Intrinsic Mitochondrial Membrane Potential and Associated Tumor Phenotype Are Independent of MUC1 Over-Expression

We have established previously that minor subpopulations of cells with stable differences in their intrinsic mitochondrial membrane potential (Δψm) exist within populations of mammary and colonic carcinoma cells and that these differences in Δψm are linked to tumorigenic phenotypes consistent with increased probability of participating in tumor progression. However, the mechanism(s) involved in generating and maintaining stable differences in intrinsic Δψm and how they are linked to phenotype are unclear. Because the mucin 1 (MUC1) oncoprotein is over-expressed in many cancers, with the cytoplasmic C-terminal fragment (MUC1 C-ter) and its integration into the outer mitochondrial membrane linked to tumorigenic phenotypes similar to those of cells with elevated intrinsic Δψm, we investigated whether endogenous differences in MUC1 levels were linked to stable differences in intrinsic Δψm and/or to the tumor phenotypes associated with the intrinsic Δψm. We report that levels of MUC1 are significantly higher in subpopulations of cells with elevated intrinsic Δψm derived from both mammary and colonic carcinoma cell lines. However, using siRNA we found that down-regulation of MUC1 failed to significantly affect either the intrinsic Δψm or the tumor phenotypes associated with increased intrinsic Δψm. Moreover, whereas pharmacologically mediated disruption of the Δψm was accompanied by attenuation of tumor phenotype, it had no impact on MUC1 levels. Therefore, while MUC1 over-expression is associated with subpopulations of cells with elevated intrinsic Δψm, it is not directly linked to the generation or maintenance of stable alterations in intrinsic Δψm, or to intrinsic Δψm associated tumor phenotypes. Since the Δψm is the focus of chemotherapeutic strategies, these data have important clinical implications in regard to effectively targeting those cells within a tumor cell population that exhibit stable elevations in intrinsic Δψm and are most likely to contribute to tumor progression

Quantization of Midisuperspace Models

We give a comprehensive review of the quantization of midisuperspace models. Though the main focus of the paper is on quantum aspects, we also provide an introduction to several classical points related to the definition of these models. We cover some important issues, in particular, the use of the principle of symmetric criticality as a very useful tool to obtain the required Hamiltonian formulations. Two main types of reductions are discussed: those involving metrics with two Killing vector fields and spherically symmetric models. We also review the more general models obtained by coupling matter fields to these systems. Throughout the paper we give separate discussions for standard quantizations using geometrodynamical variables and those relying on loop quantum gravity inspired methods.Comment: To appear in Living Review in Relativit

From Portugal to Europe. A micro-level Sociology of scientific migration in times of Eurozone crisis.

Academic international mobility and intra-European highly skilled migration are consolidated trends. Strongly stimulated by EU policies, the opportunities are highly dynamic, and circulation through different jobs and countries is a striking feature of the academic community. However, for a fragile economy and scientific system as the Portuguese ones, those trends are synonyms of brain drain, particularly in times of Eurozone crisis. In order to question the place of the economic crisis on scientists’ migration decision-making process, and considering that academic mobility is often associated with individual career perspectives and encouraged by European policies, five individual portraits are analysed

Synthesis, structural and magnetic characterization of lead-metaniobate/cobalt-ferrite nanocomposite films deposited by pulsed laser ablation

Detailed structural, microstructural and magnetic measurements were performed on (PbNb2O6)(1-x) -(CoFe2O4) (x) nanocomposite thin films deposited by laser ablation on Si(001)\Pt substrates, with different cobalt ferrite concentrations. The tuning of the lead concentration, due to the lead volatility, was found to be particularly important in order to obtain the orthorhombic (ferroelectric) lead niobate phase. The lattice parameter of CoFe2O4 was below the bulk value, indicating the presence of compressive strains on this phase. A magnetic anisotropy was observed, which favored the orientation of the magnetization in the direction perpendicular to the plane of the films, for cobalt ferrite concentrations 40-50 %. The shape, stress and magnetocrystalline anisotropy fields on the composites were calculated and compared. It was found that the perpendicular magnetic anisotropy was induced by the presence of strain on the ferrite phase in the films.- This work has been supported by Fundacao para a Ciencia e Tecnologia (FCT) and FEDER, through the projects POCI/CTM/60181/2004 and PTDC/CTM/099415/2008. J. Barbosa and I. T. Gomes gratefully acknowledge Ph.D. grants from Fundacao para a Ciencia e Tecnologia (SFRH/BD/41913/2007 and SFRH/BD/36348/2007, respectively).info:eu-repo/semantics/publishedVersio

The decision to emigrate: A study from the perspective of dispositional plurality

This paper analyses the Portuguese high-skilled emigration, focusing on the emigration decision-making process. This article aims to understand the dispositions leading to this decision, and the social processes that explain its origin, sedimentation and activation. To this end, and using the theoretical and methodological approach of Bernard Lahire, 53 sociological portraits of skilled Portuguese who emigrated to other European countries are cross-sectional analyzed. This analysis is supplemented by data from a survey previously administered. Thus, we will address how the migratory dispositions are built through the individual biographies, highlighting the heuristic potential of the individual observation scale

