Multi-country outbreaks of foodborne bacterial disease present challenges in their detection, tracking, and notification. As food is increasingly distributed across borders, such outbreaks are ...becoming more common. This increases the need for high-resolution, accessible, and replicable isolate typing schemes. Here we evaluate a core genome multilocus typing (cgMLST) scheme for the high-resolution reproducible typing of Salmonella enterica (S. enterica) isolates, by its application to a large European outbreak of S. enterica serovar Enteritidis. This outbreak had been extensively characterised using single nucleotide polymorphism (SNP)-based approaches. The cgMLST analysis was congruent with the original SNP-based analysis, the epidemiological data, and whole genome MLST (wgMLST) analysis. Combination of the cgMLST and epidemiological data confirmed that the genetic diversity among the isolates predated the outbreak, and was likely present at the infection source. There was consequently no link between country of isolation and genetic diversity, but the cgMLST clusters were congruent with date of isolation. Furthermore, comparison with publicly available Enteritidis isolate data demonstrated that the cgMLST scheme presented is highly scalable, enabling outbreaks to be contextualised within the Salmonella genus. The cgMLST scheme is therefore shown to be a standardised and scalable typing method, which allows Salmonella outbreaks to be analysed and compared across laboratories and jurisdictions.
•cgMLST is proposed as a universal typing scheme for Salmonella.•cgMLST is congruent with SNP analyses and easier to implement across laboratories.•Genomic data are consistent with the epidemiology of the outbreak.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Influenza virus exposures in childhood can establish long-lived memory B cell responses that can be recalled later in life. Here, we complete a large serological survey to elucidate the specificity ...of antibodies against contemporary H3N2 viruses in differently aged individuals who were likely primed with different H3N2 strains in childhood. We find that most humans who were first infected in childhood with H3N2 viral strains from the 1960s and 1970s possess non-neutralizing antibodies against contemporary 3c2.A H3N2 viruses. We find that 3c2.A H3N2 virus infections boost non-neutralizing H3N2 antibodies in middle-aged individuals, potentially leaving many of them in a perpetual state of 3c2.A H3N2 viral susceptibility.
We investigated the effect of stair climbing exercise “snacks” on peak oxygen uptake. Sedentary young adults were randomly assigned to perform 3 bouts/day of vigorously ascending a 3-flight stairwell ...(60 steps), separated by 1–4 h of recovery, 3 days/week for 6 weeks, or a nontraining control group (n = 12 each). Peak oxygen uptake was higher in the climbers after the intervention (P = 0.003), suggesting that stair climbing “snacks” are effective in improving cardiorespiratory fitness, although the absolute increase was modest.
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DOBA, FSPLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To investigate the ability of alkaline earth metal ions to tune ion-mediated DNA adsorption, hydrated Mg2+, Ca2+, Sr2+, and Ba2+ ions bound to a carboxylate anion, phosphate anion, and guanine ...nucleobase were modeled using density functional theory (DFT) and a combined explicit and continuum solvent model. The large first solvation shell of Ba2+ requires a larger solute cavity defined by a solvent-accessible surface, which is used to model all hydrated ions. Alkaline earth metal ions bind indirectly or directly to each binding site. DFT binding energies decrease with increasing ion size, which is likely due to ion size and hydration structure, rather than quantum effects such as charge transfer. However, charge transfer explains weaker ion binding to guanine compared to phosphate or carboxylate. Overall, carboxylate and phosphate anions are expected to compete equally for hydrated Mg2+, Ca2+, Sr2+, and Ba2+ ions and larger alkaline earth metal ions may induce weaker ion-mediated adsorption. The ion size and hydration structure of alkaline earth metal ions may effectively tune ion-mediated adsorption processes, such as DNA adsorption to functionalized surfaces.
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IJS, KILJ, NUK, PNG, UL, UM
White dwarfs represent the final state of evolution for most stars
. Certain classes of white dwarfs pulsate
, leading to observable brightness variations, and analysis of these variations with ...theoretical stellar models probes their internal structure. Modelling of these pulsating stars provides stringent tests of white dwarf models and a detailed picture of the outcome of the late stages of stellar evolution
. However, the high-energy-density states that exist in white dwarfs are extremely difficult to reach and to measure in the laboratory, so theoretical predictions are largely untested at these conditions. Here we report measurements of the relationship between pressure and density along the principal shock Hugoniot (equations describing the state of the sample material before and after the passage of the shock derived from conservation laws) of hydrocarbon to within five per cent. The observed maximum compressibility is consistent with theoretical models that include detailed electronic structure. This is relevant for the equation of state of matter at pressures ranging from 100 million to 450 million atmospheres, where the understanding of white dwarf physics is sensitive to the equation of state and where models differ considerably. The measurements test these equation-of-state relations that are used in the modelling of white dwarfs and inertial confinement fusion experiments
, and we predict an increase in compressibility due to ionization of the inner-core orbitals of carbon. We also find that a detailed treatment of the electronic structure and the electron degeneracy pressure is required to capture the measured shape of the pressure-density evolution for hydrocarbon before peak compression. Our results illuminate the equation of state of the white dwarf envelope (the region surrounding the stellar core that contains partially ionized and partially degenerate non-ideal plasmas), which is a weak link in the constitutive physics informing the structure and evolution of white dwarf stars
.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Species and subspecies within the Salmonella genus have been defined for public health purposes by biochemical properties; however, reference laboratories have increasingly adopted sequence-based, ...and especially whole genome sequence (WGS), methods for surveillance and routine identification. This leads to potential disparities in subspecies definitions, routine typing, and the ability to detect novel subspecies. A large-scale analysis of WGS data from the routine sequencing of clinical isolates was employed to define and characterise Salmonella subspecies population structure, demonstrating that the Salmonella species and subspecies were genetically distinct, including those previously identified through phylogenetic approaches, namely: S. enterica subspecies londinensis (VII), subspecies brasiliensis (VIII), subspecies hibernicus (IX) and subspecies essexiensis (X). The analysis also identified an additional novel subspecies, reptilium (XI). Further, these analyses indicated that S. enterica subspecies arizonae (IIIa) isolates were divergent from the other S. enterica subspecies, which clustered together and, on the basis of ANI analysis, subspecies IIIa was sufficiently distinct to be classified as a separate species, S. arizonae. Multiple phylogenetic and statistical approaches generated congruent results, suggesting that the proposed species and subspecies structure was sufficiently biologically robust for routine application. Biochemical analyses demonstrated that not all subspecies were distinguishable by these means and that biochemical approaches did not capture the genomic diversity of the genus. We recommend the adoption of standardised genomic definitions of species and subspecies and a genome sequence-based approach to routine typing for the identification and definition of novel subspecies.
