Gene expression regulation and lineage evolution: the North and South tale of the hybrid polyploid Squalius alburnoides complex

The evolution of hybrid polyploid vertebrates, their viability and their perpetuation over evolutionary time have always been questions of great interest. However, little is known about the impact of hybridization and polyploidization on the regulatory networks that guarantee the appropriate quantitative and qualitative gene expression programme. The Squalius alburnoides complex of hybrid fish is an attractive system to address these questions, as it includes a wide variety of diploid and polyploid forms, and intricate systems of genetic exchange. Through the study of genome-specific allele expression of seven housekeeping and tissue-specific genes, we found that a gene copy silencing mechanism of dosage compensation exists throughout the distribution range of the complex. Here we show that the allele-specific patterns of silencing vary within the complex, according to the geographical origin and the type of genome involved in the hybridization process. In southern populations, triploids of S. alburnoides show an overall tendency for silencing the allele from the minority genome, while northern population polyploids exhibit preferential biallelic gene expression patterns, irrespective of genomic composition. The present findings further suggest that gene copy silencing and variable expression of specific allele combinations may be important processes in vertebrate polyploid evolution.

Hydrogen peroxide sensing, signaling and regulation of transcription factors

The regulatory mechanisms by which hydrogen peroxide (H2O2) modulates the activity of transcription factors in bacteria (OxyR and PerR), lower eukaryotes (Yap1, Maf1, Hsf1 and Msn2/4) and mammalian cells (AP-1, NRF2, CREB, HSF1, HIF-1, TP53, NF-κB, NOTCH, SP1 and SCREB-1) are reviewed. The complexity of regulatory networks increases throughout the phylogenetic tree, reaching a high level of complexity in mammalians. Multiple H2O2 sensors and pathways are triggered converging in the regulation of transcription factors at several levels: (1) synthesis of the transcription factor by upregulating transcription or increasing both mRNA stability and translation; (ii) stability of the transcription factor by decreasing its association with the ubiquitin E3 ligase complex or by inhibiting this complex; (iii) cytoplasm-nuclear traffic by exposing/masking nuclear localization signals, or by releasing the transcription factor from partners or from membrane anchors; and, (iv) DNA binding and nuclear transactivation by modulating transcription factor affinity towards DNA, co-activators or repressors, and by targeting specific regions of chromatin to activate individual genes. We also discuss how H2O2 biological specificity results from diverse thiol protein sensors, with different reactivity of their sulfhydryl groups towards H2O2, being activated by different concentrations and times of exposure to H2O2. The specific regulation of local H2O2 concentrations is also crucial and results from H2O2 localized production and removal controlled by signals. Finally, we formulate equations to extract from typical experiments quantitative data concerning H2O2 reactivity with sensor molecules. Rate constants of 140 M-1s−1 and ≥ 1.3 × 103 M-1s−1 were estimated, respectively, for the reaction of H2O2 with KEAP1 and with an unknown target that mediates NRF2 protein synthesis. In conclusion, the multitude of H2O2 targets and mechanisms provides an opportunity for highly specific effects on gene regulation that depend on the cell type and on signals received from the cellular microenvironment.

Research practice development for nuclear medicine technologists: an innovative experience

Introduction - European nuclear medicine technologist’s education is delivered by Higher Education Institutions and students obtain a grade of Bachelor of Sciences (BSc), during which they are initiated to research during their studies. Once BSc nuclear medicine technologists are in professional practice, they have very few opportunities to develop a real research experience and they rather become passive users than active contributors the growth of scientific knowledge in nuclear medicine. Aim - To describe and discuss an innovative educational and professional experience aimed in strengthen research knowledge, skills and competencies of former nuclear medicine technologists student in the context of an international mobility stay.

