Treatment of atypical hemolytic uremic syndrome and thrombotic microangiopathies: a focus on eculizumab.

Uncontrolled complement activation is central to the occurrence of atypical hemolytic uremic syndrome (aHUS) and can result in thrombotic microangiopathies (TMAs).These terms encompass a group of heterogenic inherited or acquired diseases that recent research suggests may be triggered by the complement cascade. Pathogenetic triggers of complement activation include immunologic disorders, genetics, infections, systemic diseases, pregnancy, drug administration, metabolic diseases, transplantation, or triggers of mixed cause. Hallmarks of aHUS and other TMAs include increased vascular endothelium thromboresistance, leukocyte adhesion to damaged endothelium, complement consumption, coagulation abnormalities, and vascular shear stress, whereas common end points of these mechanisms include hemolytic anemia, thrombocytopenia with microvascular infarction, and predisposition for decreased kidney function and other organ involvement. The central role of the complement cascade as a disease trigger suggests a possible therapeutic target. Eculizumab, a first-in-class humanized monoclonal anti-C5 antibody that has been successful in the treatment of paroxysmal nocturnal hemoglobinuria, a disorder of complement-induced hemolytic anemia, received approval for the treatment of aHUS in the United States and Europe in late 2011. We review the treatment of aHUS and other TMAs, focusing on the role of eculizumab, including its pharmacology, mechanism of action, and approved dosing recommendations and health economic considerations. Finally, the potential for future indications for eculizumab use in other complement-driven diseases is discussed.

Inhibition of glial cell proinflammatory activities by peroxisome proliferator-activated receptor gamma agonist confers partial protection during antimyelin oligodendrocyte glycoprotein demyelination in vitro.

Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a member of the nuclear hormone superfamily originally characterized as a regulator of adipocyte differentiation and lipid metabolism. In addition, PPAR-gamma has important immunomodulatory functions. If the effect of PPAR-gamma's activation in T-cell-mediated demyelination has been recently demonstrated, nothing is known about the role of PPAR-gamma in antibody-induced demyelination in the absence of T-cell interactions and monocyte/macrophage activation. Therefore, we investigated PPAR-gamma's involvement by using an in vitro model of inflammatory demyelination in three-dimensional aggregating rat brain cell cultures. We found that PPAR-gamma was not constitutively expressed in these cultures but was strongly up-regulated following demyelination mediated by antibodies directed against myelin oligodendrocyte glycoprotein (MOG) in the presence of complement. Pioglitazone, a selective PPAR-gamma agonist, partially protected aggregates from anti-MOG demyelination. Heat shock responses and the expression of the proinflammatory cytokine tumor necrosis factor-alpha were diminished by pioglitazone treatment. Therefore, pioglitazone protection seems to be linked to an inhibition of glial cell proinflammatory activities following anti-MOG induced demyelination. We show that PPAR-gamma agonists act not only on T cells but also on antibody-mediated demyelination. This may represent a significant benefit in treating multiple sclerosis patients.

La integració de les energies renovables en un model energètic sostenible

La sostenibilitat del model energètic de Catalunya es veu condicionada per aspectes com la dependència energètica, la seguretat de subministrament, l’eficiència energètica, els impactes ambientals i la demanda creixent. D’altra banda, la incorporació d’energia renovable en el mix energètic implica una major autonomia energètica, seguretat de subministrament a llarg termini, i eficiència energètica, així com un menor impacte ambiental. Tanmateix, la contribució en el sistema elèctric d’un volum ja important i creixent d’energia renovable requereix una complexa tasca d’integració a nivell tècnic i econòmic. Per aconseguir-ho, és necessari desenvolupar una regulació estable que complementi el procés de liberalització del sector amb l’objectiu d’acomodar la generació renovable en un model energètic sostenible. La (in)formació i participació de la demanda es presenta com una condició clau per engegar el camí cap a una nova cultura energètica.

Glutathione S-transferases of 28kDa as major vaccine candidates against schistosomiasis

For the development of vaccine strategies to generate efficient protection against chronic infections such as parasitic diseases, and more precisely schistosomiasis, controlling pathology could be more relevant than controlling the infection itself. Such strategies, motivated by the need for a cost-effective complement to existing control measures, should focus on parasite molecules involved in fecundity, because in metazoan parasite infections pathology is usually linked to the output of viable eggs. In numerous animal models, vaccination with glutathione S-transferases of 28kDa has been shown to generate an immune response strongly limiting the worm fecundity, in addition to the reduction of the parasite burden. Recent data on acquired immunity directed to 28GST in infected human populations, and new development to draw adapted vaccine formulations, are presented.

L'enseignement et l'apprentissage de la conjugaison en FLE : comment réduire les difficultés engendrées par l'orthographe ?

