***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:  Macroscopic oscillations of different brain regions show multiple phase relationships that are persistent across time and have been implicated in routing information. While multiple cellular mechanisms influence the network oscillatory dynamics and structure the macroscopic firing motifs, one of the key questions is to identify the biophysical neuronal and synaptic properties that permit such motifs to arise. A second important issue is how the different neural activity coherence states determine the communication between the neural circuits. Here we analyse the emergence of phase-locking within bidirectionally delayed-coupled spiking circuits in which global gamma band oscillations arise from synaptic coupling among largely excitable neurons. We consider both the interneuronal (ING) and the pyramidal-interneuronal (PING) population gamma rhythms and the inter coupling targeting the pyramidal or the inhibitory neurons. Using a mean-field approach together with an exact reduction method, we reduce each spiking network to a low dimensional nonlinear system and derive the macroscopic phase resetting-curves (mPRCs) that determine how the phase of the global oscillation responds to incoming perturbations. This is made possible by the use of the quadratic integrate-and-fire model together with a Lorentzian distribution of the bias current. Depending on the type of gamma (PING vs. ING), we show that incoming excitatory inputs can either speed up the macroscopic oscillation (phase advance; type I PRC) or induce both a phase advance and a delay (type II PRC). From there we determine the structure of macroscopic coherence states (phase-locking) of two weakly synaptically-coupled networks. To do so we derive a phase equation for the coupled system which links the synaptic mechanisms to the coherence states of the system. We show that a synaptic transmission delay is a necessary condition for symmetry breaking, i.e. a non-symmetric phase lag between the macroscopic oscillations. This potentially provides an explanation to the experimentally observed variety of gamma phase-locking modes. Our analysis further shows that symmetry-broken coherence states can lead to a preferred direction of signal transfer between the oscillatory networks where this directionality also depends on the timing of the signal. Hence we suggest a causal theory for oscillatory modulation of functional connectivity between cortical circuits.


Output:

Large scale brain oscillations emerge from synaptic interactions within neuronal circuits. Over the past years, such macroscopic rhythms have been suggested to play a crucial role in routing the flow of information across cortical regions, resulting in a functional connectome. The underlying mechanism is cortical oscillations that bind together following a well-known motif called phase-locking. While there is significant experimental support for multiple phase-locking modes in the brain, it is still unclear what is the underlying mechanism that permits macroscopic rhythms to phase lock. In the present paper we take up with this issue, and to show that, one can study the emergent macroscopic phase-locking within the mathematical framework of weakly coupled oscillators. We find that under synaptic delays, fully symmetrically coupled networks can display symmetry-broken states of activity, where one network starts to lead in phase the second (also sometimes known as stuttering states). When we analyse how incoming transient signals affect the coupled system, we find that in the symmetry-broken state, the effect depends strongly on which network is targeted (the leader or the follower) as well as the timing of the input. Hence we show how the dynamics of the emergent phase-locked activity imposes a functional directionality on how signals are processed. We thus offer clarification on the synaptic and circuit properties responsible for the emergence of multiple phase-locking patterns and provide support for its functional implication in information transfer.
