Epstein Barr Virus genome variation and functional analysis of the IR-1 internal repeat

Epstein Barr Virus (EBV), a human gammaherpesvirus, establishes lifelong infection in B lymphocytes and is associated with a variety of malignancies including; Hodgkin's lymphoma, Burkitt's lymphoma and nasopharyngeal carcinoma. Due to the differences in geographical prevalence and expression patterns of EBV associated malignancies, it has been hypothesised that variation between EBV strains contributes to these malignancies. To investigate the natural variation of EBV strains, isolates were either collected or donated by contributors from a variety of sources; such as saliva, cell lines and tumour biopsies, which following DNA extraction and quantification, were Next-Generation sequenced. Analysis of saliva isolates determined that 50\% of isolates were co-infected with both type 1 and type 2 strains and, type 2 strains although most commonly found in Sub-Saharan Africa, were found to be the predominant strain within some British Caucasian individuals. Highly polymorphic proteins, EBNA-1 and LMP-1, were characterised into subtypes and following analysis, found to be both geographically and ethnically associated but not cancer associated. Certain EBNA-1 and LMP-1 subtypes were found to be linked and polymorphisms throughout the EBNA-1 protein were associated with specific 487 codons. Most of the EBV genome has been characterised but the complete function of the large internal repeat (IR-1), which typically consists of 5-8 copies of a 3 kilo base repeat unit, remains unclear. This repeat array is known to contain the latency promoter Wp, used initially during B cell infection, and the W1 and W2 exons which make up the repeat region of the EBNA-LP protein. Other components of the IR-1; the BWRF1 open reading frame and a 512bp inverted repeat both remain uncharacterised. Through the production of an inverted repeat knockout ($\Delta$invR) B95-8 EBV BAC, this study found that the inverted repeat is essential for B cell immortalisation and plays a role in virus production.Open Acces

Searching for Identity: Connecting Students to Young Adult Literature in the Classroom Through Language

Young adult literature largely influences the cultures and the lives of young people; often these popular young adult novels become well-known as they are made into movies and are in high demand. These novels are not just for young adults; these texts can be read at any age and have accessible themes that many people can relate to. However, in this research, young adult literature will be discussed in terms of how these novels affect children, mostly from ages ten to eighteen, as many of the characters in these texts are a similar age to them. Young adult literature (YA lit) is not just any book that would be read in a secondary education classroom. Novels that are considered classics, like perhaps Lord of the Flies or Oliver Twist, might be about children, but they are either not written for children and therefore not considered young adult literature. While older classics of course have literary merit, and much can be learned from them, this research will focus primarily on more recently published young adult literature that is more currently relatable to adolescents’ lives and specifically written for teenagers. Literature does not have to be relatable, because the reader will most likely learn something either way. But for teenagers specifically, who often do not enjoy reading and are questioning their own sense of identity, YA lit can serve as a powerful tool for helping students understand themselves at a time in their lives when they are trying to figure out who they are

Melhoria na Atenção à Saúde das Crianças de 0 a 72 Meses da ESF Santa Terezinha, São Lourenço do Sul/RS

O trabalho de conclusão foi realizado na Unidade de Saúde da Família Santa Terezinha localizada na zona urbana de São Lourenço do Sul/RS que conta com uma equipe de Estratégia de Saúde da Família, onde atende aproximadamente 5000 usuários na área adstrita. Esse trabalho de conclusão foi direcionado à saúde da criança pois a infância é um capítulo definidor da trajetória de vida no indivíduo, e a promoção de saúde durante essa fase pode representar a qualidade de vida quando adulto. O desenvolvimento pleno de suas capacidades cognitivas, o estado nutricional adequado, sua capacidade humoral eficaz é determinado nos primeiros anos de vida. O programa saúde da criança contempla todos esses aspectos em atenção básica durante a puericultura, portanto esse acompanhamento deve ser realizado com muita dedicação e comprometimento tanto pelo médico como por toda equipe da estratégia de saúde da família. O objetivo principal do trabalho foi implantar o programa de saúde da criança, melhorando o atendimento para os residentes de 0 a 72 meses na área adstrita. O protocolo utilizado para amparar e guiar a implantação foi o Caderno de Atenção Básica do Ministério da Saúde – 33, ano 2012. Os dados obtidos através dos registros específicos e prontuário foram mensalmente revisados para análise dos indicadores. Na área adstrita da unidade há 250 usuários na faixa etária entre 0 a 72 meses, valores estimados, já que previamente a implantação do programa, não havia nenhum registro específico para esta faixa etária. Ao término do trabalho chegamos ao total de 139 (55,6%) crianças cadastradas no programa de saúde da criança. Do total de 139 usuários cadastradas no programa, na faixa etária de 0 a 72 meses anos, 136 (97,8%) cuidadores/pais foram orientadas sobre questões próprias de desenvolvimento neurocognitivo e crescimento nutricional, estando essas com os cadastros em dia. Concluímos que através do trabalho foi possível identificar as deficiências do serviço e melhorá-las, qualificar e uniformizar o atendimento às crianças, criar registros específicos possibilitando controle contínuo e planejamento de novas ações, bem como após a implantação do programa a permanência das ações na rotina da unidade

