Biology subjects

Scheele, C.

Publications and source records attributed to Scheele, C..

11 recordsLinked to original sources

bioRxiv2026

PepHammer - a lightweight web-based tool for bioactive peptide matching and identification

Peptides are gaining increasing attention as therapeutic agents. Already, peptide-based therapeutics play a key role in the treatment of diverse diseases, including diabetes, obesity, and other complex disorders, and their clinical relevance is expected to expand further in the coming years. Technological and computational advances have substantially enriched peptidomics, massively increasing the scale and depth of peptide identification. As a result, increasingly large and information-rich datasets are now available for downstream analysis and experimental validation. However, the rapid expansion of peptidomics datasets also leads to a corresponding increase in search space, complicating the efficient identification of peptides relevant to specific biological or clinical questions. To address this challenge, we present PepHammer, a lightweight web-based tool for bioactive peptide matching and identification. PepHammer allows users to input up to 10000 peptides (2-150 amino acids in length) and compare them against extensive databases of peptides with predicted or experimentally validated bioactivities and tissue associations using Hamming distance, Grantham distance, as well as partial or exact matching strategies. Via an example study of human milk peptidomics, we demonstrate that PepHammer rapidly provides an overview of the bioactivity and tissue-relational landscape, serving as a starting point for downstream analyses. PepHammer thus enables efficient exploration of large-scale peptidomics datasets and facilitates the identification of biologically relevant peptides.

bioinformatics↗

bioRxiv2026

BioTrendFinder - an interactive web tool for exploring functional drivers in gene- and protein-level bulk omics data

The analysis of bulk omics data, such as RNA-seq and proteomics, has enabled numerous biological discoveries. Standard analytical workflows typically comprise dimensionality reduction, group-wise statistical comparisons, functional enrichment analysis, and mapping of molecules to biological networks. Although informative, these steps are often applied independently, limiting integrative interpretation and the efficient identification of functional drivers and candidate targets. To address these limitations, we developed BioTrendFinder, an interactive web tool for exploring functional drivers in gene- and protein-level bulk omics data. BioTrendFinder employs a sample-ranking strategy to identify significant molecular trendlines that capture expression patterns across ranked sample compositions in dimensionally reduced data. These trends are integrated with statistical results, sample-group metadata and functional information from STRING and eleven bio-ontologies, enabling interactive network-based exploration and the generation of entity-ranked functional modules. BioTrendFinders unique approach and functionalities add additional analytical dimensions to bulk omics data by facilitating the extraction of high-level information from alternative analytical perspectives. Using previously published proteomics and transcriptomics datasets, we demonstrate that BioTrendFinder supports both hypothesis-driven and exploratory investigations, enabling the prioritization of candidate molecular targets and effectively narrowing the search space for downstream validation steps.

bioinformatics↗

bioRxiv2025

Autophagy maintains HEV identity and function during inflammation

High endothelial venules (HEVs) play a crucial role in adaptive immune responses in secondary and tertiary lymphoid organs. They are uniquely equipped with high levels of peripheral node addressins (PNAd), harboring carbohydrate structures that serve as L-Selectin ligands to efficiently facilitate lymphocyte homing. During inflammation, the HEV network expands in SLOs, increasing lymphocyte infiltration, but the underlying mechanisms maintaining HEVs remain underexplored. Here, we report that autophagy is essential for HEV function and expansion. Using single-cell transcriptomics, intravital imaging, and an inducible HEV tracer system in mice, we demonstrate that autophagy deficiency compromises LT{beta}R-signaling and the Unfolded Protein Response in HEVs, leading to disrupted PNAd production, dedifferentiation, and reduced lymphocyte homing. Autophagy deficiency and LT{beta}R blockade impaired HEV function and reduced skin inflammation in psoriasis-bearing mice by limiting immune infiltration and cytokine release. Our work uncovers an unprecedented role of autophagy in safeguarding HEV identity and function during inflammation. HighlightsO_LIHigh endothelial venules (HEVs) exhibit heightened autophagy in comparison to non-HEV blood endothelial cells, which further increases during inflammation. C_LIO_LIAutophagy is pivotal in maintaining HEV fate and function, specifically during inflammation, via LT{beta}R signaling and the Unfolded Protein Response (UPR), ensuring the proper production of peripheral node addressins (PNAd) that serve as L-selectin ligands for the efficient influx of naive lymphocytes. C_LIO_LIBlocking autophagy in HEVs leads to disrupted PNAd production, HEV flattening and dedifferentiation, and reduced lymphocyte homing. C_LIO_LIGenetic and pharmacological perturbation of HEV function in the lymph nodes and skin lesions of psoriasis-bearing mice impaired neutrophil and lymphocyte recruitment, as well as cytokine secretion, thereby alleviating skin inflammation. C_LI

