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Jacquie L. Harper Iman M. Khalil Lisa Shaw Marie-Lise Bourguet-Kondracki Jo?lle Dubois Alexis Valentin David Barker Brent R. Copp 《Marine drugs》2015,13(8):5102-5110
In an effort to more accurately define the mechanism of cell death and to establish structure-activity relationship requirements for the marine meroterpenoid alkaloids thiaplidiaquinones A and B, we have evaluated not only the natural products but also dioxothiazine regioisomers and two precursor quinones in a range of bioassays. While the natural products were found to be weak inducers of ROS in Jurkat cells, the dioxothiazine regioisomer of thiaplidiaquinone A and a synthetic precursor to thiaplidiaquinone B were found to be moderately potent inducers. Intriguingly, and in contrast to previous reports, the mechanism of Jurkat cell death (necrosis vs. apoptosis) was found to be dependent upon the positioning of one of the geranyl sidechains in the compounds with thiaplidiaquinone A and its dioxothiazine regioisomer causing death dominantly by necrosis, while thiaplidiaquinone B and its dioxothiazine isomer caused cell death via apoptosis. The dioxothiazine regioisomer of thiaplidiaquinone A exhibited more potent in vitro antiproliferative activity against human tumor cells, with NCI sub-panel selectivity towards melanoma cell lines. The non-natural dioxothiazine regioisomers were also more active in antiplasmodial and anti-farnesyltransferase assays than their natural product counterparts. The results highlight the important role that natural product total synthesis can play in not only helping understand the structural basis of biological activity of natural products, but also the discovery of new bioactive scaffolds. 相似文献
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Efficacy of buserelin acetate combined with a dopamine antagonist for spawning induction in the bullfrog (Lithobates catesbeianus) 下载免费PDF全文
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Rozenn Jossé Yong-Wei Zhang Valentin Giroux Arun K. Ghosh Ji Luo Yves Pommier 《Marine drugs》2015,13(6):3625-3639
Lasonolide A (LSA), a potent antitumor polyketide from the marine sponge, Forcepia sp., induces rapid and reversible protein hyperphosphorylation and premature chromosome condensation (PCC) at nanomolar concentrations independent of cyclin-dependent kinases. To identify cellular targets of LSA, we screened 2951 shRNAs targeting a pool of human kinases and phosphatases (1140 RefSeqs) to identify genes that modulate PCC in response to LSA. This led to the identification of RAF1 (C-RAF) as a mediator of LSA-induced PCC, as shRNAs against RAF1 conferred resistance to LSA. We found that LSA induced RAF1 phosphorylation on Serine 338 within minutes in human colorectal carcinoma HCT-116, ovarian carcinoma OVCAR-8, and Burkitt’s lymphoma CA46 cell lines. RAF1 depletion by siRNAs attenuated LSA-induced PCC in HCT-116 and OVCAR-8 cells. Furthermore, mouse embryonic fibroblasts (MEF) with homozygous deletion in Raf1, but not deletion in the related kinase Braf, were resistant to LSA-induced PCC. Complementation of Raf1−/− MEFs with wild-type human RAF1, but not with kinase-dead RAF1 mutant, restored LSA-induced PCC. Finally, the Raf inhibitor sorafenib, but not the MEK inhibitor AZD6244, effectively suppressed LSA-induced PCC. Our findings implicate a previously unknown, MAPK-independent role of RAF1 in chromatin condensation and potent activation of this pathway by LSA. 相似文献
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Biological characteristics of the hydrological landscapes in the Bay of Biscay in spring 2009 下载免费PDF全文
Ainhoa Lezama‐Ochoa Daniel Grados Anne Lebourges‐Dhaussy Xabier Irigoien Alexis Chaigneau Arnaud Bertrand 《Fisheries Oceanography》2015,24(1):26-41
In the present study we investigated the biogeography of macrozooplankton and fish biomass in the Bay of Biscay. In this region, we defined six different landscapes based on the hydrogeographical characteristics observed in spring 2009. We then related landscape's characteristics and environmental parameters such as light attenuation depth and chlorophyll‐a with macrozooplankton and fish acoustic biomass. Hydrodynamic structures together with coastal influences (river discharges, predation pressure and depth preference) and vertical thermohaline structure/mixing (feeding modes and ability to stay in preferred layers) appeared as the main factors determining the biological distribution. Besides, variance partitioning was used to assess the respective roles played by the hydrological environment, the geographical space and the biological environment alone, and their interactions. Results revealed that: (i) macrozooplankton and fish have a preference for different hydrogeographical landscapes; (ii) the association between hydrological conditions and geographical features, i.e. the spatial structure of the hydrological environment, plays a key role in the distribution of macrozooplankton; and (iii) prey–predator relationships have to be taken into account to provide a comprehensive characterization of habitat suitability. 相似文献
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Responses of small rodents to habitat restoration and management for the imperiled Florida Scrub-Jay
Alexis A. Suazo John E. Fauth James D. Roth Christopher L. Parkinson I. Jack Stout 《Biological conservation》2009,142(10):2322-2328
Debate about the relative merits of single-species management versus more comprehensive approaches has intensified in recent years. In east-central Florida, USA, land managers use prescribed burns and mechanical cutting to manage and restore scrub habitat to benefit the imperiled Florida Scrub-Jay (Aphelocoma coerulescens). However, these land-management techniques may affect non-target taxa, especially the threatened southeastern beach mouse (Peromyscus polionotus niveiventris). We evaluated the collateral effects of single-species land management by trapping P. p. niveiventris and other small rodents in eighteen land-management compartments at Cape Canaveral Air Force Station, Florida during 2004–2005. Compartments were managed using either prescribed burns (N = 5), mechanical cutting (N = 6), checkerboarding (cut and uncut lanes alternating and overlapping, followed by a prescribed burn, N = 4) or left unburned and uncut for >50 year (N = 3). P. p. niveiventris was significantly more abundant in compartments managed with prescribed burns (mean ± SE: 4.2 ± 0.7 individuals/transect) than those managed with cutting alone (1.0 ± 0.3) or not managed for >50 y (0.2 ± 0.1 individuals/transect). In contrast, the cotton mouse (Peromyscus gossypinus) tended to be more abundant in compartments managed with mechanical cutting alone (2.6 ± 0.4 individuals/transect) compared to the other three management strategies (prescribed burns; 1.5 ± 0.4; checkerboarding, 1.1 ± 0.3; not managed, 1.6 ± 0.4 individuals/transect) but these differences were not statistically significant. Abundances of P. p. niveiventris and Florida Scrub-Jay breeding groups were positively correlated (r = 0.655), suggesting that both listed species benefit from similar management techniques. Thus, the mosaic of burned and cut patches used to improve habitat for the Florida Scrub-Jay also benefits an endemic, non-target species. Single-species management may benefit multiple species when restoration improves their shared habitat, which in this case is an endangered, fire-dependent ecosystem: Florida scrub. 相似文献
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Valentin Golosov Alexander Koiter Maxim Ivanov Kirill Maltsev Artyom Gusarov Aidar Sharifullin Irina Radchenko 《Journal of Soils and Sediments》2018,18(12):3388-3403