Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule.

Cell death is achieved by two fundamentally different mechanisms: apoptosis and necrosis. Apoptosis is dependent on caspase activation, whereas the caspase-independent necrotic signaling pathway remains largely uncharacterized. We show here that Fas kills activated primary T cells efficiently in the absence of active caspases, which results in necrotic morphological changes and late mitochondrial damage but no cytochrome c release. This Fas ligand-induced caspase-independent death is absent in T cells that are deficient in either Fas-associated death domain (FADD) or receptor-interacting protein (RIP). RIP is also required for necrotic death induced by tumor necrosis factor (TNF) and TNF-related apoptosis-inducing ligand (TRAIL). In contrast to its role in nuclear factor kappa B activation, RIP requires its own kinase activity for death signaling. Thus, Fas, TRAIL and TNF receptors can initiate cell death by two alternative pathways, one relying on caspase-8 and the other dependent on the kinase RIP.

Phylogenetic relationships in the subfamily Psychodinae (Diptera, Psychodidae)

Thanks to recent advances in molecular systematics, our knowledge of phylogenetic relationships within the order Diptera has dramatically improved. However, relationships at lower taxonomic levels remain poorly investigated in several neglected groups, such as the highly diversified moth-fly subfamily Psychodinae (Lower Diptera), which occurs in numerous terrestrial ecosystems. In this study, we aimed to understand the phylogenetic relationships among 52 Palearctic taxa from all currently known Palearctic tribes and subtribes of this subfamily, based on mitochondrial DNA. Our results demonstrate that in light of the classical systematics of Psychodinae, none of the tribes sensu Je?ek or sensu Vaillant is monophyletic, whereas at least five of the 12 sampled genera were not monophyletic. The results presented in this study provide a valuable backbone for future work aiming at identifying morphological synapomorphies to propose a new tribal classification.

La bibliothèque de Fulvio Orsini : contributions à l'histoire des collections d'Italie et à l'étude de la Renaissance / Pierre de Nolhac

Collection : Bibliothèque de l'École des Hautes-Études. Sciences philologiques et historiques ; 74

Intravenous insulin treatment in acute stroke: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Poststroke hyperglycemia has been associated with unfavorable outcome. Several trials investigated the use of intravenous insulin to control hyperglycemia in acute stroke. This meta-analysis summarizes all available evidence from randomized controlled trials in order to assess its efficacy and safety. METHODS: We searched PubMed until 15/02/2013 for randomized clinical trials using the following search items: 'intravenous insulin' or 'hyperglycemia', and 'stroke'. Eligible studies had to be randomized controlled trials of intravenous insulin in hyperglycemic patients with acute stroke. Analysis was performed on intention-to-treat basis using the Peto fixed-effects method. The efficacy outcomes were mortality and favorable functional outcome. The safety outcomes were mortality, any hypoglycemia (symptomatic or asymptomatic), and symptomatic hypoglycemia. RESULTS: Among 462 potentially eligible articles, nine studies with 1491 patients were included in the meta-analysis. There was no statistically significant difference in mortality between patients who were treated with intravenous insulin and controls (odds ratio: 1.16, 95% confidence interval: 0.89-1.49). Similarly, the rate of favorable functional outcome was not statistically different (odds ratio: 1.01, 95% confidence interval: 0.81-1.26). The rates of any hypoglycemia (odds ratio: 8.19, 95% confidence interval: 5.60-11.98) and of symptomatic hypoglycemia (odds ratio: 6.15, 95% confidence interval: 1.88-20.15) were higher in patients treated with intravenous insulin. There was no heterogeneity across the included trials in any of the outcomes studied. CONCLUSIONS: This meta-analysis of randomized controlled trials does not support the use of intravenous insulin in hyperglycemic stroke patients to improve mortality or functional outcome. The risk of hypoglycemia is increased, however.

A mutation causing pseudohypoaldosteronism type 1 identifies a conserved glycine that is involved in the gating of the epithelial sodium channel.

Pseudohypoaldosteronism type 1 (PHA-1) is an inherited disease characterized by severe neonatal salt-wasting and caused by mutations in subunits of the amiloride-sensitive epithelial sodium channel (ENaC). A missense mutation (G37S) of the human ENaC beta subunit that causes loss of ENaC function and PHA-1 replaces a glycine that is conserved in the N-terminus of all members of the ENaC gene family. We now report an investigation of the mechanism of channel inactivation by this mutation. Homologous mutations, introduced into alpha, beta or gamma subunits, all significantly reduce macroscopic sodium channel currents recorded in Xenopus laevis oocytes. Quantitative determination of the number of channel molecules present at the cell surface showed no significant differences in surface expression of mutant compared with wild-type channels. Single channel conductances and ion selectivities of the mutant channels were identical to that of wild-type. These results suggest that the decrease in macroscopic Na currents is due to a decrease in channel open probability (P(o)), suggesting that mutations of a conserved glycine in the N-terminus of ENaC subunits change ENaC channel gating, which would explain the disease pathophysiology. Single channel recordings of channels containing the mutant alpha subunit (alphaG95S) directly demonstrate a striking reduction in P(o). We propose that this mutation favors a gating mode characterized by short-open and long-closed times. We suggest that determination of the gating mode of ENaC is a key regulator of channel activity.

VOLUMES RELIES du Cabinet des titres : recherches de noblesse, armoriaux, preuves, histoires généalogiques. Mélanges sur la noblesse de Normandie.