Flow, bem-estar subjetivo, estresse e suas relações em adultos brasileiros

O principal objetivo da presente dissertação foi estudar o flow. Para isso, dois estudos foram realizados. O primeiro estudo teve como objetivo adaptar a LONG Dispositional Flow Scale DFS-2 - General para o Português Brasileiro e investigar algumas evidências de validade do instrumento nesta população. Esse primeiro estudo foi dividido em duas etapas. A primeira foi o processo de tradução e adaptação da escala. A segunda etapa foi a realização de um estudo empírico. Os participantes foram uma amostra nacional de 310 adultos (77,4% mulheres), com idade entre 18 e 63 anos (M = 31, DP = 9,1). Parâmetros de análise fatorial confirmatória do modelo de Jackson (2010) com nove fatores de primeira ordem e com um fator de segunda ordem (flow) com os mesmos nove fatores de primeira ordem foram apresentados. Também foi apresentado um novo modelo proposto com seis fatores, e também um fator de segunda ordem dos mesmos. A DFS-2 geral apresentou propriedades psicométricas adequadas, sugerindo sua utilidade na avaliação do flow no contexto brasileiro. Os resultados também mostram correlações entre flow e outras variáveis (satisfação com a vida, afetos e estresse). O segundo estudo foi uma revisão sistemática que objetivou apresentar um panorama das publicações científicas sobre instrumentos psicológicos utilizados na Avaliação Psicológica do Estresse entre 2008 e 2015. Os resultados mostram as bases de dados, número de resumos e artigos incluídos e os instrumentos mais utilizados para mensurar o estresse. As conclusões da presente dissertação mostram a importância da freqüência de flow na promoção da satisfação com a vida e afetos positivos e na prevenção ou redução do estresse na vida diária.The main purpose of the present dissertation was studying flow. In order to do so, two studies were conducted. The first study aimed to adapt the LONG Dispositional Flow Scale DFS-2 – General to Brazilian Portuguese and to investigate some validity evidences of the instrument in this population. This study was divided into two steps. The first one was the process of translation and adaptation. The second stage was the conduction of an empirical study. Participants were a nationwide sample of 310 adults (77.4% female), aged 18 to 63 years old (M= 31, SD= 9.1). Confirmatory factor analysis parameters of the Jackson (2010) model with nine first order factor and with a second order Flow factor with the same nine first order factors were presented. Also a new proposed model with six factor, with also a second order Flow factor are reported. General DFS-2 presented adequate psychometric properties, suggesting its usefulness in evaluating flow in the Brazilian context. The results also show correlations between flow and other variables (satisfaction with life, affects and stress. The second study was a sistematic review that aimed to present an overview of the scientific publications about psychological instruments used at Psychological Assessment of Stress between 2008 and 2015. Results show the ued databases, number of abstractas and papers included and the most used instruments to measure stress. The conclusions of this dissertation show the importance of flow frequency on the promotion of satisfaction with life and positive affects and on the prevention or reduction of stress in daily life

Tuning into the real effect of smartphone use on parenting: a multiverse analysis

© 2020 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health. Background: Concerns have been raised regarding the potential negative impacts of parents’ smartphone use on the parent–child relationship. A scoping literature review indicated inconsistent effects, arguably attributable to different conceptualizations of parent phone use and conflation of phone use with technological interference. Methods: Based on a sample of n = 3, 659 parents collected in partnership with a national public broadcaster, we conducted a multiverse analysis. We explored 84 different analytic choices to address whether associations were weak versus robust, and provide clearer direction for measurement, theory, and practice. Effects were assessed in relation to p values, effect sizes, and AIC; we further conducted a meta-analytic sensitivity check. Results: Direct associations between smartphone use and parenting were relatively weak and mixed. Instead, the relation between use and parenting depended on level of technological interference. This pattern was particularly robust for family displacement. At low levels of displacing time with family using technology, more smartphone use was associated with better (not worse) parenting. Conclusions: Our results indicate fragility in findings of risks for parental smartphone use on parenting; there were few concerns in this regard. Rather, at low levels of technological interference, more phone use was associated with higher parenting quality. Scholars should avoid generalized narratives of family risk and seek to uncover real effects of smartphone use on family outcomes across diverse households and contexts

Tuning into the real effect of smartphone use on parenting: A multiverse analysis

