Biology subjects

Meier, E.

Publications and source records attributed to Meier, E..

6 recordsLinked to original sources

bioRxiv2025

Disease-specific fibroblast-myeloid interactions in rheumatoid arthritis synovium

Rheumatoid arthritis (RA) is characterized by profound remodeling of the synovial microenvironment. Here we show that enhanced fibroblast-macrophage cross-talk distinguishes RA from psoriatic arthritis (PsA). MerTK-SPP1 macrophages represent the dominant inflammatory myeloid population in RA, interacting with expanded fibroblast subsets through SPP1-mediated signaling. Lining fibroblasts display induction of antigen-presentation and IL-6/JAK-STAT pathways, while a CHI3L1-producing fibroblast population arises specifically in RA and may act as a source of autoantigens. These stromal populations interact closely with FABP5 iDC3 cells and T cells within a disrupted synovial lining, creating a niche driving adaptive immune activation. In contrast, PsA exhibits increased fibroblast- endothelial interactions without major endothelial transcriptional changes. Our data identify SPP1 signaling and fibroblast-myeloid-dendritic interactions as core drivers of RA synovial inflammation that links innate immune activation to the initiation of autoimmunity. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=78 SRC="FIGDIR/small/688477v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@c76e39org.highwire.dtl.DTLVardef@11563a9org.highwire.dtl.DTLVardef@141f3fborg.highwire.dtl.DTLVardef@f90742_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2023

EEG markers of drowsiness do not predict lapses in attention during sleep deprivation

During drowsiness, maintaining consistent attention becomes difficult, leading to behavioral lapses. Oscillation bursts in the electroencephalogram (EEG) might predict such lapses, since alpha bursts increase with inattention and theta bursts increase with time spent awake. However, while lapses increase with time awake, paradoxically alpha bursts decrease, and the behavioral relevance of theta bursts is unknown. Therefore, we investigated whether theta or alpha bursts predicted lapses either when well rested (baseline, BL) or sleep deprived (SD). EEG was measured in 18 young adults performing the lateralized attention task, and the timing of bursts was related to trial outcomes (fast, slow, and lapse trials). Against expectations, neither theta nor alpha bursts were more likely during lapses, either at BL or SD. Both were more likely before fast trials, but only at BL. Fast and slow trials were followed by decreases in both theta and alpha bursts, but the effect was reduced during SD, partially due to local increases in bursts. Considering prior literature, these results indicate that bursts have a non-linear relationship with vigilance. The lack of a direct relationship to lapses may be because bursts originate from task-unrelated areas, and the differences during SD suggest these areas change with time awake.

neuroscience↗

bioRxiv2023

Theta and alpha EEG oscillations reflect sleep need -- except during the wake maintenance zone

Increasing time spent awake results in accumulated sleep need, a process known as sleep homeostasis. Sleep homeostasis combines with a 24 h circadian rhythm to determine when and for how long we sleep. Both sleep homeostasis and the circadian rhythm substantially affect spectral power of the wake electroencephalogram (EEG), but not in ways predicted by current models. Specifically, these models hypothesize that time spent awake increases neuronal synaptic strength, which increases synchronization and should therefore increase oscillatory activity. However, the dominant wake EEG oscillations, measured as theta (4-8 Hz) and alpha power (8-12 Hz), do not follow the predicted buildup in homeostatic sleep pressure with time awake. This is due to a limitation of spectral power analysis, which does not distinguish between changes in the amplitude of oscillations from changes in the quantity of oscillations present in the signal. We wished to determine whether the amplitudes of EEG oscillations would specifically reflect homeostatic sleep pressure, independently from changes in quantity. We collected data from 18 young healthy adults during a 4-h sleep / 24-h extended wake paradigm. We indeed found that theta and alpha oscillation amplitudes reflect homeostatic sleep pressure, increasing along a saturating exponential function with time awake. Instead, theta quantities increased linearly with time awake, and alpha quantities decreased. Notably, theta and alpha amplitudes temporarily decreased during the wake maintenance zone (WMZ), a 3-4 h time window just before bedtime when it is difficult to fall asleep. Using pupillometry, we also found that mean pupil diameter increased during this window, while variance decreased. These results suggest that the WMZ is dependent on an alerting signal from the ascending arousal system. The WMZ therefore counteracts the observed build-up in homeostatic sleep pressure reflected in EEG amplitudes by temporarily desynchronizing cortical activity.

