The molecular pathways mediating the role of cyclooxygenase enzymes and prostaglandins in cervical neoplasias

Includes bibliographical references (leaves 146-170).Cervical Carcinoma is one of the leading causes of cancer-related death in women. The prevalence of this disease is particularly high in South Africa, occurring on average, in 60 out of every 100 000 women. Previous studies have demonstrated over-expression of cyclooxygenase-2 enzyme and enhanced synthesis of prostanoids, such as prostaglandin E2, in cervical carcinomas. Prostaglandin E2 mediates its effects by interacting with one of four receptors termed EPI-4. Expression and signalling of EP receptors, including EP4, are elevated in cervical carcinomas. The initial aim of this study was to localise the site of expression of EP4 receptors in cervical squamous cell- and adenocarcinomas. Immunohistochemical analysis performed on paraffm wax-embedded cervical tissue sections localised the site of EP4 receptor expression to the neoplastic epithelial cells of all squamous cell carcinomas and adenocarcinomas studied. Minimal EP4 receptor immunoreactivity was detected in normal cervix. The site of localisation of the EP4 receptor within the epithelial compartment suggested that prostaglandin E2 may act in an autocrine/paracrine manner to modulate epithelial cell function and promote tumourigenesis. In addition to endogenous prostaglandin E2, EP receptors in cervical carcinomas can be activated by seminal plasma prostaglandins. Prostaglandin concentration in seminal plasma is 10,000 times higher than that found at a site of inflammation, and prostaglandin E2 is the predominant type of prostaglandin detected in semen. In order to investigate the potential activation of the EP4 receptor by prostaglandin E2 or seminal plasma prostaglandins, we developed an EP4-overexpressing adenocarcinoma cell model system using HeLa (cervical carcinoma) cells.Using this model system the signal transduction pathways activated by prostaglandin E2-or seminal plasma-EP4 receptor interaction in HeLa wild type and EP4 receptor overexpressing(EP4S) He La cells were investigated. Treatment of EP4S cells with seminal plasma or prostaglandin E2 resulted in a rapid accumulation of cAMP (p<;0.001) and phosphorylation of ERK1I2 (p<;O.OOI) in EP4S compared with wild-type cells. This elevated phosphorylation of ERK1I2 is inhibited by co-treatment of cells with chemical inhibitors of MEK (PD98059), epidermal growth factor receptor tyrosine kinase (AGI478) or EP4-selective receptor antagonist (ONO-AE2-227). We next investigated the target genes activated by seminal plasma or prostaglandin E2-EP4 ligand-receptor interaction. Treatment of EP4S cells with seminal plasma or prostaglandin E2 also resulted in elevated expression of the twnourigenic gene, cyclooxygenase-2 (p<;O.OOI), and two genes associated with angiogenesis, vascular endothelial growth factor (p<;O.OOI) and basic fibroblast growth factor (p<;O.05). Expression of these genes was inhibited by co-treatment of cells with seminal plasma or prostaglandin E2 and the MEK inhibitor, the epidermal growth factor receptor tyrosine kinase inhibitor or the EP4-selective receptor antagonist

Male coercion and female choice in wild chimpanzees

The question of whether female primates, in promiscuously breeding species, exhibit preferences for particular males, and subtly attempt to bias paternity, is famously intractable. Previous studies from three sites have shown that, in wild chimpanzees (Pan troglodytes), females mate more restrictively during the fertile period, and this has been taken as evidence for female choice. A common problem with these studies, however, was a failure to test whether females sexual solicitations and refusals, during periods when females are most attractive, resulted from free choice or from fear of male aggression. We used 10 years of data from the Kanyawara community in Kibale National Park to test whether male aggression influences female mating patterns. As with previous studies, we found that females mated more restrictively during the periovulatory period (POP), and that males who were generally approached by individual females for copulations were approached more frequently by those females during the POP. However, individual females at our site initiated periovulatory copulations most frequently with the males who had been most aggressive toward them throughout their cycles (i.e. during both estrous and non-estrous periods). We interpret this as evidence for a form of “conditioning aggression” in which males are aggressive in a variety of contexts to manipulate female sexuality over the long term. We suggest that the resulting mating patterns fit with a model of male coercion, but not with models of female choice based on preferences for “good genes”.AnthropologyHuman Evolutionary Biolog

