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Colchicine is a known tubulin binding agent enabling necrosis in tumors. A novel tubulin-directed DO3A-colchicine conjugate and its Gd(III) complex were prepared from N-deacetylcolchicine, coupling alkaloid and polyaza-alicyclic functions via a peptide coupling methodology. The longitudinal proton relaxivity of the Gd(III) complex in water at 4.7 T is 2.86 mM−1 s−1 and a similar efficacy as colchicine towards ovarian carcinoma cells in vitro. 相似文献
165.
Teng RJ Du J Xu H Bakhutashvili I Eis A Shi Y Pritchard KA Konduri GG 《American journal of physiology. Lung cellular and molecular physiology》2011,301(3):L334-L345
Persistent pulmonary hypertension of the newborn (PPHN) is associated with decreased blood vessel density that contributes to increased pulmonary vascular resistance. Previous studies showed that uncoupled endothelial nitric oxide (NO) synthase (eNOS) activity and increased NADPH oxidase activity resulted in marked decreases in NO bioavailability and impaired angiogenesis in PPHN. In the present study, we hypothesize that loss of tetrahydrobiopterin (BH4), a critical cofactor for eNOS, induces uncoupled eNOS activity and impairs angiogenesis in PPHN. Pulmonary artery endothelial cells (PAEC) isolated from fetal lambs with PPHN (HTFL-PAEC) or control lambs (NFL-PAEC) were used to investigate the cellular mechanisms impairing angiogenesis in PPHN. Cellular mechanisms were examined with respect to BH4 levels, GTP-cyclohydrolase-1 (GCH-1) expression, eNOS dimer formation, and eNOS-heat shock protein 90 (hsp90) interactions under basal conditions and after sepiapterin (Sep) supplementation. Cellular levels of BH4, GCH-1 expression, and eNOS dimer formation were decreased in HTFL-PAEC compared with NFL-PAEC. Sep supplementation decreased apoptosis and increased in vitro angiogenesis in HTFL-PAEC and ex vivo pulmonary artery sprouting angiogenesis. Sep also increased cellular BH4 content, NO production, eNOS dimer formation, and eNOS-hsp90 association and decreased the superoxide formation in HTFL-PAEC. These data demonstrate that Sep improves NO production and angiogenic potential of HTFL-PAEC by recoupling eNOS activity. Increasing BH4 levels via Sep supplementation may be an important therapy for improving eNOS function and restoring angiogenesis in PPHN. 相似文献
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Korotkov KV Johnson TL Jobling MG Pruneda J Pardon E Héroux A Turley S Steyaert J Holmes RK Sandkvist M Hol WG 《PLoS pathogens》2011,7(9):e1002228
Type II secretion systems (T2SSs) are critical for secretion of many proteins from Gram-negative bacteria. In the T2SS, the outer membrane secretin GspD forms a multimeric pore for translocation of secreted proteins. GspD and the inner membrane protein GspC interact with each other via periplasmic domains. Three different crystal structures of the homology region domain of GspC (GspC(HR)) in complex with either two or three domains of the N-terminal region of GspD from enterotoxigenic Escherichia coli show that GspC(HR) adopts an all-β topology. N-terminal β-strands of GspC and the N0 domain of GspD are major components of the interface between these inner and outer membrane proteins from the T2SS. The biological relevance of the observed GspC-GspD interface is shown by analysis of variant proteins in two-hybrid studies and by the effect of mutations in homologous genes on extracellular secretion and subcellular distribution of GspC in Vibrio cholerae. Substitutions of interface residues of GspD have a dramatic effect on the focal distribution of GspC in V. cholerae. These studies indicate that the GspC(HR)-GspD(N0) interactions observed in the crystal structure are essential for T2SS function. Possible implications of our structures for the stoichiometry of the T2SS and exoprotein secretion are discussed. 相似文献
169.
Fine Mapping QTL for Drought Resistance Traits in Rice (<Emphasis Type="Italic">Oryza sativa</Emphasis> L.) Using Bulk Segregant Analysis 总被引:1,自引:0,他引:1
Salunkhe AS Poornima R Prince KS Kanagaraj P Sheeba JA Amudha K Suji KK Senthil A Babu RC 《Molecular biotechnology》2011,49(1):90-95
Drought stress is a major limitation to rice (Oryza sativa L.) yields and its stability, especially in rainfed conditions. Developing rice cultivars with inherent capacity to withstand
drought stress would improve rainfed rice production. Mapping quantitative trait loci (QTLs) linked to drought resistance
traits will help to develop rice cultivars suitable for water-limited environments through molecular marker-assisted selection
(MAS) strategy. However, QTL mapping is usually carried out by genotyping large number of progenies, which is labour-intensive,
time-consuming and cost-ineffective. Bulk segregant analysis (BSA) serves as an affordable strategy for mapping large effect
QTLs by genotyping only the extreme phenotypes instead of the entire mapping population. We have previously mapped a QTL linked
to leaf rolling and leaf drying in recombinant inbred (RI) lines derived from two locally adapted indica rice ecotypes viz., IR20/Nootripathu using BSA. Fine mapping the QTL will facilitate its application in MAS. BSA was done
by bulking DNA of 10 drought-resistant and 12 drought-sensitive RI lines. Out of 343 rice microsatellites markers genotyped,
RM8085 co-segregated among the RI lines constituting the respective bulks. RM8085 was mapped in the middle of the QTL region
on chromosome 1 previously identified in these RI lines thus reducing the QTL interval from 7.9 to 3.8 cM. Further, the study
showed that the region, RM212–RM302–RM8085–RM3825 on chromosome 1, harbours large effect QTLs for drought-resistance traits
across several genetic backgrounds in rice. Thus, the QTL may be useful for drought resistance improvement in rice through
MAS and map-based cloning. 相似文献
170.
Abstract. Although the reproductive biology and early life‐history stages of deep‐sea corals are poorly understood, such data are crucial for their conservation and management. Here, we describe the timing of larval release, planula behavior, metamorphosis, settlement, and early juvenile growth of two species of deep‐sea soft corals from the northwest Atlantic. Live colonies of Gersemia fruticosa maintained under flow‐through laboratory conditions released 79 planulae (1.5–2.5 mm long) between April and early June 2007. Peak planulation in G. fruticosa coincided with peaks in the chlorophyll concentration and deposition rates of planktic matter. Metamorphosis and settlement occurred 3–70 d post‐release. The eight primary mesenteries typically appeared within 24 h, and primary polyps grew to a height of ~6–10 mm and a stalk diameter of ~1 mm within 2–3 months. Planulae of Duva florida (1.5–2.5 mm long) were extracted surgically from several colonies and were successfully reared in culture. Primary polyps reached a height of ~3–4 mm within 2–3 months. No budding of primary polyps was observed in either species over 11–13 months of monitoring, suggesting a very slow growth rate. 相似文献