The Dual Feminisation of HIV/AIDS

This is an Accepted Manuscript of an article published by Taylor & Francis in Globalizations on 2011, available online: http://wwww.tandfonline.com/10.1080/14747731.2010.49302

Remodeling by fibroblasts alters the rate-dependent mechanical properties of collagen

The ways that fibroblasts remodel their environment are central to wound healing, development of musculoskeletal tissues, and progression of pathologies such as fibrosis. However, the changes that fibroblasts make to the material around them and the mechanical consequences of these changes have proven difficult to quantify, especially in realistic, viscoelastic three-dimensional culture environments, leaving a critical need for quantitative data. Here, we observed the mechanisms and quantified the mechanical effects of fibroblast remodeling in engineered tissue constructs (ETCs) comprised of reconstituted rat tail (type I) collagen and human fibroblast cells. To study the effects of remodeling on tissue mechanics, stress-relaxation tests were performed on ETCs cultured for 24, 48, and 72 h. ETCs were treated with deoxycholate and tested again to assess the ECM response. Viscoelastic relaxation spectra were obtained using the generalized Maxwell model. Cells exhibited viscoelastic damping at two finite time constants over which the ECM showed little damping, approximately 0.2 s and 10-30 s. Different finite time constants in the range of 1-7000 s were attributed to ECM relaxation. Cells remodeled the ECM to produce a relaxation time constant on the order of 7000 s, and to merge relaxation finite time constants in the 0.5-2 s range into a single time content in the 1 s range. Results shed light on hierarchical deformation mechanisms in tissues, and on pathologies related to collagen relaxation such as diastolic dysfunction. Statement of Significance As fibroblasts proliferate within and remodel a tissue, they change the tissue mechanically. Quantifying these changes is critical for understanding wound healing and the development of pathologies such as cardiac fibrosis. Here, we characterize for the first time the spectrum of viscoelastic (rate-dependent) changes arising from the remodeling of reconstituted collagen by fibroblasts. The method also provides estimates of the viscoelastic spectra of fibroblasts within a three-dimensional culture environment. Results are of particular interest because of the ways that fibroblasts alter the mechanical response of collagen at loading frequencies associated with cardiac contraction in humans. © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved

MutPred mutational load analysis shows mildly deleterious mitochondrial DNA variants are not more prevalent in Alzheimer's patients, but may be under-represented in healthy older individuals

Mitochondrial DNA (mtDNA) association studies have been conducted for over a decade using the haplogroup (lineage) association method, but this frequently produces conflicting results. Here we analyzed complete mtDNA sequence data of Alzheimer's disease (AD) patients and aged controls, from the United Kingdom (UK) and the United States (US), using a new “mutational load” method. We calculated a pathogenicity score for each of the non-synonymous substitutions of the mtDNA sequences to produce a “total mutational load” for each sequence, and compared the mutational loads of cases and controls. Using these mutational load measures, we found no evidence to support the cumulative role of mtDNA variants as a susceptibility factor in AD; that is, AD patients (UK and US cohorts) did not have higher “mutational loads” than controls. However, the US aged controls, who are significantly older than the UK ones, with many showing evidence of being healthy and having good cognition in old age, had significantly lower “mutational loads”. This finding suggests that low mtDNA mutational load is more prevalent in healthy older people

Robustness and Enhancement of Neural Synchronization by Activity-Dependent Coupling

We study the synchronization of two model neurons coupled through a synapse having an activity-dependent strength. Our synapse follows the rules of Spike-Timing Dependent Plasticity (STDP). We show that this plasticity of the coupling between neurons produces enlarged frequency locking zones and results in synchronization that is more rapid and much more robust against noise than classical synchronization arising from connections with constant strength. We also present a simple discrete map model that demonstrates the generality of the phenomenon.Comment: 4 pages, accepted for publication in PR

Unfolding cross-linkers as rheology regulators in F-actin networks

We report on the nonlinear mechanical properties of a statistically homogeneous, isotropic semiflexible network cross-linked by polymers containing numerous small unfolding domains, such as the ubiquitous F-actin cross-linker Filamin. We show that the inclusion of such proteins has a dramatic effect on the large strain behavior of the network. Beyond a strain threshold, which depends on network density, the unfolding of protein domains leads to bulk shear softening. Past this critical strain, the network spontaneously organizes itself so that an appreciable fraction of the Filamin cross-linkers are at the threshold of domain unfolding. We discuss via a simple mean-field model the cause of this network organization and suggest that it may be the source of power-law relaxation observed in in vitro and in intracellular microrheology experiments. We present data which fully justifies our model for a simplified network architecture.Comment: 11 pages, 4 figures. to appear in Physical Review

Towards a Full Census of the Obscure(d) Vela Supercluster using MeerKAT

Recent spectroscopic observations of a few thousand partially obscured galaxies in the Vela constellation revealed a massive overdensity on supercluster scales straddling the Galactic Equator (l $\sim$ 272.5deg) at $cz \sim 18000$km/s. It remained unrecognised because it is located just beyond the boundaries and volumes of systematic whole-sky redshift and peculiar velocity surveys - and is obscured by the Milky Way. The structure lies close to the apex where residual bulkflows suggest considerable mass excess. The uncovered Vela Supercluster (VSCL) conforms of a confluence of merging walls, but its core remains uncharted. At the thickest foreground dust column densities (|b| < 6 deg) galaxies are not visible and optical spectroscopy is not effective. This precludes a reliable estimate of the mass of VSCL, hence its effect on the cosmic flow field and the peculiar velocity of the Local Group. Only systematic HI-surveys can bridge that gap. We have run simulations and will present early-science observing scenarios with MeerKAT 32 (M32) to complete the census of this dynamically and cosmologically relevant supercluster. M32 has been put forward because this pilot project will also serve as precursor project for HI MeerKAT Large Survey Projects, like Fornax and Laduma. Our calculations have shown that a survey area of the fully obscured part of the supercluster, where the two walls cross and the potential core of the supercluster resides, can be achieved on reasonable time-scales (200 hrs) with M32.Comment: 10 pages, 3 figures, accepted for publication, Proceedings of Science, workshop on "MeerKAT Science: On the Pathway to the SKA", held in Stellenbosch 25-27 May 201