Biology subjects

Weis, S.

Publications and source records attributed to Weis, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Hormonal Modulation of Subjective Sleep Quality and Perivascular Space Volume Across the Menstrual Cycle: An Observational Dense-Sampling Study

Background Hormonal fluctuations during the menstrual cycle (and their suppression) are accompanied by altered mood, cognition, and sleep, yet their relationship to subjective sleep quality and glymphatic function - a sleep-dependent brain waste-clearance pathway that involves perivascular spaces (PVS) - is unclear. Methods We examined daily oestradiol, progesterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), subjective sleep quality, and MRI-derived PVS volume (PVSV) in a single healthy woman across two 30-day periods: during her physiological menstrual cycle and, one year later, under oral contraceptive pill (OCP) use. We employed linear regression models to examine whether hormones are associated with sleep quality and PVSV, and whether they moderate the sleep quality-PVSV association during the physiological menstrual cycle. Subsequently, we conducted permutation-based Spearman rank correlations to assess whether day-to-day changes in sleep quality were associated with corresponding changes in PVSV across the physiological menstrual cycle and OCP use. False discovery rate (FDR) correction was used to control for multiple comparisons. Findings Higher LH levels were associated with poorer sleep quality during the physiological cycle (b=2.15, 95% CI 0.64 to 3.67, pFDR=0.028), while FSH moderated the sleep quality-PVSV association (b=-92.98, 95% CI -160.15 to -25.81, pFDR=0.034), suggesting that lower FSH was associated with lower PVSV, whereas this association reversed at elevated FSH levels characteristic of the periovulatory window. During the physiological menstrual cycle, day-to-day decreases in sleep quality were associated with synchronous increases in PVSV, driven by centrum semiovale PVSV ({rho}=0.55, 95% CI 0.30 to 0.67, pperm=0.0095). This association was absent during OCP use and differed between hormonal milieus ({Delta} {rho}=0.72, p=0.040). Interpretation Ovulation is characterized by poor sleep quality and reduced PVSV, potentially reflecting noradrenergic modulation. The association between sleep quality and PVSV day-to-day changes is shaped by the hormonal milieu, being absent under OCP. PVSV increase associated with poor sleep may reflect elevated sleep pressure promoting vasomotor-mediated cerebrospinal fluid inflow.

neuroscience↗

bioRxiv2026

Transient protein phosphorylation promotes disease tolerance to sepsis

One of the enduring paradoxes of sepsis is that organs fail despite little evidence of irreversible tissue injury. Emerging evidence suggests that this state reflects a regulated metabolic shutdown within host tissues, yet whether such hypometabolism contributes to pathology or promotes survival remains unclear. This phenomenon resembles torpor, a physiological state of profound hypometabolism induced by environmental stress and mediated through reversible protein phosphorylation. Septic hypometabolism is identified here as a conserved tissue-specific metabolic adaptation which is characterized by transient activation of Glycogen Synthase Kinase (GSK)3{beta}. This activation reduced disease severity of bacterial sepsis without affecting the hosts pathogen burden, indicating that GSK3{beta} activity promotes disease tolerance to infection. Consistent with these findings, plasma signatures associated with GSK3{beta} inhibition correlated with worse clinical outcomes in patients with sepsis. Together, these results define septic hypometabolism as a torpor-like response and identify reversible phosphorylation as a key mechanism governing host adaptation to severe bacterial infection.

immunology↗

bioRxiv2025

A bioenergetic basis for multiorgan dysfunction in sepsis

Sepsis is a life-threatening multiorgan dysfunction that develops from a maladaptive host response to infection1. With an estimated 49 million cases per year and [~]11 million related deaths2, sepsis is a global WHO health priority3. Failure to overcome sepsis morbidity and lethality4,5 calls for alternative therapeutic approaches6-8. Here we report that adipocyte lipolysis is vital to prevent the pathogenesis of sepsis in mice. This protective response is evolutionary conserved, producing a plasma lipidomic profile9,10 that reflects on the severity of clinical sepsis. Mechanistically, adipocyte lipolysis fuels energy metabolism to sustain adaptive thermoregulation to infection, via insulin production and insulin receptor (INSR) signaling in adipocytes. This metabolic-based defense strategy does not impact on bacterial burden, establishing disease tolerance to infection11-14. In conclusion, adipocyte lipolysis induces insulin to rewire energy metabolism and support organ function in response to infection.

