Modulation of Rolandic Beta-Band Oscillations during Motor Simulation of Joint Actions

Successful joint actions require precise temporal and spatial coordination between individuals who aim to achieve a common goal. A growing number of behavioral data suggest that to efficiently couple and coordinate a joint task, the actors have to represent both own and the partner’s actions. However it is unclear how the motor system is specifically recruited for joint actions. To find out how the goal and the presence of the partner’s hand can impact the motor activity during joint action, we assessed the functional state of 16 participants’ motor cortex during observation and associated motor imagery of joint actions, individual actions, and non-goal-directed actions performed with either 1 or 2 hands. As an indicator of the functional state of the motor cortex, we used the reactivity of the rolandic magnetoencephalographic (MEG) beta rhythm following median-nerve stimulation. Motor imagery combined with action observation was associated with activation of the observer’s motor cortex, mainly in the hemisphere contralateral to the viewed (and at the same time imagined) hand actions. The motor-cortex involvement was enhanced when the goal of the actions was visible but also, in the ipsilateral hemisphere, when the partner’s hand was visible in the display. During joint action, the partner’s action, in addition to the participant’s own action, thus seems to be represented in the motor cortex so that it can be triggered by the mere presence of an acting hand in the peripersonal space.Peer reviewe

Predictive habitat models integrating anthropic pressures to aid conservation of a rare species on Reunion island, the Mascarene petrel

Conservation planning requires the identification of habitat that may support focal species, and an assessment of how to prioritise lands to protect sustainable populations. Because conservation plans often guide the allocation of limited resources in the face of habitat loss, there is little room for error in the prioritisation process. However, incomplete information on the distributions of species and habitats makes prioritisation an enormous challenge, particularly if surveys cannot be conducted due to land inaccessibility or other constraints. The use of predictive habitat distribution models by land managers in the conservation management of threatened species is therefore increasing. Reunion Island (western Indian Ocean) is one of the few islands at global scale holding two endemic species of petrels, the Barau's Petrel (Pterodroma baraui), and the Mascarene Petrel (Pseudobulweria aterrima), both of which are poorly known and endangered. The principal threats to both species are introduced mammalian predators (rats and feral cats) and light pollution. In this study, we focused on the very rare Mascarene petrel whose remained mysterious for 160 years. Thanks to the recent discovery of breeding sites in 2016, it is vital, to face conservation urgency, to quickly identify all potential breeding areas and engage actions at a broader scale. Thus, we used environmental parameters mixed with anthropic pressures (predators density and level of invasive plants) to investigate and model the distribution of suitable habitat of this rare and endemic species. Predictive distribution maps revealed habitat refuges suggesting a high sensitivity of the species to anthropogenic pressures. This approach is very helpful for long-term management to 1) identify priority conservation areas, 2) design concrete actions to be implemented according to the environmental / anthropic characteristics of the habitat

Heterogeneity in the processing of ClC-5 mutants related to Dent disease

International audienceMutations in the electrogenic Cl-/H+ exchanger ClC-5 gene CLCN5 are frequently associated with Dent disease, an X-linked recessive disorder affecting the proximal tubules. Here, we investigate the consequences in X. laevis oocytes and in HEK293 cells of 9 previously reported, pathogenic, missense mutations of ClC-5, most of them which are located in regions forming the subunit interface. Two mutants trafficked normally to the cell surface and to early endosomes, and displayed complex glycosylation at the cell surface like wild-type ClC 5, but exhibited reduced currents. Three mutants displayed improper N-glycosylation, and were non-functional due to being retained and degraded at the endoplasmic reticulum. Functional characterization of four mutants allowed us to identify a novel mechanism leading to ClC-5 dysfunction in Dent disease. We report that these mutant proteins were delayed in their processing and that the stability of their complex glycosylated form was reduced, causing lower cell surface expression. The early endosome distribution of these mutants was normal. Half of these mutants displayed reduced currents, whereas the other half showed abolished currents. Our study revealed distinct cellular mechanisms accounting for ClC-5 loss-of-function in Dent disease

