Studying the Parkinson's disease metabolome and exposome in biological samples through different analytical and cheminformatics approaches: a pilot study

in Analytical and Bioanalytical Chemistry (2022)

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease, with an increasing incidence in recent years due to the ageing population. Genetic mutations alone only explain <10% of PD ... [more ▼]

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease, with an increasing incidence in recent years due to the ageing population. Genetic mutations alone only explain <10% of PD cases, while environmental factors, including small molecules, may play a significant role in PD. In the present work, 22 plasma (11 PD, 11 control) and 19 feces samples (10 PD, 9 control) were analyzed by non-target high resolution mass spectrometry (NT-HRMS) coupled to two liquid chromatography (LC) methods (reversed phase (RP) and hydrophilic interaction liquid chromatography (HILIC)). A cheminformatics workflow was optimized using open software (MS-DIAL and patRoon) and open databases (all public MSP-formatted spectral libraries for MS-DIAL, PubChemLite for Exposomics and the LITMINEDNEURO list for patRoon). Furthermore, five disease-specific databases and three suspect lists (on PD and related disorders) were developed, using PubChem functionality to identifying relevant unknown chemicals. The results showed that non-target screening with the larger databases generally provided better results compared with smaller suspect lists. However, two suspect screening approaches with patRoon were also good options to study specific chemicals in PD. The combination of chromatographic methods (RP and HILIC) as well as two ionization modes (positive and negative) enhanced the coverage of chemicals in the biological samples. While most metabolomics studies in PD have focused on blood and cerebrospinal fluid, we found a higher number of relevant features in feces, such as alanine betaine or nicotinamide, which can be directly metabolized by gut microbiota. This highlights the potential role of gut dysbiosis in PD development. [less ▲]

Einführung: Diskussion zum Spannungsfeld 'Transregionalität - Zwischenräume'

Presentation (2022, July 13)

Docteur

Doctoral thesis (2022)

The last century has been characterized by the increasing presence of synthetic chemicals in human surroundings, with as consequence, the increasing exposure of individuals to a wide variety of chemical ... [more ▼]

The last century has been characterized by the increasing presence of synthetic chemicals in human surroundings, with as consequence, the increasing exposure of individuals to a wide variety of chemical substances on a regular basis. The Lancet Commission on Pollution and Health estimated that since synthetic chemicals started to be available for common use at the end of the 1940s, more than 140,000 new chemicals have been produced, including five thousand used globally in massive volume. In parallel, awareness of the adverse effects of pollutant mixtures, possibly more severe than single-chemical exposures, has drawn attention towards the need of multi-residue analytical methods to obtain the most comprehensive information on human chemical exposome. Human biomonitoring, consisting in the measurement of pollutants in biological matrices, provides information that integrates all the possible sources of exposure, and is specific to the subject the sample is collected from. For this purpose, hair appears as a particularly promising matrix to assess chemical exposure thanks to its multiple benefits. Hair enables to detect both parent chemicals and metabolites, it is suitable to investigate exposure to chemicals from different families, and allows the detection of persistent and non-persistent chemicals. Moreover, contrary to fluids such as urine and blood, which only give information on the short-term exposure and present great variability in chemical concentration, hair is representative of wider time windows that can easily cover several months. Children represent the most vulnerable part of the population, and exposure to pollutants at young ages has been associated with severe health effects during childhood, but also during the adult life. Nevertheless, most epidemiological studies investigating exposure to pollutants are still conducted on adults, and data on children remain much more limited. The present study named “Biomonitoring of children exposure to pollutants based on hair analysis” investigated the relevance of hair analysis for assessing children exposure to pollutants. In this study, 823 hair samples were collected from children and adolescents living in 9 different countries (Luxembourg, France, Spain, Uganda, Indonesia, Ecuador, Suriname, Paraguay and Uruguay), and 117 hair samples were also collected from French adults. All samples were analysed for the detection of 153 organic compounds (140 were pesticides, 4 PCBs, 7 BDEs and 2 bisphenols). Moreover, the hair samples of French adults and children were also analysed for the detection of polycyclic aromatic hydrocarbons (PAH) and their metabolites (n = 62), nicotine, cotinine and metals (n = 36). The results obtained here clearly demonstrated that children living in different geographical areas are simultaneously exposed to multiple chemicals from different chemical classes. Furthermore, the presence of persistent organic pollutants in all children, and not only in adults, suggests that exposure to these chemicals is still ongoing, although these chemicals were banned decades ago. In the sub-group of Luxembourgish children, information collected within questionnaires in parallel to hair sample collection allowed to identify some possible determinant of exposure, such as diet (organic vs conventional), residence area (urban vs countryside), and presence of pets at home. Moreover, results showed higher levels of concentration in younger children, and higher exposure of boys to non-persistent pesticides than girls, which could possibly be attributed to differences in metabolism, behaviour and gender-specific activities. Finally, the study also highlighted high level of similarity in the chemical exposome between children from the same family compared to the rest of the population. The present study strongly supports the use of hair analysis for assessing exposure to chemical pollutants, and demonstrates the relevance of multi-residue methods to investigate exposome. [less ▲]

