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排序方式: 共有748条查询结果,搜索用时 15 毫秒
71.
MicroRNA (miRNA) transcriptome of mouse retina and identification of a sensory organ-specific miRNA cluster 总被引:6,自引:0,他引:6
72.
Dual-surface-modified bacteriophage MS2 as an ideal scaffold for a viral capsid-based drug delivery system 总被引:2,自引:0,他引:2
Kovacs EW Hooker JM Romanini DW Holder PG Berry KE Francis MB 《Bioconjugate chemistry》2007,18(4):1140-1147
With the development of covalent modification strategies for viral capsids comes the ability to convert them into modular carrier systems for drug molecules and imaging agents. With this overall goal in mind, we have used two orthogonal modification strategies to decorate the exterior surface of genome-free MS2 capsids with PEG chains, while installing 50-70 copies of a fluorescent dye inside as a drug cargo mimic. Despite the very high levels of modification, the capsids remained in the assembled state, as determined by TEM, size-exclusion chromatography, and dynamic light scattering analysis. The ability of the polymer coating to block the access of polyclonal antibodies to the capsid surface was probed using a sandwich ELISA, which indicated a 90% reduction in binding. Further experiments indicated that biotin groups placed at the distal ends of the polymer chains were still capable of binding to streptavidin, despite their proximity to the PEG layer. Finally, a modular strategy was developed for the attachment of small-molecule targeting groups to the polymer chains through an efficient oxime formation reaction. As a result of these studies, a robust and versatile new platform has emerged for the potential delivery of therapeutic cargo. 相似文献
73.
MOTIVATION: Efficient fitting tools are needed to take advantage of a fast growth of atomic models of protein domains from crystallography or comparative modeling, and low-resolution density maps of larger molecular assemblies. Here, we report a novel fitting algorithm for the exhaustive and fast overlay of partial high-resolution models into a low-resolution density map. The method incorporates a fast rotational search based on spherical harmonics (SH) combined with a simple translational scanning. RESULTS: This novel combination makes it possible to accurately dock atomic structures into low-resolution electron-density maps in times ranging from seconds to a few minutes. The high-efficiency achieved with simulated and experimental test cases preserves the exhaustiveness needed in these heterogeneous-resolution merging tools. The results demonstrate its efficiency, robustness and high-throughput coverage. AVAILABILITY: http://sbg.cib.csic.es/Software/ADP_EM. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. 相似文献
74.
Rad51, a eukaryotic homolog of RecA, is an important protein involved in DNA recombination and repair. We have characterized rad51 of Pneumocystis carinii and Pneumocystis murina. rad51 is a single copy gene that encodes a 1.2 kb mRNA, which contains an open reading frame encoding 343 amino acids. Rad51 from Pneumocystis showed high homology to those from yeast. ATP binding motifs GEFRTGKS and LLIVD, similar to those of Saccharomyces cerevisiae and Schizosaccharomyces pombe, are conserved in Pneumocystis Rad51. The recombinant protein when expressed in E. coli showed DNA-dependent ATPase activity. Since Rad51 is a key enzyme in DNA repair and recombination, it potentially plays an important role in the recombination process leading to antigenic variation and thereby resistance to host immune responses in Pneumocystis. 相似文献
75.
This paper analyses the effect of microclimatic factors (internal soil temperature, surface temperature and surface relative
humidity) on surface activity of Messor barbarus harvester ants. We selected 44 colonies in an area of Mediterranean grassland
near Madrid (Central Spain), which were monitored for activity between March 1998 and September 1999. Results indicate that
microclimatic factors are good predictors of colony activation and intensity of activity. Colonies became active above certain
critical values of internal soil temperature and relative humidity. For active colonies, surface temperature was the main
regulatory factor for worker departure rate, which peaked at around 25–30°C. Worker speed was positively correlated with surface
temperature, although the relationship was weaker for large-sized workers. Microclimatic factors were not enough, however,
to predict task allocation outside the nest. The explanation for this aspect of ant behavior probably requires the inclusion
of biotic factors in the models. 相似文献
76.
Kim DY Carey BW Wang H Ingano LA Binshtok AM Wertz MH Pettingell WH He P Lee VM Woolf CJ Kovacs DM 《Nature cell biology》2007,9(7):755-764
BACE1 activity is significantly increased in the brains of Alzheimer's disease patients, potentially contributing to neurodegeneration. The voltage-gated sodium channel (Na(v)1) beta2-subunit (beta2), a type I membrane protein that covalently binds to Na(v)1 alpha-subunits, is a substrate for BACE1 and gamma-secretase. Here, we find that BACE1-gamma-secretase cleavages release the intracellular domain of beta2, which increases mRNA and protein levels of the pore-forming Na(v)1.1 alpha-subunit in neuroblastoma cells. Similarly, endogenous beta2 processing and Na(v)1.1 protein levels are elevated in brains of BACE1-transgenic mice and Alzheimer's disease patients with high BACE1 levels. However, Na(v)1.1 is retained inside the cells and cell surface expression of the Na(v)1 alpha-subunits and sodium current densities are markedly reduced in both neuroblastoma cells and adult hippocampal neurons from BACE1-transgenic mice. BACE1, by cleaving beta2, thus regulates Na(v)1 alpha-subunit levels and controls cell-surface sodium current densities. BACE1 inhibitors may normalize membrane excitability in Alzheimer's disease patients with elevated BACE1 activity. 相似文献
77.
