Etude de la dématérialisation du processus de gestion de documents par la mise en place du système d’information Archidox en RD Congo

Cet article constitue une proposition pour la mise en place d’un système d’information permettant la gestion numérique des documents (courriers, factures, correspondance, etc) par le logiciel ArchiDox. Ce dernier, est une solution de gestion électronique de documents (GED) qui combine la gestion de contenu web, la gestion de documents et le flux de travail en une seule application web. Avec des possibilités de recherche de documents à l'aide de différents paramètres (avec autant de flexibilité que possible) une foi que les documents sont archivés. Chaque document est lié à un profil de flux de travail avec approbation dans lequel certains utilisateurs sont autorisés à effectuer certaines tâches à certains moments pendant le processus de traitement du document. Ainsi, ArchiDox permet de faire la dématérialisation de la gestion de documents pour répondre aux besoins actuels et futurs des administrations en simplifiant la communication et la collaboration au sein des services, en réduisant les coûts d’impression des documents et amélioration de l’efficacité au sein des équipes par la centralisation des documents pour tous les services au sein d’une base de données

Morphology and environment in the Jurassic Nucleatidae (Brachiopoda) from Western Tethys

Nucleatidae (Brachiopoda, Terebratulida) are commonly considered as typical members of the Mediterranean assemblages during the Jurassic. However, nucleatids occasionally also occur in the margins of Western Tethys (Northwestern European shelf). Some of these occurrences in northeastern Spain are analysed, detecting a relation between nucleatid morphology and palaeoenvironment during the Jurassic. The validity of this relationship for the whole of the representatives of the group in the Western Tethys during the Jurassic is tested by means of morphofunctional analyses (principal components analysis and discriminant analysis), concluding that reduction of the lateral expansion of the shell is the key morphological feature whereby epioceanic and epicontinental taxa differ. This change can have functional significance because it can be interpreted as a mechanism to reduce the area exposed when the valves gape, increasing protection against harmful particles in environments characterized by higher terrigenous input. Some modifications on the systematics of the Nucleatidae at the genus level are proposed on the basis of the temporal and biogeographical distribution of these adaptations

A Novel Function for 15-Lipoxygenases in Cholesterol Homeostasis and CCL17 Production in Human Macrophages

Arachidonate 15-lipoxygenase (ALOX15) and arachidonate 15-lipoxygenase, type B (ALOX15B) catalyze the dioxygenation of polyunsaturated fatty acids and are upregulated in human alternatively activated macrophages (AAMs) induced by Th2 cytokine interleukin-4 (IL-4) and/or interleukin-13. Known primarily for roles in bioactive lipid mediator synthesis, 15-lipoxygenases (15-LOXs) have been implicated in various macrophage functions including efferocytosis and ferroptosis. Using a combination of inhibitors and siRNAs to suppress 15-LOX isoforms, we studied the role of 15-LOXs in cellular cholesterol homeostasis and immune function in naïve and AAMs. Silencing or inhibiting the 15-LOX isoforms impaired sterol regulatory element binding protein (SREBP)-2 signaling by inhibiting SREBP-2 processing into mature transcription factor and reduced SREBP-2 binding to sterol regulatory elements and subsequent target gene expression. Silencing ALOX15B reduced cellular cholesterol and the cholesterol intermediates desmosterol, lanosterol, 24,25-dihydrolanosterol, and lathosterol as well as oxysterols in IL-4-stimulated macrophages. In addition, attenuating both 15-LOX isoforms did not generally affect IL-4 gene expression but rather uniquely impacted IL-4-induced CCL17 production in an SREBP-2-dependent manner resulting in reduced T cell migration to macrophage conditioned media. In conclusion, we identified a novel role for ALOX15B, and to a lesser extent ALOX15, in cholesterol homeostasis and CCL17 production in human macrophages

Mechanisms and treatment options of chronic graft dysfunction : Experimental and clinical studies

