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991.
Kuduk SD Di Marco CN Cofre V Ray WJ Ma L Wittmann M Seager MA Koeplinger KA Thompson CD Hartman GD Bilodeau MT 《Bioorganic & medicinal chemistry letters》2011,21(9):2769-2772
Fused aromatics such as naphthalene were identified as highly potent and CNS penetrant M1 positive allosteric modulators during an SAR study to replace the phenyl B-ring linkage. 相似文献
992.
993.
Attention is crucial for visual perception because it allows the visual system to effectively use its limited resources by selecting behaviorally and cognitively relevant stimuli from the large amount of information impinging on the eyes. Reflexive, stimulus-driven attention is essential for successful interactions with the environment because it can, for example, speed up responses to life-threatening events. It is commonly believed that exogenous attention operates in the retinotopic coordinates of the early visual system. Here, using a novel experimental paradigm [1], we show that a nonretinotopic cue improves both accuracy and reaction times in a visual search task. Furthermore, the influence of the cue is limited both in space and time, a characteristic typical of exogenous cueing. These and other recent findings show that many more aspects of vision are processed nonretinotopically than previously thought. 相似文献
994.
Spadoni G Bedini A Orlando P Lucarini S Tarzia G Mor M Rivara S Lucini V Pannacci M Scaglione F 《Bioorganic & medicinal chemistry》2011,19(16):4910-4916
We report the synthesis, binding properties and intrinsic activity at MT(1) and MT(2) melatonin receptors of new dimeric melatonin receptor ligands in which two units of the monomeric agonist N-{2-[(3-methoxyphenyl)methylamino]ethyl}acetamide (1) are linked together through different anchor points. Dimerization of compound 1 through the methoxy substituent leads to a substantial improvement in selectivity for the MT(1) receptor, and to a partial agonist behavior. Compound 3a, with a trimethylene linker, was the most selective for the MT(1) subtype (112-fold selectivity) and compound 3d, characterized by a hexamethylene spacer, had the highest MT(1) binding affinity (pK(iMT1)=8.47) and 54-fold MT(1)-selectivity. Dimerization through the aniline nitrogen of 1 abolished MT(1) selectivity, leading to compounds with either a full agonist or an antagonist behavior depending on the nature of the linker. 相似文献
995.
Examples of programmed tissue response after the interaction of cells with biomaterials are a hot topic in current dental research. We propose here the use
of anodic porous alumina (APA) for the programming of cell growth in oral tissues. In particular, APA may trigger cell growth by the controlled release
of specific growth factors and/or ions. Moreover, APA may be used as a scaffold to promote generation of new tissue, due to the high interconnectivity of
pores and the high surface roughness displayed by this material. 相似文献
996.
Pandozi C Galeazzi M Lavalle C Ficili S Russo M Santini M 《Indian pacing and electrophysiology journal》2011,10(12):556-561
Radiofrequency ablation procedures inside the left atrial appendage (LAA) are likely to involve dangerous complications because of a high thrombogenic effect. Cryoablation procedures are supposed to be safer. We describe two cases of successful cryoablation procedures. Two NavX-guided cryoablations of permanent focal atrial arrhythmias arising from the LAA were performed. Left atrial reconstruction and mapping allowed the zone of the earliest atrial potential to be recorded; the entire course of the ablation catheter was monitored. The arrhythmias were successfully ablated; no thrombotic complications were observed. 相似文献
997.
Simonet T Zaragosi LE Philippe C Lebrigand K Schouteden C Augereau A Bauwens S Ye J Santagostino M Giulotto E Magdinier F Horard B Barbry P Waldmann R Gilson E 《Cell research》2011,21(7):1028-1038
The study of the proteins that bind to telomeric DNA in mammals has provided a deep understanding of the mechanisms involved in chromosome-end protection. However, very little is known on the binding of these proteins to nontelomeric DNA sequences. The TTAGGG DNA repeat proteins 1 and 2 (TRF1 and TRF2) bind to mammalian telomeres as part of the shelterin complex and are essential for maintaining chromosome end stability. In this study, we combined chromatin immunoprecipitation with high-throughput sequencing to map at high sensitivity and resolution the human chromosomal sites to which TRF1 and TRF2 bind. While most of the identified sequences correspond to telomeric regions, we showed that these two proteins also bind to extratelomeric sites. The vast majority of these extratelomeric sites contains interstitial telomeric sequences (or ITSs). However, we also identified non-ITS sites, which correspond to centromeric and pericentromeric satellite DNA. Interestingly, the TRF-binding sites are often located in the proximity of genes or within introns. We propose that TRF1 and TRF2 couple the functional state of telomeres to the long-range organization of chromosomes and gene regulation networks by binding to extratelomeric sequences. 相似文献
998.
The antiproliferative activity of 2-(3,5-Dihydroxyphenyl)-6-hydroxybenzothiazole (DHB) is reported here. DHB inhibits the growth of human colon cancer HCT-15 with a 50% cell growth inhibition value of 23?μM and breast cancer MCF-7 with a 50% cell growth inhibition value of 41?μM in a dose/time dependent manner by using sulforhodamine B assay. Cell cycle analysis by flow cytometry showed that DHB-induced growth arrest could be associated with apoptosis in both cell lines. Moreover, suppression of clonogenic activity occurs after exposure to DHB at a concentration of 25?μM for HCT-15 and of 40?μM for MCF-7. 相似文献
999.
Dorothee Aydin Mikhail A Filippov Jakob-Andreas Tschäpe Norbert Gretz Marco Prinz Roland Eils Benedikt Brors Ulrike C Müller 《BMC genomics》2011,12(1):1-17
Background
SOX2 is a key gene implicated in maintaining the stemness of embryonic and adult stem cells. SOX2 appears to re-activate in several human cancers including glioblastoma multiforme (GBM), however, the detailed response program of SOX2 in GBM has not yet been defined.Results
We show that knockdown of the SOX2 gene in LN229 GBM cells reduces cell proliferation and colony formation. We then comprehensively characterize the SOX2 response program by an integrated analysis using several advanced genomic technologies including ChIP-seq, microarray profiling, and microRNA sequencing. Using ChIP-seq technology, we identified 4883 SOX2 binding regions in the GBM cancer genome. SOX2 binding regions contain the consensus sequence wwTGnwTw that occurred 3931 instances in 2312 SOX2 binding regions. Microarray analysis identified 489 genes whose expression altered in response to SOX2 knockdown. Interesting findings include that SOX2 regulates the expression of SOX family proteins SOX1 and SOX18, and that SOX2 down regulates BEX1 (brain expressed X-linked 1) and BEX2 (brain expressed X-linked 2), two genes with tumor suppressor activity in GBM. Using next generation sequencing, we identified 105 precursor microRNAs (corresponding to 95 mature miRNAs) regulated by SOX2, including down regulation of miR-143, -145, -253-5p and miR-452. We also show that miR-145 and SOX2 form a double negative feedback loop in GBM cells, potentially creating a bistable system in GBM cells.Conclusions
We present an integrated dataset of ChIP-seq, expression microarrays and microRNA sequencing representing the SOX2 response program in LN229 GBM cells. The insights gained from our integrated analysis further our understanding of the potential actions of SOX2 in carcinogenesis and serves as a useful resource for the research community. 相似文献1000.