Biology subjects

Schweitzer, R.

Publications and source records attributed to Schweitzer, R..

At least 19 recordsLinked to original sources

bioRxiv2026

From parental antibiotics to offspring locomotion: L-norvaline links microbiome disruption to intergenerational reprogramming in Drosophila

The maternal microbiome during oogenesis is a critical but underappreciated regulator of offspring physiology. Using Drosophila melanogaster as a model, we show that a single, transient antibiotic exposure during oogenesis, without direct offspring exposure, is sufficient to reprogram larval behaviour, gene expression, and metabolism. Adult flies exposed to either ciprofloxacin or vancomycin produced third-instar larvae with significantly reduced crawling speed and a significantly higher prevalence of abnormal locomotion. Transcriptomic profiling revealed widespread downregulation of genes governing energy metabolism, particularly the tricarboxylic acid cycle, as well as cuticle development and protein folding. Metabolomic profiling identified elevation of L-norvaline across both antibiotic groups, and acute parental supplementation with L-norvaline alone recapitulated the observed crawling deficits, directly implicating this metabolite in the phenotype. These findings demonstrate that even brief disruption of the microbiome during oogenesis triggers a cascade of intergenerational physiological changes, establishing this window as a key period of microbiome-dependent offspring programming.

microbiology↗

bioRxiv2026

Visual consequences of saccades explain early cortical response dynamics during natural vision

During natural vision, each saccadic eye movement evokes a large cortical potential known as the lambda response. Traditionally, lambda responses have been considered feedforward responses to new visual input arriving at fixation. In contrast, here we show that they are best explained by the retinal shifts induced by the saccade itself. We first recorded EEG data for thousands of saccades during free viewing of natural scenes and then replayed the same retinal image shifts on a high-speed display during fixation. Temporal response dynamics were virtually identical for real saccades and replayed motion, and most strongly aligned to saccadic peak velocity. A computational model based only on saccade trajectories, 1/f natural-scene statistics, and known human spatiotemporal sensitivity parsimoniously reproduced these dynamics. Our results show that saccade intervals should not be viewed as a gap in visual processing, but as a structured sensory event that shapes human cortical activity during natural viewing.

neuroscience↗

bioRxiv2026

Static masks and saccadic velocity profile jointly reduce perceived motion: Evidence from simulated saccades

Saccadic eye movements sweep the visual scene across the retina, yet the resulting motion is rarely perceived. Visual factors alone, such as the presence of static pre- and post-saccadic input, can attenuate motion perception, suggesting effective masking of the motion signal during early visual processing. Here, we isolated the visual component of this reduction in motion perception using simulated saccades presented to fixating observers. Across two experiments, we manipulated motion amplitude (6-18 dva), duration, and velocity profile and measured perceived amplitude and velocity at varying masking durations. Visual masking strongly reduced perceived motion amplitude and velocity, with short halftimes ([~]15 ms) that were largely invariant across saccade amplitudes. Critically, motion following a naturalistic saccadic velocity profile was perceived as shorter and slower than constant-velocity motion matched in amplitude and duration, even without explicit masking. This additional reduction increased with both amplitude and duration. These results show that visual mechanisms alone can account for substantial motion reduction across a wide range of amplitudes and demonstrate a partially separable contribution of the saccadic velocity profile, suggesting that the temporal structure of retinal motion itself supports perceptual continuity across eye movements.

neuroscience↗

bioRxiv2025

High-fidelity, but hypometric spatial localization of afterimages across saccades

