An insight into the complex roles of metallothioneins in malignant diseases with emphasis on (sub)isoforms/isoforms and epigenetics phenomena

L

The use of a silicone-based biomembrane for microaerobic H2S removal from biogas

A lab-scale bio-membrane unit was developed to improve H2S removal from biogas through microaeration. Biomembrane separated biogas from air and consisted of a silicone tube covered by microaerobic biofilm. This setup allowed efficient H2S removal while minimizing biogas contamination with oxygen and nitrogen. The transport and removal of H2S, N-2, O-2, CH4 and CO2 through bare membrane, wet membrane and biomembrane was investigated. Membrane allowed the transfer of gases through it as long as there was enough driving force to induce it. H2S concentration in biogas decreased much faster with the biomembrane. The permeation of gases through the membranes decreased in order: H2S > CO2 > CH4 > O-2 > N-2. H2S removal efficiency of more than 99% was observed during the continuous experiment. Light yellow deposits on the membrane indicated the possible elemental sulfur formation due to biological oxidation of H2S. Thiobacillus thioparus was detected by FISH and PCR-DGGE

European aerosol phenomenology - 8 : Harmonised source apportionment of organic aerosol using 22 Year-long ACSM/AMS datasets

Organic aerosol (OA) is a key component of total submicron particulate matter (PM1), and comprehensive knowledge of OA sources across Europe is crucial to mitigate PM1 levels. Europe has a well-established air quality research infrastructure from which yearlong datasets using 21 aerosol chemical speciation monitors (ACSMs) and 1 aerosol mass spectrometer (AMS) were gathered during 2013-2019. It includes 9 non-urban and 13 urban sites. This study developed a state-of-the-art source apportionment protocol to analyse long-term OA mass spectrum data by applying the most advanced source apportionment strategies (i.e., rolling PMF, ME-2, and bootstrap). This harmonised protocol was followed strictly for all 22 datasets, making the source apportionment results more comparable. In addition, it enables quantification of the most common OA components such as hydrocarbon-like OA (HOA), biomass burning OA (BBOA), cooking-like OA (COA), more oxidised-oxygenated OA (MO-OOA), and less oxidised-oxygenated OA (LO-OOA). Other components such as coal combustion OA (CCOA), solid fuel OA (SFOA: mainly mixture of coal and peat combustion), cigarette smoke OA (CSOA), sea salt (mostly inorganic but part of the OA mass spectrum), coffee OA, and ship industry OA could also be separated at a few specific sites. Oxygenated OA (OOA) components make up most of the submicron OA mass (average = 71.1%, range from 43.7 to 100%). Solid fuel combustion-related OA components (i.e., BBOA, CCOA, and SFOA) are still considerable with in total 16.0% yearly contribution to the OA, yet mainly during winter months (21.4%). Overall, this comprehensive protocol works effectively across all sites governed by different sources and generates robust and consistent source apportionment results. Our work presents a comprehensive overview of OA sources in Europe with a unique combination of high time resolution (30-240 min) and long-term data coverage (9-36 months), providing essential information to improve/validate air quality, health impact, and climate models.Peer reviewe

Results of the first European Source Apportionment intercomparison for Receptor and Chemical Transport Models

In this study, the performance of the source apportionment model applications were evaluated by comparing the model results provided by 44 participants adopting a methodology based on performance indicators: z-scores and RMSEu, with pre-established acceptability criteria. Involving models based on completely different and independent input data, such as receptor models (RMs) and chemical transport models (CTMs), provided a unique opportunity to cross-validate them. In addition, comparing the modelled source chemical profiles, with those measured directly at the source contributed to corroborate the chemical profile of the tested model results. The most used RM was EPA- PMF5. RMs showed very good performance for the overall dataset (91% of z-scores accepted) and more difficulties are observed with SCE time series (72% of RMSEu accepted). Industry resulted the most problematic source for RMs due to the high variability among participants. Also the results obtained with CTMs were quite comparable to their ensemble reference using all models for the overall average (>92% of successful z-scores) while the comparability of the time series is more problematic (between 58% and 77% of the candidates’ RMSEu are accepted). In the CTM models a gap was observed between the sum of source contributions and the gravimetric PM10 mass likely due to PM underestimation in the base case. Interestingly, when only the tagged species CTM results were used in the reference, the differences between the two CTM approaches (brute force and tagged species) were evident. In this case the percentage of candidates passing the z-score and RMSEu tests were only 50% and 86%, respectively. CTMs showed good comparability with RMs for the overall dataset (83% of the z-scores accepted), more differences were observed when dealing with the time series of the single source categories. In this case the share of successful RMSEu was in the range 25% - 34%.JRC.C.5-Air and Climat

