Biology subjects

Weiss, B.

Publications and source records attributed to Weiss, B..

16 recordsLinked to original sources

bioRxiv2026

Neurite Complexity and Plasticity Markers Track Synaptic Vesicle Density in the Living Human Brain: A Multimodal PET-MRI-EEG Study

Neuroplasticity, the brain's capacity to reorganise its structure and function, is a transdiagnostic feature across psychiatric and neurodegenerative diseases and a putative mechanism of action for pharmacological interventions. [11C]-UCBJ positron emission tomography (PET), which quantifies synaptic vesicle glycoprotein 2A (SV2A) density, offers the most direct in vivo measure of human synaptic density, but its relationship to complementary, more scalable neuroimaging measures of structural and functional plasticity remains uncharacterised. We combined [11C]-UCBJ PET, diffusion weighted imaging (DWI/NODDI), resting-state functional magnetic resonance imaging (rs-fMRI), and electroencephalography (EEG)-based sensory tasks (roving mismatch negativity, MMN; visual long-term potentiation, vLTP) in 18 healthy volunteers to test the relationship between synaptic terminal SV2A density and complementary structural and functional neuroplasticity measures, and whether these relationships were reproducible following pharmacological challenge with ketamine (n = 11) or N,N-dimethyltryptamine (DMT; n = 7). There were no statistically significant differences in PET-derived SV2A binding potential (BPND), DWI-derived neurite orientation dispersion (ODI) and structural weighted degree (SWD), EEG-derived MMN repetition suppression, and late-phase vLTP P2 potentiation, 1 to 8 days following DMT and ketamine exposure compared to baseline. BPND was coupled with ODI across cortical regions before and after pharmacological challenge, and this relationship was tighter within visual, attentional, and frontoparietal control brain networks. SWD showed a weaker, more spatially restricted association with BPND, primarily in regions belonging to the limbic and visual brain networks, but was not replicated post-drug. No consistent association was found between BPND and functional weighted degree (FWD), derived from rs-fMRI, at baseline or after pharmacological challenge. Frontotemporal BPND was positively associated with MMN repetition suppression (r = 0.61), and occipital BPND with late-phase vLTP P2 potentiation (r = 0.54), with the MMN-BPND association replicating after pharmacological challenge (r = 0.49). These findings link synaptic terminal SV2A density in the living human brain to neurite architecture and the capacity for short-term and Hebbian-like long-term synaptic plasticity, while dissociating these relationships from generic functional connectivity and magnitude of sensory-evoked responses. These data provide cross-modal validation for DWI- and EEG-derived measures as biological indices and surrogate measures of human synaptic plasticity.

neuroscience↗

bioRxiv2026

Cognitive exertion reshapes resting-state EEG markers across the adult lifespan

Resting-state electroencephalography (rsEEG) yields robust indices of ageing, notably individual alpha peak frequency (iAPF), alpha power, and the aperiodic exponent. Whether these markers reflect stable traits or shift with cognitive exertion remains unresolved, with direct consequences for lifespan and clinical research. We parameterised periodic and aperiodic rsEEG activity before and after cognitive tasks in a lifespan cohort (N = 390, aged 20-70), a five-year longitudinal follow-up (N = 100), and an independent older-adult dataset completing a different task (N = 71). Across datasets, cognitive exertion produced lifespan-wide iAPF slowing and increase in associated power. Notably, aperiodic shifts were age-dependent, with post-task steepening of the exponent in younger adults that progressively flattened with advancing age, resulting in a stronger effect of age on post-task exponents. Our results demonstrate that widely used spectral metrics exhibit acute state-dependency and post-task recordings offer a promising translational framework for indexing individual differences in healthy ageing and pathology. Trial registrationClinicaltrials.gov: NCT05155397

neuroscience↗

bioRxiv2025

A multi-partner symbiotic community inhabits the emerging pest Pentastiridius leporinus

