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Cruciferous vegetables contain compounds with antioxidant properties (e.g. carotenoids, vitamin C and folates) and can alter the activity of xenobiotic metabolism (i.e. isothiocyanates). These constituents may be particularly important for subjects who are exposed to free radicals and genotoxic compounds, including smokers. The aim of the study was to evaluate the effect of broccoli intake on biomarkers of DNA damage and repair. Twenty-seven young healthy smokers consumed a portion of steamed broccoli (250 g/day) or a control diet for 10 days each within a crossover design with a washout period. Blood was collected before and after each period. The level of oxidatively damaged DNA lesions (formamidopyrimidine DNA glycosylase-sensitive sites), resistance to ex vivo H2O2 treatment and repair of oxidised DNA lesions were measured in peripheral blood mononuclear cells (PBMCs). We also measured mRNA expression levels of repair and defence enzymes: 8-oxoguanine DNA glycosylase (OGG1), nucleoside diphosphate linked moiety X-type motif 1 (NUDT1) and heme oxygenase 1 (HO-1). After broccoli consumption, the level of oxidised DNA lesions decreased by 41% (95% confidence interval: 10%, 72%) and the resistance to H2O2-induced DNA strand breaks increased by 23% (95% CI: 13%, 34%). Following broccoli intake, a higher protection was observed in subjects with glutathione S-transferase (GST) M1-null genotype. The expression level and activity of repair enzymes was unaltered. In conclusion, broccoli intake was associated with increased protection against H2O2-induced DNA strand breaks and lower levels of oxidised DNA bases in PBMCs from smokers. This protective effect could be related to an overall improved antioxidant status. [ABSTRACT FROM AUTHOR]

Particulate air pollution is associated with increased risk of pulmonary diseases and detrimental outcomes related to the cardiovascular system, including altered vessel functions. This study's objective was too evaluate the effects of ambient particle exposure on the blood-gas permeability, lung function and Clara cell 16 (CC16) protein release in healthy young subjects. Twenty-nine nonsmokers participated in a randomized, two-factor crossover study with or without biking exercise for 180 min and with 24-h exposure to particle-rich (6169-15,362 particles/cm3; 7.0-11.6 μg/m3 PM2.5; 7.5-15.8 μg/m3 PM10-2.5) or filtered (91-542 particles/cm3) air collected above a busy street. The clearance rate of aerosolized 99mTc-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) was measured as an index for the alveolar epithelial membrane integrity and permeability of the lung blood-gas barrier after rush-hour exposure. Lung function was assessed using body plethysmography, flow-volume curves, and measurements of the diffusion capacity of carbon monoxide. CC16 was measured in plasma and urine as another marker of alveolar integrity. Particulate matter exposure had no significant effect on the epithelial membrane integrity using the methods available in this study. Exercise increased the clearance rate of 99mTc-DTPA indicated by a 6.8% (95% CI: 0.4-12.8%) shorter half-life and this was more pronounced in men than women. Neither particulate matter exposure nor exercise had an effect on the concentration of CC16 in plasma and urine or on the static and dynamic volumes or ventilation distribution of the lungs. The study thus demonstrates increased permeability of the alveolar blood-gas barrier following moderate exercise, whereas exposure to ambient levels of urban air particles has no detectable effects on the alveolar blood-gas barrier or lung function. [ABSTRACT FROM AUTHOR]

In all 155 specimens of the high Arctic codfish Arctogadus glacialis examined for metazoan parasites, 55 specimens were from southern and northern Baffin Bay, western Greenland, and 100 specimens from north-eastern Greenland and Scoresby Sound. A total of 20 parasite taxa were recorded. A new myxozoan Gadimyxa arctica was found in southern Baffin Bay and Scoresby Sound. The gadid myxozoan Zschokkella hildae, the digeneans Gonocerca phycidis and Lecithaster gibbosus, the gill copepod Haemobaphes cyclopterina and third-stage larvae of the nematodes Anisakis simplex and Hysterothylacium aduncum were found in Scoresby Sound only. The digenean Hemiurus levinseni and third-stage larvae of the nematode Contracaecum sp. were found at all four stations. The nematodes Ascarophis spp. were found at three stations. The parasite fauna of A. glacialis from Scoresby Sound was very similar to that of 50 specimens of the closely related Boreogadus saida from the same area. [ABSTRACT FROM AUTHOR]

BACKGROUND: Particulate matter, especially ultrafine particles (UFPs), may cause health effects through generation of oxidative stress, with resulting damage to DNA and other macromolecules. OBJECTIVES: Wc investigated oxidative damagc to DNA and related repair capacity in peripheral blood mononuclear cells (PBMCs) during controlled exposure to urban air particles with assignment of numher concentration (NC) to four size modes with average diameters of 12, 23, 57, and 212 nm. DESIGN. Twenty-nine healthy adults participated in a randomized, two-factor cross-ovcr study with or without biking excrcise for 180 min and with exposure to particles (NC 6169-15362/cm³) or filtered air (NC 91-542/cm³) for 24 hr. METHODS: The levels of DNA strand breaks (SBs), oxidized purines as formamidopyrimidine DNA glycolase (FPG) sites, and activity of 7,8-dihydro-8-oxoguanine-DNA glycosylase (OGGI) in PBMCs were measured by the Comet assay. mRNA levels of OGGI, nucleoside diphosphate linked moiety X-type motif I (NUDTI), and heme oxygenase-1 (HOl) were determined by real-time reverse transcriptase-polymerase chain reaction. RESULTS: Exposure to UFPs for 6 and 24 hr significantly increased the levels of SBs and FPG sites, with a further insignificant increase after physical exercise. The OGGI activity and expression of OGGI, NUDl, and HOl were unaltered. There was a significant dose-response relationship between NC and DNA damage, with the 57-nm mode as the major contributor to effects. Concomitant exposure to ozone, nitrogen oxides, and carbon monoxide had no influence. CONCLUSION: Our results indicate that UFPs, especially the 57-nm soot fraction from vehicle emissions, causes systemic oxidative stress with damage to DNA and no apparent compensatory up-regulation of DNA repair within 24 hr. [ABSTRACT FROM AUTHOR]

Abstract: Background: Particulate air pollution can aggravate cardiovascular disease by mechanisms suggested to involve translocation of particles to the bloodstream and impairment of endothelial function, possibly dependent on present atherosclerosis. Aim: We investigated the effects of exposure to diesel exhaust particles (DEP) in vivo and ex vivo on vasomotor functions in aorta from apoE−/− mice with slight atherosclerosis and from normal apoE+/+ mice. Methods: DEP 0, 0.5 or 5 mg/kg bodyweight in saline was administered i.p. The mice were sacrificed 1 h later and aorta ring segments were mounted on wire myographs. Segments from unexposed mice were also incubated ex vivo with 0, 10 and 100 μg DEP/ml before measurement of vasomotor functions. Results: Exposure to 0.5 mg/kg DEP in vivo caused a decrease in the endothelium-dependent acetylcholine elicited vasorelaxation in apoE−/− mice, whereas the response was enhanced in apoE+/+ mice. No significant change was observed after administration of 5 mg/kg DEP. In vivo DEP exposure did not affect constriction induced by K+ or phenylephrine. In vitro exposure to 100 μg DEP/ml enhanced acetylcholine-induced relaxation and attenuated phenylephrine-induced constriction. Vasodilation induced by sodium nitroprusside was not affected by any DEP exposure. Conclusion: Exposure to DEP has acute effect on vascular functions. Endothelial dysfunction possibly due to decreased NO production as suggested by decreased acetylcholine-induced vasorelaxation and unchanged sodium nitroprusside response can be induced by DEP in vivo only in vessels of mice with some atherosclerosis. [Copyright &y& Elsevier]

DNA repair may prevent increased levels of oxidatively damaged DNA from prolonged oxidative stress induced by, e.g. exposure to diesel exhaust particles (DEP). We studied oxidative damage to DNA in broncho-alveolar lavage cells, lungs, and liver after 4 × 1.5 h inhalations of DEP (20 mg/m3) in Ogg1- / -  and wild type (WT) mice with similar extent of inflammation. DEP exposure increased lung levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) in Ogg1- / -  mice, whereas no effect on 8-oxodG or oxidized purines in terms of formamidopyrimidine DNA glycosylase (FPG) sites was observed in WT mice. In both unexposed and exposed Ogg1- / -  mice the level of FPG sites in the lungs was 3-fold higher than in WT mice. The high basal level of FPG sites in Ogg1- / -  mice probably saturated the assay and prevented detection of DEP-generated damage. In conclusion, Ogg1- / -  mice have elevated pulmonary levels of FPG sites and accumulate genomic 8-oxodG after repeated inhalations of DEP. [ABSTRACT FROM AUTHOR]