Sexual Coercion by Male Chimpanzees Shows That Female Choice May Be More Apparent than Real

The extent to which active female mating preferences influence male reproductive success in mammals is unclear, particularly for promiscuously breeding species like chimpanzees (Pan troglodytes). Previous studies from multiple long-term study sites have shown that female chimpanzees mate more restrictively around ovulation, and this has been taken as evidence for female choice. However, none of these studies rigorously evaluated the alternative hypothesis that restrictive mating results not from unconstrained choice, but in response to coercive mate guarding, in which males use punishment and intimidation to reduce female promiscuity and promote their own mating interests. Nor did they consider evidence for the potential genetic or phenotypic benefits that females might be choosing. Using 11 years of data from the Kanyawara community in Kibale National Park, Uganda, we previously demonstrated that males achieve elevated mating success with those females toward whom they direct high levels of aggression. Here we extend those findings to show that even female copulatory approaches, which have previously been attributed to female choice, are correlated with male aggression. Specifically, individual females at our site initiated periovulatory copulations most frequently with the males who were most aggressive toward them throughout their cycles. Those males showed high rates of aggression toward females throughout estrus, despite achieving high copulation rates, demonstrating a continuing conflict of interest over the exclusivity of mating access. Because sexual coercion is potentially widespread in primates and other mammals, our results stress the importance of considering the influence of male aggression in studies of female choice.Human Evolutionary Biolog

An Electromyography (EMG) Study of Two Dynamic Surfaces: Hippotherapy and Swiss Ball

The use of horseback riding as a therapeutic intervention has been used since the fifth century, B.C.1 It has been proposed that the physical benefits of horseback riding include: improved posture, balance, muscle strength, decreased spasticity, improved gait patterns, and coordination. Unfortunately, at the current time, hippotherapy, the use of horses in physical therapy intervention, has been poorly documented due to little objective research. The purpose of this study was to provide an objective measure of children\u27s postural muscle activity through the use of electromyography (EMG) and electrogoniometry on two dynamic surfaces. Data was analyzed for differences in postural muscle activity and range of motion (ROM) when using a horse as a dynamic therapeutic surface as compared to a therapeutic ball as a dynamic surface. Goniometric data was collected in the frontal and sagittal planes for pelvic and trunk ROM. Thirteen, typically developing children between the ages of 3 and 12, and two \u27 children with developmental disabilities between the ages of 6 and 11, completed the research protocol including walking 20 feet, one trial of each of the following: static sitting for 10 seconds, static standing for 10 seconds, riding a horse for 30 seconds, and sitting on a dynamic therapeutic ball for 30 seconds. Muscle activity of the rectus abdominis (RA), external obliques (EO), and lumbar erector spinae (LES) muscles, was recorded through surface electrodes, muscle activity in each trial was compared with the muscle activity during the walking as the reference baseline. Results of this study provided objective data on the effects of two dynamic surfaces, a horse and therapeutic ball, on postural muscle activity in typically developing children. Compared to the therapeutic ball, when the subjects were on the horse they had significantly (p\u3c0.05) more muscle activity in the RA and EO muscles. Goniometric results showed that overall the subjects had more ROM in the frontal plane during the therapeutic ball activity (2.8 to 9.4 degrees) as compared to walking (1.6 to 6.9 degrees) and horse activity (2.1 to 9.9 degrees). Subjects also had more ROM in the sagittal plane during therapeutic ball activity (1.9 to 17.8 degrees) as compared to walking (2.5 to 15.0 degrees) and horse activity (0.4 to 20.9 degrees). This study provided an objective measure of postural muscle activity and pelvic and trunk ROM present in subjects during activities on two dynamic surfaces, the horse and therapeutic ball, compared to walking. It was found that there was more postural muscle activity present in subjects while on the horse versus on the therapeutic ball. Overall, subjects had more ROM in the frontal and sagittal planes during the therapeutic ball activity as compared to the walking and the horse activity, however, ROM for walking and horse activity was similar. Further research is needed in the field of hippotherapy to provide more objective and quantifiable data in order to fully determine the effects of hippotherapy, especially the long-term effects on function

Urinary C-Peptide Tracks Seasonal and Individual Variation in Energy Balance in Wild Chimpanzees

