Unfolding existing Data Publication Practice in Research Data Workflows in the Biological and Environmental Sciences – First Results from a Survey

In recent years, data publication workflows get more and more attention [1,2]. In order to obtain FAIR data [3], reviewers, data curators and other stakeholders have realized that not only the submitted data matter but also the underlying process to create that data within existing research practice. A better understanding of existing data publication practices in research workflows will help service providers such as data repositories (Pangaea [4], ENA [5], GenBank [6]) to support their users with more appropriate services and tools when submitting data, and otherwise, will sustain the role of data repositories in research practice. Such improved coordination will minimize the workload of researchers and data curators and will facilitate the review process of all stakeholders with respect to reproducibility. Furthermore, well-documented data publication workflows may improve data retrieval and finally data reuse in a long run. One obstacle towards comprehensible and properly described research workflows is the fact that data publication workflows in the life sciences are hard to define. Scholars have their very individual disciplinary background, research skills and experiences. In some domains such as biodiversity, scholars work from several weeks to years to collect and analyze often heterogeneous data from various sources, such as collections, environmental or molecular data repositories. Thus, reconstructing their work process after the project is finalized is very difficult if not impossible. However, our goal is to reveal the state of the art on how scholars manage their data in their research practices. We are in the process of setting up a survey whose general structure is organized according to the GFBio Data Lifecycle [7]. The results will allow us to reveal typical data practices workflows that can be used to evaluate the suitability of existing data repository portals, such as GFBio [8]. In our talk, we present the first insights of the survey. KEYWORDS: data publication workflows, data practices, biological and environmental data, green life sciences, biodiversity REFERENCES: 1. Dallmeier-Tiessen, S., Khodiyar, V., Murphy, F., Nurnberger, A., Raymond, L., Whyte, A., 2017. Connecting Data Publication to the Research Workflow: A Preliminary Analysis, International Journal of Digital Curation, 12, https://doi.org/10.2218/ijdc.v12i1.533. 2. González-Beltrán, A., Li, P., Zhao, J., Avila-Garcia, M. S., Roos, M., Thompson, M., van der Horst, E., Kaliyaperumal, R., Luo, R., Lee, T.-L., Lam, T., Edmunds, S.C., Sansone, S.-A., Rocca-Serra, P, 2015. From Peer-Reviewed to Peer-Reproduced in Scholarly Publishing: The Complementary Roles of Data Models and Workflows in Bioinformatics, PLOS ONE 10, 7, pp. 1–20, https://doi.org/10.1371/journal.pone.0127612. 3. Mark D. Wilkinson et al., 2016. The FAIR Guiding Principles for scientific data management and stewardship, Scientific Data 3. https://doi.org/10.1038/sdata.2016.18 4. Pangaea, https://www.pangaea.org 5. ENA, https://www.ebi.ac.uk/ena 6. GenBank, https://www.ncbi.nlm.nih.gov/genbank/ 7. GFBio Data Lifecycle, https://www.gfbio.org/training/materials/data-lifecycle 8. GFBio, https://www.gfbio.or

Vignetteninterview zur Erfassung des Sprachförderwissens pädagogischer Fachkräfte (VSW)

Die Autoren präsentieren ihr Vignetteninterview zur Erfassung von sprachförderdiagnostischem Wissen (VSW), mit dessen Hilfe das Sprachförderwissen pädagogischer Fachkräfte in Kitas in drei Bereichen (Diagnostik, Sprachfördertechniken, Kontext) erfasst werden kann. Es basiert auf einer Filmvignette, die eine dialogische Bilderbuchbetrachtung zwischen einer Fachkraft und einem Kind zeigt. Im leitfadengestützten Interview werden die pädagogischen Fachkräfte gebeten, Fragen zu den sprachlichen Kompetenzen des Kindes und den förderdiagnostischen Kompetenzen der Fachkraft im Video zu beantworten. (DIPF/Orig.

