Mossy fiber plasticity and enhanced hippocampal excitability, without hippocampal cell loss or altered neurogenesis, in an animal model of prolonged febrile seizures.

Seizures induced by fever (febrile seizures) are the most frequent seizures affecting infants and children; however, their impact on the developing hippocampal formation is not completely understood. Such understanding is highly important because of the potential relationship of prolonged febrile seizures to temporal lobe epilepsy. Using an immature rat model, we have previously demonstrated that prolonged experimental febrile seizures render the hippocampus hyperexcitable throughout life. Here we examined whether (1) neuronal loss, (2) altered neurogenesis, or (3) mossy fiber sprouting, all implicated in epileptogenesis in both animal models and humans, were involved in the generation of a pro-epileptic, hyperexcitable hippocampus by these seizures. The results demonstrated that prolonged experimental febrile seizures did not result in appreciable loss of any vulnerable hippocampal cell population, though causing strikingly enhanced sensitivity to hippocampal excitants later in life. In addition, experimental febrile seizures on postnatal day 10 did not enhance proliferation of granule cells, whereas seizures generated by kainic acid during the same developmental age increased neurogenesis in the immature hippocampus. However, prolonged febrile seizures resulted in long-term axonal reorganization in the immature hippocampal formation: Mossy fiber densities in granule cell- and molecular layers were significantly increased by 3 months (but not 10 days) after the seizures. Thus, the data indicate that prolonged febrile seizures influence connectivity of the immature hippocampus long-term, and this process requires neither significant neuronal loss nor altered neurogenesis. In addition, the temporal course of the augmented mossy fiber invasion of the granule cell and molecular layers suggests that it is a consequence, rather than the cause, of the hyperexcitable hippocampal network resulting from these seizures

Mossy fiber plasticity and enhanced hippocampal excitability, without hippocampal cell loss or altered neurogenesis, in an animal model of prolonged febrile seizures.

Seizures induced by fever (febrile seizures) are the most frequent seizures affecting infants and children; however, their impact on the developing hippocampal formation is not completely understood. Such understanding is highly important because of the potential relationship of prolonged febrile seizures to temporal lobe epilepsy. Using an immature rat model, we have previously demonstrated that prolonged experimental febrile seizures render the hippocampus hyperexcitable throughout life. Here we examined whether (1) neuronal loss, (2) altered neurogenesis, or (3) mossy fiber sprouting, all implicated in epileptogenesis in both animal models and humans, were involved in the generation of a pro-epileptic, hyperexcitable hippocampus by these seizures. The results demonstrated that prolonged experimental febrile seizures did not result in appreciable loss of any vulnerable hippocampal cell population, though causing strikingly enhanced sensitivity to hippocampal excitants later in life. In addition, experimental febrile seizures on postnatal day 10 did not enhance proliferation of granule cells, whereas seizures generated by kainic acid during the same developmental age increased neurogenesis in the immature hippocampus. However, prolonged febrile seizures resulted in long-term axonal reorganization in the immature hippocampal formation: Mossy fiber densities in granule cell- and molecular layers were significantly increased by 3 months (but not 10 days) after the seizures. Thus, the data indicate that prolonged febrile seizures influence connectivity of the immature hippocampus long-term, and this process requires neither significant neuronal loss nor altered neurogenesis. In addition, the temporal course of the augmented mossy fiber invasion of the granule cell and molecular layers suggests that it is a consequence, rather than the cause, of the hyperexcitable hippocampal network resulting from these seizures

Do the levels of industrial pollutants influence the distribution and abundance of dinoflagellate cysts in the recently-deposited sediment of a Mediterranean coastal ecosystem?

We studied the relationships between sediment industrial pollutants concentrations, sediment characteristics and the dinoflagellate cyst abundance within a coastal lagoon by investigating a total of 55 sampling stations within the Bizerte lagoon, a highly anthropized Mediterranean ecosystem. The sediment of Bizerte lagoon is char- acterized by a high dinocyst abundance, reaching a maximum value of 2742 cysts·g−1 of dry sediment. The investigated cyst diversity was characterized by the presence of 22 dominant dinocyst morphotypes belonging to 11 genera. Two dinoflagellate species dominated the assemblage: Alexandrium pseudogonyaulax and Protoperidinium claudicans, representing 29 to 89% and 5 to 38% of the total cyst abundance, respectively, depending on the station. Seven morphotypes belonging to potentially toxic species were detected, including Alexandrium minutum, A. pseudogonyaulax, Alexandrium catenella/tamarense species complex, Lingulodinium polyedrum, Gonyaulax cf. spinifera complex, Prorocentrum micans and Protoceratium reticulatum. Pearson correlation values showed a positive correlation (α = 0.05) between cyst abundance and both water content and fine silt sediment content. Clustering revealed that the highest abundance of cysts corresponds to stations presenting the higher amounts of heavy metals. The simultaneous autoregressive model (SAM) highlighted a significant correlation (α = 0.05) between cyst accumulation and two main factors: sediment water content and sediment content for several heavy metals, including Hg, Cd, Cu, Ni and Cr. These results suggest that the degree of heavy metal pollution could influence cyst accumulation patterns.peer-reviewe

