Gene induction during differentiation of human monocytes into dendritic cells: an integrated study at the RNA and protein levels

Changes in gene expression occurring during differentiation of human monocytes into dendritic cells were studied at the RNA and protein levels. These studies showed the induction of several gene classes corresponding to various biological functions. These functions encompass antigen processing and presentation, cytoskeleton, cell signalling and signal transduction, but also an increase in mitochondrial function and in the protein synthesis machinery, including some, but not all, chaperones. These changes put in perspective the events occurring during this differentiation process. On a more technical point, it appears that the studies carried out at the RNA and protein levels are highly complementary.Comment: website publisher: http://www.springerlink.com/content/ha0d2c351qhjhjdm

Research in the general area of non-linear dynamical systems Final report, 8 Jun. 1965 - 8 Jun. 1967

Nonlinear dynamical systems research on systems stability, invariance principles, Liapunov functions, and Volterra and functional integral equation

Niveau d'infestation des arbres fruitiers des groupements végétaux par Phragmanthera capitata (Sprengel) S. Balle (Loranthaceae) dans la région littorale du Cameroun

Au Cameroun, Phragmanthera capitata parasite de nombreuses essences ligneuses sauvages et cultivées, et est responsable de la réduction de leur rendement. L’optique de cette étude est de justifier le comportement de cette Loranthaceae ubiquiste dans les groupements végétaux homogènes et hétérogènes des sites retenus du littoral camerounais. Les groupements végétaux homogènes sont des plantations agricolesconstituées de Hevea brasiliensis et appartenant à la société Hévéa du Cameroun (Hévécam) située à Nyétté. Les groupements végétaux hétérogènes appartiennent à quatre sites de la région de Douala : un verger à Makondo et une plantation agricole paysanne à Cola acuminata à Penja, deux jardins de cases (Logbessou et axe routier aéroport-Bonanjo). Sur chaque arbre hôte ont été notés: le diamètre du tronc à 1,30 m du sol, les différentes espèces de Loranthaceae reconnues et le nombre de touffes comptées. Dans les groupements végétaux hétérogènes, 16 espèces hôtes réparties dans 12 genres et 10 familles sont parasitées par P. capitata. Cette dernière est la plus fréquente et la plus abondante de toutes les Loranthaceae et sa dissémination est facilitée par des facteurs d’origine anthropique. Il est indispensable et urgent de mettre en place un programme de recherche de lutte ciblée pour les plantes fruitières et ornementales

Coordinate regulation of DNA methyltransferase expression during oogenesis

<p>Abstract</p> <p>Background</p> <p>Normal mammalian development requires the action of DNA methyltransferases (DNMTs) for the establishment and maintenance of DNA methylation within repeat elements and imprinted genes. Here we report the expression dynamics of <it>Dnmt3a </it>and <it>Dnmt3b</it>, as well as a regulator of DNA methylation, <it>Dnmt3L</it>, in isolated female germ cells.</p> <p>Results</p> <p>Our results indicate that these enzymes are coordinately regulated and that their expression peaks during the stage of postnatal oocyte development when maternal methylation imprints are established. We find that Dnmt3a, Dnmt3b, Dnmt3L and Dnmt1o transcript accumulation is related to oocyte diameter. Furthermore, DNMT3L deficient 15 dpp oocytes have aberrantly methylated <it>Snrpn</it>, <it>Peg3 </it>and <it>Igf2r </it>DMRs, but normal IAP and LINE-1 methylation levels, thereby highlighting a male germ cell specific role for DNMT3L in the establishment of DNA methylation at repeat elements. Finally, real-time RT-PCR analysis indicates that the depletion of either DNMT3L or DNMT1o in growing oocytes results in the increased expression of the <it>de novo </it>methyltransferase <it>Dnmt3b</it>, suggesting a potential compensation mechanism by this enzyme for the loss of one of the other DNA methyltransferases.</p> <p>Conclusion</p> <p>Together these results provide a better understanding of the developmental regulation of <it>Dnmt3a</it>, <it>Dnmt3b </it>and <it>Dnmt3L </it>at the time of <it>de novo </it>methylation during oogenesis and demonstrate that the involvement of DNMT3L in retrotransposon silencing is restricted to the male germ line. This in turn suggests the existence of other factors in the oocyte that direct DNA methylation to transposons.</p

Collapse in the nonlocal nonlinear Schr\"odinger equation

We discuss spatial dynamics and collapse scenarios of localized waves governed by the nonlinear Schr\"{o}dinger equation with nonlocal nonlinearity. Firstly, we prove that for arbitrary nonsingular attractive nonlocal nonlinear interaction in arbitrary dimension collapse does not occur. Then we study in detail the effect of singular nonlocal kernels in arbitrary dimension using both, Lyapunoff's method and virial identities. We find that for for a one-dimensional case, i.e. for $n=1$, collapse cannot happen for nonlocal nonlinearity. On the other hand, for spatial dimension $n\geq2$ and singular kernel $\sim 1/r^\alpha$, no collapse takes place if $\alpha<2$, whereas collapse is possible if $\alpha\ge2$. Self-similar solutions allow us to find an expression for the critical distance (or time) at which collapse should occur in the particular case of $\sim 1/r^2$ kernels. Moreover, different evolution scenarios for the three dimensional physically relevant case of Bose Einstein condensate are studied numerically for both, the ground state and a higher order toroidal state with and without an additional local repulsive nonlinear interaction. In particular, we show that presence of an additional local repulsive term can prevent collapse in those cases

