{"messages":[{"status":"ok","category":"all","interval":"2018-08-21:2018-08-28","funder":"all","cursor":"45","count":30,"count_new_papers":"449","total":"629"}], "collection":[{"title":"Screening of antimicrobial activity and polyketide synthase gene identification from the Actinomycetes isolates","authors":"SRIVASTAV, A. V.","author_corresponding":"ASHU  Srivastav","author_corresponding_institution":"INSTITUTE OF CHEMICAL TECHONOLOGY","doi":"10.1101\/396846","date":"2018-08-21","version":"1","type":"confirmatory results","license":"cc_no","category":"microbiology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/396846.source.xml","abstract":"The Streptomyces genus is well studied owing to its capacity in producing more than 70% of antibiotics. This study was undertaken to characterize Streptomyces strains, occurring in soils of different districts of Tamilnadu, India as well as to evaluate their potential to produce antimicrobial compounds. Samples were collected from rice rhizosphere from different district of Tamilnadu agricultural zone. In primary screening by cross streak method, Streptomyces strains were assessed for antibiotic production and activity against different human bacterial. Then active isolates were selected for secondary screening by agar well diffusion method. Solvent extraction method was used to identify the best crude samples which are exhibiting better antibacterial activity. Then, 16S rRNA PCR was carried out for confirmation of isolates. In primary screening among all of the isolates, 50% isolates were active against at least one of the test organisms and 21.31% strains exhibited a broad-spectrum activity against almost all of the test bacteria. The minimum inhibitory concentrations (MICs) of the ethyl acetate extracts measured. Out of 26 positive strains two of the most active isolates SVG-07-15 and TK-01-05 were taken for further studies. These results highlight the importance of Streptomyces isolates in antibiotic production. Together with antibacterial activity, the PKS gene based approach can be applied for efficient screening of isolated strains of pharmaceutical value and related compounds.\n\nHighlightsO_LIIsolation of actinomycetes from soil samples collected from South India.\nC_LIO_LIScreening of isolated actinomycetes for antibacterial activity\nC_LIO_LIDetails study of potent strains against human pathogens\nC_LIO_LIIdentification of PKS gene from the active strains\nC_LI","funder":"NA","published":"10.4172\/1948-5948.1000404","server":"bioRxiv"},{"title":"A better way to define and describe Morlet wavelets for time-frequency analysis","authors":"Cohen, M. X.","author_corresponding":"Michael X Cohen","author_corresponding_institution":"Radboud University","doi":"10.1101\/397182","date":"2018-08-21","version":"1","type":"new results","license":"cc_by_nc_nd","category":"neuroscience","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/397182.source.xml","abstract":"Morlet wavelets are frequently used for time-frequency analysis of non-stationary time series data, such as neuroelectrical signals recorded from the brain. The crucial parameter of Morlet wavelets is the width of the Gaussian that tapers the sine wave. This width parameter controls the trade-off between temporal precision and frequency precision. It is typically defined as the \\\"number of cycles,\\\" but this parameter is opaque, and often leads to uncertainty and suboptimal analysis choices, as well as being difficult to interpret and evaluate. The purpose of this paper is to present alternative formulations of Morlet wavelets in time and in frequency that allow parameterizing the wavelets directly in terms of the desired temporal and spectral smoothing (as full-width at half-maximum). This formulation provides clarity on an important data analysis parameter, and should facilitate proper analyses, reporting, and interpretation of results. MATLAB code is provided.","funder":"NA","published":"10.1016\/j.neuroimage.2019.05.048","server":"bioRxiv"},{"title":"Marker-based watershed transform method for fully automatic mandibular segmentation from low-dose CBCT images","authors":"Fan, Y.; Beare, R.; Matthews, H.; Schneider, P.; Kilpatrick, N.; Clement, J.; Claes, P.; Penington, A.; Adamson, C.","author_corresponding":"Christopher  Adamson","author_corresponding_institution":"Developmental Imaging, Murdoch Childrens Research Institute, Melbourne, Australia","doi":"10.1101\/397166","date":"2018-08-21","version":"1","type":"new results","license":"cc_no","category":"bioinformatics","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/397166.source.xml","abstract":"Introduction Introduction Methods and materials Results Discussion Conclusions Funding References Three-dimensional mandibular models are useful for planning maxillofacial surgery and orthodontic treatment.1,2 In studies of growth, mandibular models are important for assessing morphological changes over time.3,4 Such models are typically obtained from conventional computed tomography (CT), using high radiation dose to capture fine detail of the bony structure. Cone beam computed tomography (CBCT) shows promise for oral and craniofacial imaging applications due to lower radiation dose, lower cost and shorter acquisition time compared to CT. However, CBCT images have lower contrast and higher levels of ...","funder":"NA","published":"10.1259\/dmfr.20180261","server":"bioRxiv"},{"title":"Long fragments achieve lower base quality in Illumina paired-end sequencing","authors":"Tan, G.; Opitz, L.; Schlapbach, R.; Rehrauer, H.","author_corresponding":"Hubert  Rehrauer","author_corresponding_institution":"University of Zurich","doi":"10.1101\/397158","date":"2018-08-21","version":"1","type":"new results","license":"cc_by_nd","category":"bioinformatics","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/397158.source.xml","abstract":"Illuminas technology provides high quality reads of DNA fragments with error rates below 1\/1000 per base. Runs typically generate a millions of reads where the vast majority of the reads has also an average error rate below 1\/1000. However, some paired-end sequencing data show the presence of a subpopulation of reads where the second read has lower average qualities. We show that the fragment length is a major driver of increased error rates in the R2 reads. Fragments above 500 nt tend to yield lower base qualities and higher error rates than shorter fragments. We demonstrate the fragment length dependency of the R2 read qualities using publicly available Illumina data generated by various library protocols, in different labs and using different sequencer models. Our finding extends the understanding of the Illumina read quality and has implications on error models for Illumina reads. It also sheds a light on the importance of the fragmentation during library preparation and the resulting fragment length distribution.","funder":"NA","published":"10.1038\/s41598-019-39076-7","server":"bioRxiv"},{"title":"Divine: Prioritizing Genes for Rare Mendelian Disease in Whole Exome Sequencing Data","authors":"Hong, C.; Clemenceau, J. R.; Yeu, Y.; Hwang, T. H.","author_corresponding":"Tae Hyun  Hwang","author_corresponding_institution":"Cleveland Clinic","doi":"10.1101\/396655","date":"2018-08-21","version":"1","type":"new results","license":"cc_by_nc","category":"bioinformatics","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/396655.source.xml","abstract":"MotivationRecent studies showed that a phenotype-driven analysis of whole exome sequencing (WES) could provide more accurate and clinically relevant genetic variants.