Search

This review addresses the acute need to acknowledge the mechanical heterogeneity of brain matter and to accurately calibrate its local viscoelastic material properties accordingly. Specifically, it is important to compile the existing and disparate literature on attenuation power-laws and dispersion to make progress in wave physics of brain matter, a field of research that has the potential to explain the mechanisms at play in diffuse axonal injury and mild traumatic brain injury in general. Currently, viscous effects in the brain are modelled using Prony-series, i.e., a sum of decaying exponentials at different relaxation times. Here we collect and synthesise the Prony-series coefficients appearing in the literature for twelve regions: brainstem, basal ganglia, cerebellum, corona radiata, corpus callosum, cortex, dentate gyrus, hippocampus, thalamus, grey matter, white matter, homogeneous brain, and for eight different mammals: pig, rat, human, mouse, cow, sheep, monkey and dog. Using this data, we compute the fractional-exponent attenuation power-laws for different tissues of the brain, the corresponding dispersion laws resulting from causality, and the averaged Prony-series coefficients. STATEMENT OF SIGNIFICANCE: Traumatic brain injuries are considered a silent epidemic and finite element methods (FEMs) are used in modelling brain deformation, requiring access to viscoelastic properties of brain. To the best of our knowledge, this work presents 1) the first multi-frequency viscoelastic atlas of the heterogeneous brain, 2) the first review focusing on viscoelastic modelling in both FEMs and experimental works, 3) the first attempt to conglomerate the disparate existing literature on the viscoelastic modelling of the brain and 4) the largest collection of viscoelastic parameters for the brain (212 different Prony-series spanning 12 different tissues and 8 different animal surrogates). Furthermore, this work presents the first brain atlas of attenuation power-laws essential for modelling shear waves in brain., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Chromatin consists of a complex of DNA and histone proteins as its core components and plays an important role in both packaging DNA and regulating DNA metabolic pathways such as DNA replication, transcription, recombination, and chromosome segregation. Proper functioning of chromatin further involves a network of interactions among molecular complexes that modify chromatin structure and organization to affect the accessibility of DNA to transcription factors leading to the activation or repression of the transcription of target DNA loci. Based on its structure and compaction state, chromatin is categorized into euchromatin, heterochromatin, and centromeric chromatin. In this review, we discuss distinct chromatin factors and molecular complexes that constitute euchromatin-open chromatin structure associated with active transcription; heterochromatin-less accessible chromatin associated with silencing; centromeric chromatin-the site of spindle binding in chromosome segregation.

Entry of human immunodeficiency virus type 1 (HIV-1) into host cells is mediated by conformational changes in the envelope glycoprotein (Env) that are triggered by Env binding to cellular CD4 and chemokine receptors. These conformational changes involve the opening of the gp120 surface subunit, exposure of the fusion peptide in the gp41 transmembrane subunit, and refolding of the gp41 N- and C-terminal heptad repeat regions (HR1 and HR2) first into an extended prehairpin intermediate and then into a compact 6-helix bundle (6HB) that facilitates fusion between viral and host cell membranes. Previously, we reported that Envs resistant to HR1 peptide fusion inhibitors acquired key resistance mutations in either HR1 or HR2 that increased 6HB stability. Here, we identify residues in HR1 that contribute not only to fusion inhibitor resistance and 6HB stability but also to reduced reactivity to CD4-induced conformational changes that lead to 6HB formation. While all Envs show increased neutralization sensitivity to mimetic CD4 (mCD4), Envs with either the E560K or Q577R HR1 mutation reduced conformational reactivity to CD4 that resisted viral inactivation and triggering to the 6HB. Using a panel of monoclonal antibodies (mAbs), we further determined that Envs from both HR1 and HR2 resistance pathways exhibit a relaxed trimer conformation due to gp120 adaptive mutations in different regions of Env that segregate by resistance pathway. These findings highlight regions of cross talk between gp120 and gp41 and identify HR1 residues that play important roles in regulating CD4-induced conformational changes in Env. IMPORTANCE Binding of the HIV envelope glycoprotein (Env) to cellular CD4 and chemokine receptors triggers conformational changes in Env that mediate virus entry, but premature triggering of Env conformational changes leads to virus inactivation. Currently, we have a limited understanding of the network of residues that regulate Env conformational changes. Here, we identify residues in HR1 of gp41 that modulate conformational changes in response to gp120 binding to CD4 and show that the mutations in HR1 and HR2 that confer resistance to fusion inhibitors are associated with gp120 mutations in different regions of Env that confer a more open conformation. These findings contribute to our understanding of the regulation of Env conformational changes and efforts to design new entry inhibitors and stable Env vaccine immunogens.