Candida albicans Is Resistant to Polyglutamine Aggregation and Toxicity

Acknowledgments We thank the Donnelly Sequencing Centre for sequencing, and Jonathan Krieger at the SikKids Proteomics, Analytics, Robotics & Chemical Biology Centre at The Hospital for Sick Children for mass spectrometry analysis. M.D.L. is supported by a Sir Henry Wellcome Postdoctoral Fellowship (Wellcome Trust grant 096072), T.K. is supported by a Queen Elizabeth II Graduate Scholarship in Science and Technology (University of Toronto), M.L.D. is supported by a Canadian Institutes of Health Research (CIHR) Operating grant 325538, L.E.C. is supported by a Canada Research Chair in Microbial Genomics and Infectious Disease, by CIHR grants MOP-119520 and MOP-86452, and by the Natural Sciences and Engineering Research Council (NSERC) of Canada (grants 06261 and 462167).Peer reviewedPublisher PD

Trajectories of self-rated health in people with diabetes: Associations with functioning in a prospective community sample

© 2013 Schmitz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Self-rated health (SRH) is a single-item measure that is one of the most widely used measures of general health in population health research. Relatively little is known about changes and the trajectories of SRH in people with chronic medical conditions. The aims of the present study were to identify and describe longitudinal trajectories of self-rated health (SRH) status in people with diabetes. Methods: A prospective community study was carried out between 2008 and 2011. SRH was assessed at baseline and yearly at follow-ups (n=1288). Analysis was carried out through trajectory modeling. The trajectory groups were subsequently compared at 4 years follow-up with respect to functioning. Results: Four distinct trajectories of SRH were identified: 1) 72.2% of the participants were assigned to a persistently good SRH trajectory; 2) 10.1% were assigned to a persistently poor SRH trajectory; 3) mean SRH scores changed from good to poor for one group (7.3%); while 4) mean SRH scores changed from poor to medium/good for another group (10.4%). Those with a persistently poor perception of health status were at higher risk for poor functioning at 4 years follow-up than those whose SRH scores decreased from good to poor. Conclusions: SRH is an important predictor for poor functioning in diabetes, but the trajectory of SRH seems to be even more important. Health professionals should pay attention to not only SRH per se, but also changes in SRH over time.This work was supported by Operating Grant MOP-84574 from the Canadian Institutes of Health Research (CIHR). GG was supported by a doctoral fellowship from the CIHR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

IL-33 signaling regulates innate and adaptive immunity to Cryptococcus neoformans.

Susceptibility to progressive infection with the fungus Cryptococcus neoformans is associated with an allergic pattern of lung inflammation, yet the factors that govern this host response are not clearly understood. Using a clinically relevant mouse model of inhalational infection with virulent C. neoformans H99, we demonstrate a role for IL-33-dependent signaling in host immune defense. Infection of BALB/c mice with 10(4) CFU of C. neoformans H99 caused a time-dependent induction of IL-33 with accumulation of type 2 pulmonary innate lymphoid cells and alternatively activated macrophages in the lungs as well as Th2-polarized CD4(+) T cells in draining lymph nodes. IL-33R subunit T1/ST2-deficient (T1/ST2(-/-)) mice infected with C. neoformans H99 had improved survival with a decreased fungal burden in the lungs, spleen, and brain, compared with wild-type mice. Signaling through T1/ST2 was required for the accumulation and early production of IL-5 and IL-13 by lung type 2 pulmonary innate lymphoid cells. Further analysis of T1/ST2(-/-) mice revealed increased fungicidal exudate macrophages in the lungs and decreased C. neoformans-specific Th2 cells in the mediastinal lymph nodes. T1/ST2 deficiency also diminished goblet cell hyperplasia, mucus hypersecretion, bronchoalveolar lavage eosinophilia, alternative activation of macrophages, and serum IgE. These observations demonstrate that IL-33-dependent signaling contributes to the expansion of innate type 2 immunity and subsequent Th2-biased lung immunopathology that facilitates C. neoformans growth and dissemination

“Science powers commerce”: Mapping the language, justifications, and perceptions of the drive to commercialize in the context of Canadian research

The push to commercialize publicly funded, academy-driven scientific research has emerged as a significant science policy challenge. In this article, we investigate whether evidence of this push exists in Canadian scientific research policies through a comprehensive review of legislation, government policy instruments, funding agencies’ program and awards guides and policy statements, political commentary, and university policies. The study maps and discusses the language and justifications used to promote this commercialization push, and examines possible impacts on the Canadian research environment. The article also presents the views of some members of Canadian scientific research community regarding the push or pressure to commercialize their work.Peer reviewe

