Measles immune suppression:lessons from the Macaque Model

Measles remains a significant childhood disease, and is associated with a transient immune suppression. Paradoxically, measles virus (MV) infection also induces robust MV-specific immune responses. Current hypotheses for the mechanism underlying measles immune suppression focus on functional impairment of lymphocytes or antigen-presenting cells, caused by infection with or exposure to MV. We have generated stable recombinant MVs that express enhanced green fluorescent protein, and remain virulent in non-human primates. By performing a comprehensive study of virological, immunological, hematological and histopathological observations made in animals euthanized at different time points after MV infection, we developed a model explaining measles immune suppression which fits with the "measles paradox". Here we show that MV preferentially infects CD45RA - memory T-lymphocytes and follicular B-lymphocytes, resulting in high infection levels in these populations. After the peak of viremia MV-infected lymphocytes were cleared within days, followed by immune activation and lymph node enlargement. During this period tuberculin-specific T-lymphocyte responses disappeared, whilst strong MV-specific T-lymphocyte responses emerged. Histopathological analysis of lymphoid tissues showed lymphocyte depletion in the B- and T-cell areas in the absence of apoptotic cells, paralleled by infiltration of T-lymphocytes into B-cell follicles and reappearance of proliferating cells. Our findings indicate an immune-mediated clearance of MV-infected CD45RA - memory T-lymphocytes and follicular B-lymphocytes, which causes temporary immunological amnesia. The rapid oligoclonal expansion of MV-specific lymphocytes and bystander cells masks this depletion, explaining the short duration of measles lymphopenia yet long duration of immune suppression. © 2012 de Vries et al.

Dynamic interaction of NtMAP65-1a with microtubules in vivo

Plant microtubules are intrinsically more dynamic than those from animals. We know little about the dynamics of the interaction of plant microtubule-associated proteins (MAPs) with microtubules. Here, we have used tobacco and Arabidopsis MAPs with relative molecular mass 65 kDa (NtMAP65-1a and AtMAP65-1), to study their interaction with microtubules in vivo. Using fluorescence recovery after photobleaching we report that the turnover of both NtMAP65-1a and AtMAP65-1 bound to microtubules is four- to fivefold faster than microtubule treadmilling (13 seconds compared with 56 seconds, respectively) and that the replacement of NtMAP65-1a on microtubules is by random association rather than by translocation along microtubules. MAP65 will only bind polymerised microtubules and not its component tubulin dimers. The turnover of NtMAP65-1a and AtMAP65-1 on microtubules is similar in the interphase cortical array, the preprophase band and the phragmoplast, strongly suggesting that their role in these arrays is the same. NtMAP65-1a and AtMAP65-1 are not observed to bind microtubules in the metaphase spindle and their rate of recovery is consistent with their cytoplasmic localisation. In addition, the dramatic reappearance of NtMAP65-1a on microtubules at the spindle midzone in anaphase B suggests that NtMAP65-1a is controlled post-translationally. We conclude that the dynamic properties of these MAPs in vivo taken together with the fact that they have been shown not to effect microtubule polymerisation in vitro, makes them ideally suited to a role in crossbridging microtubules that need to retain spatial organisation in rapidly reorganising microtubule arrays.

Early detection of leukaemic relapse after bone marrow transplantation using the polymerase chain reaction

We report a case of acute lymphoblastic leukaemia relapsing after allogeneic bone marrow transplantation in which the polymerase chain reaction (PCR) was used to assess chimeric status. This technique demonstrated the progressive reappearance of host cells prior to clinical relapse. The relapse was of host cell origin as shown by the presence of female (recipient) metaphases containing an abnormal chromosomal marker (iso 9q) which had also been present at initial diagnosis. The emergence of host cells in this case, detected only by PCR techniques but not by cytogenetic methods, appeared to herald overt relapse. PCR analysis provides a sensitive tool for detecting a progressive rise in host cell numbers which may predict clinical relapse.

