Preventing carbon nanoparticle-induced lung inflammation reduces antigen-specific sensitization and subsequent allergic reactions in a mouse model

BACKGROUND: Exposure of the airways to carbonaceous nanoparticles can contribute to the development of immune diseases both via the aggravation of the allergic immune response in sensitized individuals and by adjuvant mechanisms during the sensitization against allergens. The cellular and molecular mechanisms involved in these adverse pathways are not completely understood. We recently described that the reduction of carbon nanoparticle-induced lung inflammation by the application of the compatible solute ectoine reduced the aggravation of the allergic response in an animal system. In the current study we investigated the influence of carbon nanoparticles on the sensitization of animals to ovalbumin via the airways. Ectoine was used as a preventive strategy against nanoparticle-induced neutrophilic lung inflammation. METHODS: Balb/c mice were repetitively exposed to the antigen ovalbumin after induction of airway inflammation by carbon nanoparticles, either in the presence or in the absence of ectoine. Allergic sensitization was monitored by measurement of immunoglobulin levels and immune responses in lung and lung draining lymph nodes after challenge. Furthermore the role of dendritic cells in the effect of carbon nanoparticles was studied in vivo in the lymph nodes but also in vitro using bone marrow derived dendritic cells. RESULTS: Animals exposed to antigen in the presence of carbon nanoparticles showed increased effects with respect to ovalbumin sensitization, to the allergic airway inflammation after challenge, and to the specific T(H)2 response in the lymph nodes. The presence of ectoine during the sensitization significantly reduced these parameters. The number of antigen-loaded dendritic cells in the draining lymph nodes was identified as a possible cause for the adjuvant effect of the nanoparticles. In vitro assays indicate that the direct interaction of the particles with dendritic cells is not able to trigger CCR7 expression, while this endpoint is achieved by lung lavage fluid from nanoparticle-exposed animals. CONCLUSIONS: Using the intervention strategy of applying ectoine into the airways of animals we were able to demonstrate the relevance of neutrophilic lung inflammation for the adjuvant effect of carbon nanoparticles on allergic sensitization. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-015-0093-5) contains supplementary material, which is available to authorized users

Using the realized relationship matrix to disentangle confounding factors for the estimation of genetic variance components of complex traits

Background: In the analysis of complex traits, genetic effects can be confounded with non-genetic effects, especially when using full-sib families. Dominance and epistatic effects are typically confounded with additive genetic and non-genetic effects. This confounding may cause the estimated genetic variance components to be inaccurate and biased

Increased Local Retention of Reef Coral Larvae as a Result of Ocean Warming

Climate change will alter many aspects of the ecology of organisms, including dispersal patterns and population connectivity. Understanding these changes is essential to predict future species distributions, estimate potential for adaptation, and design effective networks of protected areas. In marine environments, dispersal is often accomplished by larvae. At higher temperatures, larvae develop faster, but suffer higher mortality, making the effect of temperature on dispersal difficult to predict. Here, we experimentally calibrate the effect of temperature on larval survival and settlement in a dynamic model of coral dispersal. Our findings imply that most reefs globally will experience several-fold increases in local retention of larvae due to ocean warming. This increase will be particularly pronounced for reefs with mean water residence times comparable to the time required for species to become competent to settle. Higher local retention rates strengthen the link between abundance and recruitment at the reef scale, suggesting that populations will be more responsive to local conservation actions. Higher rates of local retention and mortality will weaken connectivity between populations, and thus potentially retard recovery following severe disturbances that substantially deplete local populations. Conversely, on isolated reefs that are dependent on replenishment from local broodstock, increases in local retention may hasten recovery

Evaluation of internet access and utilization by medical students in Lahore, Pakistan

