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901.
902.
Ahmed Kamal D. Dastagiri M. Janaki Ramaiah E. Vijaya Bharathi J. Surendranadha Reddy G. Balakishan Pranjal Sarma S.N.C.V.L. Pushpavalli Manika Pal-Bhadra Aarti Juvekar Subrata Sen Surekha Zingde 《Bioorganic & medicinal chemistry》2010,18(18):6666-6677
A series of 2,5-diaryloxadiazole linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates have been prepared and evaluated for their anticancer activity. These conjugates have shown promising activity with GI50 values ranging from <0.1 to 0.29 μΜ. It is observed that some of these conjugates particularly 4a, 4d, 4i and 4l exhibit significant anticancer activity. Some detailed biological assays relating to the cell cycle aspects associated to Bax and caspases have been examined with a view to understand the mechanism of action of these conjugates. 相似文献
903.
Jeannie Hwang Crista Adamson David Butler David R. Janero Alexandros Makriyannis Ben A. Bahr 《Life sciences》2010,86(15-16):615-623
AimsThis review posits that fatty acid amide hydrolase (FAAH) inhibition has therapeutic potential against neuropathological states including traumatic brain injury; Alzheimer's, Huntington's, and Parkinson's diseases; and stroke.Main methodsThis proposition is supported by data from numerous in vitro and in vivo experiments establishing metabolic and pharmacological contexts for the neuroprotective role of the endogenous cannabinoid (“endocannabinoid”) system and selective FAAH inhibitors.Key findingsThe systems biology of endocannabinoid signaling involves two main cannabinoid receptors, the principal endocannabinoid lipid mediators N-arachidonoylethanolamine (“anandamide”) (AEA) and 2-arachidonoyl glycerol (2-AG), related metabolites, and the proteins involved in endocannabinoid biosynthesis, biotransformation, and transit. The endocannabinoid system is capable of activating distinct signaling pathways on-demand in response to pathogenic events or stimuli, thereby enhancing cell survival and promoting tissue repair. Accumulating data suggest that endocannabinoid system modulation at discrete targets is a promising pharmacotherapeutic strategy for treating various medical conditions. In particular, neuronal injury activates cannabinoid signaling in the central nervous system as an intrinsic neuroprotective response. Indirect potentiation of this salutary response through pharmacological inhibition of FAAH, an endocannabinoid-deactivating enzyme, and consequent activation of signaling pathways downstream from cannabinoid receptors have been shown to promote neuronal maintenance and function.SignificanceThis therapeutic modality has the potential to offer site- and event-specific neuroprotection under conditions where endocannabinoids are being produced as part of a physiological protective mechanism. In contrast, direct application of cannabinoid receptor agonists to the central nervous system may activate CB receptors indiscriminately and invite unwanted psychotrophic effects. 相似文献
904.
Hedde van de Vooren Maaike G J Gademan Cees A Swenne Ben J TenVoorde Martin J Schalij Ernst E Van der Wall 《Journal of applied physiology》2007,102(4):1348-1356
The arterial baroreflex buffers slow (<0.05 Hz) blood pressure (BP) fluctuations, mainly by controlling peripheral resistance. Baroreflex sensitivity (BRS), an important characteristic of baroreflex control, is often noninvasively assessed by relating heart rate (HR) fluctuations to BP fluctuations; more specifically, spectral BRS assessment techniques focus on the BP-to-HR transfer function around 0.1 Hz. Skepticism about the relevance of BRS to characterize baroreflex-mediated BP buffering is based on two considerations: 1) baroreflex-modulated peripheral vasomotor function is not necessarily related to baroreflex-HR transfer; and 2) although BP fluctuations around 0.1 Hz (Mayer waves) might be related to baroreflex BP buffering, they are merely a not-intended side effect of a closed-loop control system. To further investigate the relationship between BRS and baroreflex-mediated BP buffering, we set up a computer model of baroreflex BP control to simulate normal subjects and heart failure patients. Output variables for various randomly chosen combinations of feedback gains in the baroreflex arms were BP resonance, BP-buffering capacity, and BRS. Our results show that BP buffering and BP resonance are related expressions of baroreflex BP control and depend strongly on the sympathetic gain to the peripheral resistance. BRS is almost uniquely determined by the vagal baroreflex gain to the sinus node. In conclusion, BP buffering and BRS are unrelated unless coupled gains in all baroreflex limbs are assumed. Hence, the clinical benefit of a high BRS is most likely to be attributed to vagal effects on the heart instead of to effective BP buffering. 相似文献
905.
Karl L. Evans Kevin J. Gaston Stuart P. Sharp Andrew McGowan Michelle Simeoni Ben J. Hatchwell 《Oikos》2009,118(5):774-782
Despite increasing interest in urban ecology most attention has focussed on describing changes in assemblage composition and structure along urbanisation gradients, whilst relatively little research has focussed on the mechanisms behind these changes. Ecological theory predicts that alterations in biotic interactions are particularly likely to arise, especially with regard to disease risk. Here, we report on differences in prevalence of avian malaria and tick infection and intensity in 11 paired urban and rural blackbird Turdus merula populations from across the western Palearctic. We find large and consistent reductions in tick prevalence and intensity in urban areas. There are also large reductions in the prevalence of avian malaria in many, but not all, urban areas. The proportion of first year birds in urban populations is significantly lower than that in rural ones, and across the more natural rural sites southerly populations contain fewer first years than northern ones. These patterns are expected to arise if survival rates are higher in urban areas, and are negatively correlated with latitude. 相似文献
906.