The Origin and Stimuli Implicated in the Expression of Nestin(+) Cardiac Myocyte-like Cells in the Ischemic Heart

Nos études ont démontrées que la formation de la cicatrice et la guérison sont associées avec l’apparition de cellules de type myocytes cardiaques nestine(+) dans la région péri-infarcie. Présentement, l’étude examine le mécanisme, tel que l’hypoxie ou les hormones neuronales, possiblement impliqué dans leur recrutement et de dévoiler leur origine cellulaire. La présence de ces cellules a été détectée dans les coeurs infarcies d’une semaine et maintenue après neuf mois suite à une sujétion coronaire complète. Aussi, ces cellules de type myocytes cardiaques nestine(+) ont été observées dans le coeur infarci humain. L’hypoxie représente un événement prédominant suite à un infarctus de myocarde, mais l’exposition des rats normaux à un environnement hypoxique n’a pas pu promouvoir l’apparition de ces cellules. Autrement, l’infusion de l’agoniste -adrénergique non-sélectif isoprotérénol (ISO) dans les rats adultes Sprague-Dawley a augmenté la protéine nestine dans le ventricule gauche et a été associé avec la réapparition de cellules de type myocytes cardiaques nestine(+). Cela représente possiblement un effet secondaire suite à la nécrose des myocytes cardiaques par l’administration d’isoprotérénol. Dernièrement, on a identifié une sous-population de cellules nestine(+) dans le coeur normal du rat qui co-exprime les marqueurs de cellules cardiaques progénitrices Nkx-2.5 et GATA-4. Cette sous-population de cellules nestine/Nkx-2.5/GATA-4 pourrait représenter des substrats cellulaires qui puissent se différentier en cellules de type myocytes cardiaques nestine(+) suite à une ischémie. Mots clés: nestine, isoprotérénol, nécrose, cellule souche, cellule progénitrice, myocyte cardiaque

The role of ubiquitination and deubiquitination in the regulation of BRCA1 function during genotoxic stress

BRCA1 est un suppresseur de tumeur majeur jouant un rôle dans la transcription, la réparation de l’ADN et le maintien de la stabilité génomique. En effet, des mutations dans le gène BRCA1 augmentent considerablement le risque de cancers du sein et de l’ovaire. BRCA1 a été en majorité caractérisé pour son rôle dans la réparation de l’ADN par la voie de recombinaison homologue (HR) en présence de bris double brins, par example, induits par l’irradiation gamma (IR). Cependant, la fonction de BRCA1 dans d’autres voies de réparation de l’ADN, comme la réparation par excision de nucléotides (NER) ou par excision de base (BER), demeurent toutefois obscures. Il est donc important de comprendre la régulation de BRCA1 en présence d’agents génotoxiques comme le méthyle méthanesulfonate (MMS) ou l’UV, qui promouvoient le BER et le NER respectivement. Nos observations suggèrent que BRCA1 est dégradée par le protéasome après traitement avec le MMS ou les UV, et non avec l’IR. Par ailleurs, cette dégradation semble compromettre le recrutement de Rad51, suggérant que la voie de HR est inhibée. Nos résultats suggèrent que la HR est inhibée afin d’éviter l’activation simultanée de multiples voies de réparation. Nous avons aussi observé que la dégradation BRCA1 est réversible et que la restauration des niveaux de BRCA1 coïncide avec le recrutement de Rad51 aux sites de dommages. Cela suggère que la HR est réactivée tardivement par les bris double brins générés suite à l’effondrement des fourches de réplication. Ayant observé que BRCA1 est hautement régulé par l’ubiquitination et est ciblé par le protéasome pour dégradation, nous avons émis une hypothèse que BRCA1 est régulé par des déubiquitinases. Cela amène à caractériser plus en profondeur par un criblage en déplétant les déubiquitinases individuellement par RNAi et en observant leur effet sur le recrutement de BRCA1 et des protéines reliées à cette voie. Un criblage préliminaire nous a permi d’identifié candidats potentiels tel que BAP1, CXORF53, DUB3, OTUB1 et USP36.

