Performance, représentation et (il)lisibilité du genre dans la fiction sandienne des années 1830

Dans son premier roman, Indiana (1832), Sand établit un réseau de correspondances entre la langue, la performance et l'identité sexuelle qui n'ont pas encore fait l'objet d'une étude approfondie. Or, ces correspondances sous-tendent d'autres romans des années 1830, notamment Lélia (1833), Le Secrétaire intime (1834) et Gabriel (1839). Deux concepts – la performance et la lisibilité – fondent en fait les réflexions de Sand sur la représentation et le genre. Il s'agit dans cet article d'étudier ce réseau d'associations et d'explorer son évolution dans la fiction sandienne des années 1830. Cette analyse permettra de souligner comment, chez Sand, la performativité du genre met en question et trouble la représentation mimétique.

《ロ短調ミサ曲》とバッハ研究:作品の伝承と楽譜編集史からみる研究上の諸問題

This article reviews the past research of Bach's B-minor Mass as part of the reception history of the work through the discussion of how the past editors produced various types of prints since 1833, and proposes how we might approach in the 21st century.

Addressing Selective Polypharmacology of Antipsychotic Drugs Targeting the Bioaminergic Receptors through the Receptor Dynamic Conformational Ensembles

Selective polypharmacology, where a drug acts on multiple rather than single molecular targets involved in a disease, emerges to develop a structure-based system biology approach to design drugs selectively targeting a disease-active protein network. We focus on the bioaminergic receptors that belong to the group of integral membrane signalling proteins coupled to the G protein and represent targets for therapeutic agents against schizophrenia and depression. Among them, it has been shown that the serotonin (5-HT2A and 5-HT6), dopamine (D2 and D3) receptors induce a cognition-enhancing effect (group 1), while the histamine (H1) and serotonin (5-HT2C) receptors lead to metabolic side effects and the 5-HT2B serotonin receptor causes pulmonary hypertension (group 2). Thus, the problem arises to develop an approach that allows identifying drugs targeting only the disease-active receptors, i.e. group 1. The recent release of several crystal structures of the bioaminergic receptors, involving the D3 and H1 receptors provides the possibility to model the structures of all receptors and initiate a study of the structural and dynamic context of selective polypharmacology. In this work, we use molecular dynamics simulations to generate a conformational space of the receptors and subsequently characterize its binding properties applying molecular probe mapping. All-against-all comparison of the generated probe maps of the selected diverse conformations of all receptors with the Tanimoto similarity coefficient (Tc) enable to separate the receptors of group 1 from group 2. The pharmacophore built based on the Tc-selected receptor conformations, using the multiple probe maps discovers structural features that can be used to design molecules selective towards the receptors of group 1. The importance of several predicted residues to ligand selectivity is supported by the available mutagenesis and ligand structure-activity relationships studies. In addition, the Tc-selected conformations of the receptors for group 1 show good performance in isolation of known ligands from a random decoy. Our computational structure-based protocol to tackle selective polypharmacology of antipsychotic drugs could be applied for other diseases involving multiple drug targets, such as oncologic and infectious disorders.

Lung Clearance Index in cystic fibrosis subjects treated for Pulmonary Exacerbations

Pulmonary exacerbations are important clinical events for cystic fibrosis (CF) patients. Studies assessing the ability of the lung clearance index (LCI) to detect treatment response for pulmonary exacerbations have yielded heterogeneous results. Here, we conduct a retrospective analysis of pooled LCI data to assess treatment with intravenous antibiotics for pulmonary exacerbations and to understand factors explaining the heterogeneous response.

A systematic literature search was performed to identify prospective observational studies. Factors predicting the relative change in LCI and spirometry were evaluated while adjusting for within-study clustering.

Six previously reported studies and one unpublished study, which included 176 pulmonary exacerbations in both paediatric and adult patients, were included. Overall, LCI significantly decreased by 0.40 units (95% CI -0.60 -0.19, p=0.004) or 2.5% following treatment. The relative change in LCI was significantly correlated with the relative change in forced expiratory volume in 1 s (FEV1), but results were discordant in 42.5% of subjects (80 out of 188). Higher (worse) baseline LCI was associated with a greater improvement in LCI (slope: -0.9%, 95% CI -1.0- -0.4%).

