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311.
dos Santos DM Canduri F Pereira JH Vinicius Bertacine Dias M Silva RG Mendes MA Palma MS Basso LA de Azevedo WF Santos DS 《Biochemical and biophysical research communications》2003,308(3):553-559
In human, purine nucleoside phosphorylase (HsPNP) is responsible for degradation of deoxyguanosine and genetic deficiency of this enzyme leads to profound T-cell mediated immunosuppression. PNP is therefore a target for inhibitor development aiming at T-cell immune response modulation and has been submitted to extensive structure-based drug design. This work reports the first crystallographic study of human PNP complexed with acyclovir (HsPNP:Acy). Acyclovir is a potent clinically useful inhibitor of replicant herpes simplex virus that also inhibits human PNP but with a relatively lower inhibitory activity (K(i)=90 microM). Analysis of the structural differences among the HsPNP:Acy complex, PNP apoenzyme, and HsPNP:Immucillin-H provides explanation for inhibitor binding, refines the purine-binding site, and can be used for future inhibitor design. 相似文献
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313.
Filgueira de Azevedo W Canduri F Marangoni dos Santos D Pereira JH Dias MV Silva RG Mendes MA Basso LA Palma MS Santos DS 《Biochemical and biophysical research communications》2003,309(4):917-922
Purine nucleoside phosphorylase (PNP) catalyzes the phosphorolysis of the N-ribosidic bonds of purine nucleosides and deoxynucleosides. PNP is a target for inhibitor development aiming at T-cell immune response modulation. This work reports on the crystallographic study of the complex of human PNP-immucillin-H (HsPNP-ImmH) solved at 2.6A resolution using synchrotron radiation. Immucillin-H (ImmH) inhibits the growth of malignant T-cell lines in the presence of deoxyguanosine without affecting non-T-cell tumor lines. ImmH inhibits activated normal human T cells after antigenic stimulation in vitro. These biological effects of ImmH suggest that this agent may have utility in the treatment of certain human diseases characterized by abnormal T-cell growth or activation. This is the first structural report of human PNP complexed with immucillin-H. The comparison of the complex HsPNP-ImmH with recent crystallographic structures of human PNP explains the high specificity of immucillin-H for human PNP. 相似文献
314.
Recent studies have indicated that the insulin-signaling pathway controls body and organ size in Drosophila, and most metazoans, by signaling nutritional conditions to the growing organs. The temporal requirements for insulin signaling during development are, however, unknown. Using a temperature-sensitive insulin receptor (Inr) mutation in Drosophila, we show that the developmental requirements for Inr activity are organ specific and vary in time. Early in development, before larvae reach the “critical size” (the size at which they commit to metamorphosis and can complete development without further feeding), Inr activity influences total development time but not final body and organ size. After critical size, Inr activity no longer affects total development time but does influence final body and organ size. Final body size is affected by Inr activity from critical size until pupariation, whereas final organ size is sensitive to Inr activity from critical size until early pupal development. In addition, different organs show different sensitivities to changes in Inr activity for different periods of development, implicating the insulin pathway in the control of organ allometry. The reduction in Inr activity is accompanied by a two-fold increase in free-sugar levels, similar to the effect of reduced insulin signaling in mammals. Finally, we find that varying the magnitude of Inr activity has different effects on cell size and cell number in the fly wing, providing a potential linkage between the mode of action of insulin signaling and the distinct downstream controls of cell size and number. We present a model that incorporates the effects of the insulin-signaling pathway into the Drosophila life cycle. We hypothesize that the insulin-signaling pathway controls such diverse effects as total developmental time, total body size and organ size through its effects on the rate of cell growth, and proliferation in different organs. 相似文献
315.
Lopes T Silva A Thiago R Carneiro A Dorella FA Rocha FS dos Santos AR Lima AR Guimarães LC Barbosa EG Ribeiro D Fiaux KK Diniz CA de Abreu VA de Almeida SS Hassan SS Ali A Bakhtiar SM Aburjaile FF Pinto AC Soares Sde C Pereira Ude P Schneider MP Miyoshi A Edman J Spier S Azevedo V 《Journal of bacteriology》2012,194(13):3567-3568
In this work we report the genome of Corynebacterium pseudotuberculosis strain 267, isolated from a llama. This pathogen is of great veterinary and economic importance, as it is the cause of caseous lymphadenitis in several livestock species around the world and causes significant losses due to the high cost of treatment. 相似文献
316.