Cerebral tissue pO2 response to stimulation is preserved with age in awake mice

Published in final edited form as: Neurosci Lett. 2019 April 23; 699: 160–166. doi:10.1016/j.neulet.2019.02.007.Compromised oxygen supply to cerebral tissue could be an important mechanism contributing to age-related cognition decline. We recently showed in awake mice that resting cerebral tissue pO2 decreases with age, a phenomenon that manifests mainly after middle-age. To extend these findings, here we aimed to study how tissue pO2 response to neuronal stimulation is affected by aging. We used two-photon phosphorescence lifetime microscopy to directly measure the brain tissue pO2 response to whisker stimulation in healthy awake young, middle-aged and old mice. We show that despite a decrease in baseline tissue pO2, the amplitude of the tissue pO2 response to stimulation is well preserved with age. However, the response dynamics are altered towards a slower response with reduced post-stimulus undershoot in older ages, possibly due to stiffer vessel wall among other factors. An estimation of the net oxygen consumption rate using a modified Krogh model suggests that the O2 overshoot during stimulation may be necessary to secure a higher capillary O2 delivery to the tissue proportional to increased CMRO2 to maintain the capillary tissue pO2. It was observed that the coupling between the CMRO2 and capillary O2 delivery is preserved with age.Accepted manuscrip

The Evolution[s] of WLU Press: Towards Library–University Press Integration

In March 2015, Wilfrid Laurier University administration announced that WLU Press would be integrating with the Laurier Library. Media coverage of this announcement has been mixed, and is an indication of the ambivalent response to library-press collaborations or integrations, in both the university press and library communities. This article considers the WLU case at its current early stage of development, discussing this transformation not necessarily as “progress” but as one response to a rapidly shifting scholarly environment. By examining the pressure points of the negotiations to merge the press and the library at WLU, this article considers the question of how to maximize opportunities and minimize the potential negative impacts of such integration. In order for such a partnership to be successful, both must be willing to evaluate their business models, their core missions within the scholarly ecosystem and the marketplace, as well as how they measure professionalization and success

A discrete cluster of urinary biomarkers discriminates between active systemic lupus erythematosus patients with and without glomerulonephritis.

BackgroundManagement of lupus nephritis (LN) would be greatly aided by the discovery of biomarkers that accurately reflect changes in disease activity. Here, we used a proteomics approach to identify potential urinary biomarkers associated with LN.MethodsUrine was obtained from 60 LN patients with paired renal biopsies, 25 active non-LN SLE patients, and 24 healthy controls. Using Luminex, 128 analytes were quantified and normalized to urinary creatinine levels. Data were analyzed by linear modeling and non-parametric statistics, with corrections for multiple comparisons. A second cohort of 33 active LN, 16 active non-LN, and 30 remission LN SLE patients was used to validate the results.ResultsForty-four analytes were identified that were significantly increased in active LN as compared to active non-LN. This included a number of unique proteins (e.g., TIMP-1, PAI-1, PF4, vWF, and IL-15) as well as known candidate LN biomarkers (e.g., adiponectin, sVCAM-1, and IL-6), that differed markedly (>4-fold) between active LN and non-LN, all of which were confirmed in the validation cohort and normalized in remission LN patients. These proteins demonstrated an enhanced ability to discriminate between active LN and non-LN patients over several previously reported biomarkers. Ten proteins were found to significantly correlate with the activity score on renal biopsy, eight of which strongly discriminated between active proliferative and non-proliferative/chronic renal lesions.ConclusionsA number of promising urinary biomarkers that correlate with the presence of active renal disease and/or renal biopsy changes were identified and appear to outperform many of the existing proposed biomarkers

Most UK scientists who publish extremely highly-cited papers do not secure funding from major public and charity funders: A descriptive analysis

The UK is one of the largest funders of health research in the world, but little is known about how health funding is spent. Our study explores whether major UK public and charitable health research funders support the research of UK-based scientists producing the most highly-cited research. To address this question, we searched for UK-based authors of peer-reviewed papers that were published between January 2006 and February 2018 and received over 1000 citations in Scopus. We explored whether these authors have held a grant from the National Institute for Health Research (NIHR), the Medical Research Council (MRC) and the Wellcome Trust and compared the results with UK-based researchers who serve currently on the boards of these bodies. From the 1,370 papers relevant to medical, biomedical, life and health sciences with more than 1000 citations in the period examined, we identified 223 individuals from a UK institution at the time of publication who were either first/last or single authors. Of those, 164 are still in UK academic institutions, while 59 are not currently in UK academia (have left the country, are retired, or work in other sectors). Of the 164 individuals, only 59 (36%; 95% CI: 29-43%) currently hold an active grant from one of the three funders. Only 79 (48%; 95% CI: 41-56%) have held an active grant from any of the three funders between 2006-2017. Conversely, 457 of the 664 board members of MRC, Wellcome Trust, and NIHR (69%; 95% CI: 65-72%) have held an active grant in the same period by any of these funders. Only 7 out of 655 board members (1.1%) were first, last or single authors of an extremely highly-cited paper. There are many reasons why the majority of the most influential UK authors do not hold a grant from the country’s major public and charitable funding bodies. Nevertheless, the results are worrisome and subscribe to similar patterns shown in the US. We discuss possible implications and suggest ways forward

Human Rights in Action: Cambodia Country Study

human development, human rights