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排序方式: 共有329条查询结果,搜索用时 15 毫秒
281.
Marina Angelini Arash Pezhouman Nicoletta Savalli Marvin G. Chang Federica Steccanella Kyle Scranton Guillaume Calmettes Michela Ottolia Antonios Pantazis Hrayr S. Karagueuzian James N. Weiss Riccardo Olcese 《The Journal of general physiology》2021,153(12)
Ventricular arrhythmias, a leading cause of sudden cardiac death, can be triggered by cardiomyocyte early afterdepolarizations (EADs). EADs can result from an abnormal late activation of L-type Ca2+ channels (LTCCs). Current LTCC blockers (class IV antiarrhythmics), while effective at suppressing EADs, block both early and late components of ICa,L, compromising inotropy. However, computational studies have recently demonstrated that selective reduction of late ICa,L (Ca2+ influx during late phases of the action potential) is sufficient to potently suppress EADs, suggesting that effective antiarrhythmic action can be achieved without blocking the early peak ICa,L, which is essential for proper excitation–contraction coupling. We tested this new strategy using a purine analogue, roscovitine, which reduces late ICa,L with minimal effect on peak current. Scaling our investigation from a human CaV1.2 channel clone to rabbit ventricular myocytes and rat and rabbit perfused hearts, we demonstrate that (1) roscovitine selectively reduces ICa,L noninactivating component in a human CaV1.2 channel clone and in ventricular myocytes native current, (2) the pharmacological reduction of late ICa,L suppresses EADs and EATs (early after Ca2+ transients) induced by oxidative stress and hypokalemia in isolated myocytes, largely preserving cell shortening and normal Ca2+ transient, and (3) late ICa,L reduction prevents/suppresses ventricular tachycardia/fibrillation in ex vivo rabbit and rat hearts subjected to hypokalemia and/or oxidative stress. These results support the value of an antiarrhythmic strategy based on the selective reduction of late ICa,L to suppress EAD-mediated arrhythmias. Antiarrhythmic therapies based on this idea would modify the gating properties of CaV1.2 channels rather than blocking their pore, largely preserving contractility. 相似文献
282.
Konstantinos Voulgaris Anastasios Varkoulis Stefanos Zaoutsos Antonios Stratakis Dimitris Vafidis 《Ecology and evolution》2021,11(24):17734
In the Mediterranean, Paracentrotus lividus and Sphaerechinus granularis are important drivers of benthic ecosystems, often coexisting in sublittoral communities. However, the introduction of the invasive diadematoid Diadema setosum, which utilizes venomous spines, may affect these communities. To describe the mechanical properties of the test and spines of these three species, specimens were collected in winter of 2019 from the sublittoral zone of the Dodecanese island complex, southeastern Aegean Sea. This region serves as a gateway for invasive species to the Mediterranean Sea. Crushing test was conducted on live individuals, while 3‐point bending test was used to estimate spine stiffness. Porosity and mineralogy of the test and spine, thickness of the test, and breaking length of the spine were measured and compared, while the microstructural architecture was also determined. The test of S. granularis was the most robust (194.35 ± 59.59 N), while the spines of D. setosum (4.76 ± 2.13 GPa) exhibited highest flexibility. Increased porosity and thickness of the test were related to increased robustness, whereas increased flexibility of the spine was attributed to high porosity, indicating that porosity in the skeleton plays a key role in preventing fracture. The spines of S. granularis exhibited highest length after fracture % (71.54 ± 5.5%). D. setosum exhibited higher values of Mg concentration in the test (10%) compared with the spines (4%). For the first time, the mineralogy of an invasive species is compared with its native counterpart, while a comparison of the mechanical properties of different species of the same ecosystem also takes place. This study highlights different ways, in which sea urchins utilize their skeleton and showcases the ecological significance of these adaptations, one of which is the different ways of utilization of the skeleton for defensive purposes, while the other is the ability of D. setosum to decrease the Mg % of its skeleton degrading its mechanical properties, without compromising its defense, by depending on venomous bearing spines. This enables this species to occupy not only tropical habitats, where it is indigenous, but also temperate like the eastern Mediterranean, which it has recently invaded. 相似文献
283.
Kelarakis A Castelletto V Krysmann MJ Havredaki V Viras K Hamley IW 《Biomacromolecules》2008,9(5):1366-1371
The interactions of bovine serum albumin (BSA) with three ethylene oxide/butylene oxide (E/B) copolymers having different block lengths and varying molecular architectures is examined in this study in aqueous solutions. Dynamic light scattering (DLS) indicates the absence of BSA-polymer binding in micellar systems of copolymers with lengthy hydrophilic blocks. On the contrary, stable protein-polymer aggregates were observed in the case of E 18B 10 block copolymer. Results from DLS and SAXS suggest the dissociation of E/B copolymer micelles in the presence of protein and the absorption of polymer chains to BSA surface. At high protein loadings, bound BSA adopts a more compact conformation in solution. The secondary structure of the protein remains essentially unaffected even at high polymer concentrations. Raman spectroscopy was used to give insight to the configurations of the bound molecules in concentrated solutions. In the vicinity of the critical gel concentration of E 18B 10 introduction of BSA can dramatically modify the phase diagram, inducing a gel-sol-gel transition. The overall picture of the interaction diagram of the E 18B 10-BSA reflects the shrinkage of the suspended particles due to destabilization of micelles induced by BSA and the gelator nature of the globular protein. SAXS and rheology were used to further characterize the structure and flow behavior of the polymer-protein hybrid gels and sols. 相似文献
284.
