lncRNA-dependent mechanisms of androgen-receptor-regulated gene activation programs.

Although recent studies have indicated roles of long non-coding RNAs (lncRNAs) in physiological aspects of cell-type determination and tissue homeostasis, their potential involvement in regulated gene transcription programs remains rather poorly understood. The androgen receptor regulates a large repertoire of genes central to the identity and behaviour of prostate cancer cells, and functions in a ligand-independent fashion in many prostate cancers when they become hormone refractory after initial androgen deprivation therapy. Here we report that two lncRNAs highly overexpressed in aggressive prostate cancer, PRNCR1 (also known as PCAT8) and PCGEM1, bind successively to the androgen receptor and strongly enhance both ligand-dependent and ligand-independent androgen-receptor-mediated gene activation programs and proliferation in prostate cancer cells. Binding of PRNCR1 to the carboxy-terminally acetylated androgen receptor on enhancers and its association with DOT1L appear to be required for recruitment of the second lncRNA, PCGEM1, to the androgen receptor amino terminus that is methylated by DOT1L. Unexpectedly, recognition of specific protein marks by PCGEM1-recruited pygopus 2 PHD domain enhances selective looping of androgen-receptor-bound enhancers to target gene promoters in these cells. In 'resistant' prostate cancer cells, these overexpressed lncRNAs can interact with, and are required for, the robust activation of both truncated and full-length androgen receptor, causing ligand-independent activation of the androgen receptor transcriptional program and cell proliferation. Conditionally expressed short hairpin RNA targeting these lncRNAs in castration-resistant prostate cancer cell lines strongly suppressed tumour xenograft growth in vivo. Together, these results indicate that these overexpressed lncRNAs can potentially serve as a required component of castration-resistance in prostatic tumours

Male and female meiotic behaviour of an intrachromosomal insertion determined by preimplantation genetic diagnosis

<p>Abstract</p> <p>Background</p> <p>Two related family members, a female and a male balanced carrier of an intrachromosomal insertion on chromosome 7 were referred to our centre for preimplantation genetic diagnosis. This presented a rare opportunity to investigate the behaviour of the insertion chromosome during meiosis in two related carriers. The aim of this study was to carry out a detailed genetic analysis of the preimplantation embryos that were generated from the three treatment cycles for the male and two for the female carrier.</p> <p>Patients underwent <it>in vitro </it>fertilization and on day 3, 22 embryos from the female carrier and 19 embryos from the male carrier were biopsied and cells analysed by fluorescent in situ hybridization. Follow up analysis of 29 untransferred embryos was also performed for confirmation of the diagnosis and to obtain information on meiotic and mitotic outcome.</p> <p>Results</p> <p>In this study, the female carrier produced more than twice as many chromosomally balanced embryos as the male (76.5% vs. 36%), and two pregnancies were achieved for her. Follow up analysis showed that the male carrier had produced more highly abnormal embryos than the female (25% and 15% respectively) and no pregnancies occurred for the male carrier and his partner.</p> <p>Conclusion</p> <p>This study compares how an intrachromosomal insertion has behaved in the meiotic and preimplantation stages of development in sibling male and female carriers. It confirms that PGD is an appropriate treatment in such cases. Reasons for the differing outcome for the two carriers are discussed.</p

A Parassubordinação E O Poder Diretivo Do Empregador No Contrato Individual De Trabalho

This paper aims to propose a reflection about the legal requirements of the existence of an employment relationship, by analyzing the degree of importance of subordination and its nuances, practices in addition to discuss about the governing power of the employer on the “parassubordinação”, as a form of legal dependence, which came in the face of technological developments and therefore new employment relationships.O presente trabalho tem como objetivo propor uma reflexão acerca dos requisitos legais da existência da relação de emprego, analisando o grau de importância da subordinação e suas nuances práticas, além de discutir a respeito do poder diretivo do empregador diante da parassubordinação, como forma de dependência jurídica, surgida em face das inovações tecnológicas e consequentemente as novas relações de trabalho

