Gestion des connaissances : préambule à un portrait

Pour des raisons de performance, innovation ou compétitivité, les connaissances sont devenues une ressource de première importance dans les organisations de l’économie du savoir. Gérer les connaissances explicites et tacites représente une stratégie ayant ses propres concepts, méthodes, outils, qui attirent l’attention des spécialistes. En appliquant une analyse à un corpus d’articles scientifiques, cette étude se propose d’identifier les domaines traitant ou mettant en application la gestion des connaissances, afin de dresser un inventaire de ses champs d’étude et/ou d’application et contribuer ainsi à une meilleure compréhension de ses bénéfices. Ce texte présente des résultats préliminaires : douze domaines d’étude identifiés comme abordant la gestion des connaissances, à comparer aux résultats de la deuxième étape de la recherche (en cours), pour finalement élaborer un portrait de la gestion des connaissances et des aires d’études reliées.By reason of performance, innovation or competitiveness, knowledge has become an important resource for organisations in the knowledge economy. Managing the explicit and the tacit knowledge represents a strategy with its own concepts, methods, and tools, which draws the attention of specialists. Through an analysis on a corpus of scientific articles, this study aims to identify those fields related to, or utilizing knowledge management. The objective of this task is to draft an inventory of study fields and of the various applications of managing knowledge, thus to contribute to a better understanding of its benefits. This paper sums up the preliminary results of this two-part analysis : twelve fields have been identified as bearing an interest in knowledge management; they will be compared to the results obtained in the second part of the analysis (in progress), in order to work out a portrait of knowledge management and its related study areas

iPSC-Derived Vascular Cell Spheroids as Building Blocks for Scaffold-Free Biofabrication

Recently a protocol is established to obtain large quantities of human induced pluripotent stem cells (iPSC)-derived endothelial progenitors, called endothelial colony forming cells (ECFC), and of candidate smooth-muscle forming cells (SMFC). Here, the suitability for assembling in spheroids, and in larger 3D cell constructs is tested. iPSC-derived ECFC and SMFC are labeled with tdTomato and eGFP, respectively. Spheroids are formed in ultra-low adhesive wells, and their dynamic proprieties are studied by time-lapse microscopy, or by confocal microscopy. Spheroids are also tested for fusion ability either in the wells, or assembled on the Regenova 3D bioprinter which laces them in stainless steel micro-needles (the “Kenzan” method). It is found that both ECFC and SMFC formed spheroids in about 24 h. Fluorescence monitoring indicated a continuous compaction of ECFC spheroids, but stabilization in those prepared from SMFC. In mixed spheroids, the cell distribution changed continuously, with ECFC relocating to the core, and showing pre-vascular organization. All spheroids have the ability of in-well fusion, but only those containing SMFC are robust enough to sustain assembling in tubular structures. In these constructs a layered distribution of alpha smooth muscle actin-positive cells and extracellular matrix deposition is found. In conclusion, iPSC-derived vascular cell spheroids represent a promising new cellular material for scaffold-free biofabrication

Spatial Persistence of Fluctuating Interfaces

We show that the probability, P_0(l), that the height of a fluctuating (d+1)-dimensional interface in its steady state stays above its initial value up to a distance l, along any linear cut in the d-dimensional space, decays as P_0(l) \sim l^(-\theta). Here \theta is a `spatial' persistence exponent, and takes different values, \theta_s or \theta_0, depending on how the point from which l is measured is specified. While \theta_s is related to fractional Brownian motion, and can be determined exactly, \theta_0 is non-trivial even for Gaussian interfaces.Comment: 5 pages, new material adde

Adeno-Associated Virus Overexpression of Angiotensin-Converting Enzyme-2 Reverses Diabetic Retinopathy in Type 1 Diabetes in Mice

Angiotensin-converting enzyme (ACE)-2 is the primary enzyme of the vasoprotective axis of the renin angiotensin system that regulates the classic renin angiotensin system axis. We aimed to determine whether local retinal overexpression of adenoassociated virus (AAV)-ACE2 prevents or reverses diabetic retinopathy. Green fluorescent protein (GFP)-chimeric mice were generated to distinguish resident (retinal) from infiltrating bone marrow-derived inflammatory cells and were made diabetic using streptozotocin injections. Retinal digestion using trypsin was performed and acellular capillaries enumerated. Capillary occlusion by GFP(+) cells was used to measure leukostasis. Overexpression of ACE2 prevented (prevention cohort: untreated diabetic, 11.3 ± 1.4; ACE2 diabetic, 6.4 ± 0.9 per mm(2)) and partially reversed (reversal cohort: untreated diabetic, 15.7 ± 1.9; ACE2 diabetic, 6.5 ± 1.2 per mm(2)) the diabetes-associated increase of acellular capillaries and the increase of infiltrating inflammatory cells into the retina (F4/80(+)) (prevention cohort: untreated diabetic, 24.2 ± 6.7; ACE2 diabetic, 2.5 ± 1.6 per mm(2); reversal cohort: untreated diabetic, 56.8 ± 5.2; ACE2 diabetic, 5.6 ± 2.3 per mm(2)). In both study cohorts, intracapillary bone marrow-derived cells, indicative of leukostasis, were only observed in diabetic animals receiving control AAV injections. These results indicate that diabetic retinopathy, and possibly other diabetic microvascular complications, can be prevented and reversed by locally restoring the balance between the classic and vasoprotective renin angiotensin system

