67 research outputs found
Steroid Hormone Synthesis by Vaccinia Virus Suppresses the Inflammatory Response to Infection
The 3β-hydroxysteroid dehydrogenase (3β-HSD) isoenzymes play a key role in cellular steroid hormone synthesis. Vaccinia virus (VV) also synthesizes steroid hormones with a 3β-HSD enzyme (v3β-HSD) encoded by gene A44L. Here we examined the effects of v3β-HSD in VV disease using wild-type (vA44L), deletion (vΔA44L), and revertant (vA44L-rev) viruses in a murine intranasal model. Loss of A44L was associated with an attenuated phenotype. Early (days 1–3) after infection with vΔA44L or control viruses the only difference observed between groups was the reduced corticosterone level in lungs and plasma of vΔA44L-infected animals. Other parameters examined (body weight, signs of illness, temperature, virus titres, the pulmonary inflammatory infiltrate, and interferon [IFN]-γ levels) were indistinguishable between groups. Subsequently, vΔA44L-infected animals had reduced weight loss and signs of illness, and displayed a vigorous pulmonary inflammatory response. This was characterized by rapid recruitment of CD4+ and CD8+ lymphocytes, enhanced IFN-γ production and augmented cytotoxic T lymphocyte activity. These data suggest that steroid production by v3β-HSD contributes to virus virulence by inhibiting an effective inflammatory response to infection
Phylogeny and classification of novel diversity in Sainouroidea (Cercozoa, Rhizaria) sheds light on a highly diverse and divergent clade
Sainouroidea is a molecularly diverse clade of cercozoan flagellates and amoebae in the eukaryotic supergroup Rhizaria. Previous 18S rDNA environmental sequencing of globally collected fecal and soil samples revealed great diversity and high sequence divergence in the Sainouroidea. However, a very limited amount of this diversity has been observed or described. The two described genera of amoebae in this clade are Guttulinopsis, which displays aggregative multicellularity, and Rosculus, which does not. Although the identity of Guttulinopsis is straightforward due to the multicellular fruiting bodies they form, the same is not true for Rosculus, and the actual identity of the original isolate is unclear. Here we isolated amoebae with morphologies like that of Guttulinopsis and Rosculus from many environments and analyzed them using 18S rDNA sequencing, light microscopy, and transmission electron microscopy. We define a molecular species concept for Sainouroidea that resulted in the description of 4 novel genera and 12 novel species of naked amoebae. Aggregative fruiting is restricted to the genus Guttulinopsis, but other than this there is little morphological variation amongst these taxa. Taken together, simple identification of these amoebae is problematic and potentially unresolvable without the 18S rDNA sequence
Angiogenic and Inflammatory Markers of Cardiopulmonary Changes in Children and Adolescents with Sickle Cell Disease
Background: Pulmonary hypertension and left ventricular diastolic dysfunction are complications of sickle cell disease. Pulmonary hypertension is associated with hemolysis and hypoxia, but other unidentified factors are likely involved in pathogenesis as well. Design and Methods: Plasma concentrations of three angiogenic markers (fibroblast growth factor, platelet derived growth factor-BB [PDGF-BB], vascular endothelial growth factor [VEGF]) and seven inflammatory markers implicated in pulmonary hypertension in other settings were determined by Bio-Plex suspension array in 237 children and adolescents with sickle cell disease at steady state and 43 controls. Tricuspid regurgitation velocity (which reflects systolic pulmonary artery pressure), mitral valve E/Edti ratio (which reflects left ventricular diastolic dysfunction), and a hemolytic component derived from four markers of hemolysis and hemoglobin oxygen saturation were also determined. Results: Plasma concentrations of interleukin-8, interleukin-10 and VEGF were elevated in the patients with sickle cell disease compared to controls (P≤0.003). By logistic regression, greater values for PDGF-BB (P = 0.009), interleukin-6 (P = 0.019) and the hemolytic component (P = 0.026) were independently associated with increased odds of elevated tricuspid regurgitation velocity while higher VEGF concentrations were associated with decreased odds (P = 0.005) among the patients with sickle cell disease. These findings, which are consistent with reports that PDGF-BB stimulates and VEGF inhibits vascular smooth muscle cell proliferation, did not apply to E/Etdi. Conclusions: Circulating concentrations of angiogenic and pro-Inflammatory markers are altered in sickle cell disease children and adolescents with elevated tricuspid regurgitation velocity, a subgroup that may be at risk for developing worsening pulmonary hypertension. Further studies to understand the molecular changes in these children are indicated
Rabies-Specific Antibodies: Measuring Surrogates of Protection against a Fatal Disease
