Biology subjects

Neubauer, A.

Publications and source records attributed to Neubauer, A..

7 recordsLinked to original sources

bioRxiv2026

Downregulation of Satb1 is required to prevent autoimmunity by maintaining Tfh homeostasis

T follicular helper (Tfh) cells are a specialized subset of CD4 T cells that localize to germinal centers (GC), where they provide critical help to B cells through the delivery of IL-21 and other cytokines. Here, we demonstrate that the tight control of the chromatin remodeler Special AT-rich sequence-binding protein 1 (Satb1) is key for this process, as overexpression of Satb1 drives lymphoproliferation and expansion of the T cell and B cell compartments in secondary lymphoid organs. Specifically, Satb1 overexpression induces a pronounced shift towards Tfh cell differentiation and increased GC formation accompanied by an increase in non-classed switched GC B cells and auto-antibody secretion. These findings highlight the importance of the precise regulation of Satb1 in fine-tuning CD4 T cells and B cells responses and suggest a potential role for dysregulation of Satb1 in the pathogenesis of autoimmune disease such as systemic lupus erythematodes (SLE).

immunology↗

bioRxiv2026

Glucose hypometabolism and hyperphosphorylated Tau synergistically drive neuronal necroptosis

The combination of brain glucose hypometabolism and hyperphosphorylated Tau (p-Tau) pathology is the strongest known clinical predictor of imminent cognitive decline, yet how these factors cooperate to drive dementia remains unknown. Here, we show that glucose hypometabolism synergizes with p-Tau to trigger neuronal loss through necroptosis. Under low-glucose conditions, accumulated p-Tau forms a molecular scaffold that directly recruits the necroptotic kinase RIPK1, while concomitant loss of the necroptosis checkpoint protein A20 removes a critical brake on this death pathway. This dual mechanism thereby precipitates neuronal necroptosis independent of classical TNF/TNFR1 signaling paradigm. Restoring A20 expression with acetyl-L-carnitine as a dietary supplement or preventing the p-Tau - RIPK1 interaction using a RIPK1 derived competitive peptide alleviates neuronal necroptosis and brain atrophy in a Tau transgenic mouse model. Collectively, our findings uncover a previously unrecognized metabolism-driven necroptotic signaling cascade initiated by a p-Tau-RIPK1 hub, providing mechanical insight into how glucose hypometabolism synergizes with p-Tau to drive neurodegeneration.

neuroscience↗

bioRxiv2025

Claustrum volume in human lifespan trajectory and effect of age, hemisphere, and sex

The human claustrum is a bilateral, thin, irregularly shaped gray matter structure located between the striatum and insula. While previous research demonstrated the effect of distinct medical conditions, such as prematurity, schizophrenia, and Alzheimers disease, on claustrum function and structure, it is poorly understood how non-pathologic biological conditions effect the claustrum. This study aimed to investigate the effect of age, hemisphere, and sex on claustrum volume. We used T1-weighted 3 Tesla MRI scans of 3,474 healthy participants ranging from 1 to 80 years of age, deep learning-based automated claustrum segmentation, and a normative modeling approach to delineate lifespan trajectories of claustrum volumes for both hemispheres and sexes. Additionally, ordinary least squares regression analyses were applied to further characterize age, hemisphere, and sex effect. Lifespan analysis revealed a trajectory of rapid claustrum volume increase from infancy to adolescence ([~] 1-15 years, annual growth 39.300 mm3/year), a plateau phase from early to middle adulthood ([~] 15-40 years, annual change 0.153 mm3/year), and a subsequent decline from middle adulthood to old age ([~] 40-80 years, annual decrease 10.325 mm3/year). The right claustrum was on average larger than the left one across all ages. Finally, overall, females had larger total intracranial volume-adjusted claustrum volumes than males across the lifespan. Results demonstrate a distinct effect of age, hemisphere, and sex on claustrum volume. Data provide a comprehensive framework for sex- and hemisphere-sensitive claustrum structure lifespan trajectories relevant for studying neurodevelopmental and neurodegenerative effects on the claustrum.

neuroscience↗

bioRxiv2024

Heterogeneous, temporally consistent, and plastic brain development after preterm birth

The current view of neurodevelopment after preterm birth presents a strong paradox: diverse neurocognitive outcomes suggest heterogeneous neurodevelopment, yet numerous brain imaging studies focusing on average dysmaturation imply largely uniform aberrations across individuals1. Here we show both, spatially heterogeneous individual brain abnormality patterns (IBAPs) but with consistent underlying biological mechanisms of injury and plasticity. Using cross-sectional structural magnetic resonance imaging data from preterm neonates and longitudinal data from preterm children and adults in a normative reference framework2, we demonstrate that brain development after preterm birth is highly heterogeneous in both severity and patterns of deviations. Individual brain abnormalities were also consistent for their extent and location along the life course, associated with glial cell underpinnings, and plastic for influences of the early social environment. Thus, IBAPs of preterm birth are spatially heterogenous, temporally consistent for extent, spatial location, and cellular underpinnings, and plastic for social-environmental impacts. Our findings extend conventional views of preterm neurodevelopment, revealing a nuanced landscape of individual variation, with consistent commonalities between subjects. This integrated perspective of preterm neurodevelopment implies more targeted theranostic intervention strategies, specifically integrating brain charts2 and imaging at birth, as well as social interventions during early development3.