French verb morphology has always been a major challenge for learners as well as teachers of French as a foreign language. Learning difficulties arise not only from the inherent complexity of the conjugation system itself, but mostly from the traditional description found in specialized books, grammars, etc. French spelling alone tends to complexify the actual oral verb morphology by more than 60%, thus hindering efficient learning. Following Dubois (1967), Csécsy (1968), Pouradier Duteil (1997), etc., I suggest an alternative approach, exclusively based on phonetic transcription, and starting with plural forms instead of singular ones (Mayer 1969). For more than 500 verbs of the 2nd and 3rd groups, this strategy allows learners to first memorize the present tense plural form e.g. /illiz/ (ils lisent, "they read") and take the stem's final consonant away to get the singular /illi/ (il lit, "he reads").

Spermatogenesis of the Spider Crab Maja brachydactyla (Decapoda: Brachyura)

This study describes spermatogenesis in a majid crab (Maja brachydactyla) using electron microscopy and reports the origin of the different organelles present in the spermatozoa. Spermatogenesis in M. brachydactyla follows the general pattern observed in other brachyuran species but with several peculiarities. Annulate lamellae have been reported in brachyuran spermatogenesis during the diplotene stage of first spermatocytes, the early and mid-spermatids. Unlike previous observations, a Golgi complex has been found in midspermatids and is involved in the development of the acrosome. The Golgi complex produces two types of vesicles: light vesicles and electron-dense vesicles. The light vesicles merge into the cytoplasm, giving rise to the proacrosomal vesicle. The electron-dense vesicles are implicated in the formation of an electron-dense granule, which later merges with the proacrosomal vesicle. In the late spermatid, the endoplasmic reticulum and the Golgi complex degenerate and form the structures–organelles complex found in the spermatozoa. At the end of spermatogenesis, the materials in the proacrosomal vesicle aggregate in a two-step process, forming the characteristic concentric three-layered structure of the spermatozoon acrosome. The newly formed spermatozoa from testis show the typical brachyuran morphology.

'Next generation' biogeography: towards understanding the drivers of species diversification and persistence

The drivers of species diversification and persistence are of great interest to current biogeography, especially in those global biodiversity hotspots' harbouring most of Earth's animal and plant life. Classical multispecies biogeographical work has yielded fascinating insights into broad-scale patterns of diversification, and DNA-based intraspecific phylogeographical studies have started to complement this picture at much finer temporal and spatial scales. The advent of novel next-generation sequencing (NGS) technologies provides the opportunity to greatly scale up the numbers of individuals, populations and species sampled, potentially merging intraspecific and interspecific approaches to biogeographical inference. Here, we outline these prospects and issues by using the example of an undisputed hotspot, the Cape of southern Africa. We outline the current state of knowledge on the biogeography of species diversification within the Cape, review the literature for phylogeographical evidence of its likely drivers and mechanisms, and suggest possible ways forward based on NGS approaches. We demonstrate the potential of these methods and current bioinformatic issues with the help of restriction-site-associated DNA (RAD) sequencing data for three highly divergent species of the Restionaceae, an important plant radiation in the Cape. A thorough understanding of the mechanisms that facilitate species diversification and persistence in spatially structured, species-rich environments will require the adoption of novel genomic and bioinformatic tools in biogeographical studies.

Social Interaction Effects on Fertility: Intentions and Behaviors

The existing literature shows that social interactions in individuals' networks affect their reproductive attitudes and behaviors through three mechanisms: social influence, social learning, and social support. In this paper, we discuss to what extent the Theory of Planned Behavior (TPB), an individual based theorization of intentions and behavior used to model fertility, takes these social mechanisms into account. We argue that the TPB already integrates social influence and that it could easily accommodate the two other social network mechanisms. By doing so, the theory would be enriched in two respects. First, it will explain more completely how macro level changes eventually ends in micro level changes in behavioral intentions. Indeed, mechanisms of social influence may explain why changes in representations of parenthood and ideal family size can be slower than changes in socio-economic conditions and institutions. Social learning mechanisms should also be considered, since they are crucial to distinguish who adopts new behavioral beliefs and practices, when change at the macro level finally sinks in. Secondly, relationships are a capital of services that can complement institutional offering (informal child care) as well as a capital of knowledge which help individuals navigate in a complex institutional reality, providing a crucial element to explain heterogeneity in the successful realization of fertility intentions across individuals. We develop specific hypotheses concerning the effect of social interactions on fertility intentions and their realization to conclude with a critical review of the existing surveys suitable to test them and their limits.

