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991.
Schalk-Hihi C Schubert C Alexander R Bayoumy S Clemente JC Deckman I DesJarlais RL Dzordzorme KC Flores CM Grasberger B Kranz JK Lewandowski F Liu L Ma H Maguire D Macielag MJ McDonnell ME Mezzasalma Haarlander T Miller R Milligan C Reynolds C Kuo LC 《Protein science : a publication of the Protein Society》2011,20(4):670-683
A high-resolution structure of a ligand-bound, soluble form of human monoglyceride lipase (MGL) is presented. The structure highlights a novel conformation of the regulatory lid-domain present in the lipase family as well as the binding mode of a pharmaceutically relevant reversible inhibitor. Analysis of the structure lacking the inhibitor indicates that the closed conformation can accommodate the native substrate 2-arachidonoyl glycerol. A model is proposed in which MGL undergoes conformational and electrostatic changes during the catalytic cycle ultimately resulting in its dissociation from the membrane upon completion of the cycle. In addition, the study outlines a successful approach to transform membrane associated proteins, which tend to aggregate upon purification, into a monomeric and soluble form. 相似文献
992.
Labroli M Paruch K Dwyer MP Alvarez C Keertikar K Poker C Rossman R Duca JS Fischmann TO Madison V Parry D Davis N Seghezzi W Wiswell D Guzi TJ 《Bioorganic & medicinal chemistry letters》2011,21(1):471-474
Previous efforts by our group have established pyrazolo[1,5-a]pyrimidine as a viable core for the development of potent and selective CDK inhibitors. As part of an effort to utilize the pyrazolo[1,5-a]pyrimidine core as a template for the design and synthesis of potent and selective kinase inhibitors, we focused on a key regulator in the cell cycle progression, CHK1. Continued SAR development of the pyrazolo[1,5-a]pyrimidine core at the C5 and C6 positions, in conjunction with previously disclosed SAR at the C3 and C7 positions, led to the discovery of potent and selective CHK1 inhibitors. 相似文献
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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.
Moltedo JM Abello M Gustavo S Javier C Delucis PG 《Indian pacing and electrophysiology journal》2011,11(4):126-128
An 18 month old 14 kg male with symptomatic Brugada syndrome underwent placement of an epicardial automatic implantable cardiac defibrillator using a single coil transvenous lead sutured to the anterolateral aspect of the left ventricle. 相似文献
997.
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
998.
Gortazar C Torres MJ Acevedo P Aznar J Negro JJ de la Fuente J Vicente J 《BMC microbiology》2011,11(1):27
Background
We describe the diversity of two kinds of mycobacteria isolates, environmental mycobacteria and Mycobacterium bovis collected from wild boar, fallow deer, red deer and cattle in Do?ana National Park (DNP, Spain), analyzing their association with temporal, spatial and environmental factors. 相似文献999.
The 'hygiene hypothesis', or lack of microbial and parasite exposure during early life, is postulated as an explanation for the recent increase in autoimmune and allergic diseases in developed countries. The favored mechanism is that microbial and parasite-derived products interact directly with pathogen recognition receptors to subvert proinflammatory signaling via T regulatory cells, thereby inducing anti-inflammatory effects and control of autoimmune disease. Parasites, such as helminths, are considered to have a major role in the induction of immune regulatory mechanisms among children living in developing countries. Invoking Occam's razor, we believe we can select an alternative mechanism to explain the hygiene hypothesis, based on antibody-mediated inhibition of immune responses that may more simply explain the available evidence. 相似文献
1000.