98 research outputs found
Mode shifting in school travel mode: examining the prevalence and correlates of active school transport in Ontario, Canada
<p>Abstract</p> <p>Background</p> <p>Studies examining the correlates of school transport commonly fail to make the distinction between morning and afternoon school trips. The purpose of this study was to examine the prevalence and correlates of mode shift from passive in the morning to active in the afternoon among elementary and secondary school students in Ontario, Canada.</p> <p>Methods</p> <p>Data were derived from the 2009 cycle of the Ontario Student Drug Use and Health Survey (OSDUHS). 3,633 students in grades 7 through 12 completed self-administered questionnaires. Socio-demographic, behavioural, psychological, and environmental predictors of active school transport (AST) were assessed using logistic regression.</p> <p>Results</p> <p>Overall, 47% and 38% of elementary school students reported AST to and from school, respectively. The corresponding figures were 23% and 32% for secondary school students. The prevalence of AST varied temporarily and spatially. There was a higher prevalence of walking/biking found for elementary school students than for secondary school students, and there was an approximate 10% increase in AST in the afternoon. Different correlates of active school transport were also found across elementary and secondary school students. For all ages, students living in urban areas, with a shorter travel time between home and school, and having some input to the decision making process, were more likely to walk to and from school.</p> <p>Conclusions</p> <p>Future research examining AST should continue to make the analytic distinction between the morning and afternoon trip, and control for the moderating effect of age and geography in predicting mode choice. In terms of practice, these variations highlight the need for school-specific travel plans rather than 'one size fits all' interventions in promoting active school transport.</p
Thrive: Success Strategies for the Modern-Day Faculty Member
The THRIVE collection is intended to help faculty thrive in their roles as educators, scholars, researchers, and clinicians. Each section contains a variety of thought-provoking topics that are designed to be easily digested, guide personal reflection, and put into action. Please use the THRIVE collection to help: Individuals study topics on their own, whenever and wherever they want Peer-mentoring or other learning communities study topics in small groups Leaders and planners strategically insert faculty development into existing meetings
Faculty identify campus experts for additional learning, grand rounds, etc. If you have questions or want additional information on a topic, simply contact the article author or email [email protected]://digitalcommons.unmc.edu/facdev_books/1000/thumbnail.jp
Expression of hereditary hemochromatosis C282Y HFE protein in HEK293 cells activates specific endoplasmic reticulum stress responses
<p>Abstract</p> <p>Background</p> <p>Hereditary Hemochromatosis (HH) is a genetic disease associated with iron overload, in which individuals homozygous for the mutant C282Y <it>HFE </it>associated allele are at risk for the development of a range of disorders particularly liver disease. Conformational diseases are a class of disorders associated with the expression of misfolded protein. HFE C282Y is a mutant protein that does not fold correctly and consequently is retained in the Endoplasmic Reticulum (ER). In this context, we sought to identify ER stress signals associated with mutant C282Y HFE protein expression, which may have a role in the molecular pathogenesis of HH.</p> <p>Results</p> <p>Vector constructs of Wild type HFE and Mutant C282Y HFE were made and transfected into HEK293 cell lines. We have shown that expression of C282Y HFE protein triggers both an unfolded protein response (UPR), as revealed by the increased GRP78, ATF6 and CHOP expression, and an ER overload response (EOR), as indicated by NF-κB activation. Furthermore, C282Y HFE protein induced apoptotic responses associated with activation of ER stress. Inhibition studies demonstrated that tauroursodeoxycholic acid, an endogenous bile acid, downregulates these events. Finally, we found that the co-existence of both C282Y HFE and Z alpha 1-antitrypsin protein (the protein associated with the liver disease of Z alpha 1-antitrypsin deficiency) expression on ER stress responses acted as potential disease modifiers with respect to each other.</p> <p>Conclusion</p> <p>Our novel observations suggest that both the ER overload response (EOR) and the unfolded protein response (UPR) are activated by mutant C282Y HFE protein.</p
Trends and variability in weather and atmospheric deposition at UK Environmental Change Network sites (1993–2012)
We characterised temporal trends and variability in key indicators of climate and atmospheric deposition chemistry at the twelve terrestrial UK Environmental Change Network (ECN) sites over the first two decades of ECN monitoring (1993–2012) using various statistical approaches. Mean air temperatures for the monitoring period were approximately 0.7 °C higher than those modelled for 1961–1990, but there was little evidence for significant change in air temperature over either the full monthly records or within individual seasons. Some upland ECN sites, however, warmed significantly over the first decade before cooling in the second. Summers at most sites became progressively wetter, and extremes in daily rainfall increased in magnitude. Average wind speeds in winter and spring declined at the majority of sites. Directional trends in summer precipitation could be linked to an atypically prolonged negative deviation in the summer North Atlantic Oscillation (NAO) Index. Several aspects of air quality improved markedly. Concentrations and fluxes of sulphate in precipitation declined significantly and substantially across the network, particularly during the earlier years and at the most polluted sites in the south and east. Precipitation concentrations of nitrate and ammonium, and atmospheric concentrations of nitrogen dioxide also decreased at most sites. There was less evidence for reductions in the loads of wet deposited nitrogen species, while trends in atmospheric ammonia concentration varied in direction and strength between sites. Reductions in acid deposition are likely to account for widespread gradual increases in the pH of soil water at ECN sites, representing partial recovery from acidification. Overall, therefore, ECN sites have experienced marked changes in atmospheric chemistry and weather regimes over the last two decades that might be expected to have exerted detectable effects on ecosystem structure and function. While the downward trend in acid deposition is unlikely to be reversed, it is too early to conclude whether the trend towards wetter summers simply represents a phase in a multi-decadal cycle, or is indicative of a more directional shift in climate. Conversely, the first two decades of ECN now provide a relatively stable long-term baseline with respect to air temperature, against which effects of anticipated future warming on these ecosystems should be able to be assessed robustly
