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101.
Kurinchi S. Gurusamy Edward Wilson Ronald L. Koretz Victoria B. Allen Brian R. Davidson Andrew K. Burroughs Christian Gluud 《PloS one》2013,8(12)
Background
Randomised clinical trials (RCTs) of antiviral interventions in patients with chronic hepatitis C virus (HCV) infection use sustained virological response (SVR) as the main outcome. There is sparse information on long-term mortality from RCTs.Methods
We created a decision tree model based on a Cochrane systematic review on interferon retreatment for patients who did not respond to initial therapy or who relapsed following SVR. Extrapolating data to 20 years, we modelled the outcome from three scenarios: (1) observed medium-term (5 year) annual mortality rates continue to the long term (20 years); (2) long-term annual mortality in retreatment responders falls to that of the general population while retreatment non-responders continue at the medium-term mortality; (3) long-term annual mortality in retreatment non-responders is the same as control group non-responders (i.e., the increased treatment-related medium mortality “wears off”).Results
The mean differences in life expectancy over 20 years with interferon versus control in the first, second, and third scenarios were -0.34 years (95% confidence interval (CI) -0.71 to 0.03), -0.23 years (95% CI -0.69 to 0.24), and -0.01 (95% CI -0.3 to 0.27), respectively. The life expectancy was always lower in the interferon group than in the control group in scenario 1. In scenario 3, the interferon group had a longer life expectancy than the control group only when more than 7% in the interferon group achieved SVR.Conclusions
SVR may be a good prognostic marker but does not seem to be a valid surrogate marker for assessing HCV treatment efficacy of interferon retreatment. The SVR threshold at which retreatment increases life expectancy may be different for different drugs depending upon the adverse event profile and treatment efficacy. This has to be determined for each drug by RCTs and appropriate modelling before SVR can be accepted as a surrogate marker. 相似文献102.
María Victoria Martín Ayelén Mariana Distefano Eduardo Julián Zabaleta Gabriela Carolina Pagnussat 《Plant signaling & behavior》2013,8(10)
Previously considered as toxic by-products of aerobic metabolism, reactive oxygen species (ROS) are emerging as essential signaling molecules in eukaryotes. Recent evidence showed that maintenance of ROS homeostasis during female gametophyte development is crucial for embryo sac patterning and fertilization. Although ROS are exclusively detected in the central cell of mature embryo sacs, the study of mutants deficient in ROS homeostasis suggests that controlled oxidative bursts might take place earlier during gametophyte development. Also, a ROS burst that depends on pollination takes place inside the embryo sac. This oxidative response might be required for pollen tube growth arrest and for sperm cell release. In this mini-review, we will focus on new insights into the role of ROS during female gametophyte development and fertilization. Special focus will be made on the mitochondrial Mn-Superoxide dismutase (MSD1), which has been recently reported to be essential for maintaining ROS homeostasis during embryo sac formation. 相似文献
103.
A quantitative trait locus (QTL) linked with ability to find a platform in the Morris Water Maze (MWM) was located on chromosome 17 (Nav-5 QTL) using intercross between Dahl S and Dahl R rats. We developed two congenic strains, S.R17A and S.R17B introgressing Dahl R-chromosome 17 segments into Dahl S chromosome 17 region spanning putative Nav-5 QTL. Performance analysis of S.R17A, S.R17B and Dahl S rats in the Morris water maze (MWM) task showed a significantly decreased spatial navigation performance in S.R17B congenic rats when compared with Dahl S controls (P = 0.02). The S.R17A congenic segment did not affect MWM performance delimiting Nav-5 to the chromosome 17 65.02–74.66 Mbp region. Additional fine mapping is necessary to identify the specific gene variant accounting for Nav-5 effect on spatial learning and memory in Dahl rats. 相似文献
104.