The planthopper Pentastiridius leporinus has emerged as a severe crop pest, rapidly expanding both its host plant range and the affected areas in central Europe. Originating as a monophagous herbivore of reed grass, P. leporinus recently adopted polyphagous feeding and is now a pest of sugar beet, potato, carrot, and onion, suggesting rapid ecological niche expansion. P. leporinus vectors two bacterial pathogens, the {gamma}-proteobacterium Candidatus Arsenophonus phytopathogenicus (CAP) and the stolbur phytoplasma Candidatus Phytoplasma solani (CPS), which are responsible for a range of disease syndromes, including syndrome basses richesses (SBR) in sugar beet. We used long-read metagenomic sequencing to characterize the genomes of microbes associated with P. leporinus, resulting in the complete sequences of CAP and CPS, as well as primary symbionts of the genera Purcelliella, Sulcia and Vidania, and facultative symbionts Rickettsia and Wolbachia. The primary symbionts are inferred to provide all ten essential amino acids and contribute to B vitamin biosynthesis. The genomes of CPS and CAP encode numerous pathogenicity factors, enabling the colonization of different hosts. Bacterial fluorescence in situ hybridization revealed the tissue distribution, cellular localization, relative abundance and transmission patterns of these bacteria. The intracellular presence of all primary symbionts in bacteriomes, the intracellular presence of Wolbachia, and the intranuclear localization of Rickettsia, suggest vertical transmission. CPS was restricted to salivary glands, suggesting strict horizontal, plant-mediated transmission, whereas CAP colonized all tissue types, allowing for horizontal and vertical transmission. Our data suggest that P. leporinus hosts an exceptionally broad range of symbionts, encompassing mutualistic, commensal and pathogenic interactions. ImportanceThe planthopper Pentastiridius leporinus has recently expanded its host plant range and emerged as severe pest of sugar beet and potato crops in central Europe, which is exacerbated by its capacity to vector bacterial pathogens to its host plants. Because microbial symbionts may play an important role for both the host plant shifts and the transmission of pathogens, we used metagenomic sequencing and fluorescence in situ hybridization to characterize the microbial community associated with P. leporinus. We detected three bacteriome-localized primary symbionts that together provision all essential amino acids and several B-vitamins to the host, as well as two intracellular bacteria with a broader tissue distribution. In addition, we infer localization, transmission, and putative pathogenicity factors for the two major phytopathogens that are vectored by P. leporinus. Our results reveal a complex community of symbiotic bacteria that likely shapes the interaction of this emerging pest with its host plants.

systems biology↗

bioRxiv2025

Detecting neuroplastic effects induced by ketamine in healthy human subjects: a multimodal approach

We investigated ketamines neuroplastic effects in healthy human subjects using integrated Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI) measures before and 1-8 days after a single psychedelic dose of ketamine (1 mg/kg, intravenous). Eleven participants underwent two PET/MRI scans with [11C]-UCBJ (synaptic density/plasticity), 1H-MRS (Glutamate and GABA), and resting-state fMRI (intrinsic brain activity, functional connectivity, graph-theoretic metrics), before and after ketamine. While group-level analyses showed only trend-level increases in PET synaptic markers, we observed significantly elevated Anterior Cingulate Cortex (ACC) glutamate levels post-ketamine. Functional connectivity analyses revealed decreased within-network integrity, particularly in high-order networks like the default mode network (DMN), alongside increased low-to-high-order network integration. Our multimodal analysis showed that increased [11C]-UCBJ volume distribution (VT), a putative index of synaptic plasticity, correlated with reduced intrinsic activity in DMN regions and decreased influence of the posterior cingulate cortex (PCC) in global network dynamics. By linking molecular and network-level changes, our results point to the PCC as a central hub where ketamine may reshape brain hierarchies in the long term, providing new directions for understanding its therapeutic mechanisms and developing targeted treatments.

neuroscience↗

bioRxiv2024

Slow-wave sleep is associated with nucleus accumbens volume in elderly adults

Slow-wave sleep (SWS) is essential for restorative neural processes, and its decline is associated with both healthy and pathological ageing. Building on previous rodent research, this longitudinal study identified a significant association between nucleus accumbens (NAcc) volume and SWS duration in cognitively unimpaired older adults. Our findings support the involvement of the NAcc in ageing-related modulation of SWS and suggest potential therapeutic targets for improving SWS.

