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31.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(5):681-687
Protein disulphide isomerase (PDI) in the endoplasmic reticulum catalyzes the rearrangement of disulphide bridges during folding of secreted proteins. It binds various molecules that inhibit its activity. But here, we looked for molecules that would potentiate its activity. PDI reductase activity was measured in vitro using di-eosin-oxidized glutathione as substrate. Its classical inhibitor bacitracin was found to exert a biphasic effect: stimulatory at low concentrations (~10?6 M) and inhibitory only at higher concentrations (~10?4–10?3 M). The weak oestrogenic molecule bisphenol A was found to exert a weak inhibitory effect on PDI reductase activity relative to the strong oestrogens, ethynylestradiol, and diethylstilbestrol. Like 19-nortestosterone, fluoxetine was found to exert a potentiating effect on PDI reductase activity and their potentiating effects could be reversed by increasing concentrations of oestrogens. In conclusion, this paper provides the first identification of potentiators of PDI activity that are potential pharmaceuticals against pathologies affecting protein folding such as Alzheimer’s disease. 相似文献
32.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(5):744-747
A series of sulfonamide derivatives incorporating substituted 3-formylchromone moieties were investigated for the inhibition of three human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, hCA I, II, and VI. All these compounds, together with the clinically used sulfonamide acetazolamide, were investigated as inhibitors of the physiologically relevant isozymes I, II (cytosolic), and VI (secreted isoform). These sulfonamides showed effective inhibition against all these isoforms with KI’s in the range of 0.228 to 118 µM. Such molecules can be used as leads for discovery of novel effective CA inhibitors against other isoforms with medicinal chemistry applications. 相似文献
33.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(6):1274-1290
4-(4-[N-1-carboxy-3-(3,5-dibromo-4-hydroxyphenyl)-3-oxo-propylamino]phenyl)-4-oxo-butyric acid (V), 4-(3- & 4-[N-1-carboxy-3-(3,5-dibromo-4-hydroxyphenyl)-3-oxo-propylaminophenyl]-2-aryl-4-oxo-butyric acids (Xa–e) and 4-(2-alkyl-2-[N-3-(3,5-dibromo-4-hydroxyphenyl)-1-carboxy-3-oxo-propylamino]acetamido) benzoate esters (XVa–e) were designed, synthesized and biologically evaluated as anti-HCV for genotypes 1b and 4a. The design was based on their docking scores with HCV NS3/4A protease-binding site of the genotype 1b (1W3C), which is conserved in the genotype 4a structure. The docking scores predicted that most of these molecules have higher affinity to the HCV NS3/4A enzyme more than Indoline lead. These compounds were synthesized and evaluated for their cytopathic inhibitory activity against RAW HCV cell cultures of genotype 4a and also examined against Huh 5–2 HCV cell culture of genotype 1b, utilizing Luciferase and MTS assays. Compounds Xa and Xb have 95 and 80% of the activity of Ribavirin against genotype 4a and compounds XVa, XVb and XVd exerted high percentage inhibitory activity against genotype 1b equal 87.7, 84.3 and 82.8%, respectively, with low EC50 doses. 相似文献
34.
Bateman’s experimental study of Drosophila melanogaster produced conclusions that are now part of the bedrock premises of modern sexual selection. Today it is the most cited experimental study in sexual selection, and famous as the first experimental demonstration of sex differences in the relationship between number of mates and relative reproductive success. We repeated the experimental methodology of the original to evaluate its reliability. The results indicate that Bateman’s methodology of visible mutations to assign parentage and reproductive success to subject adults is significantly biased. When combined in offspring, the mutations decrease offspring survival, so that counts of mate number and reproductive success are mismeasured. Bateman’s method overestimates the number of subjects with no mates and underestimates the number with one or more mates for both sexes. Here we discuss why Bateman’s paper is important and present additional analyses of data from our monogamy trials. Monogamy trials can inform inferences about the force of sexual selection in populations because in monogamy trials male–male competition and female choice are absent. Monogamy trials also would have provided Bateman with an a priori test of the fit of his data to Mendel’s laws, an unstated, but vital assumption of his methodology for assigning parentage from which he inferred the number of mates per individual subject and their reproductive success. Even under enforced monogamous mating, offspring frequencies of double mutant, single mutant and no mutant offspring were significantly different from Mendelian expectations proving that Bateman’s method was inappropriate for answering the questions he posed. Double mutant offspring (those with a mutation from each parent) suffered significant inviability as did single mutant offspring whenever they inherited their mother’s marker but the wild-type allele at their father’s marker locus. These inviability effects produced two important inaccuracies in Bateman’s results and conclusions. (1) Some matings that actually occurred were invisible and (2) reproductive success of some mothers was under-estimated. Both observations show that Bateman’s conclusions about sex differences in number of mates and reproductive success were unwarranted, based on biased observations. We speculate about why Bateman’s classic study remained without replication for so long, and we discuss why repetition almost 60 years after the original is still timely, necessary and critical to the scientific enterprise. We highlight overlooked alternative hypotheses to urge that modern tests of Bateman’s conclusions go beyond confirmatory studies to test alternative hypotheses to explain the relationship between mate number and reproductive success. 相似文献
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36.
