Semi-automated water sampling module for repeated sampling and concentration of Bacillus cereus group spores.

Monitoring the presence of pathogenic Bacillus spores is important for industrial applications, as well as necessary for ensuring human health. Bacillus thuringiensis is used as a biopesticide against several insect pests. Bacillus cereus spores are a significant cause of food poisoning, and Bacillus anthracis is a recognized biosecurity threat. Laboratory-based methods, such as polymerase chain reaction, enzyme-linked immunosorbent assay, or matrix-assisted laser desorption ionization spectroscopy provide sensitive detection of bacteria and spores, but the application of those methods for quasi-continuous environmental monitoring presents a significant challenge requiring frequent human intervention. To address this challenge, we developed a workstation for quasi-autonomous monitoring of water reservoirs for the presence of bacteria and spores, and designed and validated the functionality of a microprocessor-controlled module capable of repetitive collection and pre-concentration of spores in liquid samples tested with fiberglass (FG), polyether sulfone and polyvinylidene fluoride filters. The best results were obtained with FG filters delivering a 20× concentration of B. thuringiensis and B. cereus spores from saline suspensions. The successful 20× pre-concentration of Bacillus spores demonstrated with FG filters could be repeated up to 3 times when bleach decontamination is applied between filtrations. Taken together, our results demonstrate an attractive instrument suitable for semi-automated, quasi-continuous sampling and pre-processing of water samples for biosensing of bacterial spores originating from a complex environment.

Rapid, Sensitive, and Selective Quantification of Bacillus cereus Spores Using xMAP Technology.

Bacillus cereus is a spore-forming ubiquitous bacterium notable as a food poisoning agent. Detection of B. cereus spores using selective media is laborious and non-specific. Herein, the quantitative detection of B. cereus spores was investigated with commercial antibodies and published aptamer sequences. Several detection reagents were screened for affinity to Bacillus collagen-like protein A (BclA), an abundant exosporium glycoprotein. Sensitivity and selectivity toward B. cereus spores were tested using immunoassays and multi-analyte profiling (xMAP). A recombinant antibody developed in llama against BclA protein showed B. cereus spore selectivity and sensitivity between 102 and 105 spores/mL using xMAP. DNA aptamer sequences demonstrated sensitivity from 103 to 107 spores/mL and no cross-reaction to B. megaterium and B. subtilis. Selectivity for B. cereus spores was also demonstrated in a mixture of several diverse microorganisms and within a food sample with no compromise of sensitivity. As proof of concept for multiplexed measurement of human pathogens, B. cereus and three other microorganisms, E. coli, P. aeruginosa, and S. cerevisiae, were simultaneously detected using xMAP. These data support the development of a rapid, sensitive, and selective system for quantitation of B. cereus spores and multiplexed monitoring of human pathogens in complex matrices.

Selective Detection of Legionella pneumophila Serogroup 1 and 5 with a Digital Photocorrosion Biosensor Using Antimicrobial Peptide-Antibody Sandwich Strategy.

Rapid detection of Legionella pneumophila (L. pneumophila) is important for monitoring the presence of these bacteria in water sources and preventing the transmission of the Legionnaires' disease. We report improved biosensing of L. pneumophila with a digital photocorrosion (DIP) biosensor functionalized with an innovative structure of cysteine-modified warnericin antimicrobial peptides for capturing bacteria that are subsequently decorated with anti-L. pneumophila polyclonal antibodies (pAbs). The application of peptides for the operation of a biosensing device was enabled by the higher bacterial-capture efficiency of peptides compared to other traditional ligands, such as those based on antibodies or aptamers. At the same time, the significantly stronger affinity of pAbs decorating the L. pneumophila serogroup-1 (SG-1) compared to serogroup-5 (SG-5) allowed for the selective detection of L. pneumophila SG-1 at 50 CFU/mL. The results suggest that the attractive sensitivity of the investigated sandwich method is related to the flow of an extra electric charge between the pAb and a charge-sensing DIP biosensor. The method has the potential to offer highly specific and sensitive detection of L. pneumophila as well as other pathogenic bacteria and viruses.

