***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:  Approximately 14 million persons living in areas endemic for lymphatic filariasis have lymphedema of the leg. Clinical studies indicate that repeated episodes of bacterial acute dermatolymphangioadenitis (ADLA) lead to progression of lymphedema and that basic lymphedema management, which emphasizes hygiene, skin care, exercise, and leg elevation, can reduce ADLA frequency. However, few studies have prospectively evaluated the effectiveness of basic lymphedema management or assessed the role of compressive bandaging for lymphedema in resource-poor settings.
Between 1995 and 1998, we prospectively monitored ADLA incidence and leg volume in 175 persons with lymphedema of the leg who enrolled in a lymphedema clinic in Leogane, Haiti, an area endemic for Wuchereria bancrofti. During the first phase of the study, when a major focus of the program was to reduce leg volume using compression bandages, ADLA incidence was 1.56 episodes per person-year. After March 1997, when hygiene and skin care were systematically emphasized and bandaging discouraged, ADLA incidence decreased to 0.48 episodes per person-year (P<0.0001). ADLA incidence was significantly associated with leg volume, stage of lymphedema, illiteracy, and use of compression bandages. Leg volume decreased in 78% of patients; over the entire study period, this reduction was statistically significant only for legs with stage 2 lymphedema (P = 0.01).
Basic lymphedema management, which emphasized hygiene and self-care, was associated with a 69% reduction in ADLA incidence. Use of compression bandages in this setting was associated with an increased risk of ADLA. Basic lymphedema management is feasible and effective in resource-limited areas that are endemic for lymphatic filariasis.


Output:

Lymphatic filariasis is a parasitic disease that is spread by mosquitoes. In tropical countries where lymphatic filariasis occurs, approximately 14 million people suffer from chronic swelling of the leg, known as lymphedema. Repeated episodes of bacterial skin infection (acute attacks) cause lymphedema to progress to its disfiguring form, elephantiasis. To help achieve the goal of eliminating lymphatic filariasis globally, the World Health Organization recommends basic lymphedema management, which emphasizes hygiene, skin care, exercise, and leg elevation. Its effectiveness in reducing acute attack frequency, as well as the role of compressive bandaging, have not been adequately evaluated in filariasis-endemic areas. Between 1995 and 1998, we studied 175 people with lymphedema of the leg in Leogane, Haiti. During Phase I of the study, when compression bandaging was used to reduce leg volume, the average acute attack rate was 1.56 episodes per year; it was greater in people who were illiterate and those who used compression bandages. After March 1997, when hygiene and skin care were emphasized and bandaging discouraged, acute attack frequency significantly decreased to 0.48 episodes per year. This study highlights the effectiveness of hygiene and skin care, as well as limitations of compressive bandaging, in managing lymphedema in filariasis-endemic areas.
