***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:  Lassa fever is a viral haemorrhagic fever caused by an arenavirus. The disease is endemic in West African countries, including Guinea. The rodents Mastomys natalensis and Mastomys erythroleucus have been identified as Lassa virus reservoirs in Guinea. In the absence of a vaccine, rodent control and human behavioural changes are the only options to prevent Lassa fever in highly endemic areas. We performed a 4 year intervention based on chemical rodent control, utilizing anticoagulant rodenticides in 3 villages and evaluating the rodent abundance before and after treatment. Three additional villages were investigated as controls. Analyses to assess the effectiveness of the intervention, bait consumption and rodent dynamics were performed. Anthropological investigations accompanied the intervention to integrate local understandings of human–rodent cohabitation and rodent control intervention. Patterns of bait consumption showed a peak at days 5–7 and no consumption at days 28–30. There was no difference between Bromadiolone and Difenacoum bait consumption. The main rodent species found in the houses was M. natalensis. The abundance of M. natalensis, as measured by the trapping success, varied between 3.6 and 16.7% before treatment and decreased significantly to 1–2% after treatment. Individuals in treated villages welcomed the intervention and trapping because mice are generally regarded as a nuisance. Immediate benefits from controlling rodents included protection of food and belongings. Before the intervention, local awareness of Lassa fever was non-existent. Despite their appreciation for the intervention, local individuals noted its limits and the need for complementary actions. Our results demonstrate that chemical treatment provides an effective tool to control local rodent populations and can serve as part of an effective, holistic approach combining rodent trapping, use of local rodenticides, environmental hygiene, house repairs and rodent-proof storage. These actions should be developed in collaboration with local stakeholders and communities.


Output:

In the absence of a Lassa fever vaccine, rodent control is the primary prevention option. An effective rodent control intervention must understand human behaviour towards the rodent such as: human–rodent interactions, cohabitation, and local rodent control measures. We conducted a rodent control intervention at community level in a Lassa Virus endemic area in Upper Guinea (Guinea) accompanied by an anthropological study on people’s perceptions and recommendations on the intervention. Based on our results we seek to broaden the rodent control intervention by including environmental hygiene, house repairs and rodent-proof storage. Chemical treatment has proven effective for rodent control but other factors involved in human-rodent interactions should also be addressed. Our findings highlight the need for Lassa fever prevention and rodent control initiatives to work in collaboration with communities and undertake a holistic approach towards rodent control.