neuroscience↗

bioRxiv2023

Extracellular symbiont colonizes insect during embryo development

Insects typically acquire their beneficial microbes early in development. Endosymbionts housed intracellularly are commonly integrated during oogenesis or embryogenesis, whereas extracellular microbes are only known to be acquired after hatching by immature instars such as larvae or nymphs. Here, however, we report on an extracellular symbiont that colonises its host during embryo development. Tortoise leaf beetles (Chrysomelidae: Cassidinae) host their digestive bacterial symbiont Stammera extracellularly within foregut symbiotic organs, and in ovary-associated glands to ensure its vertical transmission. We outline the initial stages of symbiont colonization and observe that while the foregut symbiotic organs develop three days prior to larval emergence, they remain empty until the final 24 hours of embryo development. Infection by Stammera occurs during that timeframe, and prior to hatching. By experimentally manipulating symbiont availability to embryos in the egg, we describe a 12-hour developmental window governing colonization by Stammera. Symbiotic organs form normally in aposymbiotic larvae, demonstrating that these Stammera-bearing structures develop autonomously. In adults, the foregut symbiotic organs are already colonized following metamorphosis and host a stable Stammera population to facilitate folivory. The ovary-associated glands, however, initially lack Stammera. Symbiont abundance subsequently increases within these transmission organs, thereby ensuring sufficient titers at the onset of oviposition [~]29 days following metamorphosis. Collectively, our findings reveal that Stammera colonization precedes larval emergence, where its proliferation is eventually decoupled in adult beetles to match the nutritional and reproductive requirements of its host.

evolutionary biology↗

bioRxiv2023

Lowering mutant huntingtin by small molecules relieves Huntington's disease symptoms and progression

Huntingtons disease (HD) is an incurable inherited disorder caused by repeat expansion in the huntingtin gene (Htt). The mutant protein causes neuronal degeneration leading to severe motor and psychological abnormalities. Selective downregulation of the mutant Htt expression is considered the leading therapeutic approach for HD. We report the identification of novel small molecule inhibitors of Spt5-Pol II, SPI-24 and SPI-77, which selectively lower mutant Htt mRNA and protein levels in HD cells. In the BACHD mouse model, their direct delivery to the striatum diminished mutant Htt levels, ameliorated mitochondrial dysfunction, restored BDNF expression and improved motor and anxious-like phenotypes. Pharmacokinetic studies revealed that these SPIs pass the blood-brain-barrier and prolonged subcutaneous injection or oral administration to early-stage mice significantly delayed disease deterioration. SPI-24 long-term treatment had no side effects or global changes in gene expression. Thus, lowering mutant Htt levels by small molecules can be an effective therapeutic strategy for HD.

molecular biology↗

bioRxiv2022

Lipid metabolism dysfunction following symbiont elimination is linked to altered Kennedy pathway homeostasis

Lipid metabolism is critical for insect reproduction, especially for species that invest heavily into early developmental stages of their offspring. The role of symbiotic bacteria during this process is unknown but likely essential, especially in the case of obligate microbes that fulfill key biological functions in the host. Using a combined lipidomics, functional genomics and biochemical strategy, we examined the role of lipid metabolism in the interaction between the viviparous tsetse fly (Glossina morsitans morsitans) and its obligate endosymbiotic bacteria (Wigglesworthia glossinidia) during tsetse pregnancy. We observed increased CTP:phosphocholine cytidylyltransferase (cct1) expression during pregnancy. This gene codes for the enzyme that functions as the rate limiting step in phosphatidylcholine biosynthesis in the Kennedy pathway which is critical for stored lipid metabolism and progeny development. Experimental removal of Wigglesworthia impaired lipid metabolism via disruption of the Kennedy pathway, yielding obese mothers whose developing progeny ultimately starve. Functional validation via experimental cct1 suppression revealed a phenotype similar to females lacking obligate Wigglesworthia symbionts. These results indicate that, in Glossina, symbiont-derived factors, likely B vitamins, are critical for proper function of both lipid biosynthesis and lipolysis. Loss of the symbiosis has a dramatic impact on Glossina fecundity, and may be broadly applicable to other insect systems, particularly to species that require symbiotic partners to maximize lipolysis and reproductive output.