LCI response to therapy for pulmonary exacerbations is heterogeneous in CF patients; the overall effect size is small and results are often discordant with FEV1.

Differential ecological impacts of an invader and a native under environmental change are revealed by comparative functional responses.

Predicting the ecological impacts of damaging invasive species under relevant environmental contexts is a major challenge, for which comparative functional responses (the relationship between resource availability and consumer uptake rate) have great potential. Here, the functional responses of Gammarus pulex, an ecologically damaging invader in freshwaters in Ireland and other islands, were compared with those of a native trophic equivalent Gammarus duebeni celticus. Experiments were conducted at two dissolved oxygen concentrations (80 and 50 % saturation), representative of anthropogenic water quality changes, using two larval prey, blackfly (Simuliidae spp.) and mayfly (Baetis rhodani). Overall, G. pulex had higher Type II functional responses and hence predatory impacts than G. d. celticus and the functional responses of both predators were reduced by lowered oxygen concentration. However, this reduction was of lower magnitude for the invader as compared to the native. Further, the invader functional response at low oxygen was comparable to that of the native at high oxygen. Attack rates of the two predators were similar, with low oxygen reducing these attack rates, but this effect occurred more strongly for blackfly than mayfly prey. Handling times were significantly lower for the invader compared with the native, and significantly higher at low oxygen, however, the effect of lowered oxygen on handling times was minimal for the invader and pronounced for the native. Maximum feeding rates were significantly greater for the invader compared with the native, and significantly reduced at low oxygen, with this effect again lesser for the invader as compared to the native. The greater functional responses of the invader corroborate with its impacts on recipient macroinvertebrate communities when it replaces the native. Further, our experiments predict that the impact of the invader will be less affected than the native under altered oxygen regimes driven by anthropogenic influences.

Yellow earthworms:Distinctive pigmentation associated with arsenic- and copper-tolerance in Lumbricus rubellus

Lumbricus rubellus Hoffmeister, inhabiting soil at the 19th century Devon Great Consols mine at Tavistock, Devon, UK, show high tolerance to Cu- and As-toxicity and frequently have a striking yellow coloration. Specimens from this site (mature and immature) and from an uncontaminated site on Lancaster University campus (mature) were photographed, and the slide images digitized and analyzed. All L. rubellus showed reddish-purple pigmentation of the body wall that declined in intensity posteriorly. The metal- and metalloid-resistant earthworms, whether mature or immature, showed yellowing in the posterior half of the body. The source of the coloration was intense yellow pigmentation of the chloragogenous tissue surrounding the alimentary canal. The yellow pigmentation is masked by reddish-purple body wall pigmentation anteriorly. Total As concentrations in tissues were determined for the anterior, middle and posterior sections of resistant and non-resistant L. rubellus. Highest concentrations were in the middle sections of the mature and immature resistant L. rubellus (36.17 ± 19.77 and 27.77 ± 9.02 mg As kg^-1, respectively). Resistant immature L. rubellus lost condition over 28 d in soil treated with 750 mg As kg^-1, possibly due to a higher metabolism, whilst there was no loss in condition for resistant mature L. rubellus in the treated soil. As far as the authors are aware, this is the first report of yellow pigmentation of this kind in earthworms. The pigmentation may provide a useful indicator of exposure/resistance to soil contamination. © 2002 Elsevier Science Ltd. All rights reserved.

Interleukin-8 and its receptor CXCR2 in the tumour microenvironment promote colon cancer growth, progression and metastasis

BACKGROUND: Colorectal cancer (CRC) is a leading cause of death in the United States. Increased level of interleukin-8 (IL-8) and CXCR2 on tumours and in the tumour microenvironment has been associated with CRC growth, progression and recurrence in patients. Here, we aimed to evaluate the effects of tissue microenvironment-encoded IL-8 and CXCR2 on colon cancer progression and metastasis.

