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排序方式: 共有2331条查询结果,搜索用时 109 毫秒
71.
Avi Z. Rosenberg Michael D. Armani Patricia A. Fetsch Liqiang Xi Tina Thu Pham Mark Raffeld Yun Chen Neil O’Flaherty Rebecca Stussman Adele R. Blackler Qiang Du Jeffrey C. Hanson Mark J. Roth Armando C. Filie Michael H. Roh Michael R. Emmert-Buck Jason D. Hipp Michael A. Tangrea 《PloS one》2016,11(3)
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Lukas Jaroslaw Motloch Robert Larbig Tina Gebing Sara Reda Astrid Schwaiger Johannes Leitner Martin Wolny Lars Eckardt Uta C. Hoppe 《PloS one》2016,11(2)
Introduction
The possible role of UCP2 in modulating mitochondrial Ca2+-uptake (mCa2+-uptake) via the mitochondrial calcium uniporter (MCU) is highly controversial.Methods
Thus, we analyzed mCa2+-uptake in isolated cardiac mitochondria, MCU single-channel activity in cardiac mitoplasts, dual Ca2+-transients from mitochondrial ((Ca2+)m) and intracellular compartment ((Ca2+)c) in the whole-cell configuration in cardiomyocytes of wild-type (WT) and UCP2-/- mice.Results
Isolated mitochondria showed a Ru360 sensitive mCa2+-uptake, which was significantly decreased in UCP2-/- (229.4±30.8 FU vs. 146.3±23.4 FU, P<0.05). Single-channel registrations confirmed a Ru360 sensitive voltage-gated Ca2+-channel in mitoplasts, i.e. mCa1, showing a reduced single-channel activity in UCP2-/- (Po,total: 0.34±0.05% vs. 0.07±0.01%, P<0.05). In UCP2-/- cardiomyocytes (Ca2+)m was decreased (0.050±0.009 FU vs. 0.021±0.005 FU, P<0.05) while (Ca2+)c was unchanged (0.032±0.002 FU vs. 0.028±0.004 FU, P>0.05) and transsarcolemmal Ca2+-influx was inhibited suggesting a possible compensatory mechanism. Additionally, we observed an inhibitory effect of ATP on mCa2+-uptake in WT mitoplasts and (Ca2+)m of cardiomyocytes leading to an increase of (Ca2+)c while no ATP dependent effect was observed in UCP2-/-.Conclusion
Our results indicate regulatory effects of UCP2 on mCa2+-uptake. Furthermore, we propose, that previously described inhibitory effects on MCU by ATP may be mediated via UCP2 resulting in changes of excitation contraction coupling. 相似文献74.
Michael E. Hall Tina E. Brinkley Haroon Chughtai Timothy M. Morgan Craig A. Hamilton Jennifer H. Jordan R. Brandon Stacey Sandra Soots W. Gregory Hundley 《PloS one》2016,11(1)
Background
Obesity and visceral adiposity are increasingly recognized risk factors for cardiovascular disease. Visceral fat may reduce myocardial perfusion by impairing vascular endothelial function. Women experience more anginal symptoms compared to men despite less severe coronary artery stenosis, as assessed by angiography. Women and men have different fat storage patterns which may account for the observed differences in cardiovascular disease. Therefore, our objective was to evaluate the relationship between visceral adipose tissue distributions and myocardial perfusion in men and women.Methods
Visceral and subcutaneous fat distributions and myocardial perfusion were measured in 69 men and women without coronary artery disease using magnetic resonance imaging techniques. Myocardial perfusion index was quantified after first-pass perfusion with gadolinium contrast at peak dose dobutamine stress.Results
We observed inverse relationships between female gender (r = -0.35, p = 0.003), pericardial fat (r = -0.36, p = 0.03), intraperitoneal fat (r = -0.37, p = 0.001), and retroperitoneal fat (r = -0.36, p = 0.002) and myocardial perfusion index. Visceral fat depots were not associated with reduced myocardial perfusion at peak dose dobutamine in men. However, in women, BMI (r = -0.33, p = 0.04), pericardial fat (r = -0.53, p = 0.02), subcutaneous fat (r = -0.39, p = 0.01) and intraperitoneal fat (r = -0.30, p = 0.05) were associated with reduced myocardial perfusion during dobutamine stress.Conclusions
Higher visceral fat volumes are associated with reduced left ventricular myocardial perfusion at peak dose dobutamine stress in women but not in men. These findings suggest that visceral fat may contribute to abnormal microcirculatory coronary artery perfusion syndromes, explaining why some women exhibit more anginal symptoms despite typically lower grade epicardial coronary artery stenoses than men. 相似文献75.
