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941.
Samantha Gomart Cécile Damoiseaux Pascale Jespers Martine Makanga Nathalie Labranche Stéphanie Pochet Charles Michaux Guy Berkenboom Robert Naeije Kathleen McEntee Laurence Dewachter 《Respiratory research》2014,15(1):12
Background
Systemic hypertension may be associated with an increased pulmonary vascular resistance, which we hypothesized could be, at least in part, mediated by increased leptin.Methods
Vascular reactivity to phenylephrine (1 μmol/L), endothelin-1 (10 nmol/L) and leptin (0.001–100 nmol/L) was evaluated in endothelium-intact and -denuded isolated thoracic aorta and pulmonary arteries from spontaneously hypertensive versus control Wistar rats. Arteries were sampled for pathobiological evaluation and lung tissue for morphometric evaluation.Results
In control rats, endothelin-1 induced a higher level of contraction in the pulmonary artery than in the aorta. After phenylephrine or endothelin-1 precontraction, leptin relaxed intact pulmonary artery and aortic rings, while no response was observed in denuded arteries. Spontaneously hypertensive rats presented with increased reactivity to phenylephrine and endothelin-1 in endothelium-intact pulmonary arteries. After endothelin-1 precontraction, endothelium-dependent relaxation to leptin was impaired in pulmonary arteries from hypertensive rats. In both strains of rats, aortic segments were more responsive to leptin than pulmonary artery. In hypertensive rats, pulmonary arteries exhibited increased pulmonary artery medial thickness, associated with increased expressions of preproendothelin-1, endothelin-1 receptors type A and B, inducible nitric oxide synthase and decreased endothelial nitric oxide synthase, together with decreased leptin receptor and increased suppressor of cytokine signaling 3 expressions.Conclusions
Altered pulmonary vascular reactivity in hypertension may be related to a loss of endothelial buffering of vasoconstriction and decreased leptin-induced vasodilation in conditions of increased endothelin-1. 相似文献942.
Emilie Fugier Hélène Marche Marie-Ange Thélu Zuzana Macek Jílková Nicolas Van Campenhout Tania Dufeu-Duchesne Vincent Leroy Jean-Pierre Zarski Nathalie Sturm Patrice N. Marche Evelyne Jouvin-Marche 《PloS one》2014,9(4)
During chronic hepatitis C virus (HCV) infection, the role of intra-hepatic (IH) natural killer (NK) cells is still controversial. To clarify their functions, we investigated anti-viral and cytotoxic activity of NK cells in human fresh liver biopsies. We compared the functions of IH-NK cells in HCV-infected and NASH patients in physiological conditions as well as after stimulation using flow cytometric and immunohistochemical analyses. Interestingly, few IH-NK cells produced anti-viral cytokine IFN-γ in HCV-infected patients similarly as in non-infected individuals. Spontaneous degranulation activity was extremely low in peripheral NK cells compared to IH-NK cells, and was significantly higher in IH-NK cells from HCV-infected patients compared to non-infected individuals. Immunohistochemical analysis revealed that perforin granules were polarized at the apical pole of IH-NK cells. The presence of CD107a and perforin in IH-NK cells demonstrated that NK cells exerted a cytolytic activity at the site of infection. Importantly, IH-NK cell functions from HCV-infected patients were inducible by specific exogenous stimulations. Upon ex vivo K562 target cell stimulations, the number of degranulating NK cells was significantly increased in the pool of IH-NK cells compared to circulating NK cells. Interestingly, after stimulation, the frequency of IFN-γ-producing IH-NK cells in HCV-infected patients was significantly higher at early stage of inflammation whereas the spontaneous IH-NK cell degranulation activity was significantly impaired in patients with highest inflammation and fibrosis Metavir scores. Our study highlights that some IH-NK cells in HCV-infected patients are able to produce INF-γ and degranulate and that those two activities depend on liver environment including the severity of liver injury. Thus, we conclude that critical roles of IH-NK cells have to be taken into account in the course of the liver pathogenesis associated to chronic HCV infection. 相似文献
943.
Miriam Marquis Salix Boulet Simon Mathien Justine Rousseau Paméla Thébault Jean-Fran?ois Daudelin Julie Rooney Benjamin Turgeon Claudine Beauchamp Sylvain Meloche Nathalie Labrecque 《PloS one》2014,9(1)
The classical mitogen-activated protein kinases (MAPKs) ERK1 and ERK2 are activated upon stimulation of cells with a broad range of extracellular signals (including antigens) allowing cellular responses to occur. ERK3 is an atypical member of the MAPK family with highest homology to ERK1/2. Therefore, we evaluated the role of ERK3 in mature T cell response. Mouse resting T cells do not transcribe ERK3 but its expression is induced in both CD4+ and CD8+ T cells following T cell receptor (TCR)-induced T cell activation. This induction of ERK3 expression in T lymphocytes requires activation of the classical MAPK ERK1 and ERK2. Moreover, ERK3 protein is phosphorylated and associates with MK5 in activated primary T cells. We show that ERK3-deficient T cells have a decreased proliferation rate and are impaired in cytokine secretion following in vitro stimulation with low dose of anti-CD3 antibodies. Our findings identify the atypical MAPK ERK3 as a new and important regulator of TCR-induced T cell activation. 相似文献
944.
