***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:  Sleep and wakefulness are greatly influenced by various physiological and psychological factors, but the neuronal elements responsible for organizing sleep-wake behavior in response to these factors are largely unknown. In this study, we report that a subset of neurons in the lateral hypothalamic area (LH) expressing the neuropeptide neurotensin (Nts) is critical for orchestrating sleep-wake responses to acute psychological and physiological challenges or stressors. We show that selective activation of NtsLH neurons with chemogenetic or optogenetic methods elicits rapid transitions from non-rapid eye movement (NREM) sleep to wakefulness and produces sustained arousal, higher locomotor activity (LMA), and hyperthermia, which are commonly observed after acute stress exposure. On the other hand, selective chemogenetic inhibition of NtsLH neurons attenuates the arousal, LMA, and body temperature (Tb) responses to a psychological stress (a novel environment) and augments the responses to a physiological stress (fasting).


Output:

Adjusting sleep-wake behavior in response to environmental and physiological challenges may not only be of protective value, but can also be vital for the survival of the organism. For example, while it is crucial to increase wake to explore a novel environment to search for potential threats and food sources, it is also necessary to decrease wake and reduce energy expenditure during prolonged absence of food. In this study, we report that a subset of neurons in the lateral hypothalamic area (LH) expressing the neuropeptide neurotensin (Nts) is critical for orchestrating sleep-wake responses to such challenges. We show that brief activation of NtsLH neurons in mice evokes immediate arousals from sleep, while their sustained activation increases wake, locomotor activity, and body temperature for several hours. In contrast, when NtsLH neurons are inhibited, mice are neither able to sustain wake in a novel environment nor able to reduce wake during food deprivation. These data suggest that NtsLH neurons may be necessary for generating appropriate sleep-wake responses to a wide variety of environmental and physiological challenges.