\\n\\nResultsWe develop a computational tool called Divine that integrates patients phenotype(s) and WES data with 30 prior biological knowledge (e.g., human phenotype ontology, gene ontology, pathway database, protein-protein interaction networks, pathogenicity by the amino acid change due to polymorphism, and hot-spot protein domains) to prioritize potential disease-causing genes. In a retrospective study with 22 real and four simulated data set, Divine ranks the same pathogenic genes confirmed by the original studies 5th on average out of a thousand of mutated genes and outperforms existing state-of-the-art methods.\\n\\nAvailabilityhttps:\/\/github.com\/hwanglab\/divine\\n\\nContacthwangt@ccf.org\\n\\nSupplementary informationSupplementary Document is attached at the end of the page.","funder":"NA","published":"NA","server":"bioRxiv"},{"title":"Fast Batch Alignment of Single Cell Transcriptomes Unifies Multiple Mouse Cell Atlases into an Integrated Landscape","authors":"Park, J.-E.; Polanski, K.; Meyer, K.; Teichmann, S. A.","author_corresponding":"Sarah A Teichmann","author_corresponding_institution":"Welcome Sanger Institute","doi":"10.1101\/397042","date":"2018-08-21","version":"1","type":"new results","license":"cc_by_nc","category":"bioinformatics","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/397042.source.xml","abstract":"Increasing numbers of large scale single cell RNA-Seq projects are leading to a data explosion, which can only be fully exploited through data integration. Therefore, efficient computational tools for combining diverse datasets are crucial for biology in the single cell genomics era. A number of methods have been developed to assist data integration by removing technical batch effects, but most are computationally intensive. To overcome the challenge of enormous datasets, we have developed BBKNN, an extremely fast graph-based data integration method. We illustrate the power of BBKNN for dimensionalityreduced visualisation and clustering in multiple biological scenarios, including a massive integrative study over several murine atlases. BBKNN successfully connects cell populations across experimentally heterogeneous mouse scRNA-Seq datasets, which reveals global markers of cell type and organspecificity and provides the foundation for inferring the underlying transcription factor network. BBKNN is available at https:\/\/github.com\/Teichlab\/bbknn.","funder":"NA","published":"10.1093\/bioinformatics\/btz625","server":"bioRxiv"},{"title":"ENIGMA: An Enterotype-Like Unigram Mixture Model for Microbial Association Analysis","authors":"Abe, K.; Hirayama, M.; Ohno, K.; Shimamura, T.","author_corresponding":"Teppei  Shimamura","author_corresponding_institution":"Division of Systems Biology, Nagoya University Graduate School of Medicine","doi":"10.1101\/397091","date":"2018-08-21","version":"1","type":"new results","license":"cc_by_nd","category":"bioinformatics","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/397091.source.xml","abstract":"BackgroundOne of the major challenges in microbial studies is to discover associations between microbial communities and a specific disease. A specialized feature of microbiome count data is that intestinal bacterial communities have clusters reffered as enterotype characterized by differences in specific bacterial taxa, which makes it difficult to analyze these data under health and disease conditions. Traditional probabilistic modeling cannot distinguish dysbiosis of interest with the individual differences.\\n\\nResultsWe propose a new probabilistic model, called ENIGMA (Enterotype-like uNIGram mixture model for Microbial Association analysis), to address these problems. ENIGMA enables us to simultaneously estimate enterotype-like clusters characterized by the abundances of signature bacterial genera and environmental effects associated with the disease.\\n\\nConclusionWe illustrate the performance of the proposed method both through the simulation and clinical data analysis. ENIGMA is implemented with R and is available from GitHub (https:\/\/github.com\/abikoushi\/enigma).","funder":"NA","published":"10.1186\/s12864-019-5476-9","server":"bioRxiv"},{"title":"A Multimodal Adaptive Super-Resolution and Confocal Microscope","authors":"Valiya Peedikakkal, L.; Furley, A.; Cadby, A. J.","author_corresponding":"Ashley J Cadby","author_corresponding_institution":"The University of Sheffield","doi":"10.1101\/397273","date":"2018-08-21","version":"1","type":"new results","license":"cc_no","category":"biophysics","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/397273.source.xml","abstract":"Existing optical microscopy techniques compromise between resolution, photodamage, speed of acquisition and imaging in to deep samples. This often confines a technique to a certain biological system or process. We present a versatile imaging system which can switch between imaging modalities with sub millisecond transition times to adapt to the needs of a wide range of sample types. The imaging modalities provide the minimally invasive but low-resolution epi-fluorescence though increasing invasive but higher resolution confocal and structured illumination until the highest resolution is achieved through the most intrusive, localisation microscopy. The ability of the system to overcome the limitations of conventional single mode microscopy is demonstrated by several biological investigations. The ideas presented in this work allow researchers to move away from the model of a single imaging modality to study a specific process and instead follow those processes using the most suitable method available during the lifetime of the investigation.","funder":"NA","published":"NA","server":"bioRxiv"},{"title":"Mitochondrial DNA and their nuclear copies in parasitic wasp Pteromalus puparum: A comparative analysis in Chalcidoidea","authors":"Yan, Z.; Fang, Q.; Tian, Y.; Wang, F.; Chen, X.; Werren, J. H.; Ye, G.","author_corresponding":"Gongyin  Ye","author_corresponding_institution":"Zhejiang University","doi":"10.1101\/396911","date":"2018-08-21","version":"1","type":"new results","license":"cc_by_nc_nd","category":"genomics","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/396911.source.xml","abstract":"Chalcidoidea (chalcidoid wasps) are an abundant and megadiverse insect group with both ecological and economical importance. Here we report a complete mitochondrial genome in Chalcidoidea from Pteromalus puparum (Pteromalidae). Eight tandem repeats followed by 6 reversed repeats were detected in its 3,308 bp control region. This long and complex control region may explain failures of amplifying and sequencing of complete mitochondrial genomes in some chalcidoids. In addition to 37 typical mitochondrial genes, an extra identical isoleucine tRNA (trnI) was detected. We speculate this recent mitochondrial gene duplication indicates that gene arrangements in chalcidoids are ongoing. A comparison among available chalcidoid mitochondrial genomes, reveals rapid gene order rearrangements overall, and high substitution rate in P. puparum. In addition, we identified 24 nuclear sequences of mitochondrial origin (NUMTs) in P. puparum, summing up to 9,989 bp, with 3,617 bp of these NUMTs originating from mitochondrial coding regions. NUMTs abundance in P. puparum is only one-twelfth of that in its relative, Nasonia vitripennis. Based on phylogenetic analysis, we provide evidence that a faster nuclear degradation rate contributes to the reduced NUMT numbers in P. puparum. Overall, our study shows unusually high rates of mitochondrial evolution and considerable variation in NUMT accumulation in Chalcidoidea.","funder":"NA","published":"10.1016\/j.ijbiomac.2018.10.039","server":"bioRxiv"},{"title":"A highly conserved complete accessory