<p>Abstract</p> <p>Background</p> <p>The internet is increasingly being used worldwide in imparting medical education and improving its delivery. It has become an important tool for healthcare professionals training but the data on its use by medical students in developing countries is lacking with no study on the subject from Pakistan. This study was, therefore, carried out with an aim to evaluate the pattern of internet access and utilization by medical students in Pakistan.</p> <p>Methods</p> <p>A structured pre-tested questionnaire was administered to a group of 750 medical students in clinical years studying at various public and private medical colleges in Lahore. The questions were related to patterns of internet access, purpose of use and self reported confidence in performing various internet related tasks, use of health related websites to supplement learning and the problems faced by students in using internet at the institution.</p> <p>Results</p> <p>A total of 532 medical students (70.9%) returned the questionnaire. The mean age of study participants was 21.04 years (SD 1.96 years). Majority of the respondents (84.0%) reported experience with internet use. About half of the students (42.1%) were using internet occasionally with 23.1%, 20.9% and 13.9% doing so frequently, regularly and rarely respectively. About two third of the students (61.0%) stated that they use internet for both academic and professional activities. Most of the participants preferred to use internet at home (70.5%). Self reported ability to search for required article from PubMed and PakMedinet was reported by only 34.0% of the entire sample. Students were moderately confident in performing various internet related tasks including downloading medical books from internet, searching internet for classification of diseases and downloading full text article. Health related websites were being accessed by 55.1% students to supplement their learning process. Lack of time, inadequate number of available computers and lack of support from staff were cited as the most common problems faced by students while accessing internet in the institution premises. There were significant differences among male and female students with respect to the place of internet use (p = 0.001) and the ability to search online databases for required articles (p = 0.014).</p> <p>Conclusions</p> <p>Majority of the medical students in this study had access to internet and were using it for both academic and personal reasons. Nevertheless, it was seen that there is under utilization of the potential of internet resources to augment learning. Increase in awareness, availability of requisite facilities and training in computing skills are required to enable better utilization of digital resources of digital resources by medical students.</p

Sex differences in the impact of ozone on survival and alveolar macrophage function of mice after Klebsiella pneumoniae infection

<p>Abstract</p> <p>Background</p> <p>Sex differences have been described in a number of pulmonary diseases. However, the impact of ozone exposure followed by pneumonia infection on sex-related survival and macrophage function have not been reported. The purpose of this study was to determine whether ozone exposure differentially affects: 1) survival of male and female mice infected with <it>Klebsiella pneumoniae</it>, and 2) the phagocytic ability of macrophages from these mice.</p> <p>Methods</p> <p>Male and female C57BL/6 mice were exposed to O₃or to filtered air (FA) (control) and then infected intratracheally with <it>K. pneumoniae </it>bacteria. Survival was monitored over a 14-day period, and the ability of alveolar macrophages to phagocytize the pathogen <it>in vivo </it>was investigated after 1 h.</p> <p>Results</p> <p>1) Both male and female mice exposed to O₃are significantly more susceptible to <it>K. pneumoniae </it>infection than mice treated with FA; 2) although females appeared to be more resistant to <it>K. pneumoniae </it>than males, O₃exposure significantly increased the susceptibility of females to <it>K. pneumoniae </it>infection to a greater degree than males; 3) alveolar macrophages from O₃-exposed male and female mice have impaired phagocytic ability compared to macrophages from FA-exposed mice; and 4) the O₃-dependent reduction in phagocytic ability is greater in female mice.</p> <p>Conclusion</p> <p>O₃exposure reduces the ability of mice to survive <it>K. pneumoniae </it>infection and the reduced phagocytic ability of alveolar macrophages may be one of the contributing factors. Both events are significantly more pronounced in female mice following exposure to the environmental pollutant, ozone.</p

Pulmonary Function and Incident Bronchitis and Asthma in Children: A Community-Based Prospective Cohort Study

BACKGROUND: Previous studies revealed that reduction of airway caliber in infancy might increase the risks for wheezing and asthma. However, the evidence for the predictive effects of pulmonary function on respiratory health in children was still inconsistent. METHODS: We conducted a population-based prospective cohort study among children in 14 Taiwanese communities. There were 3,160 children completed pulmonary function tests in 2007 and follow-up questionnaire in 2009. Poisson regression models were performed to estimate the effect of pulmonary function on the development of bronchitis and asthma. RESULTS: After adjustment for potential confounders, pulmonary function indices consistently showed protective effects on respiratory diseases in children. The incidence rate ratios of bronchitis and asthma were 0.86 (95% CI 0.79-0.95) and 0.91 (95% CI 0.82-0.99) for forced expiratory volume in 1 second (FEV₁). Similar adverse effects of maximal mid-expiratory flow (MMEF) were also observed on bronchitis (RR = 0.73, 95% CI 0.67-0.81) and asthma (RR = 0.85, 95% CI 0.77-0.93). We found significant decreasing trends in categorized FEV₁ (p for trend = 0.02) and categories of MMEF (p for trend = 0.01) for incident bronchitis. Significant modification effects of traffic-related air pollution were noted for FEV₁ and MMEF on bronchitis and also for MMEF on asthma. CONCLUSIONS: Children with high pulmonary function would have lower risks on the development of bronchitis and asthma. The protective effect of high pulmonary function would be modified by traffic-related air pollution exposure

The state of pediatric asthma in Chicago's Humboldt Park: a community-based study in two local elementary schools