Forest successional trajectories covering the last 2000 yr from a mixed deciduous forest in Denmark show a gradual shift in dominance fromTilia cordatatoFagus sylvaticaand a recent increase in total forest basal area since direct management ceased in 1948. The successions are reconstructed by combining a fifty-year record of direct tree observations with local pollen diagrams from Draved Forest, Denmark. Five of the seven successions record a heathland phase of Viking Age dating from 830 AD. The anthropogenic influence is considerable throughout the period of study even though Draved contains some of the most pristine forest stands in Denmark. Anthropogenic influence including felling masks the underlying natural dynamics, with the least disturbed sites showing the smallest compositional change. Some effects of former management, such as loss ofTilia cordatadominance, are irreversible. Artificial disturbance, particularly drainage, has accelerated and amplified the shift towardsFagusdominance that would have occurred on a smaller scale and at a slower rate in the absence of human intervention. [ABSTRACT FROM AUTHOR]

Several chemical mutagens and carcinogens, including polycyclic aromatic hydrocarbons (PAHs) and nitrated PAHs, are adsorbed to the surface of diesel exhaust particles (DEP). DEP can induce formation of reactive oxygen species and cause oxidative DNA damage as well as bulky carcinogen DNA adducts. Lung tissue is a target organ for DEP induced cancer following inhalation. Recent studies have provided evidence that the lung is also a target organ for DNA damage and cancer after oral exposure to other complex mixtures of PAHs. The genotoxic effect of oral administration of DEP was investigated, in terms of markers of DNA damage, mutations and repair, in the lung of Big Blue® rats fed a diet with 0, 0.2, 0.8, 2, 8, 20 or 80 mg DEP/kg feed for 21 days. There was no significant increase in the mutation frequency in the cII gene. However, an increase of DNA damage measured as DNA strand breaks (comet assay) and bulky DNA adducts (32P post labeling) was observed. The level of DNA strand breaks increased significantly at all dose levels while the level of DNA adducts increased significantly only at the intermediate dose levels. Similarly, the number of oxidized DNA bases measured as endonuclease III and fapyguanine glycosylase (FPG) sensitive sites increased at the intermediate dose levels. The induction of DNA damage by DEP exposure did not increase the expression of the repair genes OGG1 and ERCC1 at the mRNA level. The present study indicates that the lung is a target organ for primary DNA damage following oral exposure to DEP. DNA damage was induced following exposure to relatively low levels of DEP, but under the conditions used in the present experiment DNA damage did not result in an increased mutation rate. [Copyright &y& Elsevier]

Biofuels from vegetable oils or animal fats are considered to be more sustainable than petroleum-derived diesel fuel. In this study, we have assessed the effect of hydrogenated vegetable oil (HVO) exhaust on levels of DNA damage in peripheral blood mononuclear cells (PBMCs) as primary outcome, and oxidative stress and inflammation as mediators of genotoxicity. In a randomized cross-over study, healthy humans were exposed to filtered air, inorganic salt particles, exhausts from combustion of HVO in engines with aftertreatment [i.e. emission with nitrogen oxides and low amounts of particulate matter less than 2.5 µm (approximately 1 µg/m3)], or without aftertreatment (i.e. emission with nitrogen oxides and 93 ± 13 µg/m3 of PM2.5). The subjects were exposed for 3 h and blood samples were collected before, within 1 h after the exposure and 24 h after. None of the exposures caused generation of DNA strand breaks and oxidatively damaged DNA, or affected gene expression of factors related to DNA repair (Ogg1), antioxidant defense (Hmox1) or pro-inflammatory cytokines (Ccl2, Il8 and Tnfa) in PBMCs. The results from this study indicate that short-term HVO exhaust exposure is not associated with genotoxic hazard in humans. [ABSTRACT FROM AUTHOR]

The round goby (Neogobius melanostomus) was first observed in the Baltic Sea in 1990 and has since displayed substantial secondary dispersal, establishing numerous dense populations where they may outcompete native fish and negatively impact prey species. There have been multiple round goby diet studies from both the Baltic Sea and the North American Great Lakes where they are similarly invasive. However, studies that quantify their effects on recipient ecosystems and, specifically, their impacts on the benthic invertebrate macrofauna are rare, particularly from European waters. In this study, we conducted the first before-after study of the potential effects of round goby on benthic invertebrate macrofauna taxa in marine-brackish habitats in Europe, focusing of two sites in the Western Baltic Sea, Denmark. Results were in line with those from the Great Lakes, indicating negative impacts on specific molluscan taxa (e.g. Cardiidae bivalves and Neritidae gastropods, which both showed a fall in detected densities of approximately 98% within the Guldborgsund Strait). In contrast, many other groups appeared to be largely unaffected or even show positive trends following invasion. Round goby gut content data were available at one of our study sites from the period immediately after the invasion. These data confirmed that round goby had in fact been preying on the subset of taxa displaying negative trends. [ABSTRACT FROM AUTHOR]

Air force ground crew personnel are potentially exposed to fuels and lubricants, as raw materials, vapours and combustion exhaust emissions, during operation and maintenance of aircrafts. This study investigated exposure levels and biomarkers of effects for employees at a Danish air force military base. We enrolled self-reported healthy and non-smoking employees (n = 79) and grouped them by exposure based on job function, considered to be potentially exposed (aircraft engineers, crew chiefs, fuel operators and munition specialists) or as reference group with minimal occupational exposure (avionics and office workers). We measured exposure levels to polycyclic aromatic hydrocarbons (PAHs) and organophosphate esters (OPEs) by silicone bands and skin wipes (PAHs only) as well as urinary excretion of PAH metabolites (OH-PAHs). Additionally, we assessed exposure levels of ultrafine particles (UFPs) in the breathing zone for specific job functions. As biomarkers of effect, we assessed lung function, plasma levels of acute phase inflammatory markers, and genetic damage levels in peripheral blood cells. Exposure levels of total PAHs, OPEs and OH-PAHs did not differ between exposure groups or job functions, with low correlations between PAHs in different matrices. Among the measured job functions, the UFP levels were higher for the crew chiefs. The exposure level of the PAH fluorene was significantly higher for the exposed group than the reference group (15.9 ± 23.7 ng/g per 24 h vs 5.28 ± 7.87 ng/g per 24 h, p = 0.007), as was the OPE triphenyl phosphate (305 ± 606 vs 19.7 ± 33.8 ng/g per 24 h, p = 0.011). The OPE tris(1,3-dichlor-2-propyl)phosphate had a higher mean in the exposed group (60.7 ± 135 ng/g per 24 h) compared to the reference group (8.89 ± 15.7 ng/g per 24 h) but did not reach significance. No evidence of effects for biomarkers of systemic inflammation, genetic damage or lung function was found. Overall, our biomonitoring study show limited evidence of occupational exposure of air force ground crew personnel to UFPs, PAHs and OPEs. Furthermore, the OH-PAHs and the assessed biomarkers of early biological effects did not differ between exposed and reference groups. [ABSTRACT FROM AUTHOR]

Carbon nanotubes (CNTs) are speculated to cause mesothelioma by persistent inflammation, oxidative stress, tissue injury, and genotoxicity. To investigate the pleural response to CNTs, we exposed C57BL/6 mice by intrapleural injection of 0.2 or 5 µg multiwalled CNTs (MWCNT-7, NM-401, and NM-403) or single-walled CNTs (NM-411). Inflammatory response, cellular reactive oxygen species (ROS) production of pleural lavage cells, and genotoxicity in cells from the mesothelial surface were assessed at days 1 and 90 after the exposure. Long and rigid types of MWCNTs (MWCNT-7 and NM-401) caused acute inflammation, characterized by influx of macrophages, neutrophils, and eosinophils into the pleural cavity. The inflammation was still evident at 90 days after the exposure, although it had reduced dramatically. The cellular ROS production was increased at day 90 after the exposure to MWCNT-7 and NM-401. The short and tangled type of MWCNT (ie NM-403) did not cause pleural inflammation or ROS production in pleural fluid cells. The exposure to NM-411 did not cause consistent inflammation responses or cellular ROS production. Levels of DNA strand breaks and DNA oxidation damage were unaltered, except for NM-411-exposed mice that had increased levels of DNA strand breaks at 90 days after the exposure. In conclusion, the long and rigid CNTs caused prolonged inflammatory response and increased ROS production in pleural lavage cells, yet it was not reflected in higher levels of DNA damage in pleural tissue. [ABSTRACT FROM AUTHOR]

The round goby (Neogobius melanostomus) was first observed in the Baltic Sea in 1990 and has since displayed substantial secondary dispersal, establishing numerous dense populations where they may outcompete native fish and negatively impact prey species. There have been multiple round goby diet studies from both the Baltic Sea and the North American Great Lakes where they are similarly invasive. However, studies that quantify their effects on recipient ecosystems and, specifically, their impacts on the benthic invertebrate macrofauna are rare, particularly from European waters. In this study, we conducted the first before-after study of the potential effects of round goby on benthic invertebrate macrofauna taxa in marine-brackish habitats in Europe, focusing of two sites in the Western Baltic Sea, Denmark. Results were in line with those from the Great Lakes, indicating negative impacts on specific molluscan taxa (e.g. Cardiidae bivalves and Neritidae gastropods, which both showed a fall in detected densities of approximately 98% within the Guldborgsund Strait). In contrast, many other groups appeared to be largely unaffected or even show positive trends following invasion. Round goby gut content data were available at one of our study sites from the period immediately after the invasion. These data confirmed that round goby had in fact been preying on the subset of taxa displaying negative trends. [ABSTRACT FROM AUTHOR]

