Assessing the risk of importing dengue and chikungunya viruses to the European Union

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High-resolution airborne imaging DOAS measurements of NO2 above Bucharest during AROMAT

In this study we report on airborne imaging DOAS measurements of NO2 from two flights performed in Bucharest during the AROMAT campaign (Airborne ROmanian Measurements of Aerosols and Trace gases) in September 2014. These measurements were performed with the Airborne imaging Differential Optical Absorption Spectroscopy (DOAS) instrument for Measurements of Atmospheric Pollution (AirMAP) and provide nearly gapless maps of column densities of NO2 below the aircraft with a high spatial resolution of better than 100 m. The air mass factors, which are needed to convert the measured differential slant column densities (dSCDs) to vertical column densities (VCDs), have a strong dependence on the surface reflectance, which has to be accounted for in the retrieval. This is especially important for measurements above urban areas, where the surface properties vary strongly. As the instrument is not radiometrically calibrated, we have developed a method to derive the surface reflectance from intensities measured by AirMAP. This method is based on radiative transfer calculation with SCIATRAN and a reference area for which the surface reflectance is known. While surface properties are clearly apparent in the NO2 dSCD results, this effect is successfully corrected for in the VCD results. Furthermore, we investigate the influence of aerosols on the retrieval for a variety of aerosol profiles that were measured in the context of the AROMAT campaigns. The results of two research flights are presented, which reveal distinct horizontal distribution patterns and strong spatial gradients of NO2 across the city. Pollution levels range from background values in the outskirts located upwind of the city to about 4  ×  1016 molec cm−2 in the polluted city center. Validation against two co-located mobile car-DOAS measurements yields good agreement between the datasets, with correlation coefficients of R =  0.94 and R =  0.85, respectively. Estimations on the NOx emission rate of Bucharest for the two flights yield emission rates of 15.1 ± 9.4 and 13.6 ± 8.4 mol s−1, respectively

Repression of human papillomavirus oncogene expression under hypoxia is mediated by PI3K/mTORC2/AKT signaling

Oncogenic HPV types are major human carcinogens. Under hypoxia, HPV-positive cancer cells can repress the viral E6/E7 oncogenes and induce a reversible growth arrest. This response could contribute to therapy resistance, immune evasion, and tumor recurrence upon reoxygenation. Here, we uncover evidence that HPV oncogene repression is mediated by hypoxia-induced activation of canonical PI3K/mTORC2/AKT signaling. AKT-dependent downregulation of E6/E7 is only observed under hypoxia and occurs, at least in part, at the transcriptional level. Quantitative proteome analyses identify additional factors as candidates to be involved in AKT-dependent E6/E7 repression and/or hypoxic PI3K/mTORC2/AKT activation. These results connect PI3K/mTORC2/AKT signaling with HPV oncogene regulation, providing new mechanistic insights into the cross talk between oncogenic HPVs and their host cells.Hypoxia is linked to therapeutic resistance and poor clinical prognosis for many tumor entities, including human papillomavirus (HPV)-positive cancers. Notably, HPV-positive cancer cells can induce a dormant state under hypoxia, characterized by a reversible growth arrest and strong repression of viral E6/E7 oncogene expression, which could contribute to therapy resistance, immune evasion and tumor recurrence. The present work aimed to gain mechanistic insights into the pathway(s) underlying HPV oncogene repression under hypoxia. We show that E6/E7 downregulation is mediated by hypoxia-induced stimulation of AKT signaling. Ablating AKT function in hypoxic HPV-positive cancer cells by using chemical inhibitors efficiently counteracts E6/E7 repression. Isoform-specific activation or downregulation of AKT1 and AKT2 reveals that both AKT isoforms contribute to hypoxic E6/E7 repression and act in a functionally redundant manner. Hypoxic AKT activation and consecutive E6/E7 repression is dependent on the activities of the canonical upstream AKT regulators phosphoinositide 3-kinase (PI3K) and mechanistic target of rapamycin (mTOR) complex 2 (mTORC2). Hypoxic downregulation of E6/E7 occurs, at least in part, at the transcriptional level. Modulation of E6/E7 expression by the PI3K/mTORC2/AKT cascade is hypoxia specific and not observed in normoxic HPV-positive cancer cells. Quantitative proteome analyses identify additional factors as candidates to be involved in hypoxia-induced activation of the PI3K/mTORC2/AKT signaling cascade and in the AKT-dependent repression of the E6/E7 oncogenes under hypoxia. Collectively, these data uncover a functional key role of the PI3K/mTORC2/AKT signaling cascade for viral oncogene repression in hypoxic HPV-positive cancer cells and provide new insights into the poorly understood cross talk between oncogenic HPVs and their host cells under hypoxia

