Vaccination of dogs with Trypanosoma rangeli induces antibodies against Trypanosoma cruzi in a rural area of Córdoba, Argentina

Dogs play a major role in the domestic cycle of Trypanosoma cruzi, acting as reservoirs. In a previous work we have developed a model of vaccination of dogs in captivity with nonpathogenic Trypanosoma rangeli epimastigotes, resulting in the production of protective antibodies against T. cruzi, with dramatic decrease of parasitaemia upon challenge with 100,000 virulent forms of this parasite. The aim of this work was to evaluate the immunogenicity of this vaccine in dogs living in a rural area. Domestic dogs, free from T. cruziinfection, received three immunisations with fixed T. rangeliepimastigotes. Dogs were not challenged with T. cruzi, but they were left in their environment. This immunisation induced antibodies againstT. cruzi for more than three years in dogs in their natural habitat, while control dogs remained serologically negative.

Insulated retroviral vectors towards safe and efficient genetic modification of stem cells

In otherwise successful gene therapy trials for the treatment of SCID patients and others, insertional mutagenesis has resulted in leukemia development. Besides the integration of vectors that including strong enhancers, more recently, SIN-vectors have been shown to partially retain oncogenic potential. The identification of genetic elements which would both prevent such activation effects and shield the transgene from silencing, is a main challenge. Previous attempts met with difficulties in producing the vectors and poor efficacy of the insulators (GIE). The improvement of integrating vectors safety has been investigated using new candidate synthetic GIEs. The latter have been introduced in retroviral and lentiviral vectors. Native LTRs, SIN-LTRs, and SIN-insulated constructs have been designed and compared, using two sets of internal promoter, i.e. strong and housekeeping. We could establish that a specific insulator translates at best into functional activity and boundary effect in both vector types. We could also determine that other genetic elements are key determinants in order to achieve accurate expression and viral titre, from these insulated vectors. A dramatic shift in the expression profile is observed in target cells, with a homogenous pattern including data on both cell-lines and primary HSCs from cord blood. The assessment of potential genotoxicity will be presented, based on the comparison of the integration patterns ingenuity in human target cells sampled over a three months period with both reference LTRs and SIN versus test insulated vectors, using high-throughput pyro-sequencing.

DL4-mediated Notch signaling is required for the development of fetal αβ and γδ T cells.

T-cell development depends upon interactions between thymocytes and thymic epithelial cells (TECs). The engagement of delta-like 4 (DL4) on TECs by Notch1 expressed by blood-borne BM-derived precursors is essential for T-cell commitment in the adult thymus. In contrast to the adult, the earliest T-cell progenitors in the embryo originate in the fetal liver and migrate to the nonvascularized fetal thymus via chemokine signals. Within the fetal thymus, some T-cell precursors undergo programmed TCRγ and TCRδ rearrangement and selection, giving rise to unique γδ T cells. Despite these fundamental differences between fetal and adult T-cell lymphopoiesis, we show here that DL4-mediated Notch signaling is essential for the development of both αβ and γδ T-cell lineages in the embryo. Deletion of the DL4 gene in fetal TECs results in an early block in αβ T-cell development and a dramatic reduction of all γδ T-cell subsets in the fetal thymus. In contrast to the adult, no dramatic deviation of T-cell precursors to alternative fates was observed in the fetal thymus in the absence of Notch signaling. Taken together, our data reveal a common requirement for DL4-mediated Notch signaling in fetal and adult thymopoiesis.

Peroxisome proliferator-activated receptor-alpha-null mice have increased white adipose tissue glucose utilization, GLUT4, and fat mass: Role in liver and brain.

Activation of the peroxisome proliferator-activated receptor (PPAR)-alpha increases lipid catabolism and lowers the concentration of circulating lipid, but its role in the control of glucose metabolism is not as clearly established. Here we compared PPARalpha knockout mice with wild type and confirmed that the former developed hypoglycemia during fasting. This was associated with only a slight increase in insulin sensitivity but a dramatic increase in whole-body and adipose tissue glucose use rates in the fasting state. The white sc and visceral fat depots were larger due to an increase in the size and number of adipocytes, and their level of GLUT4 expression was higher and no longer regulated by the fed-to-fast transition. To evaluate whether these adipocyte deregulations were secondary to the absence of PPARalpha from liver, we reexpresssed this transcription factor in the liver of knockout mice using recombinant adenoviruses. Whereas more than 90% of the hepatocytes were infected and PPARalpha expression was restored to normal levels, the whole-body glucose use rate remained elevated. Next, to evaluate whether brain PPARalpha could affect glucose homeostasis, we activated brain PPARalpha in wild-type mice by infusing WY14643 into the lateral ventricle and showed that whole-body glucose use was reduced. Hence, our data show that PPARalpha is involved in the regulation of glucose homeostasis, insulin sensitivity, fat accumulation, and adipose tissue glucose use by a mechanism that does not require PPARalpha expression in the liver. By contrast, activation of PPARalpha in the brain stimulates peripheral glucose use. This suggests that the alteration in adipocyte glucose metabolism in the knockout mice may result from the absence of PPARalpha in the brain.

