An archaeal compound as a driver of Parkinson’s disease pathogenesis

E-print/Working paper (2022)

Patients with Parkinson’s disease (PD) exhibit differences in their gut microbiomes compared to healthy individuals. Although differences have most commonly been described in the abundances of bacterial ... [more ▼]

Patients with Parkinson’s disease (PD) exhibit differences in their gut microbiomes compared to healthy individuals. Although differences have most commonly been described in the abundances of bacterial taxa, changes to viral and archaeal populations have also been observed. Mechanistic links between gut microbes and PD pathogenesis remain elusive but could involve molecules that promote α-synuclein aggregation. Here, we show that 2-hydroxypyridine (2-HP) represents a key molecule for the pathogenesis of PD. We observe significantly elevated 2-HP levels in faecal samples from patients with PD or its prodrome, idiopathic REM sleep behaviour disorder (iRBD), compared to healthy controls. 2-HP is correlated with the archaeal species Methanobrevibacter smithii and with genes involved in methane metabolism, and it is detectable in isolate cultures of M. smithii. We demonstrate that 2-HP is selectively toxic to transgenic α-synuclein overexpressing yeast and increases α-synuclein aggregation in a yeast model as well as in human induced pluripotent stem cell derived enteric neurons. It also exacerbates PD-related motor symptoms, α-synuclein aggregation, and striatal degeneration when injected intrastriatally in transgenic mice overexpressing human α-synuclein. Our results highlight the effect of an archaeal molecule in relation to the gut-brain axis, which is critical for the diagnosis, prognosis, and treatment of PD. [less ▲]

One planet: one health. A call to support the initiative on a global science–policy body on chemicals and waste

in Environmental Sciences Europe (2022), 34(1), 21

Abstract The chemical pollution crisis severely threatens human and environmental health globally. To tackle this challenge the establishment of an overarching international science–policy body has ... [more ▼]

Abstract The chemical pollution crisis severely threatens human and environmental health globally. To tackle this challenge the establishment of an overarching international science–policy body has recently been suggested. We strongly support this initiative based on the awareness that humanity has already likely left the safe operating space within planetary boundaries for novel entities including chemical pollution. Immediate action is essential and needs to be informed by sound scientific knowledge and data compiled and critically evaluated by an overarching science–policy interface body. Major challenges for such a body are (i) to foster global knowledge production on exposure, impacts and governance going beyond data-rich regions (e.g., Europe and North America), (ii) to cover the entirety of hazardous chemicals, mixtures and wastes, (iii) to follow a one-health perspective considering the risks posed by chemicals and waste on ecosystem and human health, and (iv) to strive for solution-oriented assessments based on systems thinking. Based on multiple evidence on urgent action on a global scale, we call scientists and practitioners to mobilize their scientific networks and to intensify science–policy interaction with national governments to support the negotiations on the establishment of an intergovernmental body based on scientific knowledge explaining the anticipated benefit for human and environmental health. [less ▲]

Historical Exposomics and High Resolution Mass Spectrometry

in Exposome (2021), 00(0),

Awareness of the exposome and its influence on health has increased in the last decade. As past exposures can cause changes in human health many years later, delving into the past is relevant for both ... [more ▼]

Awareness of the exposome and its influence on health has increased in the last decade. As past exposures can cause changes in human health many years later, delving into the past is relevant for both diagnostic and prevention purposes, but remains a challenging task. Lifestyle, diet, and socioeconomic information of the past should be well documented and compatible with modern data science methods. While chemical analysis nowadays makes use of high resolution mass spectrometry (HR-MS) for highly sensitive and comprehensive coverage of samples plus retrospective analysis, these data archives are in the very early stages. Since past measurements are often only available for a limited set of chemicals, adding to this knowledge requires careful selection of sample types and sampling sites, which may not always be available. The choice of analytes and analytical methods should be suitable for the study question —which is not always clear in advance in exposomics. Data interpretation and the use of appropriate databases are indispensable for a proper exposure assessment, and as databases and knowledge grow, re-analysis of physically or digitally archived samples could enable “continuous monitoring” efforts. This review focuses on the chemical analytical approaches necessary to capture the complexity of the historical exposome. Various sample types, analytes as well as analyses and data interpretation methods are discussed in relation to chemical exposures, while the connection to health remains in focus. It ends with perspectives and challenges in assessing the historical exposome, discussing how we can “learn from the past” to build a better future. [less ▲]

Exploring the Exposomewith HPC

Presentation (2021, November 10)

Chemical contamination of the sea – (management of the knowns and) Research on the unknowns

Scientific Conference (2021, October 20)

Update on NORMAN-SusDat NORMAN-SLE (Suspect List Exchange)

Scientific Conference (2021, September 14)

Cheminformatics and Mass Spectrometry meets Clinical Metabolomics

Scientific Conference (2021, September 01)

FAIR chemical structures in the Journal of Cheminformatics

in Journal of Cheminformatics (2021), 13(1), 50

Abstract The ability to access chemical information openly is an essential part of many scientific disciplines. The Journal of Cheminformatics is leading the way for rigorous, open cheminformatics in many ... [more ▼]

Abstract The ability to access chemical information openly is an essential part of many scientific disciplines. The Journal of Cheminformatics is leading the way for rigorous, open cheminformatics in many ways, but there remains room for improvement in primary areas. This letter discusses how both authors and the journal alike can help increase the FAIR ness (Findability, Accessibility, Interoperability, Reusability) of the chemical structural information in the journal. A proposed chemical structure template can serve as an interoperable Additional File format (already accessible ), made more findable by linking the DOI of this data file to the article DOI metadata, supporting further reuse . [less ▲]

Discovering Pesticides, Pharmaceuticals TPs in Luxembourg Waters using Open Cheminformatics Approaches

Scientific Conference (2021, June 24)

Defining a Manageable, Dynamic Chemical Space for Exposomics

Scientific Conference (2021, April 27)