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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:  Since 2003, the tropical arthritogenic chikungunya (CHIK) virus has become an increasingly medical and economic burden in affected areas as it can often result in long-term disabilities. The clinical spectrum of post-CHIK (pCHIK) rheumatic disorders is wide. Evidence-based recommendations are needed to help physicians manage the treatment of afflicted patients.
We conducted a 6-year case series retrospective study in Reunion Island of patients referred to a rheumatologist due to continuous rheumatic or musculoskeletal pains that persisted following CHIK infection. These various disorders were documented in terms of their clinical and therapeutic courses. Post-CHIK de novo chronic inflammatory rheumatisms (CIRs) were identified according to validated criteria.
We reviewed 159 patient medical files. Ninety-four patients (59%) who were free of any articular disorder prior to CHIK met the CIR criteria: rheumatoid arthritis (n=40), spondyloarthritis (n=33), undifferentiated polyarthritis (n=21). Bone lesions detectable by radiography occurred in half of the patients (median time: 3.5 years pCHIK). A positive therapeutic response was achieved in 54 out of the 72 patients (75%) who were treated with methotrexate (MTX). Twelve out of the 92 patients (13%) received immunomodulatory biologic agents due to failure of contra-indication of MTX treatment. Other patients mainly presented with mechanical shoulder or knee disorders, bilateral distal polyarthralgia that was frequently associated with oedema at the extremities and tunnel syndromes. These pCHIK musculoskeletal disorders (MSDs) were managed with pain-killers, local and/or general anti-inflammatory drugs, and physiotherapy.
Rheumatologists in Reunion Island managed CHIK rheumatic disorders in a pragmatic manner following the outbreak in 2006. This retrospective study describes the common mechanical and inflammatory pCHIK disorders. We provide a diagnostic and therapeutic algorithm to help physicians deal with chronic patients, and to limit both functional and economic impacts. The therapeutic indication of MTX in pCHIK CIR could be approved in future efficacy trials.


Output:

With a 6-year insight, we extensively and retrospectively describe clinical profiles and specific treatments of mechanical and inflammatory post-chikungunya rheumatic disorders. In the current context of chikungunya’s global spread, we provide the first diagnostic and therapeutic algorithm to guide physicians according to the amount of time that has elapsed since the acute CHIK infection.
