Biology subjects

Kasper, S.

Publications and source records attributed to Kasper, S..

8 recordsLinked to original sources

bioRxiv2025

(S)-ketamine augments behavioral and physiological responses to Δ9-tetrahydrocannabinol

(S)-ketamine is a fast-acting therapeutic to manage treatment-resistant depression as well as psychiatric emergencies. As the non-prescribed use of ketamine has rapidly increased over the past decade, its possible interactions with other recreational drugs are of increasing interest. Here, we addressed if {Delta}9-tetrahydrocannabinol (THC), the main psychoactive constituent of Cannabis sp., and (S)-ketamine could affect each others psychoactive profile in a pharmacological triad. In healthy male mice, the sequential use of (S)-ketamine followed by THC at human-relevant doses did not result in either synergistic or antagonistic effects acutely. In contrast, THC-induced hypothermia was nearly doubled by subsequent (S)-ketamine administration. THC-induced hypolocomotion was not only prolonged by (S)-ketamine, but axial rotation and stumbling during ambulation in an open field were increased in subjects exposed sequentially to both drugs. Likewise, the performance of subjects exposed to THC and then (S)-ketamine worsened on a rotarod. Combined drug treatment led to unusual epinephrine and corticosterone profiles in blood plasma. We suggest that (S)-ketamine augments adverse THC effects, which at the endocrine level invoke the acute deregulation of the hypothalamus-pituitary-adrenal axis. Our findings support the clinical notion that combining cannabis and (S)-ketamine should be avoided.

pharmacology and toxicology↗

bioRxiv2025

Analysis of menstrual effluent uncovers endometriosis-specific cell populations and impaired cellular pathway processes

Endometriosis is a chronic gynecological disease affecting 1 in 10 reproductive-aged women and is characterized by the ectopic presence of endometrial tissue outside the uterus. The leading hypothesis for disease etiology is via the reflux of menstrual effluent (ME) into the peritoneal cavity. ME is a complex mixture of viable endometrial tissue, proteins, and immune cells which serve specialized functions during menstruation to support and repair the endometrium. We hypothesized shifts in the subpopulations of immune cells present during retrograde menstruation may alter the microenvironment of the peritoneal cavity leading to a favorable environment for uterine tissue attachment and survival of endometriotic lesions. Menstrual effluent collected on days 1 and 2 of menstruation identified from women with endometriosis distinct morphological features, increased subpopulations of aged neutrophils, increased anti-inflammatory macrophages, and overall impaired clearance pathways that hijack endometrial clearance likely contributing to the development and progression of endometriosis.

immunology↗

bioRxiv2025

Potassium channels mediate the inhibitory effect of exosomes on anti-tumor immunity in head and neck cancer

Head and neck squamous cell carcinomas (HNSCC) are aggressive cancers with a relatively low response rate to immunotherapy. Anti-tumor immune responses rely on cytotoxic T and NK cells infiltrating the tumor microenvironment to eliminate cancer cells. However, tumors activate multiple mechanisms to evade these responses. Tumor-derived small extracellular vesicles, also known as exosomes, reshape the tumor microenvironment by impairing cytotoxic T and NK cell function, promoting immune escape and metastasis. Transcriptomic analysis of healthy donor peripheral blood mononuclear cells (PBMCs) exposed to exosomes from HPV-negative HNSCC patient primary cancer cells revealed reduced cytotoxic cells and suppressed immune responses including cytotoxicity, chemokine production, and NK and T cell functions. Bead-based multiplex immunoassay showed that HNSCC-derived exosomes inhibited the release of effector cytokines (IL-2, TNF-, IFN-{gamma}) and cytotoxic molecules from activated CD8 T cells. While ion channels regulate Ca{superscript 2}-dependent cytotoxicity and cytokine production and release, their role in exosome-mediated immune suppression is unexplored. We found that tumor-derived exosomes selectively inhibit KCa3.1 channel activity in CD8 T cells by downregulating calmodulin, ultimately impairing Ca{superscript 2} signaling and IFN-{gamma} release. This study identifies a novel mechanism of exosome-mediated immunosuppression, positioning KCa3.1 as a promising therapeutic target to enhance immune surveillance and immunotherapy response in HNSCC.