neuroscience↗

bioRxiv2024

Systemic response to nitrogen starvation in the cyanobacteria hosting hornwort and liverwort provides little evidence for extensive priming to the cyanobiont

Mutualistic plant-microbe symbiotic interactions are thought to have evolved from a loose association between host plants and microbes when nutrients are limited. Therefore, the molecular network enabling intimate mutualistic plant-microbe symbioses may have evolved from a nutrient starvation response shared by all land plants. While the molecular link between nutrient status and symbiotic interaction is well-established, it remains poorly understood in some systems. This is especially true for the symbiotic associations between plants and cyanobacteria. To test the conservation of the starvation network across land plants as well as to investigate the link between nutrient starvation and symbiosis initiation in the plant-cyanobacteria symbiosis, here we explore the transcriptional responses to nutrient starvation in two non-vascular plant species, a hornwort Anthoceros agrestis and a liverwort Blasia pusilla, forming plant-cyanobacteria endophytic symbioses. We observe a deep conservation of the systemic starvation response across land plants. However, very few if any components of the starvation network appear to be specific to cyanobacteria hosting plants, providing little evidence for extensive and specific priming to the cyanobiont. Moreover, we found that some bioactive molecules known to be important in initiating the plant-mycorrhiza and nodule-forming bacteria symbioses, may also have a similar role in plant-cyanobacteria symbioses. HighlightOur results suggest that the most critical step in establishing plant-cyanobacteria interactions using non-host plants is the attraction of the cyanobiont. This finding has significant impact on crop engineering.

evolutionary biology↗

bioRxiv2023

IRF2BP2 counteracts the ATF7/JDP2 AP-1 heterodimer to prevent inflammatory overactivation in acute myeloid leukemia (AML) cells

Acute myeloid leukemia (AML) is a hematological malignancy characterized by abnormal proliferation and accumulation of immature myeloid cells in the bone marrow. Inflammation plays a crucial role in AML progression, but excessive activation of cell-intrinsic inflammatory pathways can also trigger cell death. IRF2BP2 is a chromatin regulator implicated in AML pathogenesis, although its precise role in this disease is not fully understood. In this study, we demonstrate that IRF2BP2 interacts with the AP-1 heterodimer ATF7/JDP2, which is involved in activating inflammatory pathways in AML cells. We show that IRF2BP2 is recruited by the ATF7/JDP2 dimer to chromatin and counteracts its gene-activating function. Loss of IRF2BP2 leads to overactivation of inflammatory pathways, resulting in strongly reduced proliferation. Our research indicates that a precise equilibrium between activating and repressive transcriptional mechanisms creates a pro-oncogenic inflammatory environment in AML cells. The ATF7/JDP2-IRF2BP2 regulatory axis is likely a key regulator of this process and may therefore represent a promising therapeutic vulnerability for AML. Thus, our study provides new insights into the molecular mechanisms underlying AML pathogenesis and identifies a potential therapeutic target for AML treatment.

molecular biology↗

bioRxiv2022

IRF4 deficiency vulnerates B cell progeny for leukemogenesis via somatically acquired Jak3 mutations conferring IL-7 hypersensitivity

The processes leading from disturbed B cell development to adult B cell progenitor acute lymphoblastic leukemia (BCP-ALL) are poorly understood. Here, we describe Irf4-/- mice as prone to developing BCP-ALL with age. Irf4-/- preB-I cells exhibited impaired differentiation but enhanced proliferation in response to IL-7, along with reduced retention in the IL-7 providing bone marrow niche due to decreased CXCL12 responsiveness. Thus selected, preB-I cells acquired Jak3 mutations, probably following irregular AID activity, resulting in malignant transformation. We demonstrate heightened IL-7 sensitivity due to Jak3 mutants, devise a model to explain it and describe structural and functional similarities to Jak2 mutations often occurring in human Ph-like ALL. Finally, targeting JAK signaling with Ruxolitinib in vivo prolonged survival of mice bearing established Irf4-/- leukemia. Intriguingly, organ infiltration including leukemic meningeosis was selectively reduced without affecting blood blast counts. In this work, we present spontaneous leukemogenesis following IRF4 deficiency with potential implications for high-risk BCP-ALL in adult humans.

cancer biology↗