JC Polyomavirus Uses Extracellular Vesicles To Infect Target Cells

The endemic human JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy in immune-suppressed patients. The mechanisms of virus infection in vivo are not understood because the major target cells for virus in the brain do not express virus receptors and do not bind virus. We found that JCPyV associates with extracellular vesicles (EVs) and can infect target cells independently of virus receptors. Virus particles were found packaged inside extracellular vesicles and attached to the outer side of vesicles. Anti-JCPyV antisera reduced infection by purified virus but had no effect on infection by EV-associated virus. Treatment of cells with the receptor-destroying enzyme neuraminidase inhibited infection with purified virus but did not inhibit infection by EV-associated virus. Mutant pseudoviruses defective in sialic acid receptor binding could not transduce cells as purified pseudovirions but could do so when associated with EVs. This alternative mechanism of infection likely plays a critical role in the dissemination and spread of JCPyV both to and within the central nervous system

The EBV-Encoded Oncoprotein, LMP1, Recruits and Transforms Fibroblasts via an ERK-MAPK-Dependent Mechanism

open access articleLatent membrane protein 1 (LMP1), the major oncoprotein encoded by Epstein–Barr virus (EBV), is expressed at widely variable levels in undifferentiated nasopharyngeal carcinoma (NPC) biopsies, fueling intense debate in the field as to the importance of this oncogenic protein in disease pathogenesis. LMP1-positive NPCs are reportedly more aggressive, and in a similar vein, the presence of cancer-associated fibroblasts (CAFs) surrounding “nests” of tumour cells in NPC serve as indicators of poor prognosis. However, there is currently no evidence linking LMP1 expression and the presence of CAFs in NPC. In this study, we demonstrate the ability of LMP1 to recruit fibroblasts in vitro in an ERK-MAPK-dependent mechanism, along with enhanced viability, invasiveness and transformation to a myofibroblast-like phenotype. Taken together, these findings support a putative role for LMP1 in recruiting CAFs to the tumour microenvironment in NPC, ultimately contributing to metastatic disease

An unmanned aerial vehicle sampling platform for atmospheric water vapor isotopes in polar environments

Above polar ice sheets, atmospheric water vapor exchange occurs across the planetary boundary layer (PBL) and is an important mechanism in a number of processes that affect the surface mass balance of the ice sheets. Yet, this exchange is not well understood and has substantial implications for modeling and remote sensing of the polar hydrologic cycle. Efforts to characterize the exchange face substantial logistical challenges including the remoteness of ice sheet field camps, extreme weather conditions, low humidity and temperature that limit the effectiveness of instruments, and dangers associated with flying manned aircraft at low altitudes. Here, we present an unmanned aerial vehicle (UAV) sampling platform for operation in extreme polar environments that is capable of sampling atmospheric water vapor for subsequent measurement of water isotopes. This system was deployed to the East Greenland Ice-core Project (EastGRIP) camp in northeast Greenland during summer 2019. Four sampling flight missions were completed. With a suite of atmospheric measurements aboard the UAV (temperature, humidity, pressure, GPS) we determine the height of the PBL using online algorithms, allowing for strategic decision-making by the pilot to sample water isotopes above and below the PBL. Water isotope data were measured by a Picarro L2130-i instrument using flasks of atmospheric air collected within the nose cone of the UAV. The internal repeatability for δD and δ18O was 2.8 ‰ and 0.45 ‰, respectively, which we also compared to independent EastGRIP tower-isotope data. Based on these results, we demonstrate the efficacy of this new UAV-isotope platform and present improvements to be utilized in future polar field campaigns. The system is also designed to be readily adaptable to other fields of study, such as measurement of carbon cycle gases or remote sensing of ground conditions.publishedVersio

Rise and Recharge: Exploring Employee Perceptions of and Contextual Factors Influencing an Individual-Level E-Health Smartphone Intervention to Reduce Office Workers' Sedentary Time at Work.

This feasibility study explored the contextual factors influencing office workers' adherence to an e-health intervention targeting total and prolonged sedentary time over 12 weeks. A three-arm quasi-randomized intervention included prompts at 30 or 60 min intervals delivered via a smartphone application, and a no-prompt comparison arm. Fifty-six office workers completed baseline (64% female) and 44 completed the 12 week follow-up (80% retention). Ecological momentary assessments (EMA) captured contextual data, with 82.8 ± 24.9 EMA prompt questionnaires completed weekly. Two focus groups with n = 8 Prompt 30 and 60 participants were conducted one-month post-intervention to address intervention acceptability and feasibility. Contextual findings indicate that when working on a sedentary task (i.e., reading or screen-based work) and located at an individual workstation, hourly prompts may be more acceptable and feasible for promoting a reduction in total and prolonged sedentary time compared to 30 min prompts. Interpersonal support also appears important for promoting subtle shifts in sedentary working practices. This novel study gives a real-time insight into the factors influencing adherence to e-health prompts. Findings identified unique, pragmatic considerations for delivering a workplace e-health intervention, indicating that further research is warranted to optimize the method of intervention delivery prior to evaluation of a large-scale intervention

Rise and Recharge: Effects on Activity Outcomes of an e-Health Smartphone Intervention to Reduce Office Workers' Sitting Time.