immunology↗

bioRxiv2022

Single-cell mapping of tumor heterogeneity in pediatric rhabdomyosarcoma reveals developmental signatures with therapeutic relevance

Rhabdomyosarcoma (RMS) is an aggressive human pediatric cancer. Despite robust expression of myogenic regulatory factors, RMS cells are blocked in a proliferative state and do not terminally differentiate. The extent to which the skeletal muscle lineage is represented in RMS tumors and the mechanisms leading to developmental arrest remain elusive. Here, we combined single-cell RNA sequencing (scRNAseq), mass cytometry (CyTOF) and high-content imaging to resolve RMS heterogeneity. ScRNAseq and CyTOF analysis of a total of 17 patient-derived primary cultures and three cell lines uncovered plastic myogenic subpopulations that delineate a branched trajectory. The less aggressive embryonal RMS (eRMS) harbor primarily muscle stem cell (MuSC)-like cells and exhibit sparse commitment to differentiation. The more aggressive alveolar RMS (aRMS) comprise primarily actively cycling committed progenitors with a paucity of differentiated cells. The oncogenic fusion protein PAX3:FOXO1 sustains aRMS cells in the cycling trajectory loop, which we show can re-wired towards differentiation upon its downregulation or by dual pharmacological RAF and MEK inhibition. Our findings provide insights into the developmental states and trajectories underlying RMS progression and identify the RAS pathway as a promising target of differentiation therapy for human aRMS. STATEMENT OF SIGNIFICANCEWe present the first comprehensive single-cell transcriptomic and proteomic atlas of pediatric rhabdomyosarcoma (RMS), in which we identify impaired myogenic trajectories with prognostic value. We demonstrate that RAS pathway inhibitors disrupt the oncogenic trajectory and induce terminal differentiation, revealing novel therapeutic targets for the aggressive alveolar RMS subtype.

cancer biology↗

bioRxiv2021

Human and wildlife use of mountain glacier habitat in western North America

ContextThe global recession of glaciers and perennial snowfields is reshaping mountain ecosystems. Beyond physical changes to the landscape and altered downstream hydrology, the implications of glacier decline for biodiversity are poorly known. Before predictions can be made about how climate change will affect wildlife in glacier-associated ecosystems, a more thorough accounting of the role that glaciers play in species life histories is needed. However, typical approaches for documenting wildlife presence and behavior--remote camera traps--are difficult to use in glaciated terrain due to limited options for securing them (e.g., no trees) and dramatic seasonal changes in snowpack. AimsIn this study, we sought to test a novel camera trap designed for glaciated mountain ecosystems. We also aimed to use this approach to gain insight into wildlife and human usage of a mountain glacier in western North America. MethodsWe deployed an elevational transect of uniquely designed camera traps along the western margin of the Paradise Glacier, a rapidly receding mountain glacier on the south side of Mount Rainier, WA, USA. Our simple camera trap design consisted of a wildlife camera attached to a camouflaged cylindrical cooler filled with snow and rocks. Key resultsOur camera design proved ideal for a mountain glacier ecosystem and from June to September 2021, we detected at least 16 vertebrate species (seven birds, nine mammals) over 770 trap nights using glacier-associated habitats. Humans, primarily skiers, were the most common species detected, but we also recorded 99 observations of wildlife (birds and mammals). These included three species of conservation concern in Washington: wolverine (Gulo gulo), Cascade red fox (Vulpes vulpes cascadensis), and white-tailed ptarmigan (Lagopus leucura). ConclusionsCollectively, our results provide proof-of-concept for a novel camera trap design that is ideal for treeless, perennially snow-covered landscapes and revealed a rich diversity of wildlife using mountain glacier habitat in the Pacific Northwest. We highlight the global need for similar studies to better understand the true scale of biodiversity that will be impacted by glacier recession in mountain ecosystems.