Dendritic cells (DC) play a pivotal role as antigen presenting cells (APC) and their maturation is crucial for effectively eliciting an antigen-specific immune response. The p41 splice variant of MHC class II-associated chaperone, called invariant chain p41 Ii, contains an amino acid sequence, the p41 fragment, which is a thyropin-type inhibitor of proteolytic enzymes. The effects of exogenous p41 fragment and related thyropin inhibitors acting on human immune cells have not been reported yet. In this study we demonstrate that exogenous p41 fragment can enter the endocytic pathway of targeted human immature DC. Internalized p41 fragment has contributed to the total amount of the immunogold labelled p41 Ii-specific epitope, as quantified by transmission electron microscopy, in particular in late endocytic compartments with multivesicular morphology where antigen processing and binding to MHC II take place. In cell lysates of treated immature DC, diminished enzymatic activity of cysteine proteases has been confirmed. Internalized exogenous p41 fragment did not affect the perinuclear clustering of acidic cathepsin S-positive vesicles typical of mature DC. p41 fragment is shown to interfere with the nuclear translocation of NF-κB p65 subunit in LPS-stimulated DC. p41 fragment is also shown to reduce the secretion of interleukin-12 (IL-12/p70) during the subsequent maturation of treated DC. The inhibition of proteolytic activity of lysosomal cysteine proteases in immature DC and the diminished capability of DC to produce IL-12 upon their subsequent maturation support the immunomodulatory potential of the examined thyropin from p41 Ii. 相似文献
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Ronja Breitkopf Ronny Uhlig Tina Drenckhan Ralf-Jörg Fischer 《Extremophiles : life under extreme conditions》2016,20(5):653-661
Moorella thermoacetica is one of the model acetogenic bacteria for the resolution of the Wood–Ljungdahl (acetyl-CoA) pathway in which CO2 is autotrophically assimilated yielding acetyl-CoA as central intermediate. Its further conversion into acetate relies on subsequent phosphotransacetylase (PTA) and acetate kinase reactions. However, the genome of M. thermoacetica contains no pta homologous gene. It has been speculated that the moth_0864 and moth_1181 gene products sharing similarities with an evolutionarily distinct phosphotransacylase involved in 1,2-propanediol utilization (PDUL) of Salmonella enterica act as PTAs in M. thermoacetica. Here, we demonstrate specific PTA activities with acetyl-CoA as substrate of 9.05 and 2.03 U/mg for the recombinant enzymes PDUL1 (Moth_1181) and PDUL2 (Moth_0864), respectively. Both showed maximal activity at 65 °C and pH 7.6. Native proteins (90 kDa) are homotetramers composed of four subunits with apparent molecular masses of about 23 kDa. Thus, one or both PDULs of M. thermoacetica might act as PTAs in vivo catalyzing the penultimate step of the Wood–Ljungdahl pathway toward the formation of acetate. In silico analysis underlined that up to now beside of M. thermoacetica, only Sporomusa ovata contains only PDUL like classIII-PTAs but no other phosphotransacetylases or phosphotransbutyrylases (PTBs). 相似文献
79.
Fatemeh Norozi Javad Mohammadi-asl Tina Vosoughi Mohammad Ali Jalali Far Amal Saki Malehi Najmaldin Saki 《生物学前沿》2016,11(5):404-411
Objectives
Targeted therapy of Philadelphia-positive ALL and CML patients using imatinib (IM) has caused significant changes in treatment course and has increased the survival of patients. A small group of patients show resistance to IM. Acquired mutations in tyrosine kinase domain of BCR-ABL protein are a mechanism for development of resistance. T315I is one of the most common acquired mutations in this domain, which occurs in ATP binding site and inhibits the formation of hydrogen bond with IM. The aim of this study was to evaluate the prevalence of this mutation in BCR/ABL-positive CML and ALL patients.Methods
To conduct this study, 60 BCR-ABL-positive patients (including 50 CML and 10 ALL patients) who were subject to treatment with IM were selected. After taking the samples, presence of T315I mutation was assessed using ARMS-PCR on cDNA and its polymorphism was evaluated by sequencing.Results
The results showed that among 60 patients, only three patients had T315I mutation, which was detected using ARMS technique. The three patients bearing mutation were afflicted with CML and no significant association was found between blood parameters with duration of treatment in presence of mutation.Conclusions
The mutation was found in three CML patients, which indicated lower likelihood and diagnostic value of this mutation in ALL patients. Given the negative direct sequencing results in T315I patients, it can be concluded that ARMS-PCR is a more sensitive technique when the number of cancer cells is low in patients during treatment.80.
Christopher B. Cooper Edward J. Beard lvaro Vzquez‐Mayagoitia Liliana Stan Gavin B. G. Stenning Daniel W. Nye Julian A. Vigil Tina Tomar Jingwen Jia Govardhana B. Bodedla Song Chen Lucía Gallego Santiago Franco Antonio Carella K. R. Justin Thomas Song Xue Xunjin Zhu Jacqueline M. Cole 《Liver Transplantation》2019,9(5)
Data‐driven materials discovery has become increasingly important in identifying materials that exhibit specific, desirable properties from a vast chemical search space. Synergic prediction and experimental validation are needed to accelerate scientific advances related to critical societal applications. A design‐to‐device study that uses high‐throughput screens with algorithmic encodings of structure–property relationships is reported to identify new materials with panchromatic optical absorption, whose photovoltaic device applications are then experimentally verified. The data‐mining methods source 9431 dye candidates, which are auto‐generated from the literature using a custom text‐mining tool. These candidates are sifted via a data‐mining workflow that is tailored to identify optimal combinations of organic dyes that have complementary optical absorption properties such that they can harvest all available sunlight when acting as co‐sensitizers for dye‐sensitized solar cells (DSSCs). Six promising dye combinations are shortlisted for device testing, whereupon one dye combination yields co‐sensitized DSSCs with power conversion efficiencies comparable to those of the high‐performance, organometallic dye, N719. These results demonstrate how data‐driven molecular engineering can accelerate materials discovery for panchromatic photovoltaic or other applications. 相似文献