Home About us Contact | |||
Early Production (early + production)
Selected AbstractsEarly production of thymic stromal lymphopoietin precedes infiltration of dendritic cells expressing its receptor in allergen-induced late phase cutaneous responses in atopic subjectsALLERGY, Issue 7 2009C. J. Corrigan Background:, Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine that triggers dendritic cell-mediated T helper (Th)2 inflammatory responses through a receptor consisting of a heterodimer of the IL-7 receptor alpha (IL-7R,) chain and the TSLP receptor (TSLPR), which resembles the cytokine receptor common gamma chain. Dendritic cells activated by TSLP prime development of CD4+ T cells into Th2 cells contributing to the pathogenesis of allergic inflammation. We hypothesized that allergen exposure induces expression of TSLP and results in recruitment of TSLPR bearing cells in the cutaneous allergen-induced late-phase reaction (LPR) in atopic subjects. Methods:, Skin biopsies were obtained from atopic subjects (n = 9) at various times after cutaneous allergen challenge. In situ hybridization and immunohistochemistry were used to determine TSLP mRNA expression and to measure infiltration of TSLPR+ DC in skin LPR. RT-PCR and flow cytometry were employed to analyse TSLPR expression on isolated blood DC. Results:, Allergen-induced skin TSLP expression occurred as early as 1 h after allergen challenge, whereas TSLPR+ and CD11c+ cells infiltrated relatively late (24,48 h). The majority of TSLPR+ cells were DC co-expressing blood DC antigen-1 (BDCA-1) or BDCA-2. Freshly isolated blood DC expressed both TSLPR and IL-7R, chains. Maturation and stimulation with TSLP or polyriboinosinic,polyribocytidylic acid in vitro upregulated the expression of both TSLPR and IL-7R, chains in DC but not in chemoattractant receptor-homologous molecule expressed on Th2 cells+ CD4+ T cells. Conclusion:, The data suggest that TSLP plays a role in augmenting, through DC recruitment and activation, the development of Th2-type T cells in allergic inflammation. [source] Diversity in commercial varieties and landraces of black eggplants and implications for broadening the breeders' gene poolANNALS OF APPLIED BIOLOGY, Issue 3 2009J.E. Muñoz-Falcón Abstract Black-coloured eggplants (Solanum melongena) represent the commercially most important group of eggplants in Europe and North America. Most of the modern varieties of black eggplants correspond to F1 hybrids, which at the same time constitute an elite gene pool for the development of new varieties. However, there are many black landraces and old varieties, which could be useful as sources of variation for black eggplant breeding programmes as well as for the broadening of the genetic diversity of the breeders' gene pool. We have studied the morphological and molecular [amplified fragment length polymorphism and simple sequence repeat (SSR)] diversity in a collection of 38 black eggplant accessions, including commercial (modern F1 hybrid and old nonhybrid) varieties and landraces as well as in six nonblack control eggplants, from different origins. The results show that black eggplants contain a considerable morphological and molecular diversity, but commercial varieties, and in particular F1 hybrids, display a reduced morphological and molecular diversity when compared with landraces. The principal components analysis morphological and principal coordinates analysis molecular analyses show that commercial F1 hybrids group together, indicating that they share a common and narrow gene pool. Commercial F1 hybrids present a series of productive advantages, like early production, intense black colour (low L*, a* and b*) values and absence of fruit calyx prickles. However, several of the landraces and old nonhybrid varieties studied present a high yield as well as other traits of interest for eggplant breeding. Furthermore, given the low genetic diversity of F1 hybrids and the moderate level of SSR heterozygosity found in these materials (0.382), introduction of black landraces and old varieties in the present breeding programmes could contribute to broadening the gene pool used by breeders and this could help increase the heterosis for yield of F1 hybrids, which is greatly favoured by high heterozygosity levels. [source] Arthritis develops but fails to resolve during inhibition of cyclooxygenase 2 in a murine model of lyme diseaseARTHRITIS & RHEUMATISM, Issue 5 2008Victoria A. Blaho Objective Recent studies have implicated products of cyclooxygenase 2 (COX-2) in not only induction but also resolution of the inflammatory response; however, the contribution of COX-2 products to the in vivo response to infection is unknown. The aim of this study was to determine the contribution of COX-2 to temporal regulation of the inflammatory response to infection in a murine model of Lyme arthritis. Methods Experimental Lyme disease was induced in both arthritis-resistant DBA/2J and arthritis-susceptible C3H/HeJ mice by inoculation in the hind footpads with Borrelia burgdorferi. COX-2 inhibitors were administered daily, and their effect on arthritis