cell biology↗

bioRxiv2025

Sex Hormone Binding Globulin Controls Gender Specific Lipolytic Activity in Human Abdominal Subcutaneous Adipocytes

Regulation of lipid metabolism is fundamental for metabolic health, and adipose tissue is a central component in this process. Adipose tissue differs dramatically between women and men with a higher subcutaneous capacity for storage and healthy metabolism in women. Sex hormone-binding globulin (SHBG) contributes to the regulation of circulating sex hormone bioavailability and has been shown to predict risk of metabolic dysfunction. We here investigate the sex-specific relationship of SHBG with metabolic status and adipocyte-dependent lipolysis. We measured serum concentrations of sex hormones, SHBG, fasting glucose and insulin in a cohort of 63 women and 27 men from which adipose biopsies were collected and mature adipocytes were isolated. We found that, in women, high serum SHBG concentrations were strongly associated with low HOMA-IR in vivo, and lower baseline lipolysis but higher responsiveness to isopropanol-induced lipolysis ex vivo. In contrast, no effect of SHBG on the above-mentioned parameters were observed in men. In vitro, cultured adipocytes also increased lipolytic capacity in response to SHBG, but only in the absence of testosterone, suggesting that testosterone inhibits the catecholmine-induced lipolysis of SHBG in adipose tissue. In conclusion, we here define a novel role for SHBG in adipocyte lipolysis. At the same time, our data emphasize sex-dependent differences in adipocyte lipid metabolism, and we propose testosterone binding to SHBG as a driving factor mediating these differences.

physiology↗

bioRxiv2024

Brown Bears activates a Satiety Hormone Cholecystokinin (CCK) pathway in adipose tissue during hibernation

The brown bear (Ursus arctos) hibernates to survive cold winters without access to food. It builds enormous subcutaneous fat stores during summer and relies on it for energy during winter. Remarkably, the weight loss during winter occurs without muscle loss despite inactivity. Studying brown bear biology can therefore provide insights for improving human health in obesity and weight loss treatments. We here investigate subcutaneous adipose tissue biopsies obtained during summer and winter from free-living brown bears. During winter, a signature of genes involved in food intake and digestion is upregulated. Among these are several regulators of satiety, substrate transport and lipid metabolism. Interestingly, in humans these genes are enriched in distinct metabolic organs including, brain, intestine, stomach, liver and even salivary glands. We focused on the satiety brain/intestinal hormone cholecystokinin (CCK), which we demonstrate is produced in adipocytes, accompanied by an upregulation of the CCK receptor CCKBR. Importantly, CCK was undetectable in the circulation during winter and presence of sensory neurons suggest a neuronal feedback mechanism within the adipose tissue. Using RNA sequencing, we predict additionally 537 secreted proteins to be seasonally regulated, 37 of which could be confirmed with plasma proteomics. In conclusion, we propose that brown bears have developed a strategy of healthy fat burning and satiety regulation through an adipose tissue-contained mechanism which includes digestion factors and satiety mediators to provide safe energy turnover during hibernation-dependent weight loss.

molecular biology↗

bioRxiv2024

An ultrasound-guided biopsy technique for obtaining supraclavicular brown fat biopsies and preadipocytes