Perceptions of unfairness in price increases: an experimental study

This experimental study investigates antecedents and consequences of perceptions of price unfairness in a price increase situation. The proposed theoretical model states that consumer dependence on the service provider as well as the relevance the consumer attributes to the service (for the consumer's life) will affect his/her degree of (a) unfairness price perception, (b) anger, and (c) intention to complain and retaliate. The results support all the hypotheses specified in the model. The findings not only indicate that some situations of unfairness price perception lead to stronger emotions and more dramatic reactions from consumers, but also allow us to predict which situations of perceived unfairness offer greater risks and have greater potential for conflict.

La crampe du musicien. A propos de la maladie de Robert Schumann [The mucisian's cramp. About the illness of Robert Schumann].

The musicians are seen in daily neurological practice facing various problems sometimes simple such as skeletal or tendon pain or even compression of a nerve trunk and sometimes more complicated such as focal dystonia. Dystonia often has a dramatic impact on the career of a musician given the complexity of the clinical and therapeutic approach and the results are often disappointing. The history of the German Romantic composer Robert Schumann illustrates this reality; through his story a discussion of both the different pathophysiological hypotheses responsible for focal dystonia, a disorder of brain plasticity, and of the multimodal therapeutic approaches, revisited in the light of neurophysiological findings will be described.

Assessment of statistical iterative reconstructions to optimize CT examination protocols for children and young adults