pathology↗

bioRxiv2025

Monocyte control of organismal energy homeostasis

Multicellular organisms rely on inter-organ communication networks to maintain vital parameters within a dynamic physiological range. Macrophages are central to this homeostatic control system, sensing deviations of those parameters and responding accordingly to support tissue function and organismal homeostasis. Here we demonstrate that dysregulation of iron metabolism in parenchyma cells, imposed by the deletion of ferritin H chain, is sensed by monocyte-derived macrophages. In response, macrophages derived from circulating monocytes support tissue function, energy metabolism and thermoregulation, as demonstrated in bone marrow chimeric and parabiotic mice. This salutary effect is contingent on a transcriptional program, controlled in macrophages by the transcription factor A mitochondria. This transcriptional response acts in a non-cell autonomous manner to support the mitochondria of parenchyma cells, irrespectively of mitochondrial transfer. In conclusion, monocyte-derived macrophages cross-regulate Fe and energy metabolism to support tissue function and organismal homeostasis.

immunology↗

bioRxiv2024

Neutrophil-chemoattractant CXCL5 induces lung barrier permeability in acute lung injury

RationaleAcute lung injury is frequently caused by pneumonia, and severity correlates with inflammatory cell recruitment and lung barrier failure. Deciphering drug-targetable pathways is of clinical importance. ObjectivesInvestigation of paracrine and autocrine effects of epithelial-derived chemokine CXCL5 in acute lung injury. MethodsWe assessed the role of CXCL5 and related chemokines in patients with severe pneumonia and primary cells or cell lines challenged with Streptococcus pneumoniae or exposed to mechanical stretch. Furthermore, we evaluated the role of CXCL5 in in vivo models of acute lung injury through use of Cxcl5-deficient mice and in vitro human lung barrier models. ResultsPneumococcal infection and mechanical ventilation were associated with CXCL5 production in human subjects and in mice. CXCL5 was produced by bronchial and alveolar epithelial cells. The alveolar-epithelial barrier was protected in acute lung injury models in Cxcl5-deficient mice, independent of alveolar neutrophil recruitment. Single-cell transcriptomics revealed enhanced cell junctional transcripts in epithelial, but not endothelial cells in Cxcl5-deficient mice. Accordingly, CXCL5 exposure disrupted the barrier function of TNF-primed human primary alveolar epithelial cells, but not pulmonary microvascular endothelial cells. ConclusionsWe describe a novel function of CXCL5 in acute lung injury. Besides its recognized role in recruiting highly inflammatory cells such as neutrophils, CXCL5 increases alveolar-epithelial barrier permeability. Thus, in severe bacterial pneumonia, targeting of CXCL5 as adjunctive therapy to antibiotics may aid in reducing overshooting inflammation as well as stabilizing lung barrier function.

immunology↗

bioRxiv2024

A type 1 immune-stromal cell network mediates disease tolerance and barrier protection against intestinal infection

Type 1 immunity mediates host defense through pathogen elimination, but whether this pathway also impacts tissue function is unknown. Here we demonstrate that rapid induction of IFN{gamma} signaling coordinates a multi-cellular response that is critical to limit tissue damage and maintain gut motility following infection of mice with a tissue-invasive helminth. IFN{gamma} production is initiated by antigen-independent activation of lamina propria CD8+ T cells following MyD88-dependent recognition of the microbiota during helminth-induced barrier invasion. IFN{gamma} acted directly on intestinal stromal cells to recruit neutrophils that limited parasite-induced tissue injury. IFN{gamma} sensing also limited the expansion of smooth muscle actin-expressing cells to prevent pathological gut dysmotility. Importantly, this tissue-protective response had limited impact on parasite burden, indicating that IFN{gamma} supports a disease tolerance defense strategy. Our results have important implications for managing the pathophysiological sequelae of post-infectious gut dysfunction and chronic inflammatory diseases associated with stromal remodelling. HIGHLIGHTSO_LIType 1 immunity is required for disease tolerance to tissue-invasive infection. C_LIO_LIGut-resident CD8+ T cells produce IFN{gamma} in an antigen-independent, yet microbiota-dependent manner. C_LIO_LIIFN{gamma} signaling recruits neutrophils in a cell-extrinsic manner to limit helminth-induced tissue injury. C_LIO_LIDirect sensing of IFN{gamma} by intestinal stroma is essential to limit tissue damage and maintain gut motility during infection. C_LI

