Biology subjects

Bartels, A.

Publications and source records attributed to Bartels, A..

14 recordsLinked to original sources

bioRxiv2026

S-Adenosyl-D-methionine as a Non-Physiological Substrate for a Wide Range of SAM-Dependent Enzymes

The ability of SAM-dependent enzymes to accept S-adenosyl-D-methionine [D-SAM, (SS,RC)-SAM] instead of the native cofactor S-adenosyl-L-methionine [L-SAM, (SS,SC)-SAM] remains largely unexplored. Challenging the stereochemical preference of SAM-dependent enzymes, we investigated the ability of different enzyme classes to accept D-SAM. Contrary to common assumptions, the tested N- and O-methyl transferases (MTs), as well as one of the examined C-MTs accepted D-SAM. Docking studies suggest that acceptance of D-SAM by C-MTs may be influenced by the angle between the transferable methyl group of SAM and the nucleophilic carbon of the substrate, along with enzyme and substrate flexibility. In addition to conventional MTs, the radical SAM glutamine C-MT QCMT showed low but detectable methylation activity with D-SAM. Furthermore, the azetidine-2-carboxylic acid synthase AzeJ not only uses D-SAM but also incorporates the stereocentre of D-methionine into the cyclic amino acid product. The pyridoxal 5'-phosphate (PLP)-dependent enzyme 1-aminocyclopropyl-1-carboxylic acid synthase (ACCS) also showed detectable turnover with D-SAM. These findings broaden the understanding of enzyme stereoselectivity, provide an overview of D-SAM-utilising enzymes, and identify first enzyme systems that may serve as starting points for engineering efforts aimed at shifting cofactor preference towards D-SAM.

biochemistry↗

bioRxiv2025

(R)-S-Adenosyl-L-methionine hydrolases counter sulfonium epimerisation in thermophilic archaea

S-Adenosyl-L-methionine (SAM) is the second most used enzyme cofactor and vital for numerous cellular reactions such as methylation or polyamine synthesis. While most stereocentres of the biologically active (SS,SC)-SAM are fixed, epimerisation at the methyl sulfonium centre is driven by heat, yielding biologically inactive (RS,SC)-SAM. This SAM diastereomer disturbs SAM-dependent pathways, posing a metabolic threat especially to thermophilic organisms. In vitro analysis shows that SAM hydrolases cleave the biologically inactive (RS,SC)-SAM, thereby constituting to a metabolic salvage pathway. For further analysis of the biological relevance, we characterised two archaeal SAM hydrolases from the thermophilic Sulfolobus acidocaldarius and the halophilic Haloferax volcanii, confirming their selectivity towards (RS,SC)-SAM in vitro. Genetic manipulation in the native hosts supports a significant role of the SAM-hydrolases in decreasing the share of intracellular (RS,SC)-SAM to sustain cellular functions in thermophilic organisms.

biochemistry↗

bioRxiv2022

Loss of Linker Histone H1 in the Maternal Genome Influences DEMETER-Mediated Demethylation and Affects the Endosperm DNA Methylation Landscape

The Arabidopsis DEMETER (DME) DNA glycosylase demethylates the central cell genome prior to fertilization. This epigenetic reconfiguration of the female gamete companion cell establishes gene imprinting in the endosperm and is essential for seed viability. DME demethylates small and genic-flanking transposons as well as intergenic and heterochromatin sequences, but how DME is recruited to these target loci remains unknown. H1.2 was identified as a DME-interacting protein in a yeast two-hybrid screen, and maternal genome H1 loss affects DNA methylation and expression of selected imprinted genes in the endosperm. Yet, the extent to which how H1 influences DME demethylation and gene imprinting in the Arabidopsis endosperm has not been investigated. Here, we showed that unlike in the vegetative cell, both canonical histone H1 variants are present in the central cell. Our endosperm methylome analysis revealed that without the maternal linker histones, DME-mediated demethylation is facilitated, particularly in the heterochromatin regions, indicating that H1-containing nucleosomes are barriers for DME demethylation. Loss of H1 in the maternal genome has a very limited effect on gene transcription or gene imprinting regulation in the endosperm; however, it variably influences euchromatin TE methylation and causes a slight hypermethylation and a reduced expression in selected imprinted genes. We conclude that loss of maternal H1 indirectly influences DME-mediated demethylation and endosperm DNA methylation landscape but does not appear to affect endosperm gene transcription and overall imprinting regulation.

plant biology↗

bioRxiv2022

Mouse primary visual cortex neurons respond to the illusory ''darker than black'' in neon color spreading.