Loss of hepatic DEPTOR alters the metabolic transition to fasting

Objective The mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that functions into distinct protein complexes (mTORC1 and mTORC2) that regulates growth and metabolism. DEP-domain containing mTOR-interacting protein (DEPTOR) is part of these complexes and is known to reduce their activity. Whether DEPTOR loss affects metabolism and organismal growth in vivo has never been tested. Methods We have generated a conditional transgenic mouse allowing the tissue-specific deletion of DEPTOR. This model was crossed with CMV-cre mice or Albumin-cre mice to generate either whole-body or liver-specific DEPTOR knockout (KO) mice. Results Whole-body DEPTOR KO mice are viable, fertile, normal in size, and do not display any gross physical and metabolic abnormalities. To circumvent possible compensatory mechanisms linked to the early and systemic loss of DEPTOR, we have deleted DEPTOR specifically in the liver, a tissue in which DEPTOR protein is expressed and affected in response to mTOR activation. Liver-specific DEPTOR null mice showed a reduction in circulating glucose upon fasting versus control mice. This effect was not associated with change in hepatic gluconeogenesis potential but was linked to a sustained reduction in circulating glucose during insulin tolerance tests. In addition to the reduction in glycemia, liver-specific DEPTOR KO mice had reduced hepatic glycogen content when fasted. We showed that loss of DEPTOR cell-autonomously increased oxidative metabolism in hepatocytes, an effect associated with increased cytochrome c expression but independent of changes in mitochondrial content or in the expression of genes controlling oxidative metabolism. We found that liver-specific DEPTOR KO mice showed sustained mTORC1 activation upon fasting, and that acute treatment with rapamycin was sufficient to normalize glycemia in these mice. Conclusion We propose a model in which hepatic DEPTOR accelerates the inhibition of mTORC1 during the transition to fasting to adjust metabolism to the nutritional status. Keywords: DEPTOR; mTOR; Liver; Glucose; Fastin

A severe case of Plasmodium falciparum malaria imported by a French traveler from Cameroon to French Guiana despite regular intake of Artemisia annua herbal tea

The use of herbal tea with Artemisia annua by travelers and traditional communities in Africa has increased in recent years as a supposed form of malaria prophylaxis, although its use is not recommended due to lack of efficacy. The risk of severe malaria complications that can lead to death is real regarding said behavior, and awareness needs to be raised. We report a case of severe Plasmodium falciparum malaria imported in the Amazon rainforest by a traveler returning from Cameroon who treated himself with Artemisia annua herbal tea

Uncovering the antimalarial potential of toad venoms through a bioassay-guided fractionation process.

peer reviewedMalaria remains to date one of the most devastating parasitic diseases worldwide. The fight against this disease is rendered more difficult by the emergence and spread of drug-resistant strains. The need for new therapeutic candidates is now greater than ever. In this study, we investigated the antiplasmodial potential of toad venoms. The wide array of bioactive compounds present in Bufonidae venoms has allowed researchers to consider many potential therapeutic applications, especially for cancers and infectious diseases. We focused on small molecules, namely bufadienolides, found in the venom of Rhinella marina (L.). The developed bio-guided fractionation process includes a four solvent-system extraction followed by fractionation using flash chromatography. Sub-fractions were obtained through preparative TLC. All samples were characterized using chromatographic and spectrometric techniques and then underwent testing on in vitro Plasmodium falciparum cultures. Two strains were considered: 3D7 (chloroquine-sensitive) and W2 (chloroquine-resistant). This strategy highlighted a promising activity for one compound named resibufogenin. With IC50 values of (29 ± 8) μg/mL and (23 ± 1) μg/mL for 3D7 and W2 respectively, this makes it an interesting candidate for further investigation. A molecular modelling approach proposed a potential binding mode of resibufogenin to Plasmodium falciparum adenine-triphosphate 4 pump as antimalarial drug target