Factors associated to medicine use among children from the 2004 Pelotas Birth Cohort (Brazil)

OBJECTIVE: To identify factors associated to medicine use among children from the 2004 Pelotas Birth Cohort, Brazil. METHODS: Prospective study to evaluate medicine use in children aged 3, 12 and 24 months regardless of the reasons, therapeutic indication or class. The study included 3,985 children followed up at three months of age, 3,907 at 12 months, and 3,868 at the last follow-up time of 24 months. Mothers were interviewed to collect information on medicine use during the recall period of 15 days prior to the interview. The outcome was studied according to sociodemographic and perinatal variables, mother's perception of child's health and breastfeeding status. Crude and adjusted analyses were performed by Poisson regression following a hierarchical model. RESULTS: The prevalence of medicine use ranged from 55% to 65% in the three follow-ups. After controlling for confounders, some variables remained associated to medicine use only at the three-month follow-up with greatest use among children of younger mothers, those children who had intrapartum complications, low birthweight, were never breastfed and were admitted to a hospital. Greatest medicine use was also associated with being a firstborn child at 3 and 12 months; mother's perception of their child health as fair or poor and children whose mothers have private health insurance at 12 and 24 months; highest maternal education level at all follow-up times. CONCLUSIONS: Different variables influence medicine use among children during the first two years of life and they change as the child ages especially maternal factors and those associated to the child's health problems.

Legal and political regulation of higher education in Portugal: an evolutionary perspective on the current policy issues and the problem of order

The higher education system in Europe is currently under stress and the debates over its reform and future are gaining momentum. Now that, for most countries, we are in a time for change, in the overall society and the whole education system, the legal and political dimensions have gained prominence, which has not been followed by a more integrative approach of the problem of order, its reform and the issue of regulation, beyond the typical static and classical cost-benefit analyses. The two classical approaches for studying (and for designing the policy measures of) the problem of the reform of the higher education system - the cost-benefit analysis and the legal scholarship description - have to be integrated. This is the argument of our paper that the very integration of economic and legal approaches, what Warren Samuels called the legal-economic nexus, is meaningful and necessary, especially if we want to address the problem of order (as formulated by Joseph Spengler) and the overall regulation of the system. On the one hand, and without neglecting the interest and insights gained from the cost-benefit analysis, or other approaches of value for money assessment, we will focus our study on the legal, social and political aspects of the regulation of the higher education system and its reform in Portugal. On the other hand, the economic and financial problems have to be taken into account, but in a more inclusive way with regard to the indirect and other socio-economic costs not contemplated in traditional or standard assessments of policies for the tertiary education sector. In the first section of the paper, we will discuss the theoretical and conceptual underpinning of our analysis, focusing on the evolutionary approach, the role of critical institutions, the legal-economic nexus and the problem of order. All these elements are related to the institutional tradition, from Veblen and Commons to Spengler and Samuels. The second section states the problem of regulation in the higher education system and the issue of policy formulation for tackling the problem. The current situation is clearly one of crisis with the expansion of the cohorts of young students coming to an end and the recurrent scandals in private institutions. In the last decade, after a protracted period of extension or expansion of the system, i. e., the continuous growth of students, universities and other institutions are competing harder to gain students and have seen their financial situation at risk. It seems that we are entering a period of radical uncertainty, higher competition and a new configuration that is slowly building up is the growth in intensity, which means upgrading the quality of the higher learning and getting more involvement in vocational training and life-long learning. With this change, and along with other deep ones in the Portuguese society and economy, the current regulation has shown signs of maladjustment. The third section consists of our conclusions on the current issue of regulation and policy challenge. First, we underline the importance of an evolutionary approach to a process of change that is essentially dynamic. A special attention will be given to the issues related to an evolutionary construe of policy analysis and formulation. Second, the integration of law and economics, through the notion of legal economic nexus, allows us to better define the issues of regulation and the concrete problems that the universities are facing. One aspect is the instability of the political measures regarding the public administration and on which the higher education system depends financially, legally and institutionally, to say the least. A corollary is the lack of clear strategy in the policy reforms. Third, our research criticizes several studies, such as the one made by the OECD in late 2006 for the Ministry of Science, Technology and Higher Education, for being too static and neglecting fundamental aspects of regulation such as the logic of actors, groups and organizations who are major players in the system. Finally, simply changing the legal rules will not necessary per se change the behaviors that the authorities want to change. By this, we mean that it is not only remiss of the policy maker to ignore some of the critical issues of regulation, namely the continuous non-respect by academic management and administrative bodies of universities of the legal rules that were once promulgated. Changing the rules does not change the problem, especially without the necessary debates form the different relevant quarters that make up the higher education system. The issues of social interaction remain as intact. Our treatment of the matter will be organized in the following way. In the first section, the theoretical principles are developed in order to be able to study more adequately the higher education transformation with a modest evolutionary theory and a legal and economic nexus of the interactions of the system and the policy challenges. After describing, in the second section, the recent evolution and current working of the higher education in Portugal, we will analyze the legal framework and the current regulatory practices and problems in light of the theoretical framework adopted. We will end with some conclusions on the current problems of regulation and the policy measures that are discusses in recent years.

