Contribution of calcium-conducting channels to the transport of zinc ions.

International audienceZinc (Zn) is a vital nutrient participating in a myriad of biological processes. The mechanisms controlling its transport through the plasma membrane are far from being completely understood. Two families of eukaryotic zinc transporters are known to date: the Zip (SLC39) and ZnT (SLC30) proteins. In addition, some types of plasmalemmal calcium (Ca)-conducting channels are implied in the cellular uptake of zinc. These ion channels are currently described as systems dedicated to the transport of Ca (and, to some extent, sodium (Na) ions). However, a growing body of evidence supports the view that some of them can also function as pathways for Zn transport. For instance, voltage-gated Ca channels and some types of glutamate-gated receptors have long been known to allow the entry of Zn. More recently, members of the TRP superfamily, another type of Ca-conducting channels, have been shown to permit the uptake of Zn into eukaryotic cells. The aim of this review article is to present the current knowledge supporting the notion that Ca-conducting channels take part in the plasmalemmal transport of Zn

Ca2+ channel sensitivity towards the blocker isradipine is affected by alternative splicing of the human α1C subunit gene

AbstractL-type Ca2+ channels are important targets for drugs, such as dihydropyridines (DHPs), in the treatment of cardiovascular diseases. Channel expression is regulated by alternative splicing. It has been suggested that in the cardiovascular system tissue-specific expression of different L-type Ca2+ channel splice variants may underlie the observed differences in sensitivities to channel block by DHPs. We investigated the sensitivity of Ca2+ channel splice variants derived from the human α1C gene to the DHP isradipine. Among seven α1C channels we observed up to 10-fold differences in IC50 values for isradipine, as well as changes in the voltage dependence of DHP action

Activation of a capacitative Ca2+ entry pathway by store depletion in cultured hippocampal neurones

AbstractIntracellular Ca2+ ([Ca2+]i) changes were measured in cell bodies of cultured rat hippocampal neurones with the fluorescent indicator Fluo-3. In the absence of external Ca2+, the cholinergic agonist carbachol (200 μM) and the sarco-endoplasmic reticulum Ca2+ pump inhibitor thapsigargin (0.4 μM) both transiently elevated [Ca2+]i. A subsequent addition of Ca2+ into the bathing medium caused a second [Ca2+]i change which was blocked by lanthanum (50 μM). Taken together, these experiments indicate that stores depletion can activate a capacitative Ca2+ entry pathway in cultured hippocampal neurones and further demonstrate the existence of such a Ca2+ entry in excitable cells

The antidepressant hyperforin increases the phosphorylation of CREB and the expression of TrkB in a tissue-specific manner.

International audienceHyperforin is one of the main bioactive compounds that underlie the antidepressant actions of the medicinal plant Hypericum perforatum (St. John's wort). However, the effects of a chronic hyperforin treatment on brain cells remains to be fully addressed. The following study was undertaken to further advance our understanding of the biological effects of this plant extract on neurons. Special attention was given to its impact on the brain-derived neurotrophic factor (BDNF) receptor TrkB and on adult hippocampal neurogenesis since they appear central to the mechanisms of action of antidepressants. The consequences of a chronic hyperforin treatment were investigated on cortical neurons in culture and on the brain of adult mice treated for 4 wk with a daily injection (i.p.) of hyperforin (4 mg/kg). Its effects on the expression of the cyclic adenosine monophosphate response element-binding protein (CREB), phospho-CREB (p-CREB), TrkB and phospho-TrkB (p-TrkB) were analysed by Western blot experiments and its impact on adult hippocampal neurogenesis was also investigated. Hyperforin stimulated the expression of TRPC6 channels and TrkB via SKF-96365-sensitive channels controlling a downstream signalling cascade involving Ca2+, protein kinase A, CREB and p-CREB. In vivo, hyperforin augmented the expression of TrkB in the cortex but not in the hippocampus where hippocampal neurogenesis remained unchanged. In conclusion, this plant extract acts on the cortical BDNF/TrkB pathway leaving adult hippocampal neurogenesis unaffected. This study provides new insights on the neuronal responses controlled by hyperforin. We propose that the cortex is an important brain structure targeted by hyperforin

Passeurs de savoirs Géoconfluences, le site de ressources scientifiques géographiques en ligne, a 15 ans

Géoconfluences, le site de ressources scientifiques géographiques en ligne fête ses 15 ans ! Quelques chiffres donnent le vertige : 2 000 ressources dont plus de 300 articles scientifiques, 1,7 million de visites et 3,3 millions de pages vues en 2017, 20 millions de pages vues depuis 2003. Hébergé à l’École normale supérieure de Lyon pour la Direction générale de l’enseignement scolaire (DGESCO) et associé à son équipe d’enseignants en géographie, le site a pour mission de faciliter l’accès aux connaissances universitaires pour la formation continue des enseignants en géographie. Au-delà cette mission initiale, le site est devenu une référence en géographie. En revenant sur ce qui fait et a fait la particularité et la success story du site, cet article d’Échogéo révèle les dessous du métier de géographes dédiés à la médiation scientifique par l’intermédiaire d’une ressource numérique. Une aventure contée par trois « passeurs de savoirs » : Sylviane Tabarly, Marie-Christine Doceul et Jean-Benoît Bouron, qui se sont succédé à la responsabilité éditoriale du site depuis 2002, date à laquelle le projet a commencé (le site a été mis en ligne la première fois en février 2003)