Impact of COVID-19 pandemic on psychological wellbeing of Oncology clinicians in the Middle East and North Africa (MENA) region.

OBJECTIVE: The reorganization of cancer services and the increased work burden on health care providers during the COVID-19 pandemic are likely to be associated with significant negative psychological impact. The aim of this study is to evaluate the impact of COVID-19 pandemic on the psychological well-being of oncology clinicians in the Middle East and North Africa (MENA) region. MATERIALS AND METHODS: We randomly invited 1500 oncology clinicians including medical oncologists, clinical oncologists, radiation oncologists and surgical oncologists from 17 countries in the MENA region to complete a web-based survey to determine the level of psychological stress during the COVID-19 pandemic from October 2020 to January 2021. The questionnaire was based on the Perceived Stress Scale (PSS), Generalized Anxiety Disorders Scale (GAD-7) and WHO Well-being Index (WHO-5). The data was analyzed using SPSS version 21 and the difference between groups was measured by t-test and ANOVA. RESULTS: Overall, 520 (35%) clinicians including 368 (71%) males and 152 (29%) females participated in the survey with 247 (47%) participants between the ages of 36 to 45 years. Average score of 29.6 for males and 30.2 on PSS-10, indicative of high-perceived stress in both the genders. Compared to males, females had significantly higher anxiety levels on GAD-7 scale (p=.04), but this difference in stress level and well-being was not observed on PSS-10 (p=.134) and WHO -5 well-being index (p=.709). Clinicians of age 25-35 years had significantly higher anxiety levels on GAD-7 scale (p=.004) and higher stress on PSS (p=.000) as compared to other age groups. Age over 55 years was associated with lower levels of anxiety and stress on GAD-7 and PSS. Oncology clinicians working in public sector experienced significantly lower stress as compared to private sector on PSS scale (p=.041). CONCLUSIONS: Anxiety and stress levels among oncology clinicians have significantly increased in COVID-19 pandemic in the MENA region. Females and young clinicians had higher anxiety and stress, while oncology clinicians over the age of 55 years and working in the public sector reported less stress and anxiety. The general wellbeing of clinicians was well preserved even in a highly stressful and anxious situation.

Strategies for capturing Bacillus thuringiensis spores on surfaces of (001) GaAs-based biosensors.

Bacillus thuringiensis (Bt) is used as a bioinsecticide since it effectively kills insect larvae. Bt is also genetically similar to Bacillus cereus (Bc), a well recognized foodborne human pathogen; they are both members of the Bacillus cereus group (BC group). Although approved Bt bioinsecticide products have been confirmed to be non-pathogenic to humans, close monitoring of Bt during dissemination is important for cost considerations and to limit impact on biodiversity towards nontarget organisms. As such, developing rapid, sensitive, and specific tools for quantitative detection of Bt spores during and following spray operations is highly desirable. The goals of this study were to investigate commercially available detection reagents for sensitivity and selectivity in detecting Bt spores, and then functionalize a surface of (001) GaAs used in photonic biosensing. To achieve these goals, we (1) screened commercial antibodies for their capacity to bind recombinant proteins from Bt spores, (2) screened antibodies and aptamers for their sensitivity and selectivity against Bt spores, and (3) tested the efficiency of selected antibodies and aptamers in capturing Bt spores on the surface of functionalized GaAs biochips. Seven genes encoding Bt spore proteins were cloned and expressed in Escherichia coli. The binding of each purified spore antigen was tested by commercially available polyclonal and monoclonal antibodies claimed to exclusively target spores. Of the seven targets, Bacillus collagen-like protein A, was the most abundant protein on Bt spores and demonstrated the strongest binding affinity to all test antibodies. The commercial antibodies (Abs) were also tested for specificity to BC Group versus non-BC Group spores. Three of six commercial antibodies showed selectivity to Bt spores, with recombinant Abs providing the most robust lower range of detection (102 to 6 × 103 spores/mL). The sensitivity and selectivity of three published DNA aptamer sequences demonstrated a wide range of detection sensitivity for Bt spores. Two of the three test aptamers also showed reasonable selectivity towards Bt spores while the third demonstrated reactivity to non-BC Group B. megaterium and B. subtilis. Of the reagents tested, a thiolated aptamer and llama recombinant Ab showed highest Bt spore capture efficiency as measured by spore coverage of the GaAs surface. These results confirm that the selected aptamer and llama rAb can be considered strong candidates for the development of GaAs-based biosensing devices.

