In endothermic species, heat released as a product of metabolism ensures stable internal temperature throughout the organism, despite varying environmental conditions. Mitochondria are major actors ...in this thermogenic process. Part of the energy released by the oxidation of respiratory substrates drives ATP synthesis and metabolite transport, but a substantial proportion is released as heat. Using a temperature-sensitive fluorescent probe targeted to mitochondria, we measured mitochondrial temperature in situ under different physiological conditions. At a constant external temperature of 38 °C, mitochondria were more than 10 °C warmer when the respiratory chain (RC) was fully functional, both in human embryonic kidney (HEK) 293 cells and primary skin fibroblasts. This differential was abolished in cells depleted of mitochondrial DNA or treated with respiratory inhibitors but preserved or enhanced by expressing thermogenic enzymes, such as the alternative oxidase or the uncoupling protein 1. The activity of various RC enzymes was maximal at or slightly above 50 °C. In view of their potential consequences, these observations need to be further validated and explored by independent methods. Our study prompts a critical re-examination of the literature on mitochondria.
El abordaje especulativo de los problemas artísticos realizado por el philosophe Denis Diderot (1713-1784) a lo largo de su carrera, desde sus tempranos Pensamientos filosóficos (1746) hasta El ...sobrino de Rameau –obra póstuma que fascinó a Goethe– ha sido objeto de estudio de una bibliografía vastísima, algunas de cuyas tesis no dejan de sorprender al estudioso: no tanto por el carácter original o provocativo que presentan sino por el mucho más simple hecho de que, a menudo, suelen contradecirse entre sí.Esto resulta evidente cuando se revisa el modo en que nuestro autor, en consonancia con las preocupaciones epocales, concibe y elabora la relación entre las artes particulares, específicamente, entre la pintura y la poesía. En efecto –y aquí está lo que nos ha llamado la atención en nuestra investigación– críticos e historiadores del arte y de la literatura que han abordado desde una perspectiva histórica y teórica las implicancias del tópico ut pictura poesis en la tradición estética occidental toman frente a Diderot.
Delphi technique is a structured process commonly used to developed healthcare quality indicators, but there is a little recommendation for researchers who wish to use it. This study aimed 1) to ...describe reporting of the Delphi method to develop quality indicators, 2) to discuss specific methodological skills for quality indicators selection 3) to give guidance about this practice.
Three electronic data bases were searched over a 30 years period (1978-2009). All articles that used the Delphi method to select quality indicators were identified. A standardized data extraction form was developed. Four domains (questionnaire preparation, expert panel, progress of the survey and Delphi results) were assessed. Of 80 included studies, quality of reporting varied significantly between items (9% for year's number of experience of the experts to 98% for the type of Delphi used). Reporting of methodological aspects needed to evaluate the reliability of the survey was insufficient: only 39% (31/80) of studies reported response rates for all rounds, 60% (48/80) that feedback was given between rounds, 77% (62/80) the method used to achieve consensus and 57% (48/80) listed quality indicators selected at the end of the survey. A modified Delphi procedure was used in 49/78 (63%) with a physical meeting of the panel members, usually between Delphi rounds. Median number of panel members was 17(Q1:11; Q3:31). In 40/70 (57%) studies, the panel included multiple stakeholders, who were healthcare professionals in 95% (38/40) of cases. Among 75 studies describing criteria to select quality indicators, 28 (37%) used validity and 17(23%) feasibility.
The use and reporting of the Delphi method for quality indicators selection need to be improved. We provide some guidance to the investigators to improve the using and reporting of the method in future surveys.
In Body and Story, Richard Terdiman explores the tension between what might seem to be two fundamentally different ways of understanding the world: as physical reality and as representation in ...language. In demonstrating the complicated relationship between these two modes of being, he also presents a new bold approach to the problem of conflicts between irreconcilable but equally compelling theoretical ideas.
Enlightenment rationalism is most often understood as maintaining that words can meaningfully refer to and grasp things in the material world, while Postmodernism famously argues that nothing exists outside of language. Terdiman challenges this clean distinction, finding the early seeds of Postmodern doubt in the Enlightenment, and demonstrating the stubborn resistance of material reality—particularly that of the body—to language even today. Building on readings of works by 18th-century encyclopedist Denis Diderot and contemporary philosopher-icon Jacques Derrida, Terdiman argues that despite their genuine and profound opposition, a constant negotiation or mutual interrogation has always been taking place between these two world-views, even as the balance at times shifts to one side or the other. In analyzing these shifts he proposes a new model for understanding how seemingly unabridgeable theories legitimately coexist in our intellectual conception of the world, and he suggests a new ethics for managing this coexistence.
