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981.
Andreia Neves Carvalho Carla Marques Elsa Rodrigues Colin J. Henderson C. Roland Wolf Paulo Pereira Maria João Gama 《Molecular neurobiology》2013,47(2):662-672
The ubiquitin–proteasome system (UPS) is the primary proteolytic complex responsible for the elimination of damaged and misfolded intracellular proteins, often formed upon oxidative stress. Parkinson’s disease (PD) is neuropathologically characterized by selective death of dopaminergic neurons in the substantia nigra (SN) and accumulation of intracytoplasmic inclusions of aggregated proteins. Along with mitochondrial dysfunction and oxidative stress, defects in the UPS have been implicated in PD. Glutathione S-transferase pi (GSTP) is a phase II detoxifying enzyme displaying important defensive roles against the accumulation of reactive metabolites that potentiate the aggression of SN neuronal cells, by regulating several processes including S-glutathionylation, modulation of glutathione levels and control of kinase-catalytic activities. In this work we used C57BL/6 wild-type and GSTP knockout mice to elucidate the effect of both MPTP and MG132 in the UPS function and to clarify if the absence of GSTP alters the response of this pathway to the neurotoxin and proteasome inhibitor insults. Our results demonstrate that different components of the UPS have different susceptibilities to oxidative stress. Importantly, when compared to the wild-type, GSTP knockout mice display decreased ubiquitination capacity and overall increased susceptibility to UPS damage and inactivation upon MPTP-induced oxidative stress. 相似文献
982.
Holten-Andersen N Michael Henderson J Walther FJ Waring AJ Ruchala P Notter RH Lee KY 《Biophysical journal》2011,101(12):2957-2965
We investigated the effects of KL4, a 21-residue amphipathic peptide approximating the overall ratio of positively charged to hydrophobic amino acids in surfactant protein B (SP-B), on the structure and collapse of dipalmitoylphosphatidylcholine and palmitoyl-oleoyl-phosphatidylglycerol monolayers. As reported in prior work on model lung surfactant phospholipid films containing SP-B and SP-B peptides, our experiments show that KL4 improves surfactant film reversibility during repetitive interfacial cycling in association with the formation of reversible collapse structures on multiple length scales. Emphasis is on exploring a general mechanistic connection between peptide-induced nano- and microscale reversible collapse structures (silos and folds). 相似文献
983.
Stable isotope labelling of lipid precursors coupled with mass spectrometry-based lipidomic analyses and determination of isotope enrichment in substrate, intermediate and product pools provide the parameters needed to determine absolute flux rates through lipid pathways in vivo. Here, as an illustration of the power of such analyses we investigated lung phosphatidylcholine (PC) synthesis in Surfactant Protein-D (SP-D) null mice. These animals develop emphysema, foamy alveolar macrophages and an alveolar lipoproteinosis with increasing age. We used the incorporation of methyl-9-[2H] choline chloride coupled with ESI-MS/MS to quantify absolute rates of lung surfactant PC synthesis and secretion in an SP-D−/− mouse model, together with an analysis of the molecular specificity of lung PC synthesis. PC synthetic rates were comparable in control (0.52 μmol/lung/h) and SP-D−/− (0.69 μmol/lung/h) mice, as were rates of surfactant PC secretion (29.8 and 30.6 nmol/lung/h, respectively). Increased lung PC in the SP-D−/− mouse was due to impaired catabolism, with a rate of accumulation of 0.057 μmol/lung/h. The relatively low rates of surfactant PC secretion compared with total lung PC synthesis were compatible with a suggested ABCA1-mediated basolateral lipid efflux from alveolar type II epithelial cells. Finally, PC molecular species analysis suggested that a proportion of newly synthesised PC is secreted rapidly into the lung air spaces in both control and SP-D−/− mice before significant PC acyl remodelling occurs. 相似文献
984.
985.
David P. Robinson Mohammed Y. Jaidah Rima W. Jabado Katie Lee-Brooks Nehad M. Nour El-Din Ameena A. Al. Malki Khaled Elmeer Paul A. McCormick Aaron C. Henderson Simon J. Pierce Rupert F. G. Ormond 《PloS one》2013,8(3)
Whale sharks, Rhincodon typus, are known to aggregate to feed in a small number of locations in tropical and subtropical waters. Here we document a newly discovered major aggregation site for whale sharks within the Al Shaheen oil field, 90 km off the coast of Qatar in the Arabian Gulf. Whale sharks were observed between April and September, with peak numbers observed between May and August. Density estimates of up to 100 sharks within an area of 1 km2 were recorded. Sharks ranged between four and eight metres’ estimated total length (mean 6.92±1.53 m). Most animals observed were actively feeding on surface zooplankton, consisting primarily of mackerel tuna, Euthynnus affinis, eggs. 相似文献
986.