Snacks extrusados funcionais com licopeno e proteína de soja

In this work, the effects of thermoplastic extrusion process parameters (raw material moisture content and temperature) and the addition of functional ingredients (lycopene and soy protein) on quality characteristics of a base-formulation for extruded corn snacks were studied, with the objective of developing an easy-to-eat functional product. A single-screw Labor PQ 30 model Inbramaq extruder was used for extrusion and a central composite rotational design (CCRD) was followed. The independent variables were: i) percentage of soy protein isolate (0-30%); ii) percentage of lycopene preparation (0-0.1%); iii) raw material moisture content (20-30%); and iv) 5th zone temperature (100-150 °C). The expansion index reached maximum values with the lowest raw material moisture content (20%) and intermediate temperatures (approximately 125 °C). Instrumental hardness was higher with high moisture and low temperature; however, increasing the percentage of soy protein was beneficial for the texture of the product, reducing hardness. The red color intensity increased with the increase in lycopene content and moisture, and with the reduction of temperature. Sensory acceptance tests were carried out for two products, with maximum percentages of the functional ingredients, 20% moisture and temperatures of 125 and 137 °C, with greater acceptance for the product extruded at 125 °C.Neste trabalho, estudou-se a influência de parâmetros do processo de extrusão termoplástica (umidade da matéria-prima e temperatura) e da adição de ingredientes funcionais (licopeno e proteína de soja) sobre características de qualidade de uma formulação-base para snacks extrusados de milho, com o objetivo de desenvolver um alimento funcional de fácil consumo. Utilizou-se um extrusor monorrosca Inbramaq, modelo Labor PQ 30, e seguiu-se um planejamento experimental com as seguintes variáveis independentes: i) teor de isolado proteico de soja (0 a 30%); ii) teor de preparado de licopeno (0 a 0,1%); iii) umidade da matéria-prima (20 a 30%); e iv) temperatura do extrusor na zona 5 (100 a 150 °C). O índice de expansão atingiu valores máximos com o menor valor de umidade da matéria-prima (20%) e temperatura intermediária (aproximadamente 125 °C). A dureza instrumental foi mais elevada com umidade alta e temperatura baixa, entretanto, o aumento do teor de proteína de soja foi benéfico para a textura do produto final, reduzindo a dureza. A intensidade da coloração vermelha aumentou com o aumento do teor de licopeno e da umidade, e com a diminuição da temperatura. Foram realizados testes de aceitação sensorial para dois produtos, com os teores máximos dos ingredientes funcionais, 20% umidade e temperaturas de 125 e 137 °C, obtendo-se maior aceitação para o produto extrusado a 125 °C.14315

Critical animal and media studies: Expanding the understanding of oppression in communication research

Critical and communication studies have traditionally neglected the oppression conducted by humans towards other animals. However, our (mis)treatment of other animals is the result of public consent supported by a morally speciesist-anthropocentric system of values. Speciesism or anthroparchy, as much as any other mainstream ideologies, feeds the media and at the same time is perpetuated by them. The goal of this article is to remedy this neglect by introducing the subdiscipline of Critical Animal and Media Studies. Critical Animal and Media Studies takes inspiration both from critical animal studies – which is so far the most consolidated critical field of research in the social sciences addressing our exploitation of other animals – and from the normative-moral stance rooted in the cornerstones of traditional critical media studies. The authors argue that the Critical Animal and Media Studies approach is an unavoidable step forward for critical media and communication studies to engage with the expanded circle of concerns of contemporary ethical thinking

Functional, motor, and sensory assessment instruments upon nerve repair in adult hands: Systematic review of psychometric properties

© 2018 The Author(s). Background: Outcome after nerve repair of the hand needs standardized psychometrically robust measures. We aimed to systematically review the psychometric properties of available functional, motor, and sensory assessment instruments after nerve repair. Methods: This systematic review of health measurement instruments searched databases from 1966 to 2017. Pairs of raters conducted data extraction and quality assessment using a structured tool for clinical measurement studies. Kappa correlation was used to define the agreement prior to consensus for individual items, and intraclass correlation coefficient (ICC) was used to assess reliability between raters. A narrative synthesis described quality and content of the evidence. Results: Sixteen studies were included for final critical appraisal scores. Kappa ranged from 0.31 to 0.82 and ICC was 0.81. Motor domain had manual muscle testing with Kappa from 0.72 to 0.93 and a dynamometer ICC reliability between 0.92 and 0.98. Sensory domain had touch threshold Semmes-Weinstein monofilaments (SWM) as the most responsive measure while two-point discrimination (2PD) was the least responsive (effect size 1.2 and 0.1). A stereognosis test, Shape and Texture Identification (STI), had Kappa test-retest reliability of 0.79 and inter-rater reliability of 0.61, with excellent sensibility and specificity. Manual tactile test had moderate to mild correlation with 2PD and SWM. Function domain presented Rosén-Lundborg score with Spearman correlations of 0.83 for total score. Patient-reported outcomes measurements had ICC of 0.85 and internal consistency from 0.88 to 0.96 with Patient-Rated Wrist and Hand Evaluation with higher score for reliability and Spearman correlation between 0.38 and 0.89 for validity. Conclusions: Few studies included nerve repair in their sample for the psychometric analysis of outcome measures, so moderate evidence could be confirmed. Manual muscle test and Rotterdam Intrinsic Hand Myometer dynamometer had excellent reliability but insufficient data on validity or responsiveness. Touch threshold testing was more responsive than 2PD test. The locognosia test and STI had limited but positive supporting data related to validity. Rosén-Lundborg score had emerging evidence of reliability and validity as a comprehensive outcome following nerve repair. Few questionnaires were considered reliable and valid to assess cold intolerance. There is no patient-reported outcome measurement following nerve repair that provides comprehensive assessment of symptoms and function by patient perspective

Correlation between centrality metrics and their application to the opinion model