Identification of motivational state in adult male Atlantic walruses inferred from changes in movement and diving behavior 下载免费PDF全文
Andrew D. Lowther Kit M. Kovacs David Griffiths Christian Lydersen 《Marine Mammal Science》2015,31(4):1291-1313
Motivational changes in animals are likely to be detectable retrospectively through observed changes in behavior. Breeding represents one of the strongest motivational states in mammals, and its timing is often tied to a seasonally optimal suite of environmental and physical conditions. While seasonal changes in behavior may be directly observable in some species, for others that breed cryptically or in difficult to access areas, detecting behavioral changes may only be feasible using data collected remotely. Herein, we explore whether behavioral changes can be used to infer motivational state for a wild, free‐ and wide‐ranging high arctic marine mammal, adult male Atlantic walruses (Odobenus rosmarus rosmarus). Using satellite‐relayed location and dive data from 23 adult male walruses instrumented in the Svalbard Archipelago, we identify seasonal movement to discrete geographic regions deep into winter pack ice. Adult male walrus diving behavior underwent marked seasonal movements between geographical areas that coincided with changes in light regime. At offshore wintering sites adult males (n = 4) shifted from a summer pattern of deep, long benthic dives to much shallower diving. Some males performed similar shallow, winter dive behavior at coastal locations (n = 12) suggesting that breeding might also occur around the coast of Svalbard. However, interpretation of behavioral changes of these coastal individuals was challenging. The presumed breeding sites at the winter off‐shore locations were situated in areas where polynyas are known to occur, making them a predictable resource even if they are located deep inside the winter pack‐ice. We demonstrate that remotely collected behavioral data can be used to identify seasonally explicit changes in the behavior of cryptic species. 相似文献
78.
Christine A. Bricault James M. Kovacs Joseph P. Nkolola Karina Yusim Elena E. Giorgi Jennifer L. Shields James Perry Christy L. Lavine Ann Cheung Katharine Ellingson-Strouss Cecelia Rademeyer Glenda E. Gray Carolyn Williamson Leonidas Stamatatos Michael S. Seaman Bette T. Korber Bing Chen Dan H. Barouch 《Journal of virology》2015,89(5):2507-2519
79.
Susan R. Kahn Ian Shrier Stan Shapiro Adrielle H. Houweling Andrew M. Hirsch Robert D. Reid Clive Kearon Khalil Rabhi Marc A. Rodger Michael J. Kovacs David R. Anderson Philip S. Wells 《CMAJ》2011,183(1):37-44
Background
Exercise training may have the potential to improve post-thrombotic syndrome, a frequent, chronic complication of deep venous thrombosis. We conducted a randomized controlled two-centre pilot trial to assess the feasibility of a multicentre-based evaluation of a six-month exercise training program to treat post-thrombotic syndrome and to obtain preliminary data on the effectiveness of such a program.Methods
Patients were randomized to receive exercise training (a six-month trainer-supervised program) or control treatment (an education session with monthly phone follow-ups). Levels of eligibility, consent, adherence and retention were used as indicators of study feasibility. Primary outcomes were change from baseline to six months in venous disease-specific quality of life (as measured using the Venous Insufficiency Epidemiological and Economic Study Quality of Life [VEINES-QOL] questionnaire) and severity of post-thrombotic syndrome (as measured by scores on the Villalta scale) in the exercise training group versus the control group, assessed by t tests. Secondary outcomes were change in generic quality of life (as measured using the Short-Form Health Survey-36 [SF-36] questionnaire), category of severity of post-thrombotic syndrome, leg strength, leg flexibility and time on treadmill.Results
Of 95 patients with post-thrombotic syndrome, 69 were eligible, 43 consented and were randomized, and 39 completed the study. Exercise training was associated with improvement in VEINES-QOL scores (exercise training mean change 6.0, standard deviation [SD] 5.1 v. control mean change 1.4, SD 7.2; difference 4.6, 95% CI 0.54 to 8.7; p = 0.027) and improvement in scores on the Villalta scale (exercise training mean change −3.6, SD 3.7 v. control mean change −1.6, SD 4.3; difference −2.0, 95% CI −4.6 to 0.6; p = 0.14). Most secondary outcomes also showed greater improvement in the exercise training group.Interpretation
Exercise training may improve post-thrombotic syndrome. It would be feasible to definitively evaluate exercise training as a treatment for post-thrombotic syndrome in a large multicentre trial.Chronic post-thrombotic syndrome develops in up to one-half of patients with deep venous thrombosis and is associated with varying combinations of leg pain, heaviness, swelling, edema, hyperpigmentation and varicose collateral veins. In severe instances, lipodermatosclerosis and venous ulcers occur.1 Patients with post-thrombotic syndrome have substantially impaired quality of life.2,3 Given that effective treatments are lacking, new approaches to managing post-thrombotic syndrome are needed.4Exercise training is an effective treatment for arterial claudication5,6 and may also improve post-thrombotic syndrome.7 Potential mechanisms include improved endurance resulting from increased aerobic capacity, reduced muscular effort from improved strength, reduced swelling and discomfort via improved function of the calf muscle pump and improved muscu-loskeletal function via increased flexibility of ankle and knee joints.8,9We performed a pilot trial to obtain data on the effectiveness of exercise training to treat post-thrombotic syndrome and to assess the feasibility of performing a multicentre study to address this question. 相似文献80.
Lisa Langsetmo Tuan V. Nguyen Nguyen D. Nguyen Christopher S. Kovacs Jerilynn C. Prior Jacqueline R. Center Suzanne Morin Robert G. Josse Jonathan D. Adachi David A. Hanley John A. Eisman the Canadian Multicentre Osteoporosis Study Research Group 《CMAJ》2011,183(2):E107-E114