FGF/heparin differentially regulates Schwann cell and olfactory ensheathing cell interactions with astrocytes: a role in astrocytosis

After injury, the CNS undergoes an astrocyte stress response characterized by reactive astrocytosis/proliferation, boundary formation, and increased glial fibrillary acidic protein (GFAP) and chondroitin sulfate proteoglycan (CSPG) expression. Previously, we showed that in vitro astrocytes exhibit this stress response when in contact with Schwann cells but not olfactory ensheathing cells (OECs). In this study, we confirm this finding in vivo by demonstrating that astrocytes mingle with OECs but not Schwann cells after injection into normal spinal cord. We show that Schwann cell-conditioned media (SCM) induces proliferation in monocultures of astrocytes and increases CSPG expression in a fibroblast growth factor receptor 1 (FGFR1)-independent manner. However, SCM added to OEC/astrocyte cocultures induces reactive astrocytosis and boundary formation, which, although sensitive to FGFR1 inhibition, was not induced by FGF2 alone. Addition of heparin to OEC/astrocyte cultures induces boundary formation, whereas heparinase or chlorate treatment of Schwann cell/astrocyte cultures reduces it, suggesting that heparan sulfate proteoglycans (HSPGs) are modulating this activity. In vivo, FGF2 and FGFR1 immunoreactivity was increased over grafted OECs and Schwann cells compared with the surrounding tissue, and HSPG immunoreactivity is increased over reactive astrocytes bordering the Schwann cell graft. These data suggest that components of the astrocyte stress response, including boundary formation, astrocyte hypertrophy, and GFAP expression, are mediated by an FGF family member, whereas proliferation and CSPG expression are not. Furthermore, after cell transplantation, HSPGs may be important for mediating the stress response in astrocytes via FGF2. Identification of factors secreted by Schwann cells that induce this negative response in astrocytes would further our ability to manipulate the inhibitory environment induced after injury to promote regeneration

In vitro and in vivo ocular biocompatibility of electrospun poly(ɛ-caprolactone) nanofibers.

Biocompatibility is a requirement for the development of nanofibers for ophthalmic applications. In this study, nanofibers were elaborated using poly(ε-caprolactone) via electrospinning. The ocular biocompatibility of this material was investigated. MIO-M1 and ARPE-19 cell cultures were incubated with nanofibers and cellular responses were monitored by viability and morphology. The in vitro biocompatibility revealed that the nanofibers were not cytotoxic to the ocular cells. These cells exposed to the nanofibers proliferated and formed an organized monolayer. ARPE-19 and MIO-M1 cells were capable of expressing GFAP, respectively, demonstrating their functionality. Nanofibers were inserted into the vitreous cavity of the rat's eye for 10days and the in vivo biocompatibility was investigated using Optical Coherence Tomography (OCT), histology and measuring the expression of pro-inflammatory genes (IL-1β, TNF-α, VEGF and iNOS) (real-time PCR). The OCT and the histological analyzes exhibited the preserved architecture of the tissues of the eye. The biomaterial did not elicit an inflammatory reaction and pro-inflammatory cytokines were not expressed by the retinal cells, and the other posterior tissues of the eye. Results from the biocompatibility studies indicated that the nanofibers exhibited a high degree of cellular biocompatibility and short-term intraocular tolerance, indicating that they might be applied as drug carrier for ophthalmic use

COMPILATION OF ACTIVE FAULT DATA IN PORTUGAL FOR USE IN SEISMIC HAZARD ANALYSIS

To estimate where future earthquakes are likely to occur, it is essential to combine information about past earthquakes with knowledge about the location and seismogenic properties of active faults. For this reason, robust probabilistic seismic hazard analysis (PSHA) integrates seismicity and active fault data. Existing seismic hazard assessments for Portugal rely exclusively on seismicity data and do not incorporate data on active faults. Project SHARE (Seismic Hazard Harmonization in Europe) is an EC-funded initiative (FP7) that aims to evaluate European seismic hazards using an integrated, standardized approach. In the context of SHARE, we are developing a fully-parameterized active fault database for Portugal that incorporates existing compilations, updated according to the most recent publications. The seismogenic source model derived for SHARE will be the first model for Portugal to include fault data and follow an internationally standardized approach. This model can be used to improve both seismic hazard and risk analyses and will be combined with the Spanish database for use in Iberian- and European-scale assessments

Template coexistence in prebiotic vesicle models

The coexistence of distinct templates is a common feature of the diverse proposals advanced to resolve the information crisis of prebiotic evolution. However, achieving robust template coexistence turned out to be such a difficult demand that only a class of models, the so-called package models, seems to have met it so far. Here we apply Wright's Island formulation of group selection to study the conditions for the coexistence of two distinct template types confined in packages (vesicles) of finite capacity. In particular, we show how selection acting at the level of the vesicles can neutralize the pressures towards the fixation of any one of the template types (random drift) and of the type with higher replication rate (deterministic competition). We give emphasis to the role of the distinct generation times of templates and vesicles as yet another obstacle to coexistence.Comment: 7 pages, 8 figure