Humans typically perceive their visual world as stable and continuous, despite frequent shifts of the retinotopic reference frame caused by saccades. This visual stability is paralleled by afterimage movement across saccades: Although retinotopically stable, afterimages appear to move in egocentric space wherever the eye moves. To investigate the mechanisms underlying this phenomenon, we tasked human observers to localize afterimages relative to briefly flashed probes in complete darkness. This psychophysical tracking of afterimages was accompanied by eye tracking, allowing us to fit a dedicated computational model to accurately predict afterimage movement based on the size of eye movements. The gain of afterimage movement was significantly hypometric, remained unaffected by post-saccadic visual feedback and saccadic adaptation, and was inversely related to saccade gain. These findings suggest that afterimage movement is driven by efference-based, feedforward prediction of visual consequences of saccades and demonstrate the potential of the afterimage-tracking technique for studying visual stability. SignificanceIn low-light environments, brief high-intensity visual stimulation can induce long-lasting retinal afterimages. When observers then make eye movements to explore their visual environment, these afterimages - albeit fixed in the retinotopic frame of reference - appear to move in egocentric space wherever the eye moves. Even though this phenomenon has been known for centuries, the underlying computations remained unexplained. Tracking eye and afterimage positions simultaneously, we found that perceived afterimage position was accurately predicted by eye position across a variety of visuomotor conditions, whereby the eye movements size was however systematically underestimated by the visual system. Considering a parsimonious model of visual localization, afterimage movement can be understood as a consequence of feedforward predictions of the visual consequences of impending eye movements.

neuroscience↗

bioRxiv2025

Early visual signatures and benefits of intra-saccadic motion streaks

Eye movements routinely induce motion streaks as they shift visual projections across the retina at high speeds. To investigate the visual consequences of intra-saccadic motion streaks, we co-registered eye tracking and EEG while gaze-contingently shifting target objects during saccades, presenting either continuous, streaky or apparent, step-like motion in four directions. We found significant reductions of secondary saccade latency, as well as improved decoding of the post-saccadic target location from the EEG signal when motion streaks were available. These signals arose as early as 50 ms after saccade offset and had a clear occipital topography. Using a physiologically plausible visual processing model, we provide evidence that the targets motion trajectory is coded in orientation-selective channels and that speed of gaze correction was linked to the visual dynamics arising from the combination of saccadic and target motion, providing a parsimonious explanation of the behavioral benefits of intra-saccadic motion streaks.

neuroscience↗

bioRxiv2024

In utero human intestine contains maternally derived bacterial metabolites

Understanding when host-microbiome interactions are first established is crucial for comprehending normal development and identifying disease prevention strategies. Furthermore, bacterially derived metabolites play critical roles in shaping the intestinal immune system. Recent studies have demonstrated that memory T cells infiltrate human intestinal tissue early in the second trimester, suggesting that intestinal immune education begins in utero. Our previous study reported a unique fetal intestinal metabolomic profile with an abundance of several bacterially derived metabolites and aryl hydrocarbon receptor (AHR) ligands implicated in mucosal immune regulation. To follow up on this work, in the current study, we demonstrate that a number of microbial byproducts present in fetal intestines in utero are maternally derived and vertically transmitted to the fetus. Notably, these bacterially derived metabolites, particularly short chain fatty acids and secondary bile acids, are likely biologically active and functional in regulating the fetal immune system and preparing the gastrointestinal tract for postnatal microbial encounters, as the transcripts for their various receptors and carrier proteins are present in second trimester intestinal tissue through single-cell transcriptomic data.

microbiology↗

bioRxiv2024

Olive mill solid waste induces beneficial mushroom-specialized metabolite diversity: a computational metabolomics study.

