1,119 research outputs found

    Using the Regular Chains Library to build cylindrical algebraic decompositions by projecting and lifting

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    Cylindrical algebraic decomposition (CAD) is an important tool, both for quantifier elimination over the reals and a range of other applications. Traditionally, a CAD is built through a process of projection and lifting to move the problem within Euclidean spaces of changing dimension. Recently, an alternative approach which first decomposes complex space using triangular decomposition before refining to real space has been introduced and implemented within the RegularChains Library of Maple. We here describe a freely available package ProjectionCAD which utilises the routines within the RegularChains Library to build CADs by projection and lifting. We detail how the projection and lifting algorithms were modified to allow this, discuss the motivation and survey the functionality of the package

    Genome analysis of Clostridium difficile PCR ribotype 014 lineage in Australian pigs and humans reveals a diverse genetic repertoire and signatures of long-range interspecies transmission

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    Clostridium difficile PCR ribotype (RT) 014 is well-established in both human and porcine populations in Australia, raising the possibility that C. difficile infection (CDI) may have a zoonotic or foodborne etiology. Here, whole genome sequencing and high-resolution core genome phylogenetics were performed on a contemporaneous collection of 40 Australian RT014 isolates of human and porcine origin. Phylogenies based on MLST (7 loci, STs 2, 13, and 49) and core orthologous genes (1260 loci) showed clustering of human and porcine strains indicative of very recent shared ancestry. Core genome single nucleotide variant (SNV) analysis found 42% of human strains showed a clonal relationship (separated by ≀2 SNVs in their core genome) with one or more porcine strains, consistent with recent inter-host transmission. Clones were spread over a vast geographic area with 50% of the human cases occurring without recent healthcare exposure. These findings suggest a persistent community reservoir with long-range dissemination, potentially due to agricultural recycling of piggery effluent. We also provide the first pan-genome analysis for this lineage, characterizing its resistome, prophage content, and in silico virulence potential. The RT014 is defined by a large “open” pan-genome (7587 genes) comprising a core genome of 2296 genes (30.3% of the total gene repertoire) and an accessory genome of 5291 genes. Antimicrobial resistance genotypes and phenotypes varied across host populations and ST lineages and were characterized by resistance to tetracycline [tetM, tetA(P), tetB(P) and tetW], clindamycin/erythromycin (ermB), and aminoglycosides (aph3-III-Sat4A-ant6-Ia). Resistance was mediated by clinically important mobile genetic elements, most notably Tn6194 (harboring ermB) and a novel variant of Tn5397 (harboring tetM). Numerous clinically important prophages (Siphoviridae and Myoviridae) were identified as well as an uncommon accessory gene regulator locus (agr3). Conservation in the pathogenicity locus and S-layer correlated with ST affiliation, further extending the concept of clonal C. difficile lineages. This study provides novel insights on the genetic variability and strain relatedness of C. difficile RT014, a lineage of emerging One Health importance. Ongoing molecular and genomic surveillance of strains in humans, animals, food, and the environment is imperative to identify opportunities to reduce the overall CDI burden

    Regulation of desmocollin transcription in mouse preimplantation embryos

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    The molecular mechanisms regulating the biogenesis of the first desmosomes to form during mouse embryogenesis have been studied. A sensitive modification of a reverse transcriptase-cDNA amplification procedure has been used to detect transcripts of the desmosomal adhesive cadherin, desmocollin. Sequencing of cDNA amplification products confirmed that two splice variants, a and b, of the DSC2 gene are transcribed coordinately. Transcripts were identified in unfertilized eggs and cumulus cells and in cleavage stages up to the early 8-cell stage, were never detected in compact 8-cell embryos, but were evident again either from the 16-cell morula or very early blastocyst (approx 32-cells) stages onwards. These two phases of transcript detection indicate DSC2 is encoded by maternal and embryonic genomes. Previously, we have shown that desmocollin protein synthesis is undetectable in eggs and cleavage stages but initiates at the early blastocyst stage when desmocollin localises at, and appears to regulate assembly of, nascent desmosomes that form in the trophectoderm but not in the inner cell mass (Fleming, T. P., Garrod, D. R. and Elsmore, A. J. (1991), Development 112, 527–539). Maternal DSC2 mRNA is therefore not translated and presumably is inherited by blastomeres before complete degradation. Our results suggest, however, that initiation of embryonic DSC2 transcription regulates desmocollin protein expression and thereby desmosome formation. Moreover, data from blastocyst single cell analyses suggest that embryonic DSC2 transcription is specific to the trophectoderm lineage. Inhibition of E-cadherin-mediated cell-cell adhesion did not influence the timing of DSC2 embryonic transcription and protein expression. However, isolation and culture of inner cell masses induced an increase in the amount of DSC2 mRNA and protein detected. Taken together, these results suggest that the presence of a contact-free cell surface activates DSC2 transcription in the mouse early embryo. <br/

    Clostridium difficile ribotype 017 – characterization, evolution and epidemiology of the dominant strain in Asia

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    Clostridium difficile ribotype (RT) 017 is an important toxigenic C. difficile RT which, due to a deletion in the repetitive region of the tcdA gene, only produces functional toxin B. Strains belonging to this RT were initially dismissed as nonpathogenic and circulated largely undetected for almost two decades until they rose to prominence following a series of outbreaks in the early 2000s. Despite lacking a functional toxin A, C. difficile RT 017 strains have been shown subsequently to be capable of causing disease as severe as that caused by strains producing both toxins A and B. While C. difficile RT 017 strains can be found in almost every continent today, epidemiological studies suggest that the RT is endemic in Asia and that the global spread of this MLST clade 4 lineage member is a relatively recent event. C. difficile RT 017 transmission appears to be mostly from human to human with only a handful of reports of isolations from animals. An important feature of C. difficile RT 017 strains is their resistance to several antimicrobials and this has been documented as a possible factor driving multiple outbreaks in different parts of the world. This review summarizes what is currently known regarding the emergence and evolution of strains belonging to C. difficile RT 017 as well as features that have allowed it to become an RT of global importance