Exposure to ambient air pollution has been associated with cancer. Ambient air contains a complex mixture of toxics, including particulate matter (PM) and benzene. Carcinogenic effects of PM may relate both to the content of PAH and to oxidative DNA damage generated by transition metals, benzene, metabolism and inflammation.By means of personal monitoring and biomarkers of internal dose, biologically effective dose and susceptibility, it should be possible to characterize individual exposure and identify air pollution sources with relevant biological effects. In a series of studies, individual exposure to PM2.5, nitrogen dioxide (NO2) and benzene has been measured in groups of 40–50 subjects. Measured biomarkers included 1-hydroxypyrene, benzene metabolites (phenylmercapturic acid (PMA) and trans-trans-muconic acid (ttMA)), 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) in urine, DNA strand breaks, base oxidation, 8-oxodG and PAH bulky adducts in lymphocytes, markers of oxidative stress in plasma and genotypes of glutathione transferases (GSTs) and NADPH:quinone reductase (NQO1).With respect to benzene, the main result indicates that DNA base oxidation is correlated with PMA excretion. With respect to exposure to PM, biomarkers of oxidative damage showed significant positive association with the individual exposure. Thus, 8-oxodG in lymphocyte DNA and markers of oxidative damage to lipids and protein in plasma associated with PM2.5 exposure. Several types of DNA damage showed seasonal variation. PAH adduct levels, DNA strand breaks and 8-oxodG in lymphocytes increased significantly in the summer period, requiring control of confounders. Similar seasonal effects on strand breaks and expression of the relevant DNA repair genes ERCC1 and OGG1 have been reported.In the present setting, biological effects of air pollutants appear mainly related to oxidative stress via personal exposure and not to urban background levels. Future developments include personal time-resolved monitors for exposure to ultrafine PM and PM2.5, use of GPS, as well as genomics and proteomics based biomarkers. [Copyright &y& Elsevier]

We investigated the interaction of BZ and lipolysaccharide (LPS), a well-known inflammation-promoting agent, in wild-type and inducible nitrogen oxide synthase (iNOS) knockout mice. BZ generated DNA strand breaks (SB) in the liver of both wild-type and iNOS-deficient mice. In the bone marrow (BM) BZ and LPS generated SB only in wild-type mice. The effects were additive, suggesting that both a redox cycling and an iNOS-dependent pathway may be involved. Formamidopyrimidine DNA glycosylase sensitive sites were elevated by BZ in the BM in both types of mice, whereas endonuclease III sensitive sites were not affected by any treatment. Since BZ is associated with leukemia in humans, it suggests that oxidative DNA base damage rather than SB may be important in the development of leukemia. [Copyright &y& Elsevier]

Carbon nanotubes (CNTs) are fiber-like nanomaterials, which are used in various applications with possible exposure to humans. The genotoxicity and carcinogenic potential of CNTs remain to be fully understood. This study assessed the genotoxicity of three different multi-walled carbon nanotubes (MWCNTs) (MWCNT-7, NM-401 and NM-403) and one single-walled carbon nanotube (SWCNT) (NM-411) in FE1-Muta™Mouse lung epithelial (MML) cells using the alkaline comet assay. With the 2',7'-dichlorodihydrofluorescein diacetate fluorescent probe, we assessed the effect of CNT-exposure on the intracellular production of reactive oxygen species (ROS). We measured the effect of a 10-week CNT exposure on telomere length using quantitative PCR. Two of the included MWCNTs (NM-401 and MWCNT-7) and the SWCNT (NM-411) caused a significant increase in the level of DNA damage at concentrations up to 40 µg/ml (all concentrations pooled, p < 0.05), but no concentration-response relationships were found. All of the CNTs caused an increase in intracellular ROS production compared to unexposed cells (ptrend < 0.05). Results from the long-term exposure showed longer telomere length in cells exposed to MWCNTs compared to unexposed cells (p < 0.01). In conclusion, our results indicated that the included CNTs cause ROS production and DNA strand breaks in FE1-MML cells. Moreover, the MWCNTs, but not the SWCNT, had an impact on telomere length in a long-term exposure scenario. [ABSTRACT FROM AUTHOR]

Summary: In the present study, we quantify the progress in overall survival (OS) during the period 2000–2016 among Danish patients with acute myeloid leukaemia (AML). This population‐based study, including 3820 adult patients with AML, demonstrates a significantly improved OS over time with the 2‐year age‐standardised OS increasing from 22% in 2002 to 31% in 2016. The improvement in OS was exclusively seen in patients with AML aged ≥50 years, with absolute improvements in 2‐year OS from 2002 to 2016 of ≥10% among patients aged 50–75 years and a small absolute increase in those aged >75 years. [ABSTRACT FROM AUTHOR]

Environmental DNA (eDNA) provides a promising supplement to traditional sampling methods for population genetic inferences, but current studies have almost entirely focused on short mitochondrial markers. Here, we develop one mitochondrial and one nuclear set of target capture probes for the whale shark (Rhincodon typus) and test them on seawater samples collected in Qatar to investigate the potential of target capture for eDNA‐based population studies. The mitochondrial target capture successfully retrieved ~235× (90× − 352× per base position) coverage of the whale shark mitogenome. Using a minor allele frequency of 5%, we find 29 variable sites throughout the mitogenome, indicative of at least five contributing individuals. We also retrieved numerous mitochondrial reads from an abundant nontarget species, mackerel tuna (Euthynnus affinis), showing a clear relationship between sequence similarity to the capture probes and the number of captured reads. The nuclear target capture probes retrieved only a few reads and polymorphic variants from the whale shark, but we successfully obtained millions of reads and thousands of polymorphic variants with different allele frequencies from E. affinis. We demonstrate that target capture of complete mitochondrial genomes and thousands of nuclear loci is possible from aquatic eDNA samples. Our results highlight that careful probe design, taking into account the range of divergence between target and nontarget sequences as well as presence of nontarget species at the sampling site, is crucial to consider. eDNA sampling coupled with target capture approaches provide an efficient means with which to retrieve population genomic data from aggregating and spawning aquatic species. [ABSTRACT FROM AUTHOR]

SORL1 is strongly associated with both sporadic and familial forms of Alzheimer's disease (AD), but a lack of information about alternatively spliced transcripts currently limits our understanding of the role of SORL1 in AD. Here, we describe a SORL1 transcript (SORL1-38b) characterized by inclusion of a novel exon (E38b) that encodes a truncated protein. We identified E38b-containing transcripts in several brain regions, with the highest expression in the cerebellum and showed that SORL1-38b is largely located in neuronal dendrites, which is in contrast to the somatic distribution of transcripts encoding the full-length SORLA protein (SORL1-fl). SORL1-38b transcript levels were significantly reduced in AD cerebellum in three independent cohorts of postmortem brains, whereas no changes were observed for SORL1-fl. A trend of lower 38b transcript level in cerebellum was found for individuals carrying the risk variant at rs2282649 (known as SNP24), although not reaching statistical significance. These findings suggest synaptic functions for SORL1-38b in the brain, uncovering novel aspects of SORL1 that can be further explored in AD research. [ABSTRACT FROM AUTHOR]

Environmental variation across the range of wild species can lead to local adaptations. The Baltic Sea was formed when the Fenno-Scandian ice sheet retreated around 12 thousand years ago, creating a new brackish water habitat colonised by both marine and freshwater fish species. The European perch (Perca fluviatilis) is a predatory freshwater fish with a large geographical distribution across Eurasia, where it inhabits a wide range of environmental niches. In the Baltic Sea region it has even developed a specialised brackish water perch variant that can tolerate environmental salinity levels, which are lethal to freshwater perch. However, very little is known about the underlying mechanisms facilitating the colonisation and adaptation of perch to the Baltic Sea. Here, we use Genotyping-By-Sequencing data from six freshwater and six brackish water localities to disclose the evolutionary relationship between freshwater and brackish water perch. Our results show that the brackish water perch occurs in multiple distinct genetic clusters. We find that gene flow between brackish water perch with full access to the sea likely led to lower levels of differentiation and higher diversity than in freshwater perch. Selection analyses suggest that genomic adaptation played a role in the colonisation of the Baltic Sea and that the top three regions under selection harbour salinity tolerance genes. We complete by discussing the implications of our findings for management of brackish water perch in the western Baltic sea. [Display omitted] • GBS data from 12 perch populations, six with brackish and six with freshwater origin. • Brackish water populations were found in all three major genetic clades. • Top three regions under selection harboured salinity tolerance genes. [ABSTRACT FROM AUTHOR]

