***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:  Adaptive immunity to Mycobacterium tuberculosis controls
                    progressive bacterial growth and disease but does not eradicate infection. Among
                        CD4+ T cells in the lungs of M.
                        tuberculosis-infected mice, we observed that few produced IFN-γ
                    without ex vivo restimulation. Therefore, we hypothesized that one mechanism
                    whereby M. tuberculosis avoids elimination is by limiting
                    activation of CD4+ effector T cells at the site of infection in
                    the lungs. To test this hypothesis, we adoptively transferred Th1-polarized
                        CD4+ effector T cells specific for M.
                        tuberculosis Ag85B peptide 25 (P25TCRTh1 cells), which trafficked
                    to the lungs of infected mice and exhibited antigen-dependent IFN-γ
                    production. During the early phase of infection, ∼10% of P25TCRTh1
                    cells produced IFN-γ in vivo; this declined to <1% as infection
                    progressed to chronic phase. Bacterial downregulation of fbpB
                    (encoding Ag85B) contributed to the decrease in effector T cell activation in
                    the lungs, as a strain of M. tuberculosis engineered to express
                        fbpB in the chronic phase stimulated P25TCRTh1 effector
                    cells at higher frequencies in vivo, and this resulted in CD4+ T
                    cell-dependent reduction of lung bacterial burdens and prolonged survival of
                    mice. Administration of synthetic peptide 25 alone also increased activation of
                    endogenous antigen-specific effector cells and reduced the bacterial burden in
                    the lungs without apparent host toxicity. These results indicate that
                        CD4+ effector T cells are activated at suboptimal
                    frequencies in tuberculosis, and that increasing effector T cell activation in
                    the lungs by providing one or more epitope peptides may be a successful strategy
                    for TB therapy.


Output:

Mycobacterium tuberculosis causes persistent infection even in
                    human or animal hosts that develop antigen-specific CD4+ and
                        CD8+ T cell responses. To understand this phenomenon, we
                    tested the hypothesis that the CD4+ effector T cells that are
                    generated in response to M. tuberculosis infection fail to
                    encounter their antigens at the site of infection in the lungs. Using mice
                    infected with M. tuberculosis, and an assay of in vivo
                    antigen-dependent activation of CD4+ T cells, we found that both
                    polyclonal CD4+ and T cell receptor transgenic
                        CD4+ T cells specific for antigen 85B peptide 25 are
                    activated at low frequencies in the lungs. We found that this is due in part to
                    downregulation of antigen gene expression by M. tuberculosis,
                    as forced expression of the antigen gene resulted in higher frequency activation
                    of CD4+ T cells, as well as CD4+ T
                    cell-dependent reduction in bacterial burdens and prolonged survival of infected
                    mice. We also found that administration of antigen 85B peptide 25, which is
                    recognized by a high proportion of M. tuberculosis-specific
                        CD4+ T cells, reduced the bacterial burden in the lungs,
                    indicating that stimulation of existing antigen-specific CD4+ T
                    cells may be a promising approach to therapy of TB.
