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941.
942.
Romagnoli R Baraldi PG Carrion MD Cara CL Cruz-Lopez O Salvador MK Preti D Tabrizi MA Shryock JC Moorman AR Vincenzi F Varani K Borea PA 《Bioorganic & medicinal chemistry》2012,20(2):996-1007
In a preliminary article, we reported the potent allosteric enhancer activity at the A(1) adenosine receptor of a small series of 2-amino-3-(4-chlorobenzoyl)-4-[4-(aryl)piperazin-1-yl)methyl]thiophene derivatives bearing electron-withdrawing or electron-releasing groups at the para-position of the phenylpiperazine moiety. In the present study, we report the development of the compounds previously studied by modifying both the number and position of substituents on the phenylpiperazine moiety, aimed at establishing a structure-activity relationship identifying additional compounds with improved activity. The nature and the position of substituents on the phenyl ring tethered to the piperazine seemed to exert a fundamental influence on the allosteric enhancer activity, with the 3,4-difluoro 4i, 3-chloro-4-fluoro 4o, and 4-trifluoromethoxy 4ak derivatives being the most active compounds in binding (saturation and competition experiments) and functional cAMP studies. This study shows that it is also possible to obtain a good separation between allosteric enhancement and antagonistic activity at the A(1) adenosine receptor. 相似文献
943.
Nicacio AC Simões R de Paula-Lopes FF de Barros FR Peres MA Assumpção ME Visintin JA 《Zygote (Cambridge, England)》2012,20(2):117-122
The aim of this work was to evaluate the effect of cryopreservation protocols on subsequent development of in vitro produced bovine embryos under different culture conditions. Expanded in vitro produced blastocysts (n = 600) harvested on days 7-9 were submitted to controlled freezing [slow freezing group: 10% ethylene glycol (EG) for 10 min and 1.2°C/min cryopreservation]; quick-freezing [rapid freezing group: 10% EG for 10 min, 20% EG + 20% glycerol (Gly) for 30 s]; or vitrification [vitrification group: 10% EG for 10 min, 25% EG + 25% Gly for 30 s] protocols. Control group embryos were not exposed to cryoprotectant or cryopreservation protocols and the hatching rate was evaluated on day 12 post-insemination. In order to evaluate development, frozen-thawed embryos were subjected to granulosa cell co-culture in TCM199 or SOFaa for 4 days. Data were analyzed by PROC MIXED model using SAS Systems for Windows?. Values were significant at p < 0.05. The hatching rate of the control group was 46.09%. In embryos cultured in TCM199, slow freezing and vitrification group hatching rates were 44.65 ± 5.94% and 9.43 ± 6.77%, respectively. In embryos cultured in SOFaa, slow freezing and vitrification groups showed hatching rates of 11.65 ± 3.37 and 8.67 ± 4.47%, respectively. In contrast, the rapid freezing group embryos did not hatch, regardless of culture medium. The slow freezing group showed higher hatching rates than other cryopreservation groups. Under such conditions, controlled freezing (1.2°C/min) can be an alternative to cryopreservation of in vitro produced bovine embryos. 相似文献
944.
Sim SB Mattsson M Feder JL Cha DH Yee WL Goughnour RB Linn CE Feder JL 《Journal of evolutionary biology》2012,25(5):961-971
Prezygotic isolation due to habitat choice is important to many models of speciation-with-gene-flow. Habitat choice is usually thought to occur through positive preferences of organisms for particular environments. However, avoidance of non-natal environments may also play a role in choice and have repercussions for post-zygotic isolation that preference does not. The recent host shift of Rhagoletis pomonella (Diptera: Tephritidae) from downy hawthorn, Crataegus mollis, to introduced apple, Malus domestica, in the eastern United States is a model for speciation-with-gene-flow. However, the fly is also present in the western United States where it was likely introduced via infested apples ≤ 60 years ago. R. pomonella now attacks two additional hawthorns in the west, the native C. douglasii (black hawthorn) and the introduced C. monogyna (English ornamental hawthorn). Flight tunnel tests have shown that western apple-, C. douglasii- and C. monogyna-origin flies all positively orient to fruit volatile blends of their respective natal hosts in flight tunnel assays. Here, we show that these laboratory differences translate to nature through field-trapping studies of flies in the state of Washington. Moreover, western R. pomonella display both positive orientation to their respective natal fruit volatiles and avoidance behaviour (negative orientation) to non-natal volatiles. Our results are consistent with the existence of behaviourally differentiated host races of R. pomonella in the west. In addition, the rapid evolution of avoidance behaviour appears to be a general phenomenon for R. pomonella during host shifts, as the eastern apple and downy hawthorn host races also are antagonized by non-natal fruit volatiles. 相似文献
945.