Many in vitro and in vivo studies have shown that exposure to carbon nanotubes (CNTs) is associated with inflammation, oxidative stress and genotoxicity, although there is a paucity of studies on these effects in the pleural cavity. In the present study, we investigated adverse outcomes of pleural exposure to multi-walled CNTs (MWCNT-7, NM-401 and NM-403) and single-walled CNTs (NM-411). Female C57BL/6 mice were exposed to 0.2 or 5 µg of CNTs by intra-pleural injection and sacrificed one-year post-exposure. Exposure to long and straight types of MWCNTs (i.e. MWCNT-7 and NM-401) was associated with decreased number of macrophages and increased number of neutrophils and eosinophils in pleural lavage fluid. Increased protein content in the pleural lavage fluid was also observed in mice exposed to MWCNT-7 and NM-401. The concentration of mesothelin was increased in mice exposed to MWCNT-7 and NM-411. Levels of DNA strand breaks and DNA oxidation damage, measured by the comet assay, were unaltered in cells from pleural scrape. Extra-pleural effects were seen in CNT exposed mice, including enlarged and pigmented mediastinal lymph nodes (all four types of CNTs), pericardial plaques (MWCNT-7 and NM-401), macroscopic abnormalities on the liver (MWCNT-7) and ovaries/uterus (NM-411). In conclusion, the results demonstrate that intra-pleural exposure to long and straight MWCNTs is associated with adverse outcomes. Certain observations such as increased content of mesothelin in pleural lavage fluid and ovarian/uterine abnormalities in mice exposed to NM-411 suggests that exposure to SWCNTs may also be associated with some adverse outcomes. [ABSTRACT FROM AUTHOR]

The ubiquitous pollution of plastic particles in most environmental matrices leads to concern about any potential adverse effects on human health. Most studies on the toxicological effect of nanoplastics has focused on standard particles of polystyrene. In reality humans are exposed to a large variety of different types and sizes of plastic material via oral intake and inhalation. In this study, we investigated the effect of polyethylene terephthalate (PET) nanoplastic particles from ground food containers from a supermarket. The aim was to investigate a possible link between exposure to PET nanoplastics and genotoxic response in a cell model of the human airway epithelial (A549) cells. Further, we investigated the combined effect of PET and chemicals known to alter the cellular redox state, as a model of partially compromised antioxidant defense system. DNA damage was assessed by the alkaline comet assay. The ground PET nanoplastics have a mean hydrodynamic diameter of 136 nm in water. The results showed that PET exposure led to increased reactive oxygen species production (approximately 30 % increase compared to unexposed cells). In addition, exposure to PET nanoplastic increased the level of DNA strand breaks (net increase = 0.10 lesions/106 base pair, 95 % confidence interval: 0.01, 0.18 lesions/106 base pair). Pre- or post-exposure to hydrogen peroxide or buthionine sulfoximine did not lead to a higher level of DNA damage. Overall, the study shows that exposure to PET nanoplastics increases both intracellular reactive oxygen production and DNA damage in A549 cells. • The hydrodynamic particle sizes of ground nanoplastics from PET food containers were 136–167 nm. • PET nanoplastic particles caused intracellular ROS production, both and in combination with pre-exposure to known oxidants. • PET nanoplastic particles, 125 µg/ml, caused DNA damage with a net increase of 0.10 lesions/106 bp. [ABSTRACT FROM AUTHOR]

Citizen Science has traditionally been applied in biodiversity monitoring, as the approach holds the potential for conducting large-scale data collections. However, involving citizens in more than data collection is still in its infancy. In this paper, we present the results of an ongoing citizen science project that expands the partnership between citizens and researchers by involving citizens in several parts of the scientific process. In the project, citizens first conduct sampling in the field, followed by analysis of their samples in our university laboratory. Finally, participants are interpreting the results of the laboratory analyses in collaboration with the researcher. The project aims to evaluate the presence of marine animals by monitoring the DNA left behind by the organisms in the environment (eDNA), using samples from the years 2017 and 2018. We found that citizens can carry out eDNA surveillance with an average success rate of 72% (where the success rate is defined as passing both the negative and positive control test) and that their data is of similar quality as a trained researcher and concur with known species distributions. Engaging and training citizen scientists in advanced laboratory analysis, such as the monitoring of eDNA in water samples, has promising applications for large-scale national monitoring of marine species that can be used in governmental mapping and monitoring efforts. [ABSTRACT FROM AUTHOR]

Fisheries enforcement relies on visual catch identification and quantification at sea or when landed. Silage (fish dissolved in acid) and fish blocks (block frozen fish) are promising methods for on-board processing and storage of low-value catches. We examined the use of non-destructive sampling and two DNA-based methods, quantitative PCR (qPCR) and metabarcoding, to assess species composition and relative abundance in industrial grade experimental silage and fish blocks. We demonstrate the ability to identify and quantify DNA from fish species in both products. qPCR analysis of small silage samples collected over 21 days detected all target control species. DNA from one species (Atlantic wolffish) was consistently overrepresented while, for three species of gadoids (Atlantic cod, haddock and whiting), the DNA content matched input tissue proportions with high accuracy. qPCR and metabarcoding of fish blocks, sampled as run-off water and exterior swabs, provided consistent species detection, with the highest variance observed in quantification from swab samples. Our analysis shows that DNA-based methods have significant potential as a tool for species identification and quantification of complex on-board-processed seafood products and are readily applicable to taxonomically and morphologically similar fish. There is, however, a need for establishing DNA/weight calibration factors for primary fisheries species. [ABSTRACT FROM AUTHOR]

Over the past decades the sampling of environmental DNA (eDNA) — encompassing the DNA of all organisms present in an environmental sample 1 — has emerged as a technique for biodiversity monitoring and discovery in a diversity of environments. Avoiding the physical collection and identification of biota, this approach is praised for its independence of taxonomic expertise and has changed the way biologists study biodiversity. However, a common result in eDNA studies is the finding of unexpected taxa which are often removed by conservative bioinformatic filters or disregarded, since the authors are uncertain about the result and rarely have the interest, time, skills, and/or resources to return to the field and confirm with actual specimens 2. Here, we report a case in which an eDNA discovery led to the physical localization of a member of the Micrognathozoa (Figure 1B) — a rare group of limnic micrometazoans, and the animal phylum to be discovered last 3 , which is the sister group to rotifers 4,5. To this day, Micrognathozoa still comprises only a single named species from Greenland and a few additional disparate places. Gonzalo Giribet and colleagues report on finding the elusive micrognathozoa based on an eDNA signal in a Pyrenean bog. [ABSTRACT FROM AUTHOR]

Mining rare earth elements (REEs) can release large amounts of metal(loid)-rich dust, which can pose significant health risks to local residents. However, compared to other types of particulates, toxicity of mining dust has been largely overlooked. To provide experimental evidence on toxicity of REE mine dust, the study assessed the oxidative stress potential and genotoxicity of inhalable particles collected in a REE mining area, and associated toxicological response with source compositions. Both source types (i.e., mine and tailing area) and distances from source (i.e., industrial and residential areas) were considered when selecting the 44 sampling sites. The particle samples contained 2.3–3.5 folds higher concentrations of tested metal(loid)s than background concentrations in soil. Specially, elevated Fe, REEs, Cd, Pb were found. In spite of low cytotoxicity in lung epithelial A549 cells, there was increased cellular ROS production by of particle exposure. Samples with higher mining-originated source contributions (Provenance Index <0.3) had higher cellular ROS production (1.72 fold, 95%CI: 1.66–1.79 fold) than samples with lower mining contributions (1.58 fold, 95%CI: 1.52–1.65 fold). The factors soil (~46%), mine (~22%), and heavy metal (~20%) sources were recognized by source apportionment analysis as the main contributors to cellular ROS production; importantly, mine and heavy metal sources counted more in industrial samples. While samples generated genotoxicity, there were no differences in DNA damage between the location groups of sampling. Collectively, the results indicate that particles in mining areas may cause ROS production and DNA damage in lung cells depending on mine dust. Coupled with the long-range transportation potential of mine dust, safety measures on open pit and dust disposal sites should be adopted. Unlabelled Image • Particles around rare earth mine and tailing areas were rich in metallic components. • The particles induced cellular ROS production and genotoxicity. • Particles collected in industrial areas induced more cellular ROS than in residential areas. • Soil , mine and heavy metal sources were the main contributors to ROS. [ABSTRACT FROM AUTHOR]

Speciation is a continuous process. Although it is known that differential adaptation can initiate divergence even in the face of gene flow, we know relatively little about the mechanisms driving complete reproductive isolation and the genomic patterns of divergence and introgression at the later stages of speciation. Sticklebacks contain many pairs of sympatric species differing in levels of reproductive isolation and divergence history. Nevertheless, most previous studies have focused on young species pairs. Here, we investigated two sympatric stickleback species, Pungitius pungitius and P. sinensis, whose habitats overlap in eastern Hokkaido; these species show hybrid male sterility, suggesting that they may be at a late stage of speciation. Our demographic analysis using whole-genome sequence data showed that these species split 1.73 Ma and came into secondary contact 37 200 years ago after a period of allopatry. This long period of allopatry might have promoted the evolution of intrinsic incompatibility. Although we detected on-going gene flow and signatures of introgression, overall genomic divergence was high, with considerable heterogeneity across the genome. The heterogeneity was significantly associated with variation in recombination rate. This sympatric pair provides new avenues to investigate the late stages of the stickleback speciation continuum. [ABSTRACT FROM AUTHOR]