Illusions are a powerful tool for studying the single neuron correlates of perception. Here, we introduce the neon color spreading (NCS) illusion in mice and report the neuronal correlates of illusory brightness, which has heretofore only been studied using human fMRI. We designed a novel NCS paradigm to evoke the percept of an illusory drifting grating and analyzed the activity of 520 single units in the mouse primary visual cortex (V1). A substantial proportion of V1 single units (60.5%) responded to illusory gratings with direction tuning matched to their preferred direction, which was determined using physically presented luminance-defined gratings (LDG). Moreover, by presenting LDG gratings with a 180{degrees} phase shift relative to NCs gratings, we show that spatial phase tuning shifted 180{degrees} for most single units. This finding conclusively demonstrates that V1 single units respond to illusory brightness. Using this novel mouse paradigm, we show that responses to illusory gratings have a lower magnitude and are delayed relative to physical gratings. We determined where V1 single units fell in the V1 cellular hierarchy (based on their susceptibility to surround suppression, their putative classification as interneuron or pyramidal neuron, and designation as a simple or complex cell) and found that higher-level V1 single units are more responsive to NCS stimuli. These findings resolve the debate of whether V1 is involved in illusory brightness processing and reveal a V1 hierarchical organization in which higher-level neurons are pivotal to the processing of illusory qualities, such as brightness.

neuroscience↗

bioRxiv2021

Integration of visual motion and pursuit signals in areas V3A and V6+ across cortical depth using 9.4T fMRI

Neural mechanisms underlying a stable perception of the world during pursuit eye movements are not fully understood. Both, perceptual stability as well as perception of real (i.e. objective) motion are the product of integration between motion signals on the retina and efference copies of eye movements. Human areas V3A and V6 have previously been shown to have strong objective ( real) motion responses. Here we used high-resolution laminar fMRI at ultra-high magnetic field (9.4T) in human subjects to examine motion integration across cortical depths in these areas. We found an increased preference for objective motion in areas V3A and V6+ i.e. V6 and possibly V6A towards the upper layers. When laminar responses were detrended to remove the upper-layer bias present in all responses, we found a unique, condition-specific laminar profile in V6+, showing reduced mid-layer responses for retinal motion only. The results provide evidence for differential, motion-type dependent laminar processing in area V6+. Mechanistically, the mid-layer dip suggests a special contribution of retinal motion to integration, either in the form of a subtractive (inhibitory) mid-layer input, or in the form of feedback into extragranular or infragranular layers. The results show that differential laminar signals can be measured in high-level motion areas in the human occipitoparietal cortex, opening the prospect of new mechanistic insights using non-invasive brain imaging. Significance StatementVisual stability and our ability to differentiate between self-induced and real motion are central to our visual sense. Both require the integration of two signals - retinal motion and copies of muscle commands used for eye movements (efference copies). A reasonable assumption is that either the efference copy or the result of integration will be conveyed to high-level visual regions along with visual retinal input, possibly differentially across cortical depth as the input sources differ. Our ultra-high field recordings present the first laminar evidence of differential signal processing of retinal and objective motion signals in area V6+, and present a first window into a mechanistic understanding of visual high-level motion processing.

neuroscience↗

bioRxiv2021

Gene flow influences the genomic architecture of local adaptation in six riverine fish species

