Expressed sequence tags from the oomycete fish pathogen Saprolegnia parasitica reveal putative virulence factors

Peer reviewedPublisher PD

The coming of age of EvoMPMI:evolutionary molecular plant-microbe interactions across multiple timescales

Plant-microbe interactions are great model systems to study co-evolutionary dynamics across multiple timescales. However, mechanistic research on plant-microbe interactions has often been conducted with little consideration of evolutionary concepts and methods. Conversely, evolutionary research has rarely integrated the range of mechanisms and models from the molecular plant-microbe interactions field. In recent years, the incipient field of evolutionary molecular plant-microbe interactions (EvoMPMI) has emerged to bridge this gap. Here, we report on some of the recent advances in EvoMPMI. In particular, we highlight new systems to study microbe interactions with early diverging land plants, and new findings from studies of adaptive evolution in pathogens and plants. By linking mechanistic and evolutionary research, EvoMPMI promises to expand our understanding of plant-microbe interactions

Réduction de la luxation de la tête radiale dans le cadre de la maladie exostosante: à propos d’un cas

La luxation de la tête radiale dans le cadre de la maladie exostosante  constitue une complication de déséquilibre de croissance des deux os del'avant bras secondaire à une exostose distale de l'ulna. Le traitement est difficile et controversé par les auteurs. Nous présentons une technique originale pour le traitement de cette entité. Après la correction de l'index radio-cubital inférieur par un allongement progressif de l'ulna, une fixation radio-cubitale inférieure par les fiches distales de l'Orthofix® et un deuxième allongement de l'ulna permet l'abaissement de la tête radiale et sa réduction. La réduction progressive par allongement de l'ulna par la méthode de callotasis constitue une technique séduisante et réalise l'inverse du ce qui passé lors de ralentissement de croissance de l'ulna sous l'effet de l'exostose ulnaire

Experience du service de medecine nucleaire sahloul sousse dans la prise en charge des carcinomes differencies de la thyroïde a thyroglobuline elevee.

But : L’objectif de notre travail est de présenter notre expérience dans la prise en charge des cancer différencié de la thyroïde (CDT) à Thyroglobuline (Tg) élevée, tout en identifiant les paramètres modifiant l’efficacité de l’Irathérapie et la valeur seuil de la Tg permettant avec un balayage post thérapeutique négatif de conclure à une rémission.Matériels et méthodes : Il s’agit d’une étude rétrospective portant sur 150 patients opérés pour CDT, suivis entre 1990 et 2006 et présentant une Tg>2ng/ml.Résultats : Il s’agit de 122 femmes et 28 hommes. L’âge moyen était de 52 ans. La Tg ne dépendait pas du type histologique mais il existait une relation statistiquement significative entre la Tg et la taille tumorale, l’atteinte ganglionnaire, l’extension locorégionale, la présence de métastases et le stade TNM. La réponse thérapeutique des CDT avec une Tg élevée dépendait de l’âge des patients, des caractéristiques anatomopathologiques de la tumeur et des valeurs de la Tg.Conclusion : L’efficacité ablative est optimisée par des cures d’iode 131 qui doivent être prolongées tant que la Tg reste élevée. La surveillance à vie, au cours de la quelle on exige des seuils de Tg infèrieurs à 2ng/ml, est nécessaire. Mots clés : Cancers différenciés de la thyroide, Thyroglobuline, Irathérapie, Pronostic, Surveillance.Purpose: The aim of our work is to present our experience in the management of differentiated thyroid cancer (DTC) with high thyroglobulin (Tg) , to identify parameters changing iodine effectiveness and Tg threshold with negative post treatment scan conclude to remission.Materials and Methods: This is a retrospective study of 150 patients undergoing CDT, followed between 1990 and 2006 and having a Tg > 2ng/ml .Results: Our study concerns 122 women and 28 men. The average age was 52 years . Tg value does not depend on the histological type but there was a statistically significant relationship between Tg and tumor size, lymph node involvement, locoregional , metastasis and TNM stage . The therapeutic response of CDT with a high Tg was dependent on the age of patients, the pathological characteristics of the tumor and the Tg values ofConclusion: The ablative efficiency is optimized by 131 cures iodine should be extended until the Tg remains high. Monitoring life is necessary and the thresholds Tg below 2ng/ml is required.Keywords: Differentiated thyroid Cancers, Thyroglobulin, Iodine 131, Prediction, Monitoring

Cutting Edge: Lessons from fraxinus, a crowd-sourced citizen science game in genomics

In 2013, in response to an epidemic of ash dieback disease in England the previous year, we launched a Facebook-based game called Fraxinus to enable non-scientists to contribute to genomics studies of the pathogen that causes the disease and the ash trees that are devastated by it. Over a period of 51 weeks players were able to match computational alignments of genetic sequences in 78% of cases, and to improve them in 15% of cases. We also found that most players were only transiently interested in the game, and that the majority of the work done was performed by a small group of dedicated players. Based on our experiences we have built a linear model for the length of time that contributors are likely to donate to a crowd-sourced citizen science project. This model could serve a guide for the design and implementation of future crowd-sourced citizen science initiatives

