418 research outputs found

    ‘What Forced Men to Kill Their Own Kind in Religious Ceremonies’? Anthropology and Metaphysics of Sacrifice in the Work of Georges Bataille and René Girard

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    Traditionally used to designate bloody rituals practiced in so-called ‘primitive societies’, the notion of sacrifice is commonly understood as a strategic investment in which the renunciation of something valuable is compensated by a more advantageous return. Sharing such a functionalist perspective, social theorists describe sacrifice as a means to renewing social and/or religious bonds through the transgression of social and/or religious boundaries. However, social theorists do not explain why men need to renew such bonds – i.e. what lies behind the human desire to unite with the divine and why violence exists in the first place – and ultimately leave unresolved the question of sacrifice’s deep origins. This article examines how two French theorists, namely Georges Bataille and René Girard, attempt to overcome the theoretical constraints faced by their predecessors and offer an innovative answer to the question of sacrifice’s deep origins, providing Western functionalist sacrifice theories with an unprecedented depth

    Bios2mds: an R package for comparing orthologous protein families by metric multidimensional scaling

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    BACKGROUND: The distance matrix computed from multiple alignments of homologous sequences is widely used by distance-based phylogenetic methods to provide information on the evolution of protein families. This matrix can also be visualized in a low dimensional space by metric multidimensional scaling (MDS). Applied to protein families, MDS provides information complementary to the information derived from tree-based methods. Moreover, MDS gives a unique opportunity to compare orthologous sequence sets because it can add supplementary elements to a reference space. RESULTS: The R package bios2mds (from BIOlogical Sequences to MultiDimensional Scaling) has been designed to analyze multiple sequence alignments by MDS. Bios2mds starts with a sequence alignment, builds a matrix of distances between the aligned sequences, and represents this matrix by MDS to visualize a sequence space. This package also offers the possibility of performing K-means clustering in the MDS derived sequence space. Most importantly, bios2mds includes a function that projects supplementary elements (a.k.a. "out of sample" elements) onto the space defined by reference or "active" elements. Orthologous sequence sets can thus be compared in a straightforward way. The data analysis and visualization tools have been specifically designed for an easy monitoring of the evolutionary drift of protein sub-families. CONCLUSIONS: The bios2mds package provides the tools for a complete integrated pipeline aimed at the MDS analysis of multiple sets of orthologous sequences in the R statistical environment. In addition, as the analysis can be carried out from user provided matrices, the projection function can be widely used on any kind of data

    Structural evolution of G-protein-coupled receptors: a sequence space approach

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    Class A G-protein-coupled receptors (GPCRs) provide a fascinating example of evolutionary success. In this review, we discuss how metric multidimensional scaling (MDS), a multivariate analysis method, complements traditional tree-based phylogenetic methods and helps decipher the mechanisms that drove the evolution of class A GPCRs. MDS provides low-dimensional representations of a distance matrix. Applied to a multiple sequence alignment, MDS represents the sequences in a Euclidean space as points whose interdistances are as close as possible to the distances in the alignment (the so-called sequence space). We detail how to perform the MDS analysis of a multiple sequence alignment and how to analyze and interpret the resulting sequence space. We also show that the projection of supplementary data (a property of the MDS method) can be used to straightforwardly monitor the evolutionary drift of specific subfamilies. The sequence space of class A GPCRs reveals the key role of mutations at the level of the TM2 and TM5 proline residues in the evolution of class A GPCRs

    In Vitro Effects of the Endocrine Disruptor p,p’-DDT on Human Follitropin Receptor

