769 research outputs found

    LIPIcs, Volume 251, ITCS 2023, Complete Volume

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    LIPIcs, Volume 251, ITCS 2023, Complete Volum

    Prevalence and risk assessment of toxoplasmosis in commercial and communal sheep and goats in the North West province and occurrence in the Free State province

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    Toxoplasmosis is one of the most widespread parasitic zoonotic diseases arising from Toxoplasma gondii infection. This disease significant impact on sheep and goat production; however, it sometimes goes unnoticed in the herd, leading to unexpected and inexplicable abortions and death among the new-born’s deaths. This study aimed to determine the prevalence and risk factors of T. gondii infections in sheep and goats from commercial and communal farms in the North West, as well as its occurrence in the Free State province. Additionally, we analysed variations and phylogenetic relationships in the T. gondii B1 and GRA6 gene sequences from isolates deposited in GenBank (https://www.ncbi.nlm.nih.gov/) to evaluate the usefulness of the two genes as phylogenetic markers. Toxoplasma gondii IgG antibodies and DNA were analysed in blood samples from 439 animals (164 sheep and 285 goats), vaginal swabs, milk, sheath scrapes from the North West province, and 11 diagnostic tissue samples from the Free State province. A questionnaire was administered to farmers used to assess potential risk factors associated with animals’ exposure to T. gondii infections. Additionally, 183 gene sequences (107 B1 and 83 GRA6 gene sequences) retrieved from GenBank from different animal species originating from different countries were analysed, and single nucleotide polymorphisms (SNP’s) were present in 17% and 83%, of the B1 and GRA6 gene sequences, respectively. Of the 439 sera tested, 13.9% (95% CI: 0.00-1.00%) were positive for antibodies against T. gondii. It was discovered that sheep and goats had seroprevalences of 19.5% and 10.5%, respectively. T. gondii was not detected by PCR in any of the analysed samples (n=198). Using the Chi-Squared test or odds ratio, the main risk factors associated with T. gondii infections were breed, gender, species, animal origin, history of abortion, disposal of aborted material, disposal of manure, type of breeding, district, municipality, feeding system, feed storage, and presence of cats on farms. The high seroprevalence in this study suggests that T. gondii exposure is widespread within the farms. The absence of genetic material associated with T. gondii by PCR even in seropositive animals suggests the animals were at some point exposed to the pathogen, but they do not shed the parasite in their reproductive tissues. Perhaps, these animals may potentially shed the pathogen in other tissues that we did not analyse. The isolates' gene sequence analysis showed that the GRA6 gene could work as a genetic marker for T. gondii in population studies compared to the B1 gene. To effectively prevent and control exposure to T. gondii infections, the identified risk factors must be considered.Agriculture and  Animal HealthM. Sc. (Agriculture

    The immune modulation on innate immunity, from pathogen recognition to fungal clearance.

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    The human lung is not sterile but a complex environment with various microorganisms. Besides commensals in the lung, hundreds to thousands of individual microbiomes enter the lung every day but without causing the symptom. Host innate immunity plays an important role in maintaining homeostasis of the lung environment and as the first defense line against pathogens. Aspergillus fumigatus (A. fumigatus) is a saprophytic filamentous fungus that can cause human disease in immune compromised patients. However, with functional innate immunity, immune cells can quickly recognize pathogen associated molecular patterns (PAMPs) from A. fumigatus through pattern recognition receptors (PRRs). The activation of PRRs can activate innate immunity and facilitate inflammatory responses through cytokine and chemokine production. As the initiation of inflammation, the recruited innate immune cells can eliminate A. fumigatus through phagocytosis and kill them in the mature phagolysosome with ROS-dependent and independent mechanisms. In this dissertation, we will cover the regulation of antifungal immunity in two specific directions: (1) investigate the immune modulation on innate immunity in the post-viral environment and the cause of viral-fungal superinfection. (2) characterize a potential fungal binding receptor and examine its role in antifungal immunity. In the first project, we demonstrated a novel mechanism within specific cell types that can contribute to defective fungal clearance and lead to high mortality in Influenza A Virus- A. fumigatus superinfection. For the second part, we used our newly generated mutant mice line and biochemistry approach to study the potential role of fungal surface binding protein in host immunity. These results further demonstrate the importance of antifungal immunity and upstream immune modulation in preventing the initiation of invasive aspergillosis

    A novel in vitro model for mature Toxoplasma gondii tissue cysts allows functional characterization of bradyzoite biology

