Biology subjects

Schulte, S.

Publications and source records attributed to Schulte, S..

5 recordsLinked to original sources

bioRxiv2026

Cortical Thinning Predicts Resting Vagally Mediated Heart Rate Variability: A Longitudinal Study Across Adolescent Development

IntroductionVagally mediated heart rate variability (vmHRV) reflects parasympathetic cardiac control and serves as a peripheral marker of brain-body interaction. While studies in adults link higher vmHRV to greater cortical thickness regions related autonomic regulatory, little is known about its association with longitudinal cortical maturation during puberty, a period of pronounced cortical thinning. MethodsThis longitudinal study examined whether individual differences in cortical thinning trajectories are associated with vmHRV in two independent cohorts of children and adolescents. Structural MRI were acquired in an accelerated longitudinal design over three time points, each one year apart in two cohorts (n = 44; ages 9 and 12 at baseline). Cortical thickness was estimated using FreeSurfer, and annualized regional thinning slopes were derived for 62 cortical regions. vmHRV was measured one year later at follow-up. Elastic net regression with stability selection identified robust predictors, which were entered into linear models separately for each cohort. ResultsAcross both cohorts, vmHRV was associated with distributed patterns of cortical thinning. Consistent associations emerged in medial and posterior midline regions, including the precuneus, isthmus of the cingulate cortex, and medial prefrontal and orbitofrontal areas. Associations showed heterogeneous directions across regions, contrasting with uniform adult findings. DiscussionvmHRV may be linked to network-level cortical maturation during adolescence, particularly within default mode and fronto-limbic systems. Findings extend adult work by demonstrating that brain-autonomic coupling emerges during development and is characterized by regionally differentiated trajectories of cortical thinning.

neuroscience↗

bioRxiv2025

Tuning Yeast Glycosylation Proximal to the FLS2-flg22 Binding Interface enables Functional Yeast Surface Display under Induced ER Stress

Pattern recognition receptors such as FLAGELLIN SENSING 2 (FLS2) are central to plant immunity and attractive targets for engineering broader detection of bacterial phytopathogens for application in pest management (and diagnostics) in food crops, and sustainable agriculture practices. However, evaluating numerous FLS2 variants for altered pathogen sensing specificity directly in plants is slow and low throughput, and have been seldom optimized for heterologous display systems. Here, we established conditions that enabled Arabidopsis thaliana FLS2 ectodomain expression on the surface of Saccharomyces cerevisiae and evaluated binding to its cognate ligand, flg22. We show how yeast high-mannose glycosylation of the FLS2 ectodomain contributes to inefficient folding and loss of detectable flg22 binding in standard yeast surface display conditions. Substitutions at all N-glycosylation motifs compromised surface expression, indicating that some glycosylation is required for trafficking. We tuned the extent of glycosylation using tunicamycin, an N-linked glycosylation inhibitor, in combination with thermal stress to modulate ER quality control. Under these conditions, we observed a reproducible subpopulation of cells with improved flg22 binding despite reduced overall expression, and we confirmed flg22 selectivity against non-FLS2 proteins using both flow cytometry and magnetic bead-based enrichment. Guided by structural modeling of high-mannose glycans on the FLS2 ectodomain, we then substituted asparagines at selected N-glycan sites to serine. We identified a key glycan site variant, N388S, which lies proximal to the flg22 binding interface and increased the binding population size under stress conditions. Binding assays against FLS2 variants and a reported non-binding variant affirmed that FLS2 selectivity was specific to FLS2 display, showing that all variants maintained low affinity interaction with flg22. Together, these results point to FLS2 display conditions, not only glycosylation state, as an underlying limitation to detect true flg22 interactions which will require more sensitive approaches to confidently resolve true binding populations. For Table of Contents Use Only O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=144 SRC="FIGDIR/small/690463v2_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@1556b0eorg.highwire.dtl.DTLVardef@e764d1org.highwire.dtl.DTLVardef@18bdcfborg.highwire.dtl.DTLVardef@1592114_HPS_FORMAT_FIGEXP M_FIG C_FIG

synthetic biology↗

bioRxiv2025

Early Aβ-induced changes in the enteric nervous system and gut: structure, function, and motility