Antonios D. Mazaris Athanasios S. Kallimanis John D. Pantis 《Journal of experimental marine biology and ecology》2008,367(2):219-226
Global climate change is likely to have an important influence on the phenology, behaviour and population dynamics of many species. We investigate climatic related changes in the breeding phenology of Mediterranean loggerhead marine turtles Caretta caretta over a 19 year period and the potential relationship between these changes and reproductive success and performance. We found that the studied population has experienced fluctuating sea surface temperatures (SST) with an increasing trend during the last century. With increasing spring SST there is a trend towards earlier nesting. However, there is no significant relationship between SST and nesting season, defined as the duration between the first recorded emergence and the last nest laid. Our analyses indicate that marine turtles display phenological changes, and thus maintain favorable thermal conditions at the nesting sites. Furthermore, increasing spring SST was correlated with decreasing clutch size and increasing hatching success that resulted in an apparent lack of correlation between SST and hatchling production. This apparent independence might be misleading since it only holds for a limited range of SST values. Thus, if we estimate the effect of climate change on loggerhead population growth as neutral, based on the apparent independence between SST and total number of hatchlings, we will be underestimating the population extinction risk. 相似文献
285.
In many ecological communities, extinctions following habitat loss do not happen immediately. Understanding this delay is a major challenge, with conservation implications. In this issue, Otsu et al. show how landscape and management features affect the time lag. With this research as a starting point, we highlight the gaps and challenges still remaining in the study of extinction debt, especially in plant communities. 相似文献
286.
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289.
A novel hydrogel system based on oligo(poly(ethylene glycol) fumarate) (OPF) is currently being investigated as an injectable carrier for marrow stromal cells (MSCs) for orthopedic tissue engineering applications. This hydrogel is cross-linked using the redox radical initiators ammonium persulfate (APS) and ascorbic acid (AA). In this study, two different persulfate oxidizing agents (APS and sodium persulfate (NaPS)) with three reducing agents derived from ascorbic acid (AA, sodium ascorbate (Asc), and magnesium ascorbate-2-phosphate (Asc-2)) and their combinations were examined to determine the relationship between pH, exposure time, and cytotoxicity for rat MSCs. In addition, gelation times for specific combinations were determined using rheometry. pH and cell viability data after 2 h for combinations ranging from 10 to 500 mM in each reagent showed that there was a smaller pH change and a corresponding higher viability at lower concentrations, regardless of the reagents used. At 10 mM, there was less than a 1.5 unit drop in pH and greater than 90% viability for all initiator combinations examined. However, MSC viability was significantly reduced with concentrations of 100 mM and higher of the initiator combinations. At 100 mM, exposure to NaPS/Asc-2 resulted in significantly more live cells than exposure to APS/AA or NaPS/Asc, but at this concentration, NaPS/Asc-2 exhibited significantly longer OPF gelation onset times than APS/AA. At all combination concentrations, exposure time (10 min vs 2 h) did not significantly affect MSC viability. These data indicate that final pH and/or radical formation have a large impact on MSC viability and that multiple, intertwined testing procedures are required for identification of appropriate initiators for cell encapsulation applications. 相似文献
290.
Parissis JT Adamopoulos S Venetsanou K Kostakis G Rigas A Karas SM Kremastinos D 《European cytokine network》2004,15(2):139-144
No in vivo data exist about the relationship of circulating granulocyte-macrophage colony stimulating factor (GM-CSF) and soluble adhesion molecules ICAM-1 and VCAM-1 (sICAM-1 and sVCAM-1) to the severity of acute myocardial infarction (AMI) and the pathophysiological events of post-infarction left ventricular dysfunction. We investigated the kinetics of these inflammatory mediators in the plasma of patients with AMI, and correlated the findings with the clinical severity of the disease during the first week of hospitalization as well as the degree of left ventricular dysfunction one month after the AMI. Plasma levels of inflammatory markers were determined in 41 AMI patients (all received thrombolytic treatment) by ELISA assays, serially during the first week of hospitalization and one month after hospital admission. Patients (n = 20) with uncomplicated AMI (Killip class I) were classified as group A, patients (n = 21) with AMI complicated by heart failure manifestations (Killip classes II and III) were classified as group B, while 20 age- and sex-matched volunteers were used as healthy controls. A sustained increase in GM-CSF, sICAM-1 and sVCAM-1 plasma concentrations was observed only in group B during the first week of the study. Patients from group B exhibited significantly higher levels of GM-CSF (P < 0.01), sICAM-1 (P < 0.05) and sVCAM-1 (P < 0.01) than patients from group A and the healthy controls (P < 0.001). In group B patients, significant correlations were observed between the peak of GM-CSF levels and the peak of serum creatine kinase-MB (r = 0.42; P < 0.05), white blood cell counts (r = 0.67; P < 0.001) and LVEF (r =- 0.51; P < 0.01). At one month follow-up, patients (n = 17) with severe post-infarction left ventricular dysfunction (LVEF 35%). Significant correlations were observed between GM-CSF levels and left ventricular end-diastolic volume index (r = 0.55; P < 0.001) or left ventricular end-systolic volume index (r = 0.49; P = 0.001). We have found a significant elevation of plasma GM-CSF and soluble adhesion molecules during the course of AMI, with the highest values in patients with AMI complicated by heart failure manifestations and severe left ventricular dysfunction. These monocyte-related inflammatory mediators may actively contribute to the pathophysiology of the disease and post-infarction cardiac dysfunction. 相似文献