Studying activated human brown adipose tissue (BAT) in vivo poses challenges due to its intricate anatomical positioning. Through the implementation of an ultrasound-guided biopsy technique, we successfully collected BAT samples from the supraclavicular region of 27 healthy individuals. As a comparative control, subcutaneous white adipose tissue (WAT) was similarly extracted from the same participants. Furthermore, we isolated progenitor cells from four tissue biopsies in both regions, subsequently subjecting them to a 12-day in vitro differentiation protocol following stimulation with 10 {micro}M norepinephrine. To assess the mRNA expression of thermogenic genes within these small tissue samples, we employed a targeted cDNA amplification procedure, followed by conventional quantitative PCR (qPCR). Our study demonstrated that, with further refinement, this biopsy methodology can be used to obtain thermogenic adipose tissue. However, the expression data exhibited considerable diversity, and no statistically significant overall trends emerged for any of the five BAT marker genes (UCP1, PPARGC1A, PRDM16, CIDEA, CITED1), nor for the WAT marker HOXC8. The differentiation capacity of the progenitor cells revealed irregularities, with only three adipocyte cultures (two WAT and one BAT) displaying satisfactory differentiation potential. Remarkably, the differentiated BAT culture displayed a significantly elevated basal UCP mRNA expression level, further induced by 1.7-fold upon stimulation with norepinephrine. In summary, based on the in vitro data, brown adipose samples can be obtained using our ultrasound-guided biopsy technique approach. However, significant refinements are necessary before robust in vivo data can be generated in future intervention studies.

physiology↗

bioRxiv2023

An autophagy program that promotes T cell egress from the lymph node controls responses to immune checkpoint blockade

Lymphatic endothelial cells (LECs) lining the lymphatic vessels of the lymph node (LN) parenchyma orchestrate leukocyte trafficking and peripheral T cell dynamics. T cell responses to immunotherapy largely rely on peripheral T cell recruitment in tumors. Yet, a systematic and molecular understanding of how LECs within the LNs control T cell dynamics under steady state and tumor-bearing conditions is lacking. Using intravital and high-resolution imaging combined with immune phenotyping, we show that LEC-specific deletion of the essential autophagy gene Atg5 alters intranodal positioning of lymphocytes and accrues their persistence in the LNs, by increasing the availability of the main egress signal S1P. Single-cell RNA-sequencing of tumor-draining LNs from WT and ATG5LEC-KO mice unveils that loss of ATG5 remodels niche-specific LEC phenotypes, involved in molecular pathways regulating lymphocyte trafficking and LEC-T cell interactions. Functionally, loss of LEC-autophagy prevents recruitment of tumor-infiltrating T cells and NK cells and abrogates tumor regression in response to anti-PD-1 or anti-CTLA4-based immunotherapy. Thus, a unique LEC-autophagy program boosts immune-checkpoint responses by guiding systemic T cell dynamics. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=143 SRC="FIGDIR/small/549282v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@1a4bfe1org.highwire.dtl.DTLVardef@1317fe2org.highwire.dtl.DTLVardef@c2fa20org.highwire.dtl.DTLVardef@b35dba_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2020

Thermogenic genes are blunted whereas brown adipose tissue identity is preserved in human obesity

Obesity associates with a reduction in cold-induced glucose tracer uptake in brown adipose tissue in humans, suggesting loss of thermogenic capacity. We therefore hypothesized that a whitening of BAT occurs in obesity and assessed the molecular characteristics of deep neck BAT in a cohort of 24 normal weight, 24 overweight and 22 obese individuals in comparison with subcutaneous abdominal white adipose tissue (WAT). We found that the major marker of BAT thermogenesis, UCP1, was associated with central but not general obesity. We performed transcriptomic analysis of BAT in a cohort of 27 individuals classified as normal weight, over-weight or obese, and additionally four subjects with type 2 diabetes (T2DM), dispersed among the 3 BMI groups. We identified 3204 differentially expressed genes between BAT and WAT in samples from normal weight individuals, including genes involved in thermogenesis, but also revealing differences in developmental and immune system related genes. In BAT from individuals with overweight or obesity, 202 genes were downregulated and 66 of these were involved in cellular respiratory pathways, likely reflecting previously observed reduction in thermogenic function with obesity. Importantly, most BAT selective genes were not affected, and isolated adipose progenitors differentiated into thermogenic adipocytes with equal frequency regardless of BMI group. In conclusion, our data suggest a retained BAT identity, with a selective reduction of thermogenic genes, in human obesity.

