The biological effects of subacute inhalation of diesel exhaust following addition of cerium oxide nanoparticles in atherosclerosis-prone mice

AbstractBackgroundCerium oxide (CeO2) nanoparticles improve the burning efficiency of fuel, however, little is known about health impacts of altered emissions from the vehicles.MethodsAtherosclerosis-prone apolipoprotein E knockout (ApoE−/−) mice were exposed by inhalation to diluted exhaust (1.7mg/m3, 20, 60 or 180min, 5 day/week, for 4 weeks), from an engine using standard diesel fuel (DE) or the same diesel fuel containing 9ppm cerium oxide nanoparticles (DCeE). Changes in hematological indices, clinical chemistry, atherosclerotic burden, tissue levels of inflammatory cytokines and pathology of the major organs were assessed.ResultsAddition of CeO2 to fuel resulted in a reduction of the number (30%) and surface area (10%) of the particles in the exhaust, whereas the gaseous co-pollutants were increased (6–8%). There was, however, a trend towards an increased size and complexity of the atherosclerotic plaques following DE exposure, which was not evident in the DCeE group. There were no clear signs of altered hematological or pathological changes induced by either treatment. However, levels of proinflammatory cytokines were modulated in a brain region and liver following DCeE exposure.ConclusionsThese results imply that addition of CeO2 nanoparticles to fuel decreases the number of particles in exhaust and may reduce atherosclerotic burden associated with exposure to standard diesel fuel. From the extensive assessment of biological parameters performed, the only concerning effect of cerium addition was a slightly raised level of cytokines in a region of the central nervous system. Overall, the use of cerium as a fuel additive may be a potentially useful way to limit the health effects of vehicle exhaust. However, further testing is required to ensure that such an approach is not associated with a chronic inflammatory response which may eventually cause long-term health effects

A closed Candidatus Odinarchaeum chromosome exposes Asgard archaeal viruses

Asgard archaea have recently been identified as the closest archaeal relatives of eukaryotes. Their ecology, and particularly their virome, remain enigmatic. We reassembled and closed the chromosome of Candidatus Odinarchaeum yellowstonii LCB_4, through long-range PCR, revealing CRISPR spacers targeting viral contigs. We found related viruses in the genomes of diverse prokaryotes from geothermal environments, including other Asgard archaea. These viruses open research avenues into the ecology and evolution of Asgard archaea

Geolocators lead to better measures of timing and renesting in black-tailed godwits and reveal the bias of traditional observational methods

Long-term population studies can identify changes in population dynamics over time. However, to realize meaningful conclusions, these studies rely on accurate measurements of individual traits and population characteristics. Here, we evaluate the accuracy of the observational methods used to measure reproductive traits in individually marked black-tailed godwits (Limosa limosa limosa). By comparing estimates from traditional methods with data obtained from light-level geolocators, we provide an accurate estimate of the likelihood of renesting in godwits and the repeatability of the lay dates of first clutches. From 2012 to 2018, we used periods of shading recorded on the light-level geolocators carried by 68 individual godwits to document their nesting behaviour. We then compared these estimates to those simultaneously obtained by our long-term observational study. We found that among recaptured geolocator-carrying godwits, all birds renested after a failed first clutch, regardless of the date of nest loss or the number of days already spent incubating. We also found that 43% of these godwits laid a second replacement clutch after a failed first replacement, and that 21% of these godwits renested after a hatched first clutch. However, the observational study correctly identified only 3% of the replacement clutches produced by geolocator-carrying individuals and designated as first clutches a number of nests that were actually replacement clutches. Additionally, on the basis of the observational study, the repeatability of lay date was 0.24 (95% CI 0.17-0.31), whereas it was 0.54 (95% CI 0.28-0.75) using geolocator-carrying individuals. We use examples from our own and other godwit studies to illustrate how the biases in our observational study discovered here may have affected the outcome of demographic estimates, individual-level comparisons, and the design, implementation and evaluation of conservation practices. These examples emphasize the importance of improving and validating field methodologies and show how the addition of new tools can be transformational

Effects of particulate matter on the pulmonary and vascular system: time course in spontaneously hypertensive rats

