Cross-sectional associations between air pollution and chronic bronchitis: an ESCAPE meta-analysis across five cohorts

BACKGROUND: This study aimed to assess associations of outdoor air pollution on prevalence of chronic bronchitis symptoms in adults in five cohort studies (Asthma-E3N, ECRHS, NSHD, SALIA, SAPALDIA) participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE) project. METHODS: Annual average particulate matter (PM10, PM2.5, PMabsorbance, PMcoarse), NO2, nitrogen oxides (NOx) and road traffic measures modelled from ESCAPE measurement campaigns 2008-2011 were assigned to home address at most recent assessments (1998-2011). Symptoms examined were chronic bronchitis (cough and phlegm for ≥3 months of the year for ≥2 years), chronic cough (with/without phlegm) and chronic phlegm (with/without cough). Cohort-specific cross-sectional multivariable logistic regression analyses were conducted using common confounder sets (age, sex, smoking, interview season, education), followed by meta-analysis. RESULTS: 15 279 and 10 537 participants respectively were included in the main NO2 and PM analyses at assessments in 1998-2011. Overall, there were no statistically significant associations with any air pollutant or traffic exposure. Sensitivity analyses including in asthmatics only, females only or using back-extrapolated NO2 and PM10 for assessments in 1985-2002 (ECRHS, NSHD, SALIA, SAPALDIA) did not alter conclusions. In never-smokers, all associations were positive, but reached statistical significance only for chronic phlegm with PMcoarse OR 1.31 (1.05 to 1.64) per 5 µg/m(3) increase and PM10 with similar effect size. Sensitivity analyses of older cohorts showed increased risk of chronic cough with PM2.5abs (black carbon) exposures. CONCLUSIONS: Results do not show consistent associations between chronic bronchitis symptoms and current traffic-related air pollution in adult European populations

Simulation of population-based commuter exposure to NO2 using different air pollution models

We simulated commuter routes and long-term exposure to traffic-related air pollution during commute in a representative population sample in Basel (Switzerland), and evaluated three air pollution models with different spatial resolution for estimating commute exposures to nitrogen dioxide (NO2) as a marker of long-term exposure to traffic-related air pollution. Our approach includes spatially and temporally resolved data on actual commuter routes, travel modes and three air pollution models. Annual mean NO2 commuter exposures were similar between models. However, we found more within-city and within-subject variability in annual mean (±SD) NO2 commuter exposure with a high resolution dispersion model (40 ± 7 µg m−3, range: 21–61) than with a dispersion model with a lower resolution (39 ± 5 µg m−3; range: 24–51), and a land use regression model (41 ± 5 µg m−3; range: 24–54). Highest median cumulative exposures were calculated along motorized transport and bicycle routes, and the lowest for walking. For estimating commuter exposure within a city and being interested also in small-scale variability between roads, a model with a high resolution is recommended. For larger scale epidemiological health assessment studies, models with a coarser spatial resolution are likely sufficient, especially when study areas include suburban and rural areas

A Comparison of Scent Marking between a Monogamous and Promiscuous Species of Peromyscus: Pair Bonded Males Do Not Advertise to Novel Females

Scent marking can provide behavioral and physiological information including territory ownership and mate advertisement. It is unknown how mating status and pair cohabitation influence marking by males from different social systems. We compared the highly territorial and monogamous California mouse (Peromyscus californicus) to the less territorial and promiscuous white-footed mouse (P. leucopus). Single and mated males of both species were assigned to one of the following arenas lined with filter paper: control (unscented arena), male scented (previously scent-marked by a male conspecific), or females present (containing females in small cages). As expected, the territorial P. californicus scent marked and overmarked an unfamiliar male conspecific's scent marks more frequently than P. leucopus. Species differences in responses to novel females were also found based on mating status. The presence of unfamiliar females failed to induce changes in scent marking in pair bonded P. californicus even though virgin males increased marking behavior. Pair bonding appears to reduce male advertisement for novel females. This is in contrast to P. leucopus males that continue to advertise regardless of mating status. Our data suggest that communication through scent-marking can diverge significantly between species based on mating system and that there are physiological mechanisms that can inhibit responsiveness of males to female cues

