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We present experimental techniques to analyze the electroluminescence (EL) of polymer light-emitting diodes following the removal of an applied voltage pulse. We explain the fast modulation of the EL intensity at turn-off in terms of the sudden reduction of the Langevin recombination rate, and extract the time evolution the device's internal electric field at the recombination zone during the application of a voltage pulse. The results are compared to, and found to be consistent with, those of simple numerical modeling. The subsequent long-lived EL tail is analyzed to give the time evolution of the carrier distributions at the recombination zone once the voltage pulse has been removed. © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Four tributaries of Lake St-Jean (Quebec, Canada) are used for spawning and juvenile habitat by land-locked Atlantic salmon. Spawning runs have drastically declined since the mid-1980s, and consequently, a supportive-breeding programme was undertaken in 1990. In this study, we analysed seven microsatellite loci and mtDNA, and empirically estimated effective population sizes to test the hypotheses that (i) fish spawning in different tributaries form genetically distinct populations and (ii) the supportive breeding programme causes genetic perturbations on wild populations. Allele frequency distribution,molecular variance and genetic distance estimates all supported the hypothesis of genetic differentiation among salmon from different tributaries. Gene flow among some populations was much more restricted than previously reported for anadromous populations despite the small geographical scale (40 km) involved. Both mtDNA and microsatellites revealed a more pronounced differentiation between populations from two tributaries of a single river compared with their differentiation with a population from a neighbouring river. The comparison of wild and F1-hatchery fish (produced from breeders originating from the same river) indicated significant changes in allele frequenciesand losses of low-frequency alleles but no reduction in heterozygosity. Estimates of variance and inbreeding population size indicated that susceptibility to genetic drift and inbreeding in one population increased by twofold after only one generation of supplementation. [ABSTRACT FROM AUTHOR]

Lymphatic vessels are essential for preventing the accumulation of harmful components within peripheral tissues, including the artery wall. Various endogenous mechanisms maintain adequate lymphatic function throughout life, with platelets being essential for preserving lymphatic vessel integrity. However, since lymph lacks platelets, their impact on the lymphatic system has long been viewed as restricted to areas where lymphatics intersect with blood vessels. Nevertheless, platelets can also exert long range effects through the release of extracellular vesicles (EVs) upon activation. We observed that platelet EVs (PEVs) are present in lymph, a compartment to which they could transfer regulatory effects of platelets. Here, we report that PEVs in lymph exhibit a distinct signature enabling them to interact with lymphatic endothelial cells (LECs). In vitro experiments show that the internalization of PEVs by LECs maintains their functional integrity. Treatment with PEVs improves lymphatic contraction capacity in atherosclerosis-prone mice. We suggest that boosting lymphatic pumping with exogenous PEVs offers a novel therapeutic approach for chronic inflammatory diseases characterized by defective lymphatics., (© 2024. The Author(s).)

Lean patients with NAFLD may develop cardiac complications independently of pre-existent metabolic disruptions and comorbidities. To address the underlying mechanisms independent of the development of obesity, we used a murine model of hepatic mitochondrial deficiency. The liver-heart axis was studied as these mice develop microvesicular steatosis without obesity. Our results unveil a sex-dependent phenotypic remodeling beyond liver damage. Males, more than females, show fasting hypoglycemia and increased insulin sensitivity. They exhibit diastolic dysfunction, remodeling of the circulating lipoproteins and cardiac lipidome. Conversely, females do not manifest cardiac dysfunction but exhibit cardiometabolic impairments supported by impaired mitochondrial integrity and β-oxidation, remodeling of circulating lipoproteins and intracardiac accumulation of deleterious triglycerides. This study underscores metabolic defects in the liver resulting in significant sex-dependent cardiac abnormalities independent of obesity. This experimental model may prove useful to better understand the sex-related variability, notably in the heart, involved in the progression of lean-NAFLD., (© 2024. The Author(s).)

The Ca 2+ release in microdomains formed by intercompartmental contacts, such as mitochondria-associated endoplasmic reticulum membranes (MAMs), encodes a signal that contributes to Ca 2+ homeostasis and cell fate control. However, the composition and function of MAMs remain to be fully defined. Here, we focused on the transient receptor potential vanilloid 1 (TRPV1), a Ca 2+ -permeable ion channel and a polymodal nociceptor. We found TRPV1 channels in the reticular membrane, including some at MAMs, in a rat cardiomyoblast cell line (SV40-transformed H9c2) by Western blotting, immunostaining, cell fractionation, and proximity ligation assay. We used chemical and genetic probes to perform Ca 2+ imaging in four cellular compartments: the endoplasmic reticulum (ER), cytoplasm, mitochondrial matrix, and mitochondrial surface. Our results showed that the ER Ca 2+ released through TRPV1 channels is detected at the mitochondrial outer membrane and transferred to the mitochondria. Finally, we observed that prolonged TRPV1 modulation for 30 min alters the intracellular Ca 2+ equilibrium and influences the MAM structure or the hypoxia/reoxygenation-induced cell death. Thus, our study provides the first evidence that TRPV1 channels contribute to MAM Ca 2+ exchanges.