Antibodies play a central role in prophylaxis against many infectious agents. While neutralization is a primary function of antibodies, the Fc- and complement-dependent activities of these multifunctional proteins may also be critical in their ability to provide protection against most viruses. Protection against viral pathogens in vivo is complex, and while virus neutralization—the ability of antibody to inactivate virus infectivity, often measured in vitro—is important, it is often only a partial contributor in protection. The rapid fluorescent focus inhibition test (RFFIT) remains the “gold standard” assay to measure rabies virus–neutralizing antibodies. In addition to neutralization, the rabies-specific antigen-binding activity of antibodies may be measured through enzyme-linked immunosorbent assays (ELISAs), as well as other available methods. For any disease, in selecting the appropriate assay(s) to use to assess antibody titers, assay validation and how they are interpreted are important considerations—but for a fatal disease like rabies, they are of paramount importance. The innate limitations of a one-dimensional laboratory test for rabies antibody measurement, as well as the validation of the method of choice, must be carefully considered in the selection of an assay method and for the interpretation of results that might be construed as a surrogate of protection
The Relationship between Traffic-Related Air Pollution Exposures and Allostatic Load Score among Youth with Type 1 Diabetes in the SEARCH Cohort
OBJECTIVE: We investigated the effects of chronic exposures to particulate and traffic-related air pollution on allostatic load (AL) score, a marker of cumulative biological risk, among youth with type 1 diabetes. RESEARCH DESIGN AND METHODS: Participants were drawn from five clinical sites of the SEARCH for Diabetes in Youth (SEARCH) study (n=2,338). Baseline questionnaires, anthropometric measures, and a fasting blood test were taken at a clinic visit between 2001 and 2005. AL was operationalized using 10 biomarkers reflecting cardiovascular, metabolic, and inflammatory risk. Annual residential exposures to PM(2.5) and proximity to heavily-trafficked major roadways were estimated for each participant. Poisson regression models adjusted for sociodemographic and lifestyle factors were conducted for each exposure. RESULTS: No significant associations were observed between exposures to PM(2.5) or proximity to traffic and AL score, however analyses were suggestive of effect modification by race for residential distance to heavily-trafficked major roadways (p=0.02). In stratified analyses, residing <100, 100-<200 and 200-<400 m compared to 400 m or more from heavily-trafficked major roadways was associated with 11%, 26% and 14% increases in AL score, respectively (95% CIs: −4, 29; 9, 45.0; −1, 30) for non-white participants compared to 6%, −2%, and −2% changes (95% CIs: −2, 15; −10, 7; −8, 6) for white participants. CONCLUSIONS: Among this population of youth with type 1 diabetes, we did not observe consistent relationships between chronic exposures to particulate and traffic-related air pollution and changes in AL score, however associations for traffic-related pollution exposures may differ by race/ethnicity and warrant further examination
Carnivore Translocations and Conservation: Insights from Population Models and Field Data for Fishers (Martes pennanti)
Translocations are frequently used to restore extirpated carnivore populations. Understanding the factors that influence translocation success is important because carnivore translocations can be time consuming, expensive, and controversial. Using population viability software, we modeled reintroductions of the fisher, a candidate for endangered or threatened status in the Pacific states of the US. Our model predicts that the most important factor influencing successful re-establishment of a fisher population is the number of adult females reintroduced (provided some males are also released). Data from 38 translocations of fishers in North America, including 30 reintroductions, 5 augmentations and 3 introductions, show that the number of females released was, indeed, a good predictor of success but that the number of males released, geographic region and proximity of the source population to the release site were also important predictors. The contradiction between model and data regarding males may relate to the assumption in the model that all males are equally good breeders. We hypothesize that many males may need to be released to insure a sufficient number of good breeders are included, probably large males. Seventy-seven percent of reintroductions with known outcomes (success or failure) succeeded; all 5 augmentations succeeded; but none of the 3 introductions succeeded. Reintroductions were instrumental in reestablishing fisher populations within their historical range and expanding the range from its most-contracted state (43% of the historical range) to its current state (68% of the historical range). To increase the likelihood of translocation success, we recommend that managers: 1) release as many fishers as possible, 2) release more females than males (55–60% females) when possible, 3) release as many adults as possible, especially large males, 4) release fishers from a nearby source population, 5) conduct a formal feasibility assessment, and 6) develop a comprehensive implementation plan that includes an active monitoring program