IntroductionMushrooms contain besides proteins a diverse pallet of specialized metabolites bioactive in either beneficial or harmful manner. Therefore, mushrooms have been exploited by humans for centuries for dietary or medical purposes. For example, the edible and medicinal mushrooms Hericium erinaceus and Pleurotus eryngii are grown commercially around the world. In nature, H. erinaceus grows on old or dead tree trunks, and P. eryngii grows on Apiaceae plant roots, whereas in cultivation, they grow on substrates mainly consisting of dry wood chips, straw, and cereals. To make their farming more sustainable, supplements such as olive mill solid waste (OMSW) have been added to support mushroom development. However, so far, the impact of substrate additives on the edible mushroom metabolic content has not been assessed. MethodsHere, we examined the effect of different proportions of OMSW added to the substrate on the metabolic profiles of the fruiting body (FB) and mycelium of H. erinaceus and P. eryngii mushrooms. We used computational metabolomics strategies including GNPS molecular networking, MS2Query, and the FERMO dashboard, to organize, annotate, and prioritize metabolite features from the untargeted Q-Exactive Plus HR-LC-MS/MS metabolomics data. Following chromatography-based fractionation, the metabolite annotation of four metabolite features was further validated or fine-tuned using 1H-NMR, to resolve structural isomers. Results & DiscussionOur computational metabolomics strategies showed several annotated metabolite features to be affected by OSMW concentration. In general, the methanolic extracts of H. erinaceus FB and mycelium were more highly enriched with specialized metabolites than those of P. eryngii. Interestingly, OMSW increased several hericenone analogues in the H. erinaceus FB, to which beneficial properties, such as anti-inflammatory, anticancer and neuroprotective properties are assigned, as well as several erinacerin metabolites from the mycelium. In addition, high concentrations of OMSW decreased the toxic enniatin metabolite abundance. In conclusion, we demonstrate how a change in substrate composition affects the mushrooms specialized metabolome and can induce beneficial mushroom metabolite diversity. These results highlight the importance of including computational metabolomic strategies to investigate new sustainable growth options for edible mushrooms and other natural foods.

biochemistry↗

bioRxiv2023

Lawful kinematics link eye movements to the limits of high-speed perception

Perception relies on active sampling of the environment. What part of the physical world can be sensed is limited by biophysical constraints of sensory systems, but might be further constrained by the kinematic bounds of the motor actions that acquire sensory information. We tested this fundamental idea for humans fastest and most frequent behavior--saccadic eye movements--which entails retinal motion that commonly escapes visual awareness. We discover that the visibility of a high-speed stimulus, presented during fixation, is predicted by the lawful sensorimotor contingencies that saccades routinely impose on the retina, reflecting even distinctive variability between observers movements. Our results suggest that the visual systems functional and implementational properties are best understood in the context of movement kinematics that impact its sensory surface.

neuroscience↗

bioRxiv2023

Saccadic omission revisited: What saccade-induced smear looks like

During active visual exploration, saccadic eye movements rapidly shift the visual image across the human retina. Although these high-speed shifts occur at a high rate and introduce considerable amounts of motion smear during natural vision, our perceptual experience is oblivious to it. This saccadic omission, however, does not entail that saccadeinduced motion smear cannot be perceived in principle. Using tachistoscopic displays of natural scenes, we rendered saccade-induced smear highly conspicuous. By systematically manipulating peri-saccadic display durations we studied the dynamics of smear in a time-resolved manner, assessing identification performance of smeared scenes, as well as perceived smear amount and direction. Both measures showed distinctive, U-shaped time courses throughout the saccade, indicating that generation and reduction of perceived smear occurred during saccades. Moreover, low spatial frequencies and orientations parallel to the direction of the ongoing saccade were identified as the predominant visual features encoded in motion smear. We explain these findings using computational models that assume no more than saccadic velocity and human contrast sensitivity profiles, and present a motion-filter model capable of predicting observers perceived amount of smear based on their eyes trajectories, suggesting a direct link between perceptual and saccade dynamics. Replays of the visual consequences of saccades during fixation led to virtually identical results as actively making saccades, whereas the additional simulation of perisaccadic contrast suppression heavily reduced this similarity, providing strong evidence that no extra-retinal process was needed to explain our results. Saccadic omission of motion smear may be conceptualized as a parsimonious visual mechanism that emerges naturally from the interplay of retinal consequences of saccades and early visual processing.

neuroscience↗

bioRxiv2021

Definition, modeling and detection of saccades in the face of post-saccadic oscillations