immunology↗

bioRxiv2024

Test Retest Reliability of Meta Analytic Networks During Naturalistic Viewing

Functional connectivity analyses have given considerable insights into human brain function and organization. As research moves towards clinical application, test-retest reliability has become a main focus of the field. So far, the majority of studies have relied on resting-state paradigms to examine brain connectivity, based on its low demand and ease of implementation. However, the reliability of resting-state measures is mostly moderate, potentially due to its unconstrained nature. Recently, naturalistic viewing paradigms have gained popularity because they probe the human brain under more ecologically valid conditions, thereby possibly increasing reliability. Therefore, we here compared the reliability of graph metrics extracted from resting-state and naturalistic viewing in functional networks, across two sessions. We show that naturalistic viewing can increase reliability over resting-state, but that its effect varies between stimuli and networks. Furthermore, we demonstrate that the effect of naturalistic viewing differs between two cohorts with Asian and European cultural backgrounds. Taken together, our study encourages the use of naturalistic viewing to increase reliability, but emphasizes the need to carefully select the appropriate stimulus and network for the respective research question.

neuroscience↗

bioRxiv2024

Inter- and intra-subject similarity in network functional connectivity across a full narrative movie

Naturalistic paradigms, such as watching movies during functional magnetic resonance imaging (fMRI), are thought to prompt the emotional and cognitive processes typically elicited in real life situations. Therefore, naturalistic viewing (NV) holds great potential for studying individual differences. However, in how far NV elicits similarity within and between subjects on a network level, particularly depending on emotions portrayed in movies, is currently unknown. We used the studyforrest dataset to investigate the inter- and intra-subject similarity in network functional connectivity (NFC) of 14 meta-analytically defined networks across a full narrative, audio-visual movie split into 8 consecutive movie segments. We characterized the movie segments by valence and arousal portrayed within the sequences, before utilizing a linear mixed model to analyze which factors explain inter- and intra-subject similarity. Our results showed that the model best explaining inter-subject similarity comprised network, movie segment, valence and a movie segment by valence interaction. Intra-subject similarity was influenced significantly by the same factors and an additional three-way interaction between movie segment, valence and arousal. Overall, inter- and intra-subject similarity in NFC were sensitive to the ongoing narrative and emotions in the movie. Lowest similarity both within and between subjects was seen in the emotional regulation network and networks associated with long-term memory processing, which might be explained by specific features and content of the movie. We conclude that detailed characterization of movie features is crucial for NV research.

neuroscience↗

bioRxiv2023

Stimulus selection influences prediction of individual phenotypes in naturalistic conditions

Understanding individual differences and brain-behaviour relationships is an essential goal of human neuroscience. Recent studies have shown the great potential of naturalistic stimuli, e.g., movie clips, in advancing this pursuit. While the use of naturalistic stimuli attracts increasing interest, the influence of stimulus selection remains largely unclear. In this study, we show that brain activity is generally sensitive to the choice of movie stimuli at both group and individual subject levels. Using sex classification as an example, we demonstrate that brain activity elicited by different stimuli can lead to distinct prediction performance and unique predictive features. The stimuli that yield better classification performance often elicit stronger synchrony of brain activity across all subjects and are mostly derived from Hollywood films with rich social content and cohesive narratives. Our results highlight the importance of stimulus selection and provide practical guidance for choosing appropriate stimuli, opening up new avenues for future studies on individual differences and brain-behaviour relationships.

neuroscience↗

bioRxiv2023

Sex differences in intrinsic functional cortical organization reflect differences in network topology rather than cortical morphometry

Brain size robustly differs between sexes. However, the consequences of this anatomical dimorphism on sex differences in intrinsic brain function remain unclear. We investigated the extent to which sex differences in intrinsic cortical functional organization may be explained by differences in cortical morphometry, namely brain size, microstructure, and the geodesic distances of connectivity profiles. For this, we computed a low dimensional representation of functional cortical organization, the sensory-association axis, and identified widespread sex differences. Contrary to our expectations, observed sex differences in functional organization were not fundamentally associated with differences in brain size, microstructural organization, or geodesic distances, despite these morphometric properties being per se associated with functional organization and differing between sexes. Instead, functional sex differences in the sensory-association axis were associated with differences in functional connectivity profiles and network topology. Collectively, our findings suggest that sex differences in functional cortical organization extend beyond sex differences in cortical morphometry. TeaserInvestigating sex differences in functional cortical organization and their association to differences in cortical morphometry.

neuroscience↗

bioRxiv2023

Relating sex differences in cortical and hippocampal microstructure to sex hormones