physiology↗

bioRxiv2022

Lateralization of orthographic processing in fixed-gaze and natural reading conditions

Lateralized processing of orthographic information is a hallmark of proficient reading. However, how this finding obtained for fixed-gaze processing of orthographic stimuli translates to ecologically valid reading conditions remained to be clarified. To address this shortcoming, here we assessed the lateralization of early orthographic processing in fixed-gaze and natural reading conditions using concomitant eye-tracking and EEG data recorded from young adults without reading difficulties. Sensor-space analyses confirmed the well-known left-lateralized negative-going deflection of fixed-gaze EEG activity throughout the period of early orthographic processing. At the same time, fixation-related EEG activity exhibited left-lateralized followed by right-lateralized processing of text stimuli during natural reading. A strong positive relationship was found between the early leftward lateralization in fixed-gaze and natural reading conditions. Using source-space analyses, early left-lateralized brain activity was obtained in lateraloccipital and posterior ventral occipito-temporal cortices reflecting letter-level processing in both conditions. In addition, in the same time interval, left-lateralized source activity was found also in premotor and parietal brain regions during natural reading. While brain activity remained left-lateralized in later stages representing word-level processing in posterior and middle ventral temporal regions in the fixed-gaze condition, fixation-related source activity became stronger in the right hemisphere in medial and more anterior ventral temporal brain regions indicating higher-level processing of orthographic information. Although our results show a strong positive relationship between the lateralization of letter-level processing in the two conditions and suggest lateralized brain activity as a general marker for processing of orthographic information, they also clearly indicate the need for reading research in ecologically valid conditions to identify the neural basis of visuospatial attentional, oculomotor and higher-level processes specific for natural reading.

neuroscience↗

bioRxiv2022

Not1 and Not4 inversely determine mRNA solubility that sets the dynamics of co-translational events

BackgroundThe Ccr4-Not complex is most well known as the major eukaryotic deadenylase. However, several studies have uncovered roles of the complex, in particular of the Not subunits, unrelated to deadenylation and relevant for translation. In particular, the existence of Not condensates that regulate translation elongation dynamics have been reported. Typical studies that evaluate translation efficiency rely on soluble extracts obtained after disruption of cells and ribosome profiling. Yet cellular mRNAs in condensates can be actively translated and may not be present in such extracts. ResultsIn this work, by analyzing soluble and insoluble mRNA decay intermediates in yeast, we determine that insoluble mRNAs are enriched for ribosomes dwelling at non-optimal codons compared to soluble mRNAs. mRNA decay is higher for soluble RNAs, but the proportion of co-translational degradation relative to the overall mRNA decay is higher for insoluble mRNAs. We show that depletion of Not1 and Not4 inversely impact mRNA solubilities and, for soluble mRNAs, ribosome dwelling according to codon optimality. Depletion of Not4 solubilizes mRNAs with lower non-optimal codon content and higher expression that are rendered insoluble by Not1 depletion. By contrast, depletion of Not1 solubilizes mitochondrial mRNAs, which are rendered insoluble upon Not4 depletion. ConclusionOur results reveal that mRNA solubility defines dynamics of co-translation events and is oppositely regulated by Not1 and Not4, a mechanism that we additionally determine may already be set by Not1 promoter association in the nucleus.

molecular biology↗

bioRxiv2021

Investigating brain mechanisms underlying natural reading by co-registering eye tracking with combined EEG and MEG