When analyzing eye tracking data, one of the central tasks is the detection of saccades. Although many automatic saccade detection algorithms exist, the field still debates how to deal with brief periods of instability around saccade offset, so-called post-saccadic oscillations (PSOs), which are especially prominent in todays widely used video-based eye tracking techniques. There is good evidence that PSOs are caused by inertial forces that act on the elastic components of the eye, such as the iris or the lens. As this relative movement can greatly distort estimates of saccade metrics, especially saccade duration and peak velocity, video-based eye tracking has recurrently been considered unsuitable for measuring saccade kinematics. In this chapter, we review recent biophysical models that describe the relationship between pupil motion and eyeball motion. We found that these models were well capable of accurately reproducing saccade trajectories and implemented a framework for the simulation of saccades, PSOs, and fixations, which can be used - just like datasets hand-labelled by human experts - to evaluate detection algorithms and train statistical models. Moreover, as only pupil and corneal-reflection signals are observable in video-based eye tracking, one may also be able to use these models to predict the unobservable motion of the eyeball. Testing these predictions by analyzing saccade data that was registered with video-based and search-coil eye tracking techniques revealed strong relationships between the two types of measurements, especially when saccade offset is defined as the onset of the PSO. To enable eye tracking researchers to make use of this definition, we present and evaluate two novel algorithms - one based on eye-movement direction inversion, one based on linear classifiers previously trained on simulation data. These algorithms allow for the detection of PSO onset with high fidelity. Even though PSOs may still pose problems for a range of eye tracking applications, the techniques described here may help to alleviate these.

neuroscience↗

bioRxiv2020

Cell autonomous TGF-beta signaling is essential for cell recruitment into degenerating tendons

Understanding the role of cell recruitment in tendon disorders is critical for improvements in regenerative therapy. We recently reported that targeted disruption of TGF{beta} type II receptor in the tendon cell lineage (Tgfbr2ScxCre) resulted in tenocyte dedifferentiation and tendon degradation in post-natal stages. Here we extend the analysis and identify direct recruitment of stem/progenitor cells into the degenerative mutant tendons. Cre-lineage tracing indicates that these cells are not derived from tendon ensheathing tissues or from a Scleraxis-lineage, and they turned on tendon markers only upon entering the mutant tendons. Through immunohistochemistry and inducible gene deletion, we further find that the recruited cells originated from a Sox9-expressing lineage and their recruitment was dependent on cell-autonomous TGF{beta} signaling. These results thus differ from previous reports of cell recruitment into injured tendons, and suggest a critical role for TGF{beta} signaling and cell recruitment in the etiology and treatment of tendon degeneration.

cell biology↗

bioRxiv2020

Enhancer of Zeste Homolog 2 (Ezh2) is essential for patterning of multiple musculoskeletal tissues but dispensable for tendon differentiation

An efficient musculoskeletal system depends on the precise assembly and coordinated growth and function of muscles, skeleton and tendons. However, the mechanisms that drive integrated musculoskeletal development and coordinated growth and differentiation of each of these tissues are still being uncovered. Epigenetic modifiers have emerged as critical regulators of cell fate differentiation, but so far almost nothing is known about their roles in tendon biology. Previous studies have shown that epigenetic modifications driven by Enhancer of zeste homolog 2 (EZH2), a major histone methyltransferase, have significant roles in vertebrate development including skeletal patterning and bone formation. We now find that targeting Ezh2 through the limb mesenchyme also has significant effects on tendon and muscle patterning, likely reflecting the essential roles of early mesenchymal cues mediated by Ezh2 for coordinated patterning and development of all tissues of the musculoskeletal system. Conversely, loss of Ezh2 in the tendon cells did not disrupt the tendon cell fate suggesting that tenocyte differentiation and tendon maturation are independent of Ezh2 signaling.

developmental biology↗

bioRxiv2020

BMP signalling directs a fibroblast-to-myoblast conversion at the connective tissue/muscle interface to pattern limb muscles