La tomodensitométrie (CT) est une technique d'imagerie dont l'intérêt n'a cessé de croître depuis son apparition dans le début des années 70. Dans le domaine médical, son utilisation est incontournable à tel point que ce système d'imagerie pourrait être amené à devenir victime de son succès si son impact au niveau de l'exposition de la population ne fait pas l'objet d'une attention particulière. Bien évidemment, l'augmentation du nombre d'examens CT a permis d'améliorer la prise en charge des patients ou a rendu certaines procédures moins invasives. Toutefois, pour assurer que le compromis risque - bénéfice soit toujours en faveur du patient, il est nécessaire d'éviter de délivrer des doses non utiles au diagnostic.¦Si cette action est importante chez l'adulte elle doit être une priorité lorsque les examens se font chez l'enfant, en particulier lorsque l'on suit des pathologies qui nécessitent plusieurs examens CT au cours de la vie du patient. En effet, les enfants et jeunes adultes sont plus radiosensibles. De plus, leur espérance de vie étant supérieure à celle de l'adulte, ils présentent un risque accru de développer un cancer radio-induit dont la phase de latence peut être supérieure à vingt ans. Partant du principe que chaque examen radiologique est justifié, il devient dès lors nécessaire d'optimiser les protocoles d'acquisitions pour s'assurer que le patient ne soit pas irradié inutilement. L'avancée technologique au niveau du CT est très rapide et depuis 2009, de nouvelles techniques de reconstructions d'images, dites itératives, ont été introduites afin de réduire la dose et améliorer la qualité d'image.¦Le présent travail a pour objectif de déterminer le potentiel des reconstructions itératives statistiques pour réduire au minimum les doses délivrées lors d'examens CT chez l'enfant et le jeune adulte tout en conservant une qualité d'image permettant le diagnostic, ceci afin de proposer des protocoles optimisés.¦L'optimisation d'un protocole d'examen CT nécessite de pouvoir évaluer la dose délivrée et la qualité d'image utile au diagnostic. Alors que la dose est estimée au moyen d'indices CT (CTDIV0| et DLP), ce travail a la particularité d'utiliser deux approches radicalement différentes pour évaluer la qualité d'image. La première approche dite « physique », se base sur le calcul de métriques physiques (SD, MTF, NPS, etc.) mesurées dans des conditions bien définies, le plus souvent sur fantômes. Bien que cette démarche soit limitée car elle n'intègre pas la perception des radiologues, elle permet de caractériser de manière rapide et simple certaines propriétés d'une image. La seconde approche, dite « clinique », est basée sur l'évaluation de structures anatomiques (critères diagnostiques) présentes sur les images de patients. Des radiologues, impliqués dans l'étape d'évaluation, doivent qualifier la qualité des structures d'un point de vue diagnostique en utilisant une échelle de notation simple. Cette approche, lourde à mettre en place, a l'avantage d'être proche du travail du radiologue et peut être considérée comme méthode de référence.¦Parmi les principaux résultats de ce travail, il a été montré que les algorithmes itératifs statistiques étudiés en clinique (ASIR?, VEO?) ont un important potentiel pour réduire la dose au CT (jusqu'à-90%). Cependant, par leur fonctionnement, ils modifient l'apparence de l'image en entraînant un changement de texture qui pourrait affecter la qualité du diagnostic. En comparant les résultats fournis par les approches « clinique » et « physique », il a été montré que ce changement de texture se traduit par une modification du spectre fréquentiel du bruit dont l'analyse permet d'anticiper ou d'éviter une perte diagnostique. Ce travail montre également que l'intégration de ces nouvelles techniques de reconstruction en clinique ne peut se faire de manière simple sur la base de protocoles utilisant des reconstructions classiques. Les conclusions de ce travail ainsi que les outils développés pourront également guider de futures études dans le domaine de la qualité d'image, comme par exemple, l'analyse de textures ou la modélisation d'observateurs pour le CT.¦-¦Computed tomography (CT) is an imaging technique in which interest has been growing since it first began to be used in the early 1970s. In the clinical environment, this imaging system has emerged as the gold standard modality because of its high sensitivity in producing accurate diagnostic images. However, even if a direct benefit to patient healthcare is attributed to CT, the dramatic increase of the number of CT examinations performed has raised concerns about the potential negative effects of ionizing radiation on the population. To insure a benefit - risk that works in favor of a patient, it is important to balance image quality and dose in order to avoid unnecessary patient exposure.¦If this balance is important for adults, it should be an absolute priority for children undergoing CT examinations, especially for patients suffering from diseases requiring several follow-up examinations over the patient's lifetime. Indeed, children and young adults are more sensitive to ionizing radiation and have an extended life span in comparison to adults. For this population, the risk of developing cancer, whose latency period exceeds 20 years, is significantly higher than for adults. Assuming that each patient examination is justified, it then becomes a priority to optimize CT acquisition protocols in order to minimize the delivered dose to the patient. Over the past few years, CT advances have been developing at a rapid pace. Since 2009, new iterative image reconstruction techniques, called statistical iterative reconstructions, have been introduced in order to decrease patient exposure and improve image quality.¦The goal of the present work was to determine the potential of statistical iterative reconstructions to reduce dose as much as possible without compromising image quality and maintain diagnosis of children and young adult examinations.¦The optimization step requires the evaluation of the delivered dose and image quality useful to perform diagnosis. While the dose is estimated using CT indices (CTDIV0| and DLP), the particularity of this research was to use two radically different approaches to evaluate image quality. The first approach, called the "physical approach", computed physical metrics (SD, MTF, NPS, etc.) measured on phantoms in well-known conditions. Although this technique has some limitations because it does not take radiologist perspective into account, it enables the physical characterization of image properties in a simple and timely way. The second approach, called the "clinical approach", was based on the evaluation of anatomical structures (diagnostic criteria) present on patient images. Radiologists, involved in the assessment step, were asked to score image quality of structures for diagnostic purposes using a simple rating scale. This approach is relatively complicated to implement and also time-consuming. Nevertheless, it has the advantage of being very close to the practice of radiologists and is considered as a reference method.¦Primarily, this work revealed that the statistical iterative reconstructions studied in clinic (ASIR? and VECO have a strong potential to reduce CT dose (up to -90%). However, by their mechanisms, they lead to a modification of the image appearance with a change in image texture which may then effect the quality of the diagnosis. By comparing the results of the "clinical" and "physical" approach, it was showed that a change in texture is related to a modification of the noise spectrum bandwidth. The NPS analysis makes possible to anticipate or avoid a decrease in image quality. This project demonstrated that integrating these new statistical iterative reconstruction techniques can be complex and cannot be made on the basis of protocols using conventional reconstructions. The conclusions of this work and the image quality tools developed will be able to guide future studies in the field of image quality as texture analysis or model observers dedicated to CT.

The circadian clock modulates renal sodium handling.

