Biology subjects

Hartmann, S.

Publications and source records attributed to Hartmann, S..

31 records · Page 2Linked to original sources

bioRxiv2021

Public attitudes towards free-roaming dogs and dog ownership practices in Bulgaria, Italy, and Ukraine

Overabundant, free-roaming dog populations are associated with risks to public health, livestock losses, wildlife conservation, and dog health and welfare. Dog population management is conducted to mitigate these issues. Assessing dog population management strategies is important to determine their effectiveness, efficiency, and long-term impact. It is essential to also determine how the behaviour and outlook of local communities may influence the efficacy of dog population management. This study aimed to determine public attitudes towards free-roaming dogs and their management and describe dog ownership practices in three European countries using an online questionnaire survey. This study found that most surveyed respondents wanted to see a reduction in free-roaming dog numbers, and felt that this should be achieved through sheltering, catch-neuter-release, and by controlling the breeding of owned dogs. This questionnaire also identified significant associations between public attitudes and dog ownership practices with gender, religious beliefs, age, education level, reason for dog ownership, previous experience with free-roaming dogs, and country of residence. Respondents who identified as: (i) being male, (ii) holding religious beliefs, (iii) owning dogs for practical reasons, (iv) being young, and (v) having no schooling or primary education had a lower probability of neutering and a higher probability of allowing dogs to roam. Respondents who identified as: (i) being female, (ii) feeling threatened by free-roaming dogs, (iii) being older, and (iv) having more education had a higher probability of answering that an increase in free-roaming dog numbers should be prevented. These findings can help to inform future dog population management interventions in these countries and highlight the importance of considering local public attitudes and dog ownership practices in the development of effective dog population management approaches. Including these social factors will ensure that both the community and organisations involved in dog population management work cohesively towards a shared goal.

ecology↗

bioRxiv2021

Autoantibodies against Progranulin and IL-1 receptor antagonist in critically ill COVID-19

STRUCTURED ABSTRACTHyperinflammation is frequently observed in patients with severe COVID-19. Inadequate and defective IFN type I responses against SARS-CoV-2, associated with autoantibodies in a proportion of patients, lead to severe courses of disease. In addition, hyperactive responses of the humoral immune system have been described. In the current study we investigated a possible role of neutralizing autoantibodies against antiinflammatory mediators. Plasma from adult patients with severe and critical COVID-19 was screened by ELISA for antibodies against PGRN, IL-1-Ra, IL-10, IL-18BP, IL-22BP, IL-36-Ra, CD40, IFN-2, IFN-{gamma}, IFN-{omega} and serpinB1. Autoantibodies were characterized and the antigens were analyzed for immunogenic alterations. In a discovery cohort with severe to critical COVID-19 high titers of PGRN-autoantibodies were detected in 11 of 30 (36.7%), and of IL-1-Ra-autoantibodies in 14 of 30 (46.7%) patients. In a validation cohort of 64 patients with critical COVID-19 high-titer PGRN-Abs were detected in 25 (39%) and IL-1-Ra-Abs in 32 of 64 patients (50%). PGRN-Abs and IL-1-Ra-Abs belonged to IgM and several IgG subclasses. In separate cohorts with non-critical COVID-19, PGRN-Abs and IL-1-Ra-Abs were detected in low frequency (i.e. in < 5% of patients) and at low titers. Neither PGRN-nor IL-1-Ra-Abs were found in 40 healthy controls vaccinated against SARS-CoV-2 or 188 unvaccinated healthy controls. PGRN-Abs were not cross-reactive against SARS-CoV-2 structural proteins nor against IL-1-Ra. Plasma levels of both free PGRN and free IL-1-Ra were significantly decreased in autoantibody-positive patients compared to Ab-negative and non-COVID-19 controls. In vitro PGRN-Abs from patients functionally reduced PGRN-dependent inhibition of TNF- signaling, and IL-1-Ra-Abs from patients reduced IL-1-Ra- or anakinra-dependent inhibition of IL-1{beta} signaling. The pSer81 hyperphosphorylated PGRN isoform was exclusively detected in patients with high-titer PGRN-Abs; likewise, a hyperphosphorylated IL-1-Ra isoform was only found in patients with high-titer IL-1-Ra-Abs. Thr111 was identified as the hyperphophorylated amino acid of IL-1-Ra. In longitudinally collected samples hyperphosphorylated isoforms of both PGRN and IL-1-Ra emerged transiently, and preceded the appearance of autoantibodies. In hospitalized patients, the presence of IL-1-Ra-Abs or IL-1-Ra-Abs in combination with PGRN-Abs was associated with a higher morbidity and mortality. To conclude, neutralizing autoantibodies to IL-1-Ra and PGRN occur in a significant portion of patients with critical COVID-19, with a concomitant decrease in circulating free PGRN and IL-1-Ra, indicative of a misdirected, proinflammatory autoimmune response. The break of self-tolerance is likely caused by atypical hyperphosphorylated isoforms of both antigens, whose appearances precede autoantibody induction. Our data suggest that these immunogenic secondary modifications are induced by the SARS-CoV-2-infection itself or the inflammatory environment evoked by the infection and predispose for a critical course of COVID-19.

