Biology subjects

Meier, L.

Publications and source records attributed to Meier, L..

7 recordsLinked to original sources

bioRxiv2026

Auditory Evoked Potentials Differ from Controls and Correlate with Aspects of Cognition in Kabuki Syndrome and Rubinstein-Taybi Syndrome

Objective Kabuki syndrome (KS) and Rubinstein-Taybi syndrome (RSTS) are two disorders caused by dysfunctional components of the epigenetic machinery and both result in intellectual disability. Mouse models of both KS and RSTS have seen reversal of cognitive impairment with epigenetic treatments. However, a great need exists for biomarkers in these disorders to improve the likelihood of successful clinical trials. This study aimed to investigate cortical auditory evoked potentials (AEPs) in KS and RSTS so that it could potentially be developed into a response biomarker in the future. Methods The amplitude of the N1-P2-N2 complex was measured for passive listening to monotonal auditory stimuli in individuals with KS, with RSTS, and typically developing controls. A standardized cognitive assessment battery was performed and specific subtests were correlated with AEP values. Results Groups differed significantly in P2, N2, and P2-N2 amplitude although RSTS was consistently more different from typically developing controls than was KS. The mid- to late-phase AEP components (P2 and N2) also correlate with cognition within and across these groups particularly with language whereas earlier components N1 and P2 correlate more with measures of executive functioning. Conclusion Late-phase components of AEPs differ in KS and RSTS from each other and from controls. KS and RSTS differ from controls in P2 and N2 amplitude in the same direction and both show a positive correlation between language and P2 amplitude and a negative correlation between language and N2 amplitude. Together they also show an association with N1 and P2 amplitude and executive functioning. Significance AEPs may turn out to be a valuable response biomarker in KS and RSTS individually and together.

neuroscience↗

bioRxiv2026

Comparative genomics reveals extensive genomic conservation and limited microdiversification among Xenorhabdus bovienii isolates recovered from a single Steinernema feltiae isolation event.

Xenorhabdus bovienii is a symbiotic bacterium associated with entomopathogenic nematodes of the genus Steinernema. Comparative genomic analyses of closely related isolates provide an opportunity to investigate fine-scale diversification, genome plasticity, and the evolutionary processes shaping symbiotic bacterial populations. Here, we analyzed four X. bovienii isolates (XenUTI4.1-XenUTI4.4) recovered from a single Steinernema feltiae isolation event using comparative genomics approaches integrating average nucleotide identity (ANI), single-nucleotide polymorphism (SNP) analyses, pangenome reconstruction, biosynthetic gene cluster (BGC) prediction, and mobile element-associated annotation screening. Whole-genome comparisons revealed extremely high genomic similarity among isolates, with ANI values exceeding 99.84%. Read-based SNP analyses identified only 23-36 annotated variants relative to the XenUTI4.1 reference genome, indicating limited sequence divergence despite detectable microvariation. Functional annotation of these variants showed that most corresponded to missense or synonymous substitutions affecting a small number of coding sequences. Pangenome analysis identified 4,712 orthologous gene clusters, including a highly conserved core genome of 4,256 clusters (90.3%) shared by all isolates and a relatively small accessory genome comprising 456 clusters. antiSMASH analyses revealed broadly conserved secondary metabolite biosynthetic potential across the four genomes, whereas screening of genome annotations identified abundant phage-related, transposase-associated, and recombination-associated genes consistent with ongoing genome plasticity. Collectively, these results demonstrate that the analyzed X. bovienii isolates represent a highly conserved population exhibiting limited but detectable genomic microdiversification. The coexistence of a large core genome, a modest accessory gene complement, and numerous mobile element-associated functions suggests that localized sequence variation and mobile genetic elements contribute to genomic diversification within S. feltiae-associated X. bovienii populations.

genetics↗

bioRxiv2026

Lethal Sudan virus infection in IFNAR-/- mice reveals hallmarks of a cytokine storm

Sudan virus (SUDV) is a member of the family Filoviridae, which comprises highly pathogenic viruses associated with unusually high case fatality rates. The development of medical countermeasures against filoviruses, including antivirals, vaccines, and therapeutic antibodies, requires preclinical evaluation in suitable animal models. C57BL/6J IFNAR-/- mice, which lack the type I interferon (IFN-/{beta}) receptor, have been reported to be susceptible to filovirus infections, although their impaired innate immune response may represent a potential limitation of the model. Here, we show that IFNAR-/- mice constitute a suitable model for SUDV infection. Following infection, animals developed a clear clinical disease characterized by significant weight loss and pronounced changes in behaviour and appearance. Mice reached the predefined clinical endpoint 3-5 days post infection. Post mortem analysis of terminal samples revealed high viral loads and viral genome copies in all tested organs as well as in serum, indicating widespread systemic dissemination. Importantly, infection was associated with a marked increase in several key chemokines and cytokines linked to systemic inflammation, consistent with the development of a cytokine storm-like response. Together, these findings demonstrate that SUDV infection in IFNAR-/- mice induces systemic viral dissemination and a pronounced inflammatory response, supporting the suitability of this model for investigating filovirus pathogenesis and infection-associated immune dysregulation.

microbiology↗

bioRxiv2025

Monocyte Dysregulation Defines an MDD-Specific Transcriptional Signature Closely Linked to Clinical MDD Traits

