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Andrew J. Basinski Elisabeth Fichet-Calvet Anna R. Sjodin Tanner J. Varrelman Christopher H. Remien Nathan C. Layman Brian H. Bird David J. Wolking Corina Monagin Bruno M. Ghersi Peter A. Barry Michael A. Jarvis Paul E. Gessler Scott L. Nuismer 《PLoS computational biology》2021,17(3)
Forecasting the risk of pathogen spillover from reservoir populations of wild or domestic animals is essential for the effective deployment of interventions such as wildlife vaccination or culling. Due to the sporadic nature of spillover events and limited availability of data, developing and validating robust, spatially explicit, predictions is challenging. Recent efforts have begun to make progress in this direction by capitalizing on machine learning methodologies. An important weakness of existing approaches, however, is that they generally rely on combining human and reservoir infection data during the training process and thus conflate risk attributable to the prevalence of the pathogen in the reservoir population with the risk attributed to the realized rate of spillover into the human population. Because effective planning of interventions requires that these components of risk be disentangled, we developed a multi-layer machine learning framework that separates these processes. Our approach begins by training models to predict the geographic range of the primary reservoir and the subset of this range in which the pathogen occurs. The spillover risk predicted by the product of these reservoir specific models is then fit to data on realized patterns of historical spillover into the human population. The result is a geographically specific spillover risk forecast that can be easily decomposed and used to guide effective intervention. Applying our method to Lassa virus, a zoonotic pathogen that regularly spills over into the human population across West Africa, results in a model that explains a modest but statistically significant portion of geographic variation in historical patterns of spillover. When combined with a mechanistic mathematical model of infection dynamics, our spillover risk model predicts that 897,700 humans are infected by Lassa virus each year across West Africa, with Nigeria accounting for more than half of these human infections. 相似文献
54.
Due to post-translational modifications such as phosphorylation, proteins exist as distinct charge variants. Two-dimensional (2D) gel electrophoresis followed by immunoblotting enables the detection of these isoforms. For their accurate relative quantitation in different samples, a loading control is necessary to compensate for technical errors such as imprecise sample loading or transfer. The study reveals that the combinatory approach of SYPRO Ruby and chemiluminescence-based 2D Western blot analysis exhibits high linearity and excellent reproducibility and is applicable for limited sample amounts. 相似文献
55.
Runar Thyrhaug Aud Larsen Corina P. D. Brussaard Gunnar Bratbak 《Journal of phycology》2002,38(2):338-343
In this study we investigated virus production in two marine phytoplankton species and how it relates to the host's cell cycle. Phaeocystis pouchetii (Hariot) Lagerheim and Pyramimonas orientalis McFadden, Hill & Wetherby, growing synchronously in batch cultures, were infected with their respective viruses (PpV and PoV) at four different stages in the cell cycle and the production of free virus was then measured for 30 h. The virus production in P. orientalis infected with PoV depended on the time of infection, whereas no such relation was found for P. pouchetii infected with PpV. The P. orientalis cultures infected at the end of the dark period and at the beginning of the light period produced three times more virus than those infected in the middle of the light period and eight times more virus than those infected at the beginning of the dark period. The latent periods for PpV and PoV were 12–14 h and 18–20 h, respectively, and in both cases were independent of the host cell cycle. The differences in virus production may be attributed to light or cell cycle dependent regulation of host infection, metabolism, or burst size. Regardless of the mechanism, these differences may be related to differences in the ecological strategies of the hosts and their ability to form blooms. 相似文献
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A colorimetric determination of inositol monophosphates as an assay for d-glucose 6-phosphate–1l-myoinositol 1-phosphate cyclase 总被引:4,自引:0,他引:4
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A rapid and convenient chemical assay for the enzyme d-glucose 6-phosphate-1l-myoinositol 1-phosphate cyclase is described. The 1l-myoinositol 1-phosphate formed enzymically was oxidized with periodic acid liberating inorganic phosphate, which was assayed. myoInositol 2-phosphate can be assayed in the same way. Glucose 6-phosphate and other primary phosphate esters gave only very small quantities of inorganic phosphate under the conditions described. The K(m) of the enzyme for d-glucose 6-phosphate, 7.5+/-2.5x10(-4)m, was identical with that measured by the radiochemical method. 2-Deoxy-d-glucose 6-phosphate was a powerful competitive inhibitor, K(i) 2.0+/-0.5x10(-5)m, but was not a substrate for the enzyme. 相似文献
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A method has been developed for the purification of small quantities of acetic acid from bacteria. The acetic acid, with added carrier and a second isotopic species as an internal standard, was extracted into diethyl ether, the benzyl ester was formed using diazotoluene (phenyldiazomethane) and the resultant benzyl acetate purified by small-scale preparative gas-liquid chromatography on a nonpolar stationary phase. Overall recoveries were in the range 26–40%. The method was extended to show the feasibility of the preparative purification of other short chain acids, and also for the analysis of C1 to C10 acids, as their benzyl esters. 相似文献
59.