Escherichia coli type III secretion system 2 is widespread in bloodstream isolates of the ST69 lineage","authors":"Evans, T. J.; Fox, S.; Goswami, C.; Holden, M. T.; Connolly, J. P.; Roe, A. J.; Connor, M.; Leanord, A.","author_corresponding":"Tom J  Evans","author_corresponding_institution":"University of Glasgow","doi":"10.1101\/396804","date":"2018-08-21","version":"1","type":"new results","license":"cc_by_nd","category":"microbiology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/396804.source.xml","abstract":"Bacterial type III secretion systems (T3SS) play an important role in pathogenesis of Gram-negative infections. Enteropathogenic and enterohemorrhagic Escherichia coli contain a well-defined T3SS but in addition a second T3SS termed E. coli T3SS 2 (ETT2) has been described in a number of strains of E. coli. The majority of E. coli contain elements of a genetic locus encoding ETT2, but which has undergone significant mutational attrition rendering it without predicted function. Only a very few strains have been reported to contain an intact ETT2 locus. To investigate the occurrence of the ETT2 locus in strains of human pathogenic E. coli, we carried out genomic sequencing of 162 isolates obtained from patient blood cultures in Scotland. We found that all 26 ST69 isolates from this collection contained an intact ETT2 together with an associated eip locus which encodes putative secreted ETT2 effectors as well as eilA, a gene encoding a putative transcriptional regulator of ETT2 associated genes. Using a reporter gene for eilA activation, we defined conditions under which this gene was differentially activated. However, comparison of secreted proteins from ST69 strains under high and low eilA activation failed to identify any ETT2 secreted substrates. The conservation of the genes encoding ETT2 in human pathogenic ST69 strains strongly suggests it has functional importance in infection, although its exact functional role remains obscure.\\n\\nImportanceOne of the commonest bacteria causing bloodstream infections in humans is Escherichia coli, which has a significant morbidity and mortality. Better understating of the mechanisms by which this microbe can invade blood could lead to more effective prevention and treatment. One mechanism by which some strains cause disease is by elaboration of a specialized secretion system, the type III secretion system (T3SS), encoded by the locus of enterocyte effacement (LEE). In addition to this well-defined T3SS, a second T3SS has been found in some E. coli strains termed E. coli type III secretion system 2 (ETT2). Most strains carry elements of the ETT2 locus, but with significant mutational attrition rendering it functionless. The significance of our work is that we have discovered that human bloodstream isolates of E. coli of sequence type 69 contain a fully intact ETT2 and associated genes, strongly suggesting its functional importance in human infection.","funder":"NA","published":"10.1038\/s41598-020-61026-x","server":"bioRxiv"},{"title":"Pyrite formation from FeS and H2S is mediated by a novel type of microbial energy metabolism","authors":"Thiel, J.; Byrne, J.; Kappler, A.; Schink, B.; Pester, M.","author_corresponding":"Michael  Pester","author_corresponding_institution":"Leibniz Institute DSMZ - German Collection of Microorganisms and Cell Cultures","doi":"10.1101\/396978","date":"2018-08-21","version":"1","type":"new results","license":"cc_by_nc_nd","category":"microbiology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/396978.source.xml","abstract":"The exergonic reaction of FeS with H2S to form FeS2 (pyrite) and H2 was postulated to have operated as an early form of energy metabolism on primordial Earth. Since the Archean, sedimentary pyrite formation played a major role in the global iron and sulfur cycles, with direct impact on the redox chemistry of the atmosphere. To date, pyrite formation was considered a purely geochemical reaction. Here, we present microbial enrichment cultures, which grew with FeS, H2S, and CO2 as their sole substrates to produce FeS2 and CH4. Cultures grew over periods of three to eight months to cell densities of up to 2-9x106 cells mL-1. Transformation of FeS with H2S to FeS2 was followed by 57Fe Mossbauer spectroscopy and showed a clear biological temperature profile with maximum activity at 28{degrees}C and decreasing activities towards 4{degrees}C and 60{degrees}C. CH4 was formed concomitantly with FeS2 and exhibited the same temperature dependence. Addition of either penicillin or 2-bromoethanesulfonate inhibited both FeS2 and CH4 production, indicating a syntrophic coupling of pyrite formation to methanogenesis. This hypothesis was supported by a 16S rRNA gene-based phylogenetic analysis, which identified at least one archaeal and five bacterial species. The archaeon was closely related to the hydrogenotrophic methanogen Methanospirillum stamsii while the bacteria were most closely related to sulfate-reducing Deltaproteobacteria, as well as uncultured Firmicutes and Actinobacteria. We identified a novel type of microbial metabolism able to conserve energy from FeS transformation to FeS2, which may serve as a model for a postulated primordial iron-sulfur world.\\n\\nSignificance statementPyrite is the most abundant iron-sulfur mineral in sediments. Over geological times, its burial controlled oxygen levels in the atmosphere and sulfate concentrations in seawater. Its formation in sediments is so far considered a purely geochemical process that is at most indirectly supported by microbial activity. We show that lithotrophic microorganisms can directly transform FeS and H2S to FeS2 and use this exergonic reaction as a novel form of energy metabolism that is syntrophically coupled to methanogenesis. Our results provide insights into a syntrophic relationship that could sustain part of the deep biosphere and lend support to the iron-sulfur-world theory that postulated FeS transformation to FeS2 as a key energy-delivering reaction for life to emerge.","funder":"NA","published":"NA","server":"bioRxiv"},{"title":"The role of the fornix in human navigational learning","authors":"Hodgetts, C. J.; Stefani, M.; Williams, A. N.; Kolarik, B. S.; Yonelinas, A. P.; Ekstrom, A. D.; Lawrence, A. D.; Zhang, J.; Graham, K. S.","author_corresponding":"Carl J Hodgetts","author_corresponding_institution":"Cardiff University","doi":"10.1101\/391888","date":"2018-08-21","version":"1","type":"new results","license":"cc_by_nc_nd","category":"neuroscience","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/391888.source.xml","abstract":"Studies in rodents have demonstrated that transecting the white matter pathway linking the hippocampus and anterior thalamic nuclei - the fornix - impairs flexible navigational learning in the Morris Water Maze (MWM), as well as similar spatial learning tasks. While diffusion MRI studies in humans have linked fornix microstructure to scene discrimination and memory, its role in human navigation is currently unknown. We used high-angular resolution diffusion MRI to ask whether inter-individual differences in fornix microstructure would be associated with spatial learning in a virtual MWM task. To increase sensitivity to individual learning across trials, we adopted a novel curve fitting approach to estimate a single index of learning rate. We found a significant correlation between learning rate and the microstructure (mean diffusivity) of the fornix, but not that of a control tract linking occipital and anterior temporal cortices (the inferior longitudinal fasciculus, ILF). Further, this correlation remained significant when controlling for hippocampal volume. These findings extend