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      Possible cases of leprosy from the Late Copper Age (3780-3650 cal BC) in Hungary

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          Abstract

          At the Abony-Turjányos dűlő site, located in Central Hungary, a rescue excavation was carried out. More than 400 features were excavated and dated to the Protoboleráz horizon, at the beginning of the Late Copper Age in the Carpathian Basin, between 3780–3650 cal BC. Besides the domestic and economic units, there were two special areas, with nine-nine pits that differed from the other archaeological features of the site. In the northern pit group seven pits contained human remains belonging to 48 individuals. Some of them were buried carefully, while others were thrown into the pits. The aim of this study is to present the results of the paleopathological and molecular analysis of human remains from this Late Copper Age site. The ratio of neonates to adults was high, 33.3%. Examination of the skeletons revealed a large number of pathological cases, enabling reconstruction of the health profile of the buried individuals. Based on the appearance and frequency of healed ante- and peri mortem trauma, inter-personal (intra-group) violence was characteristic in the Abony Late Copper Age population. However other traces of paleopathology were observed on the bones that appear not to have been caused by warfare or inter-group violence. The remains of one individual demonstrated a rare set of bone lesions that indicate the possible presence of leprosy (Hansen’s disease). The most characteristic lesions occurred on the bones of the face, including erosion of the nasal aperture, atrophy of the anterior nasal spine, inflammation of the nasal bone and porosity on both the maxilