The interplay between tissue growth and scaffold degradation in engineered tissue constructs

In vitro tissue engineering is emerging as a potential tool to meet the high demand for replacement tissue, caused by the increased incidence of tissue degeneration and damage. A key challenge in this field is ensuring that the mechanical properties of the engineered tissue are appropriate for the in vivo environment. Achieving this goal will require detailed understanding of the interplay between cell proliferation, extracellular matrix (ECM) deposition and scaffold degradation.\ud \ud In this paper, we use a mathematical model (based upon a multiphase continuum framework) to investigate the interplay between tissue growth and scaffold degradation during tissue construct evolution in vitro. Our model accommodates a cell population and culture medium, modelled as viscous fluids, together with a porous scaffold and ECM deposited by the cells, represented as rigid porous materials. We focus on tissue growth within a perfusion bioreactor system, and investigate how the predicted tissue composition is altered under the influence of (i) differential interactions between cells and the supporting scaffold and their associated ECM, (ii) scaffold degradation, and (iii) mechanotransduction-regulated cell proliferation and ECM deposition.\ud \ud Numerical simulation of the model equations reveals that scaffold heterogeneity typical of that obtained from μCT scans of tissue engineering scaffolds can lead to significant variation in the flow-induced mechanical stimuli experienced by cells seeded in the scaffold. This leads to strong heterogeneity in the deposition of ECM. Furthermore, preferential adherence of cells to the ECM in favour of the artificial scaffold appears to have no significant influence on the eventual construct composition; adherence of cells to these supporting structures does, however, lead to cell and ECM distributions which mimic and exaggerate the heterogeneity of the underlying scaffold. Such phenomena have important ramifications for the mechanical integrity of engineered tissue constructs and their suitability for implantation in vivo

Quasars, their host galaxies, and their central black holes

We present the final results from our deep HST imaging study of the hosts of radio-quiet quasars (RQQs), radio-loud quasars (RLQs) and radio galaxies (RGs). We describe new WFPC2 R-band observations for 14 objects and model these images in conjunction with the data already reported in McLure et al (1999). We find that spheroidal hosts become more prevalent with increasing nuclear luminosity such that, for nuclear luminosities M_V < -23.5, the hosts of both radio-loud and radio-quiet AGN are virtually all massive ellipticals. Moreover we demonstrate that the basic properties of these hosts are indistinguishable from those of quiescent, evolved, low-redshift ellipticals of comparable mass. This result kills any lingering notion that radio-loudness is determined by host-galaxy morphology, and also sets severe constraints on evolutionary schemes which attempt to link low-z ULIRGs with RQQs. Instead, we show that our results are as expected given the relationship between black-hole and spheroid mass established for nearby galaxies, and apply this relation to estimate the mass of the black hole in each object. The results agree very well with completely-independent estimates based on nuclear emission-line widths; all the quasars in our sample have M(bh) > 5 x 10^8 solar masses, while the radio-loud objects are confined to M(bh) > 10^9 solar masses. This apparent mass-threshold difference, which provides a natural explanation for why RQQs outnumber RLQs by a factor of 10, appears to reflect the existence of a minimum and maximum level of black-hole radio output which is a strong function of black-hole mass. Finally, we use our results to estimate the fraction of massive spheroids/black-holes which produce quasar-level activity. This fraction is \~0.1% at the present day, rising to > 10% at z = 2-3.Comment: Revised version accepted for publication in Monthly Notices of the Royal Astronomical Society. 46 pages, the final 19 of which comprise an Appendix. 15 figures in main text. A further 14 4-panel greyscale plots and 14 line plots which appear in the Appendix have been reproduced here with reduced quality due to space limitations. A full resolution copy of the manuscript can be obtained via ftp://ftp.roe.ac.uk/pub/jsd/dunlop2002.ps.g

Spreading dynamics on spatially constrained complex brain networks

The study of dynamical systems defined on complex networks provides a natural framework with which to investigate myriad features of neural dynamics, and has been widely undertaken. Typically, however, networks employed in theoretical studies bear little relation to the spatial embedding or connectivity of the neural networks that they attempt to replicate. Here, we employ detailed neuroimaging data to define a network whose spatial embedding represents accurately the folded structure of the cortical surface of a rat and investigate the propagation of activity over this network under simple spreading and connectivity rules. By comparison with standard network models with the same coarse statistics, we show that the cortical geometry influences profoundly the speed propagation of activation through the network. Our conclusions are of high relevance to the theoretical modelling of epileptic seizure events, and indicate that such studies which omit physiological network structure risk simplifying the dynamics in a potentially significant way

Antibody-based detection of protein phosphorylation status to track the efficacy of novel therapies using nanogram protein quantities from stem cells and cell lines

This protocol describes a highly reproducible antibody-based method that provides protein level and phosphorylation status information from nanogram quantities of protein cell lysate. Nanocapillary isoelectric focusing (cIEF) combines with UV-activated linking chemistry to detect changes in phosphorylation status. As an example application, we describe how to detect changes in response to tyrosine kinase inhibitors (TKIs) in the phosphorylation status of the adaptor protein ​CrkL, a major substrate of the oncogenic tyrosine kinase ​BCR-​ABL in chronic myeloid leukemia (CML), using highly enriched CML stem cells and mature cell populations in vitro. This protocol provides a 2.5 pg/nl limit of protein detection (&#60;0.2% of a stem cell sample containing &#60;104 cells). Additional assays are described for phosphorylated tyrosine 207 (pTyr207)-​CrkL and the protein tyrosine phosphatase ​PTPRC/​CD45; these assays were developed using this protocol and applied to CML patient samples. This method is of high throughput, and it can act as a screen for in vitro cancer stem cell response to drugs and novel agents