Contribution des isoformes de la myosine à l'obstruction respiratoire dans le souffle chez le cheval

La myosine est une protéine motrice impliquée dans la contraction du muscle lisse. Un de ces isoformes, appelé (+)insert lui procure une vélocité accrue. L’objectif de cette étude était d’évaluer la contribution de cet isoforme au bronchospasme observé chez les chevaux atteints de souffle, un modèle d’asthme humain. Nous avons procédé à l’analyse de l’expression génique de l’isoforme (+)insert dans les voies respiratoires de chevaux issus de 3 cohortes afin d’évaluer 1) la présence de cet isoforme chez les chevaux atteints de souffle ; 2) la réversibilité de son expression avec 2 traitements usuels (corticostéroïdes inhalés et retrait antigénique); et 3) la cinétique de réapparition de l’isoforme suite à une période de rémission de la maladie. Les résultats révèlent 1) une expression augmentée de l’isoforme (+)insert dans l’ensemble de l’arbre bronchique des chevaux atteints de souffle en exacerbation comparée aux contrôles et aux chevaux en rémission ; 2) les deux traitements conduisent à une réduction de l’expression de l’isoforme, mais l’administration de corticostéroïdes mène à une diminution plus rapide que celle induite par le retrait antigénique; et 3) une période de 30 jours ou plus d'exposition antigénique est nécessaire pour la réapparition de l’isoforme (+)insert dans l’arbre bronchique des chevaux atteints de souffle. Cette étude montre pour la première fois une modulation et une réversibilité de l’expression de l'isoforme (+)insert de la myosine en fonction du statut médical du sujet. Les données suggèrent que cet isoforme pourrait faire partie d’un mécanisme protecteur activé en réponse à une exposition antigénique prolongée.

Le corps “mort-vivant” et la ville “détruite” dans le cinéma libanais d’après guerre.

"ENTRE DEUX", le film que j'ai écrit et réalisé pour cette recherche-création, a été filmé avec les caméras Canon 5D et 7D et monté en utilisant le logiciel final cut pro 7

Dynamics of the logistic map under discrete parametric perturbation

By introducing a periodic perturbation in the control parameter of the logistic map we have investigated the period locking properties of the map. The map then gets locked onto the periodicity of the perturbation for a wide range of values of the parameter and hence can lead to a control of the chaotic regime. This parametrically perturbed map exhibits many other interesting features like the presence of bubble structures, repeated reappearance of periodic cycles beyond the chaotic regime, dependence of the escape parameter on the seed value and also on the initial phase of the perturbation etc.

Ganglión oculto: comparación de dos técnicas quirúrgicas

Identificar y evaluar la existencia de posibles diferencias entre los resultados de dos técnicas quirúrgicas para resección de ganglión oculto usadas en el Institut Kaplan en Barcelona. Material y método: Se diseñó un estudio de casos y controles. Se intervinieron ochenta y dos muñecas que se dividieron en dos grupos. En el grupo I, se incluyeron por cincuenta y una muñecas en las que se les realizó la resección del ganglión oculto junto con todo el grosor del ligamento escafo-semilunar dorsal. En el grupo II se incluyeron treinta y una muñecas en las que se les resecó el ganglión sin resecar el ligamento escafo-semilunar. Se tomó la información de registros consignados entre 1994 hasta octubre de 2010 y se realizó un seguimiento clínico y telefónico en ambos grupos para valorar el estado actual. Dentro de los resultados postoperatorios se evaluó la reaparición del dolor, la presencia de inestabilidad postoperatoria y la fuerza con respecto al preoperatorio y la disminución de la movilidad articular. Resultados: No encontramos diferencias estadísticamente significativas entre los resultados postoperatorios de ambos grupos y ninguno de los pacientes presentó recidiva del ganglión. Conclusión: Consideramos que se requiere un estudio con mayor tamaño de muestra que pueda evidenciar las diferencias posiblemente existentes que no fueron detectadas en este estudio. Con la integridad de los otros elementos estabilizadores, la sección del ligamento escafosemilunar no hace aparecer signos clínicos de inestabilidad escafolunar.