immunology↗

bioRxiv2020

An unconventional conductance is required for pacemaking of nigral dopamine neurons

Although several ionic mechanisms are known to control rate and regularity of the pacemaker in dopamine (DA) neurons from the substantia nigra pars compacta (SNc), a conductance essential for pacing has yet to be defined. Here we provide pharmacological evidence that pacemaking of SNc DA neurons is enabled by an unconventional conductance. We found that 1-(2,4-xylyl)guanidine (XG), an established blocker of gating pore currents in mutant voltage gated sodium channels, selectively stops pacemaking of DA SNc neurons and is without effect on the main pore of their voltage-gated channels. We isolated a voltage-dependent, non-inactivating XG-sensitive current of 20-25 pA which operates in the relevant subthreshold range and is carried by both Na+ and Cl- ions. While the molecular identity of this conductance remains to be determined, we show that this XG-sensitive current is crucial to sustain pacemaking in these neurons.

neuroscience↗

bioRxiv2020

Speciation in the face of gene flow within the toothed whale superfamily Delphinoidea

AO_SCPLOWBSTRACTC_SCPLOWThe importance of post-divergence gene flow in speciation has been documented across a range of taxa in recent years, and may have been especially widespread in highly mobile, wide-ranging marine species, such as cetaceans. Here, we studied individual genomes from nine species across the three families of the toothed whale superfamily Delphinoidea (Delphinidae, Phocoenidae, Monodontidae). To investigate the role of post-divergence gene flow in the speciation process, we used a multifaceted approach, including: (i) phylogenomics, (ii) the distribution of shared derived alleles, and (iii) demographic inference. We found the divergence of lineages within Delphinoidea did not follow a process of pure bifurcation, but was much more complex. Sliding-window phylogenomics reveal a high prevalence of discordant topologies within the superfamily, with further analyses indicating these discordances arose due to both incomplete lineage sorting and gene flow. D-statistics, D-foil, and f-branch analyses supported gene flow between members of Delphinoidea, with the vast majority of gene flow occurring as ancient interfamilial events. Demographic analyses provided evidence that introgressive gene flow has likely ceased between all species pairs tested, despite reports of contemporary interspecific hybrids. Our study provides the first steps towards resolving the large complexity of speciation within Delphinoidea; we reveal the prevalence of ancient interfamilial gene flow events prior to the diversification of each family, and suggests that contemporary hybridisation events may be disadvantageous, as hybrid individuals do not appear to contribute to the parental species gene pools.

evolutionary biology↗

bioRxiv2020

Radula diversification promotes ecomorph divergence in an adaptive radiation of freshwater snails

