Shorter telomeres correlate with an increase in the number of uniparental disomies in patients with chronic lymphocytic leukemia.

This study investigated the correlation of the extent of chromosomal aberrations including uniparental disomies (UPDs) by SNP-chip analysis and FISH to telomere length in 46 patients with CLL. CLL harboring high risk aberrations, i.e. deletions of 11q22-23 or 17p13, had significantly shorter telomeres (higher ΔTL) compared to patients with CLL without such abnormalities. Patients with high chromosomal aberration rates had a worse overall survival compared to cases with lower aberration rates. Interestingly, however, an increase was found in the number of UPDs with shorter telomeres. These findings support the idea that telomeres in CLL cells play a role in the overall chromosome stability and could be involved in the occurrence of UPDs.

Valeur, fonctionnement et fonction. La filiation Saussure-Jakobson: un malentendu?

Si Jakobson, par ailleurs si critique relativement à l’apport saussurien, s’inscrit, quant à la notion de valeur, dans la filiation de Saussure, il nous semble que cette filiation revendiquée par Jakobson repose sur un malentendu. La redéfinition jakobsonienne de la notion de valeur est en effet inséparable d’une disjonction des différentes dimensions constitutives du concept saussurien de valeur. Par ailleurs et corrélativement, la valeur jakobsonienne se caractérise d’emblée par sa positivité, qui se déploie sur deux plans : celui de la consistance objectale, qui répond à une problématique des rapports forme/substance et celui de la sémioticité, qui répond à une problématique des rapports son/sens, deux problématiques aussi étrangères l’une que l’autre à la linguistique saussurienne. A la définition saussurienne de la langue comme un fonctionnement dont son et sens apparaissent comme des effets, fonctionnement qu’est la division-combinaison des deux masses amorphes de la pensée et du son, se substitue la construction jakobsonienne d’une langue structure d’appariement du son et du sens, construction fondée sur l’évidence d’une définition de la langue comme instrument de communication. On peut cependant penser que cette substitution, ce malentendu, sont tout à fait révélateurs de la spécificité de l’objet de la linguistique, particulièrement résistant à la théorisation.

A retrospective analysis of factors influencing the success of autotransplanted posterior teeth

BACKGROUND Survival and success rates of tooth transplantations even after long follow-up periods have been shown to be very high. Nevertheless, it is important to analyse factors potentially influencing these rates. The aim of this study was to assess the influence on success of potential factors. METHODS The research was based on a retrospective analysis of clinical and radiological data from a sample of 59 subjects (75 transplanted teeth). The follow-up period varied from 0.44 to 12.28 years (mean 3.95 years). Success rates were calculated and depicted with Kaplan-Meier plots. Log-rank tests were used to analyse the effect of root development stage, apex width, the use of enamel matrix proteins or the surgeon on success of transplantations. RESULTS Results for success of premolar transplantations were comparable with already published data, while molars performed worse than shown in other studies. The surgeon performing the transplantation (p = 0.001) and tooth type (p ≤ 0.001) were significantly associated with transplantation success. Use of enamel matrix proteins (p = 0.10), root development stage (p = 0.13), the recipient area (p = 0.48) and apex width (p = 0.59) were not significantly associated with success. CONCLUSIONS Molar transplantations were not as successful as premolar transplantations; however, success rates varied greatly depending on the surgeon's experience. The use of enamel matrix proteins as well as root development stage, the recipient area and apex width did not show significant associations with success of tooth transplantations.

Cellular and molecular interactions between the apicomplexan parasites Plasmodium and Theileria and their host cells

Apicomplexan parasites of the genera Theileria and Plasmodium have complicated life cycles including infection of a vertebrate intermediate host and an arthropod definitive host. As the Plasmodium parasite progresses through its life cycle, it enters a number of different cell types, both in its mammalian and mosquito hosts. The fate of these cells varies greatly, as do the parasite and host molecules involved in parasite-host interactions. In mammals, Plasmodium parasites infect hepatocytes and erythrocytes whereas Theileria infects ruminant leukocytes and erythrocytes. Survival of Plasmodium-infected hepatocytes and Theileria-infected leukocytes depends on parasite-mediated inhibition of host cell apoptosis but only Theileria-infected cells exhibit a fully transformed phenotype. As the development of both parasites progresses towards the merozoite stage, the parasites no longer promote the survival of the host cell and the infected cell is finally destroyed to release merozoites. In this review we describe similarities and differences of parasite-host cell interactions in Plasmodium-infected hepatocytes and Theileria-infected leukocytes and compare the observed phenotypes to other parasite stages interacting with host cells.

GFP-targeting allows visualization of the apicoplast throughout the life cycle of live malaria parasites.

BACKGROUND INFORMATION The Plasmodium parasite, during its life cycle, undergoes three phases of asexual reproduction, these being repeated rounds of erythrocytic schizogony, sporogony within oocysts on the mosquito midgut wall and exo-erythrocytic schizogony within the hepatocyte. During each phase of asexual reproduction, the parasite must ensure that every new daughter cell contains an apicoplast, as this organelle cannot be formed de novo and is essential for parasite survival. To date, studies visualizing the apicoplast in live Plasmodium parasites have been restricted to the blood stages of Plasmodium falciparum. RESULTS In the present study, we have generated Plasmodium berghei parasites in which GFP (green fluorescent protein) is targeted to the apicoplast using the specific targeting sequence of ACP (acyl carrier protein), which has allowed us to visualize this organelle in live Plasmodium parasites. During each phase of asexual reproduction, the apicoplast becomes highly branched, but remains as a single organelle until the completion of nuclear division, whereupon it divides and is rapidly segregated into newly forming daughter cells. We have shown that the antimicrobial agents azithromycin, clindamycin and doxycycline block development of the apicoplast during exo-erythrocytic schizogony in vitro, leading to impaired parasite maturation. CONCLUSIONS Using a range of powerful live microscopy techniques, we show for the first time the development of a Plasmodium organelle through the entire life cycle of the parasite. Evidence is provided that interference with the development of the Plasmodium apicoplast results in the failure to produce red-blood-cell-infective merozoites.

Signalling in malaria parasites. The MALSIG consortium

Depending on their developmental stage in the life cycle, malaria parasites develop within or outside host cells, and in extremely diverse contexts such as the vertebrate liver and blood circulation, or the insect midgut and hemocoel. Cellular and molecular mechanisms enabling the parasite to sense and respond to the intra- and the extra-cellular environments are therefore key elements for the proliferation and transmission of Plasmodium, and therefore are, from a public health perspective, strategic targets in the fight against this deadly disease. The MALSIG consortium, which was initiated in February 2009, was designed with the primary objective to integrate research ongoing in Europe and India on i) the properties of Plasmodium signalling molecules, and ii) developmental processes occurring at various points of the parasite life cycle. On one hand, functional studies of individual genes and their products in Plasmodium falciparum (and in the technically more manageable rodent model Plasmodium berghei) are providing information on parasite protein kinases and phosphatases, and of the molecules governing cyclic nucleotide metabolism and calcium signalling. On the other hand, cellular and molecular studies are elucidating key steps of parasite development such as merozoite invasion and egress in blood and liver parasite stages, control of DNA replication in asexual and sexual development, membrane dynamics and trafficking, production of gametocytes in the vertebrate host and further parasite development in the mosquito. This article, which synthetically reviews such signalling molecules and cellular processes, aims to provide a glimpse of the global frame in which the activities of the MALSIG consortium will develop over the next three years.