•A large-scale analysis of genomic data demonstrate Salmonella species and subspecies are genetically distinct.•Biochemical analysis does not capture the genomic diversity of the Salmonella genus but routine species and subspecies identification can be achieved with rMLST•Average Nucleotide Identify (ANI) with a 95% criteria was suitable to distinguish species and 98% to distinguish subspecies.•Five novel S. enteric subspecies (VII-XI) type strains are defined.•Reclassification of S. arizonae as a separate species is recommended.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The identity of metal ions surrounding DNA is key to its biological function and materials applications. In this work, we compare atomistic molecular dynamics simulations of double strand DNA (dsDNA) ...with four alkaline earth metal ions (Mg
2+
, Ca
2+
, Sr
2+
, and Ba
2+
) to elucidate the physical interactions that govern DNA-ion binding. Simulations accurately model the ion-phosphate distance of Mg
2+
and reproduce ion counting experiments for Ca
2+
, Sr
2+
, and Ba
2+
. Our analysis shows that alkaline earth metal ions prefer to bind at the phosphate backbone compared to the major groove and negligible binding occurs in the minor groove. Larger alkaline earth metal ions with variable first solvation shells (Ca
2+
, Sr
2+
, and Ba
2+
) show both direct and indirect binding, where indirect binding increases with ion size. Mg
2+
does not fit this trend because the strength of its first solvation shell predicts indirect binding only. Ions bound to the phosphate backbone form fewer contacts per ion compared to the major groove. Within the major groove, metal ions preferentially bind to guanine-cystosine base pairs and form simultaneous contacts with the N7 and O6 atoms of guanine. Overall, we find that the interplay among ion size, DNA-ion interaction, and the size and flexibility of the first solvation shell are key to predicting how alkaline earth metal ions interact with DNA.
Classical molecular dynamics simulations reveal size-dependent trends of alkaline earth metal ions binding to DNA are due to ion size and hydration behavior.
High-energy-density physics is the field of physics concerned with studying matter at extremely high temperatures and densities. Such conditions produce highly nonlinear plasmas, in which several ...phenomena that can normally be treated independently of one another become strongly coupled. The study of these plasmas is important for our understanding of astrophysics, nuclear fusion and fundamental physics-however, the nonlinearities and strong couplings present in these extreme physical systems makes them very difficult to understand theoretically or to optimize experimentally. Here we argue that machine learning models and data-driven methods are in the process of reshaping our exploration of these extreme systems that have hitherto proved far too nonlinear for human researchers. From a fundamental perspective, our understanding can be improved by the way in which machine learning models can rapidly discover complex interactions in large datasets. From a practical point of view, the newest generation of extreme physics facilities can perform experiments multiple times a second (as opposed to approximately daily), thus moving away from human-based control towards automatic control based on real-time interpretation of diagnostic data and updates of the physics model. To make the most of these emerging opportunities, we suggest proposals for the community in terms of research design, training, best practice and support for synthetic diagnostics and data analysis.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
This paper describes how the steady state atomic kinetics approximation can underestimate the electron temperature determined from K-shell lines in ps-time-scale transient plasmas. In particular, we ...model the temperature determination of solid FeS targets used in opacity experiments at the Orion laser facility from the ratio of sulfur He-α to Ly-α lines. Such experiments use short-pulse lasers to heat a thin microdot of FeS buried in a plastic target to temperatures of more than 1 keV and densities of approximately 1–2 g/cm3. Using atomic kinetics calculations based on a temperature history from a radiation hydrodynamic simulation of the target evolution, the peak temperature inferred from the sulfur line ratios is 1.29 keV at 3.1 ps as compared with the input peak temperature of 1.41 keV at 2.0 ps. There is a time lag of 1.2 ps at the peak, and an overall 0.5 ps time lag in the temporal history of the temperature as the plasma cools over the next 10 ps.
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