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Jitka Petrlova Arnab Bhattacherjee Wouter Boomsma Stefan Wallin Jens O. Lagerstedt Anders Irbäck 《Protein science : a publication of the Protein Society》2014,23(11):1559-1571
Several disease‐linked mutations of apolipoprotein A‐I, the major protein in high‐density lipoprotein (HDL), are known to be amyloidogenic, and the fibrils often contain N‐terminal fragments of the protein. Here, we present a combined computational and experimental study of the fibril‐associated disordered 1–93 fragment of this protein, in wild‐type and mutated (G26R, S36A, K40L, W50R) forms. In atomic‐level Monte Carlo simulations of the free monomer, validated by circular dichroism spectroscopy, we observe changes in the position‐dependent β‐strand probability induced by mutations. We find that these conformational shifts match well with the effects of these mutations in thioflavin T fluorescence and transmission electron microscopy experiments. Together, our results point to molecular mechanisms that may have a key role in disease‐linked aggregation of apolipoprotein A‐I. 相似文献
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The circadian activity rhythm undergoes changes in the course of postnatal development. Experiments without external time cues were performed to characterize the endogenous component and to investigate any age-dependent changes. Female laboratory mice were used. At the beginning of the experiment they were 3 (juvenile), 23 (adult) or 72 (senile) weeks old. Animals were kept in climatic chambers (constant darkness, food and water ad libitum, temperature: 22±2°C, rel. humidity: 55±5%). Locomotor activity was recorded continuously using infrared detectors. The data were stored and analysed by means of the “Chronobiology Kit” (Stanford University). The mean period lengths were not statistically different between age groups. The stability of the spontaneous activity rhythms was highest in adult mice, however. The mean activity/day decreased from juvenile to senile mice. A nonlinear interrelationship between period length and amount of activity was obtained. At lower activity levels the period length became shorter with increasing activity; at higher levels it became longer again. The general shape of the curve was similar in all age groups. With respect to the nonlinear curve, one could not establish a general age dependency of period length. At similar ranges of activity the period length would be shortest in senile animals. Taking into account, however, the decline with age of the amount of activity the period of old mice could be shorter than, equal to or longer than that of adult mice. The results show that the endogenous component of the circadian activity rhythm, including feedback loops, matures and stabilizes from the juvenile to the adult. An expected loss of stability in senile mice was not demonstrated, probably due to a high variance of the animals’ biological age. These age-dependent changes contribute to the changes of circadian activity rhythms obtained under entrained conditions. 相似文献
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Pregnancy and lactation involve great demands on the cardiovascular system. The purpose of this study was to investigate how
the heart rate and diurnal heart rate pattern change when dogs become pregnant or lactate. Five clinically healthy female
beagle dogs were mated, and delivered three to seven healthy puppies. The heart rate was investigated with 24-h ECG (Holter)
once during anoestrus, at 3, 5, 7 and 9 weeks of pregnancy, and at week 4 postpartum (lactation). However, at 9 weeks, the
ECG could not be recorded for the fully 24 h in 4 of 5 dogs, because labour started and the dogs then appeared disturbed by
the recordings. The results at this date are not included in the statistical comparison. The heart rate increased progressively
during pregnancy and was still elevated at 4 weeks of lactation. During late pregnancy the difference in heart rates between
daytime and nighttime became smaller, but the heart rate was significantly higher in daytime in all periods. In conclusion,
the increased heart rates during pregnancy and lactation reflect increased demands on the cardiovascular system and may be
important to consider in clinical practice. 相似文献
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Hairy roots of strawberry were cultivated in three different types of bioreactors: an air-sparged bioreactor (control), a droplet bioreactor and a mist bioreactor. The highest biomass yields (3.7 g dry wt/l) were achieved in the air-sparged and in the mist bioreactor. In the droplet bioreactor the cultivation medium was insufficiently atomized into droplets and nutrient uptake and growth were slower due to uneven wetting of hairy roots. 相似文献
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