Biology subjects

Schwarz, F.

Publications and source records attributed to Schwarz, F..

13 recordsLinked to original sources

bioRxiv2025

NKCC1 a Regulator of Glioblastoma Progression

Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults, with poor prognosis despite multimodal therapy. Chloride cotransporters NKCC1 and KCC2 are key regulators of intracellular chloride levels and thereby determine whether GABA acts inhibitory or excitatory. In GBM, disrupted chloride homeostasis promotes proliferation, migration, and stem-like properties, but its clinical relevance is not fully understood. We analysed NKCC1 and KCC2 expression in glioblastoma samples, considering clinical parameters such as age, gender, and MGMT promoter methylation. Statistical analyses included ROC-based cutoff determination, Kaplan-Meier survival analysis and subgroup. Immunohistochemistry was performed to identify cell types expressing NKCC1. NKCC1 expression was significantly higher in older patients and emerged as a prognostic marker for recurrence-free survival, with lower levels correlating with delayed recurrence, although overall survival was unaffected. NKCC1 was expressed in stem-like, astrocytic, and progenitor cells, but not in mature neurons. These findings identify NKCC1 as a regulator of GBM progression and recurrence, linking chloride transporter imbalance to GABAergic signalling. Targeting NKCC1 and restoring chloride homeostasis may provide promising new treatment strategies. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=89 SRC="FIGDIR/small/677289v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@a964f1org.highwire.dtl.DTLVardef@1224400org.highwire.dtl.DTLVardef@9e5c94org.highwire.dtl.DTLVardef@d0324f_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

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↗

bioRxiv2023

Teaching transposon classification as a means to crowd source the curation of repeat annotation - a tardigrade perspective

The advancement of sequencing technologies results in the rapid release of hundreds of new genome assemblies a year providing unprecedented resources for the study of genome evolution. Within this context, the significance of in-depth analyses of repetitive elements, transposable elements (TEs) in particular, is increasingly recognized in understanding genome evolution. Despite the plethora of available bioinformatic tools for identifying and annotating TEs, the phylogenetic distance of the target species from a curated and classified database of repetitive element sequences constrains any automated annotation effort. Manual curation of raw repeat libraries is deemed essential due to the frequent incompleteness of automatically generated consensus sequences. However, manual curation and classification are time-consuming processes that offer limited short-term academic rewards and are typically confined to a few research groups where methods are taught through hands-on experience. Crowd sourcing efforts could offer a significant opportunity to bridge the gap between learning the methods of curation effectively and empowering the scientific community with high-quality, reusable repeat libraries. Here, we present an example of such crowd sourcing effort developed through both in-person and online courses built around a collaborative peer-reviewed teaching process that can be used as teaching reference guide for similar projects. The collaborative manual curation of TEs from two tardigrade species, for which there were no TE libraries available, resulted in the successful characterization of hundreds of new and diverse TEs: A hidden treasure awaits discovery within non-model organisms.

evolutionary biology↗

bioRxiv2023

Variable PD-1 glycosylation modulates the activity of immune checkpoint inhibitors

Monoclonal antibodies targeting the immune checkpoint PD-1 have provided significant clinical benefit across a number of solid tumors, with differences in efficacy and toxicity profiles possibly related to their intrinsic molecular properties. Here, we report that camrelizumab and cemiplimab engage PD-1 through interactions with its fucosylated glycan. Using a combination of protein and cell glycoengineering, we demonstrate that the two antibodies bind preferentially to PD-1 with a core fucose at the asparagine N58 residue. We then provide evidence that the concentration of fucosylated PD-1 in the blood of non-small cell lung cancer patients varies across different stages of disease. This study illustrates how glycoprofiling of surface receptors and related circulating forms can inform the development of differentiated antibodies that discriminate glycosylation variants and achieve enhanced selectivity and paves the way towards the implementation of personalized therapeutic approaches.

immunology↗

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↗

bioRxiv2021

The distinct role of ALDH1A1 and ALDH1A3 in the regulation of prostate cancer metastases

Cancer stem cells (CSC) are characterized by high self-renewal capacity, tumor-initiating potential, and therapy resistance. Aldehyde dehydrogenase (ALDH)+ cell population serves as an indicator of prostate CSCs with increased therapy resistance, enhanced DNA double-strand break repair, and activated epithelial-mesenchymal transition (EMT) and migration. Numerous ALDH genes contribute to ALDH enzymatic activity; however, only some of them showed clinical relevance. We found that ALDH1A1 and ALDH1A3 genes functionally regulate CSC properties and radiation sensitivity of PCa. We revealed a negative correlation between ALDH1A1 and ALDH1A3 expression in publicly available prostate cancer (PCa) datasets and demonstrated that ALDH1A1 and ALDH1A3 have opposing predictive value for biochemical recurrence-free survival. Our data suggest an association of ALDH1A1 with the metastatic burden, elucidating the role of ALDH genes in the metastatic spread and homing to the bone, which can be, at least partially, attributed to regulating the transforming growth factor beta 1 (TGFB1) and matrix metalloproteinases (MMPs). ALDH genes play a diverse role in PCa development under AR and {beta}-catenin-dependent regulation, with ALDH1A1 becoming dominant in later stages of tumor development when PCa cells gain androgen independence. Taken together, our results indicate that ALDH1A1 and ALDH1A3 modulate PCa radiosensitivity, regulate CSCs phenotype, and spread of PCa cells to the bone, therefore having clinical implication for identifying patients at high risk for progression to metastatic disease.

