Biology subjects

Schumacher, E.

Publications and source records attributed to Schumacher, E..

5 recordsLinked to original sources

bioRxiv2026

Adjuvants MPLA and SMNP induce antiviral immunity and indirectly revert HIV-1 latency

Monophosphoryl lipid A (MPLA) and the saponin-MPLA nanoparticle adjuvant (SMNP) are known immunostimulants used as adjuvants in vaccines to boost immunity. These adjuvants are under investigation for use in prophylactic and therapeutic HIV-1 vaccines. However, their effects in ART-treated people with HIV-1 (PWH) remain unclear, as chronic immune activation may reduce responses and potentially reactivate latent virus reservoirs. Here we observed that both adjuvants, MPLA and SMNP, triggered TLR4-dependent cytokine production in monocyte-derived dendritic cells (DCs), but SMNP elicited a stronger response than MPLA based on costimulatory receptor expression and cytokine production. Cytokines produced by adjuvant stimulated dendritic cells were able to induce HIV-1 transcription in a J-Lat cell model. Notably, SMNP, but not MPLA, also induced a cytokine response in PBMC from PWH, albeit lower as compared to in healthy donor PBMC. Importantly, SMNP substantially reduced the size of the inducible HIV-1 reservoir in PWH ex vivo without bystander cytotoxicity. The effect on the viral reservoir was likely caused by the cytokine production induced by SMNP, as supernatants from SMNP stimulated DCs showed a similar viral reservoir reduction. Our findings demonstrate that TLR4-targeted adjuvants, especially SMNP, can effectively induce immune activation, supporting their potential use in therapeutic vaccination. However, as reservoir reduction was observed ex vivo, further evaluation is warranted to ensure safe use of such adjuvants in PWH.

immunology↗

bioRxiv2026

Fidelity of Spatiotemporal Patterns of Brain Activity Across Sampling Rate, Scan Duration, and Frequency Content

Intrinsic brain activity is characterized by large-scale spatiotemporal patterns that underpin functional connectivity and cognition. Quasi-periodic patterns (QPPs) and complex principal component analysis (cPCA) have emerged as reproducible methods for capturing spatiotem-poral network interactions in resting-state functional magnetic resonance imaging (rs-fMRI). However, these methods remain sensitive to methodological factors such as scan duration, repetition time (TR), and frequency band selection. This study systematically evaluates how these parameters influence the stability and reliability of QPP- and cPCA-derived functional connectivity patterns across multiple datasets. Using five independent rs-fMRI datasets, we evaluate the impact of scan length on pattern reliability, explore the effects of TR on spatiotemporal patterns, and compare the sensitivity of different frequency bands (Slow-5, Slow-4, infraslow) in capturing network dynamics. Our findings reveal that while both QPPs and cPCA detect intrinsic network activity, their reliability varies with acquisition parameters. QPPs exhibit greater stability in shorter scans, making them suitable for individual-level analyses, whereas cPCA provides a broader representation of phase-coherent fluctuations but shows greater between-subject variability and benefits more from longer, group-level acquisi-tions. Additionally, frequency band selection significantly influences the temporal structure of extracted patterns: in our analyses, Slow-5 (0.01-0.027 Hz) tended to emphasize more recurrent, synchronized network configurations, whereas Slow-4 (0.027-0.073 Hz) more often revealed transitions between connectivity states. These results provide critical insights into optimizing methodological choices for dynamic functional connectivity analysis, enhancing the interpretability of spatiotemporal patterns in both basic and clinical neuroimaging research.

neuroscience↗

bioRxiv2025

A developmental condensin I complex assists the Paramecium PiggyMac domesticated transposase during programmed DNA elimination