Sex hormone receptors are expressed widely in both neurons and glial cells, which allows them to interact with the brains major cell groups via several molecular mechanisms. These mechanisms lead to sex differences in brain structure as well as hormone-induced plasticity in the female brain across the menstrual cycle. Adding to the literature on volumetric changes in cortical structure, here we set out to investigate sex differences in the microstructure of the human cortex in relation to sex hormones. We assessed regional variation in cortical microstructure as a function of sex, hormonal status and sex hormone receptor gene expression distribution based on quantitative intracortical profiling in vivo using the magnetic resonance imaging based T1w/T2w ratio in 992 healthy females and males of the Human Connectome Project young adult sample. We demonstrate that microstructure in isocortex and hippocampus differs regionally between males and females, that this effect varies with hormone levels of females and that implicated brain regions overlap with estrogen receptor and sex steroid synthesis gene expression. Lastly, we show that sex and sex hormone related brain structure variations are most pronounced in areas of low laminar cortical complexity (agranular cortex), which are also predicted to be most plastic based on their cytoarchitectural properties. Together, our data thus are suggestive of sex differences in cortical and hippocampal microstructure, as well as the modulatory function of sex hormones on these measures. Albeit correlative, this study underscores the importance of incorporating sex hormone variables into the investigation of brain structure and plasticity.

neuroscience↗

bioRxiv2023

Sex classification from functional brain connectivity: Generalization to multiple datasets

Machine learning (ML) approaches are increasingly being applied to neuroimaging data. Studies in neuroscience typically have to rely on a limited set of training data which may impair the generalizability of ML models. However, it is still unclear which kind of training sample is best suited to optimize generalization performance. In the present study, we systematically investigated the generalization performance of sex classification models trained on the parcelwise connectivity profile of either single samples or a compound sample containing data from four different datasets. Generalization performance was quantified in terms of mean across-sample classification accuracy and spatial consistency of accurately classifying parcels. Our results indicate that generalization performance of pwCs trained on single dataset samples is dependent on the specific test samples. Certain datasets seem to "match" in the sense that classifiers trained on a sample from one dataset achieved a high accuracy when tested on the respected other one and vice versa. The pwC trained on the compound sample demonstrated overall highest generalization performance for all test samples, including one derived from a dataset not included in building the training samples. Thus, our results indicate that a big and heterogenous training sample comprising data of multiple datasets is best suited to achieve generalizable results.

neuroscience↗

bioRxiv2022

To start or to discontinue the pill - changes in progestogens reflected by resting-state connectivity and positive mood

Oral contraceptive (OC) intake has been associated with alterations in functional brain architecture and socio-affective processes. However, most previous studies have been limited by cross-sectional designs and/or did not account for synthetic sex hormone concentrations. The aim of this longitudinal study was to determine the effects of starting vs discontinuing OCs on socio-affective functions such as mood and emotion cognition, and to identify their possible neuroendocrinological substrates. To this end, 88 young healthy women performed the behavioral and fMRI measures twice, three to eight months apart: 26 natural cycling women twice during menstruation, 26 OC users twice during OC intake, 25 OC discontinuers and 11 OC starters before and after discontinuation or start, respectively. In addition to mean-based analyses, we used intersubject representational similarity analyses to determine relationships between interindividual variability in within-subject changes of hormone profiles, including concentrations of endogenous and synthetic hormones, region-specific resting state functional connectivity (parcelwise RSFC) and socio-affective measures. Across the whole sample, interindividual patterns of changes in RSFC of fronto-parietal regions, parts of the left hippocampus and the right cerebellum reflected change patterns of progestogen levels. For the right superior orbitofrontal gyrus (OFG), a trinity of idiosyncratic patterns was found in changes of progestogens, RSFC and positive mood. Active OC intake was associated with higher self-reported depressive symptoms in OC discontinuers (and starters). Emotion recognition performance was not associated with changes in hormone profiles or RSFC. Overall, progestogens rather than estrogens appear to be associated with functional brain architecture of the frontal and subcortical/cerebellar regions and positive mood. The right superior OFG represents a possible neural substrate for progestogen-induced changes in positive mood. This study indicates the importance of a multidimensional, longitudinal approach when being interested in effects of hormonal contraception on womens brain and behavior.

neuroscience↗

bioRxiv2022

Accurate sex prediction of cisgender and transgender individuals without brain size bias