Environmental DNA (eDNA) is increasingly used for monitoring marine organisms; however, offshore sampling and time lag from sampling to results remain problematic. In order to overcome these challenges a robotic sampler, a 2nd generation Environmental Sample Processor (ESP), was tested for autonomous analysis of eDNA from four commercial fish species in a 4.5 million liter mesocosm. The ESP enabled in situ analysis, consisting of water collection, filtration, DNA extraction and qPCR analysis, which allowed for real-time remote reporting and archival sample collection, consisting of water collection, filtration and chemical preservation followed by post-deployment laboratory analysis. The results demonstrate that the 2G ESP was able to consistently detect and quantify target molecules from the most abundant species (Atlantic mackerel) both in real-time and from the archived samples. In contrast, detection of low abundant species was challenged by both biological and technical aspects coupled to the ecology of eDNA and the 2G ESP instrumentation. Comparison of the in situ analysis and archival samples demonstrated variance, which potentially was linked to diel migration patterns of the Atlantic mackerel. The study demonstrates strong potential for remote autonomous in situ monitoring which open new possibilities for the field of eDNA and marine monitoring. [ABSTRACT FROM AUTHOR]

The aim of the study is to describe the results of reconstruction of the pelvic floor by using an absorbable biological mesh after having performed an abdomino-perineal resection with excision of whole of the pelvic floor for rectal cancer Eleven consecutive patients had reconstruction of the pelvic floor after abdominoperineal excision (APR) with a biological mesh. The peri- and postoperative courses were registered in a prospective database. Six patients received preoperative radiochemotherapy. One patient had the mesh removed due to infection and later developed local recurrence. The rest had an uneventful postoperative course despite more pain than is usually experienced in the perineal wound after traditional APR. The use of a biological mesh for pelvic floor reconstruction is feasible with satisfactory results. A randomised trial is warranted in order to evaluate this technique properly [ABSTRACT FROM AUTHOR]

Conservation and management of marine biodiversity depends on biomonitoring of marine habitats, but current approaches are resource‐intensive and require different approaches for different organisms. Environmental DNA (eDNA) extracted from water samples is an efficient and versatile approach to detecting aquatic animals. In the ocean, eDNA composition reflects local fauna at fine spatial scales, but little is known about the effectiveness of eDNA‐based monitoring of marine communities at larger scales. We investigated the potential of eDNA to characterize and distinguish marine communities at large spatial scales by comparing vertebrate species composition among marine habitats in Qatar, the Arabian Gulf (also known as the Persian Gulf), based on eDNA metabarcoding of seawater samples. We conducted species accumulation analyses to estimate how much of the vertebrate diversity we detected. We obtained eDNA sequences from a diverse assemblage of marine vertebrates, spanning 191 taxa in 73 families. These included rare and endangered species and covered 36% of the bony fish genera previously recorded in the Gulf. Sites of similar habitat type were also similar in eDNA composition. The species accumulation analyses showed that the number of sample replicates was insufficient for some sampling sites but suggested that a few hundred eDNA samples could potentially capture >90% of the marine vertebrate diversity in the study area. Our results confirm that seawater samples contain habitat‐characteristic molecular signatures and that eDNA monitoring can efficiently cover vertebrate diversity at scales relevant to national and regional conservation and management. Article impact statement: Environmental DNA provides habitat‐characteristic molecular signatures and can be used efficiently to map marine biodiversity at large spatial scales. [ABSTRACT FROM AUTHOR]

• Particles were collected in diesel-powered trains and firefighter training location. • Particles generated intracellular reactive oxygen species in A549 cells. • Long-term exposure to particles promoted shortening in telomeres in A549 cells. • Shorter telomeres were observed in mononuclear blood cells of particle-exposed humans. Particulate matter (PM) from combustion processes has been associated with oxidative stress to DNA, whereas effects related to telomere dysfunction are less investigated. We collected air-borne PM from a passenger cabin of a diesel-propelled train and at a training facility for smoke diving exercises. Effects on oxidative stress biomarkers, genotoxicity measured by the comet assay and telomere length in PM-exposed A549 cells were compared with the genotoxicity and telomere length in peripheral blood mononuclear cells (PBMCs) from human volunteers exposed to the same aerosol source. Although elevated levels of DNA strand breaks and oxidatively damaged DNA in terms of Fpg-sensitive sites were observed in PBMCs from exposed humans, the PM collected at same locations did not cause genotoxicity in the comet assay in A549 cells. Nevertheless, A549 cells displayed telomere length shortening after four weeks exposure to PM. This is in line with slightly shorter telomere length in PBMCs from exposed humans, although it was not statistically significant. In conclusion, the results indicate that genotoxic potency measured by the comet assay of PM in A549 cells may not predict genotoxicity in exposed humans, whereas telomere length measurements may be a novel indicator of genotoxic stress in cell cultures and humans. [ABSTRACT FROM AUTHOR]

Environmental DNA (eDNA) extracted from water samples has recently shown potential as a valuable source of population genetic information for aquatic macroorganisms. This approach offers several potential advantages compared with conventional tissue‐based methods, including the fact that eDNA sampling is noninvasive and generally more cost‐efficient. Currently, eDNA approaches have been limited to single‐marker studies of mitochondrial DNA (mtDNA), and the relationship between eDNA haplotype composition and true haplotype composition still needs to be thoroughly verified. This will require testing of bioinformatic and statistical software to correct for erroneous sequences, as well as biases and random variation in relative sequence abundances. However, eDNA‐based population genetic methods have far‐reaching potential for both basic and applied research. In this paper, we present a brief overview of the achievements of eDNA‐based population genetics to date, and outline the prospects for future developments in the field, including the estimation of nuclear DNA (nuDNA) variation and epigenetic information. We discuss the challenges associated with eDNA samples as opposed to those of individual tissue samples and assess whether eDNA might offer additional types of information unobtainable with tissue samples. Lastly, we provide recommendations for determining whether an eDNA approach would be a useful and suitable choice in different research settings. We limit our discussion largely to contemporary aquatic systems, but the advantages, challenges, and perspectives can to a large degree be generalized to eDNA studies with a different spatial and temporal focus. [ABSTRACT FROM AUTHOR]

The shallow, brackish waters of the western Baltic Sea play a significant role in the life cycle of several commercial fishes, both as nursery and foraging areas. The fish assemblages of the inner 100 m is, however, surprisingly poorly studied, due to lack of effective methods for monitoring all fish species. In the present study, we applied Snorkel Visual Census (SVC) as a tool in monitoring shallow water (< 5 m) fish assemblages at two brackish shallow water localities in the Sound, Denmark. The survey was conducted through 15 consecutive months (June 2013-August 2014), during which a total of 36 species were registered. Assemblages were numerically dominated by Gobiusculus flavescens (Fabricius, 1779) (50%) and Gasterosteus aculeatus Linnaeus, 1758 (45%). Analysis of temporal, spatial and environmental factors revealed that temperature was the single most powerful factor affecting species richness, and had a significant effect on fish abundance, which in addition showed significant seasonal variations. Species richness showed a quadratic correlation to temperature with an optimum of ~14°C. Abundances of individual species were affected by temperature and salinity, and showed both seasonal, spatial and diel variations. The negative effect of high temperatures on species richness was not seen at night, indicating that marine species utilize these areas as nocturnal feeding grounds or to avoid larger predators. Our findings show that SVC is effective in monitoring diversity of shallow, temperate water fish communities providing both qualitative and quantitative information on seasonal variations in species abundance and assemblage structure. [ABSTRACT FROM AUTHOR]

The Zebra Shark, in recent years known as Stegostoma fasciatum (Hermann, 1783), is well known for its dramatic ontogenetic change of color pattern, from striped ("zebra") juveniles to spotted ("leopard") adults. Nevertheless, many aspects of the species' biology, ecology, and morphology are still unknown or inadequately described, and its nomenclature is contentious. This study introduces a hitherto undescribed color morph of the Zebra Shark and provides an updated diagnosis and redescription of the species. Firstly, we establish that the Zebra Shark remains a single species based on genetic data from mitochondrial COI and ND4 markers. Secondly, through morphological analyses, we conclude that there are two morphs of the species, the known, zebra striped morph and a new, sandy colored morph. Both morphs were studied morphometrically to expose any ontogenetic changes, such as a decrease in the relative length of the tail with increasing total length (TL). The external coloration pattern clearly differentiates the two morphs, and both morphs can be further divided into three stages based on color pattern and size: juveniles (255–562 mm TL), transitionals (562–1395 mm TL), and adults (>1300 mm TL). The transitional sandy morph is dorsally covered by a swirly pattern of thin, dark brown bands edged with freckle-like brown spots. The adults are a uniform sandy beige, partially covered with brown freckles. A mature male of the zebra morph displayed a yet unknown feature of the claspers: a small, triangular spike extruding from the dorsal terminal of the clasper glands. Finally, we reviewed the nomenclature of the species and suggest that the original name Stegostoma tigrinumForster, 1781 should be used as the senior synonym for the species. [ABSTRACT FROM AUTHOR]