Developing a benchmark model for renovated, nearly zero-energy, terraced dwellings

Brussels is one of the European cities with the most significant number of Passive House buildings on the continent. In the Brussels-Capital Region, the nearly zero-energy building obligations implemented is implemented since 2010. The Brussels-Capital Region has set up ambitious energy standards for new constructions. These standards target ’nearly zero’ or ’very low energy consumption and are inspired by the ’passive house standard,’ where high-energy performance is first achieved. Ten years after boasting this groundbreaking policy, many renovated, terraced houses are renovated to comply with the nearly zero-energy building requirements. Therefore, this study aims to develop an energy performance data set and one building performance simulation benchmark model for nearly zero-energy dwellings in Brussels. The study reports an inventory and field survey conducted on a terraced house renovated after the year 2010. An analysis of energy consumption (electricity and natural gas) and a walkthrough survey were conducted. A building performance simulation model is created in EnergyPlus to benchmark the average energy consumption and building characteristics. The estimate’s validity has been further checked against the public statistics and verified through model calibration and utility bill comparison. The benchmark has an average energy use intensity of 29 kWh/m2/year and represents terraced single-family houses after renovation. The paper provides a timely opportunity to evaluate the actual performance of nearly zero-energy terraced houses. The findings on energy needs and use intensity are useful in temperate and continental climates.OCCuPANt, on the Impacts Of Climate Change on the indoor environmental and energy PerformAnce of buildiNgs in Belgium during summe

Glucagon-Like Peptide-1 Protects Human Islets against Cytokine-Mediated β-Cell Dysfunction and Death: A Proteomic Study of the Pathways Involved

Glucagon-like peptide-1 (GLP-1) has been shown to protect pancreatic β-cells against cytokine-induced dysfunction and destruction. The mechanisms through which GLP-1 exerts its effects are complex and still poorly understood. The aim of this study was to analyze the protein expression profiles of human islets of Langerhans treated with cytokines (IL-1β and IFN-γ) in the presence or absence of GLP-1 by 2D difference gel electrophoresis and subsequent protein interaction network analysis to understand the molecular pathways involved in GLP-1-mediated β-cell protection. Co-incubation of cytokine-treated human islets with GLP-1 resulted in a marked protection of β-cells against cytokine-induced apoptosis and significantly attenuated cytokine-mediated inhibition of glucose-stimulated insulin secretion. The cytoprotective effects of GLP-1 coincided with substantial alterations in the protein expression profile of cytokine-treated human islets, illustrating a counteracting effect on proteins from different functional classes such as actin cytoskeleton, chaperones, metabolic proteins, and islet regenerating proteins. In summary, GLP-1 alters in an integrated manner protein networks in cytokine-exposed human islets while protecting them against cytokine-mediated cell death and dysfunction. These data illustrate the beneficial effects of GLP-1 on human islets under immune attack, leading to a better understanding of the underlying mechanisms involved, a prerequisite for improving therapies for diabetic patients.status: publishe

Specificities of exosome versus small ectosome secretion revealed by live intracellular tracking of CD63 and CD9.

Despite their roles in intercellular communications, the different populations of extracellular vesicles (EVs) and their secretion mechanisms are not fully characterized: how and to what extent EVs form as intraluminal vesicles of endocytic compartments (exosomes), or at the plasma membrane (PM) (ectosomes) remains unclear. Here we follow intracellular trafficking of the EV markers CD9 and CD63 from the endoplasmic reticulum to their residency compartment, respectively PM and late endosomes. We observe transient co-localization at both places, before they finally segregate. CD9 and a mutant CD63 stabilized at the PM are more abundantly released in EVs than CD63. Thus, in HeLa cells, ectosomes are more prominent than exosomes. By comparative proteomic analysis and differential response to neutralization of endosomal pH, we identify a few surface proteins likely specific of either exosomes (LAMP1) or ectosomes (BSG, SLC3A2). Our work sets the path for molecular and functional discrimination of exosomes and small ectosomes in any cell type