Metallothionein gene identification and expression in the cockle ( Cerastoderma edule) under parasitism (trematodes) and cadmium contaminations

Parmi les organismes benthiques, les bivalves sont souvent utilisés comme bioindicateurs des pollutions environnementales, du fait de leur importante capacité de bioaccumulation des métaux lourds conduisant à l'induction des métallothionéines (MT). Les MT sont de petites protéines cytosoliques capables de fixer les métaux et qui sont impliquées dans l'homéostasie et la détoxication de ces métaux chez les organismes. Ces protéines peuvent être induites par un grand nombre de facteurs tels que les hormones, les stress physiques, le parasitisme. La quantification des MT en relation avec le parasitisme est rarement reportée dans la littérature, bien que le parasitisme soit omniprésent et très délétère chez les bivalves. De plus, seulement un petit nombre de gènes de MT ont été identifiés chez les mollusques. Cette étude décrit la caractérisation de la séquence partielle d'un gène de MT (Cemt1) chez la coque Cerastoderma edule, qui présente plus de 80 % d'homologie avec de nombreuses séquences de MT de bivalves. A partir de cette séquence, des amorces spécifiques, utilisables en PCR quantitative en temps réel, ont été déterminées. Le niveau d'expression du gène Cemt1, ainsi que la quantité de protéine MT ont été analysés chez des individus soumis à différents paramètres : sans parasites ou infestés par le trématode digène Himasthla elongata, et lors d'expositions au cadmium à 15 µg Cd L−1. Des résultats concordants ont été obtenus lors de la quantification des protéines MT et de l'analyse de l'expression du gène Cemt1. Ceux-ci mettent en évidence que les concentrations en MT augmentent significativement par les deux types de traitement (infestation parasitaire et exposition au cadmium).Among benthic organisms, bivalves are often used as bioindicators of environmental pollution because of their high bioaccumulation capacities for heavy metals leading to metallothioneins (MT) induction. MT are small cytosolic metal-binding proteins involved in metal homeostasis and detoxification in living organisms. These proteins can also be induced by a wide range of factors, such as hormones, physical stress, parasitism. MT quantification in relation to parasitism is rarely reported in literature, while parasites are omnipresent and have deleterious impacts on bivalves. Moreover, only a few number of MT genes have been characterized in molluscs. This study describes the partial sequence of the MT gene (Cemt1) in the edible cockle Cerastoderma edule. The cockle's MT cDNA was sequenced and showed over 80% homology to several other bivalve MT sequences. This sequence was then used to determine MT specific primers which can be used in quantitative real time PCR. MT protein and gene expression levels were quantified for individuals selected under different conditions: free from or infected by the digenean trematode Himasthla elongata, and under cadmium exposure at 15 mu g Cd L-1. Results evidenced that MT concentrations were significantly increased by both treatments; parasite infection and Cd exposure. Moreover, congruent results between MT protein and gene expression levels were obtained

Commitment to the Regulatory T Cell Lineage Requires CARMA1 in the Thymus but Not in the Periphery

Regulatory T (Treg) cells expressing forkhead box P3 (Foxp3) arise during thymic selection among thymocytes with modestly self-reactive T cell receptors. In vitro studies suggest Foxp3 can also be induced among peripheral CD4+ T cells in a cytokine dependent manner. Treg cells of thymic or peripheral origin may serve different functions in vivo, but both populations are phenotypically indistinguishable in wild-type mice. Here we show that mice with a Carma1 point mutation lack thymic CD4+Foxp3+ Treg cells and demonstrate a cell-intrinsic requirement for CARMA1 in thymic Foxp3 induction. However, peripheral Carma1-deficient Treg cells could be generated and expanded in vitro in response to the cytokines transforming growth factor beta (TGFβ) and interleukin-2 (IL-2). In vivo, a small peripheral Treg pool existed that was enriched at mucosal sites and could expand systemically after infection with mouse cytomegalovirus (MCMV). Our data provide genetic evidence for two distinct mechanisms controlling regulatory T cell lineage commitment. Furthermore, we show that peripheral Treg cells are a dynamic population that may expand to limit immunopathology or promote chronic infection

Microchromosomes are building blocks of bird, reptile, and mammal chromosomes

Microchromosomes, once considered unimportant shreds of the chicken genome, are gene-rich elements with a high GC content and few transposable elements. Their origin has been debated for decades. We used cytological and whole-genome sequence comparisons, and chromosome conformation capture, to trace their origin and fate in genomes of reptiles, birds, and mammals. We find that microchromosomes as well as macrochromosomes are highly conserved across birds and share synteny with single small chromosomes of the chordate amphioxus, attesting to their origin as elements of an ancient animal genome. Turtles and squamates (snakes and lizards) share different subsets of ancestral microchromosomes, having independently lost microchromosomes by fusion with other microchromosomes or macrochromosomes. Patterns of fusions were quite different in different lineages. Cytological observations show that microchromosomes in all lineages are spatially separated into a central compartment at interphase and during mitosis and meiosis. This reflects higher interaction between microchromosomes than with macrochromosomes, as observed by chromosome conformation capture, and suggests some functional coherence. In highly rearranged genomes fused microchromosomes retain most ancestral characteristics, but these may erode over evolutionary time; surprisingly, de novo microchromosomes have rapidly adopted high interaction. Some chromosomes of early-branching monotreme mammals align to several bird microchromosomes, suggesting multiple microchromosome fusions in a mammalian ancestor. Subsequently, multiple rearrangements fueled the extraordinary karyotypic diversity of therian mammals. Thus, microchromosomes, far from being aberrant genetic elements, represent fundamental building blocks of amniote chromosomes, and it is mammals, rather than reptiles and birds, that are atypical