Ocean circulation, geological history, geographic distance, and seascape heterogeneity play an important role in phylogeography of coral‐dependent fishes. Here, we investigate potential genetic population structure within the yellowbar angelfish (Pomacanthus maculosus) across the Northwestern Indian Ocean (NIO). We then discuss our results with respect to the above abiotic features in order to understand the contemporary distribution of genetic diversity of the species. To do so, restriction site‐associated DNA sequencing (RAD‐seq) was utilized to carry out population genetic analyses on P. maculosus sampled throughout the species' distributional range. First, genetic data were correlated to geographic and environmental distances, and tested for isolation‐by‐distance and isolation‐by‐environment, respectively, by applying the Mantel test. Secondly, we used distance‐based and model‐based methods for clustering genetic data. Our results suggest the presence of two putative barriers to dispersal; one off the southern coast of the Arabian Peninsula and the other off northern Somalia, which together create three genetic subdivisions of P. maculosus within the NIO. Around the Arabian Peninsula, one genetic cluster was associated with the Red Sea and the adjacent Gulf of Aden in the west, and another cluster was associated with the Arabian Gulf and the Sea of Oman in the east. Individuals sampled in Kenya represented a third genetic cluster. The geographic locations of genetic discontinuities observed between genetic subdivisions coincide with the presence of substantial upwelling systems, as well as habitat discontinuity. Our findings shed light on the origin and maintenance of genetic patterns in a common coral reef fish inhabiting the NIO, and reinforce the hypothesis that the evolution of marine fish species in this region has likely been shaped by multiple vicariance events. [ABSTRACT FROM AUTHOR]

The comet assay offers the opportunity to measure both DNA damage and repair. Various comet assay based methods are available to measure DNA repair activity, but some requirements should be met for their effective use in human biomonitoring studies. These conditions include i) robustness of the assay, ii) sources of inter- and intra-individual variability must be known, iii) DNA repair kinetics should be assessed to optimize sampling timing; and iv) DNA repair in accessible surrogate tissues should reflect repair activity in target tissues prone to carcinogenic effects. DNA repair phenotyping can be performed on frozen and fresh samples, and is a more direct measurement than genomic or transcriptomic approaches. There are mixed reports concerning the regulation of DNA repair by environmental and dietary factors. In general, exposure to genotoxic agents did not change base excision repair (BER) activity, whereas some studies reported that dietary interventions affected BER activity. On the other hand, in vitro and in vivo studies indicated that nucleotide excision repair (NER) can be altered by exposure to genotoxic agents, but studies on other life style related factors, such as diet, are rare. Thus, crucial questions concerning the factors regulating DNA repair and inter-individual variation remain unanswered. Intra-individual variation over a period of days to weeks seems limited, which is favourable for DNA repair phenotyping in biomonitoring studies. Despite this reported low intra-individual variation, timing of sampling remains an issue that needs further investigation. A correlation was reported between the repair activity in easily accessible peripheral blood mononuclear cells (PBMCs) and internal organs for both NER and BER. However, no correlation was found between tumour tissue and blood cells. In conclusion, although comet assay based approaches to measure BER/NER phenotypes are feasible and promising, more work is needed to further optimize their application in human biomonitoring and intervention studies. [ABSTRACT FROM AUTHOR]

The European noble crayfish Astacus astacus is threatened by crayfish plague caused by the oomycete Aphanomyces astaci, which is spread by the invasive North American crayfish (e.g. signal crayfish Pacifastacus leniusculus). Surveillance of crayfish plague status in Norway has traditionally relied on the monitoring survival of cage‐held noble crayfish, a method of ethical concern. Additionally, trapping is used in crayfish population surveillance. Here, we test whether environmental DNA (eDNA) monitoring could provide a suitable alternative to the cage method, and a supplement to trapping.We took advantage of an emerging crayfish plague outbreak in a Norwegian watercourse following illegal introduction of disease‐carrying signal crayfish, and initiated simultaneous eDNA monitoring and cage‐based surveillance, supplemented with trapping. A total of 304 water samples were filtered from several sampling stations over a 4‐year period. eDNA data (species‐specific quantitative real‐time PCR [qPCR]) for the presence of A. astaci, noble and signal crayfish within the water samples were compared to cage mortality and trapping.This is the first study comparing eDNA monitoring and cage surveillance during a natural crayfish plague outbreak. We show that eDNA monitoring corresponds well with the biological status measured in terms of crayfish mortality and trapping results. eDNA analysis also reveals the presence of A. astaci in the water up to 2.5 weeks in advance of the cage method. Estimates of A. astaci and noble crayfish eDNA concentrations increased markedly during mortality and vanished quickly thereafter. eDNA provides a snapshot of the presence, absence or disappearance of crayfish regardless of season, and constitutes a valuable supplement to the trapping method that relies on season and legislation.Synthesis and applications. Simultaneous eDNA monitoring of Aphanomyces astaci (crayfish plague) and relevant native and invasive freshwater crayfish species is well‐suited for early warning of invasion or infection, risk assessments, habitat evaluation and surveillance regarding pathogen and invasive/native crayfish status. This non‐invasive, animal welfare friendly method excludes the need for cage‐held susceptible crayfish in disease monitoring. Furthermore, eDNA monitoring is less likely to spread A. astaci than traditional methods. This study resulted in the implementation of eDNA monitoring for Norwegian crayfish plague and crayfish surveillance programmes, and we believe other countries could improve management strategies for freshwater crayfish using a similar approach. Simultaneous eDNA monitoring of Aphanomyces astaci (crayfish plague) and relevant native and invasive freshwater crayfish species is well‐suited for early warning of invasion or infection, risk assessments, habitat evaluation and surveillance regarding pathogen and invasive/native crayfish status. This non‐invasive, animal welfare friendly method excludes the need for cage‐held susceptible crayfish in disease monitoring. Furthermore, eDNA monitoring is less likely to spread A. astaci than traditional methods. This study resulted in the implementation of eDNA monitoring for Norwegian crayfish plague and crayfish surveillance programmes, and we believe other countries could improve management strategies for freshwater crayfish using a similar approach. [ABSTRACT FROM AUTHOR]

• The comet assay is widely used in human biomonitoring to measure DNA damage. • Variation in comet assay results between laboratories has been a problem. • Specific steps in the assay have been identified as causes of this variation. • Including reference standards in experiments helps to control variation. • We give recommendations for improving the reliability of the assay. The comet assay (single cell gel electrophoresis) is widely used as a biomonitoring tool to assess DNA damage – strand breaks, as well as oxidised bases; it can also be adapted to measure DNA repair. It is based on the ability of breaks in the DNA to relax supercoiling, allowing DNA loops to extend from the nuclear core (nucleoid) under an electric field to form a comet-like tail. Most commonly, it is applied to white blood cells. The range of detection is between a few hundred breaks per cell and a few thousand, encompassing levels of damage that can be repaired and tolerated by human cells. Its applications include monitoring various diseases, studying the influence of nutrition on DNA stability, and investigating effects of environmental and occupational mutagens. Here we address the issue of inter-laboratory variation in comet assay results. This variation is largely due to differences in methods. Imposing a standard protocol is not practical, but users should be aware of the crucial parameters that affect performance of the assay. These include the concentration of agarose in which the cells are embedded; the duration of cell lysis, and of enzyme incubation when oxidised bases are being measured; the duration of alkaline unwinding; the duration of electrophoresis and the voltage gradient applied; and the method used to score the comets. Including reference standards in each experiment allows experimental variability to be monitored – and if variation is not extreme, results can be normalised using reference standard values. Reference standards are also essential for inter-laboratory comparison. Finally, we offer recommendations which, we believe, will limit variability and increase the usefulness of this assay in molecular epidemiology. [ABSTRACT FROM AUTHOR]

Acute promyelocytic leukemia (APL) is highly curable. To achieve high cure rates, targeted therapy with retinoic acid (ATRA) must be started promptly at time of suspected diagnosis. Early death rates (EDRs, ≤30 days from diagnosis) differ markedly in patients treated on clinical trials compared to the general population. Objectives and methods: We used the comprehensive Danish National Acute Leukemia Registry (DNLR) to investigate the incidence, treatment, EDR, and long‐term clinical outcome in APL between 2000 and 2014. Results: Twenty‐two of 41 deaths occurring in 122 APL patients were EDs which were primarily caused by intracranial hemorrhage, disseminated intravascular coagulation (DIC), sepsis, and multiorgan failure. The overall EDR was 18.0%, whereas clinical trial participants had an EDR of 6.7%. Fifteen patients recruited to the NCRI AML17 APL trial from 2010 to 2013 were younger and had decreased mortality (HR 0.18, CI 0.04‐0.86, P = 0.02) compared to contemporarily treated patients (n = 15) not recruited to a clinical trial. Performance status, leukemia origin, and Sanz‐score were independent prognostic variables. Conclusions: The very low EDR for on‐trial patients is not observed in the general cohort of APL patients. Diagnostic awareness emerges as the greatest clinical challenge in management of APL. [ABSTRACT FROM AUTHOR]