Hermien Janneke Schutte Sofie Jansen Matthias U. Schafroth J. Carel Goslings Nathalie van der Velde Sophia E. J. A. de Rooij 《PloS one》2014,9(5)
Background
Recent studies have shown that an increased bleeding tendency can be caused by Selective Serotonin Reuptake Inhibitors (SSRI) use. We aimed to investigate the occurrence and risk of blood transfusion in SSRI users compared to non-SSRI users in a cohort of patients admitted for hip-surgery.Methods
We conducted a retrospective cohort study of patients who underwent planned or emergency hip surgery from 1996 to 2011 in the Academic Medical Center in Amsterdam. Primary outcome measure was risk of blood transfusion. Secondary outcome measures were pre- and postoperative hemoglobin level. Multivariate logistic regression was used to adjust for potential confounders.Results
One-hundred and fourteen SSRI users were compared to 1773 non-SSRI users. Risk of blood transfusion during admission was increased for SSRI users in multivariate analyses (OR 1.7 [95% CI 1.1–2.5]). Also, pre-operative hemoglobin levels were lower in SSRI users (7.8±1.0 mmol/L) compared to non-SSRI users (8.0±1.0 mmol/L) (p = 0.042)), as were postoperative hemoglobin levels (6.2±1.0 mmol/L vs. 6.4±1.0 mmol/L respectively) (p = 0.017)).Conclusions
SSRI users undergoing hip surgery have an increased risk for blood transfusion during admission, potentially explained by a lower hemoglobin level before surgery. SSRI use should be considered as a potential risk indicator for increased blood loss in patients admitted for hip surgery. These results need to be confirmed in a prospective study. 相似文献945.
The origin of vocal learning in animals has long been the subject of debate, but progress has been limited by uncertainty regarding the distribution of learning mechanisms across the tree of life, even for model systems such as birdsong. In particular, the importance of learning is well known in oscine songbirds, but disputed in suboscines. Members of this diverse group (∼1150 species) are generally assumed not to learn their songs, but empirical evidence is scarce, with previous studies restricted to the bronchophone (non-tracheophone) clade. Here, we conduct the first experimental study of song development in a tracheophone suboscine bird by rearing spotted antbird (Hylophylax naevioides) chicks in soundproofed aviaries. Individuals were raised either in silence with no tutor or exposed to standardized playback of a heterospecific tutor. All individuals surviving to maturity took a minimum of 79 days to produce a crystallized version of adult song, which in all cases was indistinguishable from wild song types of their own species. These first insights into song development in tracheophone suboscines suggest that adult songs are innate rather than learnt. Given that empirical evidence for song learning in suboscines is restricted to polygamous and lek-mating species, whereas tracheophone suboscines are mainly monogamous with long-term social bonds, our results are consistent with the view that sexual selection promotes song learning in birds. 相似文献
946.
Background
Ichthyosaurs are reptiles that inhabited the marine realm during most of the Mesozoic. Their Cretaceous representatives have traditionally been considered as the last survivors of a group declining since the Jurassic. Recently, however, an unexpected diversity has been described in Upper Jurassic–Lower Cretaceous deposits, but is widely spread across time and space, giving small clues on the adaptive potential and ecosystem control of the last ichthyosaurs. The famous but little studied English Gault Formation and ‘greensands’ deposits (the Upper Greensand Formation and the Cambridge Greensand Member of the Lower Chalk Formation) offer an unprecedented opportunity to investigate this topic, containing thousands of ichthyosaur remains spanning the Early–Late Cretaceous boundary.Methodology/Principal Findings
To assess the diversity of the ichthyosaur assemblage from these sedimentary bodies, we recognized morphotypes within each type of bones. We grouped these morphotypes together, when possible, by using articulated specimens from the same formations and from new localities in the Vocontian Basin (France); a revised taxonomic scheme is proposed. We recognize the following taxa in the ‘greensands’: the platypterygiines ‘Platypterygius’ sp. and Sisteronia seeleyi gen. et sp. nov., indeterminate ophthalmosaurines and the rare incertae sedis Cetarthrosaurus walkeri. The taxonomic diversity of late Albian ichthyosaurs now matches that of older, well-known intervals such as the Toarcian or the Tithonian. Contrasting tooth shapes and wear patterns suggest that these ichthyosaurs colonized three distinct feeding guilds, despite the presence of numerous plesiosaur taxa.Conclusion/Significance
Western Europe was a diversity hot-spot for ichthyosaurs a few million years prior to their final extinction. By contrast, the low diversity in Australia and U.S.A. suggests strong geographical disparities in the diversity pattern of Albian–early Cenomanian ichthyosaurs. This provides a whole new context to investigate the extinction of these successful marine reptiles, at the end of the Cenomanian. 相似文献947.