Short Ligand, Cysteine-Modified Warnericin RK Antimicrobial Peptides Favor Highly Sensitive Detection of Legionella pneumophila.

Culture-based methods for the detection of Legionella pneumophila are prohibitively slow and frequently inadequate. The problem has been addressed with biosensing technology that employs a variety of ligands for the specific capture of bacteria. However, the limited success of the application of mammalian antibodies, aptamers, and nucleic acid-based probes for sensitive biosensing has generated growing interest in exploring alternative biosensing architectures, such as those based on antimicrobial peptides (AMP) that are known for their attractive therapeutic applications. We report on the successful employment of cysteine-modified warnericin RK AMP for the operation of a highly sensitive biosensor of L. pneumophila based on digital photocorrosion of GaAs/AlGaAs nanoheterostructures. The replacement of the relatively cumbersome procedure commonly applied for the attachment of antibodies to COOH-terminated mercaptohexadecanoic acid self-assembled monolayers has allowed for a significant reduction in the distance at which bacteria are immobilized above the biosensor surface. An important consequence of this approach is the attractive limit of detection of L. pneumophila estimated at 2 × 102 CFU/mL. The target bacteria were captured four times more efficiently than P. fluorescens, B. subtilis, and E. coli, which is highly promising for environmental monitoring.

Hepatotoxicity of Cadmium Telluride Quantum Dots Induced by Mitochondrial Dysfunction.

The aim of this study was to investigate the detailed mechanisms of hepatotoxicity induced by cadmium telluride quantum dots (CdTe-QDs) in BALB/c mice after intravenous injection. The study investigated oxidative stress, apoptosis, and effects on mitochondria as potential mechanistic events to elucidate the observed hepatotoxicity. Oxidative stress in the liver, induced by CdTe-QD exposure, was demonstrated by depletion of total glutathione, an increase in superoxide dismutase activity, and changes in the gene expression of several oxidative stress-related biomarkers. Furthermore, CdTe-QD treatment led to apoptosis in the liver via both intrinsic and extrinsic apoptotic pathways. Effects on mitochondria were evidenced by the enlargement and increase in the number of mitochondria in hepatocytes of treated mice. CdTe-QDs also caused changes in the levels and gene expression of electron transport chain enzymes, depletion of ATP, and an increase in the level of the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a regulator of mitochondrial biogenesis. The findings from this study suggest that CdTe-QDs-induced hepatotoxicity might have originated from mitochondrial effects which resulted in oxidative stress and apoptosis in the liver cells. This study provides insight into the biological effects of CdT-QDs at the tissue level and the detailed mechanisms of their toxicity in animals. The study also provides important data for bridging the gap between in vitro and in vivo testing and risk assessment of these NPs.

Interactive effects of threonine levels and protein source on growth performance and carcass traits, gut morphology, ileal digestibility of protein and amino acids, and immunity in broilers.