ObjectiveMajor depressive disorder (MDD) is a highly heterogeneous psychiatric condition contributing significantly to the global disease burden. In a subset of MDD patients inflammatory processes accompany the disease and this has also been reported for other psychiatric conditions like schizophrenia (SZ). However, little is known regarding immune deregulation in relation to clinical symptoms. MethodsCellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq) of peripheral blood mononuclear cells (PBMCs) from patients with MDD (n=22), SZ (n=10), and healthy controls (HCs, n=26) was performed, yielding 633,284 high-quality single-cell profiles. Differential gene expression, cell composition, pathway enrichment, and weighted gene co-expression network analyses were conducted. MDD symptom severity was assessed using the Beck Depression Inventory-II (BDI-II), enabling the correlation of gene expression with individual disease symptoms. ResultsWe identified disease-specific transcriptomic signatures for MDD as well as for SZ and shared gene expression changes between the two conditions. For MDD, monocyte numbers were elevated concomitant with a strong enrichment of interferon signaling. The MDD-specific signature involving all peripheral cell types correlated strongly with key symptoms of depression like sadness or pessimism. Reactome analysis identified nuclear factor kappa-light-chain-enhancer of activated B cells (NF-{kappa}B)-associated pathways among the genes positively correlating with disease symptoms and traits. ConclusionOur findings might help to stratify psychiatric patients and provide a multidimensional framework for investigating immune contributions to psychiatric disorders and highlight potential targets for therapeutic intervention. Clinical symptoms might be reflected on a molecular level paving the way for more targeted and effective interventions.

genomics↗

bioRxiv2025

Spreading alpha-Synuclein Oligomers Trigger Astrocyte Reactivity and Astrocyte-glutamatergic Neuron system dysfunction in an Age-Dependent Manner

BackgroundParkinsons disease (PD) is characterized by the progressive accumulation and spatio-temporal spread of -synuclein (-syn) oligomers and a progressive loss of dopaminergic neurons. Many studies showed a direct cytotoxic effect of -syn oligomers on neurons. Other cell types including astrocytes were also reported to show specific responses to -syn and are believed to play a role in the spreading of PD pathology. MethodsTo investigate the transcriptional and cellular consequences of -syn oligomer spreading, we employed spatial transcriptomics and single-nucleus RNA sequencing (snRNA-seq) in a transgenic PD mouse model expressing human -syn in neurons. We further compared our findings to published public snRNA-seq datasets from human PD patients ResultsOur analysis identified -syn spreading mostly to the substantia nigra and defined a transcriptional "Spreading Signature" associated with -syn pathology. We found an age correlated increase in astrocytes, close interactions between astrocytes and -syn, and transcriptional dysregulation of the astrocyte-glutamatergic neuron axis. We further identified two subtypes of glutamatergic neurons that are vulnerable to astrocytic changes. Comparative analysis with human PD snRNA-seq data showed concordant transcriptional changes related to astrocytic dysfunctions and diminished neuronal signaling. ConclusionBased on our results, we propose a model of -syn oligomer spreading involving astrocytes, glutamatergic synapses, and a disturbance in the astrocyte-glutamatergic neuron axis.

neuroscience↗

bioRxiv2024

Detection, Isolation and Quantification of Myocardial Infarct with Four Different Histological Staining Techniques

Precise quantification of myocardial infarction is crucial for evaluating the therapeutic strategies. We developed a robust, color-based semi-automatic algorithm capable of infarct region detection, isolation and quantification with four different histological staining techniques, and the isolation and quantification of diffuse fibrosis in the heart. Our method is developed based on the color difference in the infarct and non-infarct regions after histological staining. Mouse cardiac tissues stained with Massons trichrome (MTS), hematoxylin and eosin (H&E), 2,3,5-Triphenyltetrazolium chloride and picrosirius red were included to demonstrate the performance of our method. We demonstrate that our algorithm can effectively identify and produce a clear visualization of infarct tissue for the four staining techniques. Notably, the infarct region on a H&E-stained tissue section can be clearly visualized after processing. The MATLAB-based program we developed holds promise in the infarct quantification. Additionally, our program can isolate and quantify the diffuse fibrotic elements from an MTS-stained cardiac section, which suggested the algorithms potential for evaluating pathological cardiac fibrosis in diseased cardiac tissues. In conclusion, we demonstrate that this color-based algorithm is capable of accurately identifying, isolating and quantifying cardiac infarct regions with different staining techniques, as well as the diffuse and patchy fibrosis in MTS-stained cardiac tissues.

pathology↗

bioRxiv2020

Measuring kinetics and metastatic propensity of CTCs by blood exchange between mice

Existing pre-clinical methods for acquiring dissemination kinetics of rare circulating tumor cells (CTCs) en route to forming metastases have not been capable of providing a direct measure of CTC intravasation rate and subsequent half-life in the circulation. Here, we demonstrate an approach for measuring endogenous CTC kinetics by continuously exchanging CTC-containing blood over several hours between un-anesthetized, tumor-bearing mice and healthy, tumor-free counterparts. By tracking CTC transfer rates using an autochthonous small cell lung cancer model, we extrapolated half-life times in the circulation of 50-100 seconds and intravasation rates between 4,000 and 27,000 CTCs/hour - an average daily shedding rate equivalent to [~]0.07% of the total number of primary tumor cells in the lung. Additionally, transfer of 1-2% of daily-shed CTCs from late-stage tumor-bearing mice generated macrometastases in healthy recipient mice. We envision that our technique will help further elucidate the role of CTCs and the rate-limiting steps in metastasis.

cancer biology↗