Reprogramming bone progenitor identity and potency through control of collagen density and oxygen tension

The biophysical microenvironment of the cell is being increasingly used to control cell signaling and to direct cell function. Herein, engineered 3D tuneable biomimetic scaffolds are used to control the cell microenvironment of Adipose-derived Mesenchymal Stromal Cells (AMSC), which exhibit a collagen density-specific profile for early and late stage bone cell lineage status. Cell potency was enhanced when AMSCs were cultured within low collagen density environments in hypoxic conditions. A transitional culture containing varied collagen densities in hypoxic conditions directed differential cell fate responses. The early skeletal progenitor identity (PDPN+CD146−CD73+CD164+) was rescued in the cells which migrated into low collagen density gels, with cells continuously exposed to the high collagen density gels displaying a transitioned bone-cartilage-stromal phenotype (PDPN+CD146+CD73−CD164-). This study uncovers the significant contributions of the physical and physiological cell environment and highlights a chemically independent methodology for reprogramming and isolating skeletal progenitor cells from an adipose-derived cell population

Scaling the Effects of Ocean Acidification on Coral Growth and Coral-Coral Competition on Coral Community Recovery

Ocean acidification (OA) is negatively affecting calcification in a wide variety of marine organisms. These effects are acute for many tropical scleractinian corals under short-term experimental conditions, but it is unclear how these effects interact with ecological processes, such as competition for space, to impact coral communities over multiple years. This study sought to test the use of individual-based models (IBMs) as a tool to scale up the effects of OA recorded in short-term studies to community-scale impacts, combining data from field surveys and mesocosm experiments to parameterize an IBM of coral community recovery on the fore reef of Moorea, French Polynesia. Focusing on the dominant coral genera from the fore reef, Pocillopora, Acropora, Montipora and Porites, model efficacy first was evaluated through the comparison of simulated and empirical dynamics from 2010-2016, when the reef was recovering from sequential acute disturbances (a crown-of-thorns seastar outbreak followed by a cyclone) that reduced coral cover to ~0% by 2010. The model then was used to evaluate how the effects of OA (1,100-1,200 µatm pCO2) on coral growth and competition among corals affected recovery rates (as assessed by changes in % cover y-1) of each coral population between 2010-2016. The model indicated that recovery rates for the fore reef community was halved by OA over 7 years, with cover increasing at 11% y-1 under ambient conditions and 4.8% y-1 under OA conditions. However, when OA was implemented to affect coral growth and not competition among corals, coral community recovery increased to 7.2% y-1, highlighting mechanisms other than growth suppression (i.e., competition), through which OA can impact recovery. Our study reveals the potential for IBMs to assess the impacts of OA on coral communities at temporal and spatial scales beyond the capabilities of experimental studies, but this potential will not be realized unless empirical analyses address a wider variety of response variables representing ecological, physiological and functional domains

Micro thermal analysis: A novel method of determining the extent of collagen cross-linking within a collagen construct- applications for tissue engineering

Increasingly complex designs of collagen scaffolds used in tissue engineering require more accurate and sensitive methods of testing. A new proposal to create cross-linked tunnels within a collagen scaffold for use in vascular and nerve studies will require a novel method of assessing the extent of cross-linking within the walls of the tube- to ensure maximal strength for matrix viability. To date this method has not yet been investigated. Aim: this study will investigate ways to differentiate between cross-linked and native collagen using melting characteristics found by Micro thermal analysis at point regions throughout the construct to give a detailed intra-matrix map

Mimicking the body- a novel method of Cross-linking collagen to control scaffold design- implications on human tissue engineering

Scaffold design is an essential part of tissue engineering. Cross-linked collagen matrices are often used to increase the mechanical strength of scaffolds. The ability to create and control different patterns of cross-linking within a collagen matrix would allow manipulation of scaffold characteristics (e.g. anisotropy, strength and shape) in order to tailor the design of the scaffold more appropriately to different applications. Photochemical crosslinking using Riboflavin and blue light1 has the potential to create patterns of crosslinking throughout a matrix. If successful, it can have applications in more sophisticated scaffold creation such as crosslinked tubular structures for nerve and vascular engineering. This study will assess the suitability of this method for such an application

Quantitative nanohistological investigation of scleroderma: An atomic force microscopy-based approach to disease characterization

Scleroderma (or systemic sclerosis, SSc) is a disease caused by excess crosslinking of collagen. The skin stiffens and becomes painful, while internally, organ function can be compromised by the less elastic collagen. Diagnosis of SSc is often only possible in advanced cases by which treatment time is limited. A more detailed analysis of SSc may provide better future treatment options and information of disease progression. Recently, the histological stain picrosirius red showing collagen register has been combined with atomic force microscopy (AFM) to study SSc. Skin from healthy individuals and SSc patients was biopsied, stained and studied using AFM. By investigating the crosslinking of collagen at a smaller hierarchical stage, the effects of SSc were more pronounced. Changes in morphology and Young’s elastic modulus were observed and quantified; giving rise to a novel technique, we have termed “quantitative nanohistology”. An increase in nanoscale stiffness in the collagen for SSc compared with healthy individuals was seen by a significant increase in the Young’s modulus profile for the collagen. These markers of stiffer collagen in SSc are similar to the symptoms experienced by patients, giving additional hope that in the future, nanohistology using AFM can be readily applied as a clinical tool, providing detailed information of the state of collagen