An experiment was executed to test the hypothesis that supplementation of dietary threonine (d-Thr), above NRC recommendation to diets containing poorly digestible protein source (PS) may compensate its detrimental effects on overall performance of broilers. In total, nine hundred 1-day-old mixed sex broilers (Ross-308) were randomly distributed over 6 (2 × 3) experimental diets comprising 5 replicates of 30 broilers each for 35 d. The experimental diets contain either soybean meal (SBM) or canola meal (CM) with 3 levels (100, 110, and 120% of NRC recommendation) of d-Thr. During the course of the trial (0 to 35 D), interactions (P < 0.05) between PS and d-Thr were observed for feed intake (FI), body weight gain (BWG), feed conversion ratio (FCR), carcass, and gut health parameters. The broilers fed recommended level (100%) of d-Thr had 7 and 5% poorer FCR compared with those fed diets with 110 and 120% d-Thr, respectively. For villus height (VH), an interaction (P = 0.007) was found between PS and d-Thr level. Broilers consuming SBM diets had 22% longer villi, 10% deeper crypts, and 30% greater VH to crypt depth ratio (VCR) compared to those fed CM. The broilers fed 110% d-Thr diets had 9% lower crypt depth (CD) and 15% greater VCR compared with those fed diets containing NRC recommended levels. CM resulted in 9% lower protein digestibility with lower (P < 0.05) of some AA, whereas it was improved by 7% in broilers fed 120% d-Thr supplemented diets. The bursa and spleen weights were positively affected (P < 0.001) by PS. Threonine supplementation (10%) resulted in 25% greater thymus, 18% heavier bursa, and 30% greater infectious bursal disease titer. In conclusion, supplementation of d-Thr, above NRC recommendation, resulted in a better growth performance and carcass traits, improved ileal digestibility of protein and amino acids, better gut health, and immunity in broilers.

Biodistribution and Systemic Effects in Mice Following Intravenous Administration of Cadmium Telluride Quantum Dot Nanoparticles.

Quantum dots (QDs) are engineered nanoparticles (NPs) of semiconductor structure that possess unique optical and electronic properties and are widely used in biomedical applications; however, their risks are not entirely understood. This study investigated the tissue distribution and toxic effects of cadmium telluride quantum dots (CdTe-QDs) in male BALB/c mice for up to 1 week after single-dose intravenous injections. CdTe-QDs were detected in the blood, lung, heart, liver, spleen, kidney, testis and brain. Most CdTe-QDs accumulated in the liver, followed by the spleen and kidney. At high doses, exposure to CdTe-QDs resulted in mild dehydration, lethargy, ruffled fur, hunched posture, and body weight loss. Histological analysis of the tissues, upon highest dose exposures, revealed hepatic hemorrhage and necrotic areas in the spleen. The sera of mice treated with high doses of CdTe-QDs showed significant increases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin levels, as well as a reduction in albumin. CdTe-QD exposure also led to a reduced number of platelets and elevated total white blood cell counts, including monocytes and neutrophils, serum amyloid A, and several pro-inflammatory cytokines. These results demonstrated that the liver is the main target of CdTe-QDs and that exposure to CdTe-QDs leads to hepatic and splenic injury, as well as systemic effects, in mice. By contrast, cadmium chloride (CdCl2), at an equivalent concentration of cadmium, appeared to have a different pharmacokinetic pattern from that of CdTe-QDs, having minimal effects on the aforementioned parameters, suggesting that cadmium alone cannot fully explain the toxicity of CdTe-QDs.

Exploring nutritive profile, metabolizable energy, protein, and digestible amino acids contents of indigenous protein sources of different locations for male broilers.