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    Toxoplasma gondii bildet im Nerven- und Muskelgewebe seines Zwischenwirts persistente enzystierte Bradyzoiten, die Immunreaktionen und medizinischen Behandlungen entgehen. Der experimentelle Zugang zu reifen Zysten ist auf ex vivo Modelle beschrĂ€nkt und die Bradyzoiten-Biologie unzureichend erforscht. Das Metabolom oder Wirtszell-Bradyzoiten-Interaktionen und Persistenzmechanismen sind mit aktuellen in vitro und in vivo Modellen schwer zu adressieren. Um dies zu ermöglichen, war es das Ziel dieser Arbeit ein in vitro Modell zur Generierung reifer T. gondii Zysten zu etablieren und zu charakterisieren. Dieses System wurde verwendet, um (1) das Metabolom von reifen enzystierten Bradyzoiten im Vergleich zu Tachyzoiten zu charakterisieren, (2) Wirtszell-Bradyzoiten-Interaktionen zu untersuchen und (3) einen Zellteilungsmarker fĂŒr Bradyzoiten zu etablieren. Bradyzoiten wurden in ausdifferenzierten menschlichen Myotuben generiert und zeigten typische ultrastrukturelle Charakteristika und Antigenexpression. Die Bradyzoiten zeigten auch funktionelle Merkmale wie Resistenz gegen Pepsin, Temperatur und Antiparasitika, die von der Reifungszeit abhĂ€ngig waren. Der metabolische Fingerabdruck von Bradyzoiten wurde mit Tachyzoiten mit Hilfe einer ungezielten HILIC-UHPLC / MS-basierten Metabolomik-Plattform verglichen. WĂ€hrend die Hemmung der Aconitase durch Natriumfluoracetat letal in Tachyzoiten wirkte, tolerierten Bradyzoiten eine lĂ€ngere Hemmung des Enzyms. Stabile isotopenmetabolische Markierung und pharmakologische Modulation des Wirt Lipidstoffwechsels wiesen auf eine entscheidende Rolle der Wirts Carnitinester fĂŒr den FettsĂ€ureimport und die Entgiftung der antimikrobiellen LinolsĂ€ure hin. Um einen Zellteilungsmarker auf Einzelzellebene zu entwickeln, wurden Klick-Chemie nachweisbare Nukleosidanaloga auf ToxizitĂ€t in beiden Stadien und ihr jeweiliges Inkorporationsprofil untersucht. Drei der Analoga wurden ohne toxische Wirkungen in die DNA von beiden Stadien eingebaut.Toxoplasma gondii forms persistent encysted bradyzoites inside neuronal and muscle tissue of its intermediate host, which resist immune responses and medical treatments. Experimental access to mature tissue cysts is limited to ex vivo models and the biology of bradyzoites remains understudied. Aspects like the metabolome or bradyzoite-host-interactions and mechanisms of persistence are difficult to address using current in vitro and in vivo models. To overcome these restrictions, the aim of this thesis was the establishment and characterization of an in vitro model for the generation of matured T. gondii tissue cysts. This system then should be used to (1) characterize the metabolome of matured encysted bradyzoites in comparison with tachyzoites, (2) interrogate bradyzoite-host-interactions and (3) establish a cell division marker for bradyzoites that allows studying bradyzoite heterogeneity. Encysted bradyzoites were grown in terminally differentiated human myotubes and showed typical ultrastructural hallmarks and antigen expression. These bradyzoites contained functional hallmarks like resistance to pepsin, temperature and commonly used antiparasitics that were dependent on maturation time. The metabolic fingerprint of bradyzoites was compared to tachyzoites using an untargeted HILIC-UHPLC / MS based metabolomics platform. While tachyzoites succumbed to inhibition of their aconitase by sodium fluoroacetate, bradyzoites tolerated prolonged inhibition of this enzyme. Further, stable isotope-metabolic labeling and pharmacological modulation of host lipid metabolism indicated a critical role of host carnitine esters for fatty acid import and for the detoxification of antimicrobial linoleic acid. To develop a single cell-resolved cell division marker, we screened click chemistry-detectable nucleoside analogues for toxicity on both stages and their respective incorporation profile. Three compounds labelled both bradyzoite and tachyzoite nuclei without toxic effects

    Evaluation and validation of techniques for the prevention and management of periodontal diseases