Modelling complex systems in the context of the COVID-19 pandemics

Doctoral thesis (2022)

Systems biology is an interdisciplinary approach investigating complex biological systems at different levels by combining experimental and modelling approaches to understand underlying mechanisms of ... [more ▼]

Systems biology is an interdisciplinary approach investigating complex biological systems at different levels by combining experimental and modelling approaches to understand underlying mechanisms of health and disease. Complex systems including biological systems are affected by a plethora of interactions and dynamic processes often with the aim to ensure robustness to emer- gent system properties. The need for interdisciplinary approaches became very evident in the recent COVID-19 pandemic spreading around the globe since the end of 2019. This pandemic came with a bundle of urgent epidemiological open questions including the infection and transmis- sion mechanisms of the virus, its pathogenicity and the relation to clinical symptoms. During the pandemic, mathematical modelling became an essential tool to integrate biological and healthcare data into mechanistic frameworks for projections of future developments and the assessment of different mitigation strategies. In this regard, systems biology with its interdisciplinary approach was a widely applied framework to support society in the COVID-19 crisis. In my thesis, I applied different mathematical modelling approaches as a tool to identify underlying mechanisms of the complex dynamics of the COVID-19 pandemic with a specific focus on the situation in Luxembourg. For this purpose, I analysed the COVID-19 pandemic at its different phases and from various perspectives by investigating mitigation strategies, consequences in the healthcare and economical system, and pandemic preparedness in terms of early-warning signals for re-emergence of new COVID-19 outbreaks by extended and adapted epidemiological Susceptible-Exposed-Infectious-Recovered (SEIR) models. [less ▲]

Determination of Slip Factor between CNC-Cut Serrated Surfaces of S355J2 Grade Steel Plates

in Buildings (2022), 12(995),

Determination of Slip Factor between CNC-Cut Serrated Surfaces of S355J2 Grade Steel Plates by Taygun Fırat Yolaçan and Markus SchäferStructural joint configurations realized with serrated steel surfaces ... [more ▼]

Determination of Slip Factor between CNC-Cut Serrated Surfaces of S355J2 Grade Steel Plates by Taygun Fırat Yolaçan and Markus SchäferStructural joint configurations realized with serrated steel surfaces have started to be used in the construction fields to assemble the primary and the secondary structural members of civil engineering structures. The main advantages of these joint configurations rely on their flexibility to accommodate construction tolerances and their slip-resistant load-bearing mechanism against dynamic loading conditions. Therefore, it is important to reliably establish the characteristic value of the friction coefficient or in other words the slip factor between the serrated steel surfaces to design reliable slip-resistant connections. In this study, the characteristic slip factor between the CNC-cut serrated surfaces prepared from S355J2 grade steel plates is determined to investigate the impact of the CNC-cutting procedure on the slip-resistant load-bearing behaviour of steel-to-steel interfaces. Five experimental tests were performed according to EN1090-2, Annex G. The results are presented as the load-slip curves, variation of the bolt pre-tension load level, nominal and actual slip factors for the tested configuration of the CNC-cut serrated steel-to-steel interface [less ▲]

