Future intensification of precipitation and wind gust associated thunderstorms over Lake Victoria

Severe thunderstorms affect more than 30 million people living along the shores of Lake Victoria (East Africa). Thousands of fishers lose their lives on the lake every year. While deadly waves are assumed to be initiated by severe wind gusts, knowledge about thunderstorms is restricted to precipitation or environmental proxies. Here we use a regional climate model run at convection-permitting resolution to simulate both precipitation and wind gusts over Lake Victoria for a historical 10-year period. In addition, a pseudo global warming simulation provides insight into the region’s future climate. In this simulation, ERA5’s initial and boundary conditions are perturbed with atmospheric changes between 1995–2025 and 2070–2100, projected by CMIP6’s ensemble mean. It was found that future decreases in both mean precipitation and wind gusts over Lake Victoria can be attributed to a weaker mean mesoscale circulation that reduces the trigger for over-lake nighttime convection and decreases the mean wind shear. However, an intensification of extremes is projected for both over-lake precipitation and wind gusts. The observed 7 %K−1 Clausius–Clapeyron extreme precipitation scaling is ascribed to increased water vapor content and a compensation of weaker mesoscale circulations and stronger thunderstorm dynamics. More frequent wind gust extremes result from higher wind shear conditions and more compound thunderstorms with both intense rainfall and severe wind gusts. Overall, our study emphasizes Lake Victoria’s modulating role in determining regional current and future extremes, in addition to changes expected from the Clausius–Clapeyron relation

Modulation and functions of dopamine receptor heteromers in drugs of abuse-induced adaptations

Drug addiction is a chronic and relapsing disorder that leads to compulsive drug intake despite deleterious consequences. By increasing dopamine (DA) in the mesolimbic system, drugs of abuse hijack the brain reward circuitry, which is critical for the development of enduring behavioral alterations. DA mainly acts onto DA D1 (D1R) and D2 (D2R) receptor subtypes, which are positively and negatively coupled to adenylyl cyclase, respectively. Extensive research has aimed at targeting these receptors for the treatment of addiction, however this often results in unwanted side-effects due to the implication of DA receptors in numerous physiological functions. A growing body of evidence indicates that the physical interaction of DA receptors with other receptors can finely tune their function, making DA receptor heteromers promising targets for more specific treatment strategies. An increasing number of articles highlighted the ability of both D1R and D2R to form heteromers, however, most studies carried out to date stem from observations in heterologous systems and the biological significance of DA receptor heteromers in vivo is only emerging. We focused this review on studies that were able to provide insights into functions on D1R and D2R heteromers in drug-evoked adaptations and discuss the limitations of current approaches to study receptor heteromers in vivo. This article is part of the Special Issue entitled 'Receptor heteromers and their allosteric receptor-receptor interactions'.Rôle des heteromères formés par les récepteurs dopamine-glutamate et de signalisation dépendante du calcium nucléaire associée dans l'addictionImpact de la composition lipidique membranaire sur la transmission dopaminergique dépendante du récepteur D2 et la motivationProgram Initiative d’Excellenc

Calculation of solubility in titanium alloys from first-principles

We present an approach to calculate the atomic bulk solubility in binary alloys based on the statistical-thermodynamic theory of dilute lattice gas. The model considers all the appropriate ground states of the alloy and results in a simple Arrhenius-type temperature dependence determined by a {\it "low-solubility formation enthalpy"}. This quantity, directly obtainable from first-principle calculations, is defined as the composition derivative of the compound formation enthalpy with respect to nearby ground states. We apply the framework and calculate the solubility of the A specie in A-Ti alloys (A=Ag,Au,Cd,Co,Cr,Ir,W,Zn). In addition to determining unknown low-temperature ground states for the eight alloys, we find qualitative agreements with solubility experimental results. The presented formalism, correct in the low-solubility limit, should be considered as an appropriate starting point for determining if more computationally expensive formalisms are otherwise needed.Comment: 10 pages, 12 figure

Detecting G protein-coupled receptor complexes in postmortem human brain with proximity ligation assay and a Bayesian classifier

Despite the controversy regarding the existence and physiological relevance of class A G protein-coupled receptor dimerization, there is substantial evidence for functional interactions between the dopamine D2 receptor (D2R) and the adenosine A2A receptor (A2AR). A2AR-D2R complexes have been detected in rodent brains by proximity ligation assay; however, their existence in the human brain has not been demonstrated. In this study, we used Brightfield proximity ligation assay, combined with a systematic sampling and a parameter-free naive Bayesian classifier, and demonstrated proximity between the D2R and the A2AR in the adult human ventral striatum, consistent with their colocalization within complexes and the possible existence of D2R-A2AR heteromers. These methods are applicable to the relative quantification of proximity of two proteins, as well as the expression levels of individual proteins

COSMO-CLM regional climate simulations in the Coordinated Regional Climate Downscaling Experiment (CORDEX) framework: a review

