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Background: Ship engine emissions are important with regard to lung and cardiovascular diseases especially in coastal regions worldwide. Known cellular responses to combustion particles include oxidative stress and inflammatory signalling. Objectives: To provide a molecular link between the chemical and physical characteristics of ship emission particles and the cellular responses they elicit and to identify potentially harmful fractions in shipping emission aerosols. Methods: Through an air-liquid interface exposure system, we exposed human lung cells under realistic in vitro conditions to exhaust fumes from a ship engine running on either common heavy fuel oil (HFO) or cleaner-burning diesel fuel (DF). Advanced chemical analyses of the exhaust aerosols were combined with transcriptional, proteomic and metabolomic profiling including isotope labelling methods to characterise the lung cell responses. Results: The HFO emissions contained high concentrations of toxic compounds such as metals and polycyclic aromatic hydrocarbon, and were higher in particle mass. These compounds were lower in DF emissions, which in turn had higher concentrations of elemental carbon ("soot"). Common cellular reactions included cellular stress responses and endocytosis. Reactions to HFO emissions were dominated by oxidative stress and inflammatory responses, whereas DF emissions induced generally a broader biological response than HFO emissions and affected essential cellular pathways such as energy metabolism, protein synthesis, and chromatin modification. Conclusions: Despite a lower content of known toxic compounds, combustion particles from the clean shipping fuel DF influenced several essential pathways of lung cell metabolism more strongly than particles from the unrefined fuel HFO. This might be attributable to a higher soot content in DF. Thus the role of diesel soot, which is a known carcinogen in acute air pollution-induced health effects should be further investigated. For the use of HFO and DF we recommend a reduction of carbonaceous soot in the ship emissions by implementation of filtration devices.

Computation of a prearticulatory phonological representation (phonological access, or phonological retrieval) is an essential process in speech production whose neural localization is not clear. This study combined a specific behavioral measure of phonological access and multivariate voxel-based lesion-symptom mapping (VLSM) in a series of left hemisphere stroke patients to identify brain regions critical for this process.Phonological access was assessed in 40 chronic ischemic stroke patients using a silent rhyming task to avoid confounds with motor planning and articulation deficits. Additional covariates were incorporated in the VLSM analysis to control for orthographic and working memory demands of the rhyming task, and for age, education, and total lesion volume. The resulting t statistic maps were thresholded at voxelwise p0.001 and cluster-corrected at a familywise error of p0.05.Phonological access impairment was correlated with damage to a focal region of cortex and white matter caudal to the posterior sylvian fissure, which included the posterior supramarginal gyrus and adjacent anterior angular gyrus, planum temporale, and posterior superior temporal gyrus. No correlation was observed with Broca's area, insula, or sensorimotor cortex. An additional VLSM showed no correlation between damage in this posterior perisylvian region and spoken word comprehension.This is the first demonstration of a specific lesion correlate for phonological access impairment. Although this posterior perisylvian region overlaps with some versions of the classical Wernicke area, the present results demonstrate its involvement in prearticulatory phonological production rather than speech perception or lexical-semantic processes.

The correlation between semantic deficits and exception word regularization errors ("surface dyslexia") in semantic dementia has been taken as strong evidence for involvement of semantic codes in exception word pronunciation. Rare cases with semantic deficits but no exception word reading deficit have been explained as due to individual differences in reading strategy, but this account is hotly debated. Semantic dementia is a diffuse process that always includes semantic impairment, making lesion localization difficult and independent assessment of semantic deficits and reading errors impossible. We addressed this problem using voxel-based lesion symptom mapping in 38 patients with left hemisphere stroke. Patients were all right-handed, native English speakers and at least 6 months from stroke onset. Patients performed an oral reading task that included 80 exception words (words with inconsistent orthographic-phonologic correspondence, e.g., pint, plaid, glove). Regularization errors were defined as plausible but incorrect pronunciations based on application of spelling-sound correspondence rules (e.g., 'plaid' pronounced as "played"). Two additional tests examined explicit semantic knowledge and retrieval. The first measured semantic substitution errors during naming of 80 standard line drawings of objects. This error type is generally presumed to arise at the level of concept selection. The second test (semantic matching) required patients to match a printed sample word (e.g., bus) with one of two alternative choice words (e.g., car, taxi) on the basis of greater similarity of meaning. Lesions were labeled on high-resolution T1 MRI volumes using a semi-automated segmentation method, followed by diffeomorphic registration to a template. VLSM used an ANCOVA approach to remove variance due to age, education, and total lesion volume. Regularization errors during reading were correlated with damage in the posterior half of the middle temporal gyrus and adjacent posterior inferior temporal gyrus (blue in figure 1). In contrast, semantic errors during picture naming (red and pink in figure 1) and impaired performance on the semantic matching task (yellow and pink in figure 1) were correlated with more anterior temporal lobe damage and with inferior frontal gyrus involvement. There was substantial overlap between lesion correlates for the two explicit semantic tasks (pink in figure 1), but none between these areas and those correlated with regularization errors. This double dissociation is difficult to accommodate in terms of a common impairment underlying semantic deficits and regularization errors. Lesions in relatively anterior temporal regions appear to produce semantic deficits but not regularization errors, whereas more posterior temporal lesions produce regularization errors but not explicit semantic errors. One possibility is that this posterior temporal region stores whole word representations that do not include semantic information. Alternatively, these representations may include highly abstract and word-specific semantic information useful for computing phonology but not for more complex semantic tasks.

