Origin of modern syphilis and emergence of a pandemic Treponema pallidum cluster

The abrupt onslaught of the syphilis pandemic that started in the late fifteenth century established this devastating infectious disease as one of the most feared in human history. Surprisingly, despite the availability of effective antibiotic treatment since the mid-twentieth century, this bacterial infection, which is caused by Treponema pallidum subsp. pallidum (TPA), has been re-emerging globally in the last few decades with an estimated 10.6 million cases in 2008. Although resistance to penicillin has not yet been identified, an increasing number of strains fail to respond to the secondline antibiotic azithromycin. Little is known about the genetic patterns in current infections or the evolutionary origins of the disease due to the low quantities of treponemal DNA in clinical samples and difficulties in cultivating the pathogen. Here, we used DNA capture and whole-genome sequencing to successfully interrogate genome-wide variation from syphilis patient specimens, combined with laboratory samples of TPA and two other subspecies. Phylogenetic comparisons based on the sequenced genomes indicate that the TPA strains examined share a common ancestor after the fifteenth century, within the early modern era. Moreover, most contemporary strains are azithromycin-resistant and are members of a globally dominant cluster, named here as SS14-Ω. The cluster diversified from a common ancestor in the mid-twentieth century subsequent to the discovery of antibiotics. Its recent phylogenetic divergence and global presence point to the emergence of a pandemic strain cluster

Advancing the understanding of treponemal disease in the past and present

Syphilis was perceived to be a new disease in Europe in the late 15th century, igniting a debate about its origin that continues today in anthropological, historical, and medical circles. We move beyond this age-old debate using an interdisciplinary approach that tackles broader questions to advance the understanding of treponemal infection (syphilis, yaws, bejel, and pinta). How did the causative organism(s) and humans co-evolve? How did the related diseases caused by Treponema pallidum emerge in different parts of the world and affect people across both time and space? How are T. pallidum subspecies related to the treponeme causing pinta? The current state of scholarship in specific areas is reviewed with recommendations made to stimulate future work. Understanding treponemal biology, genetic relationships, epidemiology, and clinical manifestations is crucial for vaccine development today and for investigating the distribution of infection in both modern and past populations. Paleopathologists must improve diagnostic criteria and use a standard approach for recording skeletal lesions on archaeological human remains. Adequate contextualization of cultural and environmental conditions is necessary, including site dating and justification for any corrections made for marine or freshwater reservoir effects. Biogeochemical analyses may assess aquatic contributions to diet, physiological changes arising from treponemal disease and its treatments (e.g., mercury), or residential mobility of those affected. Shifting the focus from point of origin to investigating who is affected (e.g., by age/sex or socioeconomic status) and disease distribution (e.g., coastal/ inland, rural/urban) will advance our understanding of the treponemal disease and its impact on people through time

Combining isotopic signatures of n(87Sr)/n(86Sr) and light stable elements (C, N, O, S) with multi-elemental profiling for the authentication of provenance of European cereal samples

The aim of this work (from the FP6 project TRACE) was to develop methods based on the use of geochemical markers for the authentication of the geographical origin of cereal samples in Europe (cf. EC regulations 2081/92 and 1898/06). For the first time, the potential usefulness of combining n(87Sr)/n(86Sr) and δ13C, δ15N, δ18O and δ34S isotopic signatures, alone or with key element concentrations ([Na], [K], [Ca], [Cu] and [Rb], progressively identified out of 31 sets of results), was investigated through multiple step multivariate statistics for more than 500 cereal samples collected over 2 years from 17 sampling sites across Europe representing an extensive range of geographical and environmental characteristics. From the classification categories compared (north/south; proximity to the Atlantic Ocean/to the Mediterranean Sea/to else; bed rock geologies) the first two were the most efficient (particularly with the ten variables selected together). In some instances element concentrations made a greater impact than the isotopic tracers. Validation of models included external prediction tests on 20% of the data randomly selected and, rarely done, a study on the robustness of these multivariate data treatments to uncertainties on measurement results. With the models tested it was possible to individualise 15 of the sampling sites

Neutron capture studies of

Gamma-ray transitions following neutron capture in 206Pb have been studied at the cold neutron beam facility of the Budapest Neutron Centre using a metallic sample enriched in 206Pb and a natural lead nitrate powder pellet. The measurements were performed using a coaxial HPGe detector with Compton suppression. The observed $\gamma$ -rays have been incorporated into a decay scheme for neutron capture in 206Pb . Partial capture cross sections for 206Pb(n,$\gamma$) at thermal energy have been derived relative to the cross section for the 1884keV transition after neutron capture in 14N . From the average crossing sum a total thermal neutron capture cross section of $29^{+2}_{-1}$ mb was derived for the 206Pb(n,$\gamma$) reaction. The thermal neutron capture cross section for 206Pb has been compared with contributions due to both direct capture and distant unbound s-wave resonances. From the same measurements a thermal neutron-induced capture cross section of $(649 \pm 14)$ mb was determined for the 207Pb(n,$\gamma$) reaction

Flow injection analysis as a tool for enhancing oceanographic nutrient measurements: A review