Positional information driving limb muscle patterning is contained in lateral plate mesoderm-derived tissues, such as tendon or muscle connective tissue but not in myogenic cells themselves. The long-standing consensus is that myogenic cells originate from the somitic mesoderm, while connective tissue fibroblasts originate from the lateral plate mesoderm. We challenged this model using cell and genetic lineage tracing experiments in birds and mice, respectively, and identified a subpopulation of myogenic cells at the muscle tips close to tendons originating from the lateral plate mesoderm and derived from connective tissue gene lineages. Analysis of single-cell RNA-sequencing data obtained from limb cells at successive developmental stages revealed a subpopulation of cells displaying a dual muscle and connective tissue signature, in addition to independent muscle and connective tissue populations. Active BMP signalling was detected in this junctional cell sub-population and at the tendon/muscle interface in developing limbs. BMP gain- and loss-of-function experiments performed in vivo and in vitro showed that this signalling pathway regulated a fibroblast-to-myoblast conversion. We propose that localised BMP signalling converts a subset of lateral plate mesoderm-derived fibroblasts to a myogenic fate and establishes a boundary of fibroblast-derived myonuclei at the muscle/tendon interface to control the muscle pattern during limb development.

developmental biology↗

bioRxiv2020

Intra-saccadic motion streaks jump-start gaze correction

Rapid eye movements (saccades) incessantly shift objects across the retina. To establish object correspondence, the visual system is thought to match surface features of objects across saccades. Here we show that an objects intra-saccadic retinal trace - a signal previously considered unavailable to visual processing - facilitates this match-making. Human observers made saccades to a cued target in a circular stimulus array. Using high-speed visual projection, we swiftly rotated this array during the eyes flight, displaying continuous intra-saccadic target motion. Observers saccades landed between the target and a distractor, prompting secondary saccades. Independently of the availability of object features, which we controlled tightly, target motion increased the rate and reduced the latency of gaze-correcting saccades to the initial pre-saccadic target, in particular when the targets stimulus features incidentally gave rise to efficient motion streaks. These results suggest that intra-saccadic visual information informs the establishment of object correspondence and jump-starts gaze correction.

neuroscience↗

bioRxiv2020

Local retinoic acid directs emergence of the extraocular muscle functional unit

Coordinated development of muscles, tendons, and their attachment sites ensures emergence of functional musculoskeletal units that are adapted to diverse anatomical demands among different species. How these different tissues are patterned and functionally assembled during embryogenesis is poorly understood. Here, we investigated the morphogenesis of extraocular muscles (EOMs), an evolutionary conserved cranial muscle group that is crucial for the coordinated movement of the eyeballs and for visual acuity. By means of lineage analysis, we redefined the cellular origins of periocular connective tissues interacting with the EOMs, which do not arise exclusively from neural crest mesenchyme as previously thought. Using 3D imaging approaches, we established an integrative blueprint for the EOM functional unit. By doing so, we identified a developmental time window where individual EOMs emerge from a unique muscle anlage and establish insertions in the sclera, which sets these muscles apart from classical muscle-to-bone type of insertions. Further, we demonstrate that the eyeballs are a source of diffusible retinoic acid that allow their targeting by the EOMs in a temporal and dose dependent manner. Using genetically modified mice and inhibitor treatments, we find that endogenous local variations in the concentration of retinoids contribute to the establishment of tendon condensations and attachment sites that precede the initiation of muscle patterning. Collectively, our results highlight how global and site-specific programs are deployed for the assembly of muscle functional units with precise definition of muscle shapes and topographical wiring of their tendon attachments.

