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Kohl, C.

Publications and source records attributed to Kohl, C..

10 recordsLinked to original sources
bioRxiv2025

Pro-endometriosis macrophage release of IL-33 is key for endometriosis pain and lesion formation

Endometriosis is a painful gynecological inflammatory disease affecting up to 10% of females. When released by sensory neurons, calcitonin gene-related peptide (CGRP) shapes immunity, a process known as neuroimmune communication. We previously showed that nociceptor-derived CGRP polarizes macrophages into pro-endometriosis macrophages (PEMs) that mediates endometrial epithelial (endo-epi) cell proliferation and pain. However, the key mediators involved in this PEM-induced cell proliferation were unknown. Using unbiased approaches, we discovered that nociceptor-derived CGRP induces PEMs to produce IL-33. IL-33 binding to its receptor ST2 is key for endometriotic lesion growth and pain during endometriosis in mice as anti-IL-33 antibody treatment reduced evoked and spontaneous pain as well as lesion size. Chemical or genetic ablation of nociceptors or macrophages also resulted in lower levels of lesion IL-33, demonstrating a neuroimmune-driven mechanism for IL-33 production during endometriosis. In humans, we found that IL-33 is correlated with increased number of glands and fibrosis in lesions and that IL-33 expression in macrophages is also associated with genetic risk of endometriosis. We also provided evidence that suggests a dual role for IL-33 in endometriosis, in which, it is initially required for lesion formation and later for lesion maintenance only, and associated pain. Therefore, targeting IL-33/ST2 signaling may effectively treat endometriosis pain.

neuroscience↗
bioRxiv2025

CAdir: Fast Clustering and Visualization of Single-Cell Transcriptomics Data by Direction in CA Space

Clustering for single-cell RNA-seq aims at finding similar cells and grouping them into biologically meaningful clusters. Many available clustering algorithms however do not not provide the cluster defining marker genes or are unable to infer the number of clusters in an unsupervised manner as well as lack tools to easily determine the quality of the label assignments. Therefore, clustering quality is commonly evaluated by visually inspecting low-dimensional embeddings as produced by e.g. UMAP or t-SNE. These embeddings can, however, distort the true cluster structure and are known to produce radically different embeddings depending on the chosen hyperparameters. Determining clustering quality therefore still heavily relies on domain knowledge to assess if cells should be clustered together. In order to improve the interpretability of clustering results, we developed CAdir (https://github.com/VingronLab/CAdir), a clustering algorithm that can infer the number of clusters in the data, determine cluster specific genes and provides easy to interpret diagnostic plots. CAdir exploits the geometry induced by correspondence analysis (CA) to cluster cells as well as cluster associated genes based on their direction in CA space. Using the angle between the cluster directions, it is able to automatically infer the number of clusters in the data by merging and splitting clusters. A comprehensive set of diagnostic and explanatory plots provides users with valuable feedback about the clustering decisions and the quality of the final as well as intermediary clusters. CAdir is scalable to even the largest data set and provides similar clustering performance to other state-of-the-art cell clustering algorithms in our benchmarking. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=90 SRC="FIGDIR/small/643234v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@bcabd5org.highwire.dtl.DTLVardef@b53ec4org.highwire.dtl.DTLVardef@12bbe6dorg.highwire.dtl.DTLVardef@e31d13_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗
bioRxiv2024

First report of pathogenic Leptospira in Sri Lankan bats: A potential reservoir risk

