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Background: The development of particokinetic models describing the delivery of insoluble or poorly soluble nanoparticles to cells in liquid cell culture systems has improved the basis for dose-response analysis, hazard ranking from high-throughput systems, and now allows for translation of exposures across in vitro and in vivo test systems. Complimentary particokinetic models that address processes controlling delivery of both particles and released ions to cells, and the influence of particle size changes from dissolution on particle delivery for cell-culture systems would help advance our understanding of the role of particles and ion dosimetry on cellular toxicology. We developed ISD3, an extension of our previously published model for insoluble particles, by deriving a specific formulation of the Population Balance Equation for soluble particles. Results: ISD3 describes the time, concentration and particle size dependent dissolution of particles, their delivery to cells, and the delivery and uptake of ions to cells in in vitro liquid test systems. We applied the model to calculate the particle and ion dosimetry of nanosilver and silver ions in vitro after calibration of two empirical models, one for particle dissolution and one for ion uptake. Total media ion concentration, particle concentration and total cell-associated silver time-courses were well described by the model, across 2 concentrations of 20 and 110 nm particles. ISD3 was calibrated to dissolution data for 20 nm particles as a function of serum protein concentration, but successfully described the media and cell dosimetry time-course for both particles at all concentrations and time points. We also report the finding that protein content in media affects the initial rate of dissolution and the resulting near-steady state ion concentration in solution for the systems we have studied. Conclusions: By combining experiments and modeling, we were able to quantify the influence of proteins on silver particle solubility, determine the relative amounts of silver ions and particles in exposed cells, and demonstrate the influence of particle size changes resulting from dissolution on particle delivery to cells in culture. ISD3 is modular and can be adapted to new applications by replacing descriptions of dissolution, sedimentation and boundary conditions with those appropriate for particles other than silver. [ABSTRACT FROM AUTHOR]

Background: Graphene, a monolayer of carbon, is an engineered nanomaterial (ENM) with physical and chemical properties that may offer application advantages over other carbonaceous ENMs, such as carbon nanotubes (CNT). The goal of this study was to comparatively assess pulmonary and systemic toxicity of graphite nanoplates, a member of the graphene-based nanomaterial family, with respect to nanoplate size. Methods: Three sizes of graphite nanoplates [20 μm lateral (Gr20), 5 μm lateral (Gr5), and <2 μm lateral (Gr1)] ranging from 8-25 nm in thickness were characterized for difference in surface area, structure,, zeta potential, and agglomeration in dispersion medium, the vehicle for in vivo studies. Mice were exposed by pharyngeal aspiration to these 3 sizes of graphite nanoplates at doses of 4 or 40 μg/mouse, or to carbon black (CB) as a carbonaceous control material. At 4 h, 1 day, 7 days, 1 month, and 2 months post-exposure, bronchoalveolar lavage was performed to collect fluid and cells for analysis of lung injury and inflammation. Particle clearance, histopathology and gene expression in lung tissue were evaluated. In addition, protein levels and gene expression were measured in blood, heart, aorta and liver to assess systemic responses. Results: All Gr samples were found to be similarly composed of two graphite structures and agglomerated to varying degrees in DM in proportion to the lateral dimension. Surface area for Gr1 was approximately 7-fold greater than Gr5 and Gr20, but was less reactive reactive per m2. At the low dose, none of the Gr materials induced toxicity. At the high dose, Gr20 and Gr5 exposure increased indices of lung inflammation and injury in lavage fluid and tissue gene expression to a greater degree and duration than Gr1 and CB. Gr5 and Gr20 showed no or minimal lung epithelial hypertrophy and hyperplasia, and no development of fibrosis by 2 months post-exposure. In addition, the aorta and liver inflammatory and acute phase genes were transiently elevated in Gr5 and Gr20, relative to Gr1. Conclusions: Pulmonary and systemic toxicity of graphite nanoplates may be dependent on lateral size and/or surface reactivity, with the graphite nanoplates > 5 μm laterally inducing greater toxicity which peaked at the early time points post-exposure relative to the 1-2 μm graphite nanoplate. [ABSTRACT FROM AUTHOR]

Background: Salmonella enterica subsp. enterica serovar Napoli (S. Napoli) is among the top serovars causing human infections in Italy, although it is relatively uncommon in other European countries; it is mainly isolated from humans and the environment, but neither the reservoir nor its route of infection are clearly defined. This serovar is characterized by high genomic diversity, and molecular evidences revealed important similarities with typhoidal serovars. Results: 179 S. Napoli genomes as well as 239 genomes of typhoidal and non-typhoidal serovars were analyzed in a comparative genomic study. Phylogenetic analysis and draft genome characterization in terms of Multi Locus Sequence Typing (MLST), plasmid replicons, Salmonella Pathogenicity Islands (SPIs), antimicrobial resistance genes (ARGs), phages, biocide and metal-tolerance genes confirm the high genetic variability of S. Napoli, also revealing a within-serovar phylogenetic structure more complex than previously known. Our work also confirms genomic similarity of S. Napoli to typhoidal serovars (S. Typhi and S. Paratyphi A), with S. Napoli samples clustering primarily according to ST, each being characterized by specific genomic traits. Moreover, two major subclades of S. Napoli can be clearly identified, with ST-474 being biphyletic. All STs span among isolation sources and years of isolation, highlighting the challenge this serovar poses to define its epidemiology and evolution. Altogether, S. Napoli strains carry less SPIs and less ARGs than other non-typhoidal serovars and seldom acquire plasmids. However, we here report the second case of an extended-spectrum β–lactamases (ESBLs) producing S. Napoli strain and the first cases of multidrug resistant (MDR) S. Napoli strains, all isolated from humans. Conclusions: Our results provide evidence of genomic plasticity of S. Napoli, highlighting genomic similarity with typhoidal serovars and genomic features typical of non-typhoidal serovars, supporting the possibility of survival in different niches, both enteric and non-enteric. Presence of horizontally acquired ARGs and MDR profiles rises concerns regarding possible selective pressure exerted by human environment on this pathogen. [ABSTRACT FROM AUTHOR]