previous animal studies by demonstrating the functional relevance of the fornix for human navigational learning, and highlight the importance of a distributed neuroanatomical network, underpinned by key white matter pathways, such as the fornix, in complex spatial behaviour.","funder":"NA","published":"10.1016\/j.cortex.2019.10.017","server":"bioRxiv"},{"title":"Altered dendritic spine function and integration in a mouse model of Fragile X Syndrome","authors":"Booker, S. A.; Domanski, A. P.; Dando, O. R.; Jackson, A. D.; Isaac, J. T.; Hardingham, G. E.; Wyllie, D. J.; Kind, P. C.","author_corresponding":"Peter C Kind","author_corresponding_institution":"University of Edinburgh","doi":"10.1101\/396986","date":"2018-08-21","version":"1","type":"new results","license":"cc_by_nc_nd","category":"neuroscience","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/396986.source.xml","abstract":"Cellular and circuit hyperexcitability are core features of Fragile X Syndrome and related autism spectrum disorder models. However, a synaptic basis for this hyperexcitability has proved elusive. We show in a mouse model of Fragile X Syndrome, glutamate uncaging onto individual dendritic spines yields stronger single-spine excitation than wild-type, with more silent spines. Furthermore, near-simultaneous uncaging at multiple spines revealed fewer spines are required to trigger an action potential. This arose, in part, from increased dendritic gain due to increased intrinsic excitability, resulting from reduced hyperpolarization-activated currents. Super-resolution microscopy revealed no change in dendritic spine morphology, pointing to an absence of a structure-function relationship. However, ultrastructural analysis revealed a 3-fold increase in multiply-innervated spines, accounting for the increased single-spine excitatory currents following glutamate uncaging. Thus, loss of FMRP causes abnormal synaptogenesis, leading to large numbers of poly-synaptic spines despite normal spine morphology, thus explaining the synaptic perturbations underlying circuit hyperexcitability.","funder":"NA","published":"10.1038\/s41467-019-11891-6","server":"bioRxiv"},{"title":"Regional low-frequency oscillations in human rapid-eye movement sleep","authors":"Bernardi, G.; Betta, M.; Ricciardi, E.; Pietrini, P.; Tononi, G.; Siclari, F.","author_corresponding":"Francesca  Siclari","author_corresponding_institution":"Lausanne University Hospital","doi":"10.1101\/397224","date":"2018-08-21","version":"1","type":"new results","license":"cc_no","category":"neuroscience","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/397224.source.xml","abstract":"Although the EEG slow wave of sleep is typically considered to be a hallmark of Non Rapid Eye Movement (NREM) sleep, recent work in mice has shown that slow waves can also occur in REM sleep. Here we investigated the presence and cortical distribution of low-frequency (1-4 Hz) oscillations in human REM sleep by analyzing high-density EEG sleep recordings obtained in 28 healthy subjects. We identified two clusters of low-frequency oscillations with distinctive properties: 1) a fronto-central cluster characterized by [~]2.5-3.0 Hz, relatively large, notched delta waves (so-called  sawtooth waves) that tended to occur in bursts, were associated with increased gamma activity and rapid eye movements, and upon source modeling, displayed an occipito-temporal and a fronto-central component; and 2) a medial occipital cluster characterized by more isolated, slower (<2 Hz) and smaller waves that were not associated with rapid eye movements, displayed a negative correlation with gamma activity and were also found in NREM sleep. Thus, low-frequency oscillations are an integral part of REM sleep in humans, and the two identified subtypes (sawtooth and medial-occipital slow waves) may reflect distinct generation mechanisms and functional roles. Sawtooth waves, which are exclusive to REM sleep, share many characteristics with ponto-geniculo-occipital (PGO) waves described in animals and may represent the human equivalent or a closely related event while medio-occipital slow waves appear similar to NREM sleep slow waves.","funder":"NA","published":"10.1523\/JNEUROSCI.2298-18.2019","server":"bioRxiv"},{"title":"Farmers perceptions on the causes of cassava root bitterness in konzo-affected areas of Mtwara Region, Tanzania","authors":"Imakumbili, M. L. E.; Semu, E.; Semoka, J. M. R.; Abass, A.; Mkamilo, G.","author_corresponding":"Matema L. E. Imakumbili","author_corresponding_institution":"Sokoine University of Agriculture","doi":"10.1101\/397018","date":"2018-08-21","version":"1","type":"new results","license":"cc_no","category":"pharmacology and toxicology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/397018.source.xml","abstract":"The agronomic factors influencing increased cyanogenic glucoside levels, particularly in bitter cassava varieties during periods without water stress, in areas where konzo (a cassava cyanide related paralytic disorder also called spastic paraparesis) persists, are hardly known. However, through their assessment of bitter taste, farmers may have noticed factors unrelated to water stress and variety type that additionally influence cassava root cyanogenic glucoside content in these environments. Bitterness in cassava is usually associated with high cyanogenic glucoside levels. Using some konzo-affected areas in Mtwara region of Tanzania as a case study, a survey was thus carried out to identify the factors, hitherto overlooked, that may additionally influence cyanogenic glucoside levels in cassava. A total of 120 farmers were interviewed. A number of factors unrelated to water stress and variety type that could be additionally influencing cyanogenic glucoside production in cassava plants were mentioned. The mentioned factors included nutrient poor soils, plant age at harvest, weeds, piecemeal harvesting, and branch pruning; the factors, respectively, constituted 14.2%, 7.5%, 0.8%, 0.8%, and 0.8% of the total responses given. The revealed factors constitute permanent environmental characteristics and commonly used crop management practices by farmers living in konzo-prone Mtwara region of Tanzania that could be additionally resulting in high cyanogenic glucoside levels in cassava, regardless of water stress.","funder":"NA","published":"10.1371\/journal.pone.0215527","server":"bioRxiv"},{"title":"Mutual synchronization pattern as a complementary indicator of the short-term blood pressure - heart rate feedback regulation activity","authors":"Pyko, N. S.; Pyko, S. A.; Markelov, O. A.; Mamontov, O. V.; Bogachev, M.","author_corresponding":"Mikhail  Bogachev","author_corresponding_institution":"St. Petersburg Electrotechnical University","doi":"10.1101\/397208","date":"2018-08-21","version":"1","type":"new results","license":"cc_no","category":"physiology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/397208.source.xml","abstract":"We suggest a complementary indicator of the blood pressure - heart rate feedback regulation based on their synchronization pattern assessed by Hilbert transform. We determine the synchronization coefficient Sync as the fraction of time fragments where the standard deviation of the differences between instantaneous phases of blood pressure and pulse intervals are below a certain threshold. While BRS characterizes the intensity of the pulse intervals response to the blood pressure changes during observed feedback responses, the Sync likely indicates how often such responses are activated in the first place. Data from 95 tilt test records indicate that in both healthy subjects and patients with moderate autonomic dysfunction BRS and Sync