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51.
Symbiodinium transcriptome and global responses of cells to immediate changes in light intensity when grown under autotrophic or mixotrophic conditions
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52.
The 3-aryl-2-cyanoacrylamide scaffold was designed as core pharmacophore for inhibitors of the Dengue and West Nile virus serine proteases (NS2B-NS3). A total of 86 analogs was prepared to study the structure–activity relationships in detail. Thereby, it turned out that the electron density of the aryl moiety and the central double bond have a crucial influence on the activity of the compounds, whereas the influence of substituents of the amide residue is less relevant. The para-hydroxy substituted analog was found to be the most potent inhibitor in this series with a Ki-value of 35.7 μM at the Dengue and 44.6 μM at the West Nile virus protease. The aprotinin competition assay demonstrates a direct interaction of the inhibitor molecule with active centre of the Dengue virus protease. The target selectivity was studied in a counterscreen with thrombin and found to be 2.8:1 in favor of DEN protease and 2.3:1 in favor of WNV protease, respectively. 相似文献
53.
目的:评价宫腔镜辅助下分段诊刮在子宫内膜癌检查中的临床价值,探讨提高子宫内膜癌诊断准确性的检查方法。方法:选择经分段诊刮诊断为子宫内膜癌患者132例,59例患者分为对照组,术前采取单纯分段诊刮的方式;73例患者分为观察组,术前采取宫腔镜辅助下分段诊刮的方式。根据术后患者病理检查结果,比较两组患者术前诊断的准确性及术中腹腔冲洗液细胞阳性率。结果:观察组检查方式的准确性优于对照组,差异具有统计学意5C(P〈0.05),两组术中腹腔冲洗液细胞阳性病例比较,差异无统计学意义(P〉0.05)。结论:宫腔镜辅助下分段诊刮的方式可提高子宫内膜癌检查的准确性,且不增加肿瘤细胞散播的风险。 相似文献
54.
Kim JY Cho SW Song WC Lee MJ Cai J Ohk SH Song HK Degan A Jung HS 《Differentiation; research in biological diversity》2005,73(5):240-248
Chick feather buds develop sequentially in a hexagonal array. Each feather bud develops with anterior posterior polarity, which is thought to develop in response to signals derived from specialized regions of mesenchymal condensation and epithelial thickening. These developmental processes are performed by cellular mechanisms, such as cell proliferation and migration, which occur during chick feather bud development. In order to understand the mechanisms regulating the formation of mesenchymal condensation and their role in feather bud development, we explanted chick dorsal skin at stage HH29+ with cytochalasin D, which inhibits cytoskeletal formation. We show that the aggregation of mesenchymal cells can be prevented by cytochalasin D treatment in a concentration-dependent manner. Subsequently, cytochalasin D disrupts the spacing pattern and inhibits feather bud axis formation as well. In addition, expression patterns of Bmp-4 and Msx-2, key molecules for early feather bud development, were disturbed by cytochalasin D treatment. Our results fully indicate that both the cytoskeletal structure and cell activity via gene regulation are of fundamental importance in mesenchymal condensation leading to proper morphogenesis of feather bud and spacing pattern formation. 相似文献
55.
Recently, we found that intracellular washout of cGMP induces gap junction uncoupling and proposed a link between gap junction
uncoupling and stimulation of apoptotic reactions in GFSHR-17 granulosa cells. In the present report we show that an inhibitor
of guanylyl cyclase, ODQ, reduces gap junction coupling and promotes apoptotic reactions such as chromatin condensation and
DNA strand breaks. To analyze whether gap junction uncoupling and induction of apoptotic reactions are related, the cells
were treated with heptanol and 18β-GA, two known gap junction uncouplers. Gap junction coupling of GFSHR-17 cells could be
restored if the incubation time with the gap junction uncouplers was less than 10 min. A prolonged incubation time irreversibly
suppressed gap junction coupling and caused chromatin condensation as well as DNA degradation. The promotion of apoptotic
reactions by heptanol or 18β-GA was not observed in cells with low gap junction coupling like HeLa cells, indicating that
the observed genotoxic reactions are not caused by unspecific effects of gap junction uncouplers. Additionally, it was observed
that heptanol or 18β-GA did not induce a sustained rise of [Ca2+]i. The effects of gap junction uncouplers could not be suppressed by the presence of 8-Br-cGMP. It is discussed that irreversible
gap junction uncoupling can be mediated by cGMP-dependent as well as cGMP-independent pathways and in turn could lead to stimulation
of apoptotic reactions in granulosa cells. 相似文献
56.