METHODS: A novel immunodeficient, skin-specific IL-8-expressing transgenic model was generated to evaluate colon cancer growth and metastasis. Syngeneic mouse colon cancer cells were grafted in CXCR2 knockout (KO) mice to study the contribution of CXCR2 in the microenvironment to cancer growth.

RESULTS: Elevated levels of IL-8 in the serum and tumour microenvironment profoundly enhanced the growth of human and mouse colon cancer cells with increased peri-tumoural angiogenesis, and also promoted the extravasation of the cancer cells into the lung and liver. The tumour growth was inhibited in CXCR2 KO mice with significantly reduced tumour angiogenesis and increased tumour necrosis.

CONCLUSION: Increased expression of IL-8 in the tumour microenvironment enhanced colon cancer growth and metastasis. Moreover, the absence of its receptor CXCR2 in the tumour microenvironment prevented colon cancer cell growth. Together, our study demonstrates the critical roles of the tumour microenvironment-encoded IL-8/CXCR2 in colon cancer pathogenesis, validating the pathway as an important therapeutic target.

Combining Bio- and Chemo-Catalysis for the Conversion of Bio-Renewable Alcohols: Homogeneous Iridium Catalysed Hydrogen Transfer Initiated Dehydration of 1,3-Propanediol to Aldehydes

Combining whole cell biocatalysis and chemocatalysis in a single reaction sequence avoids unnecessary separations, and the associated waste and energy consumption. Bacterial fermentation has been employed to convert waste glycerol from biodiesel production into 1,3-propanediol. This 1,3-propanediol can be extracted selectively from the aqueous fermentation broth using ionic liquids. 1,3-propanediol in ionic liquid solution was converted to propanal by hydrogen transfer initiated dehydration (HTID) catalysed by a Cp*IrCl2(NHC) (Cp* = pentamethylcyclopentadienyl; NHC = carbene ligand) complex. The use of an ionic liquid solvent enabled the reaction to be performed under reduced pressure, facilitating the isolation of the product, and improving the reaction selectivity. The Ir(III) catalyst in ionic liquid was found to be highly recyclable.

Characteristics, complications, and gaps in evidence-based interventions in rheumatic heart disease: the Global Rheumatic Heart Disease Registry (the REMEDY study)

AIMS: Rheumatic heart disease (RHD) accounts for over a million premature deaths annually; however, there is little contemporary information on presentation, complications, and treatment.

METHODS AND RESULTS: This prospective registry enrolled 3343 patients (median age 28 years, 66.2% female) presenting with RHD at 25 hospitals in 12 African countries, India, and Yemen between January 2010 and November 2012. The majority (63.9%) had moderate-to-severe multivalvular disease complicated by congestive heart failure (33.4%), pulmonary hypertension (28.8%), atrial fibrillation (AF) (21.8%), stroke (7.1%), infective endocarditis (4%), and major bleeding (2.7%). One-quarter of adults and 5.3% of children had decreased left ventricular (LV) systolic function; 23% of adults and 14.1% of children had dilated LVs. Fifty-five percent (n = 1761) of patients were on secondary antibiotic prophylaxis. Oral anti-coagulants were prescribed in 69.5% (n = 946) of patients with mechanical valves (n = 501), AF (n = 397), and high-risk mitral stenosis in sinus rhythm (n = 48). However, only 28.3% (n = 269) had a therapeutic international normalized ratio. Among 1825 women of childbearing age (12-51 years), only 3.6% (n = 65) were on contraception. The utilization of valvuloplasty and valve surgery was higher in upper-middle compared with lower-income countries.

CONCLUSION: Rheumatic heart disease patients were young, predominantly female, and had high prevalence of major cardiovascular complications. There is suboptimal utilization of secondary antibiotic prophylaxis, oral anti-coagulation, and contraception, and variations in the use of percutaneous and surgical interventions by country income level.