***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:
Output:

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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:  Mass drug administration (MDA) using praziquantel is the WHO-recommended approach for control of schistosomiasis. However, few studies have compared the impact of different schedules of MDA on the resultant infection levels. We wished to evaluate whether annual MDA was more effective than less frequent treatments for reducing community-level prevalence and intensity of Schistosoma mansoni infections.
We performed a cluster randomized trial (ISRCTN 14849830) of 3 different MDA frequencies over a 5 year period in 75 villages with moderate (10%-24%) initial prevalence of S. mansoni in school children in western Kenya. Praziquantel was distributed by school teachers to students either annually, the first 2 years, or every other year over a 4 year period. Prevalence and intensity of infection were measured by stool examination in 9–12 year old students using the Kato-Katz method at baseline, each treatment year, and for the final evaluation at year 5. S. mansoni prevalence and intensity were also measured in first year students at baseline and year 5.
Twenty-five schools were randomly assigned to each arm. S. mansoni prevalence and infection intensity in 9–12 year old students significantly decreased within each arm from baseline to year 5 but there were no differences between arms. There were no differences in infection levels in first year students either within or between arms.
Strategies employing 2 or 4 rounds of MDA had a similar impact in schools with moderate initial prevalence, suggesting that schistosomiasis control can be sustained by school-based MDA, even if provided only every other year.


Output:

The World Health Organization (WHO) guidelines recommend mass drug administration (MDA) of praziquantel for control of schistosomiasis. The target group for and the frequency of treatment are based on infections levels in school age children at the initiation of the control program. However, these guidelines have not been rigorously evaluated. Through the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE), we had the opportunity to compare the impact of school-based treatment in an area of western Kenya with moderate (10%-24%) initial prevalence of Schistosoma mansoni infections. We found that providing MDA every year or every other year over a 4 year period provided similar benefits for reducing prevalence and intensity of infection in the final evaluation at year 5. Annual or biennial MDA moved villages from the “moderate risk” to the “low risk category” prescribed in the WHO guidelines. The results from this study and parallel SCORE studies in other African countries should provide the evidence base necessary for improved WHO guidelines for schistosomiasis.
