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排序方式: 共有1007条查询结果,搜索用时 31 毫秒
81.
Ramtohul YK Powell D Leclerc JP Leger S Oballa R Black C Isabel E Li CS Crane S Robichaud J Guay J Guiral S Zhang L Huang Z 《Bioorganic & medicinal chemistry letters》2011,21(19):5692-5696
Optimization of a lead thiazole amide MF-152 led to the identification of potent bicyclic heteroaryl SCD1 inhibitors with good mouse pharmacokinetic profiles. In a view to target the liver for efficacy and to avoid SCD1 inhibition in the skin and eyes where adverse effects were previously observed in rodents, representative systemically-distributed SCD1 inhibitors were converted into liver-targeting SCD1 inhibitors. 相似文献
82.
Sicard A Semblat JP Doerig C Hamelin R Moniatte M Dorin-Semblat D Spicer JA Srivastava A Retzlaff S Heussler V Waters AP Doerig C 《Cellular microbiology》2011,13(6):836-845
Merozoites of malaria parasites invade red blood cells (RBCs), where they multiply by schizogony, undergoing development through ring, trophozoite and schizont stages that are responsible for malaria pathogenesis. Here, we report that a protein kinase-mediated signalling pathway involving host RBC PAK1 and MEK1, which do not have orthologues in the Plasmodium kinome, is selectively stimulated in Plasmodium falciparum-infected (versus uninfected) RBCs, as determined by the use of phospho-specific antibodies directed against the activated forms of these enzymes. Pharmacological interference with host MEK and PAK function using highly specific allosteric inhibitors in their known cellular IC50 ranges results in parasite death. Furthermore, MEK inhibitors have parasiticidal effects in vitro on hepatocyte and erythrocyte stages of the rodent malaria parasite Plasmodium berghei, indicating conservation of this subversive strategy in malaria parasites. These findings have profound implications for the development of novel strategies for antimalarial chemotherapy. 相似文献
83.
Yann Aubert Louis-Jérome Leba Cécilia Cheval Benoit Ranty Alain Vavasseur Didier Aldon Jean-Philippe Galaud 《Plant signaling & behavior》2011,6(4):538-540
The RD20 gene encodes a member of the caleosin family, which is primarily known to function in the mobilization of seed storage lipids during germination. In contrast to other caleosins, RD20 expression is early-induced by water deficit conditions and we recently provided genetic evidence for its positive role in drought tolerance in Arabidopsis. RD20 is also responsive to pathogen infection and is constitutively expressed in diverse tissues and organs during development suggesting additional roles for this caleosin. This addendum describes further exploration of phenotypic alterations in T-DNA insertional rd20 mutant and knock-out complemented transgenic plants in the context of early development and susceptibility to a phytopathogenic bacteria. We show that the RD20 gene is involved in ABA-mediated inhibition of germination and does not play a significant role in plant defense against Pseudomonas syringae.Key words: ABA, Arabidopsis thaliana, biotic stress, caleosin, germination, RD20 相似文献
84.
85.
Mateescu B Batista L Cardon M Gruosso T de Feraudy Y Mariani O Nicolas A Meyniel JP Cottu P Sastre-Garau X Mechta-Grigoriou F 《Nature medicine》2011,17(12):1627-1635
Although there is evidence that redox regulation has an essential role in malignancies, its impact on tumor prognosis remains unclear. Here we show crosstalk between oxidative stress and the miR-200 family of microRNAs that affects tumorigenesis and chemosensitivity. miR-141 and miR-200a target p38α and modulate the oxidative stress response. Enhanced expression of these microRNAs mimics p38α deficiency and increases tumor growth in mouse models, but it also improves the response to chemotherapeutic agents. High-grade human ovarian adenocarcinomas that accumulate miR-200a have low concentrations of p38α and an associated oxidative stress signature. The miR200a-dependent stress signature correlates with improved survival of patients in response to treatment. Therefore, the role of miR-200a in stress could be a predictive marker for clinical outcome in ovarian cancer. In addition, although oxidative stress promotes tumor growth, it also sensitizes tumors to treatment, which could account for the limited success of antioxidants in clinical trials. 相似文献
86.
Bayer M Hellio C Maréchal JP Frank W Lin W Weber H Proksch P 《Marine biotechnology (New York, N.Y.)》2011,13(6):1148-1158
Synthetically prepared congeners of sponge-derived bastadin derivatives such as 5,5′-dibromohemibastadin-1 (DBHB) that suppress
the settling of barnacle larvae were identified in this study as strong inhibitors of blue mussel phenoloxidase that is involved
in the firm attachment of mussels to a given substrate. The IC50 value of DBHB as the most active enzyme inhibitor encountered in this study amounts to 0.84 μM. Inhibition of phenoloxidase
by DBHB is likely due to complexation of copper(II) ions from the catalytic centre of the enzyme by the α-oxo-oxime moiety
of the compound as shown here for the first time by structure activity studies and by X-ray structure determination of a copper(II)
complex of DBHB. 相似文献
87.
