Targeted ablation of the 25-hydroxyvitamin D 1α-hydroxylase enzyme: Evidence for skeletal, reproductive, and immune dysfunction

The active form of vitamin D, 1α,25-dihydroxyvitamin D [1α,25(OH)2D], is synthesized from its precursor 25 hydroxyvitamin D [25(OH)D] via the catalytic action of the 25(OH)D-1α-hydroxylase [1α(OH)ase] enzyme. Many roles in cell growth and differentiation have been attributed to 1,25(OH)2D, including a central role in calcium homeostasis and skeletal metabolism. To investigate the in vivo functions of 1,25(OH)2D and the molecular basis of its actions, we developed a mouse model deficient in 1α(OH)ase by targeted ablation of the hormone-binding and heme-binding domains of the 1α(OH)ase gene. After weaning, mice developed hypocalcemia, secondary hyperparathyroidism, retarded growth, and the skeletal abnormalities characteristic of rickets. These abnormalities are similar to those described in humans with the genetic disorder vitamin D dependent rickets type I [VDDR-I; also known as pseudovitamin D-deficiency rickets (PDDR)]. Altered non-collagenous matrix protein expression and reduced numbers of osteoclasts were also observed in bone. Female mutant mice were infertile and exhibited uterine hypoplasia and absent corpora lutea. Furthermore, histologically enlarged lymph nodes in the vicinity of the thyroid gland and a reduction in CD4- and CD8-positive peripheral T lymphocytes were observed. Alopecia, reported in vitamin D receptor (VDR)-deficient mice and in humans with VDDR-II, was not seen. The findings establish a critical role for the 1α(OH)ase enzyme in mineral and skeletal homeostasis as well as in female reproduction and also point to an important role in regulating immune function.

La Main ou le théâtre de l'identité trafiquée chez Michel Tremblay

Ce mémoire veut, de prime abord, porter un regard sur la rue Saint-Laurent qui, depuis ses débuts, joue un rôle fondamental dans le tissu montréalais. Grâce à son visage bigarré et à son hétérogénéité, elle a su marquer l’histoire de la métropole et alimenter l’imaginaire d’un bon nombre d’écrivains. Michel Tremblay demeure un de ceux qui, dans l’ensemble de son oeuvre, explore le plus abondamment les clairs-obscurs et l’étrangeté de ce corridor urbain. Son écriture à la fois crue, marginale et théâtrale, s’inscrit pertinemment dans l’univers de la Main et, plus particulièrement, dans la partie du Redlight où aboutissent et se meuvent ses personnages les plus colorés. Ayant délaissé leur milieu d’origine, ces derniers s’imposent des changements radicaux afin de mieux cadrer avec la nature et les activités de leur terre d’accueil. Ce mémoire visera donc à penser l’« identité trafiquée » des personnages de Tremblay comme condition de leur inscription sur la rue Saint-Laurent. En outre, il sera question de l’esprit théâtral de cette artère qui pousse les travestis et les artistes en tout genre à se donner « en représentation » et à incarner un rôle de composition. Par l’entremise des masques – notamment celui du déguisement, du maquillage et du travestissement, mais aussi celui de la langue qu’ils modulent afin de mieux coller à leur personnage –, ils projettent une identité individuelle instable qui dévoile l’ambiguïté qui les habite. Plus largement, la présente étude s’intéressera à l’ensemble des marginaux qui arpentent la Main et qui cherchent à (re)définir leur identité culturelle, au milieu des cultures américaine et française. Bien qu’elle essaie de se forger une identité propre, cette collectivité peine à se définir sans calquer les modèles dont elle tente de se dissocier. Une telle contradiction évoque à bien des égards le paradoxe auquel se sont heurtées les communautés immigrantes de la rue Saint-Laurent, dont la lente adaptation à la culture nord-américaine s’est faite non sans un difficile constat de pertes et de gains face à la culture d’origine. Il s’agira donc de voir comment ces groupes, en apparence irréconciliables, trouvent dans le même univers un contexte favorable pour mener leur quête identitaire.