Background Concerns have been raised regarding the potential negative impacts of parents' smartphone use on the parent-child relationship. A scoping literature review indicated inconsistent effects, arguably attributable to different conceptualizations of parent phone use and conflation of phone use with technological interference. Methods Based on a sample of n = 3, 659 parents collected in partnership with a national public broadcaster, we conducted a multiverse analysis. We explored 84 different analytic choices to address whether associations were weak versus robust, and provide clearer direction for measurement, theory, and practice. Effects were assessed in relation to p values, effect sizes, and AIC; we further conducted a meta‐analytic sensitivity check. Results Direct associations between smartphone use and parenting were relatively weak and mixed. Instead, the relation between use and parenting depended on level of technological interference. This pattern was particularly robust for family displacement. At low levels of displacing time with family using technology, more smartphone use was associated with better (not worse) parenting. Conclusions Our results indicate fragility in findings of risks for parental smartphone use on parenting; there were few concerns in this regard. Rather, at low levels of technological interference, more phone use was associated with higher parenting quality. Scholars should avoid generalized narratives of family risk and seek to uncover real effects of smartphone use on family outcomes across diverse households and contexts

Folding and Hydrodynamics of a DNA i-Motif from the c-MYC Promoter Determined by Fluorescent Cytidine Analogs

AbstractThe four-stranded i-motif (iM) conformation of cytosine-rich DNA has importance to a wide variety of biochemical systems that range from their use in nanomaterials to potential roles in oncogene regulation. The iM structure is formed at slightly acidic pH, where hemiprotonation of cytosine results in a stable C-C+ basepair. Here, we performed fundamental studies to examine iM formation from a C-rich strand from the promoter of the human c-MYC gene. We used a number of biophysical techniques to characterize both the hydrodynamic properties and folding kinetics of a folded iM. Our hydrodynamic studies using fluorescence anisotropy decay and analytical ultracentrifugation show that the iM structure has a compact size in solution and displays the rigidity of a double strand. By studying the rates of circular dichroism spectral changes and quenching of fluorescent cytidine analogs, we also established a mechanism for the folding of a random coil oligo into the iM. In the course of determining this folding pathway, we established that the fluorescent dC analogs tC° and PdC can be used to monitor individual residues of an iM structure and to determine the pKa of an iM. We established that the C-C+ hydrogen bonding of certain bases initiates the folding of the iM structure. We also showed that substitutions in the loop regions of iMs give a distinctly different kinetic signature during folding compared with bases that are intercalated. Our data reveal that the iM passes through a distinct intermediate form between the unfolded and folded forms. Taken together, our results lay the foundation for using fluorescent dC analogs to follow structural changes during iM formation. Our technique may also be useful for examining folding and structural changes in more complex iMs

Prognostic value of HLA-I homozygosity in patients with non-small cell lung cancer treated with single agent immunotherapy

Background We aimed to assess the impact of genomic human leukocyte antigen (HLA)-I/II homozygosity on the survival benefit of patients with unresectable locally advanced, metastatic non-small lung cancer treated by single-agent programmed cell death protein-1/programmed death ligand 1 (PD1/PDL1) inhibitors. Methods We collected blood from 170 patients with advanced lung cancer treated with immunotherapy at two major oncology centers in Western Australia. Genomic DNA was extracted from white blood cells and used for HLA-I/II high-resolution typing. HLA-I/II homozygosity was tested for association with survival outcomes. Univariable and multivariable Cox regression models were constructed to determine whether HLA homozygosity was an independent prognostic factor affecting Overall Survival (OS) and Progression Free Survival (PFS). We also investigated the association between individual HLA-A and -B supertypes with OS. Results Homozygosity at HLA-I loci, but not HLA-II, was significantly associated with shorter OS (HR=2.17, 95% CI 1.13 to 4.17, p=0.02) in both univariable and multivariable analysis. The effect of HLA-I homozygosity in OS was particularly relevant for patients with tumors expressing PDL1 ≥ 50% (HR=3.93, 95% CI 1.30 to 11.85, p \u3c 0.001). The adverse effect of HLA-I homozygosity on PFS was only apparent after controlling for interactions between PDL1 status and HLA-I genotype (HR=2.21, 95% CI 1.04 to 4.70, p=0.038). The presence of HLA-A02 supertype was the only HLA-I supertype to be associated with improved OS (HR=0.56, 95% CI 0.34 to 0.93, p=0.023). Conclusion Our results suggest that homozygosity at ≥ 1 HLA-I loci is associated with short OS and PFS in patients with advanced non-small cell lung cancer with PDL1 ≥ 50% treated with single-agent immunotherapy. Carriers of HLA-A02 supertype reported better survival outcomes in this cohort of patients