Understanding how gene flow influences adaptive divergence is important for predicting adaptive responses. Theoretical studies suggest that when gene flow is high, clustering of adaptive genes in fewer genomic regions would protect adaptive alleles from among-population recombination and thus be selected for, but few studies have tested this hypothesis with empirical data. Here, we used RADseq to generate genomic data for six fish species with contrasting life histories from six reaches of the Upper Mississippi River System, USA. We then conducted genome scans for genomic islands of divergence to examine the distribution of adaptive loci and investigated whether these loci were found in inversions. We found that gene flow varied among species, and adaptive loci were clustered more tightly in species with higher gene flow. For example, the two species with the highest overall FST (0.03 - 0.07) and therefore lowest gene flow showed little evidence of clusters of adaptive loci, with adaptive loci spread uniformly across the genome. In contrast, nearly all adaptive loci in the species with the lowest FST (0.0004) were found in a single large putative inversion. Two other species with intermediate gene flow (FST ~ 0.004) also showed clustered genomic architectures, with most islands of divergence clustered on a few chromosomes. These results provide important empirical evidence to support the hypothesis that increasingly clustered architectures of local adaptation are associated with high gene flow. Our study utilized a unique system with species spanning a large gradient of life histories to highlight the importance of gene flow in shaping adaptive divergence.

evolutionary biology↗

bioRxiv2021

Disrupting short-term memory in premotor but not visual cortex affects serial dependence in visuomotor integration

Human behavior is biased by past experience. For example, when intercepting a moving target, the speed of previous targets will bias responses in future trials. Neural mechanisms underlying this so-called serial dependence are still under debate. Here, we tested the hypothesis that the previous trial leaves a neural trace in brain regions associated with encoding task-relevant information in visual and/or motor regions. We reasoned that injecting noise by means of transcranial magnetic stimulation (TMS) over premotor and visual areas would degrade such memory traces and hence reduce serial dependence. To test this hypothesis, we applied bursts of TMS pulses to right visual motion processing region hV5/MT+ and to left dorsal premotor cortex during inter-trial intervals of a coincident timing task performed by twenty healthy human participants (15 female). Without TMS, participants presented a bias towards the speed of the previous trial when intercepting moving targets. TMS over dorsal premotor cortex decreased serial dependence in comparison to the control Vertex stimulation, whereas TMS applied over hV5/MT+ did not. In addition, TMS seems to have specifically affected the memory trace that leads to serial dependence, as we found no evidence that participants behavior worsened after applying TMS. These results provide causal evidence that an implicit short-term memory mechanism in premotor cortex keeps information from one trial to the next, and that this information is blended with current trial information so that it biases behavior in a visuomotor integration task with moving objects. Significance StatementHuman perception and action are biased by the recent past. The origin of such serial bias is still not fully understood, but a few components seem to be fundamental for its emergence: the brain needs to keep previous trial information in short-term memory and blend it with incoming information. Here, we present evidence that a premotor area has a potential role in storing previous trial information in short-term memory in a visuomotor task, and that this information is responsible for biasing ongoing behavior. These results corroborate the perspective that areas associated with processing information of a stimulus or task also participate in maintaining that information in short-term memory even when this information is no longer relevant for current behavior.

neuroscience↗

bioRxiv2021

Separated and overlapping neural coding of face and body identity

Recognising a persons identity often relies on face and body information, and is tolerant to changes in low-level visual input (e.g. viewpoint changes). Previous studies have suggested that face identity is disentangled from low-level visual input in the anterior face-responsive regions. It remains unclear which regions disentangle body identity from variations in viewpoint, and whether face and body identity are encoded separately or combined into a coherent person identity representation. We trained participants to recognize three identities, and then recorded their brain activity using fMRI while they viewed face and body images of the three identities from different viewpoints. Participants task was to respond to either the stimulus identity or viewpoint. We found consistent decoding of body identity across viewpoint in the fusiform body area, right anterior temporal cortex, middle frontal gyrus and right insula. This finding demonstrates a similar function of fusiform and anterior temporal cortex for bodies as has previously been shown for faces, suggesting these regions may play a general role in extracting high-level identity information. Moreover, we could decode identity across neural activity evoked by faces and bodies in the early visual cortex, right inferior occipital cortex, right parahippocampal cortex and right superior parietal cortex, revealing a distributed network that encodes person identity abstractly. Lastly, identity decoding was consistently better when participants attended to identity, indicating that attention to identity enhances its neural representation. These results offer new insights into how the brain develops an abstract neural coding of person identity, shared by faces and bodies.