2 experiments were conducted to explore nutrient composition, AME, AMEn, standardized ileal digestibility (SID) of CP, and amino acids (AA) of 4 indigenous protein sources including canola meal (CM), rapeseed meal (RSM), guar meal (GM), and sunflower meal (SFM) collected from 2 different locations, Multan (MUL; n = 3) and Sukkur (SKR; n = 3), of Pakistan. Higher (P < 0.05) dry matter (DM), CP, and gross energy (GE), whereas lower (P < 0.05) ash contents were found in SKR, CM, and RSM compared with those from MUL. The MUL GM had higher (P < 0.05) crude fiber (CF) and CP, whereas lower (P < 0.05) GE compared with those from SKR. The SFM from MUL had higher DM, whereas lower CF and CP contents than SKR. In the first experiment, 216 21-d-old male broilers (Ross 308) were distributed over 8 test diets (4 ingredients × 2 locations) and 1 basal diet, with 4 replicates containing 6 birds each (9 × 4 × 6), in a complete randomized design to determine AME and AMEn. The results indicated higher (P < 0.05) AME and AMEn in MUL CM than SKR. In the second experiment, 216 21-d-old male broilers (Ross 308) were raised in 36 cages (6 birds each) to determine SID of CP and AA in a complete randomized design. 8 test diets (4 ingredients × 2 locations) and a protein-free diet, with 4 replicates each, were tested. The SID of CP and some AA were higher (P < 0.05) in MUL CM and RSM than SKR. The SKR GM had a higher (P < 0.05) SID of CP, arginine, methionine, threonine, valine, and cysteine compared with that from MUL. The SFM from MUL had higher (P < 0.05) SID of CP, arginine, histidine, methionine, valine, alanine, aspartate, cysteine, and serine than SKR. In conclusion, major differences do exist between CM, GM, RSM, and SFM from different locations in terms of nutrients, AME, digestible CP, and AA contents for male broilers.

Acellular filtrate of a microbial-based cleaning product potentiates house dust mite allergic lung inflammation.

Microbial-based cleaning products (MBCPs) contain bacteria and chemical constituents. They are used in consumer applications such as odor reduction, unclogging drains, and surface cleaning. To determine the capacity of a model MBCP to contribute to acute allergic lung inflammation, a two-week repeated exposure regimen was used. Mice were exposed by endotracheal instillation to saline alone, MBCP alone, house dust mites (HDM) alone, or sequentially (i.e., MBCP followed by HDM, HDM followed by MBCP, or HDM + MBCP followed by HDM). Both whole MBCP and acellular MBCP filtrate were investigated, and showed minimal differences in the endpoints examined. HDM exposure caused pulmonary perivascular inflammation, bronchiolar mucous cell metaplasia, elevated bronchoalveolar lavage fluid (BALF) eosinophils, and HDM-specific IgG1. For MBCP, notable changes were associated with sequential exposures. MBCP/HDM caused elevated TH2 cytokines in BALF, and elevated neutrophils, eosinophils and IL-5 in peripheral blood. Co-administration of MBCP and HDM followed by HDM resulted in elevated blood and BALF eosinophils and HDM-specific IgE and IgG1. These results demonstrated that acellular MBCP filtrate, and not bacteria within MBCPs, potentiated the acute allergic inflammation to HDM. This methodology could be extended to investigate chronic allergic inflammation and inflammatory potential of other MBCPs and biotechnology products with complex compositions.

The molecular genetics of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis.

Chemotherapy-induced peripheral neuropathy (CIPN) can adversely affect completion of systemic anti-cancer treatment and cause long-term morbidity. Increasingly pharmacogenetic studies have been performed to explore susceptibility to this important adverse effect. A systematic review was conducted to identify pharmacogenetic studies, assess their quality and findings and undertake meta-analysis where possible. 93 studies were included. Notable methodological issues included lack of standardisation and detail in phenotype definition and acknowledgement of potential confounding factors. Insufficient data was presented in many studies meaning only a minority could be included in meta-analysis showing mainly non-significant effects. Nonetheless, SNPs in CYP2C8, CYP3A4, ARHGEF10, EPHA and TUBB2A genes (taxanes), FARS2, ACYP2 and TAC1 (oxaliplatin), and CEP75 and CYP3A5 (vincristine) are of potential interest. These require exploration in large cohort studies with robust methodology and well-defined phenotypes. Seeking standardisation of phenotype, collaboration and subsequently, individual-patient-data meta-analysis may facilitate identifying contributory SNPs which could be combined in a polygenic risk score to predict those most at risk of CIPN.

Incorporating Aptamers in the Multiple Analyte Profiling Assays (xMAP): Detection of C-Reactive Protein.

