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I Leck 《BMJ (Clinical research ed.)》1983,286(6379):1679-1680
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V KW Wong T Li B YK Law E DL Ma N C Yip F Michelangeli C KM Law M M Zhang K YC Lam P L Chan L Liu 《Cell death & disease》2013,4(7):e720
Autophagy is an important cellular process that controls cells in a normal homeostatic state by recycling nutrients to maintain cellular energy levels for cell survival via the turnover of proteins and damaged organelles. However, persistent activation of autophagy can lead to excessive depletion of cellular organelles and essential proteins, leading to caspase-independent autophagic cell death. As such, inducing cell death through this autophagic mechanism could be an alternative approach to the treatment of cancers. Recently, we have identified a novel autophagic inducer, saikosaponin-d (Ssd), from a medicinal plant that induces autophagy in various types of cancer cells through the formation of autophagosomes as measured by GFP-LC3 puncta formation. By computational virtual docking analysis, biochemical assays and advanced live-cell imaging techniques, Ssd was shown to increase cytosolic calcium level via direct inhibition of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump, leading to autophagy induction through the activation of the Ca2+/calmodulin-dependent kinase kinase–AMP-activated protein kinase–mammalian target of rapamycin pathway. In addition, Ssd treatment causes the disruption of calcium homeostasis, which induces endoplasmic reticulum stress as well as the unfolded protein responses pathway. Ssd also proved to be a potent cytotoxic agent in apoptosis-defective or apoptosis-resistant mouse embryonic fibroblast cells, which either lack caspases 3, 7 or 8 or had the Bax-Bak double knockout. These results provide a detailed understanding of the mechanism of action of Ssd, as a novel autophagic inducer, which has the potential of being developed into an anti-cancer agent for targeting apoptosis-resistant cancer cells. 相似文献
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S?Blair?HedgesEmail author Hsiong?Chen Sudhir?Kumar Daniel?YC?Wang Amanda?S?Thompson Hidemi?Watanabe 《BMC evolutionary biology》2001,1(1):4
Background
Genomic sequence analyses have shown that horizontal gene transfer occurred during the origin of eukaryotes as a consequence of symbiosis. However, details of the timing and number of symbiotic events are unclear. A timescale for the early evolution of eukaryotes would help to better understand the relationship between these biological events and changes in Earth's environment, such as the rise in oxygen. We used refined methods of sequence alignment, site selection, and time estimation to address these questions with protein sequences from complete genomes of prokaryotes and eukaryotes. 相似文献5.
Study of seed banks, field seedling emergence, and survival of macrophytes in four zones (steep bank—SB; gentle bank—GB; midbank—MB; high marsh —HM) along transects perpendicular to a stream channel in a freshwater tidal wetland showed that many species are widely distributed. Of the 35 species in the seed bank, 50% were common to all zones; of the 20 species emerging in the field, 77% were observed in all zones. Density of seeds, seedlings, and mature plants of most species, however, varied significantly with habitat. The seed bank of each zone reflected the dominant vegetation of that zone. Most species, even those with high potential for water dispersal, were not evenly distributed. Reciprocal transplants and survival persistence data of dominants corresponded with their habitat preferences. Seed bank densities differed from zone to zone (SB 1,717 m-2; GB 1,645; MB 2,730; HM 3,620). In all zones the maximum field seedling density was less than the comparable seed bank one (SB 38% less; GB 33%; MB 46%; and HM 10%). These data, coupled with the higher proportion of the total seed bank and total field seedlings occurring in the HM, suggest that the stream channel sites were more stressful early in the growing season than the HM. Because of differential establishment and survival, importance of a species relative to the rest of the vegetation may change with time and occurrence of a species in the vegetation may greatly outweigh its importance in the seed bank or even the seedling stage. Although seeds of annual species were numerous with seven species making up 85% of the seed bank, annual species comprised only about half of the species recorded in the seed bank of each zone. It is not possible at our present level of understanding of seed banks in the freshwater tidal marsh to predict vegetation change. Various combinations of species attributes contribute to the zonation patterns observed in the freshwater tidal wetland. 相似文献