Adaptive diversification of complex traits plays a pivotal role for the evolution of organismal diversity. However, the underlying molecular mechanisms remain largely elusive. In the freshwater snail genus Tylomelania, adaptive radiations were likely promoted by trophic specialization via diversification of their key foraging organ, the radula. To investigate the molecular basis of radula diversification and its contribution to lineage divergence, we use pooled tissue-specific transcriptomes of two sympatric Tylomelania sarasinorum ecomorphs. We show that divergence in both gene expression and coding sequences is stronger between radula transcriptomes compared to mantle and foot transcriptomes. These findings support the hypothesis that diversifying selection on the radula is driving speciation in Tylomelania radiations. We also identify several candidate genes for radula divergence. Putative homologs of some candidates (hh, arx, gbb) also contributed to trophic specialization in cichlids and Darwins finches, indicating that some molecular pathways may be especially prone to adaptive diversification.

evolutionary biology↗

bioRxiv2019

Functional insights from the GC-poor genomes of two aphid parasitoids, Aphidius ervi and Lysiphlebus fabarum

BackgroundParasitoid wasps have fascinating life cycles and play an important role in trophic networks, yet little is known about their genome content and function. Parasitoids that infect aphids are an important group with the potential for biocontrol, and infecting aphids requires overcoming both aphid defenses and their defensive endosymbionts. ResultsWe present the de novo genome assemblies, detailed annotation, and comparative analysis of two closely related parasitoid wasps that target pest aphids: Aphidius ervi and Lysiphlebus fabarum (Hymenoptera: Braconidae: Aphidiinae). The genomes are small (139 and 141 Mbp), highly syntenic, and the most AT-rich reported thus far for any arthropod (GC content: 25.8% and 23.8%). This nucleotide bias is accompanied by skewed codon usage, and is stronger in genes with adult-biased expression. AT-richness may be the consequence of reduced genome size, a near absence of DNA methylation, and age-specific energy demands. We identify expansions of F-box/Leucine-rich-repeat proteins, suggesting that diversification in this gene family may be associated with their broad host range or with countering defenses from aphids endosymbionts. The absence of some immune genes (Toll and Imd pathways) resembles similar losses in their aphid hosts, highlighting the potential impact of symbiosis on both aphids and their parasitoids. ConclusionsThese findings are of fundamental interest for insect evolution and beyond. This will provide a strong foundation for further functional studies including coevolution with respect to their hosts, the basis of successful infection, and biocontrol. Both genomes are available at https://bipaa.genouest.org.

genomics↗

bioRxiv2019

CD4+ Th immunogenicity of the Ascaris spp. secreted products

Ascaris spp. is a major health problem of humans and animals alike, and understanding the immunogenicity of its antigens is required for developing urgently needed vaccines. The parasite-secreted products represent the most relevant, yet highly complex (>250 proteins) antigens of Ascaris spp. as defining the pathogen-host interplay. We applied an in vitro antigen processing system coupled to quantitative proteomics to identify potential CD4+ Th cell epitopes in Ascaris suum-secreted products. This approach restricts the theoretical list of epitopes, based on affinity prediction, by a factor of [~]1200. More importantly, selection of 2 candidate peptides based on experimental evidence demonstrated the presence of epitope-reactive T cells in Ascaris-specific T cell lines generated from healthy human individuals. Thus, this stringent work pipeline identifies a human haplotype-specific T cell epitope of a major human pathogen. The methodology described represents an easily adaptable platform for characterization of highly complex pathogenic antigens and their MHCII-restriction.

immunology↗

bioRxiv2019

A helminth chitinase structurally similar to mammalian chitinase displays immunomodulatory properties