Aptamers are short oligonucleotide sequences used in detection systems because of their high affinity binding to a variety of macromolecules. With the introduction of aptamers over 25 years ago came the exploration of their use in many different applications as a substitute for antibodies. Aptamers have several advantages; they are easy to synthesize, can bind to analytes for which it is difficult to obtain antibodies, and in some cases bind better than antibodies. As such, aptamer applications have significantly expanded as an adjunct to a variety of different immunoassay designs. The Multiple-Analyte Profiling (xMAP) technology developed by Luminex Corporation commonly uses antibodies for the detection of analytes in small sample volumes through the use of fluorescently coded microbeads. This technology permits the simultaneous detection of multiple analytes in each sample tested and hence could be applied in many research fields. Although little work has been performed adapting this technology for use with apatmers, optimizing aptamer-based xMAP assays would dramatically increase the versatility of analyte detection. We report herein on the development of an xMAP bead-based aptamer/antibody sandwich assay for a biomarker of inflammation (C-reactive protein or CRP). Protocols for the coupling of aptamers to xMAP beads, validation of coupling, and for an aptamer/antibody sandwich-type assay for CRP are detailed. The optimized conditions, protocols and findings described in this research could serve as a starting point for the development of new aptamer-based xMAP assays.

Composition and pathogenic potential of a microbial bioremediation product used for crude oil degradation.

A microbial bioremediation product (MBP) used for large-scale oil degradation was investigated for microbial constituents and possible pathogenicity. Aerobic growth on various media yielded >108 colonies mL-1. Full-length 16S rDNA sequencing and fatty acid profiling from morphologically distinct colonies revealed ≥13 distinct genera. Full-length 16S rDNA library sequencing, by either Sanger or long-read PacBio technology, suggested that up to 21% of the MBP was composed of Arcobacter. Other high abundance microbial constituents (>6%) included the genera Proteus, Enterococcus, Dysgonomonas and several genera in the order Bacteroidales. The MBP was most susceptible to ciprofloxacin, doxycycline, gentamicin, and meropenam. MBP exposure of human HT29 and A549 cells caused significant cytotoxicity, and bacterial growth and adherence. An acellular MBP filtrate was also cytotoxic to HT29, but not A549. Both MBP and filtrate exposures elevated the neutrophil chemoattractant IL-8. In endotracheal murine exposures, bacterial pulmonary clearance was complete after one-week. Elevation of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α, and chemokines KC and MCP-1 occurred between 2h and 48h post-exposure, followed by restoration to baseline levels at 96h. Cytokine/chemokine signalling was accompanied by elevated blood neutrophils and monocytes at 4h and 48h, respectively. Peripheral acute phase response markers were maximal at 24h. All indicators examined returned to baseline values by 168h. In contrast to HT29, but similar to A549 observations, MBP filtrate did not induce significant murine effects with the indicators examined. The results demonstrated the potentially complex nature of MBPs and transient immunological effects during exposure. Products containing microbes should be scrutinized for pathogenic components and subjected to characterisation and quality validation prior to commercial release.

Immunomodulation by gastrointestinal carbon black nanoparticle exposure in ovalbumin T cell receptor transgenic mice.

Humans could become exposed to carbon black nanoparticles (CBNPs) in consumer products or an occupational setting. In rodent models, acute respiratory, subcutaneous, and direct immune cell exposure to CBNPs has been shown to enhance allergic sensitization to co-administered ovalbumin (OVA) protein from chicken egg. However, little is known about the effects of ingested CBNPs on immunological responses and oral tolerance to food antigens. We hypothesized that ingestion of CBNPs would enhance the development of food allergy to OVA. Allergy prone DO11.10 mice were orally exposed to CBNPs every second day for 2 weeks (total dose 10.8 (LOW) or 108 µg (HI)), with and without (±) co-administered OVA. Systemic immune parameters were measured at necropsy. Exposure to OVA resulted in significant increases in serum anti-OVA IgG1, anti-OVA IgM, and anti-OVA IgA antibodies relative to vehicle control. Immunophenotyping revealed a reduction in the number of OVA-specific CD4+ T helper cells upon OVA ± CBNPHI treatment in the spleen. Yet, secretion of the allergy-associated Th2 cytokines IL-4, IL-9, and IL-13 was greater in OVA323-339 peptide-pulsed splenocytes from OVA + CBNPHI-treated mice compared with control. Transcriptome analysis at necropsy of splenocytes from OVA + CBNPHI dose mice compared with OVA mice revealed increases in the allergy associated genes Il4 and Stat6 and decreases in Csf3r and Retnlg. Although oral exposure to high-dose CBNPs did not impact OVA-specific antibody production relative to OVA, we did observe increased expression of genes and cytokines associated with allergy in peripheral splenocytes. This work suggests that CBNP gastrointestinal exposure may potentiate allergy pathways.