Key Aspects of Health Policy Development to Improve Surgical Services in Uganda

Recently, surgical services have been gaining greater attention as an integral part of public health in low-income countries due to the significant volume and burden of surgical conditions, growing evidence of the cost-effectiveness of surgical intervention, and global disparities in surgical care. Nonetheless, there has been limited discussion of the key aspects of health policy related to surgical services in low-income countries. Uganda, like other low-income sub-Saharan African countries, bears a heavy burden of surgical conditions with low surgical output in health facilities and significant unmet need for surgical care. To address this lack of adequate surgical services in Uganda, a diverse group of local stakeholders met in Kampala, Uganda, in May 2008 to develop a roadmap of key policy actions that would improve surgical services at the national level. The group identified a list of health policy priorities to improve surgical services in Uganda. The priorities were classified into three areas: (1) human resources, (2) health systems, and (3) research and advocacy. This article is a critical discussion of these health policy priorities with references to recent literature. This was the first such multidisciplinary meeting in Uganda with a focus on surgical services and its output may have relevance to health policy development in other low-income countries planning to improve delivery of surgical services

Pooling and expanding registries of familial hypercholesterolaemia to assess gaps in care and improve disease management and outcomes : Rationale and design of the global EAS Familial Hypercholesterolaemia Studies Collaboration

Background: The potential for global collaborations to better inform public health policy regarding major non-hypercholesterolaemia (FH), a common genetic disorder associated with premature cardiovascular disease, is yet to be reliably ascertained using similar approaches. The European Atherosclerosis Society FH Studies Collaboration (EAS FHSC) is a new initiative of international stakeholders which will help establish a global FH registry to generate large-scale, robust data on the burden of FH worldwide. Methods: The EAS FHSC will maximise the potential exploitation of currently available and future FH data (retrospective and prospective) by bringing together regional/national/international data sources with access to individuals with a clinical and/or genetic diagnosis of heterozygous or homozygous FH. A novel bespoke electronic platform and FH Data Warehouse will be developed to allow secure data sharing, validation, cleaning, pooling, harmonisation and analysis irrespective of the source or format. Standard statistical procedures will allow us to investigate cross-sectional associations, patterns of real-world practice, trends over time, and analyse risk and outcomes (e.g. cardiovascular outcomes, all-cause death), accounting for potential confounders and subgroup effects. Conclusions: The EAS FHSC represents an excellent opportunity to integrate individual efforts across the world to tackle the global burden of FH. The information garnered from the registry will help reduce gaps in knowledge, inform best practices, assist in clinical trials design, support clinical guidelines and policies development, and ultimately improve the care of FH patients. (C) 2016 Elsevier Ireland Ltd.Peer reviewe

In Vitro Surfactant Structure-Toxicity Relationships: Implications for Surfactant Use in Sexually Transmitted Infection Prophylaxis and Contraception

Background The need for woman-controlled, cheap, safe, effective, easy-to-use and easy-to-store topical applications for prophylaxis against sexually transmitted infections (STIs) makes surfactant-containing formulations an interesting option that requires a more fundamental knowledge concerning surfactant toxicology and structure-activity relationships. Methodology/Principal Findings We report in vitro effects of surfactant concentration, exposure time and structure on the viability of mammalian cell types typically encountered in the vagina, namely, fully polarized and confluent epithelial cells, confluent but non-polarized epithelial-like cells, dendritic cells, and human sperm. Representatives of the different families of commercially available surfactants – nonionic (Triton X-100 and monolaurin), zwitterionic (DDPS), anionic (SDS), and cationic (CnTAB (n = 10 to 16), C12PB, and C12BZK) – were examined. Triton X-100, monolaurin, DDPS and SDS were toxic to all cell types at concentrations around their critical micelle concentration (CMC) suggesting a non-selective mode of action involving cell membrane destabilization and/or destruction. All cationic surfactants were toxic at concentrations far below their CMC and showed significant differences in their toxicity toward polarized as compared with non-polarized cells. Their toxicity was also dependent on the chemical nature of the polar head group. Our results suggest an intracellular locus of action for cationic surfactants and show that their structure-activity relationships could be profitably exploited for STI prophylaxis in vaginal gel formulations. The therapeutic indices comparing polarized epithelial cell toxicity to sperm toxicity for all surfactants examined, except C12PB and C12BZK, does not justify their use as contraceptive agents. C12PB and C12BZK are shown to have a narrow therapeutic index recommending caution in their use in contraceptive formulations. Conclusions/Significance Our results contribute to understanding the mechanisms involved in surfactant toxicity, have a predictive value with regard to their safety, and may be used to design more effective and less harmful surfactants for use in topical applications for STI prophylaxis.Foundation for Science and Technology of the Portuguese Ministry of Science and Higher Educatio

Targeting neuroinflammation for therapeutic intervention in neurodegenerative pathologies: A role for the peptide analogue of thymulin (PAT)

Introduction: Inflammation has a vital task in protecting the organism, but when deregulated, it can have serious pathological consequences. The central nervous system (CNS) is capable of mounting immune and inflammatory responses, albeit different from that observed in the periphery. Neuroinflammation, however, can be a major contributor to neurodegenerative diseases and constitute a major challenge for medicine and basic research. Areas covered: Both innate and adaptive immune responses normally play an important role in homeostasis within the CNS. Microglia, astrocytes and neuronal cells express a wide array of toll-like receptors (TLR) that can be upregulated by infection, trauma, injuries and various exogenic or endogenic factors. Chronic hyper activation of brain immune cells can result in neurotoxic actions due to excessive production of several pro-inflammatory mediators. Several studies have recently described an important role for targeting receptors such as nicotinic receptors located on cells in the CNS or in other tissues for the control of inflammation. Expert opinion: Thymulin and its synthetic peptide analogue (PAT) appear to exert potent anti-inflammatory effects at the level of peripheral tissues as well as at the level of the brain. This effect involves, at least partially, the activation of cholinergic mechanisms. © 2012 Informa UK, Ltd