El Soft Power para la construccion y el posicionamiento hegemonico de Venezuela a traves de la Alianza Bolivariana de las Americas (ALBA), 2005-2008

Este documento muestra la posibilidad del resurgimiento de la teoria del Soft Power en el siglo XXI en Latinoamerica, especificamente en Venezuela. Se desarrolla la idea de la construccion y el posicionamiento hegemonico de Venezuela a traves de la Naturaleza cambiante del poder y sus recursos intangibles. Todo esto aplicado a traves del ALBA en el periodo de 2005 a 2008.

Inversión extranjera de España en Cuba a partir de 1991. Perspectivas de una transición económica.

El interés que presenta esta investigación es analizar la manera en que la inversión española influye en la economía cubana para generar en la isla perspectivas de transición económica desde 1991. Se explica la situación de expectativa en relación con la posible transición económica cubana por las reformas legislativas, los lazos económicos generados con nuevos socios y la reentrada en escena de la propiedad privada en el entorno cubano. No obstante, el embargo económico estadounidense, la persistencia del régimen castrista, su aparente falta de voluntad hacia el cambio y la no ejecución de algunas decisiones de la Asamblea Nacional actúan como obstáculos para dicho proceso de transición. La metodología de investigación es de tipo descriptivo-analítico, en donde se emplean conceptos de relaciones internacionales para alcanzar un mayor grado de comprensión.

The Dark Monarch: magic and modernity in British art

This major curated exhibition, publication and events builds on Rowlands’ curatorial research. Working in collaboration with co-curators Martin Clark, Artistic Director, Tate St Ives and Michael Bracewell, cultural historian, the exhibition sought to explore new narratives within British art. The innovative curatorial methodology developed from a fiction found in the infamous novel, The Dark Monarch by Sven Berlin, Gallery Press 1962. The research sought specific archival and collection work that allowed thematic strands to emerge that represented influences across generations. The exhibition features two-hundred artworks, from the Tate Collection, archives and other significant British public and private collections. It examines the development of early Modernism, in the UK, as well as the reappearance of esoteric and arcane references in a significant strand of contemporary art practice. Historical works from Samuel Palmer, Graham Sutherland, Henry Moore and Paul Nash are shown alongside contemporary artists including Derek Jarman, Cerith Wyn Evans, Eva Rothschild, Linder and John Russell. The exhibition includes a key work by Damien Hirst ¬ the first time he has been shown at Tate St Ives and a number of contemporary commissions. The Dark Monarch publication extended the discourse of the research critically examining the tension between progressive modernity and romantic knowledge, the book focuses on the way that artworks are encoded with various histories - geological, mythical and magical. Essays examine magic as a counterpoint to modernity’s transparency and rational progress, but also draw out the links modernity has with notions such as fetishism, mana, totem, and the taboo. Often viewed as counter to Modernism, this collection of essays suggest that these products of illusion and delusion in fact belong to modernity. Drawing together 15 different writers commissioned to explore magic as a counterpoint of liberal understanding of modernity, drawing out links that modernity has with notions of fetish, taboo and occult philosophy. Including essays by Marina Warner, Ilsa Colsell, Philip Hoare, Chris Stephens, Jennifer Higgie and Morrissey.

Recurrent Parasitemias and Population Dynamics of Plasmodium vivax Polymorphisms in Rural Amazonia

Clinical trials documented alarming post-treatment Plasmodium vivax recurrence rates caused by recrudescence of surviving asexual blood stages, relapse from hypnozoites, or new infections. Here we describe high rates of P vivax recurrence (26-40% 180 days after treatment) in two cohorts of rural Amazonians exposed to low levels of malaria transmission after a vivax malaria episode treated with chloroquine-primaquine. Microsatellite analysis of 28 paired acute infection and recurrence parasites showed only two pairs of identical haplotypes (consistent with recrudescences or reactivation of homologous hypnozoites) and four pairs of related haplotypes (sharing alleles at 11-13 of 14 microsatellites analyzed). Local isolates of P vivax were extraordinarily diverse and rarely shared the same haplotype, indicating that frequent recurrences did not favor the persistence or reappearance of clonal lineages of parasites in the Population. This fast haplotype replacement rate may represent the typical population dynamics Of neutral polymorphisms in parasites from low-endemicity areas.