Weaving Promising Practices to Transform Indigenous Population Health and Wellness Reporting by Indigenizing Indicators in First Nations Health
In Canada and across the globe, indicators play a fundamental role in measuring, tracking, and reporting on the overall health of the population. Mainstream population health indicators used to measure the health and well-being of First Nations peoples are constrained by the Western biomedical paradigm which focuses solely on illness and disease. These indicators are limited and fail to capture aspects of cultural, spiritual, and interconnected aspects of Indigenous health such as spirit, ceremony, and the connection to land. To advance First Nations self-determination in the healthcare system, it is essential for Indigenous narratives and knowledges to thrive in population health data and reporting. Five promising practices are shared to guide the development of First Nations health and wellness indicators and reporting: (1) be culturally relevant and centred on First Nations worldviews on health and wellness (2) must honour Indigenous knowledges and methods; (3) must involve respectful relationships & meaningful engagement with Indigenous peoples’; (4) “Nothing about us, without us”- Indigenous leadership and self-determination at all stages of indicator development; and (5) taking a strength-based approach & contextualizing indicators within historical, socio-political contexts. The co-development of indicators between the [First Nations Health Organization] and the [Office of the Executive Health Officer] in the Province of [Name of Canadian Province] are discussed as promising practices in action. Celebrating the strength and resilience of First Nations health which is required to pave a new way forward in Indigenous grounded population health
Shifting nitrous oxide source/sink behaviour in a subtropical estuary revealed by automated time series observations
The oceans are a major source of the potent greenhouse gas nitrous oxide (N2O) to the atmosphere. However, little information is available on how estuaries and the coastal ocean may contribute to N2O budgets, and on the drivers of N2O in aquatic environments. This study utilised five time series stations along the freshwater to marine continuum in a sub-tropical estuary in Australia (Coffs Creek, Australia). Each time series station captured N2O, radon (222Rn, a natural submarine groundwater discharge tracer), dissolved nitrogen, and dissolved organic carbon (DOC) concentrations for a minimum of 25 h. The use of automated time series observations enabled spatial and tidal-scale variability of N2O to be captured. Groundwater was highly enriched in N2O (up to 306 nM) compared to the receiving surface water. Dissolved N2O supersaturation as high as 386% (27.4 nM) was observed in the upstream freshwater and brackish water areas which represented only a small (∼13%) proportion of the total estuary area. A large area of N2O undersaturation (as low as 53% or 3.9 nM) was observed in the mangrove-dominated lower estuary. This undersaturated area likely resulted from N2O consumption due to nitrate/nitrite (NOx) limitation in mangrove sediments subject to shallow porewater exchange. Overall, the estuary was a minor source of N2O to the atmosphere as the lower mangrove-dominated estuary sink of N2O counteracted groundwater-dominated source of N2O in the upper estuary. Average area-weighted N2O fluxes at the water-air interface approached zero (0.2–0.7 μmol m−2 d−1, depending on piston velocity model used), and were much lower than nitrogen-rich Northern Hemisphere estuaries that are considered large sources of N2O to the atmosphere. This study revealed a temporally and spatially diverse estuary, with areas of N2O production and consumption related to oxygen and total dissolved nitrogen availability, submarine groundwater discharge, and uptake within mangroves
Supporting Indigenous Graduate Student Health Research Capacity: Mentorship through a Provincial Health Research Network Environment in British Columbia
The British Columbia Network Environment for Indigenous Health Research (BC NEIHR), funded by the Canadian Institute of Health Research, is an Indigenous-led network that supports the research development and knowledge sharing of Indigenous communities, collectives and organizations and Indigenous graduate students in BC. To understand how we impacted the health research journey of Indigenous graduate students, we conducted a critical analysis of our annual evaluation reports and offer a reflective narrative of our operations. In this article, we share our Indigenous mentorship model and describe how we supported and enhanced Indigenous-led research among Indigenous graduate students in BC by: addressing common challenges related to financial costs of pursuing health research; prioritizing cultural and land-based learning opportunities; providing exceptional academic and professional development opportunities; and promoting Indigenous cultural safety, equity, and self-determination by creating systems-level change through partnerships. We conclude that as we work toward systems change, the BC NEIHR offers a promising approach towards enhancing Indigenous health research capacity through mentorship. 
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