are typically reciprocal suggesting that low intensity of the feedback responses characterized by low BRS is rather compensated by their more frequent activation indicated by higher Sync. In contrast, in diabetes patients with autonomic neuropathy BRS and Sync are positively correlated likely indicating the breakdown of this compensation in some of the diabetic patients. Therefore we suggest that Sync could be used as an additional indicator of the blood pressure - heart rate feedback regulation activity that is complementary to the widely used baroreflex sensitivity (BRS).","funder":"NA","published":"NA","server":"bioRxiv"},{"title":"Systems therapeutics analyses identify genomic signatures defining responsiveness to allopurinol and combination therapy for lung cancer","authors":"Tavassoly, I.; Hu, Y.; Zhao, S.; Mariottini, C.; Boran, A.; Chen, Y.; Li, L.; Tolentino, R. E.; Jayaraman, G.; Goldfarb, J.; Gallo, J.; Iyengar, R.","author_corresponding":"Ravi  Iyengar","author_corresponding_institution":"Icahn School of Medicine at Mount Sinai","doi":"10.1101\/396697","date":"2018-08-21","version":"1","type":"new results","license":"cc_no","category":"systems biology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/396697.source.xml","abstract":"The ability to predict responsiveness to drugs in individual patients is limited. We hypothesized that integrating molecular information from databases would yield predictions that could be experimentally tested to develop genomic signatures for sensitivity or resistance to specific drugs. We analyzed TCGA data for lung adenocarcinoma (LUAD) patients and identified a subset where xanthine dehydrogenase expression correlated with decreased survival. We tested allopurinol, a FDA approved drug that inhibits xanthine dehydrogenase on a library of human Non Small Cell Lung Cancer (NSCLC) cell lines from CCLE and identified sensitive and resistant cell lines. We utilized the gene expression profiles of these cell lines to identify six-gene signatures for allopurinol sensitive and resistant cell lines. Network building and analyses identified JAK2 as an additional target in allopurinol-resistant lines. Treatment of resistant cell lines with allopurinol and CEP-33779 (a JAK2 inhibitor) resulted in cell death. The effectiveness of allopurinol alone or allopurinol and CEP-33779 were verified in vivo using tumor formation in NCR-nude mice. We utilized the six-gene signatures to predict five additional allopurinolsensitive NSCLC lines, and four allopurinol-resistant lines susceptible to combination therapy. We found that drug treatment of all cell lines yielded responses as predicted by the genomic signatures. We searched the library of patient derived NSCLC tumors from Jackson Laboratory to identify tumors that would be predicted to be sensitive or resistant to allopurinol treatment. Both patient derived tumors predicted to be allopurinol sensitive showed the predicted sensitivity, and the predicted resistant tumors were sensitive to combination therapy. These data indicate that we can use integrated molecular information from cancer databases to predict drug responsiveness in individual patients and thus enable precision medicine.","funder":"NA","published":"10.1002\/1878-0261.12521","server":"bioRxiv"},{"title":"DocClustering: An implementation of the novel PS-Document Clustering algorithm","authors":"Doerpinghaus, J.; Schaaf, S.; Jacobs, M.","author_corresponding":"Jens  Doerpinghaus","author_corresponding_institution":"Fraunhofer Institute for Algorithms and Scientific Computing SCAI","doi":"10.1101\/397133","date":"2018-08-21","version":"1","type":"confirmatory results","license":"cc_no","category":"bioinformatics","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/397133.source.xml","abstract":"AO_SCPCAPBSTRACTC_SCPCAPDocument clustering is widely used in science for data retrieval and organisation. DocClustering is developed to include and use a novel algorithm called PS-Document Clustering that has been first introduced in 2017. This method combines approaches of graph theory with state of the art NLP-technologies. This new heuristic has been shown to be superior to conventional algorithms and it provides - given a suiting similarity measure - a more accurate clustering on biological and medical data.\\n\\nSince the application is written for research on biomedical literature, interfaces for PubMed and SCAIView are available. In this brief report the source code as well as a short overview about the new features, novel heuristics and approaches are provided.\\n\\nThe software can be obtained from the authors or directly downloaded from GitHub, see https:\/\/github.com\/jd-s\/DocClustering.","funder":"NA","published":"NA","server":"bioRxiv"},{"title":"Little variation in the morphology of the atria across 13 orders of birds","authors":"Kroneman, J.; Faber, J.; Wolschrijn, C.; Christoffels, V.; Jensen, B.","author_corresponding":"Bjarke  Jensen","author_corresponding_institution":"University of Amsterdam","doi":"10.1101\/397034","date":"2018-08-21","version":"1","type":"new results","license":"cc_by_nd","category":"evolutionary biology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/397034.source.xml","abstract":"Mammals and birds acquired high performance hearts and endothermy during their independent evolution from amniotes with many reptile characters. A literature review shows that the variation in atrial morphology is greater in mammals than in ectothermic reptiles. We therefore hypothesized that the transition from ectothermy to endothermy associated with greater variation in cardiac structure. We tested the hypothesis in birds, by assessing the variation in 15 characters in hearts from 13 orders of birds. Hearts were assessed by gross morphology and histology, and we focused on the atria as they have multiple features that lend themselves to quantification. We found bird hearts to have multiple features in common with ectothermic reptiles (synapomorphies), for instance the presence of three sinus horns. Convergent features were shared with crocodylians and mammals, such as the cranial offset of the left atrioventricular junction. Other convergent features like the compact organization of the atrial walls were shared with mammals only. Sinus myocardium expressing Isl1 was node-like (Mallard), thickened (chicken), or anatomically indistinct from surrounding myocardium (Lesser redpoll). Some features were distinctively avian (apomorphies), including the presence of a left atrial antechamber, and the ventral merger of the left and right atrium, which was found in parrots and passerine birds. Most features, however, exhibited little variation. For instance, there were always three systemic veins and two pulmonary veins, whereas among mammals there are 2-3 and 1-7, respectively. Our findings suggest that the transition to high cardiac performance does not necessarily lead to greater variation in cardiac structure.","funder":"NA","published":"10.1002\/jmor.20952","server":"bioRxiv"},{"title":"Defining the core essential genome of Pseudomonas aeruginosa","authors":"Poulsen, B. E.; Yang, R.; Clatworthy, A. E.; White, T.; Osmulski, S. J.; Li, L.; Penaranda, C.; Shoresh, N.; Hung, D. T.","author_corresponding":"Deborah T Hung","author_corresponding_institution":"Massachusetts General Hospital","doi":"10.1101\/396689","date":"2018-08-21","version":"1","type":"new results","license":"cc_no","category":"microbiology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/396689.source.xml","abstract":"Genomics offered the promise of transforming antibiotic discovery by revealing many new essential genes as good targets, but the results fell short of the