ecology↗

bioRxiv2021

Effects of Escitalopram and Relearning on Cortical and Subcortical Grey Matter in Healthy Humans

The antidepressant effect of selective serotonin reuptake inhibitors (SSRI) is related to increased neuroplasticity during relearning. Stress-induced dendritic atrophy in key brain areas for learning and memory such as the hippocampus and prefrontal cortex is reversed by SSRI treatment. This finding is accompanied by behavioral stabilization. The aim of this study was to investigated serotonergic modulation effects on structural neuroplasticity (cortical thickness, subcortical volumes) during relearning in healthy subjects. Participants performed daily associative learning tasks over 3 weeks followed by a 3-week relearning phase combined with intake of the SSRI escitalopram or placebo. Evidence suggests that SSRIs promote the brains susceptibility to change on the basis of environment factors. We found no effect of SSRI on grey matter measures during relearning. Here, non-findings might be a consequence of the implemented intensity and duration of study interventions. With sparse literature on healthy participants in this field, future studies will have to further elucidate SSRIs properties on relearning and structural neuroplasticity.

neuroscience↗

bioRxiv2021

JNK activation in TA and EDL muscle is load-dependent in rats receiving identical excitation patterns

ABSTACTO_ST_ABSAimC_ST_ABSAs the excitation-contraction coupling is inseparable during voluntary exercise, the relative contribution of the mechanical and neural input is poorly understood. Herein, we use a rat in-vivo strength training setup with an electrically induced standardized excitation pattern previously shown to lead to a load-dependent increase in myonuclear number and hypertrophy, to study acute effects of load per se on molecular signalling. MethodsAnaesthetized rats were subjected to unliteral identical electrically-paced contractions of the TA and EDL muscles under a high or low load for a duration of 2, 10 or 28-minutes. Muscle soluble proteins were extracted, and abundance and specific phosphorylations of FAK, mTOR, p70S6K and JNK were measured. Effects of exercise, load, muscle and exercise duration were assessed. ResultsSpecific phosphorylation of S2448-mTOR, T421/S424-p70S6K and T183/Y185-JNK was increased after 28-minutes of exercise under the high- and low-load protocol. Elevated phosphorylation of mTOR and JNK was detectable already after 2 and 10 minutes of exercise, respectively, but greatest after 28-minutes of exercise. T183/Y185-JNK and S2448-mTOR demonstrated a load-dependent increase in phosphorylation in the exercised muscles that for mTOR depended on muscle type. The abundance of all four kinases was higher in TA compared to EDL muscle. FAK and JNK abundance was reduced after 28 minutes of exercise in both the exercised and control muscle. ConclusionThe current study shows that JNK and mTOR activation is load-driven, and together with muscle-type specific mTOR and p70S6K effects it may drive muscle-type specific exercise and load-responses.

physiology↗

bioRxiv2020

Regional expression profiles of risk genes for depression are associated with brain activation patterns in emotion and reward tasks

The spatial relationship between gene expression profiles and neural response patterns known to be altered in neuropsychiatric disorders, e.g. depression, can guide the development of more targeted therapies. Here, we estimated the correlation between human transcriptome data and two different brain activation maps measured with functional magnetic resonance imaging (fMRI) in healthy subjects. Whole-brain activation patterns evoked during an emotional face recognition task were associated with topological mRNA expression of genes involved in cellular transport. In contrast, fMRI activation patterns related to the acceptance of monetary rewards were associated with genes implicated in neuronal development, synapse regulation, and gene transcription. An overlap of these genes with risk genes from major depressive disorder genome-wide associations studies revealed the involvement of the master regulators TCF4 and MEF2C. These results were further validated by means of meta-analytic fMRI data. Overall, the identification of stable relationships between spatial gene expression profiles and fMRI data may reshape the prospects for imaging transcriptomics studies.

neuroscience↗