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    The periodontal disease burden is high globally as is periodontitis susceptibility. The management of this disease continuum (gingivitis-periodontitis) is vitality important to reduce the negative quality of life impact on individuals as well as the adverse health implications associated with periodontitis.The aim of this thesis is to evaluate emerging advances in technology for the diagnosis of periodontal diseases, their treatment and management, which will augment and offer alternatives to existing strategies. A study to determine if intraoral scanner (IOS) images provide sufficient quality to enable the diagnosis of gingivitis to be reached demonstrated that the same clinical conclusions were reached irrespective of whether data was collected clinically or via IOS. A randomised controlled trial (RCT) to determine whether images taken from IOS can improve patient understanding of oral hygiene techniques and improve plaque levels and gingival inflammation more than standard oral hygiene advice showed that a personalised approach to oral hygiene instruction improved gum outcomes.An RCT to determine if an anti-gingivitis toothpaste (TP) containing enzymes and other proteins (ZendiumÂź) is an effective adjunct to toothbrushing in the prevention of gingivitis, demonstrated that ZendiumÂź improved gingival inflammation and reduced plaque and bleeding on probing, when compared with a standard fluoride TP.A split mouth, crossover RCT of periodontally susceptible individuals to determine if the professional plaque removal experience improved when using an ultrasonic scaler that can deliver warm water irrigant compared to standard room temperature, indicated that the provision of warm water reduced the pain and discomfort experienced by patients and could improve the overall acceptance of treatment.This thesis demonstrates that advances in technology can improve patient education and behaviour change, and that with improved adjuncts to treatment and patient treatment experiences, better oral health outcomes can be achieved. <br/

    Investigating neutral and climate-linked morphological variation in human femora: A geometric morphometrics approach

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    This thesis aimed to differentiate climatic and ‘neutral’ morphological signatures in the human femur, allowing anthropologists to improve their interpretations of behaviour in the past. A dataset of geometric morphometric data and traditional linear measurements for eleven globally distributed hunter-gatherer groups, measures of distance from an estimated African Origin, and a set of climatic variables were used to separate the relative effect of neutral demographic processes and climatic selection on femoral morphology. Within-population shape variance was not significantly predicted by any of the variables tested. Adherence to Bergmann’s rule was identified in the linear measurements on the individual and population level, while within-population variance in femoral length was found to be significantly associated with maximum temperature. These results suggest that climatic selection may have overwritten any neutral signatures. Future research should expand the sample to clarify if the interesting but non-significant patterns identified represent real relationships

    Animal venoms: a novel source of anti-Toxoplasma gondii drug candidates

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    Toxoplasma gondii (T. gondii) is a nucleated intracellular parasitic protozoan with a broad host selectivity. It causes toxoplasmosis in immunocompromised or immunodeficient patients. The currently available treatments for toxoplasmosis have significant side effects as well as certain limitations, and the development of vaccines remains to be explored. Animal venoms are considered to be an important source of novel antimicrobial agents. Some peptides from animal venoms have amphipathic alpha-helix structures. They inhibit the growth of pathogens by targeting membranes to produce lethal pores and cause membrane rupture. Venom molecules generally possess immunomodulatory properties and play key roles in the suppression of pathogenic organisms. Here, we summarized literatures of the last 15 years on the interaction of animal venom peptides with T. gondii and attempt to explore the mechanisms of their interaction with parasites that involve membrane and organelle damage, immune response regulation and ion homeostasis. Finally, we analyzed some limitations of venom peptides for drug therapy and some insights into their development in future studies. It is hoped that more research will be stimulated to turn attention to the medical value of animal venoms in toxoplasmosis

    Optimizing Collective Communication for Scalable Scientific Computing and Deep Learning

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    In the realm of distributed computing, collective operations involve coordinated communication and synchronization among multiple processing units, enabling efficient data exchange and collaboration. Scientific applications, such as simulations, computational fluid dynamics, and scalable deep learning, require complex computations that can be parallelized across multiple nodes in a distributed system. These applications often involve data-dependent communication patterns, where collective operations are critical for achieving high performance in data exchange. Optimizing collective operations for scientific applications and deep learning involves improving the algorithms, communication patterns, and data distribution strategies to minimize communication overhead and maximize computational efficiency. Within the context of this dissertation, the specific focus is on optimizing the alltoall operation in 3D Fast Fourier Transform (FFT) applications and the allreduce operation in parallel deep learning, particularly on High-Performance Computing (HPC) systems. Advanced communication algorithms and methods are explored and implemented to improve communication efficiency, consequently enhancing the overall performance of 3D FFT applications. Furthermore, this dissertation investigates the identification of performance bottlenecks during collective communication over Horovod on distributed systems. These bottlenecks are addressed by proposing an optimized parallel communication pattern specifically tailored to alleviate the aforementioned limitations during the training phase in distributed deep learning. The objective is to achieve faster convergence and improve the overall training efficiency. Moreover, this dissertation proposes fault tolerance and elastic scaling features for distributed deep learning by leveraging the User-Level Failure Mitigation (ULFM) from Message Passing Interface (MPI). By incorporating ULFM MPI, the dissertation aims to enhance the elastic capabilities of distributed deep learning systems. This approach enables graceful and lightweight handling of failures while facilitating seamless scaling in dynamic computing environments

