***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*** 
Input:
Output:

***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:  The outcome of viral infections is dependent on the function of CD8+ T cells
                    which are tightly regulated by costimulatory molecules. The NK cell receptor 2B4
                    (CD244) is a transmembrane protein belonging to the Ig superfamily which can
                    also be expressed by CD8+ T cells. The aim of this study was to analyze the
                    role of 2B4 as an additional costimulatory receptor regulating CD8+ T cell
                    function and in particular to investigate its implication for exhaustion of
                    hepatitis C virus (HCV)-specific CD8+ T cells during persistent infection.
                    We demonstrate that (i) 2B4 is expressed on virus-specific CD8+ T cells
                    during acute and chronic hepatitis C, (ii) that 2B4 cross-linking can lead to
                    both inhibition and activation of HCV-specific CD8+ T cell function,
                    depending on expression levels of 2B4 and the intracellular adaptor molecule SAP
                    and (iii) that 2B4 stimulation may counteract enhanced proliferation of
                    HCV-specific CD8+ T cells induced by PD1 blockade. We suggest that 2B4 is
                    another important molecule within the network of costimulatory/inhibitory
                    receptors regulating CD8+ T cell function in acute and chronic hepatitis C
                    and that 2B4 expression levels could also be a marker of CD8+ T cell
                    dysfunction. Understanding in more detail how 2B4 exerts its differential
                    effects could have implications for the development of novel immunotherapies of
                    HCV infection aiming to achieve immune control.


Output:

Infection with the hepatitis C Virus (HCV) is a world-wide health burden, the
                    infection becomes persistent in the majority of cases. In chronic patients
                    HCV-specific immune responses are weak, HCV-specific CD8+ T cells were
                    shown to be functionally exhausted and to be negatively controlled by
                    costimulatory molecules like PD-1. Here, we show that the costimulatory molecule
                    2B4 (CD244) is also involved in the regulation of HCV-specific CD8+ T cell
                    responses and that 2B4 expression is selectively upregulated on virus-specific
                    CD8+ T cells in persistent infections. Proliferation of HCV-specific
                    CD8+ T cells from chronic patients increased by 2B4 cross-linking only if
                    the ex vivo 2B4 expression was low, while we could observe no
                    effect on samples with high 2B4 expression levels. Of note, expression of the
                    intracellular 2B4 adaptor molecule SAP, which leads to an activation of the
                    cell, decreased with higher 2B4 expression levels. Finally, we were able to show
                    that 2B4 cross-linking can counter-act enhanced proliferation of HCV-specific
                    CD8+ T cells seen upon PD-1 blockade. Thus, our study provides new insights
                    into the regulation of CD8+ T cell responses demonstrating an implication
                    of the costimulatory molecule 2B4.