Ursinus College Bulletin Vol. 9, No. 5, February 1893

A digitized copy of the February 1893 Ursinus College Bulletin.https://digitalcommons.ursinus.edu/ucbulletin/1083/thumbnail.jp

Studies of the horizontal inhomogeneities in NO2 concentrations above a shipping lane using ground-based multi-axis differential optical absorption spectroscopy (MAX-DOAS) measurements and validation with airborne imaging DOAS measurements

This study describes a novel application of an “onion-peeling” approach to multi-axis differential optical absorption spectroscopy (MAX-DOAS) measurements of shipping emissions aiming at investigating the strong horizontal inhomogeneities in NO2 over a shipping lane. To monitor ship emissions on the main shipping route towards the port of Hamburg, a two-channel (UV and visible) MAX-DOAS instrument was deployed on the island Neuwerk in the German Bight, 6–7 km south of the main shipping lane. Utilizing the fact that the effective light path length in the atmosphere depends systematically on wavelength, simultaneous measurements and DOAS retrievals in the UV and visible spectral ranges are used to probe air masses at different horizontal distances to the instrument to estimate two-dimensional pollutant distributions. Two case studies have been selected to demonstrate the ability to derive the approximate plume positions in the observed area. A situation with northerly wind shows high NO2 concentrations close to the measurement site and low values in the north of the shipping lane. The opposite situation with southerly wind, unfavorable for the on-site in situ instrumentation, demonstrates the ability to detect enhanced NO2 concentrations several kilometers away from the instrument. Using a Gaussian plume model, in-plume NO2 volume mixing ratios can be derived from the MAX-DOAS measurements. For validation, a comparison to airborne imaging DOAS measurements during the NOSE campaign in July 2013 is performed, showing good agreement between the approximate plume position derived from the onion-peeling MAX-DOAS and the airborne measurements as well as between the derived in-plume NO2 volume mixing ratios (VMRs)

Subtype-specific differentiation of cardiac pacemaker cell clusters from human induced pluripotent stem cells

Background: Human induced pluripotent stem cells (hiPSC) harbor the potential to differentiate into diverse cardiac cell types. Previous experimental efforts were primarily directed at the generation of hiPSC-derived cells with ventricular cardiomyocyte characteristics. Aiming at a straightforward approach for pacemaker cell modeling and replacement, we sought to selectively differentiate cells with nodal-type properties. Methods: hiPSC were differentiated into spontaneously beating clusters by co-culturing with visceral endoderm-like cells in a serum-free medium. Subsequent culturing in a specified fetal bovine serum (FBS)-enriched cell medium produced a pacemaker-type phenotype that was studied in detail using quantitative real-time polymerase chain reaction (qRT-PCR), immunocytochemistry, and patch-clamp electrophysiology. Further investigations comprised pharmacological stimulations and co-culturing with neonatal cardiomyocytes. Results: hiPSC co-cultured in a serum-free medium with the visceral endoderm-like cell line END-2 produced spontaneously beating clusters after 10–12 days of culture. The pacemaker-specific genes HCN4, TBX3, and TBX18 were abundantly expressed at this early developmental stage, while levels of sarcomeric gene products remained low. We observed that working-type cardiomyogenic differentiation can be suppressed by transfer of early clusters into a FBS-enriched cell medium immediately after beating onset. After 6 weeks under these conditions, sinoatrial node (SAN) hallmark genes remained at high levels, while working-type myocardial transcripts (NKX2.5, TBX5) were low. Clusters were characterized by regular activity and robust beating rates (70–90 beats/min) and were triggered by spontaneous Ca2+ transients recapitulating calcium clock properties of genuine pacemaker cells. They were responsive to adrenergic/cholinergic stimulation and able to pace neonatal rat ventricular myocytes in co-culture experiments. Action potential (AP) measurements of cells individualized from clusters exhibited nodal-type (63.4%) and atrial-type (36.6%) AP morphologies, while ventricular AP configurations were not observed. Conclusion: We provide a novel culture media-based, transgene-free approach for targeted generation of hiPSC-derived pacemaker-type cells that grow in clusters and offer the potential for disease modeling, drug testing, and individualized cell-based replacement therapy of the SAN