    Comparative analysis of gene expression associations between mammalian hosts and Plasmodium

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    ArtenĂŒbergreifende Interaktionen helfen uns, Krankheitsmechanismen zu verstehen und Targets fĂŒr Therapien zu finden. Die Koexpression von Genen, gemessen an der mRNA-HĂ€ufigkeit, kann Interaktionen zwischen Wirt und Pathogen aufzeigen. Die RNA-Sequenzierung von Wirt und Pathogen wird als "duale RNA-Sequenzierung" bezeichnet. Malaria ist eine der am besten untersuchten parasitĂ€ren Krankheiten, so dass eine FĂŒlle von RNA-seq-DatensĂ€tzen öffentlich zugĂ€nglich ist. Die Autoren fĂŒhren entweder duale RNA-seq durch, um den Wirt und den Parasiten gleichzeitig zu untersuchen, oder sie erhalten kontaminierende Sequenzierungs-Reads aus dem Nicht-Zielorganismus. Ich habe eine Meta-Analyse durchgefĂŒhrt, bei diese beiden Arten von RNA-seq-Studien verwendet wurden, um ĂŒber korrelierte Genexpression auf Wirt-Parasit-Interaktionen zu schließen. Ich habe Studien mit Homo sapiens, Mus musculus und Macaca mulatta als Wirte und ihre Plasmodium-Parasiten einbezogen. Ich benutzte orthologe Einzelkopien von Genen, um ein Repertoire von Interaktionen bei Malaria und in diesen Modellsystemen zu erstellen. Ich verknĂŒpfte die Daten von 63 Plasmodium-Phasen-spezifischen Studien und reduzierte die Zahl der Interaktionen von potenziell 56 Millionen auf eine kleinere, relevantere Menge. Die ZentralitĂ€t in den Netzwerken der Blutphasen konnte die EssentialitĂ€t der Plasmodium-Gene erklĂ€ren. Das aus den verketteten Daten sagte die GenessenzialitĂ€t besser vor als die einzelnen Studien - ein Vorteil der Meta-Analyse. Neutrophile und Monozyten Immunmarkergene waren ĂŒberreprĂ€sentiert, was auf eine FĂŒlle von phagozytĂ€ren und respiratorischen Reaktionen hindeutet. Die Analyse der Leberphase ergab Wirts- und Parasitenprozesse in frĂŒhen und spĂ€ten Entwicklungsphasen. Ich fand bekannte Wirt-Parasit-Interaktionen, die fĂŒr beide Phasen gleich sind, sowie bisher unbekannte Interaktionen. Dieses Prinzip lĂ€sst sich auch auf andere Krankheiten anwenden, um Mechanismen und therapeutische Ziele zu verstehen.Cross-species interactions help us understand disease mechanisms and find targets for therapy. Gene co-expression, measured by mRNA abundance, can identify host-pathogen interactions. The RNA-sequencing of host and pathogen is termed “dual RNA-sequencing”. Malaria is one of the most studied eukayotic parasitic diseases, making an abundance of RNA-seq data sets publicly available. Authors either perform dual RNA-seq to study the host and parasite simultaneously or acquire contaminant sequencing reads from the non-target organism. I performed a meta-analysis using these two kinds of RNA-seq studies to infer host-parasite interactions using correlated gene expression. I included studies of Homo sapiens, Mus musculus and Macaca mulatta as hosts and their corresponding Plasmodium parasites. I used single-copy orthologous genes to generate a repertoire of interactions in human malaria and in these model systems. I found 63 malaria RNA-seq studies. I concatenated sequencing runs from Plasmodium stage-specific studies and reduced the number of interactions from a potential 56 million to a smaller, more relevant set. Centrality in the blood stage networks was able to explain Plasmodium gene essentiality. The network from the concatenated data predicted gene essentiality better than the individual studies, indicating a benefit of the meta-analysis. Immune marker genes for neutrophils and monocytes were over-represented, suggesting an abundance of phagocytic and respiratory burst-related responses. The liver stage analysis revealed linked host and parasite processes at early stages until late developmental stages. I found linked host and parasite processes that are common to the two stages, e.g. parasite cell gliding and invasion and host response to hypoxia and immune response. I showed that existing data can be explored for new information. This principle can be applied to other diseases to understand mechanisms and therapeutic targets
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