promise. It is becoming clear that a major limitation was that essential genes for a bacterial species were often defined based on a single or limited number of strains grown under a single or limited number of in vitro laboratory conditions. In fact, the essentiality of a gene can depend on both genetic background and growth condition. We thus developed a strategy for more rigorously defining the core essential genome of a bacterial species by studying many pathogen strains and growth conditions. We assessed how many strains must be examined to converge on a set of core essential genes for a species. We used transposon insertion sequencing (Tn-Seq) to define essential genes in nine strains of Pseudomonas aeruginosa on five different media and developed a novel statistical model, FiTnEss, to classify genes as essential versus non-essential across all strain-media combinations. We defined a set of 321 core essential genes, representing 6.6% of the genome. We determined that analysis of 4 strains was typically sufficient in P. aeruginosa to converge on a set of core essential genes likely to be essential across the species across a wide range of conditions relevant to in vivo infection, and thus to represent attractive targets for novel drug discovery.","funder":"NA","published":"10.1073\/pnas.1900570116","server":"bioRxiv"},{"title":"Altered Bacteria-Fungi Inter-Kingdom Network in Gut of Ankylosing Spondylitis Patients","authors":"li, M.; Dai, B.; Tang, Y.; Lei, L.; Li, N.; Liu, C.; Ge, T.; Zhang, L.; Xu, Y.; Hu, Y.; Li, P.; Zhang, Y.; Yuan, J.; Li, X.","author_corresponding":"Xia  Li","author_corresponding_institution":"Dalian Medical University","doi":"10.1101\/396812","date":"2018-08-21","version":"1","type":"new results","license":"cc_no","category":"microbiology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/396812.source.xml","abstract":"Intestinal bacterial dysbiosis has been increasingly linked to Ankylosing Spondylitis (AS), which is a prototypic and best studied subtype of Spondyloarthritis (SpA). Fungi and bacteria coexist in human gut and interact with each other, although they have been shown to contribute actively to health or diseases, no studies have investigated whether fungal microbiota in AS patients is perturbed. In this study, fecal samples of 22 AS patients, with clinical and radiographic assessments, and 16 healthy controls (HCs) were collected to systematically characterize the gut microbiota and mycobiota in AS patients by 16S rDNA and ITS2-based DNA sequencing. The relationships between therapeutic regimens, disease activity, radiographic damage of AS and gut micro\/mycobiome were investigated. Our results showed a distinct mycobiota pattern in AS in addition to microbiota dysbiosis. The gut mycobiome of AS patients was characterized by higher taxonomic levels of Ascomycota, especially the class of Dothideomycetes, and decreased abundance of Basidiomycota, which was mainly contributed by the decease of Agaricales. Compared to HCs, changing of the ITS2\/16S biodiversity ratio, and bacteria-fungi interkingdom network were observed in AS patients. Alteration of gut mycobiota was associated with different therapeutic regimens, disease activity, as well as different degrees of radiographic damage. Moreover, we unraveled a disease-specific interkingdom network alteration in AS. Finally, we also identified some trends suggesting that different therapeutic regimens may induce changing of both bacterial and fungal microbiota in AS.\\n\\nIMPORTANCEHuman gut is colonized by diverse fungi (mycobiome), and they have long been suspected in the pathogenesis of Spondyloarthritis (SpA). Our study unraveled a disease-specific interkingdom network alteration in AS, suggesting that fungi, or the interkingdom interactions between bacteria and fungi, may play an essential role in AS development. However, limited by sample size and indeep mechanism studies, further large scale investigations on the characterization of gut mycobiome in AS patients are needed to form a foundation for research into the relationship between mycobiota dysbiosis and AS development.","funder":"NA","published":"NA","server":"bioRxiv"},{"title":"Senescent, dysfunctional human cardiac progenitor cells (CPCs) accumulate in the aged heart and elimination of senescent cells enhances CPC activation and cardiomyocyte proliferation in aged mice","authors":"Lewis-McDougall, F. C.; Ruchaya, P. J.; Domenjo-Vila, E.; Teoh, T. S.; Prata, L.; Cottle, B. J.; Clark, J. E.; Punjabi, P. P.; Awad, W.; Torella, D.; Tchkonia, T.; Kirkland, J. L.; Ellison-Hughes, G. M.","author_corresponding":"Georgina M Ellison-Hughes","author_corresponding_institution":"Kings College London","doi":"10.1101\/397216","date":"2018-08-21","version":"1","type":"new results","license":"cc_by_nc_nd","category":"physiology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/397216.source.xml","abstract":"Aging leads to increased cellular senescence and is associated with decreased potency of tissue-specific stem\/progenitor cells. Here we have done an extensive analysis of cardiac progenitor cells (CPCs) isolated from human subjects with cardiovascular disease (n=119), aged 32-86 years. In aged subjects (>74 years old) over half of CPCs are senescent (p16INK4A, SA-{beta}-gal, DNA damage {gamma}H2AX, telomere length, Senescence-Associated Secretory Phenotype (SASP)), unable to replicate, differentiate, regenerate or restore cardiac function following transplantation into the infarcted heart. SASP factors secreted by senescent CPCs renders otherwise healthy CPCs to senescence. Elimination of senescent CPCs using senolytics abrogates the SASP and its debilitative effect in vitro. Global elimination of senescent cells in aged mice (INK-ATTAC or wildtype mice treated with D+Q senolytics) in vivo activates resident CPCs (0.23{+\/-}0.06% vs. 0.01{+\/-}0.01% vehicle; p<0.05) and increased the number of small, proliferating Ki67-, EdU-positive cardiomyocytes (0.25{+\/-}0.07% vs. 0.03{+\/-}0.03% vehicle; p<0.05). Therapeutic approaches that eliminate senescent cells may alleviate cardiac deterioration with aging and rejuvenate the regenerative capacity of the heart.","funder":"NA","published":"10.1111\/acel.12931","server":"bioRxiv"},{"title":"Plug-and-Play Metabolic Transducers Expand the Chemical Detection Space of Cell-Free Biosensors","authors":"Voyvodic, P. L.; Pandi, A.; Koch, M.; Faulon, J.-L.; Bonnet, J.","author_corresponding":"Jerome  Bonnet","author_corresponding_institution":"Centre de Biochimie Structurale, INSERM U1054, CNRS UMR5048, University of Montpellier","doi":"10.1101\/397315","date":"2018-08-21","version":"1","type":"new results","license":"cc_by_nc_nd","category":"synthetic biology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/397315.source.xml","abstract":"Cell-free transcription-translation systems have great potential for biosensing, yet the range of detectable chemicals is limited. Here we provide a framework to expand the range of molecules detectable by cell-free biosensors by combining synthetic metabolic cascades with transcription factor-based networks. These hybrid cell-free biosensors are highly-sensitive and have a fast response and high-dynamic range. This work provides a foundation to engineer modular cell-free biosensors tailored for many applications.","funder":"NA","published":"10.1038\/s41467-019-09722-9","server":"bioRxiv"},{"title":"tmap: topological analysis of population-scale microbiome data","authors":"Liao, T.; Wei, Y.; Luo, M.; Zhao, G.; Zhou, H.","author_corresponding":"Haokui  Zhou","author_corresponding_institution":"Shenzhen Institutes of Advanced Technology","doi":"10.1101\/396960","date":"2018-08-21","version":"1","type":"new results","license":"cc_no","category":"bioinformatics","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/396960.source.xml","abstract":"Population-scale microbiome study poses specific challenges in data analysis, from enterotype analysis, identification of driver species, to microbiome-wide association of host covariates. Application of advanced data mining techniques to high-dimensional complex dataset is expected to meet the rapid advancement in large scale and integrative microbiome research. Here, we present tmap, a topological data analysis framework for population-scale microbiome study. This framework can capture complex shape of large scale microbiome data into a compressive network representation. We also develop network-based statistical analysis for driver species identification and microbiome-wide association analysis. tmap can be used for exploring variations in a population-scale microbiome landscape to study host-microbiome association.