***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*** 
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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:  Systemic insecticides in dogs have been suggested as a public health intervention to prevent human cases of Zoonotic Visceral Leishmaniasis (ZVL). But, currently there are no systemic insecticides for dogs registered against zoo-anthropophilic pool blood feeding phlebotomine flies. We predict the impact of community-wide use of systemic insecticide in dog populations as a public health measure to control transmission of Leishmania infantum to humans using a mathematical model. We developed a Susceptible-Exposed-Infected (SEI) compartmental model to describe L. infantum transmission dynamics in dogs, with a vectorial capacity term to represent transmission between L. infantum-hosting dogs via phlebotomine flies. For Infected (I) dogs two levels of infectiousness were modelled, high infectiousness and low infectiousness. Human incidence was estimated through its relationship to infection in the dog population. We evaluated outcomes from a wide range of scenarios comprising different combinations of initial insecticide efficacy, duration of insecticide efficacy over time, and proportion of the dog population treated (60%, 70% & 80%). The same reduction in human infection incidence can be achieved via different combinations of insecticide efficacy, duration and dog coverage. For example, a systemic insecticide with an initial efficacy of 80% and 6 months above 65% efficacy would require treating at least 70% of the dogs to reduce the human infection incidence by 50%. Sensitivity analysis showed that the model outcome was most sensitive to baseline values of phlebotomine fly daily survival rate and insecticide coverage. Community-wide use of systemic insecticides applied to the “L. infantum canine reservoir” can significantly reduce human incidence of L. infantum infection. The results of this mathematical model can help defining the insecticide target product profile and how the insecticide should be applied to maximise effectiveness.


Output:

Zoonotic visceral leishmaniasis (ZVL) is a potentially deadly disease in humans caused by Leishmania infantum. This leishmania species can be delivered by pool blood feeding zoo-anthropophilic phlebotomine flies to several mammals, the dog population being recognized as the main reservoir. Transmission from infected dogs to humans is through the bite of female phlebotomine sand flies. The disease is endemic in several countries and Brazil has a high prevalence of cases with over 3000 ZVL cases reported per year. The main, inefficient and highly controversial, control measure in Brazil has been culling sero-positive dogs. The community-wide use of systemic insecticides in dogs could be an alternative to control L. infantum transmission from phlebotomine flies to humans. The rationale is that phlebotomine flies which sampled their blood meals from dogs treated with systemic insecticides would die reducing the risk of L. infantum transmission. To reduce the number of ZVL cases, a large proportion of dogs in the community should be treated and the systemic insecticide used should be effective in killing phlebotomine flies acting as vectors of L. infantum parasites for a significant amount of time. We used a mathematical model mimicking L. infantum transmission to show that this novel vector control strategy could be effective. We identified the combination of different key parameters (e.g. insecticide efficacy, duration and proportion of dogs treated) that could lead to a significant reduction of the risk of L. infantum infection in humans.