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Wing Ki Wong Terrenz Kelly Jingjing Li Hoi Tang Ma Randy YC Poon 《Cell cycle (Georgetown, Tex.)》2015,14(24):3965-3977
Shugoshin (SGO1) plays a pivotal role in sister chromatid cohesion during mitosis by protecting the centromeric cohesin from mitotic kinases and WAPL. Mammalian cells contain at least 6 alternatively spliced isoforms of SGO1. The relationship between the canonical SGO1A with shorter isoforms including SGO1C remains obscure. Here we show that SGO1C was unable to replace the loss of SGO1A. Instead, expression of SGO1C alone induced aberrant mitosis similar to depletion of SGO1A, promoting premature sister chromatid separation, activation of the spindle-assembly checkpoint, and mitotic arrest. In disagreement with previously published data, we found that SGO1C localized to kinetochores. However, the ability to induce aberrant mitosis did not correlate with its kinetochore localization. SGO1C mutants that abolished binding to kinetochores still triggered premature sister chromatid separation. We provide evidence that SGO1C-mediated mitotic arrest involved the sequestering of PP2A–B56 pool. Accordingly, SGO1C mutants that abolished binding to PP2A localized to kinetochores but did not induce aberrant mitosis. These studies imply that the expression of SGO1C should be tightly regulated to prevent dominant-negative effects on SGO1A and genome instability. 相似文献
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Yiying Cai Hui Leck Tze Peng Lim Jocelyn Teo Winnie Lee Li Yang Hsu Tse Hsien Koh Thuan Tong Tan Thean-Yen Tan Andrea Lay-Hoon Kwa 《PloS one》2015,10(10)
Background
Current in vitro combination testing methods involve enumeration by bacterial plating, which is labor-intensive and time-consuming. Measurement of bioluminescence, released when bacterial adenosine triphosphate binds to firefly luciferin-luciferase, has been proposed as a surrogate for bacterial counts. We developed an ATP bioluminescent combination testing assay with a rapid turnaround time of 24h to determine effective antibiotic combinations.Methods
100 strains of carbapenem-resistant (CR) GNB [30 Acinetobacter baumannii (AB), 30 Pseudomonas aeruginosa (PA) and 40 Klebsiella pneumoniae (KP)] were used. Bacterial suspensions (105 CFU/ml) were added to 96-well plates containing clinically achievable concentrations of multiple single and two-antibiotic combinations. At 24h, the luminescence intensity of each well was measured. Receiver operator characteristic curves were plotted to determine optimal luminescence threshold (TRLU) to discriminate between inhibitory/non-inhibitory combinations when compared to viable plating. The unweighted accuracy (UA) [(sensitivity + specificity)/2] of TRLU values was determined. External validation was further done using 50 additional CR-GNB.Results
Predictive accuracies of TRLU were high for when all antibiotic combinations and species were collectively analyzed (TRLU = 0.81, UA = 89%). When individual thresholds for each species were determined, UA remained high. Predictive accuracy was highest for KP (TRLU = 0.81, UA = 91%), and lowest for AB (TRLU = 0.83, UA = 87%). Upon external validation, high overall accuracy (91%) was observed. The assay distinguished inhibitory/non-inhibitory combinations with UA of 80%, 94% and 93% for AB, PA and KP respectively.Conclusion
We developed an assay that is robust at identifying useful combinations with a rapid turn-around time of 24h, and may be employed to guide the timely selection of effective antibiotic combinations. 相似文献8.
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Following a recent report that neoplasia of the lymphatic and haematopoietic tissues is commoner than average in children whose mothers have had influenza in pregnancy, the incidence of neoplasms in 1954-68 in children of the Manchester Hospital Region was examined in relation to date of birth. There were no significant differences between cohorts born in different quinquennia. Incidence among children born after six influenza epidemics in 1951-68 was no higher than among other children born in these years. It is concluded that if there is an association between maternal influenza and childhood neoplasia it is probably due to factors such as immunological deficiencies which may predispose independently to both conditions. 相似文献
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