The complex TIE between macrophages and angiogenesis

Macrophages are primarily known as phagocytic immune cells, but they also play a role in diverse processes, such as morphogenesis, homeostasis and regeneration. In this review, we discuss the influence of macrophages on angiogenesis, the process of new blood vessel formation from the pre-existing vasculature. Macrophages play crucial roles at each step of the angiogenic cascade, starting from new blood vessel sprouting to the remodelling of the vascular plexus and vessel maturation. Macrophages form promising targets for both pro- and anti-angiogenic treatments. However, to target macrophages, we will first need to understand the mechanisms that control the functional plasticity of macrophages during each of the steps of the angiogenic cascade. Here, we review recent insights in this topic. Special attention will be given to the TIE2-expressing macrophage (TEM), which is a subtype of highly angiogenic macrophages that is able to influence angiogenesis via the angiopoietin-TIE pathway

Identification of Cellular Host Factors That Associate With LINE-1 ORF1p and the Effect of the Zinc Finger Antiviral Protein Zap on LINE-1 Retrotransposition.

Long INterspersed Element-1 (LINE-1 or L1) is the only active autonomous retrotransposon in the human genome. The human genome contains over 500,000 L1 sequences, which account for approximately 17% of human DNA. L1 sequences mobilize throughout the human genome by a copy-and-paste mechanism known as retrotransposition. Most genomic L1 sequences are incapable of mobility (i.e., retrotransposition) because they are either 5'-truncated, internally rearranged, and/or mutated; however, it is estimated that each human cell contains at least 80-100 intact L1 sequences that are retrotransposition capable. L1 retrotransposition is inherently mutagenic and on occasion can disrupt gene expression leading to diseases such as hemophilia A and cancer. Due to the mutagenic potential of L1 retrotransposition, it thus stands to reason that the host cell has evolved mechanisms to protect the cell from unabated retrotransposition. In this thesis I identified cellular host factors that associate with the first L1 open reading frame protein, ORF1p. I demonstrate that the zinc finger antiviral protein ZAP associates with L1 ORF1p and inhibits human L1 and Alu retrotransposition as well as the retrotransposition of LINE elements from mice and zebrafish. Molecular genetic, biochemical, and fluorescence microscopy data suggest that ZAP interacts with L1 RNA and reduces the expression of full-length L1 RNA and the L1-encoded proteins, thereby providing mechanistic insight into how ZAP may restrict retrotransposition. In addition to ZAP, I show that the ORF1p-associated cellular host factors MOV10, hnRNPL, and PAR-4 also inhibit L1 retrotransposition. Mechanistic data suggest that ZAP, MOV10, hnRNPL, and PAR-4 restrict L1 retrotransposition by distinct mechanisms, suggesting that each of these cellular host factors may target different post-transcriptional steps in the L1 retrotransposition cycle. Importantly, ZAP and MOV10 were first characterized as antiviral proteins due to their ability to suppress retroviral activity. Notably, several other host cell antiviral factors such as APOBEC3 proteins, TREX1, SAMHD1 and RNase L have recently been demonstrated to inhibit L1 retrotransposition. Thus, these data suggest that ZAP, MOV10 and perhaps other ORF1p-associated cellular host factors initially may have evolved to combat L1 and other endogenous retrotransposons and subsequently were co-opted as viral restriction factors.PHDCellular and Molecular BiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/113417/1/jmoldova_1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/113417/2/jmoldova_2.pd

Phase transitions in biological membranes

Native membranes of biological cells display melting transitions of their lipids at a temperature of 10-20 degrees below body temperature. Such transitions can be observed in various bacterial cells, in nerves, in cancer cells, but also in lung surfactant. It seems as if the presence of transitions slightly below physiological temperature is a generic property of most cells. They are important because they influence many physical properties of the membranes. At the transition temperature, membranes display a larger permeability that is accompanied by ion-channel-like phenomena even in the complete absence of proteins. Membranes are softer, which implies that phenomena such as endocytosis and exocytosis are facilitated. Mechanical signal propagation phenomena related to nerve pulses are strongly enhanced. The position of transitions can be affected by changes in temperature, pressure, pH and salt concentration or by the presence of anesthetics. Thus, even at physiological temperature, these transitions are of relevance. There position and thereby the physical properties of the membrane can be controlled by changes in the intensive thermodynamic variables. Here, we review some of the experimental findings and the thermodynamics that describes the control of the membrane function.Comment: 23 pages, 15 figure