Linking brain and behavior is one of the great challenges in cognitive neuroscience. Ultimately, we want to understand how the brain processes information to guide every-day behavior. However, most neuroscientific studies employ very simplistic experimental paradigms whose ecological validity is doubtful. Reading is a case in point, since most neuroscientific studies to date have used unnatural word-by-word stimulus presentation and have often focused on single word processing. Previous research has therefore actively avoided factors that are important for natural reading, such as rapid self-paced voluntary saccadic eye movements. Recent methodological developments have made it possible to deal with associated problems such as eye movement artefacts and the overlap of brain responses to successive stimuli, using a combination of eye-tracking and neuroimaging. A growing number of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are successfully using this methodology. Here, we provide a proof-of-concept that this methodology can be applied to combined EEG and magnetoencephalography (MEG) data. Our participants naturally read 4-word sentences that could end in a plausible or implausible word while eye-tracking, EEG and MEG were being simultaneously recorded. Eye-movement artefacts were removed using independent-component analysis. Fixation-related potentials and fields for sentence-final words were subjected to minimum-norm source estimation. We detected an N400-type brain response in our EEG data starting around 200 ms after fixation of the sentence-final word. The brain sources of this effect, estimated from combined EEG and MEG data, were mostly located in left temporal lobe areas. We discuss the possible use of this method for future neuroscientific research on language and cognition.

neuroscience↗

bioRxiv2021

Paratransgenic manipulation of tsetse miR275 alters the physiological homeostasis of the flys midgut environment

Tsetse flies are vectors of parasitic African trypanosomes (Trypanosoma spp.). Current disease control methods include fly-repelling pesticides, trapping flies, and chemotherapeutic treatment of infected people. Inhibiting tsetses ability to transmit trypanosomes by strengthening the flys natural barriers can serve as an alternative approach to reduce disease. The peritrophic matrix (PM) is a chitinous and proteinaceous barrier that lines tsetses midgut. It protects the epithelial cells from the gut lumen content such as food and invading trypanosomes, which have to overcome this physical barrier to establish an infection. Bloodstream form trypanosomes shed variant surface glycoproteins (VSG) into tsetses gut lumen early during the infection establishment. The VSG molecules are internalized by the flys PM-producing cardia, which results in a reduction in tsetse miR275 expression and a sequential molecular cascade that compromises the PM integrity. In the present study, we investigated the role(s) of miR275 in tsetses midgut physiology and trypanosome infection processes by developing a paratransgenic expression system. We used tsetses facultative bacterial endosymbiont Sodalis glossinidius to express tandem antagomir-275 repeats (or miR275 sponge) that constitutively reduce miR275 transcript abundance. This paratransgenic system successfully knocked down miR275 levels in the flys midgut, which consequently obstructed blood digestion and modulated infection outcomes with an entomopathogenic bacteria and with trypanosomes. RNA sequencing of cardia and midgut tissues from the paratransgenic tsetse confirmed that miR275 regulates processes related to the expression of PM-associated proteins and digestive enzymes as well as genes that encode abundant secretory proteins. Our study demonstrates that paratransgenesis can be employed to study microRNA-regulated pathways in arthropods housing symbiotic bacteria. Author SummaryTsetse flies transmit African trypanosomes, which are the parasites that cause sleeping sickness in human in sub-Saharan Africa. When tsetse ingests a blood meal containing trypanosomes, the expression level of a microRNA (miR275) decreases in the flys gut. This process results in a series of events that interrupt the physiological homeostasis of the gut environment. To further understand the function of miR275 in tsetse fly, we genetically modified a tsetses native bacterial symbiont, reintroduced the genetically modified bacterium back into the fly, and successfully knocked down the miR275 expression in tsetses midgut. These paratransgenic flies (which house genetically modified bacteria) presented impaired digestive processes and were highly susceptible to infection with trypanosomes. Lastly, we discovered that miR275 regulates tsetse secretory pathways. Our novel paratransgenic expression system can be applied to study the function of other microRNAs and how they regulate disease transmission in tsetse and other insect systems.

microbiology↗

bioRxiv2021

eIF4E3 Forms an Active eIF4F Complex during Stresses (eIF4FS) Targeting mTOR and Re-Programs the Translatome.

