Biology subjects

Fels, J.

Publications and source records attributed to Fels, J..

4 recordsLinked to original sources

bioRxiv2021

Lysosomal Exocytosis Releases Pathogenic α-Synuclein Species from Neurons

Considerable evidence supports the release of pathogenic aggregates of the neuronal protein -Synuclein (Syn) into the extracellular space. While this release is proposed to instigate the neuron-to-neuron transmission and spread of Syn pathology in synucleinopathies including Parkinsons disease, the molecular-cellular mechanism(s) remain unclear. Here we show that pathogenic species of Syn accumulate within neuronal lysosomes in mouse brains and primary neurons. We then find that neurons release these pathogenic Syn species via SNARE-dependent lysosomal exocytosis; proposing a central mechanism for exocytosis of aggregated and degradation-resistant proteins from neurons.

cell biology↗

bioRxiv2020

Sex and estrogen receptor β have modest effects on gene expression in the mouse brain posterior cortex

IntroductionSex differences in brain cortical function affect cognition, behavior, and susceptibility to neural diseases, but the molecular basis of sexual dimorphism in cortical function is still largely unknown. Estrogen and estrogen receptors (ERs), specifically ER{beta}, the most abundant ER in the cortex, may play a role in determining sex differences in gene expression, which could underlie functional sex differences. However, further investigation is needed to address brain region specificity of the effects of sex and ER{beta} on gene expression. The goal of this study was to investigate sex differences in gene expression in the mouse posterior cortex, where sex differences in transcription have never been examined, and to determine how genetic ablation of ER{beta} affects transcription. MethodsIn this study, we performed unbiased transcriptomics on RNA from the posterior cortex of adult wild-type and ER{beta} knockout mice (n=4/sex/genotype). We used unbiased clustering to analyze whole-transcriptome changes between the groups. We also performed differential expression analysis on the data using DESeq2 to identify specific changes in gene expression. ResultsWe found only 27 significantly differentially expressed genes (DEGs) in wild-type (WT) males vs females, of which 17 were autosomal genes. Interestingly, in ER{beta}KO males vs females all the autosomal DEGs were lost. Gene Ontology analysis of the subset of DEGs with sex differences only in the WT cortex revealed a significant enrichment of genes annotated with the function cation channel activity. Moreover, within each sex we found only a few DEGs in ER{beta}KO vs WT mice (8 and 5 in males and females, respectively). ConclusionsOverall, our results suggest that in the adult mouse posterior cortex there are surprisingly few sex differences in gene expression, and those that exist are mainly related to cation channel activity. Additionally, they indicate that brain region-specific functional effects of ER{beta} may be largely post-transcriptional.

neuroscience↗

bioRxiv2020

Experiments on localization accuracy with non-individual and individual HRTFs comparing static and dynamic reproduction methods

Binaural reproduction can be used in listening experiments under real-life conditions to achieve a high realism and good reproducibility. In recent years a clear trend to more individual reproduction can be observed as the ability to measure individual head-related-transfer-functions (HRTFs) is becoming more widespread. The question of the accuracy and reproduction methods needed for a realistic playback however has not been sufficiently answered. To evaluate an appropriate approach for binaural reproduction via headphones different head-related-transfer-functions (HRTFs) and reproduction methods were compared in this paper. In a listening test eleven explicitly trained participants were asked to localize eleven sound sources positioned in the right hemisphere using the proximal pointing method. Binaural stimuli based on individually measured HRTFs were compared to those of an artificial head in a static reproduction of stimuli and in three dynamic reproduction methods of different resolutions (5{degrees}, 2.5{degrees} and 1{degrees}). Unsigned errors in azimuth and elevation as well as front-back-confusions and in-head-localization were observed. Dynamic reproduction of any resolution applied turned out fundamental for a reduction of undesired front-back-confusions and in-head-localization. Individually measured HRTFs showed a smaller effect on localization accuracy compared to the influence of dynamic sound reproduction. They were mainly observed to reduce the front-back-confusion rate.

neuroscience↗

bioRxiv2019

MobiLab - A Mobile Laboratory for On-Site Listening Experiments in Virtual Acoustic Environments

Research in the last decades has pointed out negative effects of noise on cognitive processing and general health. Depending on the frequency and level of exposure as well as individual shielding potential, risk groups like children or elderly people may be particularly vulnerable to commonly known consequences including a reduced attention span, influencing the learning success during education, increased blood pressure and cardiovascular problems or sleep disturbances. To better understand the susceptibility to noise, specifically designed listening experiments in controlled laboratory environments are indispensable but might put high demands on older study participants whose travel expenses to test locations could increase due to reduced mobility. For children, organizational issues like insured transport and supervision during waiting periods, necessitating additional resources, need to be resolved. In order to facilitate practical and efficient study execution, we therefore implemented a mobile hearing laboratory by acoustically optimizing the interior of a caravan. All necessary technical facilities were integrated to perform listening experiments in virtual acoustic environments under controlled conditions directly on site, for example, in front of schools or senior residential centers. The design and construction of this laboratory are presented here and evaluated through acoustic measurements.

neuroscience↗