Pandemic stress and SARS-CoV-2 infection are associated with pathological changes at the maternal-fetal interface

Introduction The reported effects of SARS-CoV-2 on pregnancy outcomes are conflicting; studies frequently overlook the placenta, which is critical for the health of the mother and infant(s). This study aimed to determine the effect of pandemic stress ± SARS CoV-2 infection on placental histopathology. Methods Women were recruited in Canada (n = 69); France (n = 21) or in the UK (n = 25), between March and October 2020. Historic controls (N = 20) were also included. Placenta and fetal membrane samples were collected rapidly after delivery and were fixed and stained for histopathological analysis. Maternal demographical data and obstetric outcomes were recorded. Results Over 80% of the placentas from SARS-CoV-2+ pregnancies had histopathological abnormalities: predominantly structural (71–86%) or inflammatory (9–22%), depending on geographical location. Excessive fibrin was seen in all sites, whereas deciduitis (Canada), calcifications (UK), agglutinations and chorangiosis (France) predominated in different locations. The frequency of abnormalities was significantly higher than in SARS-CoV-2 negative women (50%, p < 0.05). Demographic and obstetric data were similar in the SARS-CoV-2+ women across all sites - characterised by predominantly Black/Middle Eastern women, and women with elevated body mass index. Discussion Overall, the frequency of placental abnormalities is increased in SARS-CoV-2+ women, but the incidence of placental abnormalities is also higher in SARS-CoV-2- women that gave birth during the pandemic, which highlights the importance of appropriate control groups to ascertain the roles of pandemic stress and SARS-CoV-2 infection on the placenta and pregnancy outcomes

Thermal Behavior of a Novel Solar Hybrid Road for Energy Harvesting

International audienceTransportation is undergoing a radical transformation toward a novel way of thinking about road pavement: a sustainable, multifunctional infrastructure able to satisfy mobility needs, ensuring high safety standards, low carbon impact, automated detection through smart sensors, and resilience against natural and anthropogenic hazards. In this scenario, the road could also play a role for energy harvesting, thanks to the exploitation of solar radiation. The latter can be directly converted into electricity by solar cells placed under a semitransparent layer, or it can be harvested through a calorific flowing fluid. The aim of this paper is to introduce the concept of “hybrid road,” which is able to exploit both approaches. The innovative pavement is a multilayered structure composed by a semitransparent top layer made of glass aggregates bonded together thanks to a semitransparent resin, an electrical layer containing the solar cells, a porous asphalt layer for the circulation of the calorific fluid, and finally, a base waterproof layer. The hybrid road can generate electricity, contrast the heat-island effect, exploit the harvested energy to run a heat pump for heating purposes, or facilitate road deicing during winter. The present paper details experimental data obtained through energetic tests performed with a laboratory-size prototype of the hybrid road. The results show that the prototype is able to harvest around 55.2 W through the heat-transfer fluid. Furthermore, the heat exchange between water and asphalt has a cooling effect on the entire prototype

The Battle of the Schedulers: FreeBSD ULE vs. Linux CFS

International audienceThis paper analyzes the impact on application performance of the design and implementation choices made in two widely used open-source schedulers: ULE, the default FreeBSD scheduler, and CFS, the default Linux scheduler. We compare ULE and CFS in otherwise identical circumstances. We have ported ULE to Linux, and use it to schedule all threads that are normally scheduled by CFS. We compare the performance of a large suite of applications on the modified kernel running ULE and on the standard Linux kernel running CFS. The observed performance differences are solely the result of scheduling decisions, and do not reflect differences in other subsystems between FreeBSD and Linux. There is no overall winner. On many workloads the two schedulers perform similarly, but for some work-loads there are significant and even surprising differences. ULE may cause starvation, even when executing a single application with identical threads, but this starvation may actually lead to better application performance for some workloads. The more complex load balancing mechanism of CFS reacts more quickly to work-load changes, but ULE achieves better load balance in the long run

Interaction between Intrathecal Gabapentin and Adenosine in the Formalin Test of Rats

Spinal gabapentin and adenosine have been known to display an antinociceptive effect. We evaluated the nature of the interaction between gabapentin and adenosine in formalin-induced nociception at the spinal level. Male Sprague-Dawley rats were prepared for intrathecal catheterization. Pain was evoked by injection of formalin solution (5%, 50 µL) into the hindpaw. After examination of the effects of gabapentin and adenosine, the resulting interaction was investigated with isobolographic and fractional analyses. Neither gabapentin nor adenosine affected motor function. Gabapentin or adenosine decreased the sum of the number of flinches during phase 2, but not during phase 1 in the formalin test. Isobolographic analysis, in phase 2, revealed an additive interaction between gabapentin and adenosine. Taken together, intrathecal gabapentin and adenosine attenuated the facilitated state and interacted additively with each other