Influència de la música sobre l'atenció humana: especial a la metodologia d'anàlisi, tot combinant metodologia quantitavia amb qualitativa (mix method)

Projecte de recerca elaborat a partir d’una estada a la University of Calgary, Canadà, entre desembre del 2007 i febrer del 2008. El projecte ha consistit en l'anàlisi de les dades d'una recerca en el camp de la psicologia de la música, concretament en com influeix la música en l'atenció a través de les vies dels estats emocionals i enèrgics de la persona. Per a la recerca es feu ús de videu en les sessions, obtenint dades visuals i auditives per a complementar les dades de tipus quantitatiu provinents dels resultats d'uns tests d'atenció subministrats. L'anàlisi es realitzà segons mètodes i tècniques de caràcter qualitatiu, apresos durant l'estada. Així mateix també s'ha aprofundit en la comprensió del paradigma qualitatiu com a paradigma vàlid i realment complementari del paradigma qualitatiu. S'ha focalitzat especialment en l'anàlisi de la conversa des d'un punt de vista interpretatiu així com l'anàlisi de llenguatge corporal i facial a partir de l'observació de videu, tot formulant descriptors i subdescriptors de la conducta que està relacionada amb la hipòtesis. Alguns descriptors havien estat formulats prèviament a l’anàlisi, en base a altres investigacions i al background de la investigadora; altres s’han anat descobrint durant l’anàlisi. Els descriptors i subdescriptors de la conducta estan relacionats amb l'intent dels estats anímics i enèrgics dels diferents participants. L'anàlisi s'ha realitzat com un estudi de casos, fent un anàlisi exhaustiu persona per persona amb l'objectiu de trobar patrons de reacció intrapersonals i intrapersonals. Els patrons observats s'utilitzaran com a contrast amb la informació quantitativa, tot realitzant triangulació amb les dades per trobar-ne possibles recolzaments o contradiccions entre sí. Els resultats preliminars indiquen relació entre el tipus de música i el comportament, sent que la música d'emotivitat negativa està associada a un tancament de la persona, però quan la música és enèrgica els participants s'activen (conductualment observat) i somriuen si aquesta és positiva.

Forensic examination of ink by high-performance thin layer chromatography - The United States Secret Service Digital Ink Library

Forensic examinations of ink have been performed since the beginning of the 20th century. Since the 1960s, the International Ink Library, maintained by the United States Secret Service, has supported those analyses. Until 2009, the search and identification of inks were essentially performed manually. This paper describes the results of a project designed to improve ink samples' analytical and search processes. The project focused on the development of improved standardization procedures to ensure the best possible reproducibility between analyses run on different HPTLC plates. The successful implementation of this new calibration method enabled the development of mathematical algorithms and of a software package to complement the existing ink library.

Evaluating the ability of habitat suitability models to predict species presences.

Models predicting species spatial distribution are increasingly applied to wildlife management issues, emphasising the need for reliable methods to evaluate the accuracy of their predictions. As many available datasets (e.g. museums, herbariums, atlas) do not provide reliable information about species absences, several presence-only based analyses have been developed. However, methods to evaluate the accuracy of their predictions are few and have never been validated. The aim of this paper is to compare existing and new presenceonly evaluators to usual presence/absence measures. We use a reliable, diverse, presence/absence dataset of 114 plant species to test how common presence/absence indices (Kappa, MaxKappa, AUC, adjusted D-2) compare to presenceonly measures (AVI, CVI, Boyce index) for evaluating generalised linear models (GLM). Moreover we propose a new, threshold-independent evaluator, which we call "continuous Boyce index". All indices were implemented in the B10MAPPER software. We show that the presence-only evaluators are fairly correlated (p > 0.7) to the presence/absence ones. The Boyce indices are closer to AUC than to MaxKappa and are fairly insensitive to species prevalence. In addition, the Boyce indices provide predicted-toexpected ratio curves that offer further insights into the model quality: robustness, habitat suitability resolution and deviation from randomness. This information helps reclassifying predicted maps into meaningful habitat suitability classes. The continuous Boyce index is thus both a complement to usual evaluation of presence/absence models and a reliable measure of presence-only based predictions.

Immunological follow-up of hydatid cyst cases

Hydatid disease is caused by Echinococcus granulosus. In this study, we aimed to investigate the benefit of monitoring cases with hydatid cyst by means of immune components in patients in a long-term follow-up after surgery. Eighty-four preoperative and postoperative serum samples from 14 cases undergoing surgery for hydatid disease were evaluated in terms of immune parameters, such as total and specific IgE, IgG, IgM, IgA and complement. Total and specific IgE were determined by ELISA. Specific IgG levels were measured by indirect hemaglutination.Total IgG, IgM, IgA and complement (C3 and C4) were detected by nephelometry. Imaging studies were also carried out during the follow-up. In none of the patients hydatid cysts were detected during the follow-up. Total IgE levels in the sera of the patients decreased to normal six months after surgery. Although specific IgE against echinococcal antigens decreased one year after operation, levels were still significantly high. There were no changes in the levels of anti-Echinococcus IgG and total IgG in follow-up period. Additionally, other parameters, such as IgA, IgM, C3 and C4, were not affected.