neuroscience↗

bioRxiv2020

Large-scale color biases in the retinotopic functional architecture are shared across human brains

Despite the functional specialization in visual cortex, there is growing evidence that the processing of chromatic and spatial visual features is intertwined. While past studies focused on visual field biases in retina and behaviour, large-scale dependencies between coding of color and retinotopic space are largely unexplored in the cortex. Here we asked whether spatial color biases are shared across different human observers, and whether they are idiosyncratic for distinct areas. We tested this by predicting the color a person was seeing using a linear classifier that has never been trained on chromatic responses from that same brain, solely by taking into account: (1) the chromatic responses in other individuals brains and (2) commonalities between the spatial coding in brains used for training and the test brain. We were able to predict the color (and luminance) of stimuli seen by an observer based on other subjects activity patterns in areas V1-V3, hV4 and LO1. In addition, we found that different colors elicited systematic, large-scale retinotopic biases that were idiosyncratic for distinct areas and common across brains. The area-specific spatial color codes and their conservation across individuals suggest functional or evolutionary organization pressures that remain to be elucidated. Significance statementDoes a color elicit comparable neural activity in two different observers? We addressed these questions, which involved the central test to predict what color someone is seeing based on their brain activity if it is only known how other brains respond to color. We estimated the commonalities across brains in the way they respond to achromatic, spatial stimulation, which allowed us to retinotopically align different brain responses to each other in a common response space. In this space derived without any color responses we could decode across brains what color an observer was seeing and found that spatial color biases differed between areas. Our results demonstrate systematic dependencies between chromatic and visual field representations that are area-specific and preserved across observers.

neuroscience↗

bioRxiv2019

Conscious perception of flickering stimuli in binocular rivalry and continuous flash suppression is not affected by tACS-induced SSR modulation

The content of conscious perception is known to correlate with steady-state responses (SSRs), yet their causal relationship remains unclear. Can we manipulate conscious perception by directly interfering with SSRs through transcranial alternating current stimulation (tACS)? Here, we directly addressed this question in three experiments involving binocular rivalry and continuous flash suppression (CFS). Specifically, while participants (N=24) viewed either binocular rivalry or tried to detect stimuli masked by CFS, we applied sham or real tACS across parieto-occipital cortex at either the same or a different frequency and phase as an SSR eliciting flicker stimulus. We found that tACS did not differentially affect conscious perception in the forms of predominance, CFS detection accuracy, reaction time, or metacognitive sensitivity, confirmed by Bayesian statistics. We conclude that tACS application at frequencies of stimulus-induced SSRs does not have perceptual effects and that SSRs may be epiphenomenal to conscious perception.

neuroscience↗

bioRxiv2019

Family aggregation analysis reveals a heritable background of equine grass sickness (dysautonomia)

Equine grass sickness (also known as dysautonomia) is a life-threatening polyneuropathic disease affecting horses with approx. 80% mortality. Since its first description over a hundred years ago, several factors including phenotypic, environmental, management, climate, and intestinal microbiome) have been associated with increased risk of dysautonomia. But despite the extensive research on dysautonomia, its causative factors have yet been identified. A retrospective pedigree and phenotype based genetic epidemiological study was performed to analyze the associations of disease occurrence and the kinship in a Hungarian large scale stud. The pedigree data set containing 1233 horses with 49 affected animals was used in the analysis. The first finding was that among the descendants of some stallions the proportion of affected animals are unexpectedly high, with a maximum of 25% of a stallions descendants affected. Animals with affected siblings have higher odds to be a case (OR: 1.27, 95% CI: 1.01-1.57, p=0.033). Among males in the affected population the odds of dysautonomia is higher than in females (OR: 1.76, 95% CI: 0.95-3.29, p=0.057). Significant familial clustering was observed among the affected animals (GIF p=0.001). Further subgroups were identified with significant (p<0.001) aggregation among close relatives using kinship-based methods. Our analysis of the data and the observed higher disease frequency in males suggests that dysautonomia may have X-linked recessive inheritance as a causal factor. This is the first study providing ancestry data and suggesting a genetic contribution to the likely multifactorial causes of the disease.