Previously, we reported significant immunomodulatory effects of the entire excretory-secretory (ES) proteins of the first larval stage (L1) of the gastrointestinal nematode Trichuris suis in a rodent model of allergic hyperreactivity. In the present study, we aimed to identify the proteins accounting for the modulatory effects of the T. suis L1 ES proteins and thus studied selected components for their immunomodulatory efficacy in an OVA-induced allergic airway disease model. In particular, an enzymatically active T. suis chitinase mediated amelioration of airway hyperreactivity, primarily associated with suppression of eosinophil recruitment into the lung. The three-dimensional structure of the T. suis chitinase as determined by high-resolution X-ray crystallography revealed significant similarities to mouse acidic mammalian chitinase (AMCase). In addition, the unique ability of T. suis chitinase to form dimers, as well as acidic surface patches within the dimerization region may contribute to the formation of cross-reactive antibodies to the mouse homologs. This hypothesis is supported by the observation that T. suis chitinase treatment induced cross-reactive antibodies to mouse AMCase and chitinase-like protein BRP-39 in the AHR model. In conclusion, a biologically active T. suis chitinase exhibits immunomodulatory properties despite its structural similarity to the mammalian counterpart.\n\nAuthor summaryExperimental immunotherapy via reintroduction of intestinal worms to treat and prevent autoimmune, chronic inflammatory or allergic diseases is being discussed but the underlying mechanisms are still not fully understood. Here, we investigated the immunomodulatory potential of specific proteins of the whipworm Trichuris suis that are secreted very early during larval development. Using a murine model of allergic lung disease, we show that in particular one T. suis protein, functionally characterized as an active chitinase, is reducing the lung inflammation. The T. suis chitinases three-dimensional protein structure revealed remarkable similarities to the hosts chitinase, an enzyme known to play a pivotal role in lung allergy. We also show that treatment with the helminth chitinase induced cross-reactive antibody responses against murine chitinase and chitinase-like proteins, both being inflammatory marker and regulators of type 2 immunity. Thus, our study provides a novel mechanism of immunomodulation by helminth components and may contribute to a better understanding of clinical responses of patients receiving helminthic therapy.

immunology↗

bioRxiv2018

Consensify: a method for generating pseudohaploid genome sequences from palaeogenomic datasets with reduced error rates

A standard practise in palaeogenome analysis is the conversion of mapped short read data into pseudohaploid sequences, typically by selecting a single high quality nucleotide at random from the stack of mapped reads. This controls for biases due to differential sequencing coverage but it does not control for differential rates and types of sequencing error, which are frequently large and variable in datasets obtained from ancient samples. These errors have the potential to distort phylogenetic and population clustering analyses, and to mislead tests of admixture using D statistics. We introduce Consensify, a method for generating pseudohaploid sequences which controls for biases resulting from differential sequencing coverage while greatly reducing error rates. The error correction is derived directly from the data itself, without the requirement for additional genomic resources or simplifying assumptions such as contemporaneous sampling. For phylogenetic analysis, we find that Consensify is less affected by branch length artefacts than methods based on standard pseudohaploidisation, and it performs similarly for population clustering analysis based on genetic distances. For D statistics, Consensify is more resistant to false positives and appears to be less affected by biases resulting from different laboratory protocols than other available methods. Although Consensify is developed with palaeogenomic data in mind, it is applicable for any low to medium coverage short read datasets. We predict that Consenify will be a useful tool for future studies of palaeogenomes.

genomics↗

bioRxiv2018

A novel non-invasive method to detect gut barrier related changes during a gastrointestinal nematode infection.

Currently, methods for monitoring changes of gut barrier integrity and the associated immune response via non-invasive means are limited. Therefore, we aimed to develop a novel non-invasive technique to investigate immunological host responses representing gut barrier changes in response to infection. We identified the mucous layer on feces from mice to be mainly composed of exfoliated intestinal epithelial cells. Expression of RELM-{beta}, a gene prominently expressed in intestinal nematode infections, was used as an indicator of intestinal cellular barrier changes to infection. RELM-{beta} was detected as early as 6 days post-infection (dpi) in exfoliated epithelial cells. Interestingly, RELM-{beta} expression also mirrored the quality of the immune response, with higher amounts being detectable in a secondary infection and in high dose nematode infection in laboratory mice. This technique was also applicable to captured worm-infected wild house mice. We have therefore developed a novel non-invasive method reflecting gut barrier changes associated with alterations in cellular responses to a gastrointestinal nematode infection.