Aspectos metabólicos y multivitamínicos del maíz

La deficiencia de vitamina A causa 2.2 millones de muertes al año. Por tanto, investigadores intentan elevar el contenido de β-caroteno y otros carotenoides en cereales mediante la ingeniería genética. Mi trabajo consistió en analizar carotenoides en maíz y callos de arroz transgénico con el fin de indentificar y cuantificar estos pigmentos y además analizar la ruta metabólica de los mismos. Por tal motivo, desarrollaré una técnica analítica por HPLC y UHPLC que me permitió separar la mezcla de carotenoides. Estas moléculas se detectaton utilizando un detector de arreglo de diodos y masas. Con éste último se probaron distintas técnicas de ionización (ESI, APCI y APPI) para encontrar la mejor técnica que ionizara carotenos y xantófilas. Además se hallaron transiciones para identificar a cada uno de los carotenoides. Para mostrar la confiabilidad del método analítico, realicé la validación del mismo y determiné factores importantes que influyen en el análisis de carotenoides, como por ejemplo, su estabilidad química. Para analizar la ruta metabólica de los carotenoides, se realizaron distintos experimentos, entre ellos, introducir distintas combinaciones de genes en el maíz y arroz que permitieran entender cuáles eran las enzimas importantes que permitían la acumulación de carotenoides. También se analizó la biosíntesis de carotenoides a distintas etapas del desarrollo de la semilla de maíz, desde los 15 días después de la polinización (DAP) hasta los 60 DAP y su estabilidad química a lo largo de todo este período. Finalmente, se profundizó en la identificación de nuevos carotenoides encontrados en las muestras, como los oxo-carotenoides (utilizados en la industria como colorantes). Para llevar acabo su identificación, se realizaron pruebas químicas, se determinaron sus espectros visibles y sus fragmentos por masas.   

Deletion of hypothetical wall teichoic acid ligases in Staphylococcus aureus activates the cell wall stress response.

The Staphylococcus aureus cell wall stress stimulon (CWSS) is activated by cell envelope-targeting antibiotics or depletion of essential cell wall biosynthesis enzymes. The functionally uncharacterized S. aureus LytR-CpsA-Psr (LCP) proteins, MsrR, SA0908 and SA2103, all belong to the CWSS. Although not essential, deletion of all three LCP proteins severely impairs cell division. We show here that VraSR-dependent CWSS expression was up to 250-fold higher in single, double and triple LCP mutants than in wild type S. aureus in the absence of external stress. The LCP triple mutant was virtually depleted of wall teichoic acids (WTA), which could be restored to different degrees by any of the single LCP proteins. Subinhibitory concentrations of tunicamycin, which inhibits the first WTA synthesis enzyme TarO (TagO), could partially complement the severe growth defect of the LCP triple mutant. Both of the latter findings support a role for S. aureus LCP proteins in late WTA synthesis, as in Bacillus subtilis where LCP proteins were recently proposed to transfer WTA from lipid carriers to the cell wall peptidoglycan. Intrinsic activation of the CWSS upon LCP deletion and the fact that LCP proteins were essential for WTA-loading of the cell wall, highlight their important role(s) in S. aureus cell envelope biogenesis.

Ultrastructural, Antigenic and Physicochemical Characterization of the Mojuí dos Campos (Bunyavirus) Isolated from Bat in the Brazilian Amazon Region

The Mojuí dos Campos virus (MDCV) was isolated from the blood of an unidentified bat (Chiroptera) captured in Mojuí dos Campos, Santarém, State of Pará, Brazil, in 1975 and considerated to be antigenically different from other 102 arboviruses belonging to several antigenic groups isolated in the Amazon region or another region by complement fixation tests. The objective of this work was to develop a morphologic, an antigenic and physicochemical characterization of this virus. MDCV produces cytopathic effect in Vero cells, 24 h post-infection (p.i), and the degree of cellular destruction increases after a few hours. Negative staining electron microscopy of the supernatant of Vero cell cultures showed the presence of coated viral particles with a diameter of around 98 nm. Ultrathin sections of Vero cells, and brain and liver of newborn mice infected with MDCV showed an assembly of the viral particles into the Golgi vesicles. The synthesis kinetics of the proteins for MDCV were similar to that observed for other bunyaviruses, and viral proteins could be detected as early as 6 h p.i. Our results reinforce the original studies which had classified MDCV in the family Bunyaviridae, genus Bunyavirus as an ungrouped virus, and it may represent the prototype of a new serogroup.