cell biology↗

bioRxiv2018

Proteomics-based comparative mapping of the human brown and white adipocyte secretome reveals EPDR1 as a novel batokine

Secreted proteins from adipose tissue play a role in metabolic cross-talk and homeostasis. We performed high sensitivity mass spectrometry-based proteomics on the cell media of in vitro differentiated, non-immortalized brown adipocytes derived from supraclavicular adipose of adult humans and white adipocytes derived from subcutaneous adipose of adult humans. We identified 471 potentially secreted proteins covering interesting protein categories such as hormones, growth factors, growth factor binding proteins, cytokines, extracellular matrix proteins, and proteins of the complement system, which were differentially regulated in brown and white adipocytes. A total of 101 proteins were exclusively quantified in brown adipocytes, among these ependymin-related protein 1 (EPDR1). Ablation of EPDR1 impaired the induction of thermogenic transcripts in response to norepinephrine in brown adipocytes, while EPDR1-treated mice increased their energy consumption, suggesting a role in brown fat commitment and activation. Our work reveals substantial differences between the secretomes of brown and white human adipocytes and identifies novel candidate batokines.

physiology↗

bioRxiv2018

Asymmetric perirenal brown adipose dormancy in adult humans is defined by local sympathetic activity

We here detect dormant brown adipose tissue (BAT) in adult humans, occurring in most of the perirenal fat depot and characterized by a unilocular morphology. This phenotype was contrasted by multilocular BAT accumulating near the adrenal gland. Transcriptomic analysis revealed a gene expression profile of unilocular BAT that was approaching, yet was still distinct from, the expression profile of subcutaneous white adipose tissue (WAT). Candidate gene signatures were recapitulated in a murine model of unilocular brown fat induced by thermoneutrality and high fat diet. We identified SPARC as a candidate adipokine representing a dormant BAT state in the absence of sympathetic activation and CLSTN3 as a novel marker for multilocular BAT. Brown fat precursor cells were present in the entire perirenal fat depot, regardless of state. When differentiated in vitro, these cells responded to acute norepinephrine stimulation by increasing UCP1 gene expression and uncoupled respiration, confirming a BAT phenotype. We thus propose a mechanism for the reduction of functionally competent BAT in adult humans and we provide a solid data set for future research on factors that can reactivate dormant BAT as a potential strategy for combatting obesity and metabolic disease.

physiology↗

bioRxiv2018

A long-non-coding RNA, LINC00473, confers the human adipose tissue thermogenic phenotype through enhanced cAMP responsiveness.

Specialized adipocytes localized in distinct depots mediate the many physiological functions of adipose tissue. In humans, paucity of thermogenic adipocytes correlates with high metabolic disease risk, raising much interest in the mechanisms by which these cells arise. Here we report molecular signatures associated with adipocyte development in different human depots and identify a long non-coding RNA, LINC00473, as the transcript most closely associated with enrichment of thermogenic adipocytes. LINC00473 expression is low in subjects with obesity or type-2 diabetes and is highly correlated with cAMP signaling and mitochondrial oxidative phosphorylation pathways. LINC00473 is localized in the nucleus and the cytoplasm, and its knockdown impairs induction of UCP1 and mitochondrial respiration. These results reveal that depot-enriched genes that modulate responsiveness to external stimuli, specifically LINC00473, are important determinants of the adipose tissue thermogenic phenotype, and potential targets for metabolic disease therapy.

cell biology↗