BACKGROUND: This study was performed within the scope of two multi-center European Commission-funded projects (HEPMEAP and PAMCHAR) concerning source-composition-toxicity relationship for particulate matter (PM) sampled in Europe. The present study aimed to optimize the design for PM in vivo toxicity screening studies in terms of dose and time between a single exposure and the determination of the biological responses in a rat model mimicking human disease resulting in susceptibility to ambient PM. Dust in thoracic PM size-range (aerodynamic diameter <10 μm) was sampled nearby a road tunnel (RTD) using a high volume cascade impactor. Spontaneously hypertensive rats were exposed to urban dust collected in Ottawa, Canada (EHC-93 10 mg/kg of body weight; reference PM) or different RTD doses (0.3, 1, 3, 10 mg/kg of body weight) by intratracheal instillation. Necropsy was performed at 4, 24, or 48 hr after exposure. RESULTS: The neutrophil numbers in bronchoalveolar lavage fluid increased tremendously after exposure to the highest RTD doses or EHC-93. Furthermore, PM exposure slightly affected blood coagulation since there was a small but significant increase in the plasma fibrinogen levels (factor 1.2). Pulmonary inflammation and oxidative stress as well as changes in blood coagulation factors and circulating blood cell populations were observed within the range of 3 to 10 mg PM/kg of body weight without significant pulmonary injury. CONCLUSION: The optimal dose for determining the toxicity ranking of ambient derived PM samples in spontaneously hypertensive rats is suggested to be between 3 and 10 mg PM/kg of body weight under the conditions used in the present study. At a lower dose only some inflammatory effects were detected, which will probably be too few to be able to discriminate between PM samples while a completely different response pattern was observed with the highest dose. In addition to the dose, a 24-hr interval from exposure to sacrifice seemed appropriate to assess the relative toxic potency of PM since the majority of the health effects were observed one day after PM exposure compared to the other times examined. The aforementioned considerations provide a good basis for conducting PM toxicity screening studies in spontaneously hypertensive rats

The human fungal pathogen Aspergillus fumigatus can produce the highest known number of meiotic crossovers

Sexual reproduction involving meiosis is essential in most eukaryotes. This produces offspring with novel genotypes, both by segregation of parental chromosomes as well as crossovers between homologous chromosomes. A sexual cycle for the opportunistic human pathogenic fungus Aspergillus fumigatus is known, but the genetic consequences of meiosis have remained unknown. Among other Aspergilli, it is known that A. flavus has a moderately high recombination rate with an average of 4.2 crossovers per chromosome pair, whereas A. nidulans has in contrast a higher rate with 9.3 crossovers per chromosome pair. Here, we show in a cross between A. fumigatus strains that they produce an average of 29.9 crossovers per chromosome pair and large variation in total map length across additional strain crosses. This rate of crossovers per chromosome is more than twice that seen for any known organism, which we discuss in relation to other genetic model systems. We validate this high rate of crossovers through mapping of resistance to the laboratory antifungal acriflavine by using standing variation in an undescribed ABC efflux transporter. We then demonstrate that this rate of crossovers is sufficient to produce one of the common multidrug resistant haplotypes found in the cyp51A gene (TR34/L98H) in crosses among parents harboring either of 2 nearby genetic variants, possibly explaining the early spread of such haplotypes. Our results suggest that genomic studies in this species should reassess common assumptions about linkage between genetic regions. The finding of an unparalleled crossover rate in A. fumigatus provides opportunities to understand why these rates are not generally higher in other eukaryotes

Early and long-term outcome of elective stenting of the infarct-related artery in patients with viability in the infarct-area: Rationale and design of the Viability-guided Angioplasty after acute Myocardial Infarction-trial (The VIAMI-trial)

BACKGROUND: Although percutaneous coronary intervention (PCI) is becoming the standard therapy in ST-segment elevation myocardial infarction (STEMI), to date most patients, even in developed countries, are reperfused with intravenous thrombolysis or do not receive a reperfusion therapy at all. In the post-lysis period these patients are at high risk for recurrent ischemic events. Early identification of these patients is mandatory as this subgroup could possibly benefit from an angioplasty of the infarct-related artery. Since viability seems to be related to ischemic adverse events, we initiated a clinical trial to investigate the benefits of PCI with stenting of the infarct-related artery in patients with viability detected early after acute myocardial infarction. METHODS: The VIAMI-study is designed as a prospective, multicenter, randomized, controlled clinical trial. Patients who are hospitalized with an acute myocardial infarction and who did not have primary or rescue PCI, undergo viability testing by low-dose dobutamine echocardiography (LDDE) within 3 days of admission. Consequently, patients with demonstrated viability are randomized to an invasive or conservative strategy. In the invasive strategy patients undergo coronary angiography with the intention to perform PCI with stenting of the infarct-related coronary artery and concomitant use of abciximab. In the conservative group an ischemia-guided approach is adopted (standard optimal care). The primary end point is the composite of death from any cause, reinfarction and unstable angina during a follow-up period of three years. CONCLUSION: The primary objective of the VIAMI-trial is to demonstrate that angioplasty of the infarct-related coronary artery with stenting and concomitant use of abciximab results in a clinically important risk reduction of future cardiac events in patients with viability in the infarct-area, detected early after myocardial infarction