Toxicological evaluation of representative silver nanoparticles in macrophages and epithelial cells.

Silver nanoparticles (Ag-NPs) are highly relevant for human and environmental exposure due to their widespread use in consumer and medical products and various applications. Thus, there is a need for evaluating potential toxicity of these NPs. The objective of this study was to investigate the toxic effects of the OECD (Organization for Economic Co-operation and Development) representative Ag-NPs, NM300K, in mouse macrophage J774A.1 and human colonic epithelial HT29 cells, using multiple endpoint assays. Exposure of test cells to different concentrations (1-250 µg/mL; total silver content) of NM300K for 24h showed a dose-dependent decrease in cell viability. At high doses, NM300K altered cell shape and induced the formation of vacuolar structures, as examined by confocal and electron microscopy. Moreover, NM300K induced inflammation as evidenced by the elevated levels of pro-inflammatory cytokines. Finally, high doses of NM300K led to increased production of reactive oxygen species and induction of oxidative stress, leading to oxidative DNA damage and apoptosis in test cells. At equivalent silver concentrations, NM300K were less cytotoxic than AgNO3. However, the similar patterns in the effects of NM300K and AgNO3 throughout the assessed toxicological endpoints suggest that Ag(+) released from these NPs by dissolution could be a primary contributor to toxicity. This study is among the first to characterize the potential toxicity of OECD representative AgNPs in vitro, and provides additional insight into the biological mechanisms associated with Ag-NP toxicity.

UTLS water vapour from SCIAMACHY limb measurementsV3.01 (2002-2012).

The SCanning Imaging Absorption spectroMeter for Atmospheric CHartographY (SCIAMACHY) aboard the Envisat satellite provided measurements from August 2002 until April 2012. SCIAMACHY measured the scattered or direct sunlight using different observation geometries. The limb viewing geometry allows the retrieval of water vapour at about 10-25 km height from the near-infrared spectral range (1353-1410 nm). These data cover the upper troposphere and lower stratosphere (UTLS), a region in the atmosphere which is of special interest for a variety of dynamical and chemical processes as well as for the radiative forcing. Here, the latest data version of water vapour (V3.01) from SCIAMACHY limb measurements is presented and validated by comparisons with data sets from other satellite and in situ measurements. Considering retrieval tests and the results of these comparisons, the V3.01 data are reliable from about 11 to 23 km and the best results are found in the middle of the profiles between about 14 and 20 km. Above 20 km in the extra tropics V3.01 is drier than all other data sets. Additionally, for altitudes above about 19 km, the vertical resolution of the retrieved profile is not sufficient to resolve signals with a short vertical structure like the tape recorder. Below 14 km, SCIAMACHY water vapour V3.01 is wetter than most collocated data sets, but the high variability of water vapour in the troposphere complicates the comparison. For 14-20 km height, the expected errors from the retrieval and simulations and the mean differences to collocated data sets are usually smaller than 10 % when the resolution of the SCIAMACHY data is taken into account. In general, the temporal changes agree well with collocated data sets except for the Northern Hemisphere extratropical stratosphere, where larger differences are observed. This indicates a possible drift in V3.01 most probably caused by the incomplete treatment of volcanic aerosols in the retrieval. In all other regions a good temporal stability is shown. In the tropical stratosphere an increase in water vapour is found between 2002 and 2012, which is in agreement with other satellite data sets for overlapping time periods.