Over the past decade, a genomics revolution, made possible through the development of high-throughput sequencing, has triggered considerable progress in the study of ancient DNA, enabling complete ...genomes of past organisms to be reconstructed. A newly established branch of this field, ancient pathogen genomics, affords an in-depth view of microbial evolution by providing a molecular fossil record for a number of human-associated pathogens. Recent accomplishments include the confident identification of causative agents from past pandemics, the discovery of microbial lineages that are now extinct, the extrapolation of past emergence events on a chronological scale and the characterization of long-term evolutionary history of microorganisms that remain relevant to public health today. In this Review, we discuss methodological advancements, persistent challenges and novel revelations gained through the study of ancient pathogen genomes.
The origin of Yersinia pestis and the early stages of its evolution are fundamental subjects of investigation given its high virulence and mortality that resulted from past pandemics. Although the ...earliest evidence of Y. pestis infections in humans has been identified in Late Neolithic/Bronze Age Eurasia (LNBA 5000-3500y BP), these strains lack key genetic components required for flea adaptation, thus making their mode of transmission and disease presentation in humans unclear. Here, we reconstruct ancient Y. pestis genomes from individuals associated with the Late Bronze Age period (~3800 BP) in the Samara region of modern-day Russia. We show clear distinctions between our new strains and the LNBA lineage, and suggest that the full ability for flea-mediated transmission causing bubonic plague evolved more than 1000 years earlier than previously suggested. Finally, we propose that several Y. pestis lineages were established during the Bronze Age, some of which persist to the present day.
Yersinia pestis, the etiologic agent of plague, is a bacterium associated with wild rodents and their fleas. Historically it was responsible for three pandemics: the Plague of Justinian in the 6th ...century AD, which persisted until the 8th century 1; the renowned Black Death of the 14th century 2, 3, with recurrent outbreaks until the 18th century 4; and the most recent 19th century pandemic, in which Y. pestis spread worldwide 5 and became endemic in several regions 6. The discovery of molecular signatures of Y. pestis in prehistoric Eurasian individuals and two genomes from Southern Siberia suggest that Y. pestis caused some form of disease in humans prior to the first historically documented pandemic 7. Here, we present six new European Y. pestis genomes spanning the Late Neolithic to the Bronze Age (LNBA; 4,800 to 3,700 calibrated years before present). This time period is characterized by major transformative cultural and social changes that led to cross-European networks of contact and exchange 8, 9. We show that all known LNBA strains form a single putatively extinct clade in the Y. pestis phylogeny. Interpreting our data within the context of recent ancient human genomic evidence that suggests an increase in human mobility during the LNBA, we propose a possible scenario for the early spread of Y. pestis: the pathogen may have entered Europe from Central Eurasia following an expansion of people from the steppe, persisted within Europe until the mid-Bronze Age, and moved back toward Central Eurasia in parallel with human populations.
•Six Late Neolithic–Early Bronze Age European Y. pestis genomes were reconstructed•All Late Neolithic and Early Bronze Age Y. pestis form a single phylogenetic branch
Andrades Valtueña et al. present the first six European Y. pestis genomes dating from the Late Neolithic and the Early Bronze Age. These data suggest that Y. pestis entered Europe during a human migration around 4800 BP, persisted in Europe, and traveled back to Central Eurasia.
Ancient DNA analysis has revealed an involvement of the bacterial pathogen Yersinia pestis in several historical pandemics, including the second plague pandemic (Europe, mid-14th century Black Death ...until the mid-18th century AD). Here we present reconstructed Y. pestis genomes from plague victims of the Black Death and two subsequent historical outbreaks spanning Europe and its vicinity, namely Barcelona, Spain (1300–1420 cal AD), Bolgar City, Russia (1362–1400 AD), and Ellwangen, Germany (1485–1627 cal AD). Our results provide support for (1) a single entry of Y. pestis in Europe during the Black Death, (2) a wave of plague that traveled toward Asia to later become the source population for contemporary worldwide epidemics, and (3) the presence of an historical European plague focus involved in post-Black Death outbreaks that is now likely extinct.
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•Three historical Yersinia pestis genomes from the second plague pandemic in Europe•Low genetic diversity of the pathogen during the Black Death•Indication for link between the Black Death and 19th century plague pandemic lineages•Connection between post-Black Death outbreaks in Europe supports a local plague focus
Spyrou et al. have sequenced historical Yersinia pestis genomes from victims of the Black Death and subsequent outbreaks in Europe. Their data suggest a connection between the Black Death and the modern-day plague pandemic as well as the persistence of plague in Europe between the 14th and 18th centuries.