This feasibility study evaluated the effects of an individual-level intervention to target office workers total and prolonged sedentary behaviour during working hours, using an e-health smartphone application. A three-arm (Prompt-30 or 60 min Intervention arm and a No-Prompt Comparison arm), quasi-randomised intervention was conducted over 12 weeks. Behavioural outcomes (worktime sitting, standing, stepping, prolonged sitting, and physical activity) were monitored using accelerometers and anthropometrics measured at baseline, 6 weeks and 12 weeks. Cardiometabolic measures were taken at baseline and 12 weeks. Fifty-six office workers (64% female) completed baseline assessments. The Prompt-60 arm was associated with a reduction in occupational sitting time at 6 (-46.8 min/8 h workday [95% confidence interval = -86.4, -6.6], p 0.05). Both Intervention arms reduced time in prolonged sitting bouts at 12 weeks (Prompt-30: -27.0 [-99.0, 45.0]; Prompt-60: -25.8 [-98.4, 47.4] min/8 h workday; both p > 0.05). There were no changes in steps or cardiometabolic risk. Findings highlight the potential of a smartphone e-health application, suggesting 60 min prompts may present an optimal frequency to reduce total occupational sedentary behaviour

Obese endometrial cancer survivors\u27 perceptions of weight loss strategies and characteristics that may influence participation in behavioral interventions

We aimed to evaluate obese endometrial cancer (EC) survivors\u27 perceptions of weight loss barriers and previously attempted weight loss methods and to identify characteristics that predicted willingness to enroll in a behavioral intervention trial. We administered a 27-question baseline survey at an academic institution to EC survivors with body mass index ≥ 30 kg/

Anti-müllerian hormone is not associated with cardiometabolic risk factors in adolescent females

<p>Objectives: Epidemiological evidence for associations of Anti-Müllerian hormone (AMH) with cardiometabolic risk factors is lacking. Existing evidence comes from small studies in select adult populations, and findings are conflicting. We aimed to assess whether AMH is associated with cardiometabolic risk factors in a general population of adolescent females.</p> <p>Methods: AMH, fasting insulin, glucose, HDLc, LDLc, triglycerides and C-reactive protein (CRP) were measured at a mean age 15.5 years in 1,308 female participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Multivariable linear regression was used to examine associations of AMH with these cardiometabolic outcomes.</p> <p>Results: AMH values ranged from 0.16–35.84 ng/ml and median AMH was 3.57 ng/ml (IQR: 2.41, 5.49). For females classified as post-pubertal (n = 848) at the time of assessment median (IQR) AMH was 3.81 ng/ml (2.55, 5.82) compared with 3.25 ng/ml (2.23, 5.05) in those classed as early pubertal (n = 460, P≤0.001). After adjusting for birth weight, gestational age, pubertal stage, age, ethnicity, socioeconomic position, adiposity and use of hormonal contraceptives, there were no associations with any of the cardiometabolic outcomes. For example fasting insulin changed by 0% per doubling of AMH (95%CI: −3%,+2%) p = 0.70, with identical results if HOMA-IR was used. Results were similar after additional adjustment for smoking, physical activity and age at menarche, after exclusion of 3% of females with the highest AMH values, after excluding those that had not started menarche and after excluding those using hormonal contraceptives.</p> <p>Conclusion: Our results suggest that in healthy adolescent females, AMH is not associated with cardiometabolic risk factors.</p&gt

An unmanned aerial vehicle sampling platform for atmospheric water vapor isotopes in polar environments

Above polar ice sheets, atmospheric water vapor exchange occurs across the planetary boundary layer (PBL) and is an important mechanism in a number of processes that affect the surface mass balance of the ice sheets. Yet, this exchange is not well understood and has substantial implications for modeling and remote sensing of the polar hydrologic cycle. Efforts to characterize the exchange face substantial logistical challenges including the remoteness of ice sheet field camps, extreme weather conditions, low humidity and temperature that limit the effectiveness of instruments, and dangers associated with flying manned aircraft at low altitudes. Here, we present an unmanned aerial vehicle (UAV) sampling platform for operation in extreme polar environments that is capable of sampling atmospheric water vapor for subsequent measurement of water isotopes. This system was deployed to the East Greenland Ice-core Project (East-GRIP) camp in northeast Greenland during summer 2019. Four sampling flight missions were completed. With a suite of atmospheric measurements aboard the UAV (temperature, humidity, pressure, GPS) we determine the height of the PBL using online algorithms, allowing for strategic decision making by the pilot to sample water isotopes above and below the PBL. Water isotope data were measured by a Picarro L2130-i instrument using flasks of atmospheric air collected within the nose cone of the UAV. The internal repeatability for �D and �18O was 2.8&permil; and 0.45 &permil;, respectively, which we also compared to independent EastGRIP tower-isotope data. Based on these results, we demonstrate the efficacy of this new UAV-isotope platform and present improvements to be utilized in future polar field campaigns. The system is also designed to be readily adaptable to other fields of study, such as measurement of carbon cycle gases or remote sensing of ground conditions.</p