Leiden University Scholary Publications
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Special section introduction: threats and opportunities: the contestation of gender and sexuality in international organizations
Get PDFThe politics and administration of institutional chang
Spatially resolved mapping of monoacylglycerol lipase activity in the brain
Get PDFVisualizing signaling systems in the brain with high spatial resolution is critical to understand brain function and to develop therapeutics. Especially enzymes are often regulated on the post-translational level, resulting in a disconnect between protein levels and activity. Conventional antibody-based methods have limitations, including potential cross reactivity and the inability of antibodies to discriminate between active and inactive enzyme states. Monoacylglycerol lipase (MAGL), an enzyme degrading the neuroprotective endocannabinoid 2-arachidonoylglycerol, is the target of inhibitors currently in clinical trials for the treatment of several neurological disorders. To support translational and (pre)clinical studies and fully realize the therapeutic opportunities of MAGL inhibitors, it is essential to map the spatial distribution of MAGL activity throughout the brain in both health and disease. Here, we introduce selective fluorescent activity-based probes for MAGL enabling direct visualization of its enzymatic activity in lysates, cultured cells and tissue sections. We show that oxidative stress, which inactivates MAGL through the oxidation of regulatory cysteines, reduces probe labeling, thereby validating the probes activity-dependence. Extending this approach, we developed an activity-based histology protocol to visualize MAGL activity in fresh-frozen mouse and human brain tissues. This approach revealed robust MAGL activity in astrocytes and presynaptic terminals within the mouse hippocampus, and further allows detection of MAGL activity in the human cerebral cortex. Collectively, these findings establish selective activity-based probes as powerful tools mapping MAGL activity with high spatial resolution across mammalian brain tissue.Molecular Physiolog
Examining the patenting activities of universities in the Middle East and North Africa
Get PDFThis paper aims to examine universities' patenting activities in the Middle East and North Africa (MENA) region. Patent data from Derwent Innovation is analyzed to provide key insights about such activities. Saudi Arabia leads the region in terms of the number of patents, followed by Turkey and Morocco. These three countries, which represent 87% of all academic patents, are also home to the most patenting academic institutions. Although the academic sector in MENA grew its patenting activity faster than the world, its patent volume base is still relatively low. The results also show the profile of the technological developments covered in MENA academic patents. Some of these inventions directly tackle societal health-related issues but also public environmental ones. The main academic assignees show a certain degree of collaboration with academic and corporate organizations. This study provides important input to research managers as well as policymakers to assess the research produced by universities from a technological and economic perspective. Merit, Expertise and Measuremen
Summary report of the targeted public consultation on protection of minors guidelines: summary of feedback received on the Commission's draft guidelines on Article 28(1) of Regulation (EU) 2022/2065
Get PDFEffective Protection of Fundamental Rights in a pluralist worl
Transformation and sublimation of interstellar ices: insights from laboratory experiments and astronomical observations
Get PDFStars and planets form within cold, dense clouds of gas and dust drifting through interstellar space. Although dust makes up only a small fraction of this material, it plays a key role in shaping the chemical evolution of these environments. On the surfaces of tiny dust grains, smaller than the diameter of a human hair, atoms and molecules freeze out to form interstellar ices and undergo reactions that yield complex molecules, including precursors to life. This thesis explores how these ices evolve across different stages of star and planet formation, combining laboratory experiments and astronomical observations. In the lab, cryogenic ultra-high vacuum setups were used to simulate and isolate processes such as molecule formation and desorption under interstellar conditions. Experiments focused on key species like methanol (CH3OH) and hydrogen sulfide (H2S), uncovering new reaction pathways and mechanisms for their destruction and desorption. Observational data at radio and infrared wavelengths were used to anchor these findings in real astrophysical environments. This thesis provides a deeper understanding of how molecules are formed and transformed in ices, and how this chemistry influences the volatile content inherited by comets and planetesimals---helping trace the molecular origins of planetary systems, including our own.Laboratory astrophysics and astrochemistr
NAD-dependent dehydrogenases enable efficient growth of Paracoccus denitrificans on the PET monomer ethylene glycol
Get PDFMicrobial Biotechnolog
Onterechte bezwaren tegen gebruik salbutamol/ipratropium
No full textIn acute bronchospasm due to asthma/COPD exacerbations two bronchodilators are frequently used: ipratropium, an acetylcholine antagonist, and salbutamol, a β2-agonist. The combination ipratropium/salbutamol gives more bronchodilation than ipratropium monotherapy in asthma/COPD exacerbations, but there are concerns about cardiac safety of salbutamol.Salbutamol in regular dosage does not affect heart rate in diverse populations (ED, ICU and children). Only a dosage 5-10x the standard dosage of 2,5 mg leads to a 20-30-beat increase in heart rate. High-dose salbutamol induced a mild increase of QTc interval (±360 to ±390ms) and QTc dispersion (maximum minus minimum QTc; marker for susceptibility to arrhythmia), but not to a clinically relevant extent. Most importantly, literature shows that the incidence of arrhythmia is similar between salbutamol and placebo. Salbutamol did not induce severe arrhythmias, including in arrhythmogenic ICU populations or in patients with severe COPD with cardiac comorbidity.We therefore argue that the current caution exercised with the use ipratropium/salbutamol is unjustified. Treatment should not be withheld in case of tachycardia or underlying heart disease.</p
Naschrift: [bij ‘Rechtsbescherming tegen risicoprofilering op basis van de AVG, het EVRM en het Handvest’]
Get PDFThe Legitimacy and Effectiveness of Law & Governance in a World of Multilevel Jurisdiction
Economic and monetary union and the Euro crisis
No full textThis chapter introduces Economic and Monetary Union (EMU). It describes the key components of EMU and what happens when countries join the euro area. EMU was the result of decades of collaboration and learning starting in the 1960s. It built on the experience of exchange rate cooperation and subsequently became firmly embedded in the Maastricht Treaty. Once the euro was introduced the member states were soon after confronted with the global financial crisis, the sovereign debt crisis and its aftermath (2009–19), and then with the COVID-19 pandemic (from 2020). These crises brought to the fore various imperfections in the design of EMU and provided opportunities for further development.Institutions, Decisions and Collective Behaviou