The circadian clock contributes to the control of BP, but the underlying mechanisms remain unclear. We analyzed circadian rhythms in kidneys of wild-type mice and mice lacking the circadian transcriptional activator clock gene. Mice deficient in clock exhibited dramatic changes in the circadian rhythm of renal sodium excretion. In parallel, these mice lost the normal circadian rhythm of plasma aldosterone levels. Analysis of renal circadian transcriptomes demonstrated changes in multiple mechanisms involved in maintaining sodium balance. Pathway analysis revealed the strongest effect on the enzymatic system involved in the formation of 20-HETE, a powerful regulator of renal sodium excretion, renal vascular tone, and BP. This correlated with a significant decrease in the renal and urinary content of 20-HETE in clock-deficient mice. In summary, this study demonstrates that the circadian clock modulates renal function and identifies the 20-HETE synthesis pathway as one of its principal renal targets. It also suggests that the circadian clock affects BP, at least in part, by exerting dynamic control over renal sodium handling.

Llocs, formes i textos de la protohistòria literària catalana. Segles XV-XVII: del marquès de Santillana a Nicolás Antonio (1676)

Es presenten notícies sobre l’activitat dels els inicis de la història literària catalana, la multiplicitat dels vehicles on apareix, les formes que adopta i l’evolució que experimenta

Wildflower areas within revitalized agricultural matrices boost small mammal populations but not breeding Barn Owls

Agro-ecosystems have recently experienced dramatic losses of biodiversity due to more intensive production methods. In order to increase species diversity, agri-environment schemes provide subsidies to farmers who devote a fraction of their land to ecological compensation areas (ECA). Several studies have shown that invertebrate biodiversity is actually higher in ECA than in nearby intensively cultivated farmland. It remains poorly understood, however, to what extent ECA also favour vertebrates, such as small mammals and their predators, which would contribute to restore functioning food chains within revitalized agricultural matrices. We studied small mammal populations among eight habitat types - including wildflower areas, a specific ECA in Switzerland - and habitat selection (radiotracking) by the barn owl Tyto alba, one of their principal predators. Our prediction was that habitats with higher abundances of small mammals would be more visited by foraging Barn owls during the period of chicks' provisioning. Small mammal abundance tended to be higher in wildflower areas than in any other habitat type. Barn owls, however, preferred to forage in cereal fields and grassland. They avoided all types of crops other than cereals, as well as wildflower areas, which suggests that they do not select their hunting habitat primarily with respect to prey density. Instead of prey abundance, prey accessibility may play a more crucial role: wildflower areas have a dense vegetation cover, which may impede access to prey for foraging owls. The exploitation of wildflower areas by the owls might be enhanced by creating open foraging corridors within or around wildflower areas. Wildflower areas managed in that way might contribute to restore functioning food chains within agro-ecosystems.

Correlation between vasoconstrictor roles and mRNA expression of alpha1-adrenoceptor subtypes in blood vessels of genetically engineered mice.

We examined the contribution of each alpha(1)-adrenoceptor (AR) subtype in noradrenaline (NAd)-evoked contraction in the thoracic aortas and mesenteric arteries of mice. Compared with the concentration-response curves (CRCs) for NAd in the thoracic aortas of wild-type (WT) mice, the CRCs of mutant mice showed a significantly lower sensitivity. The pD(2) value in rank order is as follows: WT mice (8.21) > alpha(1B)-adrenoceptor knockout (alpha(1B)-KO) (7.77) > alpha(1D)-AR knockout (alpha(1D)-KO) (6.44) > alpha(1B)- and alpha(1D)-AR double knockout (alpha(1BD)-KO) (5.15). In the mesenteric artery, CRCs for NAd did not differ significantly between either WT (6.52) and alpha(1B)-KO mice (7.12) or alpha(1D)-KO (6.19) and alpha(1BD)-KO (6.29) mice. However, the CRC maximum responses to NAd in alpha(1D)- and alpha(1BD)-KO mice were significantly lower than those in WT and alpha(1B)-KO mice. Except in the thoracic aortas of alpha(1BD)-KO mice, the competitive antagonist prazosin inhibited the contraction response to NAd with high affinity. However, prazosin produced shallow Schild slopes in the vessels of mice lacking the alpha(1D)-AR gene. In the thoracic aorta, pA(2) values in WT mice for KMD-3213 and BMY7378 were 8.25 and 8.46, respectively, and in alpha(1B)-KO mice they were 8.49 and 9.13, respectively. In the mesenteric artery, pA(2) values in WT mice for KMD-3213 and BMY7378 were 8.34 and 7.47, respectively, and in alpha(1B)-KO mice they were 8.11 and 7.82, respectively. These pharmacological findings were in fairly good agreement with findings from comparison of CRCs, with the exception of the mesenteric arteries of WT and alpha(1B)-KO mice, which showed low affinities to BMY7378. We performed a quantitative analysis of the mRNA expression of each alpha(1)-AR subtype in these vessels in order to examine the correlation between mRNA expression level and the predominance of each alpha(1)-AR subtype in mediating vascular contraction. The rank order of each alpha(1)-AR subtype in terms of its vasoconstrictor role was in fairly good agreement with the level of expression of mRNA of each subtype, that is, alpha(1D)-AR > alpha(1B)-AR > alpha(1A)-AR in the thoracic aorta and alpha(1D)-AR > alpha(1A)-AR > alpha(1B)-AR in the mesenteric artery. No dramatic compensatory change of alpha(1)-AR subtype in mutant mice was observed in pharmacological or quantitative mRNA expression analysis.