Regulation of histone H2A.Z expression is mediated by sirtuin 1 in prostate cancer

Histone variants seem to play a major role in gene expression regulation. In prostate cancer, H2A.Z and its acetylated form are implicated in oncogenes’ upregulation. SIRT1, which may act either as tumor suppressor or oncogene, reduces H2A.Z levels in cardiomyocytes, via proteasome-mediated degradation, and this mechanism might be impaired in prostate cancer cells due to sirtuin 1 downregulation. Thus, we aimed to characterize the mechanisms underlying H2A.Z and SIRT1 deregulation in prostate carcinogenesis and how they interact. We found that H2AFZ and SIRT1 were up- and downregulated, respectively, at transcript level in primary prostate cancer and high-grade prostatic intraepithelial neoplasia compared to normal prostatic tissues. Induced SIRT1 overexpression in prostate cancer cell lines resulted in almost complete absence of H2A.Z. Inhibition of mTOR had a modest effect on H2A.Z levels, but proteasome inhibition prevented the marked reduction of H2A.Z due to sirtuin 1 overexpression. Prostate cancer cells exposed to epigenetic modifying drugs trichostatin A, alone or combined with 5-aza-2’-deoxycytidine, increased H2AFZ transcript, although with a concomitant decrease in protein levels. Conversely, SIRT1 transcript and protein levels increased after exposure. ChIP revealed an increase of activation marks within the TSS region for both genes. Remarkably, inhibition of sirtuin 1 with nicotinamide, increased H2A.Z levels, whereas activation of sirtuin 1 by resveratrol led to an abrupt decrease in H2A.Z. Finally, protein-ligation assay showed that exposure to epigenetic modifying drugs fostered the interaction between sirtuin 1 and H2A.Z. We concluded that sirtuin 1 and H2A.Z deregulation in prostate cancer are reciprocally related. Epigenetic mechanisms, mostly histone post-translational modifications, are likely involved and impair sirtuin 1-mediated downregulation of H2A.Z via proteasome-mediated degradation. Epigenetic modifying drugs in conjunction with enzymatic modulators are able to restore the normal functions of sirtuin 1 and might constitute relevant tools for targeted therapy of prostate cancer patients

Psychological well-being and perception of disease severity in people with multiple sclerosis, who underwent a program of self-regulation to promote physical activity

Rehabilitation is very important for in the results of treatment in individuals with multiple sclerosis. Rehabilitation processes occur through gradual changes. These changes integrate intrinsic and extrinsic mechanisms of the individual, promoting adaptations to the needs and activities of daily living according to individual goals. Recommendations for exercise in multiple sclerosis: these recommendations apply only to patients with EDSS less than 7; moderate intensity aerobic exercise for a total of 20 to 30 minutes, twice or three times for week; the resistance training with low or moderate intensity is well tolerated by patients with MS; associated with these exercises were recommended flexibility exercises of moderate intensity, as well as strengthening exercises. The aim of this study is to examine the implications of the program of self-regulation in the perception of illness and mental health (psychological well-being domain) in multiple sclerosis patients.

