20 research outputs found
The mortality impact of bicycle paths and lanes related to physical activity, air pollution exposure and road safety
© 2015 Elsevier Ltd. Objective: Guidelines for bicycle infrastructure design tend to consider safety issues but not wider health issues. This paper explores the overall health impact of bicycle infrastructure provision, including not just road safety impacts, but also the population health impacts stemming from physical activity as well as cyclists' exposure to air pollution. Data and methods: We have summarised key publications on how bicycle paths and lanes affect cyclists' exposure to physical activity, air pollution, and road safety. The health impact is modelled using all-cause mortality as a metric for a scenario with new bicycle lanes and paths in a hypothetical city. Results: The outcomes of the study suggest that, based on currently available research, a reduction of all-cause mortality is to be expected from building bicycle lanes and paths along busy roads with mixed traffic. Increased physical activity through more time spent cycling is the major contribution, but is also the most uncertain aspect. Effects related to air pollution and cycling safety are likely to reduce mortality but are small. The overall benefits are large enough to achieve a high benefit-cost ratio for bicycle infrastructure. Conclusions: The introduction of bicycle paths and lanes is likely to be associated with health benefits, primarily due to increased physical activity. More research is needed to estimate the absolute size of the health benefits. In particular, evaluations of the effects of bicycle infrastructure on time spent cycling are limited or of insufficient quality to infer causality. We recommend before-after studies measuring the effects of different interventions and in areas representing a wide range of base levels of cycling participation
Intrinsic transcriptional heterogeneity in B cells controls early class switching to IgE.
Noncoding transcripts originating upstream of the immunoglobulin constant region (I transcripts) are required to direct activation-induced deaminase to initiate class switching in B cells. Differential regulation of Iε and Iγ1 transcription in response to interleukin 4 (IL-4), hence class switching to IgE and IgG1, is not fully understood. In this study, we combine novel mouse reporters and single-cell RNA sequencing to reveal the heterogeneity in IL-4-induced I transcription. We identify an early population of cells expressing Iε but not Iγ1 and demonstrate that early Iε transcription leads to switching to IgE and occurs at lower activation levels than Iγ1. Our results reveal how probabilistic transcription with a lower activation threshold for Iε directs the early choice of IgE versus IgG1, a key physiological response against parasitic infestations and a mediator of allergy and asthma
Synaptic NMDA receptor activity boosts intrinsic antioxidant defenses
Intrinsic antioxidant defenses are important for neuronal longevity. We found that in rat neurons, synaptic activity, acting via NMDA receptor (NMDAR) signaling, boosted antioxidant defenses by making changes to the thioredoxin-peroxiredoxin (Prx) system. Synaptic activity enhanced thioredoxin activity, facilitated the reduction of overoxidized Prxs and promoted resistance to oxidative stress. Resistance was mediated by coordinated transcriptional changes; synaptic NMDAR activity inactivated a previously unknown Forkhead box O target gene, the thioredoxin inhibitor Txnip. Conversely, NMDAR blockade upregulated Txnip in vivo and in vitro, where it bound thioredoxin and promoted vulnerability to oxidative damage. Synaptic activity also upregulated the Prx reactivating genes Sesn2 (sestrin 2) and Srxn1 (sulfiredoxin), via C/EBPβ and AP-1, respectively. Mimicking these expression changes was sufficient to strengthen antioxidant defenses. Trans-synaptic stimulation of synaptic NMDARs was crucial for boosting antioxidant defenses; chronic bath activation of all (synaptic and extrasynaptic) NMDARs induced no antioxidative effects. Thus, synaptic NMDAR activity may influence the progression of pathological processes associated with oxidative damage
THE MINNESOTA RURAL REAL ESTATE MARKET IN 1990... INCLUDING SPECIAL STUDIES OF: ECONOMIC DEVELOPMENT REGIONS, THE GREATER TWIN CITIES METROPOLITAN AREA, THE RED RIVER VALLEY, SOUTHWESTERN MINNESOTA, DAIRY REGION
THE MINNESOTA RURAL REAL ESTATE MARKET IN 1990... INCLUDING SPECIAL STUDIES OF: ECONOMIC DEVELOPMENT REGIONS, THE GREATER TWIN CITIES METROPOLITAN AREA, THE RED RIVER VALLEY, SOUTHWESTERN MINNESOTA, DAIRY REGION
Land Economics/Use,