Bisphenol A (BPA) is a synthetic compound widely used for the production of polycarbonate plasticware and epoxy resins. BPA exposure is widespread and more than 90% of individuals have detectable amounts of the molecule in their body fluids, which originates primarily from diet. Here, we investigated whether prenatal exposure to BPA affects the mevalonate (MVA) pathway in rat brain fetuses, and whether potential effects are sex-dependent. The MVA pathway is important for brain development and function. Our results demonstrate that the fetal brain, exposed in utero to a very low dose of BPA (2.5 µg/kg/day), displayed altered MVA pathway activation, increased protein prenylation, and a decreased level of pro-BDNF. Interestingly, the BPA-induced effects on estrogen receptor α were sex-dependent. In conclusion, this work demonstrates intergenerational effects of BPA on the brain at very low doses. Our results reveal new targets for BPA-induced interference and underline the impacts of BPA on health.

Long-term homogeneous climate data records (CDRs) are essential to diagnose changes in our climate, understand its variability, and assess and contextualize future climate projections (Cramer et al., 2018). Use of CDRs influenced by residual non-climatic factors may lead to incorrect conclusions about the changing state of the climate (Kivinen et al., 2017). Therefore, when CDRs are used it is highly desirable to:

Climate trends estimated using historical radiosounding time series may be significantly affected by the choice of the regression method to use, as well as by a subsampling of the dataset often adopted in specific applications. These are contributions to the uncertainty of trend estimations, which have been quantified in literature, although on specific pairs of regression methods, and in the not very recent past characterized by smaller trends in temperature than those observed over the last two decades. This paper investigates the sensitivity of trend estimations to four linear regression methods (parametric and nonparametric) and to the artificial subsampling of the same dataset using historical radiosounding time series from 1978 onwards, available in the version 2 of the Integrated Global Radiosonde Archive (IGRA). Results show that long-term decadal trends may have not negligible uncertainties related to the choice of the regression method, the percentage of data available, the amount of missing data and the number of stations selected in the dataset. The choice of the regression methods increases uncertainties in the decadal trends ranging from −0.10 to −0.01 KÁda-1 for temperature in the lower stratosphere at 100 hPa and from 0.2 to 0.8% da-1 for relative humidity (RH) in the middle troposphere at 300 hPa. Differences can also increase up to 0.4 KÁda-1 at 300 hPa when the amount of missing data exceeds 50% of the original dataset for temperature, while for RH, significant differences are observed in the lower troposphere at 925 hPa for almost all datasets. Finally, subsampling effects on trend estimation are quantified by artificially reducing the size of the IGRA dataset: Results show that subsampling effects on trend estimations when at least 60 stations, up to 76% of data available, are considered for temperature and at least 40 stations for RH.

Abstract. Observational records are essential for assessing long-term changes in our climate. However, these records are more often than not influenced by residual non‐climatic factors which must be detected and adjusted prior to their usage. Ideally, measurement uncertainties should be properly quantified and validated. In the context of the Copernicus Climate Change Service (C3S), a novel approach, named RHARM (Radiosounding HARMonization), has been developed to provide a harmonized dataset of temperature, humidity and wind profiles along with an estimation of the measurement uncertainties for about 650 radiosounding stations globally. The RHARM method has been applied to IGRA daily (0000 and 1200 UTC) radiosonde data holdings on 16 standard pressure levels (from 1000 to 10 hPa) from 1978 to present. Relative humidity adjustment and data provision has been limited to 250 hPa owing to pervasive issues on sensors' performance in the upper troposphere and lower stratosphere. The applied adjustments are interpolated to all reported significant levels to retain information content contained within each individual ascent profile. Each historical station time series is harmonized using two distinct methods. Firstly, the most recent period of the records when modern radiosonde models have been in operation at each station (typically starting between 2004 and 2010 but varying on a station-by-station basis) are post-processed and adjusted using reference datasets from the GCOS Reference Upper Air Network (GRUAN) and from the 2010 WMO/CIMO (World Meteorological Organization/Commission for Instruments and Methods of Observation) radiosonde intercomparison. Subsequently, at each mandatory pressure level, the remaining historical data are scanned backward in time to detect structural breaks due to prolonged systematic effects in the measurements and then adjusted to homogenize the time series. This paper describes the dataset portion related to the adjustment of post-2004 measurements only. A step-by-step description of the algorithm is reported and comparisons with GRUAN and atmospheric reanalysis data for temperature and relative humidity data are discussed. The evaluation shows that the strongest benefit of RHARM compared to existing products is related to the substantive adjustments applied to relative humidity time series for values below 15 % and above 55 % as well as to the provision of the uncertainties for all variables. Uncertainties have been validated using the ECMWF reanalysis short-range forecast outputs. The RHARM algorithm is the first to provide homogenized time series of temperature, relative humidity and wind profiles alongside an estimation of the observational uncertainty for each single observation at each pressure level. A subset of RHARM dataisavailable at https://doi.org/10.5281/zenodo.3973353 (Madonnaet al., 2020a)

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