BackgroundLeptospirosis is a bacterial infection caused by spirochetes of the genus Leptospira. It affects both humans and animals, posing a significant public health threat worldwide. In Sri Lanka, leptospirosis causes annual outbreaks, particularly during the monsoon seasons. The disease is often difficult to diagnose and can have a high mortality rate. Bats are potential reservoirs for Leptospira in other countries. This study investigated the presence and diversity of Leptospira in bats inhabiting the Wavulgalge, a natural cave in Sri Lanka. Methodology/Principal FindingsUsing PCR and Sanger sequencing techniques, Leptospira borgpetersenii and Leptospira kirschneri were identified in Miniopterus fuliginosus and Rousettus leschenaultii bats. Out of 148 bat urine samples, 16 tested positive via RT-qPCR, with M. fuliginosus samples harboring L. borgpetersenii and one R. leschenaultii sample harboring L. kirschneri revealed by Sanger sequencing method. Conclusions/SignificanceThese findings enhance the understanding of the zoonotic role of Sri Lankan bats in Leptospira transmission. Author SummaryLeptospirosis is a bacterial disease that affects both humans and animals, particularly in tropical regions. It spreads through contact with water or soil contaminated by the urine of infected animals. In Sri Lanka, leptospirosis poses a significant public health challenge, with frequent outbreaks during the rainy season. However, while much research has focused on domestic animals as potential carriers, the role of bats in the transmission of this disease has not been fully explored. In this study, we investigated whether bats in Sri Lanka can act as carriers of Leptospira bacteria, which could contribute to the spread of leptospirosis to humans. We focused on a population of bats from the Wavulgalge cave and tested them for the presence of Leptospira using molecular methods. Our results provide the first evidence that Leptospira is present in Sri Lankan bats, highlighting their potential role as a reservoir for the bacteria. These findings are important because they suggest that bats, like rodents and livestock, could contribute to the spread of leptospirosis in Sri Lanka. Understanding which animals carry the bacteria helps inform public health strategies, allowing for more targeted surveillance and control measures. By including bats in these efforts, we can better prevent future outbreaks of leptospirosis and protect at-risk communities. This study also contributes to the broader understanding of how wildlife can influence human health, especially in tropical environments where human-animal interactions are common. Our work emphasizes the need for a One Health approach, which considers the connections between human, animal, and environmental health, to tackle neglected diseases like leptospirosis.

microbiology↗
bioRxiv2024

First Report of Nipah virus shed in urine by fruit bats (Pteropus medius), Sri Lanka

Nipah virus is an emerging pathogen with high public health relevance, causing outbreaks in South- and Southeast Asia with high case fatality rates. The natural reservoir host are fruit bats (Pteropus spp). In this study, we confirmed the presence of Nipah virus for the first time in Sri Lanka and are proving the genetic relatedness to Nipah virus strains from southern India, causing outbreaks in 2007, 2018, 2019 and 2023. It is noteworthy that the shedding of the Nipah Virus may have a temporal variation that correlates with the breeding season of Pteropus medius. Furthermore, preventive measures and possible mechanisms influencing viral shedding are discussed.

microbiology↗
bioRxiv2022

CAbiNet: Joint visualization of cells and genes based on a gene-cell graph

In routine single-cell RNA-sequencing (scRNA-seq) analysis workflows, cells are commonly visualized in 2D to show the patterns in the data. However, these visualization approaches do not give any information about the genes that define the cell groups or clusters. It is therefore desirable to display cells and genes simultaneously such that by their relative position to each other information about the genes expression in a cluster can be obtained. Here we propose "Correspondence Analysis based Biclustering on Networks" (CAbiNet) as a novel approach to jointly visualize cells and genes by a non-linear embedding approach, called biMAP. The biMAP allows for easy and interactive exploration of cells and their corresponding marker genes in a single plot. CabiNet additionally offers an intuitive way to perform biclustering jointly on cells and genes, providing a simplified workflow to annotate cell types on the biMAP. CAbiNet is accessible through GitHub as an R package.

bioinformatics↗
bioRxiv2022

Possible adaption of the 2022 Monkeypox virus to the human host through gene duplication and loss

Poxviruses are known to evolve slower than RNA viruses, with rearrangements such as gene gain and loss as the main driver for host adaption. In 2022 the world is being challenged by the largest global outbreak so far of Monkeypox virus, and the virus seems to have established itself in the human community. Here we report five MPXV genomes with extensive gene duplication and loss, including duplications of up to 18,000 bp to the opposed genome end, and deletions at the site of insertion of up to 16,000 bp, as a possible adaption to the human host.

molecular biology↗
bioRxiv2022

One Health Approach for the sampling of different bat species living in a sympatric colony

