Irimia, A. | bioRxiv Science

bioRxiv2020

Cross-sectional volumes and trajectories of the human brain, gray matter, white matter and cerebrospinal fluid in 9,473 typically aging adults

Accurate knowledge of adult human brain volume (BV) is critical for studies of aging- and disease-related brain alterations, and for monitoring the trajectories of neural and cognitive functions in conditions like Alzheimers disease and traumatic brain injury. This scoping meta-analysis aggregates normative reference values for BV and three related volumetrics--gray matter volume (GMV), white matter volume (WMV) and cerebrospinal fluid volume (CSFV)--from typically-aging adults studied cross-sectionally using magnetic resonance imaging (MRI). Drawing from an aggregate sample of 9,473 adults, this study provides (A) regression coefficients {beta} describing the age-dependent trajectories of volumetric measures by sex within the range from 20 to 70 years based on both linear and quadratic models, and (B) average values for BV, GMV, WMV and CSFV at the representative ages of 20 (young age), 45 (middle age) and 70 (old age). The results provided synthesize [~]20 years of brain volumetrics research and allow one to estimate BV at any age between 20 and 70. Importantly, however, such estimates should be used and interpreted with caution because they depend on MRI hardware specifications (e.g. scanner manufacturer, magnetic field strength), data acquisition parameters (e.g. spatial resolution, weighting), and brain segmentation algorithms. Guidelines are proposed to facilitate future meta- and mega-analyses of brain volumetrics. Disclosure statementThe author declares that he has no actual or potential conflicts of interest.

neuroscience↗

bioRxiv2019

HIV-1 Envelope and MPER antibody structures in lipid assemblies

Structural and functional studies of HIV Env as a transmembrane protein have long been complicated by challenges associated with inherent flexibility of the molecule and the membrane-embedded hydrophobic regions. Thus, most structural studies have utilized soluble forms where the regions C-terminal to the ectodomain are deleted. Here, we present approaches for incorporating full-length, wild-type HIV-1 Env, as well as C-terminally truncated and stabilized versions, into lipid assemblies, providing a modular platform for Env structural studies by single particle electron microscopy. We reconstituted a full-length Env clone into a nanodisc with MSP1D1 scaffold, complexed it with an MPER targeting antibody 10E8, and structurally defined the full quaternary epitope of 10E8 consisting of lipid, MPER and ectodomain contacts. By aligning this and other Env-MPER antibody complex reconstructions with the lipid bilayer, we observe evidence of Env tilting as part of the neutralization mechanism for MPER-targeting antibodies. We also adapted the platform toward vaccine design purposes by introducing stabilizing mutations that allow purification of unliganded Env with peptidisc scaffold.

immunology↗