Anti-vascular endothelial growth factor treatment normalizes tuberculosis granuloma vasculature and improves small molecule delivery

Tuberculosis (TB) causes almost 2 million deaths annually, and an increasing number of patients are resistant to existing therapies. Patients who have TB require lengthy chemotherapy, possibly because of poor penetration of antibiotics into granulomas where the bacilli reside. Granulomas are morphologically similar to solid cancerous tumors in that they contain hypoxic microenvironments and can be highly fibrotic. Here, we show that TB-infected rabbits have impaired small molecule distribution into these disease sites due to a functionally abnormal vasculature, with a low-molecular-weight tracer accumulating only in peripheral regions of granulomatous lesions. Granuloma-associated vessels are morphologically and spatially heterogeneous, with poor vessel pericyte coverage in both human and experimental rabbit TB granulomas. Moreover, we found enhanced VEGF expression in both species. In tumors, antiangiogenic, specifically anti-VEGF, treatments can “normalize” their vasculature, reducing hypoxia and creating a window of opportunity for concurrent chemotherapy; thus, we investigated vessel normalization in rabbit TB granulomas. Treatment of TB-infected rabbits with the anti-VEGF antibody bevacizumab significantly decreased the total number of vessels while normalizing those vessels that remained. As a result, hypoxic fractions of these granulomas were reduced and small molecule tracer delivery was increased. These findings demonstrate that bevacizumab treatment promotes vascular normalization, improves small molecule delivery, and decreases hypoxia in TB granulomas, thereby providing a potential avenue to improve delivery and efficacy of current treatment regimens

Arginine at positions 13 or 70-71 in pocket 4 of HLA-DRB1 alleles is associated with susceptibility to tuberculoid leprosy

Evaluation of human histocompatibility leukocyte antigen (HLA) class II genes in 54 cases of tuberculoid leprosy (TL) and 44 controls has shown a positive association with HLA-DRB1 alleles that contain Arg13 or Arg70-Arg71. Among TL patients, 87% carry specific alleles of DRB1 Arg13 or Arg70-Arg71 as compared to 43% among controls (p = 5 x 10(-6)) conferring a relative risk of 8.8. Thus, susceptibility to TL involves three critical amino acid positions of the beta chain, the side chains of which, when modeled on the DR1 crystal structure, line a pocket (pocket 4) accommodating the side chain of a bound peptide. This study suggests that disease susceptibility may be determined by the independent contribution of polymorphic residues participating in the formation of a functional arrangement (i.e., pocket) within the binding cleft of an HLA molecule

Quantum dot/antibody conjugates for in vivo cytometric imaging in mice

Multiplexed, phenotypic, intravital cytometric imaging requires novel fluorophore conjugates that have an appropriate size for long circulation and diffusion and show virtually no nonspecific binding to cells/serum while binding to cells of interest with high specificity. In addition, these conjugates must be stable and maintain a high quantum yield in the in vivo environments. Here, we show that this can be achieved using compact (~15 nm in hydrodynamic diameter) and biocompatible quantum dot (QD) -Ab conjugates. We developed these conjugates by coupling whole mAbs to QDs coated with norbornene-displaying polyimidazole ligands using tetrazine–norbornene cycloaddition. Our QD immunoconstructs were used for in vivo single-cell labeling in bone marrow. The intravital imaging studies using a chronic calvarial bone window showed that our QD-Ab conjugates diffuse into the entire bone marrow and efficiently label single cells belonging to rare populations of hematopoietic stem and progenitor cells (Sca1[superscript +]c-Kit[superscript +] cells). This in vivo cytometric technique may be useful in a wide range of structural and functional imaging to study the interactions between cells and between a cell and its environment in intact and diseased tissues.National Institutes of Health (U.S.) (Grant U54-CA151884)National Institutes of Health (U.S.) (Grant P41-EB015871-26A1)Samsung Scholarship Foundation (Graduate Student Fellowship)Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies (Grant W911NF-07-D-0004

Natural history of Arabidopsis thaliana and oomycete symbioses

Molecular ecology of plant–microbe interactions has immediate significance for filling a gap in knowledge between the laboratory discipline of molecular biology and the largely theoretical discipline of evolutionary ecology. Somewhere in between lies conservation biology, aimed at protection of habitats and the diversity of species housed within them. A seemingly insignificant wildflower called Arabidopsis thaliana has an important contribution to make in this endeavour. It has already transformed botanical research with deepening understanding of molecular processes within the species and across the Plant Kingdom; and has begun to revolutionize plant breeding by providing an invaluable catalogue of gene sequences that can be used to design the most precise molecular markers attainable for marker-assisted selection of valued traits. This review describes how A. thaliana and two of its natural biotrophic parasites could be seminal as a model for exploring the biogeography and molecular ecology of plant–microbe interactions, and specifically, for testing hypotheses proposed from the geographic mosaic theory of co-evolution