Biology subjects

Weiser, M.

Publications and source records attributed to Weiser, M..

7 recordsLinked to original sources

bioRxiv2026

Longitudinal White Matter Microstructure and Transition to Psychosis in Individuals at Clinical High Risk

Altered white matter microstructure, commonly indexed by fractional anisotropy (FA), has been reported in individuals at clinical high-risk of psychosis (CHR-P) across multiple white matter tracts. However, the relationship between these alterations and later transition to psychosis remains unclear. To address this gap, we investigated whether baseline and longitudinally updated FA measurements were associated with risk of transition to psychosis in a large cohort of individuals at CHR-P. We analysed diffusion tensor imaging data from N = 205 participants at CHR-P, 23 of whom developed psychosis within 3 years of follow-up. Data were collected at baseline, 6 months, and 12 months. Associations between global and tract-specific FA and transition risk were examined using Cox proportional hazards models of baseline data and longitudinally updated data. Point estimates were directionally consistent, with hazard ratios <1 for FA across all white matter tracts in both baseline and longitudinal models. Associations reached nominal significance in the hippocampal cingulum, anterior thalamic radiation, and forceps minor, but none of these remained significant after correcting for multiple comparisons (pcorr > .05). The directionally consistent estimates are compatible with small, distributed effects across multiple white matter pathways being associated with transition to psychosis, although this requires replication. Longitudinally updated FA measurements did not yield stronger associations than were available from baseline imaging data alone. Studies at an even larger scale are needed to establish whether these associations are robust and clinically meaningful.

neuroscience↗

bioRxiv2026

Longitudinal White Matter Trajectories in Clinical High Risk and First-Episode Psychosis: Findings from the Multi-Centre PSYSCAN Study

Psychosis has been linked to changes in diffusion-derived fractional anisotropy (FA) across multiple white matter tracts, yet most evidence is cross-sectional. Longitudinal findings are inconsistent, and the clinical relevance of white matter changes over time remains unclear. To address this gap, we investigated longitudinal white matter changes and their clinical correlates in early psychosis in a large, multi-centre diffusion-tensor imaging study. Across 18 sites, 407 participants (healthy controls: n = 97, 59.8% men, mean age 23.9{+/-}4.6 years; clinical high risk of psychosis: n = 158, 53.5% men, mean age 23.0{+/-}4.9 years; first-episode psychosis: n = 152, 71.1% men, mean age 25.1{+/-}5.4 years) were scanned at up to three time points over 12 months. FA was assessed in the cingulum bundle, the superior longitudinal fasciculus, the inferior fronto-occipital fasciculus, and at the whole brain level. FA trajectories were analysed using linear mixed-effects models to test effects of group, social and occupational functioning, and (attenuated) psychotic symptoms, while controlling for demographic and socioeconomic covariates. No significant group differences in FA were observed, either globally or within tracts (p > .05). Longitudinal FA trajectories were not associated with changes in (attenuated) psychotic symptoms or functioning (p > .05). In contrast, higher baseline antipsychotic medication dose was significantly associated with lower FA (pcorr < .05). Overall, these findings indicate that white matter microstructure is relatively stable during the clinical-high-risk and first-episode phases of psychosis, and that it is not clearly associated with variation in symptom severity or functional outcomes over time.

neuroscience↗

bioRxiv2025

Reconstructing Ambient Temperature in Forensic Death Time Estimation

Ambient temperature TA has a strong impact on temperature based time since death estimation (TTDE). Frequently TA is lowered instantaneously at a time t0 from a start value TA0 to TA1 < TA0 e.g. by window or door opening. We focus on reconstructing TA0 and t0. TTDE literature suggests temperature measurements in closed compartments as e.g. cupboards or neighboring rooms, where TA0 could have been preserved after t0. We aim to estimate t0 and TA0 from temperature measurements TZ(t) in closed compartments Z at times t > t0. We obtained promising results assuming Newtonian cooling for boxes filled with air, with heaps of clothes or even with books in two different experimental scenarios. Two different parameter estimators, (t0^, TA0^) forsingle quadruple temperature measurement and (t0*, TA0*) for N quadruple measurements were tested. Our results in a climate chamber were partially appropriate for TTDE input. A decline at time t0 from TA0 = 22.5{degrees}C {downarrow} TA1 = 14{degrees}C was reconstructed at t = t0 + 95min with relative deviations {rho}t0^ = 27% and {rho}TA0^ = 19% relative to t - t0 and TA0 - TA1 respectively, for N = 1 quadruple measurement with span {Delta}t = 50min. For N = 200 quadruple measurements in [t = t0 + 95min, t = t0 + 295min] we found {rho}t0^ = 5% and {rho}TA0^ = 11% with the same {Delta}t. Further research is necessary to guarantee applicability in routine casework. We will investigate more elaborate cooling models, estimation algorithms, and evaluation localization.

biophysics↗

bioRxiv2024

The Dual Roles of the CXCL10-CXCR3 Axis and Its Therapeutic Potential in Osteosarcoma

