1,326 research outputs found

    A changing penal economy in French society: in search of a historical view

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    Indem verfügbare historische Studien, die speziell das Ende des Ancien Regime und das 19. Jahrhundert behandeln, reanalyisert werden, wird in dem Beitrag eine historische Sicht beschrieben, die die gegenwärtige Umgestaltung des Wirtschaftsstrafrechts im zeitgenössischen Frankreich hervorhebt. (KWübers.)'Reanalyzing available historical studies that deal especially with the end of the Ancien Regime and the XIXth century, the authors take a historical view highlighting the current recomposition of the penal economy of contemporary France.' (author's abstract

    Innate immune receptor NOD2 mediates LGR5+ intestinal stem cell protection against ROS cytotoxicity via mitophagy stimulation

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    International audienceThe nucleotide-binding oligomerization domain-containing protein 2 (NOD2) agonist muramyl dipeptide (MDP), a peptidoglycan motif common to all bacteria, supports leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5)+ intestinal stem cell (ISC) survival through NOD2 activation upon an otherwise lethal oxidative stress-mediated signal. However, the underlying protective mechanisms remain unknown. Here, using irradiation as stressor and primarily murine-derived intestinal organoids as a model system, we show that MDP induced a significant reduction of total and mitochondrial reactive oxygen species (ROS) within ISCs, which was associated with mitophagy induction. ATG16L1 knockout (KO) and NOD2 KO organoids did not benefit from the MDP-induced cytoprotection. We confirmed the MDP-dependent induction of ISC mitophagy upon stress in vivo. These findings elucidate the NOD2-mediated mechanism of cytoprotection involving the clearance of the lethal excess of ROS molecules through mitophagy, triggered by the coordinated activation of NOD2 and ATG16L1 by a nuclear factor κB (NF-κB)-independent pathway

    Quantum Kagome antiferromagnet ZnCu3(OH)6Cl2

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    The frustration of antiferromagnetic interactions on the loosely connected kagome lattice associated to the enhancement of quantum fluctuations for S=1/2 spins was acknowledged long ago as a keypoint to stabilize novel ground states of magnetic matter. Only very recently, the model compound Herbersmithite, ZnCu3(OH)6Cl2, a structurally perfect kagome antiferromagnet, could be synthesized and enables a close comparison to theories. We review and classify various experimental results obtained over the past years and underline some of the pending issues.Comment: 23 pages, 16 figures, invited paper in J. Phys. Soc. Jpn, special topics issue on "Novel States of Matter Induced by Frustration", to be published in Jan. 201

    Receptor-Mediated Transcytosis of Leptin through Human Intestinal Cells In Vitro

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    Gastric Leptin is absorbed by duodenal enterocytes and released on the basolateral side towards the bloodstream. We investigated in vitro some of the mechanisms of this transport. Caco-2/15 cells internalize leptin from the apical medium and release it through transcytosis in the basal medium in a time- temperature-dependent and saturable fashion. Leptin receptors are revealed on the apical brush-border membrane of the Caco-2 cells. RNA-mediated silencing of the receptor led to decreases in the uptake and basolateral release. Leptin in the basal medium was found bound to the soluble form of its receptor. An inhibitor of clathrin-dependent endocytosis (chlorpromazine) decreased leptin uptake. Confocal immunocytochemistry and the use of brefeldin A and okadaic acid revealed the passage of leptin through the Golgi apparatus. We propose that leptin transcytosis by intestinal cells depends on its receptor, on clathrin-coated vesicles and transits through the Golgi apparatus

    Human Immunodeficiency Virus and Malaria in a Representative Sample of Childbearing Women in Kigali, Rwanda