88.
Jean-Philippe Puyravaud Céline Dufour Subramanian Aravajy 《Journal of Biogeography》2003,30(7):1067-1080
Aim The objective of this study was to document succession from grassland thickets to rain forest, and to provide evidence for their potential as restoration tools. Location The Linganamakki region (State of Karnataka) of the Central Western Ghats of India. Method We selected thirty vegetation thickets ranging from 4 to 439 m2 in area in the vicinity of rain forest. The area of each small thicket was estimated as an oval using its maximum length and its maximum width. When the shape was irregular (mostly in large thickets) the limits of the thicket were mapped and the area calculated from the map. Plant species were identified, the number of individuals was estimated and their heights measured. Results There was a progression in the thickets from early to late successional species. Small thickets were characterized by ecotone species and savanna trees such as Catunaregam dumetorum. Savanna trees served as a nucleus for thicket formation. Colonizing species were mostly bird‐dispersed. As succession proceeded in larger thickets, the proportion of evergreen, late‐successional rain forest trees increased. The species composition of the large thickets differed depending on the species composition of reproductive adults in the nearby forested areas. The species within small thickets were also found in the large thickets. The nestedness in species composition suggested that species turnover was deterministic based on thicket size. Human disturbance (leaf and wood collection by the local populations) affected the species composition and the species–area relationship of thickets. Main conclusions Vegetation thickets are nodal centres for rain forest colonization within grasslands. They expand and replace savanna. Early successional bird‐dispersed species established around savanna trees followed by late‐successional rain forest trees dispersed from the nearby forest by birds. Restoration programmes that reproduce natural successional processes such as those observed in thickets will be more successful and less expensive than the methods currently being employed, where trees are individually planted in grassland. Wood harvesting is the only factor that prevents thicket growth and coalescence and hampers forest expansion. 相似文献
89.
Dubois D Pihet M Clec'h CL Croué A Beguin H Bouchara JP Chabasse D 《Mycopathologia》2005,160(2):117-123
Here we report a case of cutaneous alternariosis in a 74-year-old man treated by corticotherapy for myasthenia, and presenting
with papular, crusted lesions on the left elbow and the right knee. Histological examination of the biopsy specimens showed
fungal hyphae associated with round-shaped cells which were highly suggestive of alternariosis. Mycological culture allowed
the isolation of a dematiaceous fungus which was identified as a member of the Alternaria infectoria species-group. This was
confirmed by PCR amplification and sequencing of the internal transcribed spacer domain of the gene encoding nuclear ribosomal
DNA and of the mitochondrial small subunit ribosomal DNA domain. The fungus was therefore referred to the Scientific Institute
of Public Health where it was identified as Alternaria infectoria, on the basis of its very small 1 or 2-celled conidia often
arranged in long chains and presenting with very long secondary conidiophores. Corticotherapy was stopped and a local antifungal
treatment with ketoconazole was initiated, allowing the stabilisation of the cutaneous lesions within 2 months. 相似文献
90.
BQ-788 [N-cis-2,6-dimethylpiperidine-1-carbonyl-L-gamma-methylleucyl-D-1-methoxycarbonyltryptophanyl-D-norleucine sodium salt] is a very potent and selective ETB receptor antagonist. The formation of the highly hindered trisubstituted urea functionality in the peptide chain and the carbamination on the indole nitrogen of the tryptophan side chain are major challenges in the synthesis of this particular antagonist. Furthermore, the high cost of the unnatural amino acids in the sequence of BQ-788 and its reported synthesis render this pseudopeptide very expensive to produce. In order to improve the yield and to reduce the number of steps compared to previous reported syntheses, we developed an efficient strategy involving a novel one-pot procedure for the synthesis of a highly hindered trisubstituted urea. Under very mild conditions, the urea was obtained by using triphosgene and sodium iodide. This strategy allowed us to synthesize BQ-788 in seven steps with an overall yield of 53%. We also generalized the use of this powerful methodology by creating some new structural analogues of the cis-2,6-dimethylpiperidine moiety by replacing it with other bulky secondary amines. We evaluated the antagonist properties of those three new analogues of BQ-788 in two bioassays in vitro. These new antagonists were less potent than BQ-788 in an ETB rich preparation and inactive in an ETA rich preparation. 相似文献