Citizen science for public deliberation of local environment policies

Broadening citizen participation in scientific knowledge production has become a priority of national and supra-national institutions and research agencies. Out of their interest for scientific research and public learning, citizen science projects are often presented as offering a unique opportunity to involve more directly the public in policy-making. However, despite twenty years of flourishment of participative scientific research, making citizen science a tool to foster participatory democracy remains a challenge. Political outputs of citizen science are indeed often restricted to its role in the production of data to inform policy making processes. In this paper, we propose an innovative theoretical model of democratization through citizen science, in which participative data collection is associated with public online deliberation. Drawing both on online political deliberation research and citizen science literature, we argue that citizens’ engagement in contributory science could help create the conditions of good-quality public deliberations. We then present a technical device (an online platform) that put this model into practice in the context of the regulation of public lighting in two French municipalities

Direct observation of ion dynamics in supercapacitor electrodes using in situ diffusion NMR spectroscopy

Ionic transport inside porous carbon electrodes underpins the storage of energy in supercapacitors and the rate at which they can charge and discharge, yet few studies have elucidated the materials properties that influence ion dynamics. Here we use in situ pulsed field gradient NMR spectroscopy to measure ionic diffusion in supercapacitors directly. We find that confinement in the nanoporous electrode structures decreases the effective self-diffusion coefficients of ions by over two orders of magnitude compared with neat electrolyte, and in-pore diffusion is modulated by changes in ion populations at the electrode/electrolyte interface during charging. Electrolyte concentration and carbon pore size distributions also affect in-pore diffusion and the movement of ions in and out of the nanopores. In light of our findings we propose that controlling the charging mechanism may allow the tuning of the energy and power performances of supercapacitors for a range of different applications

Catalogue of parasites and diseases of the common cockle Cerastoderma edule

Sem resumo disponível.publishe

RANK signaling increases after anti-HER2 therapy contributing to the emergence of resistance in HER2-positive breast cancer

Background: Around 15-20% of primary breast cancers are characterized by HER2 protein overexpression and/or HER2 gene amplification. Despite the successful development of anti-HER2 drugs, intrinsic and acquired resistance represents a major hurdle. This study was performed to analyze the RANK pathway contribution in HER2-positive breast cancer and anti-HER2 therapy resistance. Methods: RANK and RANKL protein expression was assessed in samples from HER2-positive breast cancer patients resistant to anti-HER2 therapy and treatment-naive patients. RANK and RANKL gene expression was analyzed in paired samples from patients treated with neoadjuvant dual HER2-blockade (lapatinib and trastuzumab) from the SOLTI-1114 PAMELA trial. Additionally, HER2-positive breast cancer cell lines were used to modulate RANK expression and analyze in vitro the contribution of RANK signaling to anti-HER2 resistance and downstream signaling. Results: RANK and RANKL proteins are more frequently detected in HER2-positive tumors that have acquired resistance to anti-HER2 therapies than in treatment-naive ones. RANK (but not RANKL) gene expression increased after dual anti-HER2 neoadjuvant therapy in the cohort from the SOLTI-1114 PAMELA trial. Results in HER2-positive breast cancer cell lines recapitulate the clinical observations, with increased RANK expression observed after short-term treatment with the HER2 inhibitor lapatinib or dual anti-HER2 therapy and in lapatinib-resistant cells. After RANKL stimulation, lapatinib-resistant cells show increased NF-κB activation compared to their sensitive counterparts, confirming the enhanced functionality of the RANK pathway in anti-HER2-resistant breast cancer. Overactivation of the RANK signaling pathway enhances ERK and NF-κB signaling and increases lapatinib resistance in different HER2-positive breast cancer cell lines, whereas RANK loss sensitizes lapatinib-resistant cells to the drug. Our results indicate that ErbB signaling is required for RANK/RANKL-driven activation of ERK in several HER2-positive cell lines. In contrast, lapatinib is not able to counteract the NF-κB activation elicited after RANKL treatment in RANK-overexpressing cells. Finally, we show that RANK binds to HER2 in breast cancer cells and that enhanced RANK pathway activation alters HER2 phosphorylation status. Conclusions: Our data support a physical and functional link between RANK and HER2 signaling in breast cancer and demonstrate that increased RANK signaling may contribute to the development of lapatinib resistance through NF-κB activation. Whether HER2-positive breast cancer patients with tumoral RANK expression might benefit from dual HER2 and RANK inhibition therapy remains to be elucidated