FE Pethick AF Lainson R Yaga A Flockhart DG Smith W Donachie LT Cerdeira A Silva E Bol TS Lopes MS Barbosa AC Pinto AR Dos Santos SC Soares SS Almeida LC Guimaraes FF Aburjaile VA Abreu D Ribeiro KK Fiaux CA Diniz EG Barbosa UP Pereira SS Hassan A Ali SM Bakhtiar FA Dorella AR Carneiro RT Ramos FS Rocha MP Schneider A Miyoshi V Azevedo MC Fontaine 《Journal of bacteriology》2012,194(16):4476
Corynebacterium pseudotuberculosis causes disease in several animal species, although distinct biovars exist that appear to be restricted to specific hosts. In order to facilitate a better understanding of the differences between biovars, we report here the complete genome sequence of the equine pathogen Corynebacterium pseudotuberculosis strain 1/06-A. 相似文献
317.
Begossi A Salyvonchyk S Nora V Lopes PF Silvano RA 《Journal of ethnobiology and ethnomedicine》2012,8(1):22-19
ABSTRACT: This study intends to give recommendations to the management of Paraty fishery in Brazil through an interplay of local and scientific knowledge. In particular, the objectives are the following: 1) to describe the Paraty fishery; 2) to compare the fishermen's local ecological knowledge with recorded fish landings and previous studies in Paraty; 3) to combine the data on local fishing and on local/Caicara livelihoods with the SES (social-ecological systems) Model. The methods include a systematic survey of fishing in Tarituba and Praia Grande, which are located in the northern end and the central part of the Paraty municipality, respectively. For four days each month, systematic data on catches at landing points were collected, as well as macroscopic gonad analysis data for the fishes Centropomus parallelus and C. undecimalis (snook, robalo), Epinephelus marginatus (grouper, garoupa), Scomberomorus cavalla (King mackerel, cavala), and Lutjanus synagris (Lane snapper, vermelho). Spring and summer are important seasons during which some species reproduce, and the integration of fishing periods for some target species could assist in fishing management through the use of closed seasons. Fishermen could obtain complementary earnings from tourism and from the "defeso system" (closed season including a salary payment) to conserve fishing stocks. The SES model facilitates an understanding of the historical context of fishing, its economic importance for local livelihoods, the constraints from conservation measures that affect fishermen, and the management processes that already exist, such as the defeso. If used to integrate fishing with complementary activities (tourism), such a system could improve the responsibility of fishermen regarding the conservation of fish stocks. 相似文献
318.
Fill TP da Silva JV de Oliveira KT da Silva BF Rodrigues-Fo E 《Journal of microbiology and biotechnology》2012,22(6):832-837
The oxidative potential of the fungus Penicillium brasilianum, a strain isolated as an endophyte from a Meliaceae plant (Melia azedarach), was investigated using 1-indanone as a substrate to track the production of monooxygenases. The fungus produced the dihydrocoumarin from 1-indanone with the classical Baeyer-Villiger reaction regiochemistry, and (-)-(R)-3-hydroxy-1-indanone with 78% ee. Minor compounds resulting from lipase and SAM activities were also detected. The biotransformation procedures were also applied to a collection of Penicillium and Aspergillus fungi obtained from M. azedarach and Murraya paniculata. The results showed that Baeyer-Villiger were mostly active in fungi isolated from M. azedarach. Almost all of the fungi tested produced 3-hydroxy-1-indanone.. 相似文献
319.