WFPC2 LRF Imaging of Emission Line Nebulae in 3CR Radio Galaxies

We present HST/WFPC2 Linear Ramp Filter images of high surface brightness emission lines (either [OII], [OIII], or H-alpha+[NII]) in 80 3CR radio sources. We overlay the emission line images on high resolution VLA radio images (eight of which are new reductions of archival data) in order to examine the spatial relationship between the optical and radio emission. We confirm that the radio and optical emission line structures are consistent with weak alignment at low redshift (z < 0.6) except in the Compact Steep Spectrum (CSS) radio galaxies where both the radio source and the emission line nebulae are on galactic scales and strong alignment is seen at all redshifts. There are weak trends for the aligned emission line nebulae to be more luminous, and for the emission line nebula size to increase with redshift and/or radio power. The combination of these results suggests that there is a limited but real capacity for the radio source to influence the properties of the emission line nebulae at these low redshifts (z < 0.6). Our results are consistent with previous suggestions that both mechanical and radiant energy are responsible for generating alignment between the radio source and emission line gas.Comment: 80 pages, 54 figures. Accepted for publication in ApJ

Consideration of nutritional value and food labels are associated with food intake in adults with depression

Background/Aims: Individuals with depression are more likely to consume poor diets and as a result are at increased risk of poor cardiometabolic health. Healthy diet may reduce depressive symptoms, however better understanding is needed of factors that support healthy eating in this population. There is limited evidence about how much consideration of the nutritional value of foods may be associated with food choices. The aim of this study was to investigate associations between food intake and consideration of nutritional value of foods in adults with depression. Methods: Adults (n = 161) with depression completed a semi-quantitative food frequency questionnaire and shopping and budgeting questionnaire. Associations between consideration of nutritional value and nutrition label use with vegetable, wholegrain, legume, snack food and soft drink intake were evaluated using linear regression, adjusting for age, gender and education. Results: In adjusted models, more consideration of the nutrition value of foods was positively associated with vegetable intake (β = 0.188; p = 0.025), wholegrain intake (β = 0.213; p = 0.015) and negatively associated with snack food intake (β = -0.236, p = 0.006). More frequent reading of nutrition labels was positively associated with legume intake (β = 0.185; p = 0.036). Better understanding of nutrition labels was positively associated with vegetable intake (β = 0.780; p = 0.035), wholegrain intake (β = 0.233; p = 0.008), and legume intake (β = 0.254; p = 0.004). There were no associations between soft drink intake and nutrition value consideration or nutrition label use. Conclusions: These findings suggest that increasing consideration of the nutrition value of foods and nutrition label use may support healthy eating in adults with depression

Evidence for Ordered Magnetic Fields in the Quasar Environment

At a distance of 20 pc from the purported supermassive black hole powering quasars, temperatures and densities are inferred from optical observations to be ~10**4 K and ~10**4 cm**-3. Here we present Very Long Baseline Interferometry radio observations revealing organized magnetic fields on the parsec scale in the hot plasma surrounding the quasar OQ172 (1442+101). These magnetic fields rotate the plane of polarization of the radio emission coming from the core and inner jet of the quasar. The derived rotation measure (RM) is 40,000 rad m**-2 in the rest frame of the quasar. Only 10 mas (a projected distance of 68 pc) from the nucleus the jet absolute values of RM fall to less than 100 rad m**-2.Comment: in press at ApJ Letters, 12 page LaTeX document includes 4 postscript figure

Structure-function clustering in multiplex brain networks

A key question in neuroscience is to understand how a rich functional repertoire of brain activity arises within relatively static networks of structurally-connected neural populations: elucidating the subtle interactions between evoked ‘functional connectivity’ and the underlying ‘structural connectivity’ has the potential to address this. These structural-functional networks (and neural networks more generally) are more naturally described using a multilayer or multiplex network approach, in favour of standard single-layer network analyses that are more typically applied to such systems. In this letter, we address such issues by exploring important structure-function relations in the Macaque cortical network by modelling it as a duplex network that comprises an anatomical layer, describing the known (macro-scale) network topology of the Macaque monkey, and a functional layer derived from simulated neural activity. We investigate and characterize correlations between structural and functional layers, as system parameters controlling simulated neural activity are varied, by employing recently described multiplex network measures. Moreover, we propose a novel measure of multiplex structure-function clustering which allows us to investigate the emergence of functional connections that are distinct from the underlying cortical structure, and to highlight the dependence of multiplex structure on the neural dynamical regime

HST/STIS low dispersion spectroscopy of three Compact Steep Spectrum sources Evidence for jet-cloud interaction

We present Hubble Space Telescope Imaging Spectrograph long-slit spectroscopy of the emission line nebulae in the compact steep spectrum radio sources 3C 67, 3C 277.1, and 3C 303.1. We derive BPT (Baldwin- Philips-Terlevich; Baldwin et al. 1981) diagnostic emission line ratios for the nebulae which are consistent with a mix of shock excitation and photoionization in the extended gas. In addition, line ratios indicative of lower ionization gas are found to be associated with higher gas velocities. The results are consistent with a picture in which these galaxy scale radio sources interact with dense clouds in the interstellar medium of the host galaxies, shocking the clouds thereby ionizing and accelerating them.Comment: Accepted for publication in A&A. 6 pages, 8 figure