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    BACKGROUND: 1-chloro-4-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl]benzene (p,p\u27-DDT) is a persistent environmental endocrine disruptor (ED). Several studies have shown an association between p,p\u27-DDT exposure and reproductive abnormalities. OBJECTIVES: To investigate the putative effects of p,p\u27-DDT on the human follitropin receptor (FSHR) function. METHODS AND RESULTS: We used Chinese hamster ovary (CHO) cells stably expressing human FSHR to investigate the impact of p,p\u27-DDT on FSHR activity and its interaction with the receptor. At a concentration of 5 μM p,p\u27-DDT increased the maximum response of the FSHR to follitropin by 32 ± 7.45%. However, 5 μM p,p\u27-DDT decreased the basal activity and did not influence the maximal response of the closely related LH/hCG receptor to human chorionic gonadotropin (hCG). The potentiating effect of p,p\u27-DDT was specific for the FSHR. Moreover, in cells that did not express FSHR, p,p\u27-DDT had no effect on cAMP response. Thus, the potentiating effect of p,p\u27-DDT was dependent on the FSHR. In addition, p,p\u27-DDT increased the sensitivity of FSHR to hCG and to a low molecular weight agonist of the FSHR, 3-((5methyl)-2-(4-benzyloxy-phenyl)-5-{[2-[3-ethoxy-4-methoxy-phenyl)-ethylcarbamoyl]-methyl}-4-oxo-thiazolidin-3-yl)-benzamide (16a). Basal activity in response to p,p\u27-DDT and potentiation of the FSHR response to FSH by p,p\u27-DDT varied among FSHR mutants with altered transmembrane domains (TMDs), consistent with an effect of p,p\u27-DDT via TMD binding. This finding was corroborated by the results of simultaneously docking p,p\u27-DDT and 16a into the FSHR transmembrane bundle. CONCLUSION:p,p\u27-DDT acted as a positive allosteric modulator of the FSHR in our experimental model. These findings suggest that G protein-coupled receptors are additional targets of endocrine disruptor

    Le développement de l'embryon zygotique chez Vitis vinifera L.

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    The development of the zygotic embryo of Vitis vinifera L.The embryonic development of Vitis vinifera from the zygote to the mature embryo has been studied. The planes of early cell divisions are irregular, thus leading to formation of a large globular proembryo comprising about 1500 undifferentiated cells above a bulky suspensor. Organogenesis of the embryo sta rts with initiation of the cotyledons and constitution of the radicular meristem. The intercotyledonary zone, future shoot apex, is formed by about 300 cells. In this zone, cells remain undifferentiated throughout embryogenesis; its organization begins to be completed only after germination. The radicular meristem, on the other hand, is functioning from the embryonic stage. The meristem of the embryonic radicle and the meristem of the adventitious root are identical in their ('open' type) organization

    Traitement médical de l’endométriose douloureuse sans infertilité, RPC Endométriose CNGOF-HAS

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    OBJECTIVE: To provide clinical practice guidelines for the management of painful endometriosis in women without infertility. METHODS: Systematic review of the literature literature since 2006, level of evidence rating, external proofreading and grading of the recommendation grade by an expert group according to HAS methodology. RESULTS: Combined hormonal contraceptives (COP) and the levonorgestrel-releasing intra-uterin system (LNG-IUS) are recommended as first-line hormonal therapies for the treatment of painful endometriosis (grade B). Second-line therapy relies on oral desogestrel microprogestative, etonogestrel-releasing implant, GnRH analogs (GnRHa) and dienogest (grade C). It is recommended to use add-back therapy containing estrogen in association with GnRHa (grade B). After endometriosis surgery, hormonal treatment relying on COP or LNG-IUS is recommended to prevent pain recurrence (grade B). COP is recommended to reduce the risk of endometrioma recurrence after surgery (grade B) but the prescription of GnRHa is not recommended (grade C). Continuous COP is recommended in case of dysmenorrhea (grade B). GnRHa is not recommended as first line endometriosis treatment for adolescent girl because of the risk of bone demineralization (grade B). The management of endometriosis-induced chronic pain requires an interdisciplinary evaluation. Physical therapies improving the quality of life such as yoga, relaxation or osteopathy can be proposed (expert agreement). Promising medical alternatives are currently under preclinical and clinical evaluation