Research in the epilepsy field is moving from a primary focus on controlling seizures to addressing disease pathophysiology. This requires the adoption of resource- and time-consuming animal models of chronic epilepsy which are no longer able to sustain the testing of even moderate numbers of compounds. Therefore, new in vitro functional assays of epilepsy are needed that are able to provide a medium throughput while still preserving sufficient biological context to allow for the identification of compounds with new modes of action. Here we describe a robust and simple fluorescence-based calcium assay to measure epileptiform network activity using rat primary cortical cultures in a 96-well format. The assay measures synchronized intracellular calcium oscillations occurring in the population of primary neurons and is amenable to medium throughput screening. We have adapted this assay format to the low magnesium and the 4-aminopyridine epilepsy models and confirmed the contribution of voltage-gated ion channels and AMPA, NMDA and GABA receptors to epileptiform activity in both models. We have also evaluated its translatability using a panel of antiepileptic drugs with a variety of modes of action. Given its throughput and translatability, the calcium oscillations assay bridges the gap between simplified target-based screenings and compound testing in animal models of epilepsy. This phenotypic assay also has the potential to be used directly as a functional screen to help identify novel antiepileptic compounds with new modes of action, as well as pathways with previously unknown contribution to disease pathophysiology. 相似文献
948.
Nikolaos Tertipis Linnea Haeggblom Cecilia Nordfors Nathalie Grün Anders N?sman Andrea Vlastos Tina Dalianis Torbj?rn Ramqvist 《PloS one》2014,9(4)
Aim
To examine LMP10 expression and its possible impact on clinical outcome in human papillomavirus (HPV) positive and HPV-negative tonsillar and base of tongue squamous cell carcinoma (TSCC and BOTSCC).Background
Outcome is better in HPV-positive TSCC and BOTSCC compared to matching HPV-negative tumours, with roughly 80% vs. 40% 5-year disease free survival (DFS) with less aggressive treatment than today’s chemoradiotherapy. Since current treatment often results in harmful side effects, less intensive therapy, with sustained patient survival would be an attractive alternative. However, other markers together with HPV status are necessary to select patients and for this purpose LMP10 expression is investigated here in parallel to HPV status and clinical outcome.Materials and Methods
From 385 patients diagnosed between 2000 and 2007 at the Karolinska University Hospital, 278 formalin fixed paraffin embedded TSCC and BOTSCC biopsies, with known HPV DNA status, were tested for LMP10 nuclear and cytoplasmic expression (fraction of positive cells and staining intensity). The data was then correlated to clinical outcome.Results
An absent/low compared to a moderate/high LMP10 nuclear fraction of positive cells was correlated to a better 3-year DFS in the HPV-positive group of patients (log-rank p = 0.005), but not in the HPV-negative group. In the HPV-negative group of patients, in contrast to the HPV-positive group, moderate/high LMP10 cytoplasmic fraction and weak/moderate/high LMP10 cytoplasmic intensity correlated to a better 3-year DFS (p = 0.003 and p = 0.001) and 3-year overall survival (p = 0.001 and 0.009).Conclusion
LMP10 nuclear expression in the HPV-positive group and LMP10 cytoplasmic expression in the HPV-negative group of patients correlated to better clinical outcome. 相似文献949.
Céline Druart Audrey M. Neyrinck Bruno Vlaeminck Veerle Fievez Patrice D. Cani Nathalie M. Delzenne 《PloS one》2014,9(1)
In vitro studies have suggested that isolated gut bacteria are able to metabolize PUFA into CLA (conjugated linoleic acids) and CLnA (conjugated linolenic acids). However, the bioavailability of fatty acid metabolites produced in vivo by the gut microbes remains to be studied. Therefore, we measured intestinal concentration and plasma accumulation of bacterial metabolites produced from dietary PUFA in mice, first injected with a lipoprotein lipase inhibitor, then force-fed with either sunflower oil (200 µl) rich in n-6 PUFA or linseed oil (200 µl) rich in n-3 PUFA. The greatest production of bacterial metabolites was observed in the caecum and colon, and at a much lesser extent in the jejunum and ileum. In the caecal content, CLA proportions were higher in sunflower oil force-fed mice whereas CLnA proportions were higher in linseed oil force-fed mice. The accumulation of the main metabolites (CLA cis-9,trans-11-18:2 and CLnA cis-9,trans-11,cis-15-18:3) in the caecal tissue was not associated with their increase in the plasma, therefore suggesting that, if endogenously produced CLA and CLnA have any biological role in host metabolism regulation, their effect would be confined at the intestinal level, where the microbiota is abundant. 相似文献
950.
Emilie Montastier Sébastien Déjean Caroline Le Gall Wim H. M. Saris Dominique Langin Nathalie Viguerie 《PloS one》2014,9(7)