This is an exciting time for the study of r-process nucleosynthesis. Recently, a neutron star merger GW170817 was observed in extraordinary detail with gravitational waves and electromagnetic ...radiation from radio to γ rays. The very red color of the associated kilonova suggests that neutron star mergers are an important r-process site. Astrophysical simulations of neutron star mergers and core collapse supernovae are making rapid progress. Detection of both electron neutrinos and antineutrinos from the next galactic supernova will constrain the composition of neutrino-driven winds and provide unique nucleosynthesis information. Finally, FRIB and other rare-isotope beam facilities will soon have dramatic new capabilities to synthesize many neutron-rich nuclei that are involved in the r-process. The new capabilities can significantly improve our understanding of the r-process and likely resolve one of the main outstanding problems in classical nuclear astrophysics. However, to make best use of the new experimental capabilities and to fully interpret the results, a great deal of infrastructure is needed in many related areas of astronomy, astrophysics, and nuclear theory. We place these experiments in context by discussing astrophysical simulations and observations of r-process sites, observations of stellar abundances, galactic chemical evolution, and nuclear theory for the structure and reactions of very neutron-rich nuclei. This review paper was initiated at a three-week International Collaborations in Nuclear Theory program in June 2016, where we explored promising r-process experiments and discussed their likely impact, and their astronomical, astrophysical, and nuclear theory context.
A novel multiscale modeling framework for skeletal muscles based on analytical and numerical homogenization methods is presented to study the mechanical muscle response at finite strains under ...three-dimensional loading conditions. First an analytical microstructure-based constitutive model is developed and numerically implemented in a general purpose finite element program. The analytical model takes into account explicitly the volume fractions, the material properties, and the spatial distribution of muscle's constituents by using homogenization techniques to bridge the different length scales of the muscle structure. Next, a numerical homogenization model is developed using periodic eroded Voronoi tessellation to virtually represent skeletal muscle microstructures. The eroded Voronoi unit cells are then resolved by finite element simulations and are used to assess the analytical homogenization model. The material parameters of the analytical model are identified successfully by use of available experimental data. The analytical model is found to be in very good agreement with the numerical model for the full range of loadings, and a wide range of different volume fractions and heterogeneity contrasts between muscle's constituents. A qualitative application of the model on fusiform and pennate muscle structures shows its efficiency to examine the effect of muscle fiber concentration variations in an organ-scale model simulation.
Modern humans expanded into Eurasia more than 40,000 years ago following their dispersal out of Africa. These Eurasians carried ~2-3% Neanderthal ancestry in their genomes, originating from admixture ...with Neanderthals that took place sometime between 50,000 and 60,000 years ago, probably in the Middle East. In Europe, the modern human expansion preceded the disappearance of Neanderthals from the fossil record by 3,000-5,000 years. The genetic makeup of the first Europeans who colonized the continent more than 40,000 years ago remains poorly understood since few specimens have been studied. Here, we analyse a genome generated from the skull of a female individual from Zlatý kůň, Czechia. We found that she belonged to a population that appears to have contributed genetically neither to later Europeans nor to Asians. Her genome carries ~3% Neanderthal ancestry, similar to those of other Upper Palaeolithic hunter-gatherers. However, the lengths of the Neanderthal segments are longer than those observed in the currently oldest modern human genome of the ~45,000-year-old Ust'-Ishim individual from Siberia, suggesting that this individual from Zlatý kůň is one of the earliest Eurasian inhabitants following the expansion out of Africa.
The last century has witnessed progress in the study of ancient infectious disease from purely medical descriptions of past ailments to dynamic interpretations of past population health that draw ...upon multiple perspectives. The recent adoption of high-throughput DNA sequencing has led to an expanded understanding of pathogen presence, evolution, and ecology across the globe. This genomic revolution has led to the identification of disease-causing microbes in both expected and unexpected contexts, while also providing for the genomic characterization of ancient pathogens previously believed to be unattainable by available methods. In this review we explore the development of DNA-based ancient pathogen research, the specialized methods and tools that have emerged to authenticate and explore infectious disease of the past, and the unique challenges that persist in molecular paleopathology. We offer guidelines to mitigate the impact of these challenges, which will allow for more reliable interpretations of data in this rapidly evolving field of investigation.
In this work, we propose a novel technique for in-vivo proton therapy range verification. This technique makes use of a molybdenum hadron tumour marker, implanted at a short distance from the ...clinical treatment volume. Signals emitted from the marker during treatment can provide a direct measurement of the proton beam energy at the marker's position. Fusion-evaporation reactions between the proton beam and marker nucleus result in the emission of delayed characteristic γ rays, which are detected off-beam for an improved signal-to-noise ratio. In order to determine the viability of this technique and to establish an experimental setup for future work, the Monte Carlo package GEANT4 was used in combination with ROOT to simulate a treatment scenario with the new method outlined in this work. These simulations show that the intensity of delayed γ rays produced from competing reactions yields a precise measurement of the range of the proton beam relative to the marker, with sub-millimetre uncertainty.
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