Hémato-oncologie pédiatrique: de la biologie cellulaire aux traitements ciblés et individualisés [Pediatric hemato-oncology: from cellular biology to individualized targeted therapies].

Progresses in pediatric oncology over the last decades have been dramatic and allow current cure rates above 80%. There are mainly due to multicentre clinical trials aiming at optimizing chemotherapy protocols as well as local therapies in a stepwise approach. Most of the new anticancer drugs currently in development are based on targeted therapies, directed to specific targets present only in or on tumor cells, like growth factor receptors, mechanisms involved in proliferation, DNA repair, apoptosis, tumor invasion or angiogenesis. Concerning bone marrow transplantation also, new strategic approaches are in advanced development. They aim at reducing treatment induced toxicity and enhancing efficacy at the same time. This short paper would like to point out these new technologies, which should be known by the general practitioner.

Introducció a l’obra de Bassam Kanaan (catàleg raonat 1960-1987)

Recull, identificació i documentació d'aproximadament 130 obres de l'artista sirià Bassam Kanaan entre 1960 i 1987. El treball inclou un apunt biogràfic de l'artista que, com diu la seva autora, va evitar conscientment formar part del sistema, cosa que ha complicat la tasca de rescatar de l'oblit informacions sobre Kanaan

Greenberg i Danto : De l'últim gran relat a la fi de l'art

A partir de l'anàlisi comparatiu de l'obra de dos grans teòrics de la modernitat i la postmodernitat com són Clement Greenberg i Arthur C. Danto es fa un estudi de com aquests dos autors han arribat a construir els seus discursos i, en relació a això, com ha anat evolucionant el concepte d'art de la modernitat a la postmodernitat. La qüestió central que se'ns planteja és: què ha canviat en la idea d'art de la postmodernitat respecte a la idea o a la concepció d'art anterior, per arribar-nos a qüestionar si realment hi ha art i, si n'hi ha, què és art i que no ho és? Existeix una idea universal de què ha de ser art? O aquesta és una qüestió intrínsicament relacionada amb la societat en què es produeix; en aquest cas, la societat occidental?

Sib mating without inbreeding in the longhorn crazy ant.

Sib matings increase homozygosity and, hence, the frequency of detrimental phenotypes caused by recessive deleterious alleles. However, many species have evolved adaptations that prevent the genetic costs associated with inbreeding. We discovered that the highly invasive longhorn crazy ant, Paratrechina longicornis, has evolved an unusual mode of reproduction whereby sib mating does not result in inbreeding. A population genetic study of P. longicornis revealed dramatic differences in allele frequencies between queens, males and workers. Mother-offspring analyses demonstrated that these allele frequency differences resulted from the fact that the three castes were all produced through different means. Workers developed through normal sexual reproduction between queens and males. However, queens were produced clonally and, thus, were genetically identical to their mothers. In contrast, males never inherited maternal alleles and were genetically identical to their fathers. The outcome of this system is that genetic inbreeding is impossible because queen and male genomes remain completely separate. Moreover, the sexually produced worker offspring retain the same genotype, combining alleles from both the maternal and paternal lineage over generations. Thus, queens may mate with their brothers in the parental nest, yet their offspring are no more homozygous than if the queen mated with a male randomly chosen from the population. The complete segregation of the male and female gene pools allows the queens to circumvent the costs associated with inbreeding and therefore may act as an important pre-adaptation for the crazy ant's tremendous invasive success.