Biology subjects

van Es, M.

Publications and source records attributed to van Es, M..

3 recordsLinked to original sources

bioRxiv2025

Distinct Alpha Networks Modulate Different Aspects of Perceptual Decision-Making

Why do we sometimes perceive a faint stimulus but miss it at other times? One explanation is that conscious perception fluctuates with the brains internal state, influencing how external stimuli are processed. Ongoing brain oscillations in the alpha band (8-13 Hz), thought to reflect neuronal excitability levels1-5 and play a role in functional inhibition6,7, have been shown as a key contributor to such perceptual variability8,9. Under high alpha conditions, faint stimuli are more likely to be missed8. Some studies suggested alpha oscillations modulate perceptual criterion (c)10-14, shifting the threshold for interpreting sensory information; while others (including our prior work15) suggested alpha modulates sensitivity (d)15-19, changing the precision of sensory encoding. Few studies observed modulations in both metrics, making these results appear mutually exclusive. Most studies have focused solely on overall alpha activity-- whether within a region of interest or across the whole brain--and overlooked the coexistence of multiple distinct alpha networks20-26, which fluctuate in terms of predominance20,27,28 and adapt to behavioural demands29,30. Hence, it remained unclear whether different networks contributions to perception vary with their momentary state. Here, aiming to characterize how different alpha networks influence perceptual decision-making, we analyzed magnetoencephalography (MEG) data recorded while participants performed a visual detection task with threshold-level stimuli. We found that while the visual alpha network modulates perceptual sensitivity, the sensorimotor alpha network modulates criterion in perceptual decision-making. These findings reconcile previous conflicting results and highlight the functional diversity of alpha networks in shaping perception.

neuroscience↗

bioRxiv2024

Sex-specific DNA methylation differences in Amyotrophic lateral sclerosis

Sex is an important covariate in all genetic and epigenetic research due to its role in the incidence, progression and outcome of many phenotypic characteristics and human diseases. Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with a sex bias towards higher incidence in males. Here, we report for the first time a blood-based epigenome-wide association study meta-analysis in 9274 individuals after stringent quality control (5529 males and 3975 females). We identified a total of 226 ALS saDMPs (sex-associated DMPs) annotated to a total of 159 unique genes. These ALS saDMPs were depleted at transposable elements yet significantly enriched at enhancers and slightly enriched at 3UTRs. These ALS saDMPs were enriched for transcription factor motifs such as ESR1 and REST. Moreover, we identified an additional 10 genes associated with ALS saDMPs through chromatin loop interactions, suggesting a potential regulatory role for these saDMPs on distant genes. Furthermore, we investigated the relationship between DNA methylation at specific CpG sites and overall survival in ALS using Cox proportional hazards models. We identified two ALS saDMPs, cg14380013 and cg06729676, that showed significant associations with survival. Overall, our study reports a reliable catalogue of sex-associated ALS saDMPs in ALS and elucidates several characteristics of these sites using a large-scale dataset. This resource will benefit future studies aiming to investigate the role of sex in the incidence, progression and risk for ALS.

genomics↗

bioRxiv2020

Nafamostat Mesylate in lipid carrier for nasal SARS-CoV2 titer reduction in a hamster model

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) has been responsible for the largest pandemic in recent decades. After seemingly being in control due to consequent lock-downs and social distancing, the majority of countries faces currently a second wave of exponentially increasing infections, hospital referrals and deaths due to SARS-CoV-2-mediated disease (COVID-19). To date, no effective vaccination has been found, and wearing masks and social distancing are the only effective approaches to reduce further spreading. However, unwillingness in the societies to distance again and consequently wear masks might be reasons for the second SARS-CoV-2 infection wave. User-friendly chemicals interfering at the host site with viral entry might be an approach to contain the pandemic. In addition, such an approach would work synergistic with vaccinations that miss new virus mutants. Nafamostat (NM) has been shown in vitro to interfere with cellular virus entry by inhibition of the host transmembrane protease serine 2 (TMPRSS2), an enzyme required for SARS-CoV-2 spike protein cleavage, a prerequisite for cell entry. We hypothesized that nasal application of NM in a liposomal layer (as additional mechanical barrier) could lower the nasal viral load and subsequently reduce the severity of COVID-19. We found, indeed, that nasal viral load one day post single NM application, was lowered in a hamster SARS-CoV-2 infection model. However, severity of subsequent local tissue destruction and weight loss due to pneumonitis was not favorably altered. In conclusion, a single NM application reduced nasal viral load, but did not favorably improve the outcome of COVID-19, likely due to the short half-time of NM. Improvement of NM stability or repetitive application (which was not permitted in this animal model according to Dutch law) might circumvent these challenges.

microbiology↗