Machine learning in the differentiation of follicular lymphoma from diffuse large B-cell lymphoma with radiomic [F-18]FDG PET/CT features

Background One of the challenges in the management of patients with follicular lymphoma (FL) is the identification of individuals with histological transformation, most commonly into diffuse large B-cell lymphoma (DLBCL). [F-18]FDG-PET/CT is used for staging of patients with lymphoma, but visual interpretation cannot reliably discern FL from DLBCL. This study evaluated whether radiomic features extracted from clinical baseline [F-18]FDG PET/CT and analyzed by machine learning algorithms may help discriminate FL from DLBCL. Materials and methods Patients were selected based on confirmed histopathological diagnosis of primary FL (n=44) or DLBCL (n=76) and available [F-18]FDG PET/CT with EARL reconstruction parameters within 6 months of diagnosis. Radiomic features were extracted from the volume of interest on co-registered [F-18]FDG PET and CT images. Analysis of selected radiomic features was performed with machine learning classifiers based on logistic regression and tree-based ensemble classifiers (AdaBoosting, Gradient Boosting, and XG Boosting). The performance of radiomic features was compared with a SUVmax-based logistic regression model. Results From the segmented lesions, 121 FL and 227 DLBCL lesions were included for radiomic feature extraction. In total, 79 radiomic features were extracted from the SUVmap, 51 from CT, and 6 shape features. Machine learning classifier Gradient Boosting achieved the best discrimination performance using 136 radiomic features (AUC of 0.86 and accuracy of 80%). SUVmax-based logistic regression model achieved an AUC of 0.79 and an accuracy of 70%. Gradient Boosting classifier had a significantly greater AUC and accuracy compared to the SUVmax-based logistic regression (p Conclusion Machine learning analysis of radiomic features may be of diagnostic value for discriminating FL from DLBCL tumor lesions, beyond that of the SUVmax alone

Comparative evaluation of the effects of short-term inhalation exposure to diesel engine exhaust on rat lung and brain

Combustion-derived nanoparticles, such as diesel engine exhaust particles, have been implicated in the adverse health effects of particulate air pollution. Recent studies suggest that inhaled nanoparticles may also reach and/or affect the brain. The aim of our study was to comparatively evaluate the effects of short-term diesel engine exhaust (DEE) inhalation exposure on rat brain and lung. After 4 or 18 h recovery from a 2 h nose-only exposure to DEE (1.9 mg/m(3)), the mRNA expressions of heme oxygenase-1 (HO-1), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and cytochrome P450 1A1 (CYP1A1) were investigated in lung as well as in pituitary gland, hypothalamus, olfactory bulb, olfactory tubercles, cerebral cortex, and cerebellum. HO-1 protein expression in brain was investigated by immunohistochemistry and ELISA. In the lung, 4 h post-exposure, CYP1A1 and iNOS mRNA levels were increased, while 18 h post-exposure HO-1 was increased. In the pituitary at 4 h post-exposure, both CYP1A1 and HO-1 were increased; HO-1 was also elevated in the olfactory tuberculum at this time point. At 18 h post-exposure, increased expression of HO-1 and COX-2 was observed in cerebral cortex and cerebellum, respectively. Induction of HO-1 protein was not observed after DEE exposure. Bronchoalveolar lavage analysis of inflammatory cell influx, TNF-α, and IL-6 indicated that the mRNA expression changes occurred in the absence of lung inflammation. Our study shows that a single, short-term inhalation exposure to DEE triggers region-specific gene expression changes in rat brain to an extent comparable to those observed in the lung