Abstract Background Pediatric asthma is a serious public health problem in Chicago and has been designated a high priority concern by residents of Chicago's Humboldt Park, a diverse community area with a large number of Puerto Rican, African American, and Mexican American families. Methods In May 2009, following the principles of community-based participatory research, a cross-sectional asthma screening survey was administered to adult caregivers of children attending two Humboldt Park elementary schools. Data were analyzed to determine the prevalence of diagnosed and probable asthma as well as the degree of asthma control among affected children; associations between asthma outcomes and mutable triggers were evaluated. Results Surveys from 494 children were evaluated. Physician-diagnosed asthma was reported for 24.9% of children and probable asthma identified in an additional 16.2% of children. Asthma was poorly or moderately controlled in 60.0% of diagnosed children. Smoking occurred inside 25.0% of households and 75.0% of caregivers reported idling of vehicles in their community. Report of general stress among caregivers, stress due to community crime, and/or an inability to cope with everyday life were significantly and positively associated with poor asthma morbidity and control among affected children. Conclusions Despite high prevalence rates and poor asthma morbidity and control in Humboldt Park, the association of these measures with mutable variables is promising. A community-based asthma intervention to address the issues identified in this study is needed to affect positive change.http://deepblue.lib.umich.edu/bitstream/2027.42/112574/1/12887_2010_Article_357.pd

Survival in amoeba: a major selection pressure on the presence of bacterial copper and zinc resistance determinants?: identification of a "copper pathogenicity island"

The presence of metal resistance determinants in bacteria usually is attributed to geological or anthropogenic metal contamination in different environments or associated with the use of antimicrobial metals in human healthcare or in agriculture. While this is certainly true, we hypothesize that protozoan predation and macrophage killing are also responsible for selection of copper/zinc resistance genes in bacteria. In this review, we outline evidence supporting this hypothesis, as well as highlight the correlation between metal resistance and pathogenicity in bacteria. In addition, we introduce and characterize the "copper pathogenicity island" identified in Escherichia coli and Salmonella strains isolated from copper- and zinc-fed Danish pigs

Sidestream cigarette smoke effects on cardiovascular responses in conscious rats: involvement of oxidative stress in the fourth cerebral ventricle

Background: Cigarette exposure increases brain oxidative stress. The literature showed that increased brain oxidative stress affects cardiovascular regulation. However, no previous study investigated the involvement of brain oxidative stress in animals exposed to cigarette and its relationship with cardiovascular regulation. We aimed to evaluate the effects of central catalase inhibition on baroreflex and cardiovascular responses in rats exposed to sidestream cigarette smoke (SSCS). Methods: We evaluated males Wistar rats (320-370 g), which were implanted with a stainless steel guide cannula into the fourth cerebral ventricle (4th V). Femoral artery and vein were cannulated for mean arterial pressure (MAP) and heart rate (HR) measurement and drug infusion, respectively. Rats were exposed to SSCS during three weeks, 180 minutes, 5 days/week (CO: 100-300 ppm). Baroreflex was tested with a pressor dose of phenylephrine (PHE, 8 mu g/kg, bolus) to induce bradycardic reflex and a depressor dose of sodium nitroprusside (SNP, 50 mu g/kg, bolus) to induce tachycardic reflex. Cardiovascular responses were evaluated before, 5, 15, 30 and 60 minutes after 3-amino-1,2,4-triazole (ATZ, catalase inhibitor, 0.001 g/100 mu L) injection into the 4th V. Results: Central catalase inhibition increased basal HR in the control group during the first 5 minutes. SSCS exposure increased basal HR and attenuated bradycardic peak during the first 15 minutes. Conclusion: We suggest that SSCS exposure affects cardiovascular regulation through its influence on catalase activity.Foundation of Support to Research of Sao Paulo State (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP [07/59127-9

Identification of Spt5 Target Genes in Zebrafish Development Reveals Its Dual Activity In Vivo

Spt5 is a conserved essential protein that represses or stimulates transcription elongation in vitro. Immunolocalization studies on Drosophila polytene chromosomes suggest that Spt5 is associated with many loci throughout the genome. However, little is known about the prevalence and identity of Spt5 target genes in vivo during development. Here, we identify direct target genes of Spt5 using fogsk8 zebrafish mutant, which disrupts the foggy/spt5 gene. We identified that fogsk8 and their wildtype siblings differentially express less than 5% of genes examined. These genes participate in diverse biological processes from stress response to cell fate specification. Up-regulated genes exhibit shorter overall gene length compared to all genes examined. Through chromatin immunoprecipitation in zebrafish embryos, we identified a subset of developmentally critical genes that are bound by both Spt5 and RNA polymerase II. The protein occupancy patterns on these genes are characteristic of both repressive and stimulatory elongation regulation. Together our findings establish Spt5 as a dual regulator of transcription elongation in vivo and identify a small but diverse set of target genes critically dependent on Spt5 during development