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蓖麻蚕Philosamia cynthia ricni血淋巴含两种凝集素,一种凝集兔新鲜红血球,凝血活力被L-鼠李糖和D-半乳糖抑制;另一种凝集戊二醛固定的人和鸡的红血球,凝血活力被岩藻糖抑制.它们在蚕的不同生长阶段及在蚕体各组织中的分布和凝血活力显著不同.血淋巴中这两种凝集素的凝血活力明显比其他组织中高.卵中测不到这两种凝集素活力.本文对这两种凝集素在蚕体中可能的生理功能进行了讨论. 相似文献
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Directed evolution of human T-cell receptors with picomolar affinities by phage display 总被引:6,自引:0,他引:6
Li Y Moysey R Molloy PE Vuidepot AL Mahon T Baston E Dunn S Liddy N Jacob J Jakobsen BK Boulter JM 《Nature biotechnology》2005,23(3):349-354
Peptides derived from almost all proteins, including disease-associated proteins, can be presented on the cell surface as peptide-human leukocyte antigen (pHLA) complexes. T cells specifically recognize pHLA with their clonally rearranged T-cell receptors (TCRs), whose natural affinities are limited to approximately 1-100 muM. Here we describe the display of ten different human TCRs on the surface of bacteriophage, stabilized by a nonnative interchain disulfide bond. We report the directed evolution of high-affinity TCRs specific for two different pHLAs: the human T-cell lymphotropic virus type 1 (HTLV-1) tax(11-19) peptide-HLA-A(*)0201 complex and the NY-ESO-1(157-165) tumor-associated peptide antigen-HLA-A(*)0201 complex, with affinities of up to 2.5 nM and 26 pM, respectively, and we demonstrate their high specificity and sensitivity for targeting of cell-surface pHLAs. 相似文献
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Background
Estimators of free energies are routinely used to judge the quality of protein structural models. As these estimators still present inaccuracies, they are frequently evaluated by discriminating native or native-like conformations from large ensembles of so-called decoy structures. 相似文献24.
BackgroundPractice facilitation (PF), a multifaceted approach in which facilitators (external health care professionals) help family physicians to improve their adoption of best practices, has been highly successful. Improved Delivery of Cardiovascular Care (IDOCC) was an innovative PF trial designed to improve evidence-based care for people who have, or are at risk of, cardiovascular disease (CVD). The intervention was found to be ineffective as assessed by a patient-level composite score based on chart reviews from a subsample of patients (N = 5292). Here, we used population-based administrative data to examine IDOCC’s effect on CVD-related hospitalizations.MethodsIDOCC used a pragmatic, stepped wedge cluster randomized controlled design involving primary care providers recruited across Eastern Ontario, Canada. IDOCC’s effect on CVD-related hospitalizations was assessed in the 2 years of active intervention and post-intervention years. Marginal and mixed-effects regression analyses were used to account for the study design and to control for patient, physician, and practice characteristics. Secondary and subgroup analyses investigated robustness.ResultsOur sample included 262,996 patient/year observations representing 54,085 unique patients who had, or were at risk of, CVD, from 70 practices. There was a strong decreasing secular trend in CVD-related hospitalizations but no statistically significant effect of IDOCC. Relative to patients in the control condition, patients in the intervention condition were estimated to have 4 % lower odds of CVD-related hospitalizations (adjOR = 0.96, 99 % CI 0.83 to 1.11). The nonsignificant result persisted across robustness analyses.ConclusionsClinical outcomes from administrative databases were examined to form a more complete picture of the (in)effectiveness of a large-scale quality improvement intervention. IDOCC did not have a significant effect on CVD hospitalizations, suggesting that the results from the primary composite adherence score analysis were neither due to choice of outcome nor relatively short follow-up period.
Trial registration
ClinicalTrials.gov , registered on 14 December 2007. NCT00574808Electronic supplementary material
The online version of this article (doi:10.1186/s13063-016-1547-2) contains supplementary material, which is available to authorized users. 相似文献25.
