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991.
Seminal fluid is a biochemically complex mixture of glandular secretions that is transferred to the females sexual tract as part of the ejaculate. Seminal fluid has received increasing scientific interest in the fields of evolutionary and reproductive biology, as it seems a major determinant of male fertility/infertility and reproductive success. Here we used the honeybee Apis mellifera, where seminal fluid can be collected as part of a male's ejaculate, and performed a series of experiments to investigate the effects of seminal fluid and its components on sperm viability. We show that honeybee seminal fluid is highly potent in keeping sperm alive and this positive effect is present over a 24 h time span, comparable to the timing of the sperm storage process in the queen. We furthermore show that the presence of proteins within the seminal fluid and their structural integrity are crucial for this effect. Finally, we activated sperm using fructose and provide evidence that the positive effect of seminal fluid proteins on sperm survival cannot be replicated using generic protein substitutes. Our data provide experimental insights into the complex molecular interplay between sperm and seminal fluid defining male fertility and reproductive success. 相似文献
992.
Shiryaev SA Aleshin AE Ratnikov BI Smith JW Liddington RC Strongin AY 《Protein expression and purification》2007,52(2):334-339
Regulated proteolysis of the polyprotein precursor of West Nile virus (WNV) by the essential NS2B–NS3(pro)tease, a promising drug target for WNV inhibitors, is required for the propagation of infectious virions. Structural and drug design studies, however, require pilot-scale quantities of a pure and catalytically active WNV protease that is resistant to self-proteolysis. Autolytic cleavage at the NS2B–NS3 boundary leads to individual, non-covalently associated, NS2B and NS3 domains, together with residual amounts of the intact NS2B–NS3, in the NS2B–NS3pro samples. We modified the cleavage site sequence of the NS2B–NS3 junction region and then developed expression and purification procedures to prepare a covalently linked, single-chain, NS2B–NS3pro K48A mutant construct. This construct exhibits high stability and functional activity and is thus well suited for the follow-up purification and structural and drug design studies. 相似文献
993.
Guillaume Chastanet Boris Le Guennic Christophe Aronica Guillaume Pilet Dominique Luneau Marie-Laure Bonnet Vincent Robert 《Inorganica chimica acta》2008,361(14-15):3847-3855
The ability of the azido ligand to generate various chemical architectures and magnetic couplings is surveyed, using Cu(II) and Ni(II) derivatives. Depending on the ratio between the azide salt, the metal salt and the tridentate Schiff base LH (L?:1,1,1-trifluoro-7-(dimethylamino)-4-methyl-5-aza-3-hepten-2-onato), molecular bimetallic [CuL(μ1,3-N3)]2 (1) and monometallic [NiL(μ1-N3)] (2) as well as extended {[CuL(μ1,1-N3)]}n (3) and {[Ni2(μ1,1-N3)(μ1,3-N3)(L)2(MeOH)2]}n (4) chains were obtained. These systems were fully characterized by X-ray diffraction and magnetic susceptibility measurements. In 1, the asymmetrical double μ1,3-N3 bridge mediates a ferromagnetic exchange whereas 3 and 4 exhibit unusual symmetric and asymmetric single μ1,1-N3 coordination modes that transmit weak ferromagnetic interactions. Ab initio calculations were systematically performed to clarify the origin of the observed magnetic exchanges and to study the role of the asymmetric coordination modes on the magnetic coupling. 相似文献
994.
Noronha G Barrett K Boccia A Brodhag T Cao J Chow CP Dneprovskaia E Doukas J Fine R Gong X Gritzen C Gu H Hanna E Hood JD Hu S Kang X Key J Klebansky B Kousba A Li G Lohse D Mak CC McPherson A Palanki MS Pathak VP Renick J Shi F Soll R Splittgerber U Stoughton S Tang S Yee S Zeng B Zhao N Zhu H 《Bioorganic & medicinal chemistry letters》2007,17(3):602-608
We describe the identification of [7-(2,6-dichlorophenyl)-5-methylbenzo [1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]amine (3), a potent, orally active Src inhibitor with desirable PK properties, demonstrated activity in human tumor cell lines and in animal models of tumor growth. 相似文献
995.
G Chen B Rubinstein R Li 《BioEssays : news and reviews in molecular, cellular and developmental biology》2012,34(10):893-900
Despite its widespread existence, the adaptive role of aneuploidy (the abnormal state of having an unequal number of different chromosomes) has been a subject of debate. Cellular aneuploidy has been associated with enhanced resistance to stress, whereas on the organismal level it is detrimental to multicellular species. Certain aneuploid karyotypes are deleterious for specific environments, but karyotype diversity in a population potentiates adaptive evolution. To reconcile these paradoxical observations, this review distinguishes the role of aneuploidy in cellular versus organismal evolution. Further, it proposes a population genetics perspective to examine the behavior of aneuploidy on a populational versus individual level. By altering the copy number of a significant portion of the genome, aneuploidy introduces large phenotypic leaps that enable small cell populations to explore a wide phenotypic landscape, from which adaptive traits can be selected. The production of chromosome number variation can be further increased by stress- or mutation-induced chromosomal instability, fueling rapid cellular adaptation. 相似文献
996.