Some epidemiological studies have raised health concerns following the chronic exposure of pregnant women and children to pesticides in the domestic environment. In France very little is known about potential exposure to pesticides at home. An observational study called Pesti'home was carried out in continental France between July and November 2014. The residential use of pesticides was investigated and an inventory of pesticides and active ingredients used and stored at home was drawn up. Plant protection products, biocides, and human and animal external pest control products were listed during face-to-face interviews. A random sample of households including at least one adult (18-79 years old) was selected following a two-stage stratified random sampling method using the national census database. Within each household, an adult was appointed to answer survey questions. Data related to the interviewee's sociodemographic and housing characteristics, the reported use of pesticides at home, and a visual inventory of all stored pesticides were collected. Overall, 1507 households participated. The participation rate was between 36% and 57% according to the definition chosen. Over the previous 12 months, 75% of households declared that they had used at least one pesticide. Households who used and stored at least one product most frequently used an insecticide (84%). The active ingredients most frequently used by these households as insecticides were pyrethroids, namely tetramethrin and permethrin. The Pesti'home survey collected detailed data on the residential use of pesticides for risk assessment at national and European levels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Despite the advancement of vaccination and therapies currently available, deaths due to the coronavirus disease 2019 (COVID-19) are still heavily documented. Severely infected individuals experience a generalized inflammatory storm, caused by massive secretion of pro-inflammatory cytokines that can lead to endothelial dysfunction, cardiovascular disease, multi-organ failure, and even death. COVID-19 convalescent plasma (CCP) therapy, selected primarily based on anti-SARS-CoV-2 antibody levels, has not been as convincing as expected in the fight against COVID-19. Given the consequences of a dysfunctional endothelium on the progression of the disease, we propose that the selection of plasma for CCP therapy should be based on more specific parameters that take into consideration the effect on vascular inflammation. Thus, in the present study, we have characterized a subset of CCP that have been used for CCP therapy and measured their anti- or pro-inflammatory effect on human coronary artery endothelial cells (HCAECs). Our data revealed that the longer the time lapse between the onset of symptoms and the plasma donation, the more mitochondrial dysfunction can be evidenced. The concentration of blood endothelial cell extracellular vesicles (BEC-EVs) was increased in the plasma of young individuals with mild symptoms. This type of selected convalescent plasma promoted the activation of the blood vascular endothelium, as reflected by the overexpression of ICAM1 and NFκB1 and the downregulation of VE-Cadherin. We propose this mechanism is a warning signal sent by the injured endothelium to trigger self-defense of peripheral blood vessels against excessive inflammation. Therefore, these results are in line with our previous data. They suggest that a more specific selection of COVID-19 convalescent plasma should be based on the time of donation following the onset of the clinical symptoms of the donor, the severity of the symptoms, and the age of the donor. These characteristics are relatively easy to identify in any hospital and would reflect the concentration of plasma BEC-EVs and be optimal in CCP therapy.

In response to many stresses, such as oncogene activation or DNA damage, cells can enter cellular senescence, a state of proliferation arrest accompanied by a senescence-associated secretory phenotype (SASP). Cellular senescence plays a key role in many physiopathological contexts, including cancer, aging and aging-associated diseases, therefore, it is critical to understand how senescence is regulated. Calcium ions (Ca 2+ ) recently emerged as pivotal regulators of cellular senescence. However, how Ca 2+ levels are controlled during this process is barely known. Here, we report that intracellular Ca 2+ contents increase in response to many senescence inducers in immortalized human mammary epithelial cells (HMECs) and that expression of calbindin 1 (CALB1), a Ca 2+ -binding protein, is upregulated in this context, through the Ca 2+ -dependent calcineurin/NFAT pathway. We further show that overexpression of CALB1 buffers the rise in intracellular Ca 2+ levels observed in senescent cells. Finally, we suggest that increased expression of Ca 2+ -binding proteins calbindins is a frequent mark of senescent cells. This work thus supports that, together with Ca 2+ channels, Ca 2+ -binding proteins modulate Ca 2+ levels and flux during cellular senescence. This opens potential avenues of research to better understand the role of Ca 2+ and of Ca 2+ -binding proteins in regulating cellular senescence.

