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31.
The S100A1 protein mediates a wide variety of physiological processes through its binding of calcium (Ca2+) and endogenous target proteins. S100A1 presents two Ca2+-binding domains: a high-affinity “canonical” EF (cEF) hand and a low-affinity “pseudo” EF (pEF) hand. Accumulating evidence suggests that both Ca2+-binding sites must be saturated to stabilize an open state conducive to peptide recognition, yet the pEF hand’s low affinity limits Ca2+ binding at normal physiological concentrations. To understand the molecular basis of Ca2+ binding and open-state stabilization, we performed 100 ns molecular dynamics simulations of S100A1 in the apo/holo (Ca2+-free/bound) states and a half-saturated state, for which only the cEF sites are Ca2+-bound. Our simulations indicate that the pattern of oxygen coordination about Ca2+ in the cEF relative to the pEF site contributes to the former’s higher affinity, whereas Ca2+ binding strongly reshapes the protein’s conformational dynamics by disrupting β-sheet coupling between EF hands. Moreover, modeling of the half-saturated configuration suggests that the open state is unstable and reverts toward a closed state in the absence of the pEF Ca2+ ion. These findings indicate that Ca2+ binding at the cEF site alone is insufficient to stabilize opening; thus, posttranslational modification of the protein may be required for target peptide binding at subsaturating intracellular Ca2+ levels. 相似文献
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Professional workers and consumers frequently use hard-surface cleaning products and these products may contain glycol ethers (GEs), such as 2-Butoxyethanol (2-BE). Governmental agencies have set exposure limits for some chemicals used in cleaning products and these exposure limits have been used as guides to protect human health. The study objectives were to determine realistic inhalation exposures for professional workers performing multiple, sequential cleaning tasks and compare the exposures to the acute reference exposure level (REL), which California established for 2-BE. The ConsExpo model was acceptable for evaluating exposure based on a comparison of its predictions to experimentally measured 2-BE vapor concentrations from hard-surface cleaning. The typical worker exposure was predicted for a cleaning scenario consisting of three bathrooms and three kitchens (or three bedrooms) in a 1-h period. This exposure scenario would not be expected to result in significant health consequences because the predicted exposure was much lower than the REL. The predicted chronic and aggregate exposures were also acceptable. This analysis identified two important variables that affect inhalation exposure: cleaners should be used with adequate ventilation and wet wiping towels should be properly disposed so that they are not a source of continuing exposure. 相似文献
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Jonathan Shoag Rizwan Haq Mingfeng Zhang Laura Liu Glenn C. Rowe Aihua Jiang Nicole Koulisis Caitlin Farrel Christopher I. Amos Qingyi Wei Jeffrey E. Lee Jiangwen Zhang Thomas S. Kupper Abrar A. Qureshi Rutao Cui Jiali Han David E. Fisher Zoltan Arany 《Molecular cell》2013,49(1):145-157
Highlights? PGC-1 induces pigment formation in melanocytes ? PGC-1s activate expression of MITF ? α-MSH induces PGC-1s, which are required for induction of melanogenic genes ? eQTLs in human PGC-1β are associated with tanning ability and melanoma protection 相似文献
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We developed a sensitive fluorometric assay to study in vitro fusion between early endosomes isolated from the human hepatoma, Hep G2. Biochemical characterization of this assay showed that fusion between endosomal vesicles was dependent on physiologic temperature, cytosol, and ATP. Fusion was inhibited by pretreatment of vesicles and cytosol with either 1 mM N-ethylmaleimide or 20 microM GTP gamma S. Neither 3 mM ethylene glycol-bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid nor 1 mM CaCl2 significantly affected fusion. In addition, ATP gamma S neither inhibited fusion at 50 microM nor supported fusion at 5 mM. To further our understanding of the factors regulating fusion, inhibitors of endoprotease activity and phosphotyrosine phosphatase activity were assayed for their effect on fusion. The dipeptide inhibitor of endoprotease activity, Cbz-gly-phe-amide, inhibited fusion 70% at 3 mM whereas a dipeptide analogue, Cbz-gly-gly-amide, was without effect. Furthermore, orthovanadate, an inhibitor of phosphotyrosine phosphatase activity, stimulated fusion twofold at 0.5 mM. These results suggest that both tyrosine dephosphorylation and endoprotease activity contribute to the regulation of endosome fusion. 相似文献
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Chen Wu Cecilia Deng Elena Hilario Nick W. Albert Declan Lafferty Ella R. P. Grierson Blue J. Plunkett Caitlin Elborough Ali Saei Catrin S. Günther Hilary Ireland Alan Yocca Patrick P. Edger Laura Jaakola Katja Karppinen Adrian Grande Ritva Kylli Veli-Pekka Lehtola Andrew C. Allan Richard V. Espley David Chagn 《Molecular ecology resources》2022,22(1):345-360