Analysis of the capacity of google trends to measure interest in conservation topics and the role of online news

With the continuous growth of internet usage, Google Trends has emerged as a source of information to investigate how social trends evolve over time. Knowing how the level of interest in conservation topics--approximated using Google search volume--varies over time can help support targeted conservation science communication. However, the evolution of search volume over time and the mechanisms that drive peaks in searches are poorly understood. We conducted time series analyses on Google search data from 2004 to 2013 to investigate: (i) whether interests in selected conservation topics have declined and (ii) the effect of news reporting and academic publishing on search volume. Although trends were sensitive to the term used as benchmark, we did not find that public interest towards conservation topics such as climate change, ecosystem services, deforestation, orangutan, invasive species and habitat loss was declining. We found, however, a robust downward trend for endangered species and an upward trend for ecosystem services. The quantity of news articles was related to patterns in Google search volume, whereas the number of research articles was not a good predictor but lagged behind Google search volume, indicating the role of news in the transfer of conservation science to the public

Disruption of TLR3 Signaling Due to Cleavage of TRIF by the Hepatitis A Virus Protease-Polymerase Processing Intermediate, 3CD

Toll-like receptor 3 (TLR3) and cytosolic RIG-I-like helicases (RIG-I and MDA5) sense viral RNAs and activate innate immune signaling pathways that induce expression of interferon (IFN) through specific adaptor proteins, TIR domain-containing adaptor inducing interferon-β (TRIF), and mitochondrial antiviral signaling protein (MAVS), respectively. Previously, we demonstrated that hepatitis A virus (HAV), a unique hepatotropic human picornavirus, disrupts RIG-I/MDA5 signaling by targeting MAVS for cleavage by 3ABC, a precursor of the sole HAV protease, 3Cpro, that is derived by auto-processing of the P3 (3ABCD) segment of the viral polyprotein. Here, we show that HAV also disrupts TLR3 signaling, inhibiting poly(I:C)-stimulated dimerization of IFN regulatory factor 3 (IRF-3), IRF-3 translocation to the nucleus, and IFN-β promoter activation, by targeting TRIF for degradation by a distinct 3ABCD processing intermediate, the 3CD protease-polymerase precursor. TRIF is proteolytically cleaved by 3CD, but not by the mature 3Cpro protease or the 3ABC precursor that degrades MAVS. 3CD-mediated degradation of TRIF depends on both the cysteine protease activity of 3Cpro and downstream 3Dpol sequence, but not 3Dpol polymerase activity. Cleavage occurs at two non-canonical 3Cpro recognition sequences in TRIF, and involves a hierarchical process in which primary cleavage at Gln-554 is a prerequisite for scission at Gln-190. The results of mutational studies indicate that 3Dpol sequence modulates the substrate specificity of the upstream 3Cpro protease when fused to it in cis in 3CD, allowing 3CD to target cleavage sites not normally recognized by 3Cpro. HAV thus disrupts both RIG-I/MDA5 and TLR3 signaling pathways through cleavage of essential adaptor proteins by two distinct protease precursors derived from the common 3ABCD polyprotein processing intermediate

In Vivo Approaches Reveal a Key Role for DCs in CD4+ T Cell Activation and Parasite Clearance during the Acute Phase of Experimental Blood-Stage Malaria