Macronutrient elements (C, N and P) and micronutrient elements (Fe, Co, Cu, Zn and Mn) are widely measured in their various physico-chemical forms in open ocean, shelf sea, coastal and estuarine waters. These measurements help to elucidate the biogeochemical cycling of these elements in marine waters and highlight the ecological and socio-economic importance of the oceans. Due to the dynamic nature of marine waters in terms of chemical, biological and physical processes, it is advantageous to make these measurements in situ and in this regard flow injection analysis (FIA) provides a suitable shipboard platform. This review, therefore, discusses the role of FIA in the determination of macro-and micro-nutrient elements, with an emphasis on manifold design and detection strategies for the reliable shipboard determination of specific nutrient species. The application of various FIA manifolds to oceanographic nutrient determinations is discussed, with an emphasis on sensitivity, selectivity, high throughput analysis and suitability for underway analysis and depth profiles. Strategies for enhancing sensitivity and minimizing matrix effects, e.g. refractive index (schlieren) effects and the important role of uncertainty budgets in underpinning method validation and data quality are discussed in some detail

Mass discrimination during MC-ICPMS isotopic ratio measurements: investigation by means of synthetic isotopic mixtures (IRMM-007 series) and application to the calibration of natural-like zinc materials (including IRMM-3702 and IRMM-651)

Calibration of mass spectrometry (MS) isotope ratio measurement results by means of gravimetrically prepared isotopic mixtures is a long known way of anchoring isotopic values to the SI system. Thermal ionisation (TI) MS is the technique traditionally associated with this strategy, while multi-collector double focusing inductively coupled plasma (MC-ICP) ? MS, with a flexible ion source operated at atmospheric pressure and the possibility to achieve 0.01% or less repeatability on isotope ratio measurements, now appears to be an attractive alternative. However, this absolute calibration strategy necessitates that mass discrimination effects remain invariant in time (at least during the duration of all the experiments) and across the range of isotope ratios measured, which is not the case with MC-ICPMS measurements. This issue is illustrated here with Zn isotopic measurements obtained using locally produced synthetic Zn isotope mixtures. The necessary adjustments to specific characteristics of MC-ICPMS are described. Firstly, variations in the mass discrimination effects across the measurement sequence are propagated as an uncertainty component. Secondly, linear proportionality during each individual measurement between normalised mass discrimination and the average mass of the isotope ratios is used to evaluate mass discrimination for the ratios involving 66Zn and 70Zn. Thirdly, linear proportionality after iterative calculations between mass discrimination and the isotope ratio values for n(67Zn)/n(64Zn) and n(68Zn)/n(64Zn) in the mixtures is used to evaluate mass discrimination for the same ratios but specific to the isotopically enriched materials, and additional iterations are introduced until the last significant digit in the isotope ratios in the mixtures is stabilised. Fourthly, ratios in final unknown materials (various natural Zn solutions, including IRMM-3702 and IRMM-651) are calibrated by external bracketing using the isotopic mixtures.The relative expanded uncertainty (k = 2) estimated for n(68Zn)/n(64Zn) and n(67Zn)/n(64Zn) ratio values in the synthetic isotopic mixtures and the natural zinc samples was in the range of 0.034 - 0.048%. The uncertainty on the weighing (r.s.u. = 0.01%, k = 1) was by far the major contributor to the total budget, followed by the uncertainty on the correction for the impurity content in the enriched materials. The effect of the repeatability on isotope ratio measurements was minimal (=2% of the total uncertainty budget). This work was further validated from the agreement achieved for the same set of samples between these results and those obtained with a single detector TIMS (much larger uncertainty estimates) and with another MC-ICP-MS.The absolute isotope ratio values found for the candidate isotopic certified reference material IRMM-3702 ? also proposed as ?Delta 0? for delta-scale isotopic measurements ? were n(66Zn)/n(64Zn) = 0.56397(30), n(67Zn)/n(64Zn) = 0.082166(36), n(68Zn)/n(64Zn) = 0.37519(13) and n(70Zn)/n(64Zn) = 0.012422(24). The derived Zn atomic weight value Ar(Zn) = 65.37778 (22) differs significantly from the current IUPAC value by Chang et al.[ ]. Re-measurement with the IRMM-007 series of synthetic isotopic mixtures of the Zn isotope ratios in the natural material measured by Chang et al. [1] have revealed also large systematic differences (1.73% to 5.6%) that suggest unrecognized measurement biases in their results

Flow injection analysis as a tool for enhancing oceanographic nutrient measurements-A review

Macronutrient elements (C, N and P) and micronutrient elements (Fe, Co, Cu, Zn and Mn) are widely measured in their various physico-chemical forms in open ocean, shelf sea, coastal and estuarine waters. These measurements help to elucidate the biogeochemical cycling of these elements in marine waters and highlight the ecological and socio-economic importance of the oceans. Due to the dynamic nature of marine waters in terms of chemical, biological and physical processes, it is advantageous to make these measurements in situ and in this regard flow injection analysis (FIA) provides a suitable shipboard platform. This review, therefore, discusses the role of FIA in the determination of macro- and micro-nutrient elements, with an emphasis on manifold design and detection strategies for the reliable shipboard determination of specific nutrient species. The application of various FIA manifolds to oceanographic nutrient determinations is discussed, with an emphasis on sensitivity, selectivity, high throughput analysis and suitability for underway analysis and depth profiles. Strategies for enhancing sensitivity and minimizing matrix effects, e.g. refractive index (schlieren) effects and the important role of uncertainty budgets in underpinning method validation and data quality are discussed in some detail.</p