Inhibition of Histone Deacetylases Induces K+ Channel Remodeling and Action Potential Prolongation in HL-1 Atrial Cardiomyocytes

Background/Aims: Cardiac arrhythmias are triggered by environmental stimuli that may modulate expression of cardiac ion channels. Underlying epigenetic regulation of cardiac electrophysiology remains incompletely understood. Histone deacetylases (HDACs) control gene expression and cardiac integrity. We hypothesized that class I/II HDACs transcriptionally regulate ion channel expression and determine action potential duration (APD) in cardiac myocytes. Methods: Global class I/II HDAC inhibition was achieved by administration of trichostatin A (TSA). HDAC-mediated effects on K+ channel expression and electrophysiological function were evaluated in murine atrial cardiomyocytes (HL-1 cells) using real-time PCR, Western blot, and patch clamp analyses. Electrical tachypacing was employed to recapitulate arrhythmia-related effects on ion channel remodeling in the absence and presence of HDAC inhibition. Results: Global HDAC inhibition increased histone acetylation and prolonged APD90 in atrial cardiomyocytes compared to untreated control cells. Transcript levels of voltage-gated or inwardly rectifying K+ channels Kcnq1, Kcnj3 and Kcnj5 were significantly reduced, whereas Kcnk2, Kcnj2 and Kcnd3 mRNAs were upregulated. Ion channel remodeling was similarly observed at protein level. Short-term tachypacing did not induce significant transcriptional K+ channel remodeling. Conclusion: The present findings link class I/II HDAC activity to regulation of ion channel expression and action potential duration in atrial cardiomyocytes. Clinical implications for HDAC-based antiarrhythmic therapy and cardiac safety of HDAC inhibitors require further investigation

Validation of Sentinel-5P TROPOMI tropospheric NO2 products by comparison with NO2 measurements from airborne imaging, ground-based stationary, and mobile car DOAS measurements during the S5P-VAL-DE-Ruhr campaign