Neïla Hamza Frédéric Silvestre Mohamed Mhetli Ines Ben Khemis Marc Dieu Martine Raes Chantal Cahu Patrick Kestemont 《Comparative biochemistry and physiology. Part D, Genomics & proteomics》2010,5(2):130-137
A comparative proteomic approach was used to assess the protein expression profile in the liver of 34 days old pikeperch larvae fed from day 10 post hatching, with three isoproteic and isolipidic formulated diets varying by their phospholipid (PL) contents (% dry diet weight): 1.4% (PL1), 4.7% (PL5) and 9.5% (PL9). Using 2D-DIGE minimal labelling of liver extracts, we were able to show 56 protein spots with a differential intensity (p < 0.05) depending on the dietary PL content. Among these spots, 11 proteins were unambiguously identified using nanoLC-MS/MS tandem mass spectrometry. In the PL9 larvae, our results indicate that the glycolytic pathway could be down-regulated due to the under-expression of the fructose biphosphate aldolase B and the phosphoglucomutase 1. Meanwhile, propionyl coenzyme A carboxylase (a gluconeogenic enzyme) was under-expressed. In addition, another gluconeogenic and lipogenic enzyme, pyruvate carboxylase, was identified in 3 different spots as being under-expressed in fish fed with the intermediate PL level (PL5). A high PL content increased the expression of sarcosine dehydrogenase, an enzyme involved in methionine metabolism, along with vinculin, a structural protein. Moreover, several stress proteins (glutathione S-transferase M, glucose regulated protein 75 and peroxiredoxin-1) were modulated in response to the dietary PL level and fatty acid composition. In the larvae fed with the lowest dietary PL content (PL1), over-expression of both GSTM and GRP75 might indicate a cellular stress in this experimental treatment, while the under-expression of Prx1 might indicate a lower defence against oxidative stress. In conclusion, this nutriproteomic approach showed significant modifications of protein expression in the liver of pikeperch larvae fed different PL contents, highlighting the importance of these nutrients and their influence on metabolism processes and on stress response. 相似文献
907.
908.
Glutamate receptors are the most prevalent excitatory neurotransmitter receptors in the vertebrate central nervous system. Determining the structural differences between the binding sites of different subtypes is crucial to our understanding of neuronal circuits and to the development of subtype specific drugs. The structures of the binding domain (S1S2) of the GluR3 (flip) AMPA receptor subunit bound to glutamate and AMPA and the GluR2 (flop) subunit bound to glutamate were determined by X‐ray crystallography to 1.9, 2.1, and 1.55 Å, respectively. Overall, the structure of GluR3 (flip) S1S2 is very similar to GluR2 (flop) S1S2 (backbone RMSD of 0.30 ± 0.05 for glutamate‐bound and 0.26 ± 0.01 for AMPA‐bound). The differences in the flip and flop isoforms are subtle and largely arise from one hydrogen bond across the dimer interface and associated water molecules. Comparison of the binding affinity for various agonists and partial agonists suggest that the S1S2 domains of GluR2 and GluR3 show only small differences in affinity, unlike what is found for the intact receptors (with the exception of one ligand, Cl‐HIBO, which has a 10‐fold difference in affinity for GluR2 vs. GluR3). Proteins 2009. © 2008 Wiley‐Liss, Inc. 相似文献
909.
F. Ben Rebah F. Frikha W. Kamoun L. Belbahri Y. Gargouri N. Miled 《Letters in applied microbiology》2008,47(6):549-554
Aims: The objective of this study was to demonstrate that fish‐processing by‐products could be used as sole raw material to sustain the growth of Staphylococcus xylosus for lipase production. Methods and Results: Bacterial growth was tested on supernatants generated by boiling (100°C for 20 min) of tuna, sardine, cuttlefish and shrimp by‐products from fish processing industries. Among all samples tested, only supernatants generated from shrimp and cuttlefish by‐products sustained the growth of S. xylosus. Shrimp‐based medium gave the highest growth (A600 = 22) after 22 h of culture and exhibited the maximum lipase activity (28 U ml?1). This effect may be explained by better availability of nutrients, especially, in shrimp by‐products. Standard medium (SM) amendments to sardine and tuna by‐product‐based media stimulated the growth of S. xylosus and the highest A600 values were obtained with 75% SM. Lipase activity, however, remained below 4 U ml?1 for both sardine and tuna by‐product‐based media. Conclusions: Fish by‐products could be used for the production of highly valuable enzymes. Significance and Impact of the Study: The use of fish by‐products in producing S. xylosus‐growth media can reduce environmental problems associated with waste disposal and, simultaneously, lower the cost of biomass and enzyme production. 相似文献
910.
The settlement and recruitment patterns of Chromis viridis were followed during three consecutive seasons along the reefs of Eilat, Red Sea. The findings, based on intensive field surveys and a translocation experiment, indicated a strong and repeatable preference for some, but not other, colonies of the branching coral Acropora eurystoma; with significantly more larvae settling onto preferred colonies that house conspecific adults and juveniles. Furthermore, these findings showed that, given high recruitment rates, settlement‐site selection could drive migration by adults and older juveniles. As only some C. viridis schools received direct settlement, it was suggested that settlement‐driven migration is responsible for the replenishment of those schools that do not receive settlement and to the colonization of previously unoccupied coral colonies. 相似文献