Mitigating the negative impacts of declining worldwide forest cover remains a significant socio-ecological challenge, due to the dominant role of human decision-making. Here we use a Markov chain model of land-use dynamics to examine the impact of governance on forest cover in a region. Each land parcel can be either forested or barren (deforested), and landowners decide whether to deforest their parcel according to perceived value (utility). We focus on three governance strategies: yearly incentive for conservation, one-time penalty for deforestation and one-time incentive for reforestation. The incentive and penalty are incorporated into the expected utility of forested land, which decreases the net gain of deforestation. By analyzing the equilibrium and stability of the landscape dynamics, we observe four possible outcomes: a stationary-forested landscape, a stationary-deforested landscape, an unstable landscape fluctuating near the equilibrium, and a cyclic-forested landscape induced by synchronized deforestation. We find that the two incentive-based strategies often result in highly fluctuating forest cover over decadal time scales or longer, and in a few cases, reforestation incentives actually decrease the average forest cover. In contrast, a penalty for deforestation results in the stable persistence of forest cover (generally >30%). The idea that larger conservation incentives will always yield higher and more stable forest cover is not supported in our findings. The decision to deforest is influenced by more than a simple, “rational” cost-benefit analysis: social learning and myopic, stochastic decision-making also have important effects. We conclude that design of incentive programs may need to account for potential counter-productive long-term effects due to behavioural feedbacks. 相似文献
987.
Huizhong Xiong Antonio Maraver Jo-Ann Latkowski Tanya Henderson Karni Schlessinger Yi Ding Jie Shen Carlos E. Tadokoro Juan J. Lafaille 《PloS one》2013,8(12)
Notch signaling is essential for the development of T cell progenitors through the interaction of NOTCH1 receptor on their surface with the ligand, Delta-like 4 (DLL4), which is expressed by the thymic epithelial cells. Notch signaling is quickly shut down once the cells pass β-selection, and CD4/CD8 double positive (DP) cells are unresponsive to Notch. Over the past two decades a number of papers reported that over-activation of Notch signaling causes T cell acute lymphoblastic leukemia (T-ALL), a cancer that prominently features circulating monoclonal CD4/CD8 double positive T cells in different mouse models. However, the possible outcomes of Notch over-activation at different stages of T cell development are unknown, and the fine timing of Notch signaling that results in T-ALL is poorly understood. Here we report, by using a murine model that ectopically expresses DLL4 on developing T cells, that the T-ALL onset is highly dependent on a sustained Notch activity throughout the DP stage, which induces additional mutations to further boost the signaling. In contrast, a shorter period of Notch activation that terminates at the DP stage causes a polyclonal, non-transmissible lymphoproliferative disorder that is also lethal. These observations resolved the discrepancy of previous papers on DLL4 driven hematological diseases in mice, and show the critical importance of the timing and duration of Notch activity. 相似文献
988.
989.
Daisuke Ogawa Susan D. Johnson Steven T. Henderson Anna M. G. Koltunow 《Sexual plant reproduction》2013,26(2):113-123
In apomictic Hieracium subgenus Pilosella species, embryo sacs develop in ovules without meiosis. Embryo and endosperm formation then occur without fertilization, producing seeds with a maternal genotype encased in a fruit (achene). Genetic analyses in H. praealtum indicate a dominant locus (LOA) controls meiotic avoidance, and another dominant locus (LOP) controls both fertilization-independent embryogenesis and endosperm formation. While cytologically examining developmental events in ovules of progeny from crosses between different wild-type and mutant Hieracium apomicts, and a sexual Hieracium species, we identified two plants, AutE196 and AutE24, which have lost the capacity for meiotic avoidance and fertilization-independent embryo formation. AutE196 and AutE24 exhibit autonomous endosperm formation and set parthenocarpic, seedless achenes at a penetrance of 18 %. Viable seed form after pollination. Cytological examination of 102 progeny from a backcross of AutE196 with sexual H. pilosella showed that autonomous endosperm formation is a heritable, dominant, qualitative trait, detected in 51 % of progeny. Variation in quantitative trait penetrance indicates other factors influence its expression. The correlation between autonomous endosperm development and mature parthenocarpic achene formation suggests the former is sufficient to trigger fruit maturation in Hieracium. The developmental component of autonomous endosperm formation is therefore genetically separable from those controlling meiotic avoidance and autonomous embryogenesis in Hieracium and has been denoted as AutE. We postulate that tight linkage of AutE and genes controlling autonomous embryogenesis at the LOP locus in H. praealtum may explain why inheritance of autonomous seed formation is typically observed as a single component. 相似文献
990.