Serine proteases have proven to be promising pharmacological targets in contemporary drug discovery for cancer treatment. Since azaphenylalanine-based compounds manifest cytotoxic activity, we have selected serine protease inhibitors designed and synthesized in-house with large hydrophobic naphthalene moiety for screening. The cytotoxic potential of screened molecules was correlated to modifications of R(1) residues. The most cytotoxic were compounds with greater basicity; amidinopiperidines, piperidines and benzamidines. Amidinopiperidine-based compounds exert cytotoxicity in low μM range, with IC(50) 18 μM and 22 μM for inhibitors 15 and 16 respectively. These compounds exhibited selective cytotoxicity towards the Burkitt's lymphoma cells Ramos and Daudi, and proved nontoxic to PMBC, Jurkat and U937. They induce caspase-dependent apoptotic cell death, as demonstrated by the use of a pan-caspase inihibitor, zVADfmk, which was able to rescue Ramos cells from compound(s)-induced apoptosis. We confirm a disruption of the pro-survival pathway in Burkitt's lymphoma through NFκB inhibition. The accumulation of phosphorylated precursor (p105) and inhibitory (IκB) molecules with no subsequent release of active NFκB implicated the involvement of proteasome. Indeed, we show that the amidinopiperidine-based compounds inhibit all three proteolytical activities of the human 20S proteasome, with the most prominent effect being on the trypsin-like activity. Consistently, treatment of Ramos cells with these compounds led to an increase in ubiquitinated proteins. The amidinopiperidine-based serine protease inhibitors presented are, as selective inducers of apoptosis in Burkitt's lymphoma cells, promising leads for the development of novel chemotherapeutics. 相似文献
997.
The meiofauna from seagrass meadows in the western sector of the Gulf of Batabanó, Cuba were studied to describe the spatial and temporal variations in community structure. Replicated cores were taken in three locations (arranged in m- and km-scales) and in two seasons (dry and wet). The meiofauna (metazoans between 500 and 45 microm) were identified to major taxa. Temporal changes in the meiofaunal communities could not be detected and they are not linked to the subtle seasonal changes in the water column. A larger variation in community structure was observed in the spatial m-scale (among cores in a station) probably accredited to heterogeneity of microenvironment and biological processes. A second source of variation in the km-scale (among locations) was identified relating to physical processes affecting seagrass meadows: marine currents and anthropogenic disturbances. Distribution patterns of meiofauna across locations coincide with one study from 20 years ago in seagrass beds (i.e. higher densities in area closer to break-shelf and diminution of fauna at southern of Pinar del Rio); however, cumulative anthropogenic disturbances on seagrass meadows would most likely explain the depletion of communities observed in our survey in comparison with decades ago. Estimates of meiofaunal density and richness of major taxa from our study (and other areas from the Cuban shelf) are consistently lower than other temperate and tropical sites; possibly caused by low primary productivity due to narrow tidal amplitude and oligotrophic waters. 相似文献
998.
999.
Monte FL Kramer T Boländer A Plotkin B Eldar-Finkelman H Fuertes A Dominguez J Schmidt B 《Bioorganic & medicinal chemistry letters》2011,21(18):5610-5615
The glycogen synthase kinase 3 (GSK-3) is implicated in multiple cellular processes and has been linked to the pathogenesis of Alzheimer's disease (AD). In the course of our research topic we synthesized a library of potent GSK-3 inhibitors. We utilized the urea scaffold present in the potent and highly selective GSK-3 inhibitor AR-A014418 (AstraZeneca). This moiety suits both (a) a convergent approach utilizing readily accessible building blocks and (b) a divergent approach based on a microwave heating assisted Suzuki coupling. We established a chromatography-free purification method to generate products with sufficient purity for the biological assays. The structure-activity relationship of the library provided the rationale for the synthesis of the benzothiazolylurea 66 (IC(50)=140 nM) and the pyridylurea 62 (IC(50)=98 nM), which displayed two to threefold enhanced activity versus the reference compound 18 (AR-A014418: IC(50)=330 nM) in our assays. 相似文献
1000.
Genetic control of grain yield and grain physical characteristics in a bread wheat population grown under a range of environmental conditions 总被引:1,自引:0,他引:1
Lancelot Maphosa Peter Langridge Helen Taylor Boris Parent Livinus C. Emebiri Haydn Kuchel Matthew P. Reynolds Ken J. Chalmers Anzu Okada James Edwards Diane E. Mather 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2014,127(7):1607-1624