Bats are important contributors to the global ecosystems; at the same time, they are known to be a natural reservoir host for a number of human pathogenic viruses. These and many other unique features make them an interdisciplinary research object in the context of One Health, comprising zoology, ecology, virology, microbiology, molecular biology, immunology and public health issues. Performing field studies for bat research often aims to cover several of these topics and requires the combination of specific expertise in different fields. We carried out three individual field studies in Wavul Galge cave (Koslanda, Sri Lanka), where several bat species roost sympatrically. The main goals were to study the bat colony for ecological aspects and to sample bats for virological and molecular biological analyses. In the course of the field studies, we optimized the sampling procedure regarding safety aspects, a preferably low impact on the captured bats and an improved output of high-quality samples for further analysis. Different sampling methods and procedures were compared in order to establish a suitable strategy for frequent sampling and monitoring of these bats. In the present case study, we report on this process of optimizing our field work and provide suggestions for bat sampling methods that cause comparably less stress for the captured animals. We also report on constraints and obstacles encountered during the practical implementation and possible measures to overcome these. With these practical experiences, we hope to give support to other interdisciplinary research teams preparing for bat field work. Furthermore, we emphasize the need for the respectful treatment of the animals and minimized disturbance of their natural habitat when carrying out sustainable bat research.

zoology↗
bioRxiv2022

Comparative virome analysis of individual shedding routes of Miniopterus fuliginosus bats inhabiting the Wavul Galge Cave, Sri Lanka

Bats are described as the natural reservoir host for a wide range of viruses. Although an increasing number of bat-associated, potentially human pathogenic viruses were discovered in the past, the full picture of the bat viromes is not explored yet. In this study, the virome composition from Miniopterus fuliginosus bats inhabiting the Wavul Galge cave, Sri Lanka, was analyzed. To assess different possible shedding routes, oral swabs, feces and urine were collected and analyzed individually by using metagenomic NGS. The data obtained was further evaluated by using phylogenetic reconstructions. Two different alphacoronavirus strains were detected in feces and urine samples. Furthermore, a paramyxovirus was detected in urine samples. Sequences related to Picornaviridae, Iflaviridae, unclassified Riboviria and Astroviridae were identified in feces samples, and further sequences related to Astroviridae in urine samples. No further viruses were detected in oral swab samples. The comparative virome analysis in this study revealed a diversity in the virome composition between the collected sample types which also represent different potential shedding routes for the detected viruses. At the same time, several viruses were detected for the first time in bats in Sri Lanka. The detection of two different coronaviruses in the samples indicates the potential general persistence of this virus species in M. fuliginosus bats. Based on phylogenetics, the identified viruses are closer related to bat-associated viruses with comparably low human pathogenic potential. In further studies, the seasonal variation of the virome will be analyzed to identify possible shedding patterns for particular viruses.

molecular biology↗
bioRxiv2021

Molecular identification of bats from Wavulgalge cave, Wellawaya, Sri Lanka

This is the first report on the molecular identification and phylogeny of Rousettus leschenaultii, Rhinolophus rouxii, Hipposideros speoris, Hipposideros lankadiva, Miniopterus fuliginosus bat species in Sri Lanka, inferred from mitochondrially encoded cytochrome b gene sequences. Wellawaya Wavulgalge cave in Sri Lanka is one of the largest sympatric colonies found on the island, occupied by five species of bats. Recent research has indicated that bats show enormous cryptic genetic diversity. Moreover, even in the same species, acoustic properties of echolocation calls and morphological features such as fur colour could vary in different populations. Therefore, we have used molecular techniques for the accurate identification of five bat species recorded in one of the largest cave populations in Sri Lanka. Bats were caught using a hand net and saliva samples were collected non-invasively from each bat using a sterile oral swab. Nucleic acids were extracted from oral swab samples and mitochondrial DNA was amplified using primers targeting the mitochondrially encoded cytochrome b gene. This study identified the bat species recorded in the Wellawaya cave as Rousettus leschenaultii, Rhinolophus rouxii, Hipposideros speoris, Hipposideros lankadiva and Miniopterus fuliginosus. Our findings will contribute to future conservation and systematic studies of bats in Sri Lanka. This study will also provide the basis for a genetic database of Sri Lankan bats.

zoology↗