***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:  Trypanosoma cruzi is the etiologic agent of Chagas disease throughout the Americas. Few population-level studies have examined the epidemiology of canine infection and strain types of T. cruzi that infect canines in the USA. We conducted a cross-sectional study of T. cruzi infection in working hound dogs in south central Texas, including analysis of triatomine vectors collected within kennel environments.
Paired IFA and Chagas Stat-Pak serological testing showed an overall seroprevalence of 57.6% (n = 85), with significant variation across kennels. Dog age had a marginally significant effect on seropositivity, with one year of age increase associated with a 19.6% increase in odds of being seropositive (odds ratio 95% CI 0.996–1.435; p = 0.055). PCR analyses of blood revealed 17.4% of dogs harbored parasite DNA in their blood, including both seronegative and seropositive dogs. Molecular screening of organs from opportunistically sampled seropositive dogs revealed parasite DNA in heart, uterus, and mammary tissues. Strain-typing showed parasite discrete typing units (DTU) TcI and TcIV present in dog samples, including a co-occurrence of both DTUs in two individual dogs. Bloodmeal analysis of Triatoma gerstaeckeri and Triatoma sanguisuga insects collected from the kennels revealed exclusively dog DNA. Vector infection with T. cruzi was 80.6% (n = 36), in which T. gerstaeckeri disproportionately harbored TcI (p = 0.045) and T. sanguisuga disproportionately harbored TcIV (p = 0.029). Tracing infection status across dog litters showed some seropositive offspring of seronegative dams, suggesting infection of pups from local triatomine vectors rather than congenital transmission.
Canine kennels are high-risk environments for T. cruzi transmission, in which dogs likely serve as the predominant parasite reservoir. Disease and death of working dogs from Chagas disease is associated with unmeasured yet undoubtedly significant financial consequences because working dogs are highly trained and highly valued.


Output:

The parasite Trypanosoma cruzi can cause Chagas disease in humans and dogs. The parasite is typically spread through the feces of a blood-sucking ‘kissing bug’ insect. Despite many documented cases in dogs across Texas, there are few population-level research studies investigating canine Chagas disease in multi-dog kennels in Texas. We sampled a total of 86 dogs from three kennels in south central Texas. We found 58% of the dogs had antibodies indicating they had been exposed to the parasite, and 17% of the dogs had parasite DNA circulating in their blood. We found that over 80% of kissing bugs collected from the kennels were infected. Further, using a bloodmeal analysis technique, we detected that all tested bugs had recently fed on dog blood. Our findings indicate that dog kennels can serve as an environment where kissing bugs and dogs interact, and that outdoor, multi-dog kennels in areas with kissing bugs are high risk areas for Trypanosoma cruzi transmission in dogs.