\\n\\nAvailability and implementationtmap is available at GitHub (https:\/\/github.com\/GPZ-Bioinfo\/tmap), accompanied with online documentation and tutorial (http:\/\/tmap.readthedocs.io).\\n\\nContacthttp:\/\/hk.zhou@siat.ac.cn","funder":"NA","published":"NA","server":"bioRxiv"},{"title":"Blood, sweat and tears: a review of non-invasive DNA sampling","authors":"Lefort, M.-C.; Cruickshank, R. H.; Descovich, K.; Adams, N. J.; Barun, A.; Emami-Khoyi, A.; Ridden, J.; Smith, V. R.; Sprague, R.; Waterhouse, B.; Boyer, S.","author_corresponding":"Stephane  Boyer","author_corresponding_institution":"University of Tours","doi":"10.1101\/385120","date":"2018-08-21","version":"1","type":"new results","license":"cc_by_nc_nd","category":"ecology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/385120.source.xml","abstract":"AO_SCPLOWBSTRACTC_SCPLOWThe use of DNA data is ubiquitous across animal sciences. DNA may be obtained from an organism for a myriad of reasons including identification and distinction between cryptic species, sex identification, comparisons of different morphocryptic genotypes or assessments of relatedness between organisms prior to a behavioural study. DNA should be obtained while minimizing the impact on the fitness, behaviour or welfare of the subject being tested, as this can bias experimental results and cause long-lasting effects on wild animals. Furthermore, minimizing impact on experimental animals is a key Refinement principle within the  3Rs framework which aims to ensure that animal welfare during experimentation is optimised. The term  non-invasive DNA sampling has been defined to indicate collection methods that do not require capture or cause disturbance to the animal, including any effects on behaviour or fitness. In practice this is not always the case, as the term  non-invasive is commonly used in the literature to describe studies where animals are restrained or subjected to aversive procedures. We reviewed the non-invasive DNA sampling literature for the past six years (380 papers published in 2013-2018) and uncovered the existence of a significant gap between the current use of this terminology (i.e.  non-invasive DNA sampling) and its original definition. We show that 58% of the reviewed papers did not comply with the original definition. We discuss the main experimental and ethical issues surrounding the potential confusion or misuse of the phrase  non-invasive DNA sampling in the current literature and provide potential solutions. In addition, we introduce the terms  non-disruptive and  minimally disruptive DNA sampling, to indicate methods that eliminate or minimise impacts not on the physical integrity\/structure of the animal, but on its behaviour, fitness and welfare, which in the literature reviewed corresponds to the situation for which an accurate term is clearly missing. Furthermore, we outline when these methods are appropriate to use.","funder":"NA","published":"10.24072\/pcjournal.98","server":"bioRxiv"},{"title":"A comprehensive genomics solution for HIV surveillance and clinical monitoring in a global health setting","authors":"Bonsall, D.; Golubchik, T.; de Cesare, M.; Limbada, M.; Kosloff, B.; MacIntyre-Cockett, G.; Hall, M.; Wymant, C.; Ansari, A.; Abeler-Dorner, L.; Schaap, A.; Brown, A.; Barnes, E.; Piwowar-Manning, E.; Wilson, E.; Emel, L.; Hayes, R.; Fidler, S.; Ayles, H.; Bowden, R.; Fraser, C.","author_corresponding":"David  Bonsall","author_corresponding_institution":"Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom","doi":"10.1101\/397083","date":"2018-08-21","version":"1","type":"new results","license":"cc_by_nc_nd","category":"genomics","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/397083.source.xml","abstract":"High-throughput viral genetic sequencing is needed to monitor the spread of drug resistance, direct optimal antiretroviral regimes, and to identify transmission dynamics in generalised HIV epidemics. Public health efforts to sequence HIV genomes at scale face three major technical challenges: (i) minimising assay cost and protocol complexity, (ii) maximising sensitivity, and (iii) recovering accurate and unbiased sequences of both the genome consensus and the within-host viral diversity. Here we present a novel, high-throughput, virus-enriched sequencing method and computational pipeline tailored specifically to HIV (veSEQ-HIV), which addresses all three technical challenges, and can be used directly on leftover blood drawn for routine CD4 testing. We demonstrate its performance on 1,620 plasma samples collected from consenting individuals attending 10 large urban clinics in Zambia, partners of HPTN 071 (PopART). We show that veSEQ-HIV consistently recovers complete HIV genomes from the majority of samples of different subtypes, and is also quantitative: the number of HIV reads per sample obtained by veSEQ-HIV estimates viral load without the need for additional testing. Both quantitativity and sensitivity were assessed on a subset of 126 samples with clinically measured viral loads, and with standardized quantification controls (VL 100 - 5,000,000 RNA copies\/ml). Complete HIV genomes were recovered from 93% (85\/91) of samples when viral load was over 1,000 copies per ml. The quantitative nature of the assay implies that variant frequencies estimated with veSEQ-HIV are representative of true variant frequencies in the sample. Detection of minority variants can be exploited for epidemiological analysis of transmission and drug resistance, and we show how the information contained in individual reads of a veSEQ-HIV sample can be used to detect linkage between multiple mutations associated with resistance to antiretroviral therapy. Less than 2% of reads obtained by veSEQ-HIV were identified as in silico contamination events using updates to the phyloscanner software (phyloscanner clean) that we show to be 95% sensitive and 99% specific at  decontaminating NGS data. The cost of the assay -- approximately 45 USD per sample -- compares favourably with existing VL and HIV genotyping tests, and provides the additional value of viral load quantification and inference of drug resistance with a single test. veSEQ-HIV is well suited to large public health efforts and is being applied to all [~]9000 samples collected for the HPTN 071-2 (PopART Phylogenetics) study.","funder":"NA","published":"NA","server":"bioRxiv"},{"title":"Increased rates of genomic mutation in a biofilm co-culture model of P. aeruginosa and S. aureus","authors":"Frapwell, C. J.; Howlin, R. P.; Soren, O.; McDonagh, B. T.; Duignan, C. M.; Allan, R. N.; Horswill, A. R.; Stoodley, P.; Hu, Y.; Coates, A. R.; Webb, J. S.","author_corresponding":"Jeremy S Webb","author_corresponding_institution":"Centre for Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK","doi":"10.1101\/387233","date":"2018-08-21","version":"1","type":"new results","license":"cc_no","category":"microbiology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/387233.source.xml","abstract":"Biofilms are major contributors to disease chronicity and are typically multi-species in nature. Pseudomonas aeruginosa and Staphylococcus aureus are leading causes of morbidity and mortality in a variety of chronic diseases but current in vitro dual-species biofilms models involving these pathogens are limited by short co-culture times (24 to 48 hours). Here, we describe the establishment of a stable (240 hour) co-culture biofilm model of P. aeruginosa and S. aureus that is reproducible and more representative of chronic disease.