Letting go of Neo-Liberalism (with some help from Michel Foucault)

Neo-liberalism has become one of the boom concepts of our time. From its original reference point as a descriptor of the economics of the “Chicago School” such as Milton Friedman, or authors such as Friedrich von Hayek, neo-liberalism has become an all-purpose descriptor and explanatory device for phenomena as diverse as Bollywood weddings, standardized testing in schools, violence in Australian cinema, and the digitization of content in public libraries. Moreover, it has become an entirely pejorative term: no-one refers to their own views as “neo-liberal”, but it rather refers to the erroneous views held by others, whether they acknowledge this or not. Neo-liberalism as it has come to be used, then, bears many of the hallmarks of a dominant ideology theory in the classical Marxist sense, even if it is often not explored in these terms. This presentation will take the opportunity provided by the English language publication of Michel Foucault’s 1978-79 lectures, under the title of The Birth of Biopolitics, to consider how he used the term neo-liberalism, and how this equates with its current uses in critical social and cultural theory. It will be argued that Foucault did not understand neo-liberalism as a dominant ideology in these lectures, but rather as marking a point of inflection in the historical evolution of liberal political philosophies of government. It will also be argued that his interpretation of neo-liberalism was more nuanced and more comparative than the more recent uses of Foucault in the literature on neo-liberalism. It will also look at how Foucault develops comparative historical models of liberal capitalism in The Birth of Biopolitics, arguing that this dimension of his work has been lost in more recent interpretations, which tend to retro-fit Foucault to contemporary critiques of either U.S. neo-conservatism or the “Third Way” of Tony Blair’s New Labour in the UK.

Michel Foucault's 'the birth of biopolitics' and contemporary neo-liberalism debates

Neo-liberalism has become one of the boom concepts of our time. From its original reference point as a descriptor of the economics of the ‘Chicago School’ or authors such as Friedrich von Hayek, neo-liberalism has become an all-purpose concept, explanatory device and basis for social critique. This presentation evaluates Michel Foucault’s 1978–79 lectures, published as The Birth of Biopolitics, to consider how he used the term neo-liberalism, and how this equates with its current uses in critical social and cultural theory. It will be argued that Foucault did not understand neo-liberalism as a dominant ideology in these lectures, but rather as marking a point of inflection in the historical evolution of liberal political philosophies of government. It will also be argued that his interpretation of neo-liberalism was more nuanced and more comparative than more recent contributions. The article points towards an attempt to theorize comparative historical models of liberal capitalism.

Michel Foucault : the unconscious of history and culture

Michel Foucault: The unconscious of history and culture The French thinker, Michel Foucault (1926–84), is noted for his extensive and controversial forays into the historical disciplines. When his work first began to circulate in the 1950s and 1960s, historians did not quite know what to make of it and philosophers resented the appearance of what they saw as the importation of the tedium of concrete events into the pure untainted realm of ideas. If these responses to his work remain alive and well decades after Foucault's death, the uptake of his work has become far more complex. To restrict ourselves to the discipline of history here: if one very visible and vocal camp of historians remains deeply ambivalent about his work, this merely disguises the fact that a far larger contingent of historians of all kinds – not just those located in history departments – use his ideas quite unremarkably ...

Spatial metaphor as spatial technique in the work of Michel Foucault

This essay argues that the deployment of spatial metaphor in the writing of Michel Foucault is indivisible from his spatial politics. Beginning with his 1967 essay "Of Other Spaces," the development of Foucault's spatial politics and his growing awareness of the importance to his work of spatial (particularly geographic) metaphors can be charted. The focus here is not the concretisation of Foucault's early spatial obsessions—particularly with regard to the concept of "heterotopia"—into a theory or model. Rather, I am concerned with the way in which those obsessions inform Foucault's major works, in particular The Archaeology of Knowledge and Discipline and Punish. These works, I argue, do not develop a theory of space, but instead perform, through their rhetoric, a kind of spatial praxis. In this sense, Foucault's metaphors become "spatial techniques" for the practice and production of power–knowledge.

