The Drosophila gut response to infection:a systems approach

Genetic, physiological, and biochemical studies have successfully ascribed functions to genes in diverse processes. However, the majority of our knowledge in biology is qualitative in nature and is usually based on classical screens, where large effects on a qualitative phenotype are usually sought. While very essential to our mechanistic understanding, these methods can be inadequate when it comes to understanding inter-individual differences in complex quantitative traits. The intensive characterization of the Drosophila gut response to infection has led to the identification of many of its major players and canonical pathways. However, knowledge of what genes and pathways are relevant in determining inter-individual differences in a natural population is still lacking. This study addresses this question by using a systems genetics approach where the effects of natural genomic perturbations on the outcome of enteric infection are explored, often revealing unexpected determinants of infection resistance

Terahertz imaging and spectroscopy : application to defense and security

The aim of this work is to demonstrate the potential and capabilities of terahertz technology for parcels screening and inspection to detect threats such as weapons and explosives, without the need to open the parcel.In this study, we first present terahertz time-domain spectroscopy and spectral imaging for explosives detection. Two types of explosives as well as their binary mixture is analyzed. Due to the complexity of extracting information when facing such mixtures of samples, three chemometric tools are used: principal component analysis (PCA), partial least square analysis (PLS) and partial least squares-discriminant analysis (PLS-DA). The analyses are applied to terahertz spectral data and to spectral-images in order to: (i) describe a set of unknown data and identify similarities between samples by PCA; (ii) create a classification model and predict the belonging of unknown samples to each of the classes, by PLS-DA; (iii) create a model able to quantify and predict the explosive concentrations in a pure state or in mixtures, by PLS.The second part of this work focuses on millimeter wave imaging for weapon detection in parcels. Three different imaging techniques are studied: passive imaging, continuous wave (CW) active imaging and frequency modulated continuous wave (FMCW) active imaging. The performances, the advantages and the limitations of each of the three techniques, for parcel inspection, are exhibited. Moreover, computed tomography is applied to each of the three techniques to visualize data in 3D and inspect parcels in volume. Thus, a special tomography algorithm is developed by taking in consideration the Gaussian propagation of the wave.Le but de ce travail est de quantifier le potentiel et les capacités de la technologie térahertz à contrôler des colis afin de détecter les menaces telles que les armes et les explosifs, sans avoir besoin d'ouvrir le colis.Dans cette étude, nous présentons la spectroscopie térahertz résolue en temps et l'imagerie multi-spectrale pour la détection des explosifs. Deux types d’explosifs, ainsi que leurs mélanges binaires sont analysés. En raison de la complexité de l'extraction des informations face à tels échantillons, trois outils de chimiométrie sont utilisés: l’analyse en composantes principales (ACP), l'analyse des moindres carrés partiels (PLS) et l'analyse des moindres carrés partiels discriminante (PLS-DA). Les méthodes sont appliquées sur des données spectrales térahertz et sur des images spectrales pour : (i) décrire un ensemble de données inconnues et identifier des similitudes entre les échantillons par l'ACP ; (ii) créer des classes, ensuite classer les échantillons inconnus par PLS-DA ; (iii) créer un modèle capable de prédire les concentrations d’un explosif, à l'état pur ou dans des mélanges, par PLS.Dans la deuxième partie de ce travail, nous présentons l'imagerie par les ondes millimétriques pour la détection d'armes dans les colis. Trois techniques d'imagerie différentes sont étudiées : l'imagerie passive, l’imagerie active par des ondes continues (CW) et l’imagerie active par modulation de fréquence (FMCW). Les performances, les avantages et les limitations de chacune de ces techniques, pour l’inspection de colis, sont présentés. En outre, la technique de reconstruction tomographique est appliquée à chacune de ces trois techniques, pour visualiser en 3D et inspecter les colis en volume. Dans cet ordre, un algorithme de tomographie spécial est développé en prenant en considération la propagation gaussienne de l'onde

Allograft Selection for Transepiphyseal Tumor Resection Around the Knee Using Three-Dimensional Surface Registration

Transepiphyseal tumor resection is a common surgical procedure in patients with malignant bone tumors. The aim of this study is to develop and validate a computer-assisted method for selecting the most appropriate allograft from a cadaver bone bank. Fifty tibiae and femora were 3D reconstructed from computed tomography (CT) images. A transepiphyseal resection was applied to all of them in a virtual environment. A tool was developed and evaluated that compares each metaphyseal piece against all other bones in the data bank. This is done through a template matching process, where the template is extracted from the contralateral healthy bone of the same patient. The method was validated using surface distance metrics and statistical tests comparing it against manual methods. The developed algorithm was able to accurately detect the bone segment that best matches the patient's anatomy. The automatic method showed improvement over the manual counterpart. The proposed method also substantially reduced computation time when compared to state-of-the-art methods as well as the manual selection. Our findings suggest that the accuracy, robustness, and speed of the developed method are suitable for clinical trials and that it can be readily applied for preoperative allograft selectio

