A scaling law of multilevel evolution: how the balance between within- and among-collective evolution is determined

Numerous living systems are hierarchically organized, whereby replicating components are grouped into reproducing collectives—e.g., organelles are grouped into cells, and cells are grouped into multicellular organisms. In such systems, evolution can operate at two levels: evolution among collectives, which tends to promote selfless cooperation among components within collectives (called altruism), and evolution within collectives, which tends to promote cheating among components within collectives. The balance between within- and among-collective evolution thus exerts profound impacts on the fitness of these systems. Here, we investigate how this balance depends on the size of a collective (denoted by N) and the mutation rate of components (m) through mathematical analyses and computer simulations of multiple population genetics models. We first confirm a previous result that increasing N or m accelerates within-collective evolution relative to among-collective evolution, thus promoting the evolution of cheating. Moreover, we show that when within- and among-collective evolution exactly balance each other out, the following scaling relation generally holds: Nmα is a constant, where scaling exponent α depends on multiple parameters, such as the strength of selection and whether altruism is a binary or quantitative trait. This relation indicates that although N and m have quantitatively distinct impacts on the balance between within- and among-collective evolution, their impacts become identical if m is scaled with a proper exponent. Our results thus provide a novel insight into conditions under which cheating or altruism evolves in hierarchically organized replicating systems.     

The Statistical Trends of Protein Evolution: A Lesson from AlphaFold Database

The recent development of artificial intelligence provides us with new and powerful tools for studying the mysterious relationship between organism evolution and protein evolution. In this work, based on the AlphaFold Protein Structure Database (AlphaFold DB), we perform comparative analyses of the proteins of different organisms. The statistics of AlphaFold-predicted structures show that, for organisms with higher complexity, their constituent proteins will have larger radii of gyration, higher coil fractions, and slower vibrations, statistically. By conducting normal mode analysis and scaling analyses, we demonstrate that higher organismal complexity correlates with lower fractal dimensions in both the structure and dynamics of the constituent proteins, suggesting that higher functional specialization is associated with higher organismal complexity. We also uncover the topology and sequence bases of these correlations. As the organismal complexity increases, the residue contact networks of the constituent proteins will be more assortative, and these proteins will have a higher degree of hydrophilic–hydrophobic segregation in the sequences. Furthermore, by comparing the statistical structural proximity across the proteomes with the phylogenetic tree of homologous proteins, we show that, statistical structural proximity across the proteomes may indirectly reflect the phylogenetic proximity, indicating a statistical trend of protein evolution in parallel with organism evolution. This study provides new insights into how the diversity in the functionality of proteins increases and how the dimensionality of the manifold of protein dynamics reduces during evolution, contributing to the understanding of the origin and evolution of lives.     

PARK2-mediated mitophagy is involved in regulation of HBEC senescence in COPD pathogenesis

Cigarette smoke (CS)-induced mitochondrial damage with increased reactive oxygen species (ROS) production has been implicated in COPD pathogenesis by accelerating senescence. Mitophagy may play a pivotal role for removal of CS-induced damaged mitochondria, and the PINK1 (PTEN-induced putative kinase 1)-PARK2 pathway has been proposed as a crucial mechanism for mitophagic degradation. Therefore, we sought to investigate to determine if PINK1-PARK2-mediated mitophagy is involved in the regulation of CS extract (CSE)-induced cell senescence and in COPD pathogenesis. Mitochondrial damage, ROS production, and cell senescence were evaluated in primary human bronchial epithelial cells (HBEC). Mitophagy was assessed in BEAS-2B cells stably expressing EGFP-LC3B, using confocal microscopy to measure colocalization between TOMM20-stained mitochondria and EGFP-LC3B dots as a representation of autophagosome formation. To elucidate the involvement of PINK1 and PARK2 in mitophagy, knockdown and overexpression experiments were performed. PINK1 and PARK2 protein levels in lungs from patients were evaluated by means of lung homogenate and immunohistochemistry. We demonstrated that CSE-induced mitochondrial damage was accompanied by increased ROS production and HBEC senescence. CSE-induced mitophagy was inhibited by PINK1 and PARK2 knockdown, resulting in enhanced mitochondrial ROS production and cellular senescence in HBEC. Evaluation of protein levels demonstrated decreased PARK2 in COPD lungs compared with non-COPD lungs. These results suggest that PINK1-PARK2 pathway-mediated mitophagy plays a key regulatory role in CSE-induced mitochondrial ROS production and cellular senescence in HBEC. Reduced PARK2 expression levels in COPD lung suggest that insufficient mitophagy is a part of the pathogenic sequence of COPD.     

