Pharmacological targeting of neuroinflammation in distinct models of genetically mediated disorders of the central nervous system (CNS) has been shown to attenuate disease outcome significantly. These include mouse models mimicking distinct subtypes of neuronal ceroid lipofuscinoses (NCL, CLN diseases) as well as hereditary spastic paraplegia type 2 (HSP/SPG2). We here show in a model of another, complicated HSP form (SPG11) that there is neuroinflammation in distinct compartments of the diseased CNS.
View Article and Find Full Text PDFThe COVID-19 pandemic has prompted severe restrictions on everyday life to curb the spread of infections. For example, teaching at universities has been switched to an online format, reducing students' opportunities for exchange, and social interaction. Consequently, their self-reported mental health has significantly decreased and there is a pressing need to elucidate the underlying mechanisms-ideally considering not only data collected during the pandemic, but also before.
View Article and Find Full Text PDFThe autophagy-lysosome pathway (ALP) regulates intracellular homeostasis of the cytosolic protein SNCA/alpha-synuclein and is impaired in synucleinopathies, including Parkinson disease and dementia with Lewy bodies (DLB). Emerging evidence suggests that ALP influences SNCA release, but the underlying cellular mechanisms are not well understood. Several studies identified SNCA in exosome/extracellular vesicle (EV) fractions.
View Article and Find Full Text PDFDetergents are commonly applied in lipase assays to solubilize sparingly soluble model substrates. However, detergents affect lipases as well as substrates in multiple ways. The effect of detergents on lipase activity is commonly attributed to conformational changes in the lid region.
View Article and Find Full Text PDFBecause of their vast diversity of substrate specificity and reaction conditions, lipases are versatile materials for biocatalysis. Lipase A from Bacillus subtilis (BSLA) is the smallest lipase yet discovered. It has the typical α/β hydrolase fold but lacks a lid covering the substrate cleft.
View Article and Find Full Text PDFVirulence of the fungal pathogen Aspergillus fumigatus is in part based on the saprophytic lifestyle that this mold has evolved. A crucial function for saprophytism resides in secreted proteases that allow assimilation of proteinaceous substrates. The impact of extracellular proteolytic activities on the pathogenesis of aspergillosis, however, remains controversial.
View Article and Find Full Text PDFUnlabelled: In 2005 the European Resuscitation Council published new guidelines for advanced life support. One of the issues was to reduce the "no flow time", which is defined as the time without chest compression in the first period of cardiac arrest. In a manikin study, we evaluated whether using the laryngeal tube instead of endotracheal intubation for airway management during cardiac arrest could reduce the "no flow time".
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