Dendritic cells (DCs) are phagocytes that are highly specialized for antigen presentation. Heterogeneous populations of macrophages and DCs form a phagocyte network inside the red pulp (RP) of the spleen, which is a major site for the control of blood-borne infections such as malaria. However, the dynamics of splenic DCs during Plasmodium infections are poorly understood, limiting our knowledge regarding their protective role in malaria. Here, we used in vivo experimental approaches that enabled us to deplete or visualize DCs in order to clarify these issues. To elucidate the roles of DCs and marginal zone macrophages in the protection against blood-stage malaria, we infected DTx (diphtheria toxin)-treated C57BL/6.CD11c-DTR mice, as well as C57BL/6 mice treated with low doses of clodronate liposomes (ClLip), with Plasmodium chabaudi AS (Pc) parasites. The first evidence suggesting that DCs could contribute directly to parasite clearance was an early effect of the DTx treatment, but not of the ClLip treatment, in parasitemia control. DCs were also required for CD4+ T cell responses during infection. The phagocytosis of infected red blood cells (iRBCs) by splenic DCs was analyzed by confocal intravital microscopy, as well as by flow cytometry and immunofluorescence, at three distinct phases of Pc malaria: at the first encounter, at pre-crisis concomitant with parasitemia growth and at crisis when the parasitemia decline coincides with spleen closure. In vivo and ex vivo imaging of the spleen revealed that DCs actively phagocytize iRBCs and interact with CD4+ T cells both in T cell-rich areas and in the RP. Subcapsular RP DCs were highly efficient in the recognition and capture of iRBCs during pre-crisis, while complete DC maturation was only achieved during crisis. These findings indicate that, beyond their classical role in antigen presentation, DCs also contribute to the direct elimination of iRBCs during acute Plasmodium infection.São Paulo Research Foundation grants: (2011/24038-1 [MRDL], 2009/08559-1 [HBdS], CAPES/IGC 04/ 2012 [MRDL, CET])

What Constitutes a Natural Fire Regime? Insight from the Ecology and Distribution of Coniferous Forest Birds in North America

Bird species that specialize in the use of burned forest conditions can provide insight into the prehistoric fire regimes associated with the forest types that they have occupied over evolutionary time. The nature of their adaptations reflects the specific post-fire conditions that occurred prior to the unnatural influence of humans after European settlement. Specifically, the post-fire conditions, nest site locations, and social systems of two species (Bachman\u27s sparrow [Aimophila aestivalis] and red-cockaded woodpecker [Picoides borealis]) suggest that, prehistorically, a frequent, low-severity fire regime characterized the southeastern pine system in which they evolved. In contrast, the patterns of distribution and abundance for several other bird species (black-backed woodpecker [Picoides arcticus], buff-breasted flycatcher [Empidonax fulvifrons], Lewis\u27 woodpecker [Melanerpes lewis], northern hawk owl [Surnia ulula], and Kirtland\u27s warbler [Dendroica kirtlandii]) suggest that severe fire has been an important component of the fire regimes with which they evolved. Patterns of habitat use by the latter species indicate that severe fires are important components not only of higher-elevation and high-latitude conifer forest types, which are known to be dominated by such fires, but also of mid-elevation and even low-elevation conifer forest types that are not normally assumed to have had high-severity fire as an integral part of their natural fire regimes. Because plant and animal adaptations can serve as reliable sources of information about what constitutes a natural fire regime, it might be wise to supplement traditional historical methods with careful consideration of information related to plant and animal adaptations when attempting to restore what are thought to be natural fire regimes

Who fans the flames of Alzheimer's disease brains? Misfolded tau on the crossroad of neurodegenerative and inflammatory pathways

Neurodegeneration, induced by misfolded tau protein, and neuroinflammation, driven by glial cells, represent the salient features of Alzheimer's disease (AD) and related human tauopathies. While tau neurodegeneration significantly correlates with disease progression, brain inflammation seems to be an important factor in regulating the resistance or susceptibility to AD neurodegeneration. Previously, it has been shown that there is a reciprocal relationship between the local inflammatory response and neurofibrillary lesions. Numerous independent studies have reported that inflammatory responses may contribute to the development of tau pathology and thus accelerate the course of disease. It has been shown that various cytokines can significantly affect the functional and structural properties of intracellular tau. Notwithstanding, anti-inflammatory approaches have not unequivocally demonstrated that inhibition of the brain immune response can lead to reduction of neurofibrillary lesions. On the other hand, our recent data show that misfolded tau could represent a trigger for microglial activation, suggesting the dual role of misfolded tau in the Alzheimer's disease inflammatory cascade. On the basis of current knowledge, we can conclude that misfolded tau is located at the crossroad of the neurodegenerative and neuroinflammatory pathways. Thus disease-modified tau represents an important target for potential therapeutic strategies for patients with Alzheimer's disease