The effect of memory on relaxation in a scalar field theory

We derive a kinetic equation with a non-Markovian collision term which includes a memory effect, from Kadanoff-Baym equations in $\phi^4$ theory within the three-loop level for the two-particle irreducible (2PI) effective action. The memory effect is incorporated into the kinetic equation by a generalized Kadanoff-Baym ansatz.Based on the kinetic equations with and without the memory effect, we investigate an influence of this effect on decay of a single particle excitation with zero momentum in 3+1 dimensions and the spatially homogeneous case. Numerical results show that, while the time evolution of the zero mode is completely unaffected by the memory effect due to a separation of scales in the weak coupling regime, this effect leads first to faster relaxation than the case without it and then to slower relaxation as the coupling constant increases.Comment: 12 pages, 6 eps figure

Loss of spermatogonia and wide-spread DNA methylation defects in newborn male mice deficient in DNMT3L

<p>Abstract</p> <p>Background</p> <p>Formation of haploid spermatozoa capable of fertilization requires proper programming of epigenetic information. Exactly how DNMT3L (DNA methyltransferase 3-Like), a postulated regulator of DNA methyltransferase activity, contributes to DNA methylation pattern acquisition during gametogenesis remains unclear. Here we report on the role of DNMT3L in male germ cell development.</p> <p>Results</p> <p>A developmental study covering the first 12 days following birth was conducted on a <it>Dnmt3L </it>mutant mouse model; lower germ cell numbers and delayed entry into meiosis were observed in <it>Dnmt3L</it>^-/-males, pointing to a mitotic defect. A temporal expression study showed that expression of <it>Dnmt3L </it>is highest in prenatal gonocytes but is also detected and developmentally regulated during spermatogenesis. Using a restriction enzyme qPCR assay (qAMP), DNA methylation analyses were conducted on postnatal primitive type A spermatogonia lacking DNMT3L. Methylation levels along 61 sites across chromosomes 4 and X decreased significantly by approximately 50% compared to the levels observed in <it>Dnmt3L</it>^+/+germ cells, suggesting that many loci throughout the genome are marked for methylation by DNMT3L. More so, hypomethylation was more pronounced in regions of lower GC content than in regions of higher GC content.</p> <p>Conclusion</p> <p>Taken together, these data suggest that DNMT3L plays a more global role in genomic methylation patterning than previously believed.</p

Phenotypic Studies of Natural Killer Cell Subsets in Human Transporter Associated with Antigen Processing Deficiency

Peripheral blood natural killer (NK) cells from patients with transporter associated with antigen processing (TAP) deficiency are hyporesponsive. The mechanism of this defect is unknown, but the phenotype of TAP-deficient NK cells is almost normal. However, we noticed a high percentage of CD56bright cells among total NK cells from two patients. We further investigated TAP-deficient NK cells in these patients and compared them to NK cells from two other TAP-deficient patients with no clinical symptoms and to individuals with chronic inflammatory diseases other than TAP deficiency (chronic lung diseases or vasculitis). Peripheral blood mononuclear cells isolated from venous blood were stained with fluorochrome-conjugated antibodies and the phenotype of NK cells was analyzed by flow cytometry. In addition, 51Chromium release assays were performed to assess the cytotoxic activity of NK cells. In the symptomatic patients, CD56bright NK cells represented 28% and 45%, respectively, of all NK cells (higher than in healthy donors). The patients also displayed a higher percentage of CD56dimCD16− NK cells than controls. Interestingly, this unusual NK cell subtype distribution was not found in the two asymptomatic TAP-deficient cases, but was instead present in several of the other patients. Over-expression of the inhibitory receptor CD94/NKG2A by TAP-deficient NK cells was confirmed and extended to the inhibitory receptor ILT2 (CD85j). These inhibitory receptors were not involved in regulating the cytotoxicity of TAP-deficient NK cells. We conclude that expansion of the CD56bright NK cell subtype in peripheral blood is not a hallmark of TAP deficiency, but can be found in other diseases as well. This might reflect a reaction of the immune system to pathologic conditions. It could be interesting to investigate the relative distribution of NK cell subsets in various respiratory and autoimmune diseases

Platelet FcγRIIA-induced serotonin release exacerbates the severity of Transfusion-Related Acute Lung Injury in mice

Transfusion-related acute lung injury (TRALI) remains a major cause of transfusion-related fatalities. The mechanism of human antibody-mediated TRALI, especially the involvement of the Fcγ receptors, is not clearly established. Contrary to mice, human platelets are unique in their expression of the FcγRIIA/CD32A receptor, suggesting that our understanding of the pathogenesis of antibody-mediated TRALI is partial, as the current murine models incompletely recapitulate the human immunology. We evaluated the role of FcγRIIA/CD32A in TRALI using a humanized mouse model expressing the FcγRIIA/CD32A receptor. When challenged with a recombinant chimeric human immunoglobulin G1/mouse anti–major histocompatibility complex class I monoclonal antibody, these mice exhibited exacerbated alveolar edema and higher mortality compared with wild-type (WT) mice. Unlike in WT mice, monocytes/macrophages in CD32A(+) mice were accessory for TRALI initiation, indicating the decisive contribution of another cell type. Platelet activation was dramatically increased in CD32A(+) animals, resulting in their increased consumption and massive release of their granule contents. Platelet depletion prevented the exacerbation of TRALI in CD32A(+) mice but did not affect TRALI in WT animals. By blocking platelet serotonin uptake with fluoxetine, we showed that the severity of TRALI in CD32A(+) mice resulted from the serotonin released by the activated platelets. Furthermore, inhibition of 5-hydroxytryptamine 2A serotonin receptor with sarpogrelate, before or after the induction of TRALI, abolished the aggravation of lung edema in CD32A(+) mice. Our findings show that platelet FcγRIIA/CD32A activation exacerbates antibody-mediated TRALI and provide a rationale for designing prophylactic and therapeutic strategies targeting the serotonin pathway to attenuate TRALI in patients