The CXCL10-CXCR3 axis is recognized for its dual role in tumor biology, promoting tumor growth and metastasis via autocrine signaling while also eliciting anti-tumor responses through paracrine signaling. However, its specific functions in osteosarcoma (OS), the most prevalent malignant bone tumor in children, remain poorly understood. Our previous research has demonstrated that elevated circulating CXCL10 levels correlate with poor prognosis in OS patients. Analysis of the TARGET OS RNAseq dataset revealed that high expression levels of CXCL10 or its receptor CXCR3 are associated with improved prognosis. Given the known role of CXCL10 in recruiting CXCR3+ immune cells to combat cancer, we further analyzed single-cell RNAseq data and found that CXCR3 is predominantly expressed in CD3+ T cell populations. These findings suggest that CXCL10 may also play a protective role in OS by recruiting anti-tumor immune cells. To elucidate the causal role of the CXCL10-CXCR3 axis in OS, we conducted in vitro phenotypic assays on three OS cell lines with and without CXCL10. The chemokine was found to enhance tumor cell migration and AKT phosphorylation. Utilizing a CRISPR-mediated CXCR3 deletion mutant, we demonstrated that the absence of CXCR3 significantly inhibited OS tumor growth and pulmonary metastasis in an orthotopic xenograft mouse model. Transfection with the CXCR3A isoform, but not the CXCR3B isoform, restored the migratory phenotype of the CXCR3 deletion mutant to levels comparable to the parental cell line. Additionally, pharmacological inhibition of CXCR3 with AMG487 markedly reduced OS cell migration in vitro and metastasis development in the orthotopic xenograft mouse model. Our research highlights the complex interplay of the CXCL10-CXCR3 axis in both tumor and immune cells. We propose a working model for the roles of the CXCL10-CXCR3 axis in OS, suggesting that targeting CXCR3 may be an effective strategy to inhibit OS metastasis, particularly in immune-cold OS subtypes.

cancer biology↗

bioRxiv2020

Predicting Individual Variability in Task-Evoked Brain Activity in Schizophrenia

BACKGROUNDPatients suffering from schizophrenia demonstrate abnormal brain activity, as well as alterations in patterns of functional connectivity assessed by functional magnetic resonance imaging (fMRI). Previous studies in healthy participants suggest a strong association between resting-state functional connectivity and task-evoked brain activity that could be detected at an individual level, and show that brain activation in various tasks could be predicted from task-free fMRI scans. In the current study we aimed to predict brain activity in patients diagnosed with schizophrenia, using a prediction model based on healthy individuals exclusively. This offers novel insights regarding the interrelations between brain connectivity and activity in schizophrenia. METHODSWe generated a prediction model using a group of 80 healthy controls that performed the well-validated N-back task, and used it to predict individual variability in task-evoked brain activation in 20 patients diagnosed with schizophrenia. RESULTSWe demonstrated a successful prediction of individual variability in the task-evoked brain activation based on resting-state functional connectivity. The predictions were highly sensitive, reflected by high correlations between predicted and actual activation maps (Median = 0.589, SD = 0.193) and specific, evaluated by a Kolomogrov-Smirnov test (D = 0.25, p < 0.0001). CONCLUSIONSA Successful prediction of brain activity from resting-state functional connectivity highlights the strong coupling between the two. Moreover, our results support the notion that even though resting-state functional connectivity and task-evoked brain activity are frequently reported to be altered in schizophrenia, the relations between them remains unaffected. This may allow to generate task activity maps for clinical populations without the need the actually perform the task.

neuroscience↗

bioRxiv2019

Comprehensive post mortem brain samples analysis detects global reduction of multiple proteasome subunits expression in schizophrenia

OBJECTIVEA main challenge in the study of schizophrenia is its high heterogeneity. While it is generally accepted that there exist several biological mechanisms that may define distinct schizophrenia subtypes, they havent been identified yet. We applied comprehensive gene expression analysis, searching for molecular signals that differentiate patients with schizophrenia from healthy controls, and examined whether the identified signal characterizes a particular subgroup of the patients. METHODSWe performed transcriptome sequencing of 14 superior temporal gyrus (STG) samples of relatively young (mean age: 44) subjects with schizophrenia and 15 matched controls from the Stanley Medical Research Institute. Analyses of differential expression and pathway enrichment were applied and the results were compared with those obtained from an independent cohort of elderly (mean age: 74) patients. Replicability was then tested on six additional independent datasets of various brain regions. RESULTSThe two STG cohorts of relatively young and elderly subjects showed high replicability. Pathway enrichment analysis of the down-regulated genes pointed to proteasome-related pathways. Meta-analysis of differential expression identified down-regulation of 12 of 39 proteasome subunits in schizophrenia. Down-regulation of multiple proteasome subunits was replicated in six additional datasets (overall 8 cohorts, with 267 schizophrenia and 266 control samples, from 5 brain regions, were studied). This signal was concentrated in a subgroup of the patients. CONCLUSIONSWe detect global down-regulation of proteasome subunits in a subgroup of the patients with schizophrenia. The proteasome is a major intracellular protein degradation system, where ubiquitinated proteins (proteins bound by the small protein called ubiquitin) are targeted for degradation. We hypothesize that the down-regulation we detect leads to proteasome dysfunction that causes accumulation of ubiquitinated proteins. Such accumulation has recently been identified, also in a subgroup of the studied patients with schizophrenia. Thus, down-regulation of proteasome subunits might define a biological subtype of schizophrenia.

neuroscience↗

bioRxiv2018

Serial synapse formation through filopodial competition for synaptic seeding factors

Following axon pathfinding, growth cones transition from stochastic filopodial exploration to the formation of a limited number of synapses. How the interplay of filopodia and synapse assembly ensures robust connectivity in the brain has remained a challenging problem. Here, we developed a new 4D analysis method for filopodial dynamics and a data-driven computational model of synapse formation for R7 photoreceptor axons in developing Drosophila brains. Our live data support a serial synapse formation model, where at any time point only a single synaptogenic filopodium suppresses the synaptic competence of other filopodia through competition for synaptic seeding factors. Loss of the synaptic seeding factors Syd-1 and Liprin- leads to a loss of this suppression, filopodial destabilization and reduced synapse formation, which is sufficient to cause the destabilization of entire axon terminals. Our model provides a filopodial winner-takes-all mechanism that ensures the formation of an appropriate number of synapses.

neuroscience↗