Stable Mutated tau441 Transfected SH-SY5Y Cells as Screening Tool for Alzheimer’s Disease Drug Candidates

The role of hyperphosphorylation of the microtubule-associated protein tau in the pathological processes of several neurodegenerative diseases is becoming better understood. Consequently, development of new compounds capable of preventing tau hyperphosphorylation is an increasingly hot topic. For this reason, dependable in vitro and in vivo models that reflect tau hyperphosphorylation in human diseases are needed. In this study, we generated and validated an in vitro model appropriate to test potential curative and preventive compound effects on tau phosphorylation. For this purpose, a stably transfected SH-SY5Y cell line was constructed over-expressing mutant human tau441 (SH-SY5Y-TMHT441). Analyses of expression levels and tau phosphorylation status in untreated cells confirmed relevance to human diseases. Subsequently, the effect of different established kinase inhibitors on tau phosphorylation (e.g., residues Thr231, Thr181, and Ser396) was examined. It was shown with several methods including immunosorbent assays and mass spectrometry that the phosphorylation pattern of tau in SH-SY5Y-TMHT441 cells can be reliably modulated by these compounds, specifically targeting JNK, GSK-3, CDK1/5, and CK1. These four protein kinases are known to be involved in in vivo tau phosphorylation and are therefore authentic indicators for the suitability of this new cell culture model for tauopathies

Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens

Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection

Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study

BackgroundThe PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice.MethodsFebrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed.FindingsOf 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92-5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07-7.59), Group A streptococcus (OR 2.73, 95% CI 1.13-6.09) and E. coli (OR 2.7, 95% CI 1.02-6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11-0.46), influenza B (OR 0.12, 95% CI 0.02-0.37) and RSV (OR 0.16, 95% CI: 0.06-0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23-0.72) and EBV (OR 0.71, 95% CI 0.56-0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively.InterpretationMost febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics.FundingEU Horizon 2020 grant 668303

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Impact of ApoB-100 expression on cognition and brain pathology in wild-type and hAPPsl mice

During their lifetime, people are commonly exposed to several vascular risk factors that may affect brain ageing and cognitive function. In the last few years, increasing evidence suggests that pathological plasma lipid profiles contribute to the pathogenesis of late-onset Alzheimer's disease. Importantly, hypercholesterolemia, especially elevated low-density lipoprotein cholesterol values, that is, increased apolipoprotein B-100 (ApoB-100) levels, represents an independent risk factor. In this study, the effects of ApoB-100 overexpression, either alone or in combination with cerebral expression of human amyloid precursor protein (hAPP), on cognitive functions and brain pathology were assessed. Our results show that ApoB-100 overexpression induces memory decline and increases cerebral lipid peroxidation and amyloid beta levels compared to those in wild-type animals. Although double-transgenic ApoBxAPP animals did not develop more distinct behavioral deficits than single-transgenic hAPP littermates, hApoB-100 expression caused additional pathophysiological features, such as high LDL and low HDL-cholesterol levels, increased lipid peroxidation, and pronounced ApoB-100 accumulation in cerebral vessels. Thus, our results indicate that ApoBxAPP mice might better reflect the situation of elderly humans than hAPPsl overexpression alone. (C) 2013 Elsevier Inc. All rights reserved

Brain cortical cholesterol metabolism is highly affected by human APP overexpression in mice

Processing of the amyloid precursor protein (APP) and amyloid beta (A beta) has been for decades in the center of Alzheimer's disease (AD) research. Beside many other variables, lipids, especially cholesterol and its derivatives, are discussed to contribute to AD pathogenesis. Several studies show that cholesterol affects APP metabolism. Also the converse mechanism, the direct influence of A beta on cholesterol metabolism, has been described. To further investigate this crosstalk between cholesterol- and APP metabolism, a high-fat feeding study was conducted with animals overexpressing human APP(SL) and/or human ApoB-100. The impact of diet and genotype on cerebral cholesterol metabolism and content as well as spatial learning and memory was examined. While behavioral performance was not influenced by this high fat diet (HFD), reduction of cortical free cholesterol levels and mRNA expression patterns under normal diet and HFD conditions in human APP(SL) overexpressing mice argue for an important role of APP in cerebral lipid metabolism. From our results we conclude that increased APP metabolism in ApoBxAPP and APP(SL) mice induces mechanisms to reduce free cholesterol levels. (C) 2016 Elsevier Inc. All rights reserved