***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
***DOCUMENTATION*** 
***EXAMPLES*** 
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***EXAMPLES***
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:  Although bubonic plague is an endemic zoonosis in many countries around the world, the factors responsible for the persistence of this highly virulent disease remain poorly known. Classically, the endemic persistence of plague is suspected to be due to the coexistence of plague resistant and plague susceptible rodents in natural foci, and/or to a metapopulation structure of reservoirs. Here, we test separately the effect of each of these factors on the long-term persistence of plague. We analyse the dynamics and equilibria of a model of plague propagation, consistent with plague ecology in Madagascar, a major focus where this disease is endemic since the 1920s in central highlands. By combining deterministic and stochastic analyses of this model, and including sensitivity analyses, we show that (i) endemicity is favoured by intermediate host population sizes, (ii) in large host populations, the presence of resistant rats is sufficient to explain long-term persistence of plague, and (iii) the metapopulation structure of susceptible host populations alone can also account for plague endemicity, thanks to both subdivision and the subsequent reduction in the size of subpopulations, and extinction-recolonization dynamics of the disease. In the light of these results, we suggest scenarios to explain the localized presence of plague in Madagascar.


Output:

Bubonic plague, known to have marked human history by three deadly pandemics, is an infectious disease which mainly circulates in wild rodent populations and is transmitted by fleas. Although this disease can be quickly lethal to its host, it has persisted on long-term in many rodent populations around the world. The reasons for this persistence remain poorly known. Two mechanisms have been invoked, but not yet explicitly and independently tested: first, the spatial structure of rodent populations (subdivision into several subpopulations) and secondly, the presence of, not only plague-susceptible rodents, but also plague-resistant ones. To gain insight into the role of the above two factors in plague persistence, we analysed a mathematical model of plague propagation. We applied our analyses to the case of Madagascar, where plague has persisted on central highlands since the 1920s and is responsible for about 30% of the human cases worldwide. We found that the long-term persistence of plague can be explained by the presence of any of the above two factors. These results allowed us to propose scenarios to explain the localized presence of plague in the Malagasy highlands, and help understand the persistence of plague in many wild foci.