    Microvascular vasodilator properties of the angiotensin II type 2 receptor in a mouse model of type 1 diabetes

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    Diabetes Mellitus is associated with severe cardiovascular disorders involving the renin-angiotensin system, mainly through activation of the angiotensin II type 1 receptor (AT1R). Although the type 2 receptor (AT2R) opposes the effects of AT1R, with vasodilator and anti-trophic properties, its role in diabetes is debatable. Thus we investigated AT2R-mediated dilatation in a model of type 1 diabetes induced by streptozotocin in 5-month-old male mice lacking AT2R (AT2R). Glucose tolerance was reduced and markers of inflammation and oxidative stress (cyclooxygenase-2, gp91phox p22phox and p67phox) were increased in AT2R mice compared to wild-type (WT) animals. Streptozotocin-induced hyperglycaemia was higher in AT2R than in WT mice. Arterial gp91phox and MnSOD expression levels in addition to blood 8-isoprostane and creatinine were further increased in diabetic AT2R mice compared to diabetic WT mice. AT2R-dependent dilatation in both isolated mesenteric resistance arteries and perfused kidneys was greater in diabetic mice than in non-diabetic animals. Thus, in type 1 diabetes, AT2R may reduce glycaemia and display anti-oxidant and/or anti-inflammatory properties in association with greater vasodilatation in mesenteric arteries and in the renal vasculature, a major target of diabetes. Therefore AT2R might represent a new therapeutic target in diabetes

    Traitement médical de l’endométriose douloureuse chez l’adolescente, RPC Endométriose CNGOF-HAS

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    OBJECTIVE: To analyse the literature on the treatment of adolescent painful endometriosis. METHOD: This work is based on a Review of the literature between January 2006 and December 2017. The Medline (Pubmed) and Cochrane database were searched for meta-analyzes, randomized trials, literature reviews, controlled, not controlled and retrospective studies published on the subject. Studies concerning adolescent\u27s dysmenorrhea without endometriosis were excluded. RESULTS: Study quality is heterogeneous. Dienogest and GnRH agonists (GnRHa) are the only treatments specifically evaluated for the treatment of adolescent endometriosis. They reduce the pain associated with endometriosis. Combined oral contraceptives have not been studied in the context of endometriosis but they are effective on dysmenorrhea. Add back therapy, containing estrogens improves bone mineral density and quality of life for young women treated with GnRHa. CONCLUSION: Medical treatment of endometriosis in adolescent is associated with risks related to the young age. The therapeutic strategy should take into account the adverse effects of each treatment

    Traitement médical de l’endométriose : prise en charge de la douleur et de l’évolution des lésions par traitement hormonal. RPC Endométriose CNGOF-HAS

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    The available literature, from 2006 to 2017, on hormonal treatment has been analysed as a contribution to the HAS-CNGOF task force for the treatment of endometriosis. Available data are heterogeneous and the general level of evidence is moderate. Hormonal treatment is usually offered as the primary option to women suffering from endometriosis. It cannot be used in women willing to conceive. In women who have not been operated, the first line of hormonal treatment includes combined oral contraceptives (COC) and the levonorgestrel-releasing intra uterine system (52mg LNG-IUS). As a second line, desogestrel progestin only pills, etonogestrel implants, GnRH analogs (GnRHa) with add back therapy and dienogest can be offered. Add back therapy should include estrogens to prevent bone loss and improve quality of life, it can be introduced before the third month of treatment to prevent side effects. The literature does not support preoperative hormonal treatment for the sole purpose of reducing complications or recurrence, or facilitating surgical procedures. After surgical treatment, hormonal treatment is recommended to prevent pain recurrence and improve quality of life. COCs or LNG IUS are recommended as a first line. To prevent recurrence of endometriomas COC is advised and maintained as long as tolerance is good in the absence of pregnancy plans. In case of dysmenorrhea, postoperative COC should be used in a continuous scheme. GnRHa are not recommended in the sole purpose of reducing endometrioma recurrence risk
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