***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:  T cell memory is a cornerstone of protective immunity, and is the key element in successful vaccination. Upon encountering the relevant pathogen, memory T cells are thought to initiate cell division much more rapidly than their naïve counterparts, and this is thought to confer a significant biological advantage upon an immune host. Here, we use traceable TCR-transgenic T cells to evaluate this proposed characteristic in CD4+ and CD8+ memory T cells. We find that, even in the presence of abundant antigen that was sufficient to induce in vivo IFNγ production by memory T cells, both memory and naïve T cells show an extended, and indistinguishable, delay in the onset of proliferation. Although memory cells can detect, and respond to, virus infection within a few hours, their proliferation did not begin until ∼3 days after infection, and occurred simultaneously in all anatomical compartments. Thereafter, cell division was extraordinarily rapid for both naïve and memory cells, with the latter showing a somewhat accelerated accumulation. We propose that, by permitting memory T cells to rapidly exert their effector functions while delaying the onset of their proliferation, evolution has provided a safeguard that balances the risk of infection against the consequences of severe T cell–mediated immunopathology.


Output:

Vaccines are the only medical products that should be administered to almost every human worldwide, and it is well-known that they act by inducing so-called “memory” cells that can protect against subsequent encounter with the related micro-organism. Surprisingly, we do not understand precisely how these memory cells work: in what way are they better than non-memory (“naïve”) cells, and how do they exert their life-saving functions? It was thought that, following exposure to the relevant microbial antigen, memory cells responded by increasing in number much more quickly than naïve cells and that they achieved this greater abundance by two means: first, by initiating cell division sooner after infection; and, second, by multiplying more rapidly thereafter. Here, we show that neither is true. Memory cells, like naïve cells, begin to divide only after lengthy (2–3 day) delay after virus infection, and their subsequent rate of division is no faster than that of naïve cells. We speculate on the possible evolutionary benefits that might accrue from this lengthy delay before cell division begins.