\\n\\nThe ability of two P. aeruginosa strains, (PAO1 and a cystic fibrosis isolate, PA21), to form co-culture biofilms with S. aureus was investigated. Co-culture was stable for longer periods using P. aeruginosa PA21 and S. aureus viability within the model improved in the presence of exogenous hemin. Biofilm co-culture was associated with increased tolerance of P. aeruginosa to tobramycin and increased susceptibility of S. aureus to tobramycin and a novel antimicrobial, HT61, previously shown to be more effective against non-dividing cultures of Staphylococcal spp. Biofilm growth was also associated with increased short-term mutation rates; 10-fold for P. aeruginosa and 500-fold for S. aureus.\\n\\nBy describing a reproducible 240 hour co-culture biofilm model of P. aeruginosa and S. aureus, we have shown that interspecies interactions between these organisms may influence short-term mutation rates and evolution, which could be of importance in understanding the adaptive processes that lead to the development of antimicrobial resistance.","funder":"NA","published":"NA","server":"bioRxiv"},{"title":"A Latent Allocation Model for the Analysis of Microbial Composition and Disease","authors":"Abe, K.; Hirayama, M.; Ohno, K.; Shimamura, T.","author_corresponding":"Teppei  Shimamura","author_corresponding_institution":"Division of Systems Biology, Nagoya University Graduate School of Medicine","doi":"10.1101\/396903","date":"2018-08-21","version":"1","type":"new results","license":"cc_by_nd","category":"bioinformatics","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/396903.source.xml","abstract":"BackgroundEstablishing the relationship between microbiota and specific disease is important but requires appropriate statistical methodology. A specialized feature of microbiome count data is the presence of a large number of zeros, which makes it difficult to analyze in case-control studies. Most existing approaches either add a small number called a pseudo-count or use probability models such as the multinomial and Dirichlet-multinomial distributions to explain the excess zero counts, which may produce unnecessary biases and impose a correlation structure taht is unsuitable for microbiome data.\\n\\nResultsThe purpose of this article is to develop a new probabilistic model, called BERMUDA (BERnoulli and MUltinomial Distribution-based latent Allocation), to address these problems. BERMUDA enables us to describe the differences in bacteria composition and a certain disease among samples. We also provide a simple and efficient learning procedure for the proposed model using an annealing EM algorithm.\\n\\nConclusionWe illustrate the performance of the proposed method both through both the simulation and real data analysis. BERMUDA is implemented with R and is available from GitHub (https:\/\/github.com\/abikoushi\/Bermuda).","funder":"NA","published":"10.1186\/s12859-018-2530-6","server":"bioRxiv"},{"title":"Expected differences in diversity and rarity between communities containing sexually versus asexually reproducing taxa","authors":"Herren, C.","author_corresponding":"Cristina  Herren","author_corresponding_institution":"Harvard University","doi":"10.1101\/397174","date":"2018-08-21","version":"1","type":"new results","license":"cc_by_nc","category":"ecology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/397174.source.xml","abstract":"Recent studies evaluating the community structures of microorganisms and macro-organisms have found greater diversity and rarity within micro-scale communities, compared to macro-scale communities. However, reproductive method has been a confounding factor in these comparisons; the microbes considered generally reproduce asexually, while the macro-organisms considered generally reproduce sexually. Sexual reproduction imposes the constraint of mate finding, which can have significant demographic consequences by depressing birth rates at low population sizes. Here, I examine theoretically how the effects of mate finding in sexual populations translate to the emergent community properties of diversity, rarity, and dominance. Using continuous-time Markov chain models, I compare communities with and without constraints of mate limitation. In mate-limited sexual populations, the decreased growth rates at low population densities translates to a much higher extinction rate. In communities consisting of sexually reproducing taxa, the increased extinction rate due to mate limitation decreases expected diversity. Furthermore, mate limitation has a disproportionately strong effect on taxa with low population density, leading to fewer rare taxa. These shifts in community structure mirror recent empirical studies of micro versus macro communities, indicating that reproductive method may contribute to observed differences in emergent properties between communities at these two scales.","funder":"NA","published":"NA","server":"bioRxiv"},{"title":"Cross-scale dynamics and the evolutionary emergence of infectious diseases","authors":"Schreiber, S. J.; Ke, R.; Loverdo, C.; Park, M.; Ahsan, P.; Lloyd-Smith, J. O.","author_corresponding":"Sebastian J. Schreiber","author_corresponding_institution":"University of California, Davis","doi":"10.1101\/066688","date":"2018-08-21","version":"2","type":"new results","license":"cc_no","category":"epidemiology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2018\/08\/21\/066688.source.xml","abstract":"AO_SCPLOWBSTRACTC_SCPLOWWhen emerging pathogens encounter new host species for which they are poorly adapted, they must evolve to escape extinction. Pathogens experience selection on traits at multiple scales, including replication rates within host individuals and transmissibility between hosts. We analyze a stochastic model linking pathogen growth and competition within individuals to transmission between individuals. Our analysis reveals a new factor, the cross-scale reproductive number of a mutant virion, that quantifies how quickly mutant strains increase in frequency when they initially appear in the infected host population. This cross-scale reproductive number combines with viral mutation rates, single-strain reproductive numbers, and transmission bottleneck width to determine the likelihood of evolutionary emergence, and whether evolution occurs swiftly or gradually within chains of transmission. We find that wider transmission bottlenecks facilitate emergence of pathogens with short-term infections, but hinder emergence of pathogens exhibiting cross-scale selective conflict and long-term infections. Our results provide a framework to advance the integration of laboratory, clinical and field data in the context of evolutionary theory, laying the foundation for a new generation of evidence-based risk assessment of emergence threats.","funder":"NA","published":"10.1093\/ve\/veaa105","server":"bioRxiv"}]}