Bilberry (Vaccinium myrtillus L.) belongs to the Vaccinium genus, which includes blueberries (Vaccinium spp.) and cranberry (V. macrocarpon). Unlike its cultivated relatives, bilberry remains largely undomesticated, with berry harvesting almost entirely from the wild. As such, it represents an ideal target for genomic analysis, providing comparisons with the domesticated Vaccinium species. Bilberry is prized for its taste and health properties and has provided essential nutrition for Northern European indigenous populations. It contains high concentrations of phytonutrients, with perhaps the most important being the purple colored anthocyanins, found in both skin and flesh. Here, we present the first bilberry genome assembly, comprising 12 pseudochromosomes assembled using Oxford Nanopore (ONT) and Hi-C Technologies. The pseudochromosomes represent 96.6% complete BUSCO genes with an assessed LAI score of 16.3, showing a high conservation of synteny against the blueberry genome. Kmer analysis showed an unusual third peak, indicating the sequenced samples may have been from two individuals. The alternate alleles were purged so that the final assembly represents only one haplotype. A total of 36,404 genes were annotated after nearly 48% of the assembly was masked to remove repeats. To illustrate the genome quality, we describe the complex MYBA locus, and identify the key regulating MYB genes that determine anthocyanin production. The new bilberry genome builds on the genomic resources and knowledge of Vaccinium species, to help understand the genetics underpinning some of the quality attributes that breeding programs aspire to improve. The high conservation of synteny between bilberry and blueberry genomes means that comparative genome mapping can be applied to transfer knowledge about marker-trait association between these two species, as the loci involved in key characters are orthologous. 相似文献
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Lynn V. Dicks Hugh L. Wright Joscelyne E. Ashpole James Hutchison Caitlin G. McCormack Barbara Livoreil Klaus Peter Zulka William J. Sutherland 《Biodiversity and Conservation》2016,25(7):1383-1399
This paper documents an exercise to synthesize and assess the best available scientific knowledge on the effectiveness of different farm practices at enhancing natural pest regulation in agriculture. It demonstrates a novel combination of three approaches to evidence synthesis—systematic literature search, collated synopsis and evidence assessment using an expert panel. These approaches follow a logical sequence moving from a large volume of disparate evidence to a simple, easily understandable answer for use in policy or practice. The example of natural pest regulation in agriculture was selected as a case study within two independent science-policy interface projects, one European and one British. A third funder, a private business, supported the final stage to translate the synthesized findings into a useful, simplified output for agronomists. As a whole, the case study showcases how a network of scientific knowledge holders and knowledge users can work together to improve the use of science in policy and practice. The process identified five practices with good evidence of a benefit to natural pest regulation, with the most beneficial being ‘Combine trap and repellent crops in a push–pull system’. It highlights knowledge gaps, or potential research priorities, by showing practices considered important by stakeholders for which there is not enough evidence to make an assessment of effects on natural pest regulation, including ‘Alter the timing of pesticide application.’ Finally, the process identifies several important practices where the volume of evidence of effects on natural pest regulation was too large (>300 experimental studies) to be summarised with the resources available, and for which focused systematic reviews may be the best approach. These very well studied practices include ‘Reduce tillage’ and ‘Plant more than one crop per field’. 相似文献
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U O Ugalde A Hernandez I Galindo D Pitt J C Barnes G Wakley 《Journal of general microbiology》1992,138(10):2205-2212
A plasma membrane fraction was obtained by the combined use of differential centrifugation and aqueous polymer two-phase partitioning techniques. Vanadate-inhibited ATPase and glucan synthase activities were highly enriched in this fraction, although the presence of ATPase activity which was not inhibited by vanadate, nitrate, molybdate, anyimycin A or azide was also detected. Other intracellular membrane marker activities were present at very low or undetectable levels. A further separation step using Percoll density gradient centrifugation resulted in the separation of a fraction which exclusively contained vanadate-inhibited ATPase activity, and was enriched with silicotungstic-acid-staining membrane material. Latency tests performed on the plasma membrane markers showed that the membrane vesicles were in the right-side-out orientation. 相似文献