Historians of the Enlightenment are stymied by Denis Diderot's cloven polymathy. An insoluble dilemma arises between, on one hand, the amazing range of interests attested in his roles as both editor ...and contributor for the Encyclopédie and, on the other hand, his incorrigible dilettantism, in the centrifugal and often inconclusive pursuit of whatever topic came his way. We will do better to relinquish synthesis and highlight instead the multiplicity and versatility of Diderot's productive exuberance as such. We can then see how, rather than build arguments, he metabolized ideas into designs exhibiting a constantly increasing complexity that matched his inexhaustible energy. We can also appreciate his lifelong habit of writing in response to outside, and more or less random, prompts and assignments. An accidental polymath, Diderot preferred the pursuit of a train of thought over disciplined conclusiveness: witness his preference for dialogue over more integrative forms driven by argumentative power. A stranger to disciplinary methodology, he would nowadays be a journalist, not an academic.
As in human disease, macrophages (MØ) are central players in the development and progression of experimental atherosclerosis. In this study we have evaluated the phenotype of MØ associated with ...progression of atherosclerosis in the apolipoprotein E (ApoE) knockout (KO) mouse model.We found that bone marrow-derived MØ submitted to M1 and M2 polarization specifically expressed arginase (Arg) II and Arg I, respectively. This distinct arginase expression was used to evaluate the frequency and distribution of M1 and M2 MØ in cross-sections of atherosclerotic plaques of ApoE KO mice. Early lesions were infiltrated by Arg I(+) (M2) MØ. This type of MØ favored the proliferation of smooth muscle cells, in vitro. Arg II(+) (M1) MØ appeared and prevailed in lesions of aged ApoE KO mice and lesion progression was correlated with the dominance of M1 over the M2 MØ phenotype. In order to address whether the M2->M1 switch could be due to a phenotypic switch of the infiltrated cells, we performed in vitro repolarization experiments. We found that fully polarized MØ retained their plasticity since they could revert their phenotype. The analysis of the distribution of Arg I- and Arg II-expressing MØ also argued against a recent recruitment of M1 MØ in the lesion. The combined data therefore suggest that the M2->M1 switch observed in vivo is due to a conversion of cells already present in the lesion. Our study suggests that interventional tools able to revert the MØ infiltrate towards the M2 phenotype may exert an atheroprotective action.
The transition from enucleated reticulocytes to mature normocytes is marked by substantial remodeling of the erythrocytic cytoplasm and membrane. Despite conspicuous changes, most studies describe ...the maturing reticulocyte as a homogenous erythropoietic cell type. While reticulocyte staging based on fluorescent RNA stains such as thiazole orange have been useful in a clinical setting; these 'sub-vital' stains may confound delicate studies on reticulocyte biology and may preclude their use in heamoparasite invasion studies.
Here we use highly purified populations of reticulocytes isolated from cord blood, sorted by flow cytometry into four sequential subpopulations based on transferrin receptor (CD71) expression: CD71high, CD71medium, CD71low and CD71negative. Each of these subgroups was phenotyped in terms of their, morphology, membrane antigens, biomechanical properties and metabolomic profile.
Superficially CD71high and CD71medium reticulocytes share a similar gross morphology (large and multilobular) when compared to the smaller, smooth and increasingly concave reticulocytes as seen in the in the CD71low and CD71negativesamples. However, between each of the four sample sets we observe significant decreases in shear modulus, cytoadhesive capacity, erythroid receptor expression (CD44, CD55, CD147, CD235R, and CD242) and metabolite concentrations. Interestingly increasing amounts of boric acid was found in the mature reticulocytes.
Reticulocyte maturation is a dynamic and continuous process, confounding efforts to rigidly classify them. Certainly this study does not offer an alternative classification strategy; instead we used a nondestructive sampling method to examine key phenotypic changes of in reticulocytes. Our study emphasizes a need to focus greater attention on reticulocyte biology.
Moment ultime de la réflexion de Diderot sur l’art, les Pensées détachées sur la peinture (1781) sont interrogées au sein de leurs rapports aux Salons en général et plus particulièrement aux deux ...suppléments que constituent les Essais sur la peinture (1765) et le préambule au Salon de 1767. Si le texte fragmenté semble reprendre le discours salonnier plus qu’il ne favorise une réflexion théorique à part, il invite néanmoins à repérer et à faire dialoguer les idées esthétiques de Diderot.
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