Airborne imaging differential optical absorption spectroscopy (DOAS), ground-based stationary and car DOAS measurements were conducted during the S5P-VAL-DE-Ruhr campaign in September 2020. The campaign area is located in the Rhine-Ruhr region of North Rhine-Westphalia, Western Germany, which is a pollution hotspot in Europe comprising urban and large industrial emitters. The measurements are used to validate space-borne NO2 tropospheric vertical column density data products from the Sentinel-5 Precursor (S5P) TROPOspheric Monitoring Instrument (TROPOMI). Seven flights were performed with the airborne imaging DOAS instrument for measurements of atmospheric pollution (AirMAP), providing measurements which were used to create continuous maps of NO2 in the layer below the aircraft. These flights cover many S5P ground pixels within an area of 30 km x 35 km and were accompanied by ground-based stationary measurements and three mobile car DOAS instruments. Stationary measurements were conducted by two Pandora, two zenith-sky and two MAX-DOAS instruments distributed over three target areas. Ground-based stationary and car DOAS measurements are used to evaluate the AirMAP tropospheric NO2 vertical column densities and show high Pearson correlation coefficients of 0.87 and 0.89 and slopes of 0.93 &plusmn; 0.09 and 0.98 &plusmn; 0.02 for the stationary and car DOAS, respectively. Having a spatial resolution of about 100 m x 30 m, the AirMAP tropospheric NO2 vertical column density (VCD) data creates a link between the ground-based and the TROPOMI measurements with a resolution of 3.5 km x 5.5 km and is therefore well suited to validate the TROPOMI tropospheric NO2 VCD. The measurements on the seven flight days show strong NO2 variability, which is dependent on the different target areas, the weekday, and the meteorological conditions. The AirMAP campaign dataset is compared to the TROPOMI NO2 operational off-line (OFFL) V01.03.02 data product, the reprocessed NO2 data, using the V02.03.01 of the official L2 processor, provided by the Product Algorithm Laboratory (PAL), and several scientific TROPOMI NO2 data products. The TROPOMI data products and the AirMAP data are highly correlated with correlation coefficients between 0.72 and 0.87, and slopes of 0.38 &plusmn; 0.02 to 1.02 &plusmn; 0.07. On average, TROPOMI tropospheric NO2 VCDs are lower than the AirMAP NO2 results. The slope increased from 0.38 &plusmn; 0.02 for the operational OFFL V01.03.02 product to 0.83 &plusmn; 0.06 after the improvements in the retrieval of the PAL V02.03.01 product were implemented. Different auxiliary data, such as spatially higher resolved a priori NO2 vertical profiles, surface reflectivity and the cloud treatment, are investigated using scientific TROPOMI tropospheric NO2 VCD data products to evaluate their impact on the operational TROPOMI NO2 VCD data product. The comparison of the AirMAP campaign dataset to the scientific data products shows that the choice of surface reflectivity data base has a minor impact on the tropospheric NO2 VCD retrieval in the campaign region and season. In comparison, the replacement of the a priori NO2 profile in combination with the improvements in the retrieval of the PAL V02.03.01 product regarding cloud heights has a major impact on the tropospheric NO2 VCD retrieval and increases the slope from 0.88 &plusmn; 0.06 to 1.00 &plusmn; 0.07. This study demonstrates that the underestimation of the TROPOMI tropospheric NO2 VCD product with respect to the validation dataset has been and can be further significantly improved.</p

I-MOVE Multi-Centre Case Control Study 2010-11: Overall and Stratified Estimates of Influenza Vaccine Effectiveness in Europe

BACKGROUND: In the third season of I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe), we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in eight European Union (EU) member states to estimate 2010/11 influenza vaccine effectiveness (VE) against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. METHODS: Using systematic sampling, practitioners swabbed ILI/ARI patients within seven days of symptom onset. We compared influenza-positive to influenza laboratory-negative patients among those meeting the EU ILI case definition. A valid vaccination corresponded to > 14 days between receiving a dose of vaccine and symptom onset. We used multiple imputation with chained equations to estimate missing values. Using logistic regression with study as fixed effect we calculated influenza VE adjusting for potential confounders. We estimated influenza VE overall, by influenza type, age group and among the target group for vaccination. RESULTS: We included 2019 cases and 2391 controls in the analysis. Adjusted VE was 52% (95% CI 30-67) overall (N = 4410), 55% (95% CI 29-72) against A(H1N1) and 50% (95% CI 14-71) against influenza B. Adjusted VE against all influenza subtypes was 66% (95% CI 15-86), 41% (95% CI -3-66) and 60% (95% CI 17-81) among those aged 0-14, 15-59 and ≥60 respectively. Among target groups for vaccination (N = 1004), VE was 56% (95% CI 34-71) overall, 59% (95% CI 32-75) against A(H1N1) and 63% (95% CI 31-81) against influenza B. CONCLUSIONS: Results suggest moderate protection from 2010-11 trivalent influenza vaccines against medically-attended ILI laboratory-confirmed as influenza across Europe. Adjusted and stratified influenza VE estimates are possible with the large sample size of this multi-centre case-control. I-MOVE shows how a network can provide precise summary VE measures across Europe