Fabricia Petronilho Francieli Vuolo Letícia Selinger Galant Larissa Constantino Cristiane Damiani Tomasi Vinicius Renne Giombelli Cláudio Teodoro de Souza Sabrina da Silva Denise Frediani Barbeiro Francisco Garcia Soriano Emílio Luiz Streck Cristiane Ritter Alfeu Zanotto-Filho Matheus Augusto Pasquali Daniel Pens Gelain José Luiz Rybarczyk-Filho José Cláudio Fonseca Moreira Norman L Block Rafael Roesler Gilberto Schwartsmann Andrew V Schally Felipe Dal-Pizzol 《Molecular medicine (Cambridge, Mass.)》2012,18(1):1209-1219
In sepsis, toll-like receptor (TLR)-4 modulates the migration of neutrophils to infectious foci, favoring bacteremia and mortality. In experimental sepsis, organ dysfunction and cytokines released by activated macrophages can be reduced by gastrin-releasing peptide (GRP) receptor (GRPR) antagonist RC-3095. Here we report a link between GRPR and TLR-4 in experimental models and in sepsis patients. RAW 264.7 culture cells were exposed to lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-α and RC-3095 (10 ng/mL). Male Wistar rats were subjected to cecal ligation and puncture (CLP), and RC-3095 was administered (3 mg/kg, subcutaneously); after 6 h, we removed the blood, bronchoalveolar lavage, peritoneal lavage and lung. Human patients with a clinical diagnosis of sepsis received a continuous infusion with RC-3095 (3 mg/kg, intravenous) over a period of 12 h, and plasma was collected before and after RC-3095 administration and, in a different set of patients with systemic inflammatory response syndrome (SIRS) or sepsis, GRP plasma levels were determined. RC-3095 inhibited TLR-4, extracellular-signal–related kinase (ERK)-1/2, Jun NH2-terminal kinase (JNK) and Akt and decreased activation of activator protein 1 (AP-1), nuclear factor (NF)-κB and interleukin (IL)-6 in macrophages stimulated by LPS. It also decreased IL-6 release from macrophages stimulated by TNF-α. RC-3095 treatment in CLP rats decreased lung TLR-4, reduced the migration of cells to the lung and reduced systemic cytokines and bacterial dissemination. Patients with sepsis and systemic inflammatory response syndrome have elevated plasma levels of GRP, which associates with clinical outcome in the sepsis patients. These findings highlight the role of GRPR signaling in sepsis outcome and the beneficial action of GRPR antagonists in controlling the inflammatory response in sepsis through a mechanism involving at least inhibition of TLR-4 signaling. 相似文献
320.
Adriano Caliman Luciana S. Carneiro Jo?o J. F. Leal Vinicius F. Farjalla Reinaldo L. Bozelli Francisco A. Esteves 《PloS one》2012,7(9)
Tests of the biodiversity and ecosystem functioning (BEF) relationship have focused little attention on the importance of interactions between species diversity and other attributes of ecological communities such as community biomass. Moreover, BEF research has been mainly derived from studies measuring a single ecosystem process that often represents resource consumption within a given habitat. Focus on single processes has prevented us from exploring the characteristics of ecosystem processes that can be critical in helping us to identify how novel pathways throughout BEF mechanisms may operate. Here, we investigated whether and how the effects of biodiversity mediated by non-trophic interactions among benthic bioturbator species vary according to community biomass and ecosystem processes. We hypothesized that (1) bioturbator biomass and species richness interact to affect the rates of benthic nutrient regeneration [dissolved inorganic nitrogen (DIN) and total dissolved phosphorus (TDP)] and consequently bacterioplankton production (BP) and that (2) the complementarity effects of diversity will be stronger on BP than on nutrient regeneration because the former represents a more integrative process that can be mediated by multivariate nutrient complementarity. We show that the effects of bioturbator diversity on nutrient regeneration increased BP via multivariate nutrient complementarity. Consistent with our prediction, the complementarity effects were significantly stronger on BP than on DIN and TDP. The effects of the biomass-species richness interaction on complementarity varied among the individual processes, but the aggregated measures of complementarity over all ecosystem processes were significantly higher at the highest community biomass level. Our results suggest that the complementarity effects of biodiversity can be stronger on more integrative ecosystem processes, which integrate subsidiary “simpler” processes, via multivariate complementarity. In addition, reductions in community biomass may decrease the strength of interspecific interactions so that the enhanced effects of biodiversity on ecosystem processes can disappear well before species become extinct. 相似文献