***TASK***
the task is to simplify the input abstract of a biomedical literature

***INPUT***
the input is the abstract of a biomedical literature

***OUTPUT***
the output is the simplified abstract for the input abstract of a biomedical literature
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Input: Functionally analogous enzymes are those that catalyze similar reactions on similar substrates but do not share common ancestry, providing a window on the different structural strategies nature has used to evolve required catalysts. Identification and use of this information to improve reaction classification and computational annotation of enzymes newly discovered in the genome projects would benefit from systematic determination of reaction similarities. Here, we quantified similarity in bond changes for overall reactions and catalytic mechanisms for 95 pairs of functionally analogous enzymes (non-homologous enzymes with identical first three numbers of their EC codes) from the MACiE database. Similarity of overall reactions was computed by comparing the sets of bond changes in the transformations from substrates to products. For similarity of mechanisms, sets of bond changes occurring in each mechanistic step were compared; these similarities were then used to guide global and local alignments of mechanistic steps. Using this metric, only 44% of pairs of functionally analogous enzymes in the dataset had significantly similar overall reactions. For these enzymes, convergence to the same mechanism occurred in 33% of cases, with most pairs having at least one identical mechanistic step. Using our metric, overall reaction similarity serves as an upper bound for mechanistic similarity in functional analogs. For example, the four carbon-oxygen lyases acting on phosphates (EC 4.2.3) show neither significant overall reaction similarity nor significant mechanistic similarity. By contrast, the three carboxylic-ester hydrolases (EC 3.1.1) catalyze overall reactions with identical bond changes and have converged to almost identical mechanisms. The large proportion of enzyme pairs that do not show significant overall reaction similarity (56%) suggests that at least for the functionally analogous enzymes studied here, more stringent criteria could be used to refine definitions of EC sub-subclasses for improved discrimination in their classification of enzyme reactions. The results also indicate that mechanistic convergence of reaction steps is widespread, suggesting that quantitative measurement of mechanistic similarity can inform approaches for functional annotation.
Output:  When species evolve, their genes duplicate and diverge to allow for adaptation of their functional repertoires to the changing environment. In this scenario, unrelated genes can convergently evolve to produce proteins with the same molecular function, termed “functionally analogous.” A quantitative determination of the reaction similarities among functionally analogous enzymes could provide insight about the different structural solutions nature has used to evolve similar catalysts. Bond changes between substrates and products, and between successive reaction intermediates, were used to compare the reactions catalyzed and the mechanisms of catalysis for 95 pairs of functionally analogous enzymes. Less than half of the reactions catalyzed by unrelated enzymes, but defined as similar by the Enzyme Commission (EC) classification, are similar in terms of bond changes, suggesting that this classification often fails to capture quantitative differences between many enzyme reactions. Furthermore, we addressed for the first time whether the chemical mechanisms by which similar overall reactions are achieved in functional analogs are also similar. We conclude that convergence of reaction is often accompanied by convergence of chemical mechanism. These results will be useful for classifying enzymes, guiding functional annotation of newly determined enzyme sequences and structures and for informing the engineering of enzymes with new functions.

Input:  Rift Valley fever virus (RVFV) is a zoonotic arbovirus affecting livestock and people. This study was conducted in western Kenya where RVFV outbreaks have not previously been reported. The aims were to document the seroprevalence and risk factors for RVFV antibodies in a community-based sample from western Kenya and compare this with slaughterhouse workers in the same region who are considered a high-risk group for RVFV exposure. The study was conducted in western Kenya between July 2010 and November 2012. Individuals were recruited from randomly selected homesteads and a census of slaughterhouses. Structured questionnaire tools were used to collect information on demographic data, health, and risk factors for zoonotic disease exposure. Indirect ELISA on serum samples determined seropositivity to RVFV. Risk factor analysis for RVFV seropositivity was conducted using multi-level logistic regression. A total of 1861 individuals were sampled in 384 homesteads. The seroprevalence of RVFV in the community was 0.8% (95% CI 0.5–1.3). The variables significantly associated with RVFV seropositivity in the community were increasing age (OR 1.2; 95% CI 1.1–1.4, p<0.001), and slaughtering cattle at the homestead (OR 3.3; 95% CI 1.0–10.5, p = 0.047). A total of 553 slaughterhouse workers were sampled in 84 ruminant slaughterhouses. The seroprevalence of RVFV in slaughterhouse workers was 2.5% (95% CI 1.5–4.2). Being the slaughterman, the person who cuts the animal’s throat (OR 3.5; 95% CI 1.0–12.1, p = 0.047), was significantly associated with RVFV seropositivity. This study investigated and compared the epidemiology of RVFV between community members and slaughterhouse workers in western Kenya. The data demonstrate that slaughtering animals is a risk factor for RVFV seropositivity and that slaughterhouse workers are a high-risk group for RVFV seropositivity in this environment. These risk factors have been previously reported in other studies providing further evidence for RVFV circulation in western Kenya.


Output:

Rift Valley fever virus (RVFV) is a zoonotic virus affecting livestock and people. Periodic outbreaks in Kenya are associated with greater than average rainfall, although outbreaks have not previously been reported in western Kenya. The virus is spread between animals and to people by mosquitos. Contact with infected animal tissues and products are also risk factors for transmission of RVFV to people. This study investigated the seroprevalence of RVFV in 1861 residents of western Kenya and compared this to the seroprevalence in 553 ruminant slaughterhouse workers. The seroprevalence of RVFV in people in western Kenya was less than 1%, which is consistent with previous reports from the region. Slaughterhouse workers were shown to be a higher risk group for RVFV seropositivity, with seroprevalence of 2.5%. The identification of plausible risk factors including slaughtering is consistent with reports from other regions. The results suggest that it is plausible that RVFV virus is circulating in western Kenya. Improved surveillance in low risk areas is recommended particularly during countrywide outbreaks.