neuroscience↗

bioRxiv2022

The theta paradox: 4-8 Hz EEG oscillations reflect both local sleep and cognitive control

Human brain activity generates electroencephalographic (EEG) oscillations that characterize specific behavioral and vigilance states. The frequency of these oscillations is typically sufficient to distinguish a given state, however theta oscillations (4-8 Hz) have instead been found in near-opposite conditions of drowsiness during sleep deprivation and alert cognitive control. While the latter has been extensively studied and is often referred to as "frontal midline theta", the former has been investigated far less but is considered to be a marker for local sleep during wake. In this study we investigated to what extent theta oscillations differed during cognitive tasks and sleep deprivation. We measured high-density EEG in 18 young healthy adults performing 6 tasks under 3 levels of sleep deprivation. We found both cognitive load and sleep deprivation increased theta power in medial prefrontal cortical areas, however sleep deprivation caused additional increases in theta in many other, predominantly frontal, areas. The sources of sleep deprivation theta were task-dependent, with a visual-spatial task and short-term memory task showing the most widespread effects. Notably, theta was highest in supplementary motor areas during passive music listening, and highest in the inferior temporal cortex during a spatial game. This suggests that theta caused by sleep deprivation may preferentially occur in cortical areas not involved in ongoing behavior. While our results find differences in topography from frontal midline theta, they raise the possibility that a common mechanism may underly both theta oscillations during cognition and during sleep deprivation.

neuroscience↗

bioRxiv2021

Digital 3D Brain MRI Arterial Territories Atlas

The locus and extent of brain damage in the event of vascular insult can be quantitatively established quickly and easily with vascular atlases. Although highly anticipated by clinicians and clinical researchers, no digital MRI arterial atlas is readily available for automated data analyses. We created a digital arterial territory atlas based on lesion distributions in 1,298 patients with acute stroke. The lesions were manually traced in the diffusion-weighted MRIs, binary stroke masks were mapped to a common space, probability maps of lesions were generated and the boundaries for each arterial territory was defined based on the ratio between probabilistic maps. The atlas contains the definition of four major supra- and infra-tentorial arterial territories: Anterior, Middle, Posterior Cerebral Arteries and Vertebro-Basilar, and sub-territories (thalamoperforating, lenticulostriate, basilar and cerebellar arterial territories), in two hierarchical levels. This study provides the first publicly-available, digital, 3D deformable atlas of arterial brain territories, which may serve as a valuable resource for large-scale, reproducible processing and analysis of brain MRIs of patients with stroke and other conditions.

neuroscience↗

bioRxiv2019

The WT1-like transcription factor Klumpfuss maintains lineage commitment in the intestine

Stem cell (SC) lineages in barrier epithelia exhibit a high degree of plasticity. Mechanisms that govern the precise specification of SC daughter cells during regenerative episodes are therefore critical to maintain homeostasis. One such common mechanism is the transient activation of the Notch (N) signaling pathway. N controls the choice between absorptive and entero-endocrine cell fates in both the mammalian small intestine and the Drosophila midgut, yet how precisely N signaling promotes lineage restriction in progenitor cells remains unclear. Here, we describe a role for the WT1-like transcription factor Klumpfuss (Klu) in restricting the fate of Drosophila enteroblasts (EBs) downstream of N activation. Klu is transiently induced in Notch-positive EBs and its transient activity restricts cell fate towards the enterocyte (EC) lineage. Transcriptomics and DamID profiling show that Klu suppresses enteroendocrine (EE) cell fates by repressing E(Spl)m8-HLH and Phyllopod, both negative regulators of the proneural gene Scute, which is essential for EE differentiation. At the same time, Klu suppresses cell cycle genes, committing EBs to differentiation. Klu-mediated repression of its own transcription further sets up a negative feedback loop that ensures temporal restriction of Klu-mediated gene regulation, and is essential for subsequent differentiation of ECs. Our findings define a transient cell state in which EC lineage restriction is cemented, and establish a hierarchy of transcriptional programs critical in executing a differentiation program downstream of initial induction events governed by N signaling.

developmental biology↗