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Audio versions of bioRxiv paper abstracts

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Audio versions of bioRxiv paper abstracts

    Identifying potential hosts of short-branch Microsporidia

    Identifying potential hosts of short-branch Microsporidia

    Link to bioRxiv paper:
    http://biorxiv.org/cgi/content/short/2020.08.13.249938v1?rss=1

    Authors: Doliwa, A., Dunthorn, M. E., Rassoshanska, E., Mahe, F., Bass, D., Ritter, C. D.

    Abstract:
    Microsporidia are obligate parasites that are closely related to Fungi. While the widely-known long-branch Microsporidia infect mostly animals, the hosts of short-branch Microsporidia are only partially characterized or not known at all. Here, we used network analyses from Neotropical rainforest soil metabarcoding data, to infer co-occurrences between environmental lineages of short-branch microsporidians and their potential hosts. We found significant co-occurrences with several taxa, especially with Apicomplexa, Cercozoa, Fungi, as well as some Metazoa. Our results are the first step to identify potential hosts of the environmental lineages of short-branch microsporidians, which can be targeted in future molecular and microscopic studies.

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    Machine learning reveals time-varying microbial predictors with complex effects on glucose regulation

    Machine learning reveals time-varying microbial predictors with complex effects on glucose regulation

    Link to bioRxiv paper:
    http://biorxiv.org/cgi/content/short/2020.08.13.250423v1?rss=1

    Authors: Aasmets, O., Lüll, K., Lang, J. M., Pan, C., Kuusisto, J., Fischer, K., Laakso, M., Lusis, A. J., Org, E.

    Abstract:
    The incidence of type 2 diabetes (T2D) has been increasing globally and a growing body of evidence links type 2 diabetes with altered microbiota composition. Type 2 diabetes is preceded by a long pre-diabetic state characterized by changes in various metabolic parameters. We tested whether the gut microbiome could have predictive potential for T2D development during the healthy and pre-diabetic disease stages. We used prospective data of 608 well-phenotyped Finnish men collected from the population-based Metabolic Syndrome In Men (METSIM) study to build machine learning models for predicting continuous glucose and insulin measures in a shorter (1.5 year) and longer (4.5 year) period. Our results show that the inclusion of gut microbiome improves prediction accuracy for modelling T2D associated parameters such as glycosylated hemoglobin and insulin measures. We identified novel microbial biomarkers and described their effects on the predictions using interpretable machine learning techniques, which revealed complex linear and non-linear associations. Additionally, the modelling strategy carried out allowed us to compare the stability of model performances and biomarker selection, also revealing differences in short-term and long-term predictions. The identified microbiome biomarkers provide a predictive measure for various metabolic traits related to T2D, thus providing an additional parameter for personal risk assessment. Our work also highlights the need for robust modelling strategies and the value of interpretable machine learning.

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    Longitudinal metatranscriptomic analysis of a meat spoilage microbiome detects abundant continued fermentation and environmental stress responses during shelf life and beyond.

    Longitudinal metatranscriptomic analysis of a meat spoilage microbiome detects abundant continued fermentation and environmental stress responses during shelf life and beyond.

    Link to bioRxiv paper:
    http://biorxiv.org/cgi/content/short/2020.08.13.250449v1?rss=1

    Authors: Hultman, J., Johansson, P., Björkroth, J.

    Abstract:
    Microbial food spoilage is a complex phenomenon associated with the succession of the specific spoilage organisms (SSO) over the course of time. We performed a longitudinal metatranscriptomic study on a modified atmosphere packaged (MAP) beef product to increase understanding of the longitudinal behavior of a spoilage microbiome during shelf life and onward. Based on the annotation of the mRNA reads, we recognized three stages related to the active microbiome that were descriptive for the sensory quality of the beef: acceptable product (AP), early spoilage (ES) and late spoilage (LS). Both the 16S RNA taxonomic assignments from the total RNA and functional annotations of the active genes showed that these stages were significantly different from each other. However, the functional gene annotations showed more pronounced difference than the taxonomy assignments. Psychrotrophic lactic acid bacteria (LAB) formed the core of the SSO according to the transcribed reads. Leuconostoc species were the most abundant active LAB throughout the study period, whereas the activity of Streptococcaceae (mainly Lactococcus) increased after the product was spoiled. In the beginning of the experiment, the community managed environmental stress by cold-shock responses which were followed by the expression of the genes involved in managing oxidative stress. Glycolysis, pentose phosphate pathway and pyruvate metabolism were active throughout the study at a relatively stable level. However, the proportional activity of the enzymes in these pathways changed over time. For example, acetate kinase activity was characteristic for the AP stage whereas formate C-acetyltransferase transcription was associated with spoilage.

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    Population analysis of Legionella pneumophila reveals the basis of resistance to complement-mediated killing

    Population analysis of Legionella pneumophila reveals the basis of resistance to complement-mediated killing

    Link to bioRxiv paper:
    http://biorxiv.org/cgi/content/short/2020.08.14.250670v1?rss=1

    Authors: Fitzgerald, J. R., Wee, B., Alves, J., Lindsay, D., Cameron, R., Pickering, A., Gorzynski, J., Corander, J., Marttinen, P., Smith, A.

