‘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

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

Weighted-covariance factor fuzzy C-means clustering

In this paper, we propose a factor weighted fuzzy c-means clustering algorithm. Based on the inverse of a covariance factor, which assesses the collinearity between the centers and samples, this factor takes also into account the compactness of the samples within clusters. The proposed clustering algorithm allows to classify spherical and non-spherical structural clusters, contrary to classical fuzzy c-means algorithm that is only adapted for spherical structural clusters. Compared with other algorithms designed for non-spherical structural clusters, such as Gustafson-Kessel, Gath-Geva or adaptive Mahalanobis distance-based fuzzy c-means clustering algorithms, the proposed algorithm gives better numerical results on artificial and real well known data sets. Moreover, this algorithm can be used for high dimensional data, contrary to other algorithms that require the computation of determinants of large matrices. Application on Mid-Infrared spectra acquired on maize root and aerial parts of Miscanthus for the classification of vegetal biomass shows that this algorithm can successfully be applied on high dimensional data

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

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

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

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

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

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

Allylnitrile metabolism by CYP2E1 and other CYPs leads to distinct lethal and vestibulotoxic effects in the mouse

This study addressed the hypothesis that the vestibular or lethal toxicities of allylnitrile depend on CYP2E1-mediated bioactivation. Wild-type (129S1) and CYP2E1-null male mice were exposed to allylnitrile at doses of 0, 0.5, 0.75, or 1.0 mmol/kg (po), following exposure to drinking water with 0 or 1% acetone, which induces CYP2E1 expression. Induction of CYP2E1 activity by acetone in 129S1 mice and lack of activity in null mice was confirmed in liver microsomes. Vestibular toxicity was assessed using a behavioral test battery and illustrated by scanning electron microscopy observation of the sensory epithelia. In parallel groups, concentrations of allylnitrile and cyanide were assessed in blood after exposure to 0.75 mmol/kg of allylnitrile. Following allylnitrile exposure, mortality was lower in CYP2E1-null than in 129S1 mice, and increased after acetone pretreatment only in 129S1 mice. This increase was associated with higher blood concentrations of cyanide. In contrast, no consistent differences were recorded in vestibular toxicity between 129S1 and CYP2E1-null mice, and between animals pretreated with acetone or not. Additional experiments evaluated the effect on the toxicity of 1.0 mmol/kg allylnitrile of the nonselective P450 inhibitor, 1-aminobenzotriazole, the CYP2E1-inhibitor, diallylsulfide, and the CYP2A5 inhibitor, methoxsalen. In 129S1 mice, aminobenzotriazole decreased both mortality and vestibular toxicity, whereas diallylsulfide decreased mortality only. In CYP2E1-null mice, aminobenzotriazole and methoxsalen, but not diallylsulfide, blocked allylnitrile-induced vestibular toxicity. We conclude that CYP2E1-mediated metabolism of allylnitrile leads to cyanide release and acute mortality, probably through α-carbon hydroxylation, and hypothesize that epoxidation of the β-γ double bond by CYP2A5 mediates vestibular toxicity

