non-nominal conditions, including partial motor failures and wind gusts. We develop a robust form of a signal temporal logic to quantitatively evaluate the vehicle's behavior and measure the performance of controllers. The paper thoroughly describes the choices in training algorithms, neural net architecture, hyperparameters, observation space in view of the different performance metrics we have introduced. We discuss the robustness of the obtained controllers, both to partial loss of power for one rotor and to wind gusts and finish by drawing conclusions on practical controller design by reinforcement learning

La toxoplasmose, une complication exceptionnelle mais grave chez le transplanté rénal : à propos de deux observations

International audienceToxoplasma infection is uncommon after renal transplantation. As a result, Toxoplasma gondii is often missed from the list of microbial agents which may be responsible of an infectious complication after renal transplantation. However, establishing this diagnosis is very important because toxoplasmosis can be life-threatening in an immunocompromised host, particularly when the diagnosis is too delayed. Here we report two cases of severe toxoplasmosis after renal transplantation. In the first case, primary infection transmitted by a cat developed in a seronegative recipient five years after renal transplantation. In the second case, reactivation of latent infection developed in a seropositive recipient 9 months after transplantation. In both cases, systematic screening for Toxoplasma gondii using polymerase chain reaction (PCR) in biological fluids was essential to suggest the diagnosis. Both recipients rapidly recovered after institution of antiparasitic therapy

A few lessons learned in reinforcement learning for quadcopter attitude control

International audienceIn the context of developing safe air transportation, our work is focused on understanding how Reinforcement Learning methods can improve the state of the art in traditional control, in nominal as well as non-nominal cases. The end goal is to train provably safe controllers, by improving both training and verification methods. In this paper, we explore this path for controlling the attitude of a quadcopter: we discuss theoretical as well as practical aspects of training neural nets for controlling a crazyflie 2.0 drone. In particular we describe thoroughly the choices in training algorithms, neural net architecture, hyperparameters, observation space etc. We also discuss the robustness of the obtained controllers, both to partial loss of power for one rotor and to wind gusts. Finally, we measure the performance of the approach by using a robust form of a signal temporal logic to quantitatively evaluate the vehicle's behavior