Chronic graft dysfunction (CGD) is an important post-transplant complication. CGD can be considered as an impaired repair process, which ultimately leads to the loss of graft function.To study non-immunological factors contributing to the development of CGD in kidney grafts we used in vitro and in vivo models, and clinical studies. We studied the actions of hyperlipidemia in vitro. LDL induced increased expression of TGF-β1 and TGF-β receptors type I and type II. Smad2 phosphorylation could be induced by conditioned medium from mesangial cells incubated with LDL. The effects of Fluvastatin and AT1 receptor blocker Candesartan cilexetil on aortic graft arteriosclerosis in the rat were evaluated. Fluvastatin neither alone nor in combination with Cyclosporine A affected allograft remodelling, but reduced neointima formation in isografts. Candesartan cilexetil treatment reduced graft arteriosclerosis. The effect is explained by the reduction of TGF-β1 expression. We investigated the effects of Carvedilol in patients with CGD. Carvedilol failed to alter the CGD progression despite the efficient control of blood pressure, and a beneficial effect on lipid pattern and oxidation. Close control of CyA blood levels is recommended due to interaction between CyA and Carvedilol. Measurement of Ab-oxLDL in kidney graft recipients demonstrated that these patients had lower Ab-oxLDL levels as compared with the control group. Decreased Ab-oxLDL levels were associated with graft loss due to acute rejection and with ischemic heart disease. In this thesis we have addressed several important complex issues, which are interconnected: (1) development of chronic graft dysfunction (2) lipoproteins and their role in inducing pathological conditions like atherosclerosis and graft damage, (3) oxidation, (4) TGF-β and its' role in different pathological conditions, including renal and vascular damage

Mitochondrial dynamics in response to fatty acids in human macrophages

Obesity is considered as a type of chronic inflammation. It enhances the risk of developing cardiovascular disease, diabetes, and some cancers. The key players in the induction of inflammation in adipose tissue are macrophages. However the mechanism of macrophage activation in obese fat tissue is still not fully understood. Elevated level of saturated fatty acids in adipose tissue promotes inflammation and insulin resistance. Exposure of macrophages to saturated fatty acids stimulates pro-inflammatory c-Jun N-terminal kinase (JNK), nuclear factor kappa B (NF-kB) signaling, and production of pro-inflammatory cytokines, such as IL-6, IL-8, IL-1β, and TNFα. Palmitate is a major saturated free fatty acid released by adipocytes. It activates inflammatory pathways through Toll-like receptors (TLR) 2 and 4, provokes endoplasmic reticulum (ER) stress and increases levels of diacylglycerols (DAGs) and ceramides. Saturated fatty acids also affect cellular oxidative metabolism. Thus, mitochondrial fatty acid oxidation reduces ER-stress and expression of inflammatory cytokines in palmitate-treated macrophages. On the other hand mitochondrial reactive oxygen species (ROS) promote palmitate-mediated pro-inflammatory cytokine production. Recently, mitochondrial functions were linked to their morphology. Mitochondrial fission has been reported in β-cells and myocytes in response to high levels of glucose and free fatty acids, and was associated with disruption of mitochondrial functions, increased ROS level, and cell death. The aim of this study was to investigate the role of mitochondrial fragmentation in palmitate-induced inflammation in human macrophages. In our settings fatty acids, independently of their saturation, affected mitochondrial morphology. Mixtures of long chain saturated and unsaturated fatty acids as well as triglyceride-rich lipoprotein lipolysis products promoted mitochondrial fission. Mitochondrial fragmentation in palmitate-treated macrophages revealed a time- and concentration-dependent character, and was reversible upon palmitate removal. This observation, together with unaltered levels of mitochondrial protein and DNA content, and intact mitochondrial respiration, suggested that mitochondria were not damaged and were functionally active. Mechanistically, palmitate-induced mitochondrial fragmentation was not regulated by ER stress or loss of mitochondrial membrane potential. However, inhibition of palmitate incorporation into mitochondrial membrane phospholipids decreased mitochondrial fragmentation. Other approach to prevent mitochondrial fission was the inhibition of dynamin-related protein 1 (DRP1) activity, which drives mitochondrial fission by forming ring- like structures around mitochondria and constricting mitochondrial membranes. Palmitate altered mitochondrial membrane lipid composition and promoted DRP1-oligomerization. The inhibition of palmitate-induced mitochondrial fragmentation enhanced mitochondrial ROS production, c-Jun phosphorylation, and upregulated expression of pro-inflammatory cytokines. Taken together, these results suggest that mitochondrial fragmentation is a protective mechanism attenuating palmitate-induced inflammatory responses. Future experiments will be required to investigate the role of mitochondrial fragmentation in obesity-associated diseases in vivo