genetics↗

bioRxiv2018

Speed tuning to real-world- and retinal motion in cortical motion regions

Motion signals can arise for two reasons in the retina: due to self-motion or due to real motion in the environment. Prior studies on speed tuning always measured joint responses to real and retinal motion, and for some of the more recently identified human motion processing regions, speed tuning has not been examined in at all. We localized motion regions V3A, V6, V5/MT, MST and cingulate sulcus visual area (CSv) in 20 human participants, and then measured their responses to motion velocities from 1-24 degrees per second. Importantly, we used a pursuit paradigm that allowed us to quantify responses to objective and retinal motion separately. In order to provide optimal stimulation, we used stimuli with natural image statistics derived from Fourier scrambles of natural images. The results show that all regions increased responses with higher speeds for both, retinal and objective motion. V3A stood out in that it was the only region whose slope of the speed-response function for objective motion was higher than that for retinal motion. V6, V5/MT, MST and CSv did not differ in objective and retinal speed slopes, even though V5/MT and MST tended to respond more to objective motion at all speeds. These results reveal highly similar speed tuning functions for early and high-level motion regions, and support the view that human V3A encodes primarily objective rather than retinal motion signals.

neuroscience↗

bioRxiv2018

Motion regions are modulated by scene content

Creating a stable perception of the world during pursuit eye movements is one of the everyday roles of visual system. Some motion regions have been shown to differentiate between motion in the external world from that generated by eye movements. However, in most circumstances, perceptual stability is consistently related to content: the surrounding scene is typically stable. However, no prior study has examined to which extent motion responsive regions are modulated by scene content, and whether there is an interaction between content and motion response. In the present study we used a factorial design that has previously been shown to reveal regional involvement in integrating efference copies of eye-movements with retinal motion to mediate perceptual stability and encode real-world motion. We then added scene content as a third factor, which allowed us to examine to which extent real-motion, retinal motion, and static responses were modulated by meaningful scenes versus their Fourier scrambled counterpart. We found that motion responses in human motion responsive regions V3A, V6, V5+/MT+ and cingulate sulcus visual area (CSv) were all modulated by scene content. Depending on the region, these motion-content interactions differentially depended on whether motion was self-induced or not. V3A was the only motion responsive region that also showed responses to still scenes. Our results suggest that contrary to the two-pathway hypothesis, scene responses are not isolated to ventral regions, but also can be found in dorsal areas.

neuroscience↗

bioRxiv2017

Objective (Real-World) Motion Responses In Scene Responsive Regions

We perceive scenes as stable even when eye movements induce retinal motion, for example during pursuit of a moving object. Mechanisms mediating perceptual stability have primarily been examined in motion regions of the dorsal visual pathway. Here we examined whether motion responses in human scene regions are encoded in eye- or world centered reference frames. We recorded brain responses in human participants using fMRI while they performed a well-controlled visual pursuit paradigm previously used to examine dorsal motion regions. In addition, we examined effects of content by using either natural scenes or their Fourier scrambles. We found that parahippocampal place area (PPA) responded to motion only in world- but not in eye-centered coordinates, regardless of scene content. The occipital place area (OPA) responded to both, objective and retinal motion equally, and retrosplenial cortex (RSC) had no motion responses but responded to pursuit. Only PPAs objective motion responses were higher during scenes than scrambled images, although there was a similar trend in OPA. These results indicate a special role of PPA in representing its content in real-world coordinates. Our results question a strict subdivision of dorsal \"what\" and ventral \"where\" streams, and suggest a role of PPA in contributing to perceptual stability.

neuroscience↗