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Deliverable 4.4 is part of Task 4.2 that deals with the development of the NanoCommons Knowledge Base and Warehouse that aims to collect raw and processed data generated by different projects and to provide support and processes for preparing datasets for upload to the NanoCommons data warehouse or other specialized databases linked into the infrastructure, as well as templates for data collection (linked to the online notebooks). Additionally, repositories for protocol description directly linked to the relevant datasets are provided in order for complete coverage of the experimental procedure and results to be included into the system. The work in this task is based on the concepts and aligned with developments from previous and ongoing projects (e.g. eNanoMapper, NANoREG, NanoMILE, NanoFASE, SmartNanoTox, ACEnano, etc.) and is extended in order to cover additional areas of nano safety research. It considers requirements for regulatory reporting and Adverse Outcome Pathway (AOP) development, as well as the support of ontology development and semantic annotation. In this way, the warehouse facilitates data transfer to and from other databases as part of a federated data ecosystem.

The scope of Work Package 5 (WP5) is the integration of the state-of-the-art tools for data management, mining, handling, analysis and predictive modelling to facilitate their joint provision as tools and services for Transnational Access (TA). To achieve this, a linked data approach is being utilised to exploit, extract, and integrate knowledge from all available information types (raw and processed experimental and modelling data, and metadata) to be captured in the NanoCommons Knowledge Base (KB). These tools, once linked and interoperable via the NanoCommons platform, will be made available to the nanosafety community either as standalone or through the NanoCommons TA open calls that will offer funded access to the tools and services offered by NanoCommons to develop tailored solutions for individual user or project’s data management needs. The TA calls will allow successful applicants to take advantage of the NanoCommons tools and services free-of-charge, including help to make their existing data FAIR (Findable, Accessible, Interoperable, and Reusable), to implement data management, mining, handling, analysis, visualisation and modelling workflows into their experimental design and data collection processes and to facilitate direct integration of resulting datasets into relevant databases (experimental and in silico) with all of the required metadata and semantic annotation. NanoCommons TA Users are thus becoming part of a wider attempt at cross-field and cross-data harmonisation, leading to increased data quality and thus better predictive models for nanosafety, thereby resulting in ground breaking insights and novel materials. This advance in nanosafety and safe-by-design (SdD) NMs will also be facilitated through the further development of the existing tools and the design and creation of new tools to fill in any identified research gaps or lack of services. This deliverable (D5.1) presents the tools and respective services implemented during Year 1 within NanoCommons that are offered during the first TA call. Additional services will continue to be added to the NanoCommons portfolio and refinements to current services will also be made based on experience gained during the first round of TA provision.

The current deliverable is part of Work Package 5 (WP5) Joint Research Activity 3 (JRA3) - Analysis and Modelling Tools, which aims to integrate the current state of the art tools for data mining and data analysis, utilising a linked data approach that will exploit, extract, and integrate knowledge from all available information (raw experimental and modelling data, and metadata) contained in the NanoCommons data warehouse (DW) and KnowledgeBase (KB). These tools and the expertise to apply them and interpret the outputs in a meaningful manner, once linked and interoperable via the NanoCommons platform, will be made available to the NanoCommons User community via the open calls for Transnational Access. This Deliverable report describes the initial set of tools directed towards analysis of “omics” datasets, including transcriptomics (analysis of changes in gene expression), proteomics (analysis of changes in protein expression), metabolomics and lipidomics (changes in expression of small molecules and lipids, respectively).

The objective of the present study was to describe two non-invasive methods for fat quantification in normal canine liver by using magnetic resonance imaging (MRI) and spectroscopy. Eleven adult beagle dogs were anesthetized and underwent magnetic resonance examination of the cranial abdomen by performing morphologic, modified Dixon (mDixon) dual gradient echo sequence, and proton magnetic resonance spectroscopy (1H MRS) imaging. In addition, ultrasonographic liver examination was performed, fine-needle liver aspirates and liver biopsies were obtained, and hepatic triglyceride content was assayed. Ultrasonographic, cytologic, and histologic examination results were unremarkable in all cases. The median hepatic fat fraction calculated was 2.1% (range, 1.3%–5.5%) using mDixon, 0.3% (range, 0.1%–1.0%) using 1H MRS, and 1.6% (range 1.0%–2.5%) based on triglyceride content. The hepatic fat fractions calculated using mDixon and 1H MRS imaging were highly correlated to that based on triglyceride content. A weak correlation between mDixon and 1H MRS imaging was detected. The results show that hepatic fat content can be estimated using non-invasive techniques (mDixon or 1H MRS) in healthy dogs. Further studies are warranted to evaluate the use of these techniques in dogs with varying hepatic fat content and different hepatic disorders., Journal of Veterinary Science, 19 (4), ISSN:1229-845X, ISSN:1976-555X

Cerebrolysin (EVER Neuro Pharma, Austria) is a peptidergic drug indicated for clinical use in stroke, traumatic brain injury and dementias. The therapeutic effect of Cerebrolysin is thought to ensure from its neurotrophic activity, which shares some properties with naturally occurring neurotrophic factors. However, the exact mechanism(s) of action of Cerebrolysin is yet to be fully deciphered. This study aimed to investigate the neuroprotective effect of Cerebrolysin in a widely used in vitro model of hypoxia-induced neuronal cytotoxicity, namely CoCl2-treatment of PC12 cells. CoCl2 cytotoxicity was indicated by a reduced cell-diameter, cell shrinkage, increased pro-apoptotic caspase-activities and a decreased metabolic activity. Cerebrolysin maintained the cell-diameter of CoCl2-treated naïve PC12 cells, decreased the activation of caspase 3/7 in naïve PC12 cells and restored the cells’ metabolic activity in naïve and differentiated PC12 cells. Cerebrolysin treatment also decreased the levels of superoxides observed after exposure to CoCl2. Investigating the mechanism of action, we could demonstrate that Cerebrolysin application to CoCl2-stressed PC12 cells increased the phosphorylation of GSK3ß, resulting in the inhibition of GSK3ß. This might become clinically relevant for Alzheimer’s disease, since GSK3ß activity has been linked to the production of amyloid beta. Taken together, Cerebrolysin was found to have neuroprotective effects in CoCl2-induced cytotoxicity in PC12 cells.