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    In 1986-1987 a consecutive sample of 3702 women presenting to prenatal and pediatric clinics at the only hospital in Kigali, Rwanda, was screened for human immunodeficiency virus (HIV) and malaria infection. The prevalence of HIV antibodies was 29%, and that of malaria parasites was 9%. HIV antibodies were more prevalent in women from the urban center than in those from the outskirts (31% vs. 20%, P < .001), and malaria parasites showed the opposite prevalence pattern (8% vs. 15%, P < .001); after stratifying by location, there was no association between HIV and the presence or degree of malaria parasitemia. HIV prevalence was 45% in women who had received a blood transfusion between 1980-1985 (before screening of donated blood began), and 28% among the great majority (94%) who had never been transfused. HIV prevalence was 44% in single mothers, 34% in women in common law unions, and 20% in those in legal marriages. These high rates of infection in the general population of Kigali highlight the need to develop effective programs for preventing further spread of sexually transmitted HI

    First evidence of subclinical renal tubular injury during sickle-cell crisis

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    International audienceBACKGROUND: The pathophysiologic mechanisms classically involved in sickle-cell nephropathy include endothelial dysfunction and vascular occlusion. Arguments demonstrating that ischemia-reperfusion injury-related kidney damage might coincide with vaso-occlusive crisis (VOC) are lacking. METHODS: In this prospective study, we sought to determine whether tubular cells and glomerular permeability might be altered during VOC. Urine neutrophil gelatinase-associated lipocalin (NGAL) levels and albumin-excretion rates (AER) of 25 patients were evaluated prospectively during 25 VOC episodes and compared to their steady state (ST) values. RESULTS: During VOC, white blood-cell counts (WBC) and C-reactive protein (CRP) were significantly higher than at ST but creatinine levels were comparable. Urine NGAL levels were significantly increased during VOC vs ST (P = 0.007) and remained significant when normalized to urine creatinine (P = 0.004), while AER did not change significantly. The higher urine NGAL concentration was not associated with subsequent (24-48 hour) acute kidney injury. Univariate analysis identified no significant correlations between urine NGAL levels and laboratory parameters during VOC. CONCLUSIONS: These results demonstrated that subclinical ischemia-reperfusion tubular injury is common during VOC and highlight the importance of hydroelectrolyte monitoring and correction during VOC

    Qualitative Assessment of the Symptoms and Impact of Pancreatic Exocrine Insufficiency (PEI) to Inform the Development of a Patient-Reported Outcome (PRO) Instrument

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    Background: Pancreatic exocrine insufficiency (PEI) affects patients with chronic pancreatitis (CP) and cystic fibrosis (CF) who produce insufficient digestive pancreatic enzymes. Common symptoms include steatorrhoea, diarrhea, and abdominal pain. Objective: The objective of the study was to develop and test the content validity of a patient-reported outcome (PRO) instrument assessing PEI symptoms and their impact on health-related quality of life. Methods: Instrument development was supported by a literature review, expert physician interviews (n = 10: Germany 4, UK 3, France 3), and exploratory, qualitative, concept-elicitation interviews with patients with CF and CP with PEI (n = 61: UK 29, Germany 18, France 14) and expert physicians (n = 10). Cognitive debriefing of the draft instrument was then performed with patients with PEI (n = 37: UK 24, Germany 8, France 5), and feasibility was assessed with physicians (n = 3). For all interviews, verbatim transcripts were qualitatively analysed using thematic analysis methods and Atlas.ti computerized qualitative software. All themes were data driven rather than a priori. Results: Patient interviews elicited symptoms and impacts not reported in the literature. Six symptom concepts emerged: pain, bloating, bowel symptoms, nausea/vomiting, eating problems, and tiredness/fatigue. Six impact domains were also identified. A 45-item instrument was developed in English, French, and German for testing in cognitive debriefing patient interviews. Following cognitive debriefing, 18 items were deleted. Conclusion: Rigorous qualitative patient research and expert clinical input supported development of a PEI-specific PRO with the potential to aid management and monitoring of unmet needs among patients with PEI. The next step is to perform psychometric evaluation of the resulting instrument.</p
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