Contient : I ; « Les noms, et surnoms et demeure des nobles personnes du duché de Normandie, certifiés... par Remond de Montfault... » (1463) ; « Registre et estats des nouveaux anoblis en la province de Normandie, depuis les recherches qui furent faite par Rémont de Montfond... » (XVIe et XVIIe siècles) ; II « Généalogies des gentilshommes de l'élection de Bayeux, par eux produites, avec les titres justificatifs de leur noblesse, en l'an 1523 » ; III « Recherche des éleux de Lizieux par Nicolas Le Vallois, et François Le Roy et Jean Hédiart, escuyers, éleux de Lizieux... » (1540)

Análise de Crédito e Avaliação de Riscos em Instituições Bancárias

É indubitável que o sistema financeiro é parte integrante de qualquer sociedade. Através da sua função de intermediação, as instituições financeiras recebem recursos dos agentes superavitários e emprestam aos agentes deficitários mediante promessa de pagamento futuro. Num banco, que tem intermediação financeira como sua principal actividade, o crédito consiste em disponibilizar ao cliente recursos em valores sob a forma de financiamento e ou empréstimo mediante uma promessa de pagamento numa data acordada entre as partes. A discussão e implementação dos acordos de BASILEIA, nomeadamente o Basileia II, veio dar uma nova forma a esse relacionamento sector bancário/clientes determinando as regras no que respeita a concessão de crédito e gestão de risco, estabelecendo os limites de crédito associado ao grau de risco das operações. Surge então, por parte das instituições uma maior preocupação em gerir o crédito e os riscos inerentes a cada operação, apostando em ferramentas e metodologias adequadas ao processo creditício. As instituições bancárias passam a criar departamentos de risco, colocando a gestão de crédito e de risco nas mãos de profissionais especializados, agindo sob regras e padrões internacionais uniformizados. There is no doubt that the financial system is an integral part of any society. Through their intermediary role, financial institutions receive funds from surplus agents and lend to deficit agents, with promises of future payment. Banks, with their primary activity being the financial intermediation, the credit is provided to customers in the form of funding or loans and a promise of payment on a date agreed between the parties. The discussion and implementation of the Basel Accord, Basel II in particular, has given a new form to that relationship banking/customer, setting out the rules regarding the granting of credit and risk management, establishing credit limits associated with the degree of risk of operations. Banking institutions got more and more concerned with credit and risk management, in all of their operations, using tools and methodologies that are designed to meet the needs of crediting processes. Banking institutions are creating departments of risk, putting the management of credit risk in the hands of trained professionals, acting under internationally uniform rules and standards

Landscape of transcription in human cells.

Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic subcellular localizations are also poorly understood. Because RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell's regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three-quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations, taken together, prompt a redefinition of the concept of a gene.

The SLC2 family of facilitated hexose and polyol transporters.

The SLC2 family of glucose and polyol transporters comprises 13 members, the glucose transporters (GLUT) 1-12 and the H(+)- myo-inositol cotransporter (HMIT). These proteins all contain 12 transmembrane domains with both the amino and carboxy-terminal ends located on the cytoplasmic side of the plasma membrane and a N-linked oligosaccharide side-chain located either on the first or fifth extracellular loop. Based on sequence comparison, the GLUT isoforms can be grouped into three classes: class I comprises GLUT1-4; class II, GLUT6, 8, 10, and 12 and class III, GLUT5, 7, 9, 11 and HMIT. Despite their sequence similarity and the presence of class-specific signature sequences, these transporters carry various hexoses and HMIT is a H(+)/ myo-inositol co-transporter. Furthermore, the substrate transported by some isoforms has not yet been identified. Tissue- and cell-specific expression of the well-characterized GLUT isoforms underlies their specific role in the control of whole-body glucose homeostasis. Numerous studies with transgenic or knockout mice indeed support an important role for these transporters in the control of glucose utilization, glucose storage and glucose sensing. Much remains to be learned about the transport functions of the recently discovered isoforms (GLUT6-13 and HMIT) and their physiological role in the metabolism of glucose, myo-inositol and perhaps other substrates.

Globalization and wage inequality in South and East Asia, and Latin America: A gender approach

In this paper we analyse the reasons behind the evolution of the gender gap and wage inequality in South and East Asian and Latin American countries. Health human capital improvements, the exposure to free market openness and equal treatment enforcement laws seem to be the main exogenous variables affecting women s economic condition. During the second globalization era (in the years 1975-2000) different combinations of these variables in South East Asian and Latin American countries have had as a result the diminution of the gender gap. The main exception to this rule according to our data is China where economic reforms have been simultaneous to the increase of gender differences and inequality between men and women.This result has further normative consequences for the measure of economic inequality. Theimprovement of women s condition has as a result the diminution of the dispersion of wages.Therefore in most of the countries analysed the consequence of the diminution of the gender gapduring the second global era is the decrease of wage inequality both measured with Gini and Theil indexes.

A dilution cost approach to financial intermediation and securities markets

This paper proposes a model of financial markets and corporate finance,with asymmetric information and no taxes, where equity issues, Bankdebt and Bond financing may all co-exist in equilibrium. The paperemphasizes the relationship Banking aspect of financial intermediation:firms turn to banks as a source of investment mainly because banks aregood at helping them through times of financial distress. The debtrestructuring service that banks may offer, however, is costly. Therefore,the firms which do not expect to be financially distressed prefer toobtain a cheaper market source of funding through bond or equity issues.This explains why bank lending and bond financing may co-exist inequilibrium. The reason why firms or banks also issue equity in our modelis simply to avoid bankruptcy. Banks have the additional motive that theyneed to satisfy minimum capital adequacy requeriments. Several types ofequilibria are possible, one of which has all the main characteristics ofa "credit crunch". This multiplicity implies that the channels of monetarypolicy may depend on the type of equilibrium that prevails, leadingsometimes to support a "credit view" and other times the classical "moneyview".