Effectiveness of artemether-lumefantrine provided by community health workers in under-five children with uncomplicated malaria in rural Tanzania : an open label prospective study

Background: Home-management of malaria (HMM) strategy improves early access of anti-malarial medicines to high-risk groups in remote areas of sub-Saharan Africa. However, limited data are available on the effectiveness of using artemisinin-based combination therapy (ACT) within the HMM strategy. The aim of this study was to assess the effectiveness of artemether-lumefantrine (AL), presently the most favoured ACT in Africa, in under-five children with uncomplicated Plasmodium falciparum malaria in Tanzania, when provided by community health workers (CHWs) and administered unsupervised by parents or guardians at home. Methods: An open label, single arm prospective study was conducted in two rural villages with high malaria transmission in Kibaha District, Tanzania. Children presenting to CHWs with uncomplicated fever and a positive rapid malaria diagnostic test (RDT) were provisionally enrolled and provided AL for unsupervised treatment at home. Patients with microscopy confirmed P. falciparum parasitaemia were definitely enrolled and reviewed weekly by the CHWs during 42 days. Primary outcome measure was PCR corrected parasitological cure rate by day 42, as estimated by Kaplan-Meier survival analysis. This trial is registered with ClinicalTrials.gov, number NCT00454961. Results: A total of 244 febrile children were enrolled between March-August 2007. Two patients were lost to follow up on day 14, and one patient withdrew consent on day 21. Some 141/241 (58.5%) patients had recurrent infection during follow-up, of whom 14 had recrudescence. The PCR corrected cure rate by day 42 was 93.0% (95% CI 88.3%-95.9%). The median lumefantrine concentration was statistically significantly lower in patients with recrudescence (97 ng/mL [IQR 0-234]; n = 10) compared with reinfections (205 ng/mL [114-390]; n = 92), or no parasite reappearance (217 [121-374] ng/mL; n = 70; p <= 0.046). Conclusions: Provision of AL by CHWs for unsupervised malaria treatment at home was highly effective, which provides evidence base for scaling-up implementation of HMM with AL in Tanzania.

"João Ferrador na República de São Bernardo" : o impacto do "novo" movimento sindical do ABC paulista no processo de transição democrática (1977-1980)

Nesta dissertação, analisa-se o impacto do surgimento do “novo” sindicalismo no ABC Paulista através da ação do Sindicato dos Metalúrgicos de São Bernardo do Campo e Diadema no processo de abertura política. A ação desse importante ator coletivo naquela conjuntura resultou numa gama de novos repertórios de ação coletiva, bem como no reaparecimento da questão operária, após quase uma década de desaparecimento público. Esse novo ímpeto para a ação, produzido na relação conflitiva com os empresários e após com o Estado, serviu não só para produzir uma identidade política para os metalúrgicos do ABC paulista, com também uma agenda de demandas que se ampliava a cada embate e, sobretudo, um tensionamento sobre a esfera política, fazendo avançar o conteúdo nitidamente conservador assumido pela abertura “pelo alto”. A análise se concentrou no período que vai do ano de 1977 ao ano de 1980, avançando, portanto, sobre a data de fundação do Partido dos Trabalhadores, que serviria de referência para a entrada do movimento num campo marcadamente político-partidário. A análise do tema, através do uso de diversos materiais, dentre os quais entrevistas inéditas com sindicalistas que vivenciaram os acontecimentos, além de farta documentação da imprensa sindical do período, possibilitou situar a dimensão alcançada pela luta sindical naquela conjuntura e a forma como repercutiu na política nacional.