《Autophagy》2013,9(1):74-92
Macroautophagy (autophagy) is a cellular recycling program essential for homeostasis and survival during cytotoxic stress. This process, which has an emerging role in disease etiology and treatment, is executed in four stages through the coordinated action of more than 30 proteins. An effective strategy for studying complicated cellular processes, such as autophagy, involves the construction and analysis of mathematical or computational models. When developed and refined from experimental knowledge, these models can be used to interrogate signaling pathways, formulate novel hypotheses about systems, and make predictions about cell signaling changes induced by specific interventions. Here, we present the development of a computational model describing autophagic vesicle dynamics in a mammalian system. We used time-resolved, live-cell microscopy to measure the synthesis and turnover of autophagic vesicles in single cells. The stochastically simulated model was consistent with data acquired during conditions of both basal and chemically-induced autophagy. The model was tested by genetic modulation of autophagic machinery and found to accurately predict vesicle dynamics observed experimentally. Furthermore, the model generated an unforeseen prediction about vesicle size that is consistent with both published findings and our experimental observations. Taken together, this model is accurate and useful and can serve as the foundation for future efforts aimed at quantitative characterization of autophagy. 相似文献
37.
刘威;袁晓婷;张艳艳;闫永庆 《植物研究》2013,33(6):697-700
胭脂红景天叶片呈胭脂红色,花开红色,具有极强的耐寒性和耐旱性,是优良的城市绿化植物。为了扩大胭脂红景天的应用范围,丰富恶劣生境的绿化材料,本试验对从哈尔滨引种到西藏日喀则表现良好的胭脂红景天进行了生理适应性研究。结果表明,随着栽植时间的延长,胭脂红景天叶片中丙二醛含量逐渐升高,但增加的幅度较小,脯氨酸含量先降低后升高,SOD、POD、CAT等保护酶的活性均呈先升高后降低的趋势。胭脂红景天可以通过增加体内渗透调节物质含量和提高保护酶活性来调节自身的生理代谢,适应日喀则地区高辐射、干旱等条件。 相似文献
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40.
<i>Aspergillus tubingensis</i> Causes Leaf Spot of Cotton (<i>Gossypium hirsutum</i> L.) in Pakistan
Maria Khizar Urooj Haroon Musrat Ali Samiah Arif Iftikhar Hussain Shah Hassan Javed Chaudhary Muhammad Farooq Hussain Munis 《Phyton》2020,89(1):103-109
Cotton (Gossypium hirsutum L.) is a key fiber crop of great commercial
importance. Numerous phytopathogens decimate crop production by causing
various diseases. During July-August 2018, leaf spot symptoms were recurrently
observed on cotton leaves in Rahim Yar Khan, Pakistan and adjacent areas. Infected
leaf samples were collected and plated on potato dextrose agar (PDA) media.
Causal agent of cotton leaf spot was isolated, characterized and identified as
Aspergillus tubingensis based on morphological and microscopic observations.
Conclusive identification of pathogen was done on the comparative molecular
analysis of CaM and β-tubulin gene sequences. BLAST analysis of both sequenced
genes showed 99% similarity with A. tubingensis. Koch’s postulates were followed
to confirm the pathogenicity of the isolated fungus. Healthy plants were inoculated
with fungus and similar disease symptoms were observed. Fungus was re-isolated
and identified to be identical to the inoculated fungus. To our knowledge, this is the
first report describing the involvement of A. tubingensis in causing leaf spot disease
of cotton in Pakistan and around the world. 相似文献