The significance of 'the visit' in an English category-B prison: Views from prisoners, prisoners' families and prison staff

A number of claims have been made regarding the importance of prisoners staying in touch with their family through prison visits, firstly from a humanitarian perspective of enabling family members to see each other, but also regarding the impact of maintaining family ties for successful rehabilitation, reintegration into society and reduced re-offending. This growing evidence base has resulted in increased support by the Prison Service for encouraging the family unit to remain intact during a prisoner’s incarceration. Despite its importance however, there has been a distinct lack of research examining the dynamics of families visiting relatives in prison. This paper explores perceptions of the same event – the visit – from the families’, prisoners’ and prison staffs' viewpoints in a category-B local prison in England. Qualitative data was collected with 30 prisoners’ families, 16 prisoners and 14 prison staff, as part of a broader evaluation of the visitors’ centre. The findings suggest that the three parties frame their perspective of visiting very differently. Prisoners’ families often see visits as an emotional minefield fraught with practical difficulties. Prisoners can view the visit as the highlight of their time in prison and often have many complaints about how visits are handled. Finally, prison staff see visits as potential security breaches and a major organisational operation. The paper addresses the current gap in our understanding of the prison visit and has implications for the Prison Service and wider social policy

Variance fluctuations in nonstationary time series: a comparative study of music genres

An important problem in physics concerns the analysis of audio time series generated by transduced acoustic phenomena. Here, we develop a new method to quantify the scaling properties of the local variance of nonstationary time series. We apply this technique to analyze audio signals obtained from selected genres of music. We find quantitative differences in the correlation properties of high art music, popular music, and dance music. We discuss the relevance of these objective findings in relation to the subjective experience of music.Comment: 13 pages, 4 fig

Anti-Inflammatory Effect of Dexamethasone Controlled Released From Anterior Suprachoroidal Polyurethane Implants on Endotoxin-Induced Uveitis in Rats.

Targeted drug delivery to the ocular tissues remains a challenge. Biodegradable intraocular implants allow prolonged controlled release of drugs directly into the eye. In this study, we evaluated an anterior suprachoroidal polyurethane implant containing dexamethasone polyurethane dispersions (DX-PUD) as a drug delivery system in the rat model of endotoxin-induced uveitis (EIU). In vitro drug release was studied using PUD implants containing 8%, 20%, and 30% (wt/wt) DX. Cytotoxicity of the degradation products of DX-PUD was assessed on human ARPE-19 cells using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) test. Short-term ocular biocompatibility of suprachoroidal DX-PUD implants was evaluated in normal rat eyes. Endotoxin-induced uveitis was then induced in rat eyes preimplanted with DX-PUD. Clinical examination was performed at 24 hours; eyes were used to assess inflammatory cell infiltration and macrophage/microglial activation. Cytokine and chemokine expression in the iris/ciliary body and in the retina was investigated using quantitative PCR. Feasibility of anterior suprachoroidal PUD implantation was also tested using postmortem human eyes. A burst release was followed by a sustained controlled release of DX from PUD implants. By-products of the DX-PUD were not toxic to human ARPE-19 cells or to rat ocular tissues. Dexamethasone-PUD implants prevented EIU in rat eyes, reducing inflammatory cell infiltration and inhibiting macrophage/microglial activation. Dexamethasone-PUD downregulated proinflammatory cytokines/chemokines (IL-1β, IL-6, cytokine-induced neutrophil chemoattractant [CINC]) and inducible nitric oxide synthase (iNOS) and upregulated IL-10 anti-inflammatory cytokine. Polyurethane dispersion was successfully implanted into postmortem human eyes. Dexamethasone-PUD implanted in the anterior suprachoroidal space may be of interest in the treatment of intraocular inflammation

Activated Random Walkers: Facts, Conjectures and Challenges

We study a particle system with hopping (random walk) dynamics on the integer lattice $\mathbb Z^d$. The particles can exist in two states, active or inactive (sleeping); only the former can hop. The dynamics conserves the number of particles; there is no limit on the number of particles at a given site. Isolated active particles fall asleep at rate $\lambda > 0$, and then remain asleep until joined by another particle at the same site. The state in which all particles are inactive is absorbing. Whether activity continues at long times depends on the relation between the particle density $\zeta$ and the sleeping rate $\lambda$. We discuss the general case, and then, for the one-dimensional totally asymmetric case, study the phase transition between an active phase (for sufficiently large particle densities and/or small $\lambda$) and an absorbing one. We also present arguments regarding the asymptotic mean hopping velocity in the active phase, the rate of fixation in the absorbing phase, and survival of the infinite system at criticality. Using mean-field theory and Monte Carlo simulation, we locate the phase boundary. The phase transition appears to be continuous in both the symmetric and asymmetric versions of the process, but the critical behavior is very different. The former case is characterized by simple integer or rational values for critical exponents ($\beta = 1$, for example), and the phase diagram is in accord with the prediction of mean-field theory. We present evidence that the symmetric version belongs to the universality class of conserved stochastic sandpiles, also known as conserved directed percolation. Simulations also reveal an interesting transient phenomenon of damped oscillations in the activity density