    Abstract:
    Legionella pneumophila is the most common cause of the severe respiratory infection known as Legionnaires disease. L. pneumophila is typically a symbiont of free-living amoeba, and our understanding of the bacterial factors that determine human pathogenicity is limited. Here we carried out a population genomic study of 900 L. pneumophila isolates from human clinical and environmental samples to examine their genetic diversity, global distribution and the basis for human pathogenicity. We found that although some clones are more commonly associated with clinical infections, the capacity for human disease is representative of the breadth of species diversity. To investigate the bacterial genetic basis for human disease potential, we carried out a genome-wide association study that identified a single gene (lag-1), to be most strongly associated with clinical isolates. Molecular evolutionary analysis showed that lag-1, which encodes an O-acetyltransferase responsible for lipopolysaccharide modification, has been distributed horizontally across all major phylogenetic clades of L. pneumophila by frequent recent recombination events. Functional analysis revealed a correlation between the presence of a functional lag-1 gene and resistance to killing in human serum and bovine broncho-alveolar lavage. In addition, L. pneumophila strains that express lag-1 escaped complement-mediated phagocytosis by neutrophils. Importantly, we discovered that the expression of lag-1 confers the capacity to evade complement-mediated killing by inhibiting deposition of classical pathway molecules on the bacterial surface. In summary, our combined population and functional analyses identified L. pneumophila genetic traits linked to human disease and revealed the molecular basis for resistance to complement-mediated killing, a previously elusive trait of direct relevance to human disease pathogenicity.

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    Mammalian deubiquitinating enzyme inhibitors display in vitro and in vivo activity against malaria parasites and potentiate artemisinin action

    Mammalian deubiquitinating enzyme inhibitors display in vitro and in vivo activity against malaria parasites and potentiate artemisinin action

    Link to bioRxiv paper:
    http://biorxiv.org/cgi/content/short/2020.08.13.249425v1?rss=1

    Authors: Simwela, N. V., Hughes, K. R. P., Rennie, M. T., Barrett, M. P., Waters, A. P.

    Abstract:
    Current malaria control efforts rely significantly on artemisinin combinational therapies which have played massive roles in alleviating the global burden of the disease. Emergence of resistance to artemisinins is therefore, not just alarming but requires immediate intervention points such as development of new antimalarial drugs or improvement of the current drugs through adjuvant or combination therapies. Artemisinin resistance is primarily conferred by Kelch13 propeller mutations which are phenotypically characterised by generalised growth quiescence, altered haemoglobin trafficking and downstream enhanced activity of the parasite stress pathways through the ubiquitin proteasome system (UPS). Previous work on artemisinin resistance selection in a rodent model of malaria, which we and others have recently validated using reverse genetics, has also shown that mutations in deubiquitinating enzymes, DUBs (upstream UPS component) modulates susceptibility of malaria parasites to both artemisinin and chloroquine. The UPS or upstream protein trafficking pathways have, therefore, been proposed to be not just potential drug targets, but also possible intervention points to overcome artemisinin resistance. Here we report the activity of small molecule inhibitors targeting mammalian DUBs in malaria parasites. We show that generic DUB inhibitors can block intraerythrocytic development of malaria parasites in vitro and possess antiparasitic activity in vivo and can be used in combination with additive effect. We also show that inhibition of these upstream components of the UPS can potentiate the activity of artemisinin in vitro as well as in vivo to the extent that ART resistance can be overcome. Combinations of DUB inhibitors anticipated to target different DUB activities and downstream 20s proteasome inhibitors are even more effective at improving the potency of artemisinins than either inhibitors alone providing proof that targeting multiple UPS activities simultaneously could be an attractive approach to overcoming artemisinin resistance. These data further validate the parasite UPS as a target to both enhance artemisinin action and potentially overcome resistance. Lastly, we confirm that DUB inhibitors can be developed into in vivo antimalarial drugs with promise for activity against all of human malaria and could thus further exploit their current pursuit as anticancer agents in rapid drug repurposing programs.

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    Quantitative analysis of the splice variants expressed by the major hepatitis B virus genotypes

    Quantitative analysis of the splice variants expressed by the major hepatitis B virus genotypes

    Link to bioRxiv paper:
    http://biorxiv.org/cgi/content/short/2020.08.12.249060v1?rss=1

    Authors: Lim, C. S., Sozzi, V., Revill, P., Brown, C.

    Abstract:
    Hepatitis B virus (HBV) is a major human pathogen that causes liver diseases. The main HBV RNAs are unspliced transcripts that encode the key viral proteins. Recent studies show that some of the HBV spliced transcript isoforms are predictive of liver cancer, yet the roles of these spliced transcripts remain elusive. Furthermore, a total of 9 major HBV genotypes were isolated from discrete geographical regions of the world, it is likely that these genotypes may express a broad variety of spliced transcript isoforms. To systematically study the HBV splice variants, we transfected the human hepatoma cells Huh7 with 4 HBV genotypes (A2, B2, C2, and D3), followed by deep RNA-sequencing. We found that 12-25% of HBV RNAs were splice variants, which were reproducibly detected across independent biological replicates. This accounted for a total of 6 novel and 6 previously identified splice variants. In particular, two highly abundant novel splice variants, in which we called the putative splice variants 1 and 5 (pSP1 and pSP5), were specifically expressed at high levels in genotypes D3 and B2, respectively. In general, the HBV splicing profiles varied across the genotypes except for the known spliced pgRNAs SP1 and SP9, which were present in all 4 major genotypes. Counterintuitively, these singly spliced SP1 and SP9 had a suboptimal 5' splice site, suggesting that splicing of HBV RNAs is tightly controlled by the viral post-transcriptional regulatory RNA element.

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