Genetic diversity within and among populations is frequently used in prioritization processes to rank populations based on their vulnerability or distinctiveness, however, connectivity and gene flow are rarely considered within these frameworks. Using a wood turtle (Glyptemys insculpta) population graph, we introduce BRIDES as a new tool to evaluate populations for conservation purpose without focusing solely on individual nodes. BRIDES characterizes different types of shortest paths among the nodes of a subgraph and compares the shortest paths among the same nodes in a complete network. The main objectives of this study were to (1) introduce a BRIDES selection process to assist conservation biologists in the prioritization of populations, and (2) use different centrality indices and node removal statistics to compare BRIDES results and assess gene flow among wood turtle populations. We constructed six population subgraphs and used a stepwise selection algorithm to choose the optimal number of additional nodes, representing different populations, required to maximize network connectivity under different weighting schemes. Our results demonstrate the robustness of the BRIDES selection process for a given scenario, while inconsistencies were observed among node-based metrics. Results showed repeated selection of certain wood turtle populations, which could have not been predicted following only genetic diversity and distinctiveness estimation, node-based metrics and node removal analysis. Contrary to centrality measures focusing on static networks, BRIDES allowed for the analysis of evolving networks. To our knowledge, this study is the first to apply graph theory for turtle conservation genetics. We show that population graphs can reveal complex gene flow dynamics and population resiliency to local extinction. As such, BRIDES offers an interesting complement to node-based metrics and node removal to better understand the global processes at play when addressing population prioritization frameworks., Competing Interests: The authors have declared that no competing interests exist.

Cellular senescence is characterized by a stable proliferation arrest in response to stresses and the acquisition of a senescence-associated secretory phenotype, called SASP, composed of numerous factors including pro-inflammatory molecules, proteases, and growth factors. The SASP affects the environment of senescent cells, especially during aging, by inducing and modulating various phenotypes such as paracrine senescence, immune cell activity, and extracellular matrix deposition and organization, which critically impact various pathophysiological situations, including fibrosis and cancer. Here, we uncover a novel paracrine effect of the SASP: the neuroendocrine transdifferentiation (NED) of some epithelial cancer cells, evidenced both in the breast and prostate. Mechanistically, this effect is mediated by NF-κB-dependent SASP factors, and leads to an increase in intracellular Ca 2+ levels. Consistently, buffering Ca 2+ by overexpressing the CALB1 buffering protein partly reverts SASP-induced NED, suggesting that the SASP promotes NED through a SASP-induced Ca 2+ signaling. Human breast cancer dataset analyses support that NED occurs mainly in p53 WT tumors and in older patients, in line with a role of senescent cells and its secretome, as they are increasing during aging. In conclusion, our work, uncovering SASP-induced NED in some cancer cells, paves the way for future studies aiming at better understanding the functional link between senescent cell accumulation during aging, NED and clinical patient outcome., (© 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Convalescent plasma therapy (CPT) has gained significant attention since the onset of the coronavirus disease 2019 (COVID-19) pandemic. However, clinical trials designed to study the efficacy of CPT based on antibody concentrations were inconclusive. Lymphatic transport is at the interplay between the immune response and the resolution of inflammation from peripheral tissues, including the artery wall. As vascular complications are a key pathogenic mechanism in COVID-19, leading to inflammation and multiple organ failure, we believe that sustaining lymphatic vessel function should be considered to define optimal CPT. We herein sought to determine what specific COVID-19 convalescent plasma (CCP) characteristics should be considered to limit inflammation-driven lymphatic endothelial cells (LEC) dysfunction. CCP donated 16 to 100 days after the last day of symptoms was characterized and incubated on inflammation-elicited adult human dermal LEC (aHDLEC). Plasma analysis revealed that late donation correlates with higher concentration of circulating pro-inflammatory cytokines. Conversely, extracellular vesicles (EVs) derived from LEC are more abundant in early donated plasma (r = -0.413, p = 0.004). Thus, secretion of LEC-EVs by an impaired endothelium could be an alarm signal that instigate the self-defense of peripheral lymphatic vessels against an excessive inflammation. Indeed, in vitro experiments suggest that CCP obtained rapidly following the onset of symptoms does not damage the aHDLEC junctions as much as late-donated plasma. We identified a particular signature of CCP that would counteract the effects of an excessive inflammation on the lymphatic endothelium. Accordingly, an easy and efficient selection of convalescent plasma based on time of donation would be essential to promote the preservation of the lymphatic and immune system of infected patients.