Vestibular role of KCNQ4 and KCNQ5 K+ channels revealed by mouse models

The function of sensory hair cells of the cochlea and vestibular organs depends on an influx of K+ through apical mechanosensitive ion channels and its subsequent removal over their basolateral membrane. The KCNQ4 (Kv7.4) K+ channel, which is mutated in DFNA2 human hearing loss, is expressed in the basal membrane of cochlear outer hair cells (OHCs) where it may mediate K+ efflux. Like the related K+ channel KCNQ5 (Kv7.5), KCNQ4 is also found at calyx terminals ensheathing type I vestibular hair cells where it may be localized pre- or postsynaptically. Making use of Kcnq4-/- mice lacking KCNQ4, as well as Kcnq4dn/dn and Kcnq5dn/dn mice expressing dominant negative channel mutants, we now show unambiguously that in adult mice both channels reside in postsynaptic calyx-forming neurons, but cannot be detected in the innervated hair cells. Accordingly whole-cell currents of vestibular hair cells did not differ between genotypes. Neither Kcnq4-/-, Kcnq5dn/dn nor Kcnq4-/-/Kcnq5dn/dn double mutant mice displayed circling behavior found with severe vestibular impairment. However, a milder form of vestibular dysfunction was apparent from altered vestibulo-ocular reflexes in Kcnq4-/-/Kcnq5dn/dn and Kcnq4-/- mice. The larger impact of KCNQ4 may result from its preferential expression in central zones of maculae and cristae, which are innervated by phasic neurons that are more sensitive than the tonic neurons predominantly present in the surrounding peripheral zones where KCNQ5 is found. The impact of postsynaptic KCNQ4 on vestibular function may be related to K+ removal and modulation of synaptic transmission.Fil: Spitzmaul, Guillermo Federico. Leibniz Institut Fur Molekulare Pharmakologie; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); ArgentinaFil: Tolosa, Leonardo. Netherlands Institute For Neuroscience; Países BajosFil: Winkelman, Beerend H. J.. Netherlands Institute For Neuroscience; Países BajosFil: Heidenreich, Matthias. Leibniz_Institut Fur Molekulare Pharmakologie (Fmp) ; AlemaniaFil: Frens, Maartens. Department Of Neurosciences, Erasmus; Países BajosFil: Chabbert, Christian. Institut Des Neurosciences De Montpellier; FranciaFil: de Zeeuw, Chris I.. Netherlands Institute For Neuroscience; Países BajosFil: Jentsch, Thomas J.. Charité-Universitätsmedizin. Cluster of Excellence NeuroCure; Alemani

Vestibular role of KCNQ4 and KCNQ5 K+ channels revealed by mouse models

The function of sensory hair cells of the cochlea and vestibular organs depends on an influx of K+ through apical mechanosensitive ion channels and its subsequent removal over their basolateral membrane. The KCNQ4 (Kv7.4) K+ channel, which is mutated in DFNA2 human hearing loss, is expressed in the basal membrane of cochlear outer hair cells (OHCs) where it may mediate K+ efflux. Like the related K+ channel KCNQ5 (Kv7.5), KCNQ4 is also found at calyx terminals ensheathing type I vestibular hair cells where it may be localized pre- or postsynaptically. Making use of Kcnq4-/- mice lacking KCNQ4, as well as Kcnq4dn/dn and Kcnq5dn/dn mice expressing dominant negative channel mutants, we now show unambiguously that in adult mice both channels reside in postsynaptic calyx-forming neurons, but cannot be detected in the innervated hair cells. Accordingly whole-cell currents of vestibular hair cells did not differ between genotypes. Neither Kcnq4-/-, Kcnq5dn/dn nor Kcnq4-/-/Kcnq5dn/dn double mutant mice displayed circling behavior found with severe vestibular impairment. However, a milder form of vestibular dysfunction was apparent from altered vestibulo-ocular reflexes in Kcnq4-/-/Kcnq5dn/dn and Kcnq4-/- mice. The larger impact of KCNQ4 may result from its preferential expression in central zones of maculae and cristae, which are innervated by phasic neurons that are more sensitive than the tonic neurons predominantly present in the surrounding peripheral zones where KCNQ5 is found. The impact of postsynaptic KCNQ4 on vestibular function may be related to K+ removal and modulation of synaptic transmission.Fil: Spitzmaul, Guillermo Federico. Leibniz Institut Fur Molekulare Pharmakologie; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); ArgentinaFil: Tolosa, Leonardo. Netherlands Institute For Neuroscience; Países BajosFil: Winkelman, Beerend H. J.. Netherlands Institute For Neuroscience; Países BajosFil: Heidenreich, Matthias. Leibniz_Institut Fur Molekulare Pharmakologie (Fmp) ; AlemaniaFil: Frens, Maartens. Department Of Neurosciences, Erasmus; Países BajosFil: Chabbert, Christian. Institut Des Neurosciences De Montpellier; FranciaFil: de Zeeuw, Chris I.. Netherlands Institute For Neuroscience; Países BajosFil: Jentsch, Thomas J.. Charité-Universitätsmedizin. Cluster of Excellence NeuroCure; Alemani