Life in the tundra

A creative thesis written for the nonfiction sequence of the Southern New Hampshire University Master of Fine Arts Creative Writing programMaster of Fine Arts (M.F.A.)School of Arts and Science

Multiplex Analysis of Serum Cytokines in Humans with Hantavirus Pulmonary Syndrome

Hantavirus pulmonary syndrome (HPS) is an acute zoonotic disease transmitted primarily through inhalation of virus-contaminated aerosols. Hantavirus infection of endothelial cells leads to increased vascular permeability without a visible cytopathic effect. For this reason, it has been suggested that the pathogenesis of HPS is indirect with immune responses, such as cytokine production, playing a dominant role. In order to investigate their potential contribution to HPS pathogenesis, we analyzed the serum of hantavirus-infected subjects and healthy controls for 68 different cytokines, chemokines, angiogenic, and growth factors. Our analysis identified differential expression of cytokines that promote tissue migration of mononuclear cells including T lymphocytes, natural killer cells, and dendritic cells. Additionally, we observed a significant upregulation of cytokines known to regulate leukocyte migration and subsequent repair of lung tissue, as well as cytokines known to increase endothelial monolayer permeability and facilitate leukocyte transendothelial migration. Conversely, we observed a downregulation of cytokines associated with platelet numbers and function, consistent with the thrombocytopenia observed in subjects with HPS. This study corroborates clinical findings and extends our current knowledge regarding immunological and laboratory findings in subjects with HPS

Who does not gain weight? Prevalence and predictors of weight maintenance in young women

OBJECTIVE: To investigate the prevalence and predictors of weight maintenance over time in a large sample of young Australian women. DESIGN: This population study examined baseline and 4 y follow-up data from the cohort of young women participating in the Australian Longitudinal Study on Women\u27s Health. SUBJECTS: A total of 8726 young women aged 18-23 y at baseline. MEASURES: Height, weight and body mass index (BMI); physical activity; time spent sitting; selected eating behaviours (eg dieting, disordered eating, takeaway food consumption); cigarette smoking, alcohol consumption; parity; and sociodemographic characteristics. RESULTS: Only 44% of the women reported their BMI at follow-up to be within 5% of their baseline BMI (maintainers); 41% had gained weight and 15% had lost weight. Weight maintainers were more likely to be in managerial or professional occupations; to have never married; to be currently studying; and not to be mothers. Controlling for sociodemographic factors, weight maintainers were more likely to be in a healthy weight range at baseline, and to report that they spent less time sitting, and consumed less takeaway food, than women who gained weight. CONCLUSIONS: Fewer than half the young women in this community sample maintained their weight over this 4 y period in their early twenties. Findings of widespread weight gain, particularly among those already overweight, suggest that early adulthood, which is a time of significant life changes for many women, may be an important time for implementing strategies to promote maintenance of healthy weight. Strategies which encourage decreased sitting time and less takeaway food consumption may be effective for encouraging weight maintenance at this life stage.<br /

Physical Activity Assessed with Three Different Methods and the Framingham Risk Score on 10-Year Coronary Heart Disease Risk

Background: Physical activity (PA) protects against coronary heart disease (CHD) by favorably altering several CHD risk factors. In order to best understand the true nature of the relationship between PA and CHD, the impact different PA assessment methods have on the relationships must first be clarified. The purpose of this study was to examine associations between the Framingham Risk Score on 10-year estimated risk of CHD (10-year CHD risk) and three different PA assessment methods. Material/methods: Female (n=143) and male (n=155) adults wore activity monitors and recorded PA in logs during a seven-day period after which they completed a seven-day PA recall and had CHD risk factors assessed. The 10-year CHD risk was calculated from the CHD risk factors. Results: Multiple regression analyses showed 10-year CHD risk was negatively associated with physical activity measured by the activity monitor (p\u3c0.05) but not the log or recall in women. In men, significant inverse relationships between 10-year CHD risk and physical activity measured by the activity monitor and recall were observed. The log was not significantly associated with 10-year CHD risk in men. Conclusions: The results of this study concur with previous research in that PA is associated with the risk of developing CHD; however, the findings clearly suggest that it is important to consider the PA assessment method when interpreting this relationship

The structure of the hantavirus zinc finger domain is conserved and represents the only natively folded region of the Gn cytoplasmic tail

Hantaviruses, of the family Bunyaviridae, are present throughout the world and cause a variety of infections ranging from the asymptomatic to mild and severe hemorrhagic fevers. Hantaviruses are enveloped anti-sense RNA viruses that contain three genomic segments that encode for a nucleocapsid protein, two membrane glycoproteins (Gn and Gc), and an RNA polymerase. Recently, the pathogenicity of hantaviruses has been mapped to the carboxyl end of the 150 residue Gn cytoplasmic tail. The Gn tail has also been shown to play a role in binding the ribonucleoprotein (RNP), a step critical for virus assembly. In this study, we use NMR spectroscopy to compare the structure of a Gn tail zinc finger domain of both a pathogenic (Andes) and a non-pathogenic (Prospect Hill) hantavirus. We demonstrate that despite a stark difference in the virulence of both of these viruses, the structure of the Gn core zinc finger domain is largely conserved in both strains. We also use NMR backbone relaxation studies to demonstrate that the regions of the Andes virus Gn tail immediately outside the zinc finger domain, sites known to bind the RNP, are disordered and flexible, thus intimating that the zinc finger domain is the only structured region of the Gn tail. These structural observations provide further insight into the role of the Gn tail during viral assembly as well as its role in pathogenesis