The chromatin remodeling factor ISW-1 integrates organismal responses against nuclear and mitochondrial stress

Age-associated changes in chromatin structure have a major impact on organismal longevity. Despite being a central part of the ageing process, the organismal responses to the changes in chromatin organization remain unclear. Here we show that moderate disturbance of histone balance during C. elegans development alters histone levels and triggers a stress response associated with increased expression of cytosolic small heat-shock proteins. This stress response is dependent on the transcription factor, HSF-1, and the chromatin remodeling factor, ISW-1. In addition, we show that mitochondrial stress during developmental stages also modulates histone levels, thereby activating a cytosolic stress response similar to that caused by changes in histone balance. These data indicate that histone and mitochondrial perturbations are both monitored through chromatin remodeling and involve the activation of a cytosolic response that affects organismal longevity. HSF-1 and ISW-1 hence emerge as a central mediator of this multi-compartment proteostatic response regulating longevity.Peer reviewe

Non-Transfusion-Dependent Thalassemia: An Update on Complications and Management

Patients with non-transfusion-dependent thalassemia (NTDT) experience many clinical complications despite their independence from frequent transfusions. Morbidities in NTDT stem from the interaction of multiple pathophysiological factors: ineffective erythropoiesis, iron overload (IOL), and hypercoagulability. Ineffective erythropoiesis and hemolysis are associated with chronic hypoxia and a hypercoagulable state. The latter are linked to a high prevalence of thromboembolic and cerebrovascular events, as well as leg ulcers and pulmonary hypertension. IOL in NTDT patients is a cumulative process that can lead to several iron-related morbidities in the liver (liver fibrosis), kidneys, endocrine glands (endocrinopathies), and vascular system (vascular disease). This review sheds light on the pathophysiology underlying morbidities associated with NTDT and summarizes the mainstays of treatment and some of the possible future therapeutic interventions

Pancreas serous cystadenoma: typical imaging aspect of a rare tumor

Abdominal ultrasonography performed in a 54-year-old woman suffering from dyspepsia revealed a large pancreatic mass (Fig. A). CT showed an 8 cm rounded shape pancreatic head mass, slightly lobulated, hypodense but of non pure hydric density at its edge (15- 20 UH) with a stellar-shaped calcified center (Fig. B). After iodine injection, multiple thin septa were visible forming multiple small lodges non-exceeding 2 cm diameter. Pancreatic head or body were not atrophic and main pancreatic duct size was < 3 mm

Genetic cartography of longevity in humans and mice: Current landscape and horizons.

Aging is a complex and highly variable process. Heritability of longevity among humans and other species is low, and this finding has given rise to the idea that it may be futile to search for DNA variants that modulate aging. We argue that the problem in mapping longevity genes is mainly one of low power and the genetic and environmental complexity of aging. In this review we highlight progress made in mapping genes and molecular networks associated with longevity, paying special attention to work in mice and humans. We summarize 40years of linkage studies using murine cohorts and 15years of studies in human populations that have exploited candidate gene and genome-wide association methods. A small but growing number of gene variants contribute to known longevity mechanisms, but a much larger set have unknown functions. We outline these and other challenges and suggest some possible solutions, including more intense collaboration between research communities that use model organisms and human cohorts. Once hundreds of gene variants have been linked to differences in longevity in mammals, it will become feasible to systematically explore gene-by-environmental interactions, dissect mechanisms with more assurance, and evaluate the roles of epistasis and epigenetics in aging. A deeper understanding of complex networks-genetic, cellular, physiological, and social-should position us well to improve healthspan

Commensal Gut Bacteria Buffer the Impact of Host Genetic Variants on Drosophila Developmental Traits under Nutritional Stress

International audienc

Iron Overload and Chelation Therapy in Non-Transfusion Dependent Thalassemia

Iron overload (IOL) due to increased intestinal iron absorption constitutes a major clinical problem in patients with non-transfusion-dependent thalassemia (NTDT), which is a cumulative process with advancing age. Current models for iron metabolism in patients with NTDT suggest that suppression of serum hepcidin leads to an increase in iron absorption and subsequent release of iron from the reticuloendothelial system, leading to depletion of macrophage iron, relatively low levels of serum ferritin, and liver iron loading. The consequences of IOL in patients with NTDT are multiple and multifactorial. Accurate and reliable methods of diagnosis and monitoring of body iron levels are essential, and the method of choice for measuring iron accumulation will depend on the patient's needs and on the available facilities. Iron chelation therapy (ICT) remains the backbone of NTDT management and is one of the most effective and practical ways of decreasing morbidity and mortality. The aim of this review is to describe the mechanism of IOL in NTDT, and the clinical complications that can develop as a result, in addition to the current and future therapeutic options available for the management of IOL in NTDT