Synergies between invasive species and climate change are widely considered to be a major biodiversity threat. However, invasive species are also hypothesized to be susceptible to population collapse, as we demonstrate for a globally important invasive species in New Zealand. We observed Argentine ant populations to have collapsed in 40 per cent of surveyed sites. Populations had a mean survival time of 14.1 years (95% CI = 12.9-15.3 years). Resident ant communities had recovered or partly recovered after their collapse. Our models suggest that climate change will delay colony collapse, as increasing temperature and decreasing rainfall significantly increased their longevity, but only by a few years. Economic and environmental costs of invasive species may be small if populations collapse on their own accord. 相似文献
946.
A major goal of microbial community ecology is to understand the forces that structure community composition. Deterministic selection by specific environmental factors is sometimes important, but in other cases stochastic or ecologically neutral processes dominate. Lacking is a unified conceptual framework aiming to understand why deterministic processes dominate in some contexts but not others. Here we work toward such a framework. By testing predictions derived from general ecological theory we aim to uncover factors that govern the relative influences of deterministic and stochastic processes. We couple spatiotemporal data on subsurface microbial communities and environmental parameters with metrics and null models of within and between community phylogenetic composition. Testing for phylogenetic signal in organismal niches showed that more closely related taxa have more similar habitat associations. Community phylogenetic analyses further showed that ecologically similar taxa coexist to a greater degree than expected by chance. Environmental filtering thus deterministically governs subsurface microbial community composition. More importantly, the influence of deterministic environmental filtering relative to stochastic factors was maximized at both ends of an environmental variation gradient. A stronger role of stochastic factors was, however, supported through analyses of phylogenetic temporal turnover. Although phylogenetic turnover was on average faster than expected, most pairwise comparisons were not themselves significantly non-random. The relative influence of deterministic environmental filtering over community dynamics was elevated, however, in the most temporally and spatially variable environments. Our results point to general rules governing the relative influences of stochastic and deterministic processes across micro- and macro-organisms. 相似文献
947.
948.
Grujic M Christensen JP Sørensen MR Abrink M Pejler G Thomsen AR 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(2):1043-1051
We previously reported that the lack of serglycin proteoglycan affects secretory granule morphology and granzyme B (GrB) storage in in vitro generated CTLs. In this study, the role of serglycin during viral infection was studied by infecting wild-type (wt) mice and serglycin-deficient (SG(-/-)) mice with lymphocytic choriomeningitis virus (LCMV). Wt and SG(-/-) mice cleared 10(3) PFU of highly invasive LCMV with the same kinetics, and the CD8(+) T lymphocytes from wt and SG(-/-) animals did not differ in GrB, perforin, IFN-gamma, or TNF-alpha content. However, when a less invasive LCMV strain was used, SG(-/-) GrB(+) CD8(+) T cells contained approximately 30% less GrB than wt GrB(+) CD8(+) T cells. Interestingly, the contraction of the antiviral CD8(+) T cell response to highly invasive LCMV was markedly delayed in SG(-/-) mice, and a delayed contraction of the virus-specific CD8(+) T cell response was also seen after infection with vesicular stomatitis virus. BrdU labeling of cells in vivo revealed that the delayed contraction was associated with sustained proliferation of Ag-specific CD8(+) T cells in SG(-/-) mice. Moreover, wt LCMV-specific CD8(+) T cells from TCR318 transgenic mice expanded much more extensively in virus-infected SG(-/-) mice than in matched wt mice, indicating that the delayed contraction represents a T cell extrinsic phenomenon. In summary, the present report points to a novel, previously unrecognized role for serglycin proteoglycan in regulating the kinetics of antiviral CD8(+) T cell responses. 相似文献
949.
950.
Sim J Ozgur S Lin BY Yu JH Broker TR Chow LT Griffith J 《Journal of molecular biology》2008,375(4):1165-1177
The human papillomavirus (HPV) DNA replication origin (ori) shares a common theme with many DNA control elements in having multiple binding sites for one or more proteins spaced over several hundreds of base pairs. The HPV type 11 ori spans 103 bp and contains three palindromic E2 binding sites (E2BS-2, E2BS-3, and E2BS-4) for the dimeric E2 ori binding protein. These sites are separated by 64 and 3 bp. E2BS-1 is located 288 bp upstream of E2BS-2 and is not required for efficient transient or cell-free replication. In this study, electron microscopy was used to visualize complexes of HPV-11 DNA ori bound by purified E2 protein. DNA containing only E2BS-2 showed a single E2 dimer bound. DNA containing E2BS-3 and E2BS-4 showed two side-by-side E2 dimers, while DNA containing E2BS-2, E2BS-3, and E2BS-4 exhibited a large disk/ring-shaped protein particle bound, indicating that the DNA had been remodeled into a discrete complex, likely containing an E2 hexamer. With all four binding sites present, up to 27% of the DNA molecules were arranged into loops by E2, the majority of which spanned E2BS-1 and one of the other three sites. Studies on the dependence of looping on salt, ATP, and DTT using full-length E2 and an E2 protein containing only the carboxyl-terminal DNA binding and protein dimerization domain suggest that looping is dependent on the N-terminal domain and factors that may affect the manner in which E2 scans DNA for binding sites. The role of these structures in the modeling and regulation of the HPV-11 ori is discussed. 相似文献