Background Ship engine emissions are important with regard to lung and cardiovascular diseases especially in coastal regions worldwide. Known cellular responses to combustion particles include oxidative stress and inflammatory signalling. Objectives To provide a molecular link between the chemical and physical characteristics of ship emission particles and the cellular responses they elicit and to identify potentially harmful fractions in shipping emission aerosols. Methods Through an air-liquid interface exposure system, we exposed human lung cells under realistic in vitro conditions to exhaust fumes from a ship engine running on either common heavy fuel oil (HFO) or cleaner-burning diesel fuel (DF). Advanced chemical analyses of the exhaust aerosols were combined with transcriptional, proteomic and metabolomic profiling including isotope labelling methods to characterise the lung cell responses. Results The HFO emissions contained high concentrations of toxic compounds such as metals and polycyclic aromatic hydrocarbon, and were higher in particle mass. These compounds were lower in DF emissions, which in turn had higher concentrations of elemental carbon (“soot”). Common cellular reactions included cellular stress responses and endocytosis. Reactions to HFO emissions were dominated by oxidative stress and inflammatory responses, whereas DF emissions induced generally a broader biological response than HFO emissions and affected essential cellular pathways such as energy metabolism, protein synthesis, and chromatin modification. Conclusions Despite a lower content of known toxic compounds, combustion particles from the clean shipping fuel DF influenced several essential pathways of lung cell metabolism more strongly than particles from the unrefined fuel HFO. This might be attributable to a higher soot content in DF. Thus the role of diesel soot, which is a known carcinogen in acute air pollution-induced health effects should be further investigated. For the use of HFO and DF we recommend a reduction of carbonaceous soot in the ship emissions by implementation of filtration devices., PLoS ONE, 10 (6), ISSN:1932-6203

Exposure to air pollution resulting from fossil fuel combustion has been linked to multiple short-term and long term health effects. In a previous study, exposure of lung epithelial cells to engine exhaust from heavy fuel oil (HFO) and diesel fuel (DF), two of the main fuels used in marine engines, led to an increased regulation of several pathways associated with adverse cellular effects, including pro-inflammatory pathways. In addition, DF exhaust exposure was shown to have a wider response on multiple cellular regulatory levels compared to HFO emissions, suggesting a potentially higher toxicity of DF emissions over HFO. In order to further understand these effects, as well as to validate these findings in another cell line, we investigated macrophages under the same conditions as a more inflammationrelevant model. An air-liquid interface aerosol exposure system was used to provide a more biologically relevant exposure system compared to submerged experiments, with cells exposed to either the complete aerosol (particle and gas phase), or the gas phase only (with particles filtered out). Data from cytotoxicity assays were integrated with metabolomics and proteomics analyses, including stable isotope-assisted metabolomics, in order to uncover pathways affected by combustion aerosol exposure in macrophages. Through this approach, we determined differing phenotypic effects associated with the different components of aerosol. The particle phase of diluted combustion aerosols was found to induce increased cell death in macrophages, while the gas phase was found more to affect the metabolic profile. In particular, a higher cytotoxicity of DF aerosol emission was observed in relation to the HFO aerosol. Furthermore, macrophage exposure to the gas phase of HFO leads to an induction of a pro-inflammatory metabolic and proteomic phenotype. These results validate the effects found in lung epithelial cells, confirming the role of inflammation and cellular stress in the response to combustion aerosols.