In recent decades, a number of centrality metrics describing network properties of nodes have been proposed to rank the importance of nodes. In order to understand the correlations between centrality metrics and to approximate a high-complexity centrality metric by a strongly correlated low-complexity metric, we first study the correlation between centrality metrics in terms of their Pearson correlation coefficient and their similarity in ranking of nodes. In addition to considering the widely used centrality metrics, we introduce a new centrality measure, the degree mass. The m order degree mass of a node is the sum of the weighted degree of the node and its neighbors no further than m hops away. We find that the B_{n}, the closeness, and the components of x_{1} are strongly correlated with the degree, the 1st-order degree mass and the 2nd-order degree mass, respectively, in both network models and real-world networks. We then theoretically prove that the Pearson correlation coefficient between x_{1} and the 2nd-order degree mass is larger than that between x_{1} and a lower order degree mass. Finally, we investigate the effect of the inflexible antagonists selected based on different centrality metrics in helping one opinion to compete with another in the inflexible antagonists opinion model. Interestingly, we find that selecting the inflexible antagonists based on the leverage, the B_{n}, or the degree is more effective in opinion-competition than using other centrality metrics in all types of networks. This observation is supported by our previous observations, i.e., that there is a strong linear correlation between the degree and the B_{n}, as well as a high centrality similarity between the leverage and the degree.Comment: 20 page

CAIXAS ENTOMOLÓGICAS COMO RECURSO DIDÁTICO PARA O ENSINO DE CIÊNCIAS NOS ANOS INICIAIS DO ENSINO FUNDAMENTAL I

A realização de atividades práticas no Ensino de Ciências na Educação Básica, em especial, nos anos iniciais do Ensino Fundamental, ainda apresenta algumas precariedades, seja por falta de estrutura da escola, seja por carência de material, seja devido à preparação docente, ou outro. Diante dessa lacuna, a presente pesquisa objetivou investigar as contribuições que a montagem e uso de caixas entomológicas trazem para o Ensino de Ciências do Ensino Fundamental I da Educação Básica. Com caráter qualitativo, o estudo consistiu em coletar insetos e utilizá-los em uma aula de Ciências com produção, pelos próprios alunos participantes, de uma caixa entomológica. A mesma foi composta por 19 exemplares de insetos. O lócus principal da pesquisa foi o Laboratório de Biodiversidade e Conservação (LABICON), do Instituto Federal de Educação, Ciência e Tecnologia do Pará – (IFPA), Campus Abaetetuba, que possui uma coleção entomológica com fins didáticos e científicos. Os resultados apontam para o envolvimento e interesse dos discentes na realização da atividade, participação ativa dos estudantes no processo de ensino e aprendizagem, aproximação entre teoria e prática, bem como para a aceitação e perspectivas docentes para uso do material produzido. Com isso, apontamos a eficiência deste recurso metodológico no Ensino de Ciências, necessitando, contudo, que os professores se apropriem de experiências e conceitos relacionados ao tema, contextualizem a temática com assuntos inerentes às vivências dos estudantes e busquem formação continuada que os auxilie no aumento da diversificação e da interdisciplinaridade de suas aulas.

Type-Specific Cervico-Vaginal Human Papillomavirus Infection Increases Risk of HIV Acquisition Independent of Other Sexually Transmitted Infections

Sexually transmitted infections (STIs) such as herpes simplex virus (HSV)-2 are associated with an increased risk of HIV infection. Human papillomavirus (HPV) is a common STI, but little is know about its role in HIV transmission. The objective of this study was to determine whether cervico-vaginal HPV infection increases the risk of HIV acquisition in women independent of other common STIs.This prospective cohort study followed 2040 HIV-negative Zimbabwean women (average age 27 years, range 18-49 years) for a median of 21 months. Participants were tested quarterly for 29 HPV types (with L1 PCR primers) and HIV (antibody testing on blood samples with DNA or RNA PCR confirmation). HIV incidence was 2.7 per 100 woman-years. Baseline HPV prevalence was 24.5%, and the most prevalent HPV types were 58 (5.0%), 16 (4.7%), 70 (2.4%), and 18 (2.3%). In separate regression models adjusting for baseline variables (including age, high risk partner, positive test for STIs, positive HSV-2 serology and condom use), HIV acquisition was associated with having baseline prevalent infection with HPV 58 (aHR 2.13; 95% CI 1.09-4.15) or HPV 70 (aHR 2.68; 95% CI 1.08-6.66). In separate regression models adjusting for both baseline variables and time-dependent variables (including HSV-2 status, incident STIs, new sexual partner and condom use), HIV acquisition was associated with concurrent infection with any non-oncogenic HPV type (aHR 1.70; 95% CI 1.02-2.85), any oncogenic HPV type (aHR 1.96; 95% CI 1.16-3.30), HPV 31 (aHR 4.25; 95% CI 1.81-9.97) or HPV 70 (aHR 3.30; 95% CI 1.50-7.20). Detection of any oncogenic HPV type within the previous 6 months was an independent predictor of HIV acquisition, regardless of whether HPV status at the HIV acquisition visit was included (aHR 1.95; 95% CI 1.19-3.21) or excluded (aHR 1.96; 95% CI 1.02-2.85) from the analysis.Cervico-vaginal HPV infection was associated with an increased risk of HIV acquisition in women, and specific HPV types were implicated in this association. The observational nature of our study precludes establishment of causation between HPV infection and HIV acquisition. However, given the high prevalence of HPV infection in women, further investigation of the role of HPV in HIV transmission is warranted