Tomader Ali George Kokotos Victoria Magrioti Robert N. Bone James A. Mobley William Hancock Sasanka Ramanadham 《PloS one》2013,8(8)
Ongoing studies suggest an important role for iPLA2β in a multitude of biological processes and it has been implicated in neurodegenerative, skeletal and vascular smooth muscle disorders, bone formation, and cardiac arrhythmias. Thus, identifying an iPLA2βinhibitor that can be reliably and safely used in vivo is warranted. Currently, the mechanism-based inhibitor bromoenol lactone (BEL) is the most widely used to discern the role of iPLA2β in biological processes. While BEL is recognized as a more potent inhibitor of iPLA2 than of cPLA2 or sPLA2, leading to its designation as a “specific” inhibitor of iPLA2, it has been shown to also inhibit non-PLA2 enzymes. A potential complication of its use is that while the S and R enantiomers of BEL exhibit preference for cytosol-associated iPLA2β and membrane-associated iPLA2γ, respectively, the selectivity is only 10-fold for both. In addition, BEL is unstable in solution, promotes irreversible inhibition, and may be cytotoxic, making BEL not amenable for in vivo use. Recently, a fluoroketone (FK)-based compound (FKGK18) was described as a potent inhibitor of iPLA2β. Here we characterized its inhibitory profile in beta-cells and find that FKGK18: (a) inhibits iPLA2β with a greater potency (100-fold) than iPLA2γ, (b) inhibition of iPLA2β is reversible, (c) is an ineffective inhibitor of α-chymotrypsin, and (d) inhibits previously described outcomes of iPLA2β activation including (i) glucose-stimulated insulin secretion, (ii) arachidonic acid hydrolysis; as reflected by PGE2 release from human islets, (iii) ER stress-induced neutral sphingomyelinase 2 expression, and (iv) ER stress-induced beta-cell apoptosis. These findings suggest that FKGK18 is similar to BEL in its ability to inhibit iPLA2β. Because, in contrast to BEL, it is reversible and not a non-specific inhibitor of proteases, it is suggested that FKGK18 is more ideal for ex vivo and in vivo assessments of iPLA2β role in biological functions. 相似文献
105.
106.
Tino Kreszies Stella Eggels Victoria Kreszies Alina Osthoff Nandhini Shellakkutti Jutta A. Baldauf Viktoria V. Zeisler-Diehl Frank Hochholdinger Kosala Ranathunge Lukas Schreiber 《Plant, cell & environment》2020,43(2):344-357
Wild barley, Hordeum vulgare spp. spontaneum, has a wider genetic diversity than its cultivated progeny, Hordeum vulgare spp. vulgare. Osmotic stress leads to a series of different responses in wild barley seminal roots, ranging from no changes in suberization to enhanced endodermal suberization of certain zones and the formation of a suberized exodermis, which was not observed in the modern cultivars studied so far. Further, as a response to osmotic stress, the hydraulic conductivity of roots was not affected in wild barley, but it was 2.5-fold reduced in cultivated barley. In both subspecies, osmotic adjustment by increasing proline concentration and decreasing osmotic potential in roots was observed. RNA-sequencing indicated that the regulation of suberin biosynthesis and water transport via aquaporins were different between wild and cultivated barley. These results indicate that wild barley uses different strategies to cope with osmotic stress compared with cultivated barley. Thus, it seems that wild barley is better adapted to cope with osmotic stress by maintaining a significantly higher hydraulic conductivity of roots during water deficit. 相似文献
107.
108.
109.
Pinheiro Kelly V. Thomaz Amanda Souza Bárbara Kunzler Metcalfe Victoria Anne Freire Natália Hogetop Brunetto André Tesainer de Farias Caroline Brunetto Jaeger Mariane Bambini Victorio Smith Christopher G. S. Shaw Lisa Roesler Rafael 《Molecular biology reports》2020,47(9):6817-6828
Molecular Biology Reports - A member of the Trk family of neurotrophin receptors, tropomyosin receptor kinase B (TrkB, encoded by the NTRK2 gene) is an increasingly important target in various... 相似文献
110.
Human disturbance from tourism and other non-consumptive activities in protected areas may be stressful to wildlife. Animals may move away in space or time to avoid human interaction. For species of particular conservation concern, such as Baird's tapirs (Tapirus bairdii) and jaguars (Panthera onca), a better understanding of how they respond to different levels and types of disturbance is needed in order to manage human visitation to parks in ways that minimize negative outcomes for wildlife. We describe the overlap in activity patterns of tapirs, jaguars, and humans at logged and unlogged sites and at places with low versus high human visitation using camera survey data from protected areas of NW Belize, 2013–2016. Tapirs were nocturnal in all study sites, with > 80% of all tapir detections occurring between 1900 hr and 0500 hr. Their activity patterns were not different in unlogged versus logged sites and did not change with increased human traffic. Jaguars were cathemeral across sites but had more nocturnal activity at the site with the most human impact. Activity pattern overlap between tapirs and jaguars did not differ significantly between logged and unlogged sites, nor between areas with low and high human activity. Human traffic increased from 2013 to 2016 at most of the study locations. In conclusion, this camera trap dataset suggests that non-consumptive human disturbance does not alter the activity patterns of tapirs and jaguars in protected areas lacking hunting pressure. 相似文献