The pressor effect of angiotensin-(1-7) in the rat rostral ventrolateral medulla involves multiple peripheral mechanisms

OBJECTIVE: In the present study, the peripheral mechanism that mediates the pressor effect of angiotensin-(1-7) in the rostral ventrolateral medulla was investigated. METHOD: Angiotensin-(1-7) (25 pmol) was bilaterally microinjected in the rostral ventrolateral medulla near the ventral surface in urethane-anesthetized male Wistar rats that were untreated or treated (intravenously) with effective doses of selective autonomic receptor antagonists (atenolol, prazosin, methyl-atropine, and hexamethonium) or a vasopressin V1 receptor antagonist [d(CH2)5 -Tyr(Me)-AVP] given alone or in combination. RESULTS: Unexpectedly, the pressor response produced by angiotensin-(1-7) (16 ± 2 mmHg, n = 12), which was not associated with significant changes in heart rate, was not significantly altered by peripheral treatment with prazosin, the vasopressin V1 receptor antagonist, hexamethonium or methyl-atropine. Similar results were obtained in experiments that tested the association of prazosin and atenolol; methyl-atropine and the vasopressin V1 antagonist or methyl-atropine and prazosin. Peripheral treatment with the combination of prazosin, atenolol and the vasopressin V1 antagonist abolished the pressor effect of glutamate; however, this treatment produced only a small decrease in the pressor effect of angiotensin-(1-7) at the rostral ventrolateral medulla. The combination of hexamethonium with the vasopressin V1 receptor antagonist or the combination of prazosin, atenolol, the vasopressin V1 receptor antagonist and methyl-atropine was effective in blocking the effect of angiotensin-(1-7) at the rostral ventrolateral medulla. CONCLUSION: These results indicate that angiotensin-(1-7) triggers a complex pressor response at the rostral ventrolateral medulla that involves an increase in sympathetic tonus, release of vasopressin and possibly the inhibition of a vasodilatory mechanism

Systems Interoperability Types: A Tertiary Study

Interoperability has been a focus of attention over at least four decades, with the emergence of several interoperability types (or levels), diverse models, frameworks, and solutions, also as a result of a continuous effort from different domains. The current heterogeneity in technologies such as blockchain, IoT and new application domains such as Industry 4.0 brings not only new interaction possibilities but also challenges for interoperability. Moreover, confusion and ambiguity in the current understanding of interoperability types exist, hampering stakeholders' communication and decision making. This work presents an updated panorama of software-intensive systems interoperability with particular attention to its types. For this, we conducted a tertiary study that scrutinized 37 secondary studies published from 2012 to 2023, from which we found 36 interoperability types associated with 117 different definitions, besides 13 interoperability models and six frameworks in various domains. This panorama reveals that the concern with interoperability has migrated from technical to social-technical issues going beyond the software systems' boundary and still requiring solving many open issues. We also address the urgent actions and also potential research opportunities to leverage interoperability as a multidisciplinary research field to achieve low-coupled, cost-effective, and interoperable systems.Comment: 33 page

Immunization and Aging: a Learning Process in the Immune Network

The immune system can be thought as a complex network of different interacting elements. A cellular automaton, defined in shape-space, was recently shown to exhibit self-regulation and complex behavior and is, therefore, a good candidate to model the immune system. Using this model to simulate a real immune system we find good agreement with recent experiments on mice. The model exhibits the experimentally observed refractory behavior of the immune system under multiple antigen presentations as well as loss of its plasticity caused by aging.Comment: 4 latex pages, 3 postscript figures attached. To be published in Physical Review Letters (Tentatively scheduled for 5th Oct. issue

Purification, crystallization and preliminary X-ray diffraction analysis of the seryl-tRNA synthetase from Candida albicans

The seryl-tRNA synthetase (SerRS) from Candida albicans exists naturally as two isoforms resulting from ambiguity in the natural genetic code. Both enzymes were crystallized by the sitting-drop vapour-diffusion method using 3.2-3.4 M ammonium sulfate as precipitant. The crystals belonged to the hexagonal space group P6(1)22 and contained one monomer per asymmetric unit, despite the synthetase existing as a homodimer (with a molecular weight of ∼116 kDa) in solution. Diffraction data were collected to 2.0 Å resolution at a synchrotron source and the crystal structures of unliganded SerRS and of its complexes with ATP and with a seryl-adenylate analogue were solved by molecular replacement. The structure of C. albicans SerRS represents the first reported structure of a eukaryotic cytoplasmic SerRS.publishe

A Genetic Code Alteration Is a Phenotype Diversity Generator in the Human Pathogen Candida albicans

BACKGROUND: The discovery of genetic code alterations and expansions in both prokaryotes and eukaryotes abolished the hypothesis of a frozen and universal genetic code and exposed unanticipated flexibility in codon and amino acid assignments. It is now clear that codon identity alterations involve sense and non-sense codons and can occur in organisms with complex genomes and proteomes. However, the biological functions, the molecular mechanisms of evolution and the diversity of genetic code alterations remain largely unknown. In various species of the genus Candida, the leucine CUG codon is decoded as serine by a unique serine tRNA that contains a leucine 5'-CAG-3'anticodon (tRNA(CAG)(Ser)). We are using this codon identity redefinition as a model system to elucidate the evolution of genetic code alterations. METHODOLOGY/PRINCIPAL FINDINGS: We have reconstructed the early stages of the Candida genetic code alteration by engineering tRNAs that partially reverted the identity of serine CUG codons back to their standard leucine meaning. Such genetic code manipulation had profound cellular consequences as it exposed important morphological variation, altered gene expression, re-arranged the karyotype, increased cell-cell adhesion and secretion of hydrolytic enzymes. CONCLUSION/SIGNIFICANCE: Our study provides the first experimental evidence for an important role of genetic code alterations as generators of phenotypic diversity of high selective potential and supports the hypothesis that they speed up evolution of new phenotypes