cancer biology↗

bioRxiv2020

Tirant stealthily invaded natural Drosophila melanogaster populations during the last century

It was long thought that solely three different transposable elements - the I-element, the P-element and hobo - invaded natural D. melanogaster populations within the last century. By sequencing the living fossils of Drosophila research, i.e. D. melanogaster strains sampled from natural populations at different time points, we show that a fourth TE, Tirant, invaded D. melanogaster populations during the past century. Tirant likely spread in D. melanogaster populations around 1938, followed by the I-element, hobo, and, lastly, the P-element. In addition to the recent insertions of the canonical Tirant, D. melanogaster strains harbour degraded Tirant sequences in the heterochromatin which are likely due to an ancient invasion, possibly predating the split of D. melanogaster and D. simulans. In contrast to the I-element, P-element and hobo, we did not find that Tirant induces any hybrid dysgenesis symptoms. This absence of apparent phenotypic effects may explain the late discovery of the Tirant invasion. Recent Tirant insertions were found in all investigated natural populations. Populations from Tasmania carry distinct Tirant sequences, likely due to a founder effect. By investigating the TE composition of natural populations and strains sampled at different time points, insertion site polymorphisms, piRNAs and phenotypic effects, we provide a comprehensive study of a natural TE invasion.

evolutionary biology↗

bioRxiv2020

Generating high quality assemblies for genomic analysis of transposable elements

The advent of long-read sequencing holds great promise for research on transposable elements (TEs). Long reads may finally allow us to obtain reliable assemblies of repetitive regions, and thus shed light on many open questions in TE biology, such as the evolution of piRNA clusters, i.e., the master loci controlling TE activity. Currently, many different assembly strategies exist and it is not clear how to obtain the most suitable assemblies for TE research. In fact, it is not even clear how to best identify suitable assemblies as classic quality metrics such as BUSCO and NG50 are ignorant of TEs. To address these problems, we introduce four novel quality metrics that assess i) how well piRNA clusters are assembled (CUSCO) and ii) to which extent an assembly captures the TE landscape of an organism (TE abundance, SNPs and internal deletions). Using these novel metrics, we evaluate the effect of assemblers, polishing, read length, coverage, residual polymorphisms, and finally, identify suitable assembly strategies. Using an optimized approach, we provide high-quality assemblies for the two Drosophila melanogaster strains Canton-S and Pi2. Around 80% of the piRNA clusters were contiguously assembled in these two strains. Such high-quality assemblies will provide novel insights into the biology of TEs. It is, for example, an open question of whether piRNA clusters contain abundant presence/absence polymorphism of TE insertions, as expected when piRNA clusters are responsible for stopping TE invasions. A comparison of the sequences of our assembled piRNA clusters reveals that such polymorphisms are indeed abundantly found in clusters.

genomics↗

bioRxiv2018

Evidence for strong fixation bias at 4-fold degenerate sites across genes in the great tit genome

It is well established that GC content varies across the genome in many species and that GC biased gene conversion, one form of meiotic recombination, is likely to contribute to this heterogeneity. Bird genomes provide an extraordinary system to study the impact of GC biased gene conversion owed to their specific genomic features. They are characterised by a high karyotype conservation with substantial heterogeneity in chromosome sizes, with up to a dozen large macrochromosomes and many smaller microchromosomes common across all bird species. This heterogeneity in chromosome morphology is also reflected by other genomic features, such as smaller chromosomes being gene denser, more compact and more GC rich relative to their macrochromosomal counterparts - illustrating that the intensity of GC biased gene conversion varies across the genome. Here we study whether it is possible to infer heterogeneity in GC biased gene conversion rates across the genome using a recently published method that accounts for GC biased gene conversion when estimating branch lengths in a phylogenetic context. To infer the strength of GC biased gene conversion we contrast branch length estimates across the genome both taking and not taking non-stationary GC composition into account. Using simulations we show that this approach works well when GC fixation bias is strong and note that the number of substitutions along a branch is consistently overestimated when GC biased gene conversion is not accounted for. We use this predictable feature to infer the strength of GC dynamics across the great tit genome by applying our new test statistic to data at 4-fold degenerate sites from three bird species - great tit, zebra finch and chicken - three species that are among the best annotated bird genomes to date. We show that using a simple one-dimensional binning we fail to capture a signal of fixation bias as observed in our simulations. However, using a multidimensional binning strategy, we find evidence for heterogeneity in the strength of fixation bias, including AT fixation bias. This highlights the difficulties when combining sequence data across different regions in the genome.

evolutionary biology↗

bioRxiv2017

How Changes in Common Practice Can Improve the Quality of Biomedical Science

Assessing the impact of recommendations rectifying the reproducibility crisis (publishing both positive and \"negative\" results and increasing statistical power) on competing objectives, such as discovering causal relationships, avoiding publishing false positive results, and reducing resource consumption, we developed a new probabilistic model. Our model quantifies the impact of each single suggestion for an individual study and their relation and consequences for the entire research process. We can prove that higher-powered experiments can save resources in the overall research process without generating excess false positives. The better the quality of the pre-study information and its exploitation, the more likely this beneficial effect is to occur. Additionally, we quantify the adverse effects of neglecting good practices in the design and conduct of hypotheses-based research, and the responsibility to publish \"negative\" findings. Our contribution is a plea for adherence to or reinforcement of the good scientific practice and publication of \"negative\" findings.

scientific communication and education↗