    Global evolutionary dynamics and resistome analysis of Clostridioides difficile ribotype 017

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    Clostridioides difficile PCR ribotype (RT) 017 ranks among the most successful strains of C. difficile in the world. In the past three decades, it has caused outbreaks on four continents, more than other ‘epidemic’ strains, but our understanding of the genomic epidemiology underpinning the spread of C. difficile RT 017 is limited. Here, we performed high-resolution phylogenomic and Bayesian evolutionary analyses on an updated and more representative dataset of 282 non-clonal C. difficile RT 017 isolates collected worldwide between 1981 and 2019. These analyses place an estimated time of global dissemination between 1953 and 1983 and identified the acquisition of the ermB-positive transposon Tn6194 as a key factor behind global emergence. This coincided with the introduction of clindamycin, a key inciter of C. difficile infection, into clinical practice in the 1960s. Based on the genomic data alone, the origin of C. difficile RT 017 could not be determined; however, geographical data and records of population movement suggest that C. difficile RT 017 had been moving between Asia and Europe since the Middle Ages and was later transported to North America around 1860 (95 % confidence interval: 1622–1954). A focused epidemiological study of 45 clinical C. difficile RT 017 genomes from a cluster in a tertiary hospital in Thailand revealed that the population consisted of two groups of multidrug-resistant (MDR) C. difficile RT 017 and a group of early, non-MDR C. difficile RT 017. The significant genomic diversity within each MDR group suggests that although they were all isolated from hospitalized patients, there was probably a reservoir of C. difficile RT 017 in the community that contributed to the spread of this pathogen

    Rendezvous of Heterogeneous Mobile Agents in Edge-weighted Networks

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    We introduce a variant of the deterministic rendezvous problem for a pair of heterogeneous agents operating in an undirected graph, which differ in the time they require to traverse particular edges of the graph. Each agent knows the complete topology of the graph and the initial positions of both agents. The agent also knows its own traversal times for all of the edges of the graph, but is unaware of the corresponding traversal times for the other agent. The goal of the agents is to meet on an edge or a node of the graph. In this scenario, we study the time required by the agents to meet, compared to the meeting time TOPTT_{OPT} in the offline scenario in which the agents have complete knowledge about each others speed characteristics. When no additional assumptions are made, we show that rendezvous in our model can be achieved after time O(nTOPT)O(n T_{OPT}) in a nn-node graph, and that such time is essentially in some cases the best possible. However, we prove that the rendezvous time can be reduced to Θ(TOPT)\Theta (T_{OPT}) when the agents are allowed to exchange Θ(n)\Theta(n) bits of information at the start of the rendezvous process. We then show that under some natural assumption about the traversal times of edges, the hardness of the heterogeneous rendezvous problem can be substantially decreased, both in terms of time required for rendezvous without communication, and the communication complexity of achieving rendezvous in time Θ(TOPT)\Theta (T_{OPT})

    Azimuthal asymmetries at HERA: theoretical aspects

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    We comment on theoretical aspects of the measurement of azimuthal asymmetries in semi-inclusive charged particle production, made recently by the ZEUS Collaboration at HERA. By taking the ratio of the two measured asymmetries, we find good agreement between the perturbative QCD prediction and the experimental data. To separate the perturbative and nonperturbative contributions to the asymmetries, we suggest that the azimuthal asymmetries of the transverse energy flow be measured as a function of a variable qTq_T related to the pseudorapidity of the energy flow.Comment: Final version: 11 pages, 2 figure

    Nutrient (C, N and P) enrichment induces significant changes in the soil metabolite profile and microbial carbon partitioning

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    The cycling of soil organic matter (SOM) and carbon (C) within the soil is governed by the presence of key macronutrients, particularly nitrogen (N) and phosphorus (P). The relative ratio of these nutrients has a direct effect on the potential rates of microbial growth and nutrient processing in soil and thus is fundamental to ecosystem functioning. However, the effect of changing soil nutrient stoichiometry on the small organic molecule (i.e., metabolite) composition and cycling by the microbial community remains poorly understood. Here, we aimed to disentangle the effect of stoichiometrically balanced nutrient addition on the soil metabolomic profile and apparent microbial carbon use efficiency (CUE) by adding a labile C source (glucose) in combination with N and/or P. After incorporation of the added glucose into the microbial biomass (48 h), metabolite profiling was undertaken by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). 494 metabolites were identified across all treatments mainly consisting of lipids (n = 199), amino acids (n = 118) and carbohydrates (n = 43), >97% of which showed significant changes in concentration between at least one treatment. Overall, glucose-C addition generally increased the synthesis of other carbohydrates in soil, while addition of C and N together increased peptide synthesis, indicative of protein formation and turnover. The combination of C and P significantly increased the number of fatty acids synthesised. There was no significant change in the PLFA-derived microbial community structure or microbial biomass following C, N and P addition. Further, N addition led to an increase in glucose-C partitioning into anabolic processes (i.e., increased CUE), suggesting the microbial community was N, but not P limited. Based on the metabolomic profiles observed here, we conclude that inorganic nutrient enrichment causes substantial shifts in both primary and secondary metabolism within the microbial community, leading to changes in resource flow and thus soil functioning, however, the microbial community illustrated significant metabolic flexibility
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