immunology↗

bioRxiv2018

High quality whole genome sequence of an abundant Holarctic odontocete, the harbour porpoise (Phocoena phocoena)

The harbour porpoise (Phocoena phocoena) is a highly mobile cetacean found in waters across the Northern hemisphere. It occurs in coastal water and inhabits water basins that vary broadly in salinity, temperature, and food availability. These diverse habitats could drive differentiation among populations. Here we report the first harbour porpoise genome, assembled de novo from a Swedish Kattegat individual. The genome is one of the most complete cetacean genomes currently available, with a total size of 2.7 Gb and 50% of the total length found in just 34 scaffolds. Using the largest 122 scaffolds, we were able to validate a high level of homology to the chromosome-level genome assembly of the closest related species for which such resource was available, the domestic cattle (Bos taurus). The draft annotation comprises 22,154 predicted gene models, which we further annotated through matches to the NCBI nucleotide database, GO categorization, and motif prediction. To infer the adaptive abilities of this species, as well as their population history, we performed a Bayesian skyline analysis, and produced results that are concordant with the demographic history of this species, including expansion and fragmentation events. Overall, this genome assembly, together with the draft annotation, represents a crucial addition to the limited genetic markers currently available for the study of porpoises and Phocoenidae conservation, phylogeny, and evolution.

genomics↗

bioRxiv2017

Bioinformatics analysis quantifies neighborhood preferences of cancer cells in Hodgkin lymphoma.

MotivationHodgkin lymphoma is a tumor of the lymphatic system and represents one of the most frequent lymphoma in the Western world. It is characterized by Hodgkin cells and Reed-Sternberg cells, which exhibit a broad morphological spectrum. The cells are visualized by immunohistochemical staining of tissue sections. In pathology, tissue images are mainly manually evaluated, relying on the expertise and experience of pathologists. Computational quantification methods become more and more essential to evaluate tissue images. In particular, the distribution of cancer cells is of great interest.\n\nResultsHere, we systematically quantified and investigated cancer cell properties and their spatial neighborhood relations by applying statistical analyses to whole slide images of Hodgkin lymphoma and lymphadenitis, which describes a non-cancerous inflammation of the lymph node. We differentiated cells by their morphology and studied the spatial neighborhood relation of more than 400,000 immunohistochemically stained cells. We found that, according to their morphological features, the cells exhibited significant preferences for and aversions to cells of specific profiles as nearest neighbor. We quantified differences between Hodgkin lymphoma and lymphadenitis concerning the neighborhood relations of cells and the sizes of cells. The approach can easily be applied to other cancer types.\n\nContactina.koch@bioinformatik.uni-frankfurt.de

bioinformatics↗

bioRxiv2017

Population and conservation genomics of the world's rarest hyena species, the brown hyena (Parahyena brunnea)

With an estimated population size of less than 10,000 individuals worldwide, the brown hyena (Parahyaena brunnea) has been listed as near threatened by the IUCN. Despite this rank, studies involving DNA analyses of the brown hyena are limited. Little consideration has been focussed towards population structure within the brown hyena, which could provide valuable insights about its evolutionary history and aid in conservation efforts of the species. Here we report both mitochondrial and nuclear genomes of wild-caught brown hyena individuals from across southern Africa. Mitochondrial DNA shows little to no phylogeographic structure, whereas low-coverage nuclear genomes reveal several potential sub-populations. Moreover, we find that brown hyenas harbour the lowest genetic diversity for a species on both the mitochondrial and nuclear level when compared to a number of mammalian species for which such information is currently available. Our data also reveal that at least on the nuclear DNA level, this low diversity could be the result of a continuous and ongoing decline in effective population size that started about one million years ago and dramatically accelerated towards the end of the Pleistocene. Moreover, our findings also show that the correlation between genetic diversity and the perceived risk of extinction is not particularly strong, since many species with higher genetic diversity than the brown hyena are considered to be at greater risk of extinction. Taken together, our results have important implications for the conservation status and conservation approaches of the brown hyena.

evolutionary biology↗