developmental biology↗

bioRxiv2019

TGF-β signaling is critical for maintenance of the tendon cell fate

Studies of cell fate focus on specification, but little is known about maintenance of the differentiated state. We find that TGF{beta} signaling plays an essential role in maintenance of the tendon cell fate. To examine the role TGF{beta} signaling in tenocytes TGF{beta} type II receptor was targeted in the Scleraxis cell lineage. Tendon development was not disrupted in mutant embryos, but shortly after birth tenocytes lost differentiation markers and reverted to a more stem/progenitor state. Targeting of Tgfbr2 using other Cre drivers did not cause tenocyte dedifferentiation suggesting a critical significance for the spatio-temporal activity of ScxCre. Viral reintroduction of Tgfbr2 to mutants was sufficient to prevent and even rescue mutant tenocytes suggesting a continuous and cell-autonomous role for TGF{beta} signaling in cell fate maintenance. These results uncover the critical importance of molecular pathways that maintain the differentiated cell fate and a key role for TGF{beta} signaling in these processes.

cell biology↗

bioRxiv2019

An adaptive algorithm for fast and reliable online saccade detection

To investigate visual perception around the time of eye movements, vision scientists manipulate stimuli contingent upon the onset of a saccade. For these experimental paradigms, timing is especially crucial, as saccade offset imposes a deadline on the display change. Although efficient online saccade detection can greatly improve timing, most algorithms rely on spatial-boundary techniques or absolute-velocity thresholds, which both suffer from their respective weaknesses: late detections and false alarms. We propose an adaptive, velocity-based algorithm for online saccade detection that surpasses both standard techniques in speed and accuracy and allows the user to freely define detection criteria. Inspired by the Engbert-Kliegl-algorithm for microsaccade detection, our algorithm computes two-dimensional velocity thresholds from variance in preceding fixation samples, while compensating for noisy or missing data samples. An optional direction criterion limits detection to the instructed saccade direction, further increasing robustness. We validated the algorithm by simulating its performance on a large saccade dataset and found that high detection accuracy (false-alarm rates of <1%) could be achieved with detection latencies of only 3 milliseconds. High accuracy was maintained even under simulated high-noise conditions. To demonstrate that purely intra-saccadic presentations are technically feasible, we devised an experimental test, in which a Gabor patch drifted at saccadic peak velocities. While this stimulus was invisible when presented during fixation, observers reliably detected it during saccades. Photodiode measurements verified that - including all system delays - stimuli were physically displayed on average 20 ms after saccade onset. Thus, the proposed algorithm provides valuable tool for gaze-contingent paradigms.

neuroscience↗

bioRxiv2018

Limb- and tendon-specific Adamtsl2 deletion identifies a soft tissue mechanism modulating bone length

Disproportionate distal limb shortening is the hallmark of acromelic dysplasias. Among them, geleophysic dysplasia is a rare, frequently lethal condition characterized by severe short stature, musculoskeletal, cardiac, pulmonary, and skin anomalies. Geleophysic dysplasia results from dominant fibrillin-1 (FBN1) or recessive ADAMTSL2 mutations, suggesting a functional link between ADAMTSL2 and FBN1. Mice lacking ADAMTSL2 die at birth, precluding analysis of postnatal skeletal growth and mechanisms underlying the skeletal anomalies of geleophysic dysplasia. We show that Adamtsl2 is expressed in limb soft tissues, predominantly in tendon. Expression in developing bones is limited to their terminal cell layers that are destined to become articular cartilage and is absent in growth plate cartilage. Adamtsl2 conditional deletion in limb mesenchyme using Prxl-Cre led to an acromelic dysplasia, providing a suitable model for investigation of geleophysic dysplasia. Unexpectedly, conditional Adamtsl2 deletion using Scx-Cre, a tendon-specific deleter, also impaired skeletal growth. Specific morphogenetic anomalies were seen in Achilles tendon, along with FBN1 accumulation. Thus, ADAMTSL2, shown here to bind fibrillin microfibrils in vitro, limits fibrillin microfibril formation in tendons and promotes tendon growth. The findings suggest that reduced bone growth in geleophysic dysplasia results from external tethering by short tendons rather than intrinsic growth plate anomalies.

developmental biology↗