A review of: "Wrong-Doing, Truth-Telling: The Function of Avowal in Justice. By Michel Foucault. Edited by Fabienne Brion and Bernard E. Harcourt. Translated by Stephen W. Sawyer"

Wrong-Doing, Truth-Telling: The Function of Avowal in Justice is a collection of seven lectures delivered by French philosopher and historian Michel Foucault at the Catholic University of Louvain in 1981. Compiled from audiovisual recordings and Foucault’s original manuscripts, these lectures explore the notion of avowal and its place within criminal justice processes. Accompanied by three contemporaneous interviews given by Foucault (only one of which has previously been available in English), and a preface and concluding essay by the editors contextualizing these lectures in Foucault’s oeuvre, this volume contributes much to Foucaultian scholarship, particularly when considered alongside the recently published volumes of Foucault’s lecture courses at the Collège de France. However, while the book promises to offer some insights of relevance to criminology, it is important to remember that this is not its key purpose, and criminologists should read it with this caveat in mind...

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10−8). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Ernest W. Michel Papers, 1698, 1938-1996 (bulk 1946-1987)

This collection contains the papers of Ernest W. Michel, Holocaust Survivor Journalist and public speaker,including clippings of newspaper articles written by and about Michel, correspondence between Michel and many important Jewish and political figures and autograph files, which Michel collected. Many of these files concern Michel’s Holocaust experiences, speaking engagements, the World Gathering of Jewish Holocaust Survivors, and Michel’s work with the United Jewish Appeal.

Max Michel Collection. 1933-1986 Bulk dates: 1933-1937

The bulk of the collections consists of correspondence from the 1930s relating to Michels’s job applications in the U.S. in different academic institutions and activities of the Hilfsverein der Juden in Deutschland. Also included is a 36 p. typescript, ‘Geschichte der Familie Wertheimer’; pamphlets by Juda Magnes and Kurt Blumenfeld on the university in Jerusalem; as well as family trees.

Käytännöt ja ajattelu Michel Foucault'n filosofiassa

Practices and Thought in Michel Foucault s Philosophy The present thesis examines Michel Foucault s (1926-1984) notion of practice and argues that it is an essential concept in his philosophy, especially in his analysis of knowledge, power and ethics. The thesis reveals a previously neglected chronological and methodological unity in Foucault s work. The first chapter clarifies Foucault s philosophy by outlining it according to four central themes. First, the main philosophical goal of his historical studies is to analyse how human subjects have become objects of their own thinking. Second, this goal calls for methodological precaution to avoid all anthropological universals. Third, Foucault s studies are directed towards fields of practices. Fourth, the analysis of practices is executed along three axes: knowledge, power and ethics. The second chapter concerns the notion of practice in Foucault s archaeological method. Foucault s archaeological analysis is not directed towards objects and subjects as such, but to the way that the rules of discursive practice form them in the discourse. Many commentators have neglected Foucault s concept of practice when discussing his ideas concerning rules of discourse and limits of knowledge. I argue that Foucault s analysis concerning the limits of knowledge relates to local and contingent rules of discursive practice, not to transcendental rules of thinking in general. The third chapter deals with power relations and practices. I clarify Foucault s concept of dispositif by defining it as a functional ensemble of practices, and argue that this concept is crucial to his understanding of power relations. I stress a conceptual definition, which separates relations of power from the practices of government and show that the latter is based on the idea that power relations are integrated into practices. This conceptual clarification also helps in understanding Foucault s critique concerning modern practices of power. The fourth chapter examines Foucault s way of perceiving ethics as a practice. He separates three essential dimensions in morals: moral codes, moral behaviour and practices of self. His ethics concern practices of self and he studies how these practices have constituted different relations that subjects have to themselves, to others and to their societies. I argue that Foucault s own ethical views can be found in the ideas on the importance of practices of self in the modern world, and emphasize that these ideas should be connected to his views concerning the tradition of the Enlightenment, and to his own political action.