Biophysica

The nervous activity of the brain takes place in higher-dimensional functional spaces. It has been proposed that the brain might be equipped with phase spaces characterized by four spatial dimensions plus time, instead of the classical three plus time. This suggests that global visualization methods for exploiting four-dimensional maps of three-dimensional experimental data sets might be used in neuroscience. We asked whether it is feasible to describe the four-dimensional trajectories (plus time) of two-dimensional (plus time) electroencephalographic traces (EEG). We made use of quaternion orthographic projections to map to the surface of four-dimensional hyperspheres EEG signal patches treated with Fourier analysis. Once achieved the proper quaternion maps, we show that this multi-dimensional procedure brings undoubted benefits. The treatment of EEG traces with Fourier analysis allows the investigation the scale-free activity of the brain in terms of trajectories on hyperspheres and quaternionic networks. Repetitive spatial and temporal patterns undetectable in three dimensions (plus time) are easily enlightened in four dimensions (plus time). Further, a quaternionic approach makes it feasible to identify spatially far apart and temporally distant periodic trajectories with the same features, such as, e.g., the same oscillatory frequency or amplitude. This leads to an incisive operational assessment of global or broken symmetries, domains of attraction inside three-dimensional projections and matching descriptions between the apparently random paths hidden in the very structure of nervous fractal signals. Full article

The origin and potential role of chiral asymmetry remain one of the most exciting issues in biology. In this paper we review the chirality of biological macromolecules, starting at the level of single molecules and continuing to the level of supramolecular assemblies. We discuss the physical and chemical consequences of the presence of chirality and their role in the self-organization and formation of structural hierarchies in cells. Homochirality may serve as an essential factor that invokes mechanisms required to control the formation of discrete structural hierarchies in macromolecules and macromolecular assemblies. Symmetry is of fundamental importance not only for all molecular biology as a systemic factor of its organization but also for pharmacology, as well as a systemic factor of drug stereospecificity. Full article

A recent report in the journal, Neurology, documents age-normalized, nation-specific (e.g., United States and Western Europe), progressive decrease of dementia, beginning about 25 years ago. This observation has, thus far, not had explanation. We begin our proposed explanation with the following previous disease construct. (1) Some dementia is caused by innate immune over-response to infections. (2) The innate immune over-response occurs via excessive conversion of amyloid protein to α-sheet conformation. (3) This conversion evolved to inhibit invading microbes by binding microbe-associated α-sheet, e.g., in hyper-expanded capsid intermediates of some viruses. The rarity of human α-sheet makes this inhibition specific for microbial invaders. As foundation, here we observe directly, for the first time, extreme, sheet-like outer shell thinness in a hyper-expanded capsid of phage T3. Based on phage/herpesvirus homology, we propose the following. The above decrease in dementia is caused by varicella-zoster virus (VZV) vaccination, USFDA-approved about 25 years ago; VZV is a herpesvirus and causes chickenpox and shingles. In China and Japan, a cotemporaneous non-decrease is explained by lower anti-VZV vaccination. Co-assembly extension of α-sheet is relatively independent of amino acid sequence. Thus, we project that additional dementia is suppressible by vaccination against other viruses, including other herpesviruses. Full article

Per-Arnt-Sim (PAS) domains are evolutionarily-conserved regions found in proteins in all living systems, involved in transcriptional regulation and the response to hypoxic and xenobiotic stress. Despite having low primary sequence similarity, they show an impressively high structural conservation. Nonetheless, understanding the underlying mechanisms that drive the biological function of the PAS domains remains elusive. In this work, we used molecular dynamics simulations and bioinformatics tools in order the investigate the molecular characteristics that govern the intrinsic dynamics of five PAS-B domains (human AhR receptor, NCOA1, HIF1α, and HIF2α transcription factors, and Drosophila Suzukii (D. Suzukii) juvenile hormone receptor JHR). First, we investigated the effects of different length of N and C terminal regions of the AhR PAS-B domain, showing that truncation of those segments directly affects structural stability and aggregation propensity of the domain. Secondly, using the recently annotated PAS-B located in the methoprene-tolerant protein/juvenile hormone receptor (JHR) from D. Suzukii, we have shown that the mutation of the highly conserved “gatekeeper” tyrosine to phenylalanine (Y322F) does not affect the stability of the domain. Finally, we investigated possible redox-regulation of the AhR PAS-B domain by focusing on the cysteinome residues within PAS-B domains. The cysteines in AhR PAS-B are directly regulating the dynamics of the small molecule ligand-gating loop (residues 305 to 326). In conclusion, we comprehensibly described several molecular features governing the behaviour of PAS-B domains in solution, which may lead to a better understanding of the forces driving their biological functions. Full article