Hantavirus infection suppresses thrombospondin-1 expression in cultured endothelial cells in a strain-specific manner

© 2016 Khaiboullina, Morzunov, St. Jeor, Rizvanov and Lombardi.Hantavirus infection is associated with two frequently fatal diseases in humans: Hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). The pathogenesis of hantavirus infection is complex and not fully understood; however, it is believed to involve virus-induced hyperinflammatory immune responses. Thrombospondin-1 (THBS1) is a large homotrimeric protein that plays a putative role in regulating blood homeostasis. Hyperresponsiveness to inflammatory stimuli has also been associated with defects in the THBS1 gene. Our data suggest that hantavirus infection of human umbilical cord vein endothelial cells (HUVEC) suppress the accumulation of THBS1 in the extracellular matrix. Additionally, this suppression is dependent on virus replication, implying a direct mechanism of action. Our data also imply that the pathogenic Andes and Hantaan strains inhibit THBS1 expression while the non-pathogenic Prospect Hill strain showed little inhibition. These observations suggest that a dysregulation of THBS1 may contribute to the pathogenesis of hantavirus infection

Multiplex analysis of serum cytokines in humans with hantavirus pulmonary syndrome

© 2015 Morzunov, Khaiboullina, St. Jeor, Rizvanov and Lombardi. Hantavirus pulmonary syndrome (HPS) is an acute zoonotic disease transmitted primarily through inhalation of virus-contaminated aerosols. Hantavirus infection of endothelial cells leads to increased vascular permeability without a visible cytopathic effect. For this reason, it has been suggested that the pathogenesis of HPS is indirect with immune responses, such as cytokine production, playing a dominant role. In order to investigate their potential contribution to HPS pathogenesis, we analyzed the serum of hantavirus-infected subjects and healthy controls for 68 different cytokines, chemokines, angiogenic, and growth factors. Our analysis identified differential expression of cytokines that promote tissue migration of mononuclear cells including T lymphocytes, natural killer cells, and dendritic cells. Additionally, we observed a significant upregulation of cytokines known to regulate leukocyte migration and subsequent repair of lung tissue, as well as cytokines known to increase endothelial monolayer permeability and facilitate leukocyte transendothelial migration. Conversely, we observed a downregulation of cytokines associated with platelet numbers and function, consistent with the thrombocytopenia observed in subjects with HPS. This study corroborates clinical findings and extends our current knowledge regarding immunological and laboratory findings in subjects with HPS

Associations of physical activity with body weight and fat in men and women

OBJECTIVE: Increasing physical activity is strongly advocated as a key public health strategy for weight gain prevention. We investigated associations of leisure-time physical activity (LTPA) and occupational/domestic physical activity with body mass index (BMI) and a skinfold-derived index of body fat (sum of six skinfolds), among normal-weight and overweight men and women.DESIGN: Analyses of cross-sectional self-report and measured anthropometric data.SUBJECTS: A total of 1302 men and women, aged 18-78 y, who were part of a randomly selected sample and who agreed to participate in a physical health assessment.MEASUREMENTS: Self-report measures of physical activity, measured height and weight, and a skinfold-derived index of body fatness.RESULTS: Higher levels of LTPA were positively associated with the likelihood of being in the normal BMI and lower body fat range for women, but few or no associations were found for men. No associations were found between measures of occupational/domestic activity and BMI or body fat for men or women.CONCLUSION: By using a skinfold sum as a more direct measure of adiposity, this study extends and confirms the previous research that has shown an association between BMI and LTPA. Our results suggest gender differences in the relationship of leisure-time physical activity with body fatness. These findings, in conjunction with a better understanding of the causes of such differences, will have important public health implications for the development and targeting of weight gain prevention strategies.<br /

ZIKV infection regulates inflammasomes pathway for replication in monocytes

© 2017 The Author(s). ZIKV causes microcephaly by crossing the placental barrier, however, the mechanism of trans-placental dissemination of ZIKV remains unknown. Here, we sought to determine whether monocytes, which can cross tissue barriers, assist ZIKV dissemination to the fetus. We determined this by infecting monocytes with two strains of ZIKV: South American (PRVABC59) and Nigerian (IBH30656) and analyzing viral replication. We found that ZIKV infects and replicates in monocytes and macrophages, which results in the modulation of a large number of cellular genes. Analysis of these genes identified multiple pathways including inflammasome to be targeted by ZIKV, which was confirmed by analyzing the transcript levels of the proteins of inflammasome pathways, NLRP3, ASC, caspase 1, IL-1 and IL-18. Interestingly, IFNα and the IFN inducible gene, MxA were not enhanced, suggesting prevention of innate antiviral defense by ZIKV. Also, inhibition of inflammasome led to an increased transcriptional activity of IFNα, MxA and CXCL10. Based on these results we suggest that ZIKV transcription is regulated by inflammasomes