In the last decade, the Climate Limited-area Modeling Community (CLM-Community) has contributed to the Coordinated Regional Climate Downscaling Experiment (CORDEX) with an extensive set of regional climate simulations. Using several versions of the COSMO-CLM-Community model, ERA-Interim reanalysis and eight global climate models from phase 5 of the Coupled Model Intercomparison Project (CMIP5) were dynamically downscaled with horizontal grid spacings of 0.44∘ (∼ 50 km), 0.22∘ (∼ 25 km), and 0.11∘ (∼ 12 km) over the CORDEX domains Europe, South Asia, East Asia, Australasia, and Africa. This major effort resulted in 80 regional climate simulations publicly available through the Earth System Grid Federation (ESGF) web portals for use in impact studies and climate scenario assessments. Here we review the production of these simulations and assess their results in terms of mean near-surface temperature and precipitation to aid the future design of the COSMO-CLM model simulations. It is found that a domain-specific parameter tuning is beneficial, while increasing horizontal model resolution (from 50 to 25 or 12 km grid spacing) alone does not always improve the performance of the simulation. Moreover, the COSMO-CLM performance depends on the driving data. This is generally more important than the dependence on horizontal resolution, model version, and configuration. Our results emphasize the importance of performing regional climate projections in a coordinated way, where guidance from both the global (GCM) and regional (RCM) climate modeling communities is needed to increase the reliability of the GCM–RCM modeling chain

The Addiction-Susceptibility TaqIA/Ankk1 Controls Reward and Metabolism Through D2 Receptor-Expressing Neurons

Background: A large body of evidence highlights the importance of genetic variants in the development of psychiatric and metabolic conditions. Among these, the TaqIA polymorphism is one of the most commonly studied in psychiatry. TaqIA is located in the gene that codes for the ankyrin repeat and kinase domain containing 1 kinase (Ankk1) near the dopamine D2 receptor (D2R) gene. Homozygous expression of the A1 allele correlates with a 30% to 40% reduction of striatal D2R, a typical feature of addiction, overeating, and other psychiatric pathologies. The mechanisms by which the variant influences dopamine signaling and behavior are unknown. Methods: Here, we used transgenic and viral-mediated strategies to reveal the role of Ankk1 in the regulation of activity and functions of the striatum. Results: We found that Ankk1 is preferentially enriched in striatal D2R-expressing neurons and that Ankk1 loss of function in the dorsal and ventral striatum leads to alteration in learning, impulsivity, and flexibility resembling endophenotypes described in A1 carriers. We also observed an unsuspected role of Ankk1 in striatal D2R-expressing neurons of the ventral striatum in the regulation of energy homeostasis and documented differential nutrient partitioning in humans with or without the A1 allele. Conclusions: Overall, our data demonstrate that the Ankk1 gene is necessary for the integrity of striatal functions and reveal a new role for Ankk1 in the regulation of body metabolism.Altérations du système de récompense dans l'anorexie mentaleRole du biostatus en acides gras polyinsaturés dans les troubles de contrôle exécuti

Coulomb dissociation of N 20,21

Neutron-rich light nuclei and their reactions play an important role in the creation of chemical elements. Here, data from a Coulomb dissociation experiment on N20,21 are reported. Relativistic N20,21 ions impinged on a lead target and the Coulomb dissociation cross section was determined in a kinematically complete experiment. Using the detailed balance theorem, the N19(n,γ)N20 and N20(n,γ)N21 excitation functions and thermonuclear reaction rates have been determined. The N19(n,γ)N20 rate is up to a factor of 5 higher at

Variability of diagnostic criteria and treatment of idiopathic nephrotic syndrome across European countries

The aim of the surveys conducted by the Idiopathic Nephrotic Syndrome Working Group of the ESPN was to study the possible variability of treatment in Europe at different stages of the disease by means of questionnaires sent to members of the Working Group. Four surveys have been completed: treatment of the first flare, treatment of the first relapse and the issue of steroid dependency, use of rituximab, and the management of steroid-resistant patients. A uniform treatment of the first flare was applied in only three countries, and ten additional centers have adopted one of the three main protocols. Reported treatment of the first relapse was relatively uniform, whereas the use of additional immunosuppressants in steroid dependency was widely variable. Rituximab had already been used in hundreds of patients, although the formal evidence of efficiency in steroid dependency was relatively recent at the time of the survey. The definition of steroid resistance was variable in the European centers, but strikingly, the first-line treatment was uniform throughout the centers and included the combination of prednisone plus calcineurin antagonists. Conclusion: The variability in the approach of idiopathic nephrotic syndrome is unexpectedly large and affects treatment of the first flare, strategies in the case of steroid dependency, as well as the definitions of steroid resistance.What is Known:• Steroids and immunosuppressants are the universal treatment of idiopathic nephrotic syndrome.What is New:• The variability of treatments and strategy of treatment in European centers of pediatric nephrology

Le rôle respectif des différents populations de neurones épineux moyens du noyau accumbens dans la motivation et la prise alimentaire