Two sisters with cardiac‐urogenital syndrome secondary to pathogenic splicing variant in the MYRF gene with unaffected parents: A case of gonadal mosaicism?

Abstract Background Cardiac‐urogenital syndrome [MIM # 618280] is a newly described very rare syndrome associated with pathogenic variants in the myelin regulatory factor (MYRF) gene that leads to loss of protein function. MYRF is a transcription factor previously associated only with the control of myelin‐related gene expression. However, it is also highly expressed in other tissues and associated with various organ anomalies. The clinical picture is primarily dominated by complex congenital cardiac developmental defects, pulmonary hypoplasia, congenital diaphragmatic hernia, and urogenital malformations. Case Presentation We present case reports of two siblings of unrelated parents in whom whole‐exome sequencing was indicated due to familial occurrence of extensive developmental defects. A new, previously undescribed splicing pathogenic variant c.1388+2T>G in the MYRF gene has been identified in both patients. Both parents are unaffected, tested negative, and have another healthy daughter. The identical de novo event in siblings suggests gonadal mosaicism, which can mimic recessive inheritance. Conclusions To our knowledge, this is the first published case of familial cardiac‐urogenital syndrome indicating gonadal mosaicism

Training and test datasets for the PredictONCO tool

<p>This dataset was used for training and validating the <a href="https://loschmidt.chemi.muni.cz/predictonco/">PredictONCO </a>web tool, supporting decision-making in precision oncology by extending the bioinformatics predictions with advanced computing and machine learning. The dataset consists of 1073 single-point mutants of 42 proteins, whose effect was classified as Oncogenic (509 data points) and Benign (564 data points). All mutations were annotated with a clinically verified effect and were compiled from the ClinVar and OncoKB databases. The dataset was manually curated based on the available information in other precision oncology databases (The Clinical Knowledgebase by The Jackson Laboratory, Personalized Cancer Therapy Knowledge Base by MD Anderson Cancer Center, cBioPortal, DoCM database) or in the primary literature. To create the dataset, we also removed any possible overlaps with the data points used in the PredictSNP consensus predictor and its constituents. This was implemented to avoid any test set data leakage due to using the PredictSNP score as one of the features (see below).</p><p>The entire dataset (<strong>SEQ</strong>) was further annotated by the pipeline of PredictONCO. Briefly, the following six features were calculated regardless of the structural information available: essentiality of the mutated residue (yes/no), the conservation of the position (the conservation grade and score), the domain where the mutation is located (cytoplasmic, extracellular, transmembrane, other), the PredictSNP score, and the number of essential residues in the protein. For approximately half of the data (<strong>STR</strong>: 377 and 76 oncogenic and benign data points, respectively), the structural information was available, and six more features were calculated: FoldX and Rosetta ddg_monomer scores, whether the residue is in the catalytic pocket (identification of residues forming the ligand-binding pocket was obtained from P2Rank), and the pKa changes (the minimum and maximum changes as well as the number of essential residues whose pKa was changed – all values obtained from PROPKA3). For both <strong>STR </strong>and <strong>SEQ </strong>datasets, 20% of the data was held out for testing. The data split was implemented at the position level to ensure that no position from the test data subset appears in the training data subset. </p><p>For more details about the tool, please visit the <a href="https://loschmidt.chemi.muni.cz/predictonco/help">help page</a> or <a href="https://loschmidt.chemi.muni.cz/peg/contact/">get in touch with us</a>.</p&gt