Biology subjects

Moser, J.

Publications and source records attributed to Moser, J..

22 records · Page 2Linked to original sources

bioRxiv2020

Rewiring PBMC responses to prevent CHIKV infection-specific monocyte subset redistribution and cytokine responses

Infection with the mosquito-borne Chikungunya virus (CHIKV) causes acute or chronic arthritis in humans. Inflammatory responses mediated by monocytes, the primary target cells of CHIKV infection in the blood, are considered to play an important role in CHIKV pathogenesis. A recent study revealed that the acute phase of CHIKV infection is characterized by a monocyte-driven response, with an expansion of the intermediate monocyte (IM) subset. In this study, we adopted a previously established in vitro model of CHIKV infection in peripheral blood mononuclear cells, to elucidate the mechanism and relevance of IM expansion in CHIKV replication and associated inflammatory responses. Our data show that infectious but not replication-incompetent CHIKV increases the frequency of IM and to a lesser extent, non-classical (NM) monocytes while reducing the number of classical monocytes (CM). The increase of IM or NM frequency coincided with the activation of inflammatory response and occurred in the absence of lymphocytes implying that monocyte-derived cues are sufficient to drive this effect. Importantly, priming of monocytes with LPS prevented expansion of IM and NM but had no effect on viral replication. It did however alter CHIKV-induced cytokine signature. Taken together, our data delineate the role of IM in CHIKV infection-specific innate immune responses and provide insight for the development of therapeutic strategies that may focus on rewiring monocyte immune responses to prevent CHIKV-mediated arthralgia and arthritis.

immunology↗

bioRxiv2020

Magnetoencephalographic Signatures of Hierarchical Rule Learning in Newborns

Estimating the extent to which newborn humans process input from their environment, especially regarding the depth of processing, is a challenging question. To approach this problem, we measured brain responses in 20 newborns with magnetoencephalography (MEG) in a "local-global" auditory oddball paradigm in which two-levels of hierarchical regularities are presented. Results suggest that infants in the first weeks of life are able to learn hierarchical rules, yet a certain level of vigilance seems to be necessary. Newborns detected violations of the first-order regularity and displayed a mismatch response between 200-400ms. Violations of the second-order regularity only evoked a late response in newborns in an active state, which was expressed by a high heart rate variability. These findings are in line with those obtained in human adults and older infants suggesting a continuity in the functional architecture from term- birth on, despite the important immaturity of the human brain at this age.

neuroscience↗

bioRxiv2020

Measuring genetic variation in the multi-ethnic Million Veteran Program (MVP)

The Million Veteran Program (MVP), initiated by the Department of Veterans Affairs (VA), aims to collect consented biosamples from at least one million Veterans. Presently, blood samples have been collected from over 800,000 enrolled participants. The size and diversity of the MVP cohort, as well as the availability of extensive VA electronic health records make it a promising resource for precision medicine. MVP is conducting array-based genotyping to provide genome-wide scan of the entire cohort, in parallel with whole genome sequencing, methylation, and other omics assays. Here, we present the design and performance of MVP 1.0 custom Axiom(R) array, which was designed and developed as a single assay to be used across the multi-ethnic MVP cohort. A unified genetic quality control analysis was developed and conducted on an initial tranche of 485,856 individuals leading to a high-quality dataset of 459,777 unique individuals. 668,418 genetic markers passed quality control and showed high quality genotypes not only on common variants but also on rare variants. We confirmed the substantial ancestral diversity of MVP with nearly 30% non-European individuals, surpassing other large biobanks. We also demonstrated the quality of the MVP dataset by replicating established genetic associations with height in European Americans and African Americans ancestries. This current data set has been made available to approved MVP researchers for genome-wide association studies and other downstream analyses. Further data releases will be available for analysis as recruitment at the VA continues and the cohort expands both in size and diversity.

genetics↗

bioRxiv2019

Evaluating Complexity of Fetal MEG Signals: A Comparison of Different Metrics and Their Applicability

In this work, we aim to investigate whether information based metrics of neural activity are a useful tool for the search for consciousness before and shortly after birth. Neural activity is measured using fetal magnetoencephalography (fMEG) in human fetuses and neonates. Based on recent theories on consciousness, information-based metrics are established to measure brain complexity and to assess different levels of consciousness. Different metrics (measures of entropy, compressibility and fractality) are, thus, explored in a reference population and their usability is evaluated. For comparative analysis, two fMEG channels were selected: one where brain activity was previously detected and one at least 15cm away, that represented a control channel. The usability of each metric was evaluated and results from the brain and control channel were compared. Concerning the ease of use with fMEG data, Lempel-Ziv-Welch (LZW) compression was evaluated as best, as it is unequivocal and needs low computational effort. The fractality measures have a high parameter space and therefore forfeit comparability, while entropy measures require a higher computational effort and more parameters to adjust compared to LZW. Comparison of a channel with brain activity and a control channel in neonatal recordings showed significant differences in most complexity metrics. This clear difference can be seen as proof of concept for the usability of complexity metrics in fMEG. For fetal data, this comparison produced less clear results which can be related to leftover maternal signals included in the control channel. Further work is necessary to conclusively interpret results from the analysis of fetal recordings. Yet this study shows that complexity metrics can be used for fMEG data on early consciousness and the evaluation gives a guidance for future work. The inconsistency of results from different metrics highlights the challenges of working with complexity metrics as neural correlates of consciousness, as well as the caution one should apply to interpret them.

neuroscience↗