C-peptide of insulin presents a promising new tool for behavioral ecologists that allows for regular, noninvasive assessment of energetic condition in wild animals. C-peptide is produced on an equimolar basis with insulin, thus is indicative of the body's response to available glucose and, with repeated measurement, provides a biomarker of energy balance. As yet, few studies have validated the efficacy of C-peptide for monitoring energy balance in wild animals. Here, we assess seasonal and interindividual variation in urinary C-peptide concentrations of East African chimpanzees (Pan troglodytes schweinfurthii). We assayed 519 urine samples from 13 adult male chimpanzees in the Kanyawara community of Kibale National Park, Uganda. Cpeptide levels were significantly predicted by the total amount of fruit and the amount of preferred fruit in the diet. However, chimpanzees had very low c-peptide titers during an epidemic of severe respiratory illness, despite highly favorable feeding conditions. Kanyawara males had significantly lower C-peptide levels than males at Ngogo, a nearby chimpanzee community occupying a more productive habitat. Among Kanyawara males, low-ranking males had consistently higher C-peptide levels than dominant males. While counterintuitive, this result supports previous findings of costs associated with dominance in male chimpanzees. Our preliminary investigations demonstrate that C-peptide has wide applications in field research, providing an accessible tool for evaluating seasonal and individual variation in energetic condition, as well as the costs of processes such as immune function and reproduction.Anthropolog

SIGCHI Research Ethics Committee Town Hall

Since 2016, the SIGCHI Research Ethics Committee has been in place to advise CSCW and other SIGCHI conferences and communities on ethical issues that arise in the course of our research. This town hall style panel provides an annual opportunity to connect with the committee, which has a remit to report back to the HCI research community on issues that arise as our methods, technologies, and best practices evolv

Vocal signals facilitate cooperative hunting in wild chimpanzees

Cooperation and communication likely co-evolved in humans. However, the evolutionary roots of this interdependence remain unclear. We address this issue by investigating the role of vocal signals in facilitating a group cooperative behavior in an ape species: hunting in wild chimpanzees. First, we show that bark vocalizations produced before hunt initiation are reliable signals of behavioral motivation, with barkers being most likely to participate in the hunt. Next, we find that barks are associated with greater hunter recruitment and more effective hunting, with shorter latencies to hunting initiation and prey capture. Our results indicate that the co-evolutionary relationship between vocal communication and group-level cooperation is not unique to humans in the ape lineage, and is likely to have been present in our last common ancestor with chimpanzees

Birth size and brain function 75 years later.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pageThere are several lines of evidence pointing to fetal and other early origins of diseases of the aging brain, but there are no data directly addressing the hypotheses in an older population. We investigated the association of fetal size to late-age measures of brain structure and function in a large cohort of older men and women and explored the modifying effect of education on these associations.Within the AGES (Age Gene/Environment Susceptibility)-Reykjavik population-based cohort (born between 1907 and 1935), archived birth records were abstracted for 1254 men and women who ∼75 years later underwent an examination that included brain MRI and extensive cognitive assessment.Adjustment for intracranial volume, demographic and medical history characteristics, and lower Ponderal index at birth (per kg/m(3)), an indicator of third-trimester fetal wasting, was significantly associated with smaller volumes of total brain and white matter; βs (95% confidence intervals) were -1.0 (-1.9 to -0.0) and -0.5 (-1.0 to -0.0) mL. Furthermore, lower Ponderal index was associated with slower processing speed and reduced executive functioning but only in those with low education (β [95% confidence interval]: -0.136 [-0.235 to -0.036] and -0.077 [-0.153 to -0.001]).This first study of its kind provides clinical measures suggesting that smaller birth size, as an indicator of a suboptimal intrauterine environment, is associated with late-life alterations in brain tissue volume and function. In addition, it shows that the effects of a suboptimal intrauterine environment on late-life cognitive function were present only in those with lower educational levels