pathology was assessed at various time points postinfection. The COX-2 deficiency was also backcrossed onto both DBA and C3H backgrounds to confirm the findings from COX-2 inhibitor,treated mice. Results In COX-2 inhibitor,treated or COX-2,/, C3H mice, arthritis developed normally but did not resolve. Cessation of COX-2 inhibitor treatment on day 14 postinfection did not induce resolution of arthritis, indicating an early onset for the molecular mechanisms governing resolution. The lack of resolution of arthritis correlated with altered COX-2 and cytosolic phospholipase A2 messenger RNA levels in the joints of C3H mice. In addition, the proresolution lipid molecule 15-deoxy-,12,14 -prostaglandin J2 was produced in response to B burgdorferi infection, and its production was attenuated by the inhibition of COX-2. Conclusion Our results demonstrate that early production of COX-2 products is necessary for resolution of the inflammatory arthritis induced by Borrelia infection, and that COX-2 inhibition may result in prolonged inflammatory states, possibly by inhibition of proresolution eicosanoids. [source] Aldehyde,alcohol dehydrogenase and/or thiolase overexpression coupled with CoA transferase downregulation lead to higher alcohol titers and selectivity in Clostridium acetobutylicum fermentationsBIOTECHNOLOGY & BIOENGINEERING, Issue 1 2009Ryan Sillers Abstract Metabolic engineering (ME) of Clostridium acetobutylicum has led to increased solvent (butanol, acetone, and ethanol) production and solvent tolerance, thus demonstrating that further efforts have the potential to create strains of industrial importance. With recently developed ME tools, it is now possible to combine genetic modifications and thus implement more advanced ME strategies. We have previously shown that antisense RNA (asRNA)-based downregulation of CoA transferase (CoAT, the first enzyme in the acetone-formation pathway) results in increased butanol to acetone selectivity, but overall reduced butanol yields and titers. In this study the alcohol/aldehyde dehydrogenase (aad) gene (encoding the bifunctional protein AAD responsible for butanol and ethanol production from butyryl-CoA and acetyl-CoA, respectively) was expressed from the phosphotransbutyrylase (ptb) promoter to enhance butanol formation and selectivity, while CoAT downregulation was used to minimize acetone production. This led to early production of high alcohol (butanol plus ethanol) titers, overall solvent titers of 30 g/L, and a higher alcohol/acetone ratio. Metabolic flux analysis revealed the likely depletion of butyryl-CoA. In order to increase then the flux towards butyryl-CoA, we examined the impact of thiolase (THL, thl) overexpression. THL converts acetyl-CoA to acetoacetyl-CoA, the first step of the pathway from acetyl-CoA to butyryl-CoA, and thus, combining thl overexpression with aad overexpression decreased, as expected, acetate and ethanol production while increasing acetone and butyrate formation. thl overexpression in strains with asRNA CoAT downregulation did not significantly alter product formation thus suggesting that a more complex metabolic engineering strategy is necessary to enhance the intracellular butyryl-CoA pool and reduce the acetyl-CoA pool in order to achieve improved butanol titers and selectivity. Biotechnol. Bioeng. 2009;102: 38,49. © 2008 Wiley Periodicals, Inc. [source] Differential regulation of nitric oxide synthase isoforms in experimental acute Chagasic cardiomyopathyCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2000B. Chandrasekar We have previously demonstrated induction and high level expression of IL-1,, IL-6 and tumour necrosis factor-alpha in the myocardium during the acute stage of experimental Trypanosoma cruzi infection (Chagas' disease). The myocardial depressive effects of these cytokines are mediated in part by the induction of nitric oxide synthase (NOS), production of nitric oxide (NO) and formation of peroxynitrite. In this study we investigated the expression, activity and localization of NOS isoforms, and the levels of NO, malondialdehyde (a measure of oxidative stress), and peroxynitrite in rats at 1·5, 5, 10 and 15 days after infection with T. cruzi trypomastigotes. The myocardial inflammatory infiltrate and number of amastigote nests increased over the course of infection. A significant increase in tissue nitrate + nitrite levels, NOS2 mRNA, and NOS2 enzyme activity was observed at all time points in the infected compared with uninfected animals. The enzyme activity of constitutive NOS, tissue malondialdehyde levels, and NOS3 mRNA levels was only transiently increased after infection. The protein levels of the NOS isoforms paralleled their mRNA expression. While no positive nitrotyrosine immunoreactivity was detected in control myocardium, its levels increased in infected animals over time. Thus, by 1·5 days post-infection, when no parasite or immune cell infiltration could be detected, the myocardium expressed high levels of NOS and NO metabolites. Nevertheless, the early production of NO in the myocardium was not sufficient to clear the parasites. [source] |