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S A McCurdy 《The Western journal of medicine》1994,160(4):338
I examined the pattern of mortality in the Donner Party, a group of emigrants who became trapped with inadequate food stores in the winter snows of the Sierra Nevada mountains in 1846-1847. The party consisted of 90 persons; the median age was 19.5 years (range, 1 to 70), 55 (61%) were male, and 72 (80%) were traveling with family members. Of the 90 persons, 42 (47%) died. Multivariate regression analysis indicated that age was the most important mortality risk factor. The lowest mortality (10%) was seen in the 6- to 14-year age group, and the highest was for persons younger than 6 years (relative risk = 6.6; 95% confidence interval [CI], 2.3 to 9.6) and persons 35 years or older (relative risk = 8.4; 95% CI, 3.4 to 10.2). Persons traveling without other family members had a relative risk of 2.0 (95% CI, 1.0 to 2.5). Men and boys were also at increased risk (relative risk = 2.0; 95% CI, 1.0 to 2.9). These factors can identify persons at increased risk for mortality in nutritionally stressed populations, and efforts to maintain intact family structures may improve survival. 相似文献
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A fibrous protein complex extracted fromEscherichia coli B/r by the method of Minkoff and Damadian [2] demonstrates arrowhead complexes when reacted with heavy meromyosin. 相似文献
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Thomas V. Magee Seungil Han Sandra P. McCurdy Thuy-Trinh Nguyen Karl Granskog Eric S. Marr Bruce A. Maguire Michael D. Huband Jinshan Michael Chen Timothy A. Subashi Veerabahu Shanmugasundaram 《Bioorganic & medicinal chemistry letters》2013,23(6):1727-1731
A novel series of 3-O-carbamoyl erythromycin A derived analogs, labeled carbamolides, with activity versus resistant bacterial isolates of staphylococci (including macrolide and oxazolidinone resistant strains) and streptococci are reported. An (R)-2-aryl substituent on a pyrrolidine carbamate appeared to be critical for achieving potency against resistant strains. Crystal structures showed a distinct aromatic interaction between the (R)-2-aryl (3-pyridyl for 4d) substituent on the pyrrolidine and G2484 (G2505, Escherichia coli) of the Deinococcus radiodurans 50S ribosome (3.2 Å resolution). 相似文献
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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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Mark J. Mitton-Fry Steven J. Brickner Judith C. Hamel Lori Brennan Jeffrey M. Casavant Michael Chen Tao Chen Xiaoyuan Ding James Driscoll Joel Hardink Thuy Hoang Erbing Hua Michael D. Huband Meghan Maloney Anthony Marfat Sandra P. McCurdy Dale McLeod Michael Plotkin Christopher Zook 《Bioorganic & medicinal chemistry letters》2013,23(10):2955-2961
A structurally novel set of inhibitors of bacterial type II topoisomerases with potent in vitro and in vivo antibacterial activity was developed. Dual-targeting ability, hERG inhibition, and pharmacokinetic properties were also assessed. 相似文献
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The first example of the use of a reporter affinity label (NNA) that contains a fluorogenic naphthalene dialdehyde moiety to identify neighboring lysine and cysteine residues at a recognition site is described. The opioid receptors have served as the proof-of-concept because they contain multiple lysine and cysteine residues. The kinetics of isoindole formation resulting from covalent binding of NNA to wild-type and mutant opioid receptors were followed in cultured cells using flow cytometry. The finding that NNA bound to mutant mu opioid receptors (K233R and C235S) without producing specific fluorescence enhancement suggested that covalent bonding occurred at these positions to produce an isoindole fluorophore in the wild-type mu receptor. The similar kinetics of fluorophore formation for wild-type mu, delta, and kappa opioid receptors suggest that these conserved residues are the cross-linking sites in all three types of opioid receptors. The combined utilization of a reporter affinity label and site-directed mutagenesis offers a more expeditious method of identifying cross-linking at a recognition site when compared to classical procedures. 相似文献
10.
Phytoplankton exhibit a diversity of morphologies, nutritional values, and potential chemical defenses that could affect the feeding and fitness of zooplankton consumers. However, how phytoplankton traits shape plant–herbivore interactions in the marine plankton is not as well understood as for terrestrial or marine macrophytes and their grazers. The occurrence of blooms of marine dinoflagellates such as Karenia brevis suggests that, for uncertain reasons, grazers are unable to capitalize on, or control, this phytoplankton growth—making these systems appealing for testing mechanisms of grazing deterrence. Using the sympatric copepod Acartia tonsa, we conducted a mixed diet feeding experiment to test whether K. brevis is beneficial, toxic, nutritionally inadequate, or behaviorally rejected as food relative to the palatable and nutritionally adequate phytoplankter Rhodomonas lens. On diets rich in K. brevis, copepods experienced decreased survivorship and decreased egg production per female, but the percentage of eggs that hatched was unaffected. Although copepods showed a 6–17% preference for R. lens over K. brevis on some mixed diets, overall high ingestion rates eliminated the possibility that reduced copepod fitness was caused by copepods avoiding K. brevis, leaving nutritional inadequacy and toxicity as remaining hypotheses. Because egg production was dependent on the amount of R. lens consumed regardless of the amount of K. brevis eaten, there was no evidence that fitness costs were caused by K. brevis toxicity. Copepods limited to K. brevis ate 480% as much as those fed only R. lens, suggesting that copepods attempted to compensate for low food quality with increased quantity ingested. Our results indicate that K. brevis is a poor food for A. tonsa, probably due to nutritional inadequacy rather than toxicity, which could affect bloom dynamics in the Gulf of Mexico where these species co-occur. 相似文献