Vegetable carbon (E153) and titanium dioxide (E171) are widely used as black and white food colour additives. The aim of this study was to assess gastrointestinal tight junction and systemic genotoxic effects in rats following exposure to E153 and E171 for 10 weeks by oral gavage once a week. The expression of tight junction proteins was assessed in intestinal tissues. Levels of DNA strand breaks, oxidatively damaged DNA and telomere length were assessed in secondary organs. Hydrodynamic suspensions of E153 and E173 indicated mean particles sizes of 230 and 270 nm, respectively, and only E153 gave rise to intracellular production of reactive oxygen species in colon epithelial (Caco-2) cells. Rats exposed to E153 (6.4 mg/kg/week) or E171 (500 mg/kg/week) had decreased gene expression of the tight junction protein TJP1 (P < 0.05). E153 (6.4 mg/kg/week) also decreased OCLN (P < 0.05) in the colon and occludin protein expression in the small intestine (P < 0.05). Furthermore, E153 or E171 exposed rats had shorter telomeres in the lung (P < 0.05). Plasma from particle-exposed rats also produced telomere shortening in cultured lung epithelial cells. There were unaltered levels of oxidatively damaged DNA in the liver and lung and no changes in the DNA repair activity of oxidatively damaged DNA in the lung. Altogether, these results indicate that intragastric exposure to E153 and E171 is associated with reduced tight junction protein expression in the intestinal barrier and telomere length shortening in the lung in rats. [ABSTRACT FROM AUTHOR]

Abstract This study investigated the capacity of an anthocyanin-rich fraction (ACN-RF) from blueberry, single anthocyanins (cyanidin, delphinidin and malvidin-3-glucoside; Cy, Dp and Mv-3-glc) and related metabolites (protocatechuic, gallic and syringic acid; PrA, GA and SA) to resolve an inflammation-driven adhesion of monocytes (THP-1) on endothelial cell (HUVECs) and secretion of cell adhesion molecules E-selectin and vascular cell adhesion molecule 1 (VCAM-1). The adhesion of THP-1 to HUVECs was induced by tumour necrosis factor α (TNF-α, 100 ng mL−1). Subsequently, ACN-RF, single ACNs and metabolites (from 0.01 to 10 μg mL−1) were incubated for 24 h. The adhesion was measured in a fluorescence spectrophotometer. E-selectin and VCAM-1 were quantified by ELISA. No toxicological effects were observed for the compounds and the doses tested. ACN-RF and Mv-3-glc reducedTHP-1 adhesion at all the concentrations with the maximum effect at 10 μg/ml (−60.2% for ACNs and-33.9% for Mv-3-glc). Cy-3-glc decreased the adhesion by about 41.8% at 10 μg mL−1, while PrA and GA reduced the adhesion of THP-1 to HUVECs both at 1 and at 10 μg mL−1 (−29.5% and −44.3% for PrA, respectively, and −18.0%and −59.3% for GA, respectively). At the same concentrations a significant reduction of E-selectin, but notVCAM-1 levels, was documented. No effect was observed following Dp-3-glc and SA supplementation. Overall, ACNs and metabolites seem to resolve, in a dose-dependent manner, the inflammation-driven adhesion of THP-1 to HUVECs by decreasing E-selectin concentrations. Interestingly, Mv-3-glc was active at physiologically relevant concentrations. Graphical abstract Anthocyanins and their metabolites are able to directly and/or indirectly modulate monocytes adhesion to endothelial cells through different pathway. They can act against oxidative stress by inducing Nrf2 expression and the activation of antioxidant and detoxifying enzymes able to counteract ROS production. Furthermore, anthocyanins are able to inhibit NF-kB pathway and suppress the production of numerous proinflammatory cytokines (e.g. TNF-α) and adhesion molecules (e.g. VCAM-1). Moreover, anthocyanins are potent inducers of vasomotor factors (i.e. NO) and repressors of vasoconstrictors (e.g. ET) and procoagulant factors (e.g. PAI). Legend: ROS (Reactive oxygen species); Nrf2 (Nuclear factor erythroid 2–related factor 2); GST (Glutathione S-transferase); SOD (Superoxide dismutase); GPx (Glutathione peroxidase); NF-kB (Nuclear factor kappa B); TNF-α (Tumor necrosis factor-alpha); IL-1β (Interleukin-1beta); IL-6 (Interleukin-6); VCAM-1 (Vascular Cell Adhesion Molecule 1); ICAM-1 (Intracellular Adhesion Molecule-1); E-selectin (endothelial-selectin); NO (Nitric oxide); EDHF (Endothelium-derived hyperpolarizing factor); ET-1 (Endothelin-1); TXA2 (Thromboxane A2); PAI-1 (Plasminogen activator inhibitor-1); PAF (Platelet-Activating Factor). Image 1 Highlights • Inflammation plays a central role in the atherosclerosis. • Polyphenols may counteract inflammation and atherosclerotic process. • Anthocyanins and metabolites resolved the adhesion process. • Anthocyanins and metabolites lowered E-selectin levels. • The effects were observed mainly at supraphysiological concentrations. [ABSTRACT FROM AUTHOR]

Abstract Biomass assesment of fish stocks is a difficult task that often involves costly fisheries trawl surveys. Trawl surveys rarely return replicate samples, as trawling attempts are expensive and difficult to reproduce. Furthermore, traditional benthic trawling is often detrimental to habitats and the organisms associated with the sea bottom. The rapidly developing field of environmental DNA (eDNA) analysis offers a new approach to non-invasive monitoring of fish. In the present study, we develop and test species-specific primers and probes for qPCR detection of eDNA from Atlantic herring (Clupea harengus), Atlantic cod (Gadus morhua), European flounder (Platichthys flesus), European plaice (Pleuronectes platessa), and Atlantic mackerel (Scomber scombrus) in the Baltic Sea. A recently published qPCR system was applied for European eel (Anguilla anguilla). Filtered water samples were collected during a stratified benthic trawl survey, enabling parallel comparisons of eDNA concentrations with biomass caught by trawling. No significant correlation was found between eDNA concentrations and the biomass of fish caught by the trawl, although an association was observed between the measured concentrations of eDNA and the known distributions and main abundances of cod, herring, plaice and flounder. This indicates that while eDNA concentrations may not be directly comparable to results from existing methods – likely because aquatic eDNA concentrations are not controlled by the same combinations of factors as e.g. trawl biomass catch – eDNA analysis could prove a useful supplement for monitoring fish stocks in the future. Graphical abstract Unlabelled Image Highlights • Species-specific qPCR assays were developed for detection of environmental DNA from six commercially important marine fishes. • All six primer- probe sets were proven to be species-specific in the North Sea and Baltic Sea. • High levels of environmental DNA were found in areas with large catches of cod, herring, plaice and flounder. • No significant correlations were found between trawled catch size and the environmental DNA quantity as measured in filtered water samples. [ABSTRACT FROM AUTHOR]

A crucial first step in assessing and managing the role and impacts of predators on their environment is knowledge on their foraging behaviour and diet. Here, we synthesize previously published and newly generated data on the diet of harbour seals, grey seals, and ringed seals in the Baltic Sea region. More than 45 000 otoliths recovered from 3147 samples of scats and digestive tracts were collected throughout all seasons and most Baltic Sea sub-basins from 1968 to 2013. The data revealed a large extent of interspecific, spatial, and seasonal variation in seal diet, implying that caution should be made when extrapolating from one species, area or season, to others. Still, a few fish species, including Atlantic herring, sprat, cod, and sandeels had high occurrence across seal species and locations. The compiled data provide the first overview of seal diet across the entire Baltic Sea region, but also comes with several limitations. Thus, while the data presented here constitutes an important reference for future inference, it also illustrates an urgent need for standardizing methodology across studies on the diet of seals and other aquatic predators. [ABSTRACT FROM AUTHOR]