Soziale Kohäsion als Reflexionskonzept zur Wohnraumproblematik im Großherzogtum Luxemburg

in Baier, Florian; Borrmann, Stefan; Hefel, Johanna M. (Eds.) et al Europäische Gesellschaften zwischen Kohäsion und Spaltung. Rolle, Herausforderungen und Perspektiven Sozialer Arbeit (2022)

Exploring the Institutionalisation of Science Diplomacy: A Comparison of German and Swiss Science and Innovation Centres

Doctoral thesis (2022)

This thesis explains and investigates the development and the institutionalisation of Science and Innovation Centres (SICs) as being distinct instruments of science diplomacy. SICs are a unique and ... [more ▼]

This thesis explains and investigates the development and the institutionalisation of Science and Innovation Centres (SICs) as being distinct instruments of science diplomacy. SICs are a unique and underexplored instrument in the science diplomacy toolbox and they are increasingly being adopted by highly innovative countries. This research responds to a growing interest in the field. Science diplomacy is commonly understood as a distinct governmental approach that mobilises science for wider foreign policy goals, such as improving international relations. However, science diplomacy discourse is characterised by a weak empirical basis and driven by normative perspectives. This research responds to these shortcomings and aims to lift the smokescreen of science diplomacy by providing an insight into its governance while also establishing a distinctly actor-centred perspective. In order to achieve this, two distinct SICs, Germany’s Deutsche Wissenschafts- und Innovationshäuser (DWIH) and Switzerland’s Swissnex are closely analysed in an original comparative and longitudinal study. While SICs are just one instrument in the governmental toolbox for promoting international collaboration and competition, they are distinct due to their holistic set- up and their role as a nucleus for the wider research and innovation system they represent. Moreover, SICs appear to have the potential to create a significant impact, despite their limited financial resources. This thesis takes a historical development perspective to outline how these two SICs were designed as well as their gradual development and institutionalisation. The thesis further probes why actors participate in SICs by unpacking their differing rationales, developing a distinctly actor-centred perspective on science diplomacy. This study has been designed in an inductive and exploratory way to account for the novelty of the topic; the research findings are based on the analysis of 41 interviews and a substantial collection of documents. The study finds evidence that SICs developed as a response to wider societal trends, although these trends differed for the two case studies. Moreover, the development of SICs has been characterised by aspects such as timing, contingency and critical junctures. SICs are inextricably connected to their national contexts and mirror distinct system characteristics, such as governance arrangements or degree of actor involvement. These aspects were also seen as explaining the exact shape that SICs take. Furthermore, this study finds evidence of an appropriation of SICs by key actors, in line with their organisational interests. In the case of the DWIH, this impacted and even limited its (potential) design and ways of operating. However, the analysis of SICs’ appropriation also revealed a distinct sense of collectivity, which developed among actors in the national research and innovation ecosystem due to this joint instrument. The research findings reaffirm that science diplomacy is clearly driven by national interests, while further highlighting that the notion of science diplomacy and its governance (actors, rationales and instruments) can only be fully understood by analysing the national context. [less ▲]

Limit theorems with Malliavin calculus and Stein's method

Doctoral thesis (2022)

We use recent tools from stochastic analysis (such as Stein's method and Malliavin calculus) to study the asymptotic behaviour of some functionals of a Gaussien Field.

European Integration Studies through Oral History and Multimedia Research - Innovative methodologie and new content creation

Presentation (2022, July 11)

Presentation of three study cases: 1.Oral Historyand MultimediaResearch–Project ‘’Pierre Werner and Europe’’ (2011-2017) 2.Collaborative Oral History Project –‘’Brexit Reality Portraits’’ (2021-2022) 3 ... [more ▼]

Presentation of three study cases: 1.Oral Historyand MultimediaResearch–Project ‘’Pierre Werner and Europe’’ (2011-2017) 2.Collaborative Oral History Project –‘’Brexit Reality Portraits’’ (2021-2022) 3.Oral History Research Project –‘’The role of women in European and international relations in Luxembourg (after the Second World War)’’ (2022-2025) [less ▲]

Creatures of reason: the imminence of constitutional courts in liberal democracies

Presentation (2022, July 11)