Alzheimers disease is increasingly recognized as affecting not only the central nervous system but also the autonomic nervous system, comprising the enteric nervous system, and thus the gut. Given the structural and functional similarities between the enteric and central nervous system, including susceptibility to A{beta}, this study investigated the early and acute effects of monomeric A{beta} on primary enteric neurons in vitro and on intestinal motility ex vivo. Acute A{beta} application caused marked neuronal hyperexcitability, with increased spike frequencies and calcium influx, and led to enhanced intestinal contractility without altering frequency or timing. Prolonged 72-hour exposure did not induce cell death or apoptosis but significantly reduced neurite outgrowth and decreased synaptic markers and beta II tubulin. These findings suggest that acute A{beta} primarily drives the excitability of enteric neurons and intestinal motility, while prolonged exposure subsequently leads to structural and synaptic changes. Overall, the study points to early dysfunction of the enteric nervous system in Alzheimers disease and highlights the gut as a potential target for early interventions. Synopsis O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=190 SRC="FIGDIR/small/678722v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@18b5292org.highwire.dtl.DTLVardef@1da0ecforg.highwire.dtl.DTLVardef@1023b09org.highwire.dtl.DTLVardef@171e3fb_HPS_FORMAT_FIGEXP M_FIG C_FIG The pathology of Alzheimers disease is increasingly recognized in the enteric nervous system (ENS), suggesting an early contribution of the gut to the onset of the disease. This study investigated the acute and short-term effects of amyloid-{beta} (A{beta}) on intestinal motility and enteric neurons to elucidate early functional and structural changes beyond the brain. O_LIAcute A{beta} exposure enhanced intestinal contractility ex vivo. C_LIO_LIEnteric neurons showed hyperexcitability and increased Ca{superscript 2} influx. C_LIO_LIAfter 72 h, neuronal viability and apoptosis remained unaffected. C_LIO_LIProlonged exposure reduced neurite outgrowth and {beta}III-tubulin expression. C_LIO_LISynaptic density was significantly decreased. C_LI

neuroscience↗

bioRxiv2021

The molecular appearance of native TRPM7 channel complexes identified by high-resolution proteomics

The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a ubiquitously expressed membrane protein consisting of ion channel and protein kinase domains. TRPM7 plays a fundamental role in the cellular uptake of divalent cations such as Zn2+, Mg2+ and Ca2+, and thus shapes cellular excitability, plasticity and metabolic activity. The molecular appearance and operation of TRPM7 channel complexes in native tissues have remained unresolved. Here, we investigated the subunit composition of endogenous TRPM7 channels in rodent brain by multi-epitope affinity purification and high-resolution quantitative MS analysis. We found that native TRPM7 channels are high molecular-weight multi-protein complexes that contain the putative metal transporter proteins CNNM1-4 and a small G-protein ARL15. Heterologous reconstitution experiments confirmed the formation of TRPM7/CNNM/ARL15 ternary complexes and indicated that ARL15 effectively and specifically impacts TRPM7 channel activity. These results open up new avenues towards a mechanistic understanding of the cellular regulation and function of TRPM7 channels. Impact StatementHigh-resolution proteomics in conjunction with biochemical and electrophysiological experiments revealed that the channel-kinase TRPM7 in the rodent brain forms macromolecular complexes containing the metal transporters CNNM1-4 and a small G protein ARL15.

biochemistry↗

bioRxiv2020

Functional and molecular early enteric biomarkers for Parkinson's disease in mice and men

Parkinsons disease (PD) usually has a late clinical onset. The lack of early biomarkers for the disease represents a major challenge for developing timely treatment interventions. Here, we use an -synuclein-overexpressing transgenic (Th-1-SNCA-A30P) mouse model of PD to identify appropriate candidate markers in the gut for early stages of PD before hallmark symptoms begin to manifest. A30P mice did not show alterations in gait parameters at 2 months of age, and these mice were therefore defined as pre-symptomatic A30P mice (psA30P). We discovered early functional motility changes in the gut and early molecular dysregulations in the myenteric plexus of psA30P mice by comparative protein and miRNA profiling and cell culture experiments. We found that the proteins neurofilament light chain, vesicle-associated membrane protein 2 and calbindin 2, together with the miRNAs that regulate them, are potential biomarkers of early PD that may facilitate timely treatment and/or prevention of PD in men.

neuroscience↗