Combining nano-physical and computational investigations to understand the nature of “aging” in dermal collagen

The extracellular matrix of the dermis is a complex, dynamic system with the various dermal components undergoing individual physiologic changes as we age. Age-related changes in the physical properties of collagen were investigated in particular by measuring the effect of aging, most likely due to the accumulation of advanced glycation end product (AGE) cross-links, on the nanomechanical properties of the collagen fibril using atomic force microscope nano-indentation. An age-related decrease in the Young’s modulus of the transverse fibril was observed (from 8.11 to 4.19 GPa in young to old volunteers, respectively, P<0.001). It is proposed that this is due to a change in the fibril density caused by age-related differences in water retention within the fibrils. The new collagen–water interaction mechanism was verified by electronic structure calculations, showing it to be energetically feasible

Carbon exchange between a shelf sea and the ocean: The Hebrides Shelf, west of Scotland

Global mass balance calculations indicate the majority of particulate organic carbon (POC) exported from shelf seas is transferred via downslope exchange processes. Here we demonstrate the downslope flux of POC from the Hebrides Shelf is approximately 3-to-5-fold larger per unit length/area than the global mean. To reach this conclusion we quantified the offshore transport of particulate and dissolved carbon fractions via the “Ekman Drain”, a strong downwelling feature of the NW European Shelf circulation, and subsequently compared these fluxes to simultaneous regional air-sea CO2 fluxes and on-shore wind-driven Ekman fluxes to constrain the carbon dynamics of this shelf. Along the shelf break we estimate a mean offshelf total carbon (dissolved + particulate) flux of 4.2 tonnes C m−1 d−1 compared to an onshelf flux of 4.5 tonnes C m−1 d−1. Organic carbon represented 3.3% of the onshelf carbon flux but 6.4% of the offshelf flux indicating net organic carbon export. Dissolved organic carbon represented 95% and POC 5% of the exported organic carbon pool. When scaled along the shelf break the total offshelf POC flux (0.007 Tg C d−1) was found to be three times larger than the regional air-sea CO2 ingassing flux (0.0021 Tg C d−1), an order of magnitude larger than the particulate inorganic carbon flux (0.0003 Tg C d−1) but far smaller than the DIC (2.03 Tg C d−1) or DOC (0.13 Tg C d−1) fluxes. Significant spatial heterogeneity in the Ekman drain transport confirms that offshelf carbon fluxes via this mechanism are also spatially heterogeneous. This article is protected by copyright. All rights reserved

Determinants and value relevance of UK CEO pay slice

This paper studies the CEO pay slice (CPS) of UK listed firms during the period 2003 to 2009. We investigate the determinants of CPS. We study the links between CPS and measures of firm performance. We find that firms with higher levels of corporate governance ratings and those with more independent boards tend to have higher CPS. In addition, we find that CEOs are more likely to receive lower compensation when they chair the board and when they work in firms with large board size. We also find that higher CPS is positively associated with firm performance after controlling for the firm-specific characteristics and corporate governance variables. We get compatible results when we examine the association between equity-based CPS and firm performance. Our results remain robust to alternative accounting measures of firm performance. Our results suggest that high UK CPS levels do indeed reflect top managerial talent rather than managerial power

Spin-Diffusion Lengths in Metals and Alloys, and Spin-Flipping at Metal/Metal Interfaces: an Experimentalist's Critical Review

In magnetoresistive (MR) studies of magnetic multilayers composed of combinations of ferromagnetic (F) and non-magnetic (N) metals, the magnetic moment (or related 'spin') of each conduction electron plays a crucial role, supplementary to that of its charge. While initial analyses of MR in such multilayers assumed that the direction of the spin of each electron stayed fixed as the electron transited the multilayer, we now know that this is true only in a certain limit. Generally, the spins 'flip' in a distance characteristic of the metal, its purity, and the temperature. They can also flip at F/N or N1/N2 interfaces. In this review we describe how to measure the lengths over which electron moments flip in pure metals and alloys, and the probability of spin-flipping at metallic interfaces. Spin-flipping within metals is described by a spin-diffusion length,l^M(sf), where the metal M = F or N. Spin-diffusion lengths are the characteristic lengths in the current-perpendicular-to-plane (CPP) and lateral non-local (LNL) geometries that we focus upon in this review. In certain simple cases, l^N(sf) sets the distance over which the CPP-MR and LNL-MR decrease as the N-layer thickness (CPP-MR) or N-film length (LNL) increases, and l^F(sf) does the same for increase of the CPP-MR with increasing F-layer thickness. Spin-flipping at M1/M2 interfaces can be described by a parameter, delta(M1/M2), which determines the spin-flipping probability, P = 1 - exp(-delta). Increasing delta(M1/M2) usually decreases the MR. We list measured values of these parameters and discuss the limitations on their determinations.Comment: Invited Review, to appear in J. Phys. Cond. Matter. 50 pages, 18 figures. The new version contains additional material and revisions to improve clarit