Patient-centeredness: contribution to the adaptation of the Patient-Practitioner Orientation Scale (PPOS)

Objetivo: Este estudo teve como objetivo traduzir e contribuir para a adaptação para a população portuguesa (Português Europeu) da Patient-Practitioner Orientation Scale (PPOS). Método: Após o processo de tradução e de pré-teste, a escala foi aplicada a 593 estudantes do 1º ao 6º ano do curso de Medicina em várias Universidades de Portugal Continental. A validade do construto e a fiabilidade do instrumento foram aferidas através da análise fatorial exploratória (ACP) e confirmatória (AFC), e do cálculo do coeficiente alpha de Cronbach. Resultados: A versão final explica 31.54% da variância total e confirma a estrutura em dois fatores: Caring, (19.56% da variância) e Sharing (11.98% da variância). Os itens 2 e 4 apresentaram inconsistências com os fatores definidos à priori (versão original do instrumento), os itens 9 e 17 obtiveram cargas fatoriais inferiores a .3, e o item 3 registou uma diferença inferior a .1 entre as cargas fatoriais para os dois domínios. Os coeficientes de alpha de Cronbach foram .65, .50 e .56 para a escala total, e subscalas Caring e Sharing, respetivamente. A AFC revelou um bom ajustamento global do modelo de medida (χ2(132, N = 593) = 344.28, p < .001; χ2/gl = 2.61; GFI = .93; AGFI = .92; CFI = .87; NNFI = .81; SRMR = .084; RMSEA = .05, 95% CI [0.045, 0.059], p = .293). As análises exploratórias posteriores sugerem a possibilidade de melhoria dos índices de validade e de fiabilidade da escala total e da sub-escala Caring, com a retirada de itens específicos. Conclusão: Não obstante as fragilidades encontradas no que concerne à fiabilidade e validade da PPOS-P para uma amostra de estudantes portugueses de Medicina, este estudo representa um contributo científico para a adaptação da escala, que pode ser considerada para efeitos de avaliação de atitudes de centração no paciente nos contextos da educação médica e da investigação.ABSTRACT - Objective: The purpose of this study was to contribute to the European Portuguese adaptation of the Patient-Practitioner Orientation Scale (PPOS). Method: A sample of 593 medical students participated in the study. After permission from the original author, the translation procedures required to ensure translation of the PPOS to European Portuguese were performed. Construct validity (exploratory and confirmatory factor analysis) and reliability (internal consistency) were assessed. Results: The final version confirmed the original structures of two factors, explaining 31.54% of total variance; Caring (19.56%) and Sharing (11.98%). Items 2 and 4 showed inconsistencies with the factors defined earlier in the original version of the instrument, items 9 and 17 obtained a factorial load less than .3, and the item 3 achieved a difference of less than .1 between factorial charges for the two domains. The internal consistency of PPOS-P scales was adequate (Cronbach’s alpha of .65, .50 and .56 for total scale, and subscales Caring and Sharing, respectively). Confirmatory factor analysis provided an acceptable adjustment for the observed variables (χ2(132, N = 593) = 344.28, p < .001; χ2/gl = 2.61; GFI = .93; AGFI = .92; CFI = .87; NNFI = .81; SRMR = .084; RMSEA = .05, 95% CI [0.045, 0.059], p = .293). Subsequent exploratory analyzes suggest the potential for improving the levels of validity and reliability of the total scale and Caring subscale, with the removal of specific items. Conclusion: Although the fragilities identified in the validity and reliability of the PPOS-P in a sample of Portuguese medical students, this work can represent an important and useful contribution to further investigations that might consider this instrument as a measure of student’s changes of patient-centeredness attitudes.info:eu-repo/semantics/publishedVersio

effects on the physical activity routine of families with children

Objective: To identify how Brazilian families with children aged under 13 years face the period of social isolation resulting from the COVID-19 pandemic, especially regarding the time spent on physical activity (PA), intellectual activity, games, outdoor activities and screen. Methods: An anonymous online survey was launched on March 24, 2020 in Brazil to assess how families with children aged up to 12 years are adjusting their daily routines to this situation. In the survey, each family reported the daily time each child spent in sedentary activity (sum of intellectual activities, play time on screen, playing without PA) and PA (sum of playing with PA and PA). Results: The main findings based on data from 816 children indicate that most parents consider there was a reduction in the time that children spend practicing PA; increase in screen play time and family activities, differences between sex were found regarding screen play time (boys>girls) and in playing without PA (girls>boys), and there was an age effect for all categories analyzed, with a tendency to increase the total time of sedentary lifestyle and complementary reducing the time of PA over age. Conclusions: The household routines of families during the period of social isolation resulting from the COVID-19 pandemic confirm the general reduction tendency in PA time during childhood.4811-99FE-2ECD | Luis Paulo RodriguesN/