Increased atmospheric CO2 will have a twofold impact on future marine ecosystems, increasing global sea surface temperatures and uptake of CO2 (Ocean Acidification). Many experiments focus on the investigation of one of these stressors, but under realistic future climate predictions, these stressors may have interactive effects on individuals. Here, we investigate the effect of warming and acidification in combination. We test for interactive effects of potential near-future (2100) temperature (+2 to 3 °C) and pCO2 (~860–940 μAtm) levels on the physiology of the tropical echinoid Echinometra sp. A. The greatest reduction in growth was under simultaneous temperature and pH/pCO2 stress (marginally significant temperature × pH/pCO2 interaction). This was mirrored by the physiological data, with highest metabolic activity (measured as respiration and ammonium excretion) occurring at the increased temperature and pCO2 treatment, although this was not significant for excretion. The perivisceral coelomic fluid pH was ~7.5–7.6, as typical for echinoids, and showed no significant changes between treatments. Indicative of active calcification, internal magnesium and calcium concentrations were reduced compared to the external medium, but were not different between treatments. Gonad weight was lower at the higher temperature, and this difference was more distinct and statistically significant for males. The condition of the gonads assessed by histology declined in increased temperature and low pH treatments. The Echinometra grew in all treatments indicating active calcification of their magnesium calcite tests even as carbonate mineral saturation decreased. Our results indicate that the interactive temperature and pH effects are more important for adult echinoids than individual stressors. Although adult specimens grow and survive in near-future conditions, higher energy demands may influence gonad development and thus population maintenance. 相似文献
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Sven Uthicke Danilo Pecorino Rebecca Albright Andrew Peter Negri Neal Cantin Michelle Liddy Symon Dworjanyn Pamela Kamya Maria Byrne Miles Lamare 《PloS one》2013,8(12)
Coral reefs are marine biodiversity hotspots, but their existence is threatened by global change and local pressures such as land-runoff and overfishing. Population explosions of coral-eating crown of thorns sea stars (COTS) are a major contributor to recent decline in coral cover on the Great Barrier Reef. Here, we investigate how projected near-future ocean acidification (OA) conditions can affect early life history stages of COTS, by investigating important milestones including sperm motility, fertilisation rates, and larval development and settlement. OA (increased pCO2 to 900–1200 µatm pCO2) significantly reduced sperm motility and, to a lesser extent, velocity, which strongly reduced fertilization rates at environmentally relevant sperm concentrations. Normal development of 10 d old larvae was significantly lower under elevated pCO2 but larval size was not significantly different between treatments. Settlement of COTS larvae was significantly reduced on crustose coralline algae (known settlement inducers of COTS) that had been exposed to OA conditions for 85 d prior to settlement assays. Effect size analyses illustrated that reduced settlement may be the largest bottleneck for overall juvenile production. Results indicate that reductions in fertilisation and settlement success alone would reduce COTS population replenishment by over 50%. However, it is unlikely that this effect is sufficient to provide respite for corals from other negative anthropogenic impacts and direct stress from OA and warming on corals. 相似文献
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Florian Madura Pierre J. Rizkallah Kim M. Miles Christopher J. Holland Anna M. Bulek Anna Fuller Andrea J. A. Schauenburg John J. Miles Nathaniel Liddy Malkit Sami Yi Li Moushumi Hossain Brian M. Baker Bent K. Jakobsen Andrew K. Sewell David K. Cole 《The Journal of biological chemistry》2013,288(26):18766-18775
The T-cell receptor (TCR) recognizes peptides bound to major histocompatibility molecules (MHC) and allows T-cells to interrogate the cellular proteome for internal anomalies from the cell surface. The TCR contacts both MHC and peptide in an interaction characterized by weak affinity (KD = 100 nm to 270 μm). We used phage-display to produce a melanoma-specific TCR (α24β17) with a 30,000-fold enhanced binding affinity (KD = 0.6 nm) to aid our exploration of the molecular mechanisms utilized to maintain peptide specificity. Remarkably, although the enhanced affinity was mediated primarily through new TCR-MHC contacts, α24β17 remained acutely sensitive to modifications at every position along the peptide backbone, mimicking the specificity of the wild type TCR. Thermodynamic analyses revealed an important role for solvation in directing peptide specificity. These findings advance our understanding of the molecular mechanisms that can govern the exquisite peptide specificity characteristic of TCR recognition. 相似文献
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We compared histochemical and immunohistochemical staining as well as fluorochrome labeling in murine bone specimens that were fixed with 10% neutral buffered formalin to those fixed with HistoChoice®. We showed that sections from undecalcified tibiae fixed for 4 h in HistoChoice® resulted in enhanced toluidine blue and Von Kossa histochemical staining compared to formalin fixation. HistoChoice® produced comparable or improved staining for alkaline phosphatase. Acid phosphatase localization was better in formalin fixed specimens, but osteoclasts were visuralized more easily in HistoChoice® fixed specimens. As expected, immunohistochemical labeling was antibody dependent; some antibodies labeled better in HistoChoice® fixed specimens while others were better in formalin fixed specimens. Toluidine blue, Von Kossa, and alkaline phosphatase staining of sections fixed for 12 h produced sections that were similar to 4 h fixed sections. Fixation for 12 h preserved acid phosphatase activity better. Increasing fixation to 12 h affected immunolocalization differentially. Bone sialoprotein labeling in HistoChoice® fixed specimens was comparable to formalin fixed samples. On the other hand, after 12 h formalin fixation, osteocalcin labeling was comparable to HistoChoice®. For most histochemical applications, fixing murine bone specimens for 4 h with HistoChoice® yielded superior staining compared to formalin fixation. If immunohistochemical localization is desired, however, individual antibodies must be tested to determine which fixation process retains antigenicity better. In addition, there was no detectable difference in the intensity of fluorochrome labeling using either fixative. Finally, fixation duration did not alter the intensity of labeling. 相似文献
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