VISIÓN DE ENFERMERAS ACERCA DE LA VULNERABILIDAD DE LOS ADOLESCENTES EN UN DISTRITO SANITARIO

Pesquisa exploratória de caráter qualitativo, fundamentada na Teoria da Intervenção Práxica da Enfermagem em Saúde Coletiva. Com objetivo de identificar as vulnerabilidades dos adolescentes segundo o olhar de enfermeiras de um Distrito Sanitário. Os dados foram coletados por meio de entrevistas semiestruturadas com dezesseis enfermeiras no período de fevereiro a março de 2014, sendo analisados por meio de análise de conteúdo, com apoio do softwarewebQDA. Foram evidenciadas quatro categorias e dezesseis subcategorias, destacandose o reconhecimento de vulnerabilidades nos adolescentes. Na construção social, naturaliza-se que meninos e meninas têm vulnerabilidades diferentes no território. Portanto, para intervenções, é necessária a capacitação dos profissionais e apoio da gestão para que, em ações intersetoriais, sejam atendidas suas necessidades. Concluise que são necessários estudos que discutam à luz de gênero o processo de determinação da vulnerabilidade dos adolescentes para instrumentalizar projetos de intervenção que levem à superação de tais vulnerabilidades.Investigación exploratoria cualitativa, fundamentada en la Teoría de la Intervención Práxica de Enfermería en Salud Colectiva. El objetivo fue identificar las vulnerabilidades de los adolescentes bajo la visión de enfermeras de un Distrito Sanitario. Los datos fueron obtenidos por medio de entrevistas semiestructuradas con dieciseis enfermeras en el periodo de febrero a marzo de 2014, siendo estudiados por medio de análisis de contenido, con el software webQDA. Fueron evidenciadas cuatro categorías y dieciseis subcategorías, destacándose el reconocimiento de vulnerabilidades en los adolescentes. En la construcción social, se percibe que chicos y chicas presentan vulnerabilidades distintas en el territorio. Por lo tanto, para intervenciones, es necesaria la capacitación de los profesionales y apoyo de la gestión para que, en acciones intersectoriales, sus necesidades sean atendidas. Se concluye que son necesarios estudios para discutir a la luz de género el proceso de determinación de la vulnerabilidad de los adolescentes para dar herramientas a proyectos de intervención para la superación de tales vulnerabilidades.This exploratory research with a qualitative character, grounded in the Theory of Nursing Praxis Intervention in Collective Health, aims to identify the adolescents’ vulnerabilities according to the view of nurses of a Health District. The data were collected using semistructured interviews held with 16 nurses in February – March 2014, these being analyzed through content analysis, using the webQDA software. Evidence was found for four categories and sixteen subcategories, with emphasis placed on the recognition of vulnerabilities among the adolescents. In the social construction, it is naturalized that boys and girls have different vulnerabilities in the territory. Therefore, for interventions, the training of the professionals and support from the management is necessary such that their needs may be met in interdepartmental actions. It is concluded that studies are necessary which discuss, in the light of gender, the process of determination of the adolescents’ vulnerability, so as to instrumentalize intervention projects which lead to overcoming these vulnerabilities

Serum cytokine profile of neonatal broiler chickens infected with Salmonella Typhimurium

The avian immune system responds to Salmonella infection by expressing cytokines and chemokines. We hypothesized that the immune status of Salmonella Typhimurium (ST) challenged neonatal broilers would differ from the uninfected treatment. The objective of this experiment was to evaluate 12 cytokines. Day of hatch male chicks were randomly allocated into a control or ST challenged group. At day three of age, sterile diluent or 5.0 × 108 CFU of ST was given orally to each chick. Blood was obtained 24 h post challenge and serum separated for later analysis (n = 30 chicks/treatment). Significant (p ≤ 0.05) increases in pro-inflammatory cytokines-interleukin-6 (IL-6), IL-16, and IL-21; anti-inflammatory cytokines- IL-10; chemokines-regulated on activation, normal T cell expressed and secreted (RANTES), macrophage inflammatory protein-1β (MIP-1β), and MIP-3α; colony stimulating factors-macrophage colony-stimulating factor (M-CSF); and growth factors-vascular endothelial growth factor (VEGF) were observed in the serum of the challenged chicks when compared to the control. No significant differences were observed in IL-2, interferon gamma (IFNγ), and IFNα. These data indicate the detection of mucosal immune responses in broiler chickens following ST infection. The heightened levels of pro-inflammatory cytokines, chemokines, and colony stimulating factors align with known inflammatory mechanisms, like the influx of immune cells. However, the elevation of IL-10 was unexpected, due to its immunoregulatory properties. Notably, the rise in VEGF levels is compelling, as it suggests the possibility of tissue repair and angiogenesis in ST infected birds