Back-Propagation Operation for Analog Neural Network Hardware with Synapse Components Having Hysteresis Characteristics

To realize an analog artificial neural network hardware, the circuit element for synapse function is important because the number of synapse elements is much larger than that of neuron elements. One of the candidates for this synapse element is a ferroelectric memristor. This device functions as a voltage controllable variable resistor, which can be applied to a synapse weight. However, its conductance shows hysteresis characteristics and dispersion to the input voltage. Therefore, the conductance values vary according to the history of the height and the width of the applied pulse voltage. Due to the difficulty of controlling the accurate conductance, it is not easy to apply the back-propagation learning algorithm to the neural network hardware having memristor synapses. To solve this problem, we proposed and simulated a learning operation procedure as follows. Employing a weight perturbation technique, we derived the error change. When the error reduced, the next pulse voltage was updated according to the back-propagation learning algorithm. If the error increased the amplitude of the next voltage pulse was set in such way as to cause similar memristor conductance but in the opposite voltage scanning direction. By this operation, we could eliminate the hysteresis and confirmed that the simulation of the learning operation converged. We also adopted conductance dispersion numerically in the simulation. We examined the probability that the error decreased to a designated value within a predetermined loop number. The ferroelectric has the characteristics that the magnitude of polarization does not become smaller when voltages having the same polarity are applied. These characteristics greatly improved the probability even if the learning rate was small, if the magnitude of the dispersion is adequate. Because the dispersion of analog circuit elements is inevitable, this learning operation procedure is useful for analog neural network hardware.     

Production and Characterization of Transgenic Mice Harboring Mutant Human UMOD Gene

Familial juvenile hyperuricemic nephropathy is caused by mutations in the UMOD gene encoding uromodulin. A transgenic mouse model was developed by introducing a human mutant UMOD (C148W) cDNA under control of the mouse umod promoter. Uromodulin accumulation was observed in the thick ascending limb cells in the kidney of transgenic mice. However, the urinary excretion of uromodulin in transgenic mice did not decrease and LC-MS/MS analysis indicated it was of mouse origin. Moreover, the creatinine clearance was not different between wildtype and transgenic animals. Consequently, the onset of the disease was not observed in transgenic mice until 24 weeks of age.     

Thermal Characterization and Cytotoxicity of Complexes Formed by Papain and Cyclodextrin

Papain is a proteolytic enzyme with restricted applications due to its limited stability. Cyclodextrins are widely used in pharmaceutical formulations once they are able to form complexes with other molecules, improving their stability and bioavailability. The purpose of the present paper was to analyze complexes formed by papain/hydroxypropyl-β-cyclodextrin and papain/β-cyclodextrin by thermal analysis and cytotoxicity tests to verify their possible interactions and toxicological behavior. Complex solutions were prepared at different molar ratios and collected as a function of time to be lyophilized and analyzed. Results showed changes in endothermic events and cytotoxicity profiles. A complex formation for both complexes is observed; nevertheless, β-cyclodextrin was able to change the enzyme characteristics more efficiently.     

Analysis of proteins showing differential changes during ATP oscillations in chondrogenesis

Prechondrogenic condensation is a critical step for skeletal pattern formation. Our previous study showed that ATP oscillations play an essential role in prechondrogenic condensation because they induce oscillatory secretion. However, the molecular mechanisms that underlie ATP oscillations remain poorly understood. We examined how differential changes in proteins are implicated in ATP oscillations during chondrogenesis by using liquid chromatography/mass spectrometry. Our analysis showed that a number of proteins involved in ATP synthesis/consumption, catabolic/anabolic processes, actin dynamics, cell migration and adhesion were detected at either the peak or the trough of ATP oscillations, which implies that these proteins have oscillatory expression patterns that are coupled to ATP oscillations. On the basis of the results, we suggest that (1) the oscillatory expression of proteins involved in ATP synthesis/consumption and catabolic/anabolic processes can contribute to the generation or maintenance of ATP oscillations and that (2) the oscillatory expression of proteins involved in actin dynamics, cell migration and adhesion plays key roles in prechondrogenic condensation by inducing collective adhesion and migration in cooperation with ATP oscillations. Copyright © 2014 John Wiley & Sons, Ltd.     

A First-Passage Time Approach to Diffusion in Liquids and Superionic Conductors

Abstract

As a new tool to investigate single-particle motion in condensed matter, a first-passage time (FPT) approach to diffusion is developed and applied to the molecular dynamics simulations of simple liquids and superionic conductor CaF₂. It is shown that a continuous diffusion model reproduces the observed FPT distribution quite well for both liquids and CaF₂, which enables us to evaluate diffusion constants with good accuracy by our method. On a length scale as small as a lattice constant, however, the effect of hopping appears in the FPT distribution of F^? ions, which can not be described by a continuous diffusion model. A simple hopping diffusion model is proposed and examined from the FPT viewpoint.