The eIF4E are a family of initiation factors that bind the mRNA 5 cap, regulating the proteome and the cellular phenotype. eIF4E1 mediates global translation and its activity is controlled via the PI3K/AKT/mTOR pathway. mTOR down-regulation results in eIF4E1 sequestration into an inactive complex with the 4E binding proteins (4EBPs). The second member, eIF4E2, regulates the translatome during hypoxia. However, the exact function of the third member, eIF4E3, has remained elusive. We have dissected its function using a range of techniques. Starting from the observation that it does not interact with 4EBP1, we demonstrate that eIF4E3 recruitment into an eIF4F complex occurs when Torin1 inhibits the mTOR pathway. Ribo-seq studies demonstrate that this complex (eIF4FS) is translationally active only during stress and that it selects specific mRNA populations based on 5 TL (UTR) length. The interactome reveals that it associates with cellular proteins beyond the cognate initiation factors, suggesting that it may have "moon-lighting" functions. Finally, we provide evidence that cellular metabolism is altered in an eIF4E3 KO background but only upon Torin1 treatment. We propose that eIF4E3 acts as a second branch of the integrated stress response, re-programming the translatome to promote "stress resistance" and adaptation.

molecular biology↗

bioRxiv2020

Honey bee suppresses the parasitic mite Vitellogenin by antimicrobial peptide

The negative effects of honey bee parasitic mites and deformed wing virus (DWV) on honey bee and colony health have been well characterized. However, the relationship between DWV and mites, particularly viral replication inside the mites, remains unclear. Furthermore, the physiological outcomes of honey bee immune responses stimulated by DWV and the mite to the host (honey bee) and perhaps the pathogen/parasite (DWV/mite) are not yet understood. To answer these questions, we studied the tripartite interactions between the honey bee, Tropilaelaps mercedesae, and DWV as the model. T. mercedesae functioned as a vector for DWV without supporting active viral replication. Thus, DWV negligibly affected mite fitness. Mite infestation induced mRNA expression of antimicrobial peptides (AMPs), Defensin-1 and Hymenoptaecin, which correlated with DWV copy number in honey bee pupae and mite feeding, respectively. Feeding T. mercedesae with fruit fly S2 cells heterologously expressing honey bee Hymenoptaecin significantly downregulated mite Vitellogenin expression, indicating that the honey bee AMP manipulates mite reproduction upon feeding on bee. Our results provide insights into the mechanism of DWV transmission by the honey bee parasitic mite to the host, and the novel role of AMP in defending against mite infestation.

microbiology↗

bioRxiv2019

Switch from translation initiation to elongation needs Not4 and Not5 collaboration

Not4 and Not5 are crucial components of the Ccr4-Not complex with pivotal functions in mRNA metabolism. Both associate with ribosomes but mechanistic insights on their function remain elusive. Here we determine that Not5 and Not4 synchronously impact translation initiation and Not5 alone alters translation elongation. Deletion of Not5 causes elongation defects in a codon-dependent fashion, increasing and decreasing the ribosome dwelling occupancy at minor and major codons, respectively. This larger difference in codons translation velocities alters translation globally and enables kinetically unfavorable processes such as nascent chain deubiquitination to take place. In turn, this leads to abortive translation and favors protein aggregation. These findings highlight the global impact of Not4 and Not5 in controlling the speed of mRNA translation and transition from initiation to elongation. SummaryNot4 and Not5 regulate translation synchronously but distinguishably, facilitating smooth transition from initiation to elongation

molecular biology↗

bioRxiv2018

PAVOOC: Designing CRISPR sgRNAs using 3D protein structures and functional domain annotation

Summary: sgRNAs targeting the same gene can significantly vary in terms of efficacy and specificity. PAVOOC (Prediction And Visualization of On- and Off-targets for CRISPR) is a web-based CRISPR sgRNA design tool that employs state-of-the art machine learning models to prioritize most effective candidate sgRNAs. In contrast to other tools, it maps sgRNAs to functional domains and protein structures and visualizes cut sites on corresponding protein crystal structures. Furthermore, PAVOOC supports HDR template generation for gene editing experiments and the visualization of the mutated amino acids in 3D.\n\nAvailability and Implementation: PAVOOC is available under https://pavooc.me and accessible using current browsers (Chrome/Chromium recommended). The source code is hosted at github.com/moritzschaefer/pavooc under the MIT License. The backend, including data processing steps, and the frontend is implemented in Python 3 and ReactJS respectively. All components run in a simple Docker environment.\n\nContact: mail@moritzs.de

bioinformatics↗