Mitocryptide-2: Identification of Its Minimum Structure for Specific Activation of FPR2-Possible Receptor Switching from FPR2 to FPR1 by Its Physiological C-terminal Cleavages.

Mitocryptides are a novel family of endogenous neutrophil-activating peptides originating from various mitochondrial proteins. Mitocryptide-2 (MCT-2) is one of such neutrophil-activating peptides, and is produced as an N-formylated pentadecapeptide from mitochondrial cytochrome b. Although MCT-2 is a specific endogenous ligand for formyl peptide receptor 2 (FPR2), the chemical structure within MCT-2 that is responsible for FPR2 activation is still obscure. Here, we demonstrate that the N-terminal heptapeptide structure of MCT-2 with an N-formyl group is the minimum structure that specifically activates FPR2. Moreover, the receptor molecule for MCT-2 is suggested to be shifted from FPR2 to its homolog formyl peptide receptor 1 (FPR1) by the physiological cleavages of its C-terminus. Indeed, N-terminal derivatives of MCT-2 with seven amino acid residues or longer caused an increase of intracellular free Ca2+ concentration in HEK-293 cells expressing FPR2, but not in those expressing FPR1. Those MCT-2 derivatives also induced ß-hexosaminidase secretion in neutrophilic/granulocytic differentiated HL-60 cells via FPR2 activation. In contrast, MCT-2(1-4), an N-terminal tetrapeptide of MCT-2, specifically activated FPR1 to promote those functions. Moreover, MCT-2 was degraded in serum to produce MCT-2(1-4) over time. These findings suggest that MCT-2 is a novel critical factor that not only initiates innate immunity via the specific activation of FPR2, but also promotes delayed responses by the activation of FPR1, which may include resolution and tissue regeneration. The present results also strongly support the necessity of considering the exact chemical structures of activating factors for the investigation of innate immune responses.

Human photoplethysmogram through the Morse graph: Searching for the saddle point in experimental data.

Photoplethysmogram (PPG) is one of the noninvasive biological signals widely used for the estimation of physiological parameters, such as heart rates in human health monitoring. Methods of its processing, its applications, and dynamics have been extensively investigated over the last several decades. However, there is still lack of the knowledge related to the fundamental structure of the PPG dynamics such as saddle equilibrium points, which have crucial importance to achieve the full understanding of the PPG dynamics and might provide useful information for establishing a mathematical model of the PPG. In this study, Morse graph theory was applied to the experimental PPG data in an attempt to verify the existence of saddle equilibrium and estimate its location with respect to the time-delay-reconstructed PPG attractor. The results demonstrated evidence that a saddle equilibrium point can be found in a neighborhood of the reconstructed PPG trajectory; moreover, it was found to be in the same reconstructed attractor's region for healthy subjects from different age groups that points toward fundamental importance of the found saddle equilibrium for a general understanding of the PPG dynamics.