Compulsive eating, found in some forms of obesity, and anorexia nervosa (AN) can be considered as opposite pathologies in regard of their symptomatology, i.e. increased/decreased food intake, decreased/increased physical activity and decreased/increased motivation in obesity and AN, respectively. Even though little is known regarding the pathophysiological mechanisms of these diseases, accumulating evidence point to a dysfunction of the mesolimbic pathway, and the Nucleus Accumbens (NAc) in particular. My PhD project aimed at determining whether manipulating the activity of discrete neuronal subpopulations of the NAc could be sufficient to mimic symptomatic dimensions of compulsive eating and/or AN. The NAc is mainly composed of medium spiny neurons (MSN) that are segregated in 2 populations based on the dopamine receptors they express, either D1 (D1-MSN) or D2 (D2-MSN). Using a chemogenetic approach coupled with analyses of i) incentive processes, ii) food intake and iii) physical activity in mice, we found that acute activation of D2-MSNs or D1-MSNs leads to obesity-like and AN-like phenotypes, respectively. I will assess whether chronic manipulations of each MSN subpopulations is sufficient to trigger obesity or anorexia like symptom or– or concomitantly thanks to a unique double-transgenic mouse model. We observe while D1 chronic activation mediate weigh lose as a result of an excessive wheel running, weigh gain trigger by chronic D2 activation is due to low physical activity and daily consumption increase.Les dérégulations de la prise alimentaire vue dans certaines formes d’obésités et anorexie nerveuse peuvent être considéré comme des pathologie opposée sur la base de leur symptomatologie, i.e. une augmentation/diminution de la prise alimentaire, diminution/augmentation de l’activité physique et la motivation dans l’obésité et AN, respectivement. Bien que les mécanismes physiopathologiques de ces pathologies restent encore obscure, plusieurs évidences suggèrent un dysfonctionnement du système mésolimbique et en particulier du noyaux accumbens (NAc). Mon projet de thèse vise à manipuler l’activité des différentes sous population neuronales du Nac et déterminer s’ils sont suffisant pour induire mimer les dimensions symptomatiques vue dans l’obésité et AN. Le Nac est principalement composé de neurones moyens épineux (MSN) qui sont ségrégés en 2 populations sur la base des récepteurs dopaminergiques qu’ils expriment, soit D1 (D1-MSN) ou D2 (D2-MSN). Par le biais d’une approche de pharmacogénétique associer à une analyse de la i) motivation ii) la prise alimentaire et iii) l’activité physique chez la souris, nous montrons que l’activation aigue des D2-MSNs ou D1-MSNs conduit respectivement à un phénotype associer à l’obésité et l’anorexie

Respective roles of the distinct populations of medium spiny neurons of the nucleus accumbens in reward processing and feeding behaviors.

Les dérégulations de la prise alimentaire vue dans certaines formes d’obésités et anorexie nerveuse peuvent être considéré comme des pathologie opposée sur la base de leur symptomatologie, i.e. une augmentation/diminution de la prise alimentaire, diminution/augmentation de l’activité physique et la motivation dans l’obésité et AN, respectivement. Bien que les mécanismes physiopathologiques de ces pathologies restent encore obscure, plusieurs évidences suggèrent un dysfonctionnement du système mésolimbique et en particulier du noyaux accumbens (NAc). Mon projet de thèse vise à manipuler l’activité des différentes sous population neuronales du Nac et déterminer s’ils sont suffisant pour induire mimer les dimensions symptomatiques vue dans l’obésité et AN. Le Nac est principalement composé de neurones moyens épineux (MSN) qui sont ségrégés en 2 populations sur la base des récepteurs dopaminergiques qu’ils expriment, soit D1 (D1-MSN) ou D2 (D2-MSN). Par le biais d’une approche de pharmacogénétique associer à une analyse de la i) motivation ii) la prise alimentaire et iii) l’activité physique chez la souris, nous montrons que l’activation aigue des D2-MSNs ou D1-MSNs conduit respectivement à un phénotype associer à l’obésité et l’anorexie.Compulsive eating, found in some forms of obesity, and anorexia nervosa (AN) can be considered as opposite pathologies in regard of their symptomatology, i.e. increased/decreased food intake, decreased/increased physical activity and decreased/increased motivation in obesity and AN, respectively. Even though little is known regarding the pathophysiological mechanisms of these diseases, accumulating evidence point to a dysfunction of the mesolimbic pathway, and the Nucleus Accumbens (NAc) in particular. My PhD project aimed at determining whether manipulating the activity of discrete neuronal subpopulations of the NAc could be sufficient to mimic symptomatic dimensions of compulsive eating and/or AN. The NAc is mainly composed of medium spiny neurons (MSN) that are segregated in 2 populations based on the dopamine receptors they express, either D1 (D1-MSN) or D2 (D2-MSN). Using a chemogenetic approach coupled with analyses of i) incentive processes, ii) food intake and iii) physical activity in mice, we found that acute activation of D2-MSNs or D1-MSNs leads to obesity-like and AN-like phenotypes, respectively. I will assess whether chronic manipulations of each MSN subpopulations is sufficient to trigger obesity or anorexia like symptom or– or concomitantly thanks to a unique double-transgenic mouse model. We observe while D1 chronic activation mediate weigh lose as a result of an excessive wheel running, weigh gain trigger by chronic D2 activation is due to low physical activity and daily consumption increase