Co-chaperones are limiting in a depleted chaperone network
To probe the limiting nodes in the chaperoning network which maintains cellular proteostasis, we expressed a dominant negative mutant of heat shock factor 1 (dnHSF1), the regulator of the cytoplasmic proteotoxic stress response. Microarray analysis of non-stressed dnHSF1 cells showed a two- or more fold decrease in the transcript level of 10 genes, amongst which are the (co-)chaperone genes HSP90AA1, HSPA6, DNAJB1 and HSPB1. Glucocorticoid signaling, which requires the Hsp70 and the Hsp90 folding machines, was severely impaired by dnHSF1, but fully rescued by expression of DNAJA1 or DNAJB1, and partially by ST13. Expression of DNAJB6, DNAJB8, HSPA1A, HSPB1, HSPB8, or STIP1 had no effect while HSP90AA1 even inhibited. PTGES3 (p23) inhibited only in control cells. Our results suggest that the DNAJ co-chaperones in particular become limiting in a depleted chaperoning network. Our results also suggest a difference between the transcriptomes of cells lacking HSF1 and cells expressing dnHSF1
Unfolded protein response in cancer: the Physician's perspective
The unfolded protein response (UPR) is a cascade of intracellular stress signaling events in response to an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum (ER). Cancer cells are often exposed to hypoxia, nutrient starvation, oxidative stress and other metabolic dysregulation that cause ER stress and activation of the UPR. Depending on the duration and degree of ER stress, the UPR can provide either survival signals by activating adaptive and antiapoptotic pathways, or death signals by inducing cell death programs. Sustained induction or repression of UPR pharmacologically may thus have beneficial and therapeutic effects against cancer. In this review, we discuss the basic mechanisms of UPR and highlight the importance of UPR in cancer biology. We also update the UPR-targeted cancer therapeutics currently in clinical trials
Post break-up tectonic inversion across the southwestern cape of South Africa: new insights from apatite and zircon fission track thermochronometry
The south-west African margin is regarded as an example of a passive continental margin formed by continental rifting following a phase of lithospheric extension and thinning. Recent attention focused on this margin has included theoretical modelling studies of rift processes, plate kinematic studies of the opening geometry and timing, and empirical studies focused on documenting the crustal structure and offshore sedimentary record. Here, we examine the onshore geomorphic and tectonic response to rifting and breakup, with a specific focus on the SW Cape of South Africa. We present 75 new apatite and 8 new zircon fission track analyses from outcrop samples and onshore borehole profiles along the western margin of South Africa. The data are used to derive robust thermal histories that record two discrete phases of accelerated erosional cooling during the Early Cretaceous (150-130 Ma) and Late Cretaceous (100-80 Ma), respectively. Both periods of enhanced erosion are regional in extent, involved km-scale erosion, and extend well inland of the current escarpment zone, albeit with spatially variable intensity and style. The Late Cretaceous episode is also expressed more locally by tectonic reactivation and inversion of major faults causing km-scale differential displacement and erosion. The new AFT data do not exclude the possibility of modest surface uplift occurring during the Cenozoic, but they restrict the depth of regional Cenozoic erosion on the western margin to less than c. 1 km. The inferred pattern and chronology of erosion onshore is consistent with the key features and sediment accumulation patterns within the offshore Orange and Bredasdorp basins. It is suggested that the Late Cretaceous event was triggered by a combination of regional dynamic uplift augmented along the western margin and in the SW Cape by local tectonic forces arising from dextral displacement of the Falkland Plateau along the Falkland-Agulhas Fracture Zone
Apophis planetary defense campaign
We describe results of a planetary defense exercise conducted during the close approach to Earth by the near-Earth asteroid (99942) Apophis during 2020 December–2021 March. The planetary defense community has been conducting observational campaigns since 2017 to test the operational readiness of the global planetary defense capabilities. These community-led global exercises were carried out with the support of NASA's Planetary Defense Coordination Office and the International Asteroid Warning Network. The Apophis campaign is the third in our series of planetary defense exercises. The goal of this campaign was to recover, track, and characterize Apophis as a potential impactor to exercise the planetary defense system including observations, hypothetical risk assessment and risk prediction, and hazard communication. Based on the campaign results, we present lessons learned about our ability to observe and model a potential impactor. Data products derived from astrometric observations were available for inclusion in our risk assessment model almost immediately, allowing real-time updates to the impact probability calculation and possible impact locations. An early NEOWISE diameter measurement provided a significant improvement in the uncertainty on the range of hypothetical impact outcomes. The availability of different characterization methods such as photometry, spectroscopy, and radar provided robustness to our ability to assess the potential impact risk
Social Capital and Regional Social Infrastructure Investment: Evidence from New Zealand
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