***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*** 
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Output:

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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:  A well-accepted model of episodic memory involves the processing of spatial and non-spatial information by segregated pathways and their association within the hippocampus. However, these pathways project to distinct proximodistal levels of the hippocampus. Moreover, spatial and non-spatial subnetworks segregated along this axis have been recently described using memory tasks with either a spatial or a non-spatial salient dimension. Here, we tested whether the concept of segregated subnetworks and the traditional model are reconcilable by studying whether activity within CA1 and CA3 remains segregated when both dimensions are salient, as is the case for episodes. Simultaneously, we investigated whether temporal or spatial information bound to objects recruits similar subnetworks as items or locations per se, respectively. To do so, we studied the correlations between brain activity and spatial and/or temporal discrimination ratios in proximal and distal CA1 and CA3 by detecting Arc RNA in mice. We report a robust proximodistal segregation in CA1 for temporal information processing and in both CA1 and CA3 for spatial information processing. Our results suggest that the traditional model of episodic memory and the concept of segregated networks are reconcilable, to a large extent and put forward distal CA1 as a possible “home” location for time cells.


Output:

Departing from the most influential model of episodic memory (the two-streams hypothesis), we have recently proposed a new concept of information processing in the hippocampus according to which “what” one remembers and “where” it happens might be processed by distinct subnetworks segregated along the proximodistal axis of the hippocampus, a brain region tied to memory function, instead of being systematically integrated at this level. Here, we focused on the processing of temporal and/or spatial information in the proximal and distal parts of CA1 and CA3 in mice to test whether the two concepts are reconcilable. To do so, we used an imaging method with cellular resolution based on the detection of the RNA of the Immediate Early Gene (IEG) Arc, which is tied to synaptic plasticity and memory demands, and correlated imaging results with memory performance. Our data confirm the existence of subnetworks segregated along the proximodistal axis of CA1 and CA3 that preferentially process spatial and non-spatial information and suggest a key involvement of distal CA1 in temporal information processing. In addition, they show that the two models are complementary to a large extent and posit the “segregated” model as a viable alternative for the two-streams hypothesis.