A novel strategy to prepare negatively charged and small DNA-containing liposomes after condensation of plasmid DNA by a cationic
lipid in deoxycholate micelle environment is described. The average diameter of resulting complexes was 62±8 nm. DNA-containing
liposomes were then prepared by dialysis. The shape of the resulting liposomes was spherical. The average diameter and the
surface charge of the liposomes were 86±6 nm and −24±3 mV, respectively. The plasmid DNA inside liposomes remained in a supercoiled
form after incubation with DNase. 相似文献
57.
58.
Verkhivker GM 《Proteins》2005,58(3):706-716
The relationship between folding mechanism coupled to binding and structure prediction of the tertiary complexes is studied for the p27(Kip) (1) protein which has an intrinsically disordered unbound form and undergoes a functional folding transition during complex formation with the phosphorylated cyclin A-cyclin-dependent kinase 2 (Cdk2) binary complex. Hierarchy of p27(Kip1) structural loss determined in our earlier studies from temperature-induced Monte Carlo simulations and subsequent characterization of the transition state ensemble (TSE) for the folding reaction have shown that simultaneous ordering of the p27(Kip1) native intermolecular interface for the beta-hairpin and beta-strand secondary structure elements is critical for nucleating a rapid kinetic transition to the native tertiary complex. In the present study, we investigate the effect of forming specific intermolecular interactions on structure prediction of the p27(Kip1) tertiary complex. By constraining different secondary structure elements of p27(Kip1) in their native bound conformations and conducting multiple simulated annealing simulations, we analyze differences in the success rate of predicting the native structure of p27(Kip1) in the tertiary complex. In accordance with the nucleation-condensation mechanism, we have found that further stabilization of the native intermolecular interface for the beta-hairpin and beta-strand elements of p27(Kip1), that become ordered in the TSE, but are hardly populated in the unbound state, results in a consistent acquisition of the native bound structure. Conversely, the excessive stablization of the local secondary structure elements, which are rarely detected in the TSE, has a detrimental effect on convergence to the native bound structure. 相似文献
59.
We characterized the air-water interfacial properties of four monofluorinated bile acids alone and in binary mixtures with a common lecithin, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), using an automated Langmuir-Pockels surface balance. We compared 7alpha-fluoromurocholic acid (FMCA), 7alpha-fluorohyodeoxycholic acid (FHDCA), 6alpha-fluoroursodeoxycholic acid (FUDCA), and 6alpha-fluorochenodeoxycholic acid (FCDCA) with their natural dihydroxy homologs, murocholic acid (MCA), hyodeoxycholic acid (HDCA), ursodeoxycholic acid (UDCA), and chenodeoxycholic acid (CDCA). For further comparison, two trihydroxy bile acids, 3alpha,6beta,7alpha-trihydroxycholanoic acid [alpha-muricholic acid (alpha-MCA)] and 3alpha,6alpha,7beta-trihydroxycholanoic acid [omega-muricholic acid (omega-MCA)], with isologous OH polar functions to FMCA and FUDCA were also studied. Pressure-area isotherms of MCA, HDCA, UDCA, CDCA, and FMCA displayed sharp collapse points. In contrast, FHDCA, FUDCA, and FCDCA formed monolayers that were less stable than the trihydroxy bile acids, displaying second-order phase transitions in their isotherms. All natural and fluorinated bile acids condensed mixed monolayers with POPC, with maximal effects at molar bile acid concentrations between 30 and 50 mol%. Examination of molecular models revealed that the 7alpha-F atom of the interfacially stable FMCA projects away from the 6beta-OH function, resulting in minimal steric interactions, whereas in FHDCA, FUDCA, and FCDCA, close vicinal interactions between OH and F polar functions result in progressive bulk solubility upon monolayer compression. These results provide a framework for designing F-modified bile acids to mimic or diverge from the natural compounds in vivo. 相似文献
60.
Accurate chromosome alignment at metaphase and subsequent segregation of condensed chromosomes is a complex process involving elaborate and only partially characterized molecular machinery. Although several spindle associated molecular motors have been shown to be essential for mitotic function, only a few chromosome arm--associated motors have been described. Here, we show that human chromokinesin human HKIF4A (HKIF4A) is an essential chromosome-associated molecular motor involved in faithful chromosome segregation. HKIF4A localizes in the nucleoplasm during interphase and on condensed chromosome arms during mitosis. It accumulates in the mid-zone from late anaphase and localizes to the cytokinetic ring during cytokinesis. RNA interference--mediated depletion of HKIF4A in human cells results in defective prometaphase organization, chromosome mis-alignment at metaphase, spindle defects, and chromosome mis-segregation. HKIF4A interacts with the condensin I and II complexes and HKIF4A depletion results in chromosome hypercondensation, suggesting that HKIF4A is required for maintaining normal chromosome architecture. Our results provide functional evidence that human KIF4A is a novel component of the chromosome condensation and segregation machinery functioning in multiple steps of mitotic division. 相似文献