After removal of tightly bound NAD(+) by using charcoal, a preparation of d-glucose 6-phosphate-1 l-myoinositol 1-phosphate cyclase catalysed the reduction of 5-keto-d-glucitol 6-phosphate and 5-keto-d-glucose 6-phosphate by [4-(3)H]NADH to give [5-(3)H]-glucitol 6-phosphate and [5-(3)H]glucose 6-phosphate respectively. The position of the tritium atom in the latter was shown by degradation. Both enzyme-catalysed reductions were strongly inhibited by 2-deoxy-d-glucose 6-phosphate, a powerful competitive inhibitor of inositol cyclase. The charcoal-treated enzyme preparation also converted 5-keto-d-glucose 6-phosphate into [(3)H]myoinositol 1-phosphate in the presence of [4-(3)H]NADH, but less effectively. These partial reactions of inositol cyclase are interpreted as providing strong evidence for the formation of 5-keto-d-glucose 6-phosphate as an enzyme-bound intermediate in the conversion of d-glucose 6-phosphate into 1 l-myoinositol 1-phosphate. The enzyme was partially inactivated by NaBH(4) in the presence of NAD(+). Glucose 6-phosphate did not increase the inactivation, and there was no inactivation in the absence of NAD(+). There was no evidence for Schiff base formation during the cyclization. d-Glucitol 6-phosphate (l-sorbitol 1-phosphate) was a good inhibitor of the overall reaction. It did not inactivate the enzyme. The apparent molecular weight of inositol cyclase as determined by Sephadex chromatography was 2.15x10(5). 相似文献
60.
Kinetics and mechanism of oxygen-independent hydrocarbon hydroxylation by ethylbenzene dehydrogenase 总被引:1,自引:0,他引:1
Ethylbenzene dehydrogenase (EBDH) from the denitrifying bacterium Azoarcus sp. strain EbN1 (to be renamed Aromatoleum aromaticum) catalyzes the oxygen-independent, stereospecific hydroxylation of ethylbenzene to (S)-1-phenylethanol, the first known example of direct anaerobic oxidation of a nonactivated hydrocarbon. The enzyme is a trimeric molybdenum/iron-sulfur/heme protein of 155 kDa that is quickly inactivated in air in its reduced state. Enzyme activity can be coupled to ferricenium tetrafluoroborate, providing a convenient way for kinetic measurements. EBDH exhibits activity with a wide range of ethylbenzene analogues, which were analyzed for their kinetic parameters, stoichiometry, and formed products. The reactivity was correlated to the chemical structures by a quantitative structure-activity relationship (QSAR) model. On the basis of these results, quantum chemical calculations of DeltaG298 for formation of carbocations of the respective substrates were performed and used in reactivity analysis. A putative reaction mechanism is proposed on the basis of the experimental results and theoretical considerations. Finally, the enzyme reaction has been established in an electrochemical reactor, allowing sustained enzymatic reaction and potential technical applications of the enzyme. 相似文献