Abstract Animal studies have shown that titanium dioxide (TiO 2) exposure affects arterial vasomotor function, whereas little is known about the effects in arteries from humans. This study investigated vasomotor responses after direct exposure of human subcutaneous arteries to food-grade TiO 2 (E171) (14 or 140 μg/ml) for 30 min and 18 h. Vasomotor responses to bradykinin, 5-hydroxytryptamine (5-HT), sarafotoxin 6c (S6c) and nitroglycerin were recorded in wire-myographs. Vasoconstrictor responses to 5-HT were increased in arteries exposed to E171 for 18 h (P < 0.05). Furthermore, an increase in S6c responses was seen in low concentration E171 exposed arteries (30 min exposure; P < 0.05). The vasorelaxation response to nitroglycerin was increased in low concentration E171 exposed arteries (30 min exposure; P < 0.05). Vasorelaxation responses to bradykinin were unaffected after treatment with E171. There was no difference in gene expression levels of intercellular cell adhesion molecule 1, vascular cell adhesion molecule 1, 5-hydroxytryptamine receptor 1B, 5-hydroxytryptamine receptor 2A, endothelin receptor A and endothelin receptor B in E171 exposed arteries after exposure to TiO 2 for 30 min or 18 h. In conclusion, this study shows that the same type of vasomotor dysfunction is found in artery segments of rats and humans following ex vivo exposure to E171. Highlights • Exposure of human arteries to E171 resulted in increased vasocontraction response. • There were unaltered expressions of 5-hydroxytryptamine or sarafotoxin 6c receptors. • The exposure did not change the expression of cell adhesion molecules in arteries. • Exposure to E171 increased the endothelial-independent vasorelaxation response. [ABSTRACT FROM AUTHOR]

Background: The current literature on single cell genomic analyses on the DNA level is conflicting regarding requirements for cell quality, amplification success rates, allelic dropouts and resolution, lacking a systematic comparison of multiple cell input down to the single cell. We hypothesized that such a correlation assay would provide an approach to address the latter issues, utilizing the leukemic cell line OCI-AML3 with a known set of genetic aberrations. Results: By analyzing single and multiple cell replicates (2 to 50 cells) purified by micromanipulation and serial dilution we stringently assessed the signal-to-noise ratio (SNR) from single as well as a discrete number of cells based on a multiple displacement amplification method, with whole exome sequencing as signal readout. In this setting, known OCI-AML3 mutations as well as large copy number alterations could be identified, adding to the current knowledge of cytogenetic status. The presence of DNMT3A R882C, NPM1 W288 fs and NRAS Q61L was consistent, in spite of uneven allelic read depths. In contrast, at the level of single cells, we observed that one-third to half of all variants were not reproduced in the replicate sample, and this allelic mismatch displayed an exponential function of cell input. Large signature duplications were discernible from 5 cells, whereas deletions were visible down to the single cell. Thus, even under highly optimized conditions, single cell whole genome amplification and interpretation must be taken with considerable caution, given that allelic change is frequent and displays low SNR. Allelic noise is rapidly alleviated with increased cell input, and the SNR is doubled from 2 to 50 cells. Conclusions: In conclusion, we demonstrate noisy allele distributions, when analyzing genetic aberrations within single cells relative to multiple cells. Based on the presented data we recommend that single cell analyses should include replicate cell dilution assays for a given setup for relative assessment of procedure-specific SNR to ensure that the resolution supports the specific hypotheses. [ABSTRACT FROM AUTHOR]

Ambient air pollution including ozone and especially particulate matter represents important causes of cardiovascular disease. However, there is limited knowledge on indoor air dust with respect to this risk and the potential interactions between dust and ozone. Here, we exposed 23 healthy elderly subjects for 5.5 h, to either clean air, house dust at 275 µg/m³ (diameter < 2.5 µm), ozone at 100 ppb or combined house dust and ozone in a double-blinded randomized cross-over study. The combined house dust and ozone exposure was associated with a 48% (95% CI 24%-65%) decrease as compared with the clean air exposure, in CD34+KDR+ late endothelial progenitor cells (EPCs) per leukocyte in the blood shortly after exposure, whereas none of the single exposures resulted in a significant effect. The combined exposure also increased reactive oxygen species production capacity in granulocytes and monocytes as well as an up-regulation of interleukin-8 mRNA levels in leukocytes. Ozone alone reduced the gene expression of tumor necrosis factor and C-C motif chemokine ligand 2, while dust alone showed no effects. The combined exposure to house dust and ozone also reduced levels of oxidized purines in DNA consistent with concomitant up-regulation of mRNA of the repair enzyme 8-oxoguanine DNA glycosylase. The reduction in late EPCs can be an indicator of cardiovascular risk caused by the combination of pulmonary oxidative stress induced by ozone and the inflammatory potential of the house dust. These data were corroborated with in vitro findings from exposed human macrophages and endothelial cells. [ABSTRACT FROM AUTHOR]

Particles from burning candles contribute to the overall indoor exposure to particulate matter (PM). However, little is known about the effects of indoor sources of particles on cardiovascular disease endpoints. This study investigated the effect of pulmonary exposure to particles from combustion of candles and progression of atherosclerosis. Telomere shortening was assessed in tissues due to its relationship to risk of cardiovascular diseases. The particles were collected from burning candles and used for toxicological studies in cultured endothelial cells and apolipoprotein E (ApoE) knockout mice. Three hours exposure to particles increased the production of reactive oxygen species in endothelial cells, whereas there was no effect on cytotoxicity. Intratracheal instillation of particles (0.5 or 5 mg/kg) once a week for 5 weeks in ApoE −/− mice was associated with an accelerated progression of atherosclerosis in aorta and telomere shortening in the lung and spleen, whereas there was no effect on inflammation in the lungs (i.e. cell numbers), cell damage (i.e. lactate dehydrogenase) and lung barrier damage (i.e. protein concentration) as measured in bronchoalveolar lavage fluid. The results indicate that particles from burning candles are hazardous and this indoor emission source is an important contribution to the health risk of exposure to PM. [ABSTRACT FROM AUTHOR]

To date, the use and translation of nanomedicine from the laboratory to the clinic has been relatively slow. Among other issues, one of the reasons for this tardiness is the lack of the availability of quick and reliable toxicity tools for the screening of nanomaterials (NMs). In this investigation, we apply a flow cytometry-based method for the detection of nanomaterialinduced oxidative stress by measurement of reactive oxygen species production in specific leukocyte subpopulations in human whole blood. The screening of a panel of relevant nanomedical-associated materials (liposomes, silica, iron oxide and functionalized single-walled carbon nanotubes) demonstrated that only the carbon nanotubes induced oxidative stress in human circulating leukocytes. In summary, we apply and corroborate a flow cytometry-based method for the simple and effective measurement of NM-induced oxidative stress in human blood subpopulations after realistic and relevant exposure scenarios which is extremely useful in future toxicological applications. [ABSTRACT FROM AUTHOR]

This study investigated a number of biomarkers, associated with systemic inflammation as well as genotoxicity, in 53 young and healthy subjects participating in a course to become firefighters, while wearing personal protective equipment (PPE). The exposure period consisted of a 3-day training course where the subjects participated in various live-fire training exercises. The subjects were instructed to extinguish fires of either wood or wood with electrical cords and mattresses. The personal exposure was measured as dermal polycyclic aromatic hydrocarbon (PAH) concentrations and urinary excretion of 1-hydroxypyrene (1-OHP). The subjects were primarily exposed to particulate matter (PM) in by-stander positions, since the self-contained breathing apparatus effectively prevented pulmonary exposure. There was increased dermal exposure to pyrene (68.1%, 95% CI: 52.5%, 83.8%) and sum of 16 polycyclic aromatic hydrocarbons (ΣPAH; 79.5%, 95% CI: 52.5%, 106.6%), and increased urinary excretion of 1-OHP (70.4%, 95% CI: 52.5%; 106.6%) after the firefighting exercise compared with the mean of two control measurements performed 2 weeks before and 2 weeks after the firefighting course, respectively. The level of Fpg-sensitive sites in peripheral blood mononuclear cells (PBMCs) was increased by 8.0% (95% CI: 0.02%, 15.9%) compared with control measurements. The level of DNA strand breaks was positively associated with dermal exposure to pyrene and ΣPAHs and urinary excretion of 1-OHP. Fpg-sensitive sites were only associated positively with PAHs. Biomarkers of inflammation and lung function showed no consistent response. In summary, the study demonstrated that PAH exposure during firefighting activity was associated with genotoxicity in PBMCs. [ABSTRACT FROM AUTHOR]

BACKGROUND: A rich body of literature exists that has demonstrated adverse human health effects following exposure to ambient air particulate matter (PM), and there is strong support for an important role of ultrafine (nanosized) particles. At present, relatively few human health or epidemiology data exist for engineered nanomaterials (NMs) despite clear parallels in their physicochemical properties and biological actions in in vitro models. OBJECTIVES: NMs are available with a range of physicochemical characteristics, which allows a more systematic toxicological analysis. Therefore, the study of ultrafine particles (UFP, <100 nm in diameter) provides an opportunity to identify plausible health effects for NMs, and the study of NMs provides an opportunity to facilitate the understanding of the mechanism of toxicity of UFP. METHODS: A workshop of experts systematically analyzed the available information and identified 19 key lessons that can facilitate knowledge exchange between these discipline areas. DISCUSSION: Key lessons range from the availability of specific techniques and standard protocols for physicochemical characterization and toxicology assessment to understanding and defining dose and the molecular mechanisms of toxicity. This review identifies a number of key areas in which additional research prioritization would facilitate both research fields simultaneously. CONCLUSION: There is now an opportunity to apply knowledge from NM toxicology and use it to better inform PM health risk research and vice versa. [ABSTRACT FROM AUTHOR]