Background: New sequencing technologies have lowered financial barriers to whole genome sequencing, but resulting assemblies are often fragmented and far from 'finished'. Updating multi-scaffold drafts to chromosome-level status can be achieved through experimental mapping or re-sequencing efforts. Avoiding the costs associated with such approaches, comparative genomic analysis of gene order conservation (synteny) to predict scaffold neighbours (adjacencies) offers a potentially useful complementary method for improving draft assemblies. Results: We evaluated and employed 3 gene synteny-based methods applied to 21 Anopheles mosquito assemblies to produce consensus sets of scaffold adjacencies. For subsets of the assemblies, we integrated these with additional supporting data to confirm and complement the synteny-based adjacencies: 6 with physical mapping data that anchor scaffolds to chromosome locations, 13 with paired-end RNA sequencing (RNAseq) data, and 3 with new assemblies based on re-scaffolding or long-read data. Our combined analyses produced 20 new superscaffolded assemblies with improved contiguities: 7 for which assignments of non-anchored scaffolds to chromosome arms span more than 75% of the assemblies, and a further 7 with chromosome anchoring including an 88% anchored Anopheles arabiensis assembly and, respectively, 73% and 84% anchored assemblies with comprehensively updated cytogenetic photomaps for Anopheles funestus and Anopheles stephensi. Conclusions: Experimental data from probe mapping, RNAseq, or long-read technologies, where available, all contribute to successful upgrading of draft assemblies. Our evaluations show that gene synteny-based computational methods represent a valuable alternative or complementary approach. Our improved Anopheles reference assemblies highlight the utility of applying comparative genomics approaches to improve community genomic resources. [ABSTRACT FROM AUTHOR]

Earlier we suggested a new hypothesis of the possible evolutionary role of hereditary tumors (Kozlov, Evolution by tumor Neofunctionalization, 2014), and described a new class of genes – tumor specifically expressed, evolutionarily novel (TSEEN) genes - that are predicted by this hypothesis (Kozlov, Infect Agents Cancer 11:34, 2016). In this paper we studied evolutionarily novel genes expressed in fish tumors after regression, as a model of evolving organs. As evolutionarily novel genes may not yet have organismal functions, we studied the acquisition of new gene functions by comparing fish evolutionarily novel genes with their human orthologs. We found that many genes involved in development of progressive traits in humans (lung, mammary gland, placenta, ventricular septum, etc.) originated in fish and are expressed in fish tumors and tumors after regression. These findings support a possible evolutionary role of hereditary tumors, and in particular the hypothesis of evolution by tumor neofunctionalization. Research highlights: Earlier we described a new class of genes that are tumor-specifically expressed and evolutionarily novel (TSEEN). As the functions of TSEEN genes are often uncertain, we decided to study TSEEN genes of fishes so that we could trace the appearance of their new functions in higher vertebrates. We found that many human genes which are involved in development of progressive traits (placenta development, mammary gland and lung development etc.,) originated in fishes and are expressed in fish tumors. [ABSTRACT FROM AUTHOR]

Background: Obligate sulfur oxidizing chemolithoauthotrophic strains of Hydrogenovibrio crunogenus have been isolated from multiple hydrothermal vent associated habitats. However, a hydrogenase gene cluster (encoding the hydrogen converting enzyme and its maturation/assembly machinery) detected on the first sequenced H. crunogenus strain (XCL-2) suggested that hydrogen conversion may also play a role in this organism. Yet, numerous experiments have underlined XCL-2's inability to consume hydrogen under the tested conditions. A recent study showed that the closely related strain SP-41 contains a homolog of the XCL-2 hydrogenase (a group 1b [NiFe]-hydrogenase), but that it can indeed use hydrogen. Hence, the question remained unresolved, why SP-41 is capable of using hydrogen, while XCL-2 is not. Results: Here, we present the genome sequence of the SP-41 strain and compare it to that of the XCL-2 strain. We show that the chromosome of SP-41 codes for a further hydrogenase gene cluster, including two additional hydrogenases: the first appears to be a group 1d periplasmic membrane-anchored hydrogenase, and the second a group 2b sensory hydrogenase. The region where these genes are located was likely acquired horizontally and exhibits similarity to other Hydrogenovibrio species (H. thermophilus MA2-6 and H. marinus MH-110 T) and other hydrogen oxidizing Proteobacteria (Cupriavidus necator H16 and Ghiorsea bivora TAG-1 T). The genomes of XCL-2 and SP-41 show a strong conservation in gene order. However, several short genomic regions are not contained in the genome of the other strain. These exclusive regions are often associated with signs of DNA mobility, such as genes coding for transposases. They code for transport systems and/or extend the metabolic potential of the strains. Conclusions: Our results suggest that horizontal gene transfer plays an important role in shaping the genomes of these strains, as a likely mechanism for habitat adaptation, including, but not limited to the transfer of the hydrogen conversion ability. [ABSTRACT FROM AUTHOR]