Brain size differs substantially between human males and females. This difference in total intracranial volume (TIV) can cause bias when employing machine-learning approaches for the investigation of sex differences in brain morphology. TIV-biased models will likely not capture actual qualitative sex differences in brain organization but rather learn to classify an individuals sex based on brain size differences, thus leading to spurious and misleading conclusions, for example when comparing brain morphology between cisgender- and transgender individuals. Here, TIV bias in sex classification models applied to cis- and transgender individuals was systematically investigated by controlling for brain size either through featurewise confound removal or by matching training samples for TIV. Our results provide evidence that non-TIV-biased models can classify the sex of both cis- and transgender individuals with high accuracy, highlighting the importance of appropriate modelling to avoid bias in automated decision making. TeaserAccurate non-biased structural sex classification in cis- and transgender individuals by matching training samples for TIV

neuroscience↗

bioRxiv2022

A topography-based predictive framework for naturalistic viewing fMRI

Recent work has shown great interest in understanding individual differences in complex brain function under naturalistic viewing (NV) conditions. However, methods specifically designed for achieving this goal remain limited. Here, we propose a novel approach, called TOpography-based Predictive Framework (TOPF), to investigate individual differences in evoked brain activity on NV fMRI data. Specifically, TOPF identifies individual-specific evoked activity topographies in a data- driven manner and examines their behavioural relevance using a machine learning predictive framework. Our results show that these topographies successfully predict individual phenotypes across cognition, emotion and personality on unseen subjects, and the identified predictive brain regions are neurobiologically interpretable. Further, the prediction accuracy exceeds that of the commonly-used functional connectivity-based features. Conceptually, we highlight the importance of examining multivariate evoked activity patterns for studying brain-behaviour relationships. In summary, we provide a powerful tool for understanding individual differences and brain-behaviour relationships on NV fMRI data.

neuroscience↗

bioRxiv2021

A HYPOMETABOLIC DEFENSE STRATEGY AGAINST PLASMODIUM INFECTION

Hypoglycemia is a clinical hallmark of severe malaria, the often-lethal presentation of Plasmodium falciparum infection of humans. Here we report that mice reduce blood glucose levels in response to Plasmodium infection via a coordinated response whereby labile heme, an alarmin produced via hemolysis, induces anorexia and represses hepatic glucose production (HGP). While protective against unfettered immune-mediated inflammation, organ damage and anemia, when sustained over time heme-driven repression of HGP can progress towards hypoglycemia, compromising host energy expenditure and thermoregulation. This hypometabolic state arrests the development of asexual stages of Plasmodium spp., which undergo pyknosis and develop mitochondrial dysfunction. In response, Plasmodium activates a transcriptional program reducing its virulence and inducing sexual differentiation towards the production of transmissible gametocytes. We infer that malaria-associated hypoglycemia represents a trade-off of an evolutionarily conserved defense strategy restricting Plasmodium spp. from accessing host-derived glucose and balancing parasite virulence and transmission.

immunology↗

bioRxiv2019

Heme induces innate immunity memory

Trained immunity defines long-lasting adaptive responses of innate immunity, mediated by transcriptional and epigenetic modifications of myeloid cells. Here, we report that labile heme, an alarmin released extracellularily upon tissue damage and hemolysis, induces trained immunity in human and murine primary cells and in mice. Heme-trainning in monocytes is associated with epigenetic and transcriptional profiles that overlap to some extent with those seen in {beta}-glucan-training, the prototype agonist of trained immunity. In sharp contrast to {beta}-glucan training however, heme-training relied on activation of the Syk/JNK-pathway. Heme training in mice was associated with long-lasting expansion of myeloid-biased progenitor cells as well as with altered chromatin accessibility in hematopoietic stem and progenitor cells. Finally, heme-induced training was protective against bacterial sepsis in mice. In conclusion, we reveal that heme, a bona fide alarmin, induces innate immune memory regulating host response to infection.

immunology↗

bioRxiv2019

Host-dependent induction of disease tolerance to infection by tetracycline antibiotics

Synergy of resistance and disease tolerance mechanisms is necessary for an effective immune response leading to survival and return to homeostasis when an organism is challenged by infection. Antibiotics are used for their resistance enhancement capabilities by decreasing pathogen load, but several classes have long been known to have beneficial effects that cannot be explained strictly on the basis of their capacity to control the infectious agent. Here we report that tetracycline antibiotics, a class of ribosome-targeting drugs, robustly protects against sepsis by inducing disease tolerance, independently from their direct antibiotic properties. Mechanistically, we find that mitochondrial inhibition of protein synthesis perturbs the electron transfer chain and leads to improved damage repair in the lung and fatty acid oxidation and glucocorticoid sensitivity in the liver. Using a partial and acute deletion of CRIF1 in the liver, a critical mitoribosomal component for protein synthesis, we find that mice are protected against bacterial sepsis, an observation which is phenocopied by the transient inhibition of complex I of ETC by phenformin. Together, we demonstrate that ribosome-targeting antibiotics are beneficial beyond their antibacterial activity and that mitochondrial protein synthesis inhibition leading to ETC perturbation is a novel mechanism for the induction of disease tolerance.

immunology↗