Nuclear medicine technologist education and training in Europe: literature and web-based findings

Purpose - The education and training of a nuclear medicine technologist (NMT) is not homogeneous among European countries, which leads to different scope of practices and, therefore, different technical skills are assigned. The goal of this research was to characterize the education and training of NMT in Europe. Materials and methods - This study was based on a literature research to characterize the education and training of NMT and support the historical evolution of this profession. It was divided into two different phases: the first phase included analysis of scientific articles and the second phase included research of curricula that allow health professionals to work as NMT in Europe. Results - The majority of the countries [N=31 (89%)] offer the NMT curriculum integrated into the high education system and only in four (11%) countries the education is provided by professional schools. The duration in each education system is not equal, varying in professional schools (2-3 years) and high education level system (2-4 years), which means that different European Credit Transfer and Accumulation System, such as 240, 230, 222, 210 or 180 European Credit Transfer and Accumulation System, are attributed to the graduates. The professional title and scope of the practice of NMT are different in different countries in Europe. In most countries of Europe, nuclear medicine training is not specific and curriculum does not demonstrate the Nuclear Medicine competencies performed in clinical practice. Conclusion - The heterogeneity in education and training for NMT is an issue prevalent among European countries. For NMT professional development, there is a huge need to formalize and unify educational and training programmes in Europe.

Necessity to review the Brazilian regulation about fluoride toothpastes

The aim of this study was to evaluate the adequacy of the Brazilian legislation about fluoride toothpaste. A search was conducted in LILACS, Medline and SciELO databases about the fluoride concentration found in Brazilians toothpastes, using descriptors on health. Publications since 1981 have shown that some Brazilian toothpastes are not able to maintain, during their expiration time, a minimum of 1,000 ppm F of soluble fluoride in the formulation. However, the Brazilian regulation (ANVISA, Resolution 79, August 28, 2000) only sets the maximum total fluoride (0.15%; 1,500 ppm F) that a toothpaste may contain but not the minimum concentration of soluble fluoride that it should contain to have anticaries potential, which according to systematic reviews should be 1,000 ppm F. Therefore, the Brazilian regulation on fluoride toothpastes needs to be revised to assure the efficacy of those products for caries control.

Validation of a new reference values’s database for semiquantification of 123I‐FP‐CIT SPECT scans in one nuclear medicine department

The DatScanTM and its Semiquantification (SQ) can provide advantages in the diagnosis of Parkinsonian Syndromes (PS). To improve the SQ is recommended the creation of adapted database (DB) with reference values for the Nuclear Medicine Departments. Previously to this work was created a adapted database (DBRV) to Nuclear Medicine Department's protocol and population of Infanta Cristina's Hospital located in Badajoz, for patients between the ages of 60 and 75, and reference values of the SQ were calculated. Aim: To evaluate the discrimination capacity of a department's adapted DB reference's values of healthy controls for DatScanTM.

Clinical classification versus semiquantification with adapted reference values for 123I-FP-CIT SPECT in a nuclear medicine department

Semi quantification (SQ) in DaTScan® studies is broadly used in clinic daily basis, however there is a suspicious about its discriminative capability, and concordance with the diagnostic classification performed by the physician. Aim: Evaluate the discriminate capability of an adapted database and reference's values of healthy controls for the Dopamine Transporters (DAT) with 123I–FP-IT named DBRV adapted to Nuclear Medicine Department's protocol and population of Infanta Cristina's Hospital, and its concordance with the physician classification.

On performance of distributed model predictive control in power system frequency regulation

This paper describes the implementation of a distributed model predictive approach for automatic generation control. Performance results are discussed by comparing classical techniques (based on integral control) with model predictive control solutions (centralized and distributed) for different operational scenarios with two interconnected networks. These scenarios include variable load levels (ranging from a small to a large unbalance generated power to power consumption ratio) and simultaneously variable distance between the interconnected networks systems. For the two networks the paper also examines the impact of load variation in an island context (a network isolated from each other).