Prokaryotes and eukaryotes use diverse strategies to cope with invading mobile genetic elements, including programmed DNA elimination (PDE). In the ciliate Paramecium, elimination of transposable elements and their relics requires the PiggyMac (Pgm) endonuclease and its five PgmL partners, yet how this machinery is targeted to cleavage sites remains unclear. Here, we identified condensin I subunits in the proximity proteomes of Pgm and PgmL4. We show that they belong to a condensin complex that is essential for PDE and localizes to developing somatic nuclei. Depleting the development-specific subunits of this complex blocks DNA elimination, phenocopying a Pgm depletion. Developmental condensin is required for the correct nuclear localization of Pgm and some of the PgmLs. Moreover, Pgm and these PgmLs co-immunoprecipitate with condensin I. Our findings uncover functional and physical interactions between a eukaryotic DNA cleavage machinery and a specialized condensin complex that is critical for PDE in a non-dividing nucleus.

molecular biology↗

bioRxiv2025

The Infraslow Fluctuation of Sigma Power During Sleep in Young Individuals with Schizophrenia

A reduction in sleep spindles, a major electrophysiological characteristic of Non-Rapid Eye Movement sleep, has been suggested as a potential biomarker of schizophrenia. While research has primarily focused on the spindle quantity, recent studies have begun to explore their temporal dynamics throughout the night. In healthy individuals, sleep spindles fluctuate on an infraslow [~]50-second timescale, alternating between phases of high and low spindle activity. This fluctuation is referred to as the infraslow fluctuation of sigma power (ISFS), which is modulated by noradrenergic activity from the locus coeruleus and linked to the organization of arousal and memory reactivation processes during sleep. Given the known deficit in sleep spindles, dysregulation of noradrenergic activity, and impairments in sleep maintenance and memory in schizophrenia, this study investigates the ISFS in sleep electroencephalography data from individuals with either Childhood-Onset Schizophrenia (COS; N = 17) or Early-Onset Schizophrenia (EOS; N = 11), aged 9 to 21 years, alongside age- and sex-matched healthy controls (N = 56). The presence and strength of the ISFS were reduced in both COS and EOS groups compared to controls, particularly in central-parietal electrodes. No significant differences in these features of the ISFS were found between the two clinical groups, despite group differences in sleep spindle density and clinical characteristics. These findings suggest that the ISFS is observable but reduced in young patients with schizophrenia and support the notion that the timing of sleep spindles may inform pathomechanistic models of the disorder, as well as future diagnostic approaches and interventions.

neuroscience↗

bioRxiv2024

Altered functional connectivity and spatiotemporal dynamics in individuals with sleep disorders

Idiopathic hypersomnia (IH) is a sleep disorder characterized by highly disruptive symptoms. Like narcolepsy type 1, a well-characterized sleep disorder, individuals with IH suffer from excessive daytime sleepiness, though there is little overlap in metabolic or neural biomarkers across these two disorders. This lack of common pathophysiology, combined with the clear overlap in symptoms presents an ideal paradigm for better understanding the impact of IH on an individuals functional activity and organization, and potentially, the underlying pathophysiology. This study examines the observed functional connectivity in patients with IH, and patients with narcolepsy type 1 (NT1) against healthy control individuals. Static functional connectivity is compared, as are quasi-periodic patterns, acquired from the BOLD timecourse, for all groups. In addition to baseline data comparison, the study also included a post-nap condition, where the individuals included in this analysis napped for at least 10 minutes prior to the scanning session, to explore why individuals with IH do not feel "refreshed" after a nap like individuals with NT1 do. Assessing the groups spatiotemporal patterns revealed key differences across both disorders and conditions: static connectivity revealed at baseline higher subcortical connectivity in the NT1 group. There was also observably less connectivity in the IH group both at baseline and post-nap, though none of these static analyses survived multiple comparisons correction to reach significance. The QPP results however found significant differences in the IH group in key networks, particularly the DAN/FPCN correlation is significantly different at baseline vs. post-nap, a trend not observed in either the control or NT1 groups. The DAN and FPCN are drastically altered both at baseline and post-nap when compared to the other groups, and may likely be a disorder-specific result. This study demonstrates that key networks for arousal are more heavily disrupted in IH patients, who are less affected by a nap, confirmed through both subject reporting and functional evidence through spatiotemporal patterns.

pathology↗