Rationale: Impairment in lymphatic transport is associated with the onset and progression of atherosclerosis in animal models. The downregulation of low-density-lipoprotein receptor (LDLR) expression, rather than increased circulating cholesterol level per se , is involved in early atherosclerosis-related lymphatic dysfunction. Enhancing lymphatic function in Ldlr -/- mice with a mutant form of VEGF-C (VEGF-C 152s), a selective VEGFR-3 agonist, successfully delayed atherosclerotic plaque onset when mice were subsequently fed a high-fat diet. However, the specific mechanisms by which LDLR protects against lymphatic function impairment is unknown. Methods and results: We have thus injected wild-type and Pcsk9 -/- mice with an adeno-associated virus type 1 expressing a shRNA for silencing Ldlr in vivo . We herein report that lymphatic contractility is reduced upon Ldlr dowregulation in wild-type mice only. Our in vitro experiments reveal that a decrease in LDLR expression at the mRNA level reduces the chromosome duplication phase and the protein expression of VEGFR-3, a membrane-bound key lymphatic marker. Furthermore, it also significantly reduced the levels of 18 lipid subclasses, including key constituents of lipid rafts as well as the transcription of several genes involved in cholesterol biosynthesis and cellular and metabolic processes. Exogenous PCSK9 only reduces lymphatic endothelial-LDLR at the protein level and does not affect lymphatic endothelial cell integrity. This puts forward that PCSK9 may act upon lymphatic muscle cells to mediate its effect on lymphatic contraction capacity in vivo . Conclusion: Our results suggest that treatments that specifically palliate the down regulation of LDLR mRNA in lymphatic endothelial cells preserve the integrity of the lymphatic endothelium and sustain lymphatic function, a prerequisite player in atherosclerosis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Context: Although there is strong evidence in the literature on the interest of the implementation of health policy and programs in schools, data on the determinants of the active participation of education professionals in health promotion programs remain scare., Objective: Our study was conducted in 2018-2019 in New Caledonia, a South Pacific archipelago rich in cultural diversity but marked by major inequalities in health and education. It aimed to identify the factors that explain the involvement of teachers in an intersectoral health promotion program (development of a health education pathway led by an intersectoral team). It involved 40 schools, which corresponds to 20% of primary schools of the archipelago., Results: Data show that of the 139 education professionals who were enrolled in the program by the education administration, 77 actively contributed. The work of these 60 teachers, 12 school principals and 5 district managers were studied in detail and categorized on the basis of the nature of their contribution., Conclusion: Analysis of the factors impacting active participation showed that two main parameters play a key role in teacher engagement: support and leadership at the school level. This work confirms, on the one hand, the stakes for primary schools to have local support in health promotion and, on the other hand, the need to strengthen the role of school principals in the field of health.

While oral agents have been the gold standard for cardiovascular disease therapy, the new generation of treatments is switching to other administration options that offer reduced dosing frequency and more efficacy. The lymphatic network is a unidirectional and low-pressure vascular system that is responsible for the absorption of interstitial fluids, molecules, and cells from the peripheral tissue, including the skin and the intestines. Targeting the lymphatic route for drug delivery employing traditional or new technologies and drug formulations is exponentially gaining attention in the quest to avoid the hepatic first-pass effect. The present review will give an overview of the current knowledge on the involvement of the lymphatic vessels in drug delivery in the context of cardiovascular disease.

Type 2 diabetic cardiomyopathy features Ca 2+ signaling abnormalities, notably an altered mitochondrial Ca 2+ handling. We here aimed to study if it might be due to a dysregulation of either the whole Ca 2+ homeostasis, the reticulum-mitochondrial Ca 2+ coupling, and/or the mitochondrial Ca 2+ entry through the uniporter. Following a 16-week high-fat high-sucrose diet (HFHSD), mice developed cardiac insulin resistance, fibrosis, hypertrophy, lipid accumulation, and diastolic dysfunction when compared to standard diet. Ultrastructural and proteomic analyses of cardiac reticulum-mitochondria interface revealed tighter interactions not compatible with Ca 2+ transport in HFHSD cardiomyocytes. Intramyocardial adenoviral injections of Ca 2+ sensors were performed to measure Ca 2+ fluxes in freshly isolated adult cardiomyocytes and to analyze the direct effects of in vivo type 2 diabetes on cardiomyocyte function. HFHSD resulted in a decreased IP3R-VDAC interaction and a reduced IP3-stimulated Ca 2+ transfer to mitochondria, with no changes in reticular Ca 2+ level, cytosolic Ca 2+ transients, and mitochondrial Ca 2+ uniporter function. Disruption of organelle Ca 2+ exchange was associated with decreased mitochondrial bioenergetics and reduced cell contraction, which was rescued by an adenovirus-mediated expression of a reticulum-mitochondria linker. An 8-week diet reversal was able to restore cardiac insulin signaling, Ca 2+ transfer, and cardiac function in HFHSD mice. Therefore, our study demonstrates that the reticulum-mitochondria Ca 2+ miscoupling may play an early and reversible role in the development of diabetic cardiomyopathy by disrupting primarily the mitochondrial bioenergetics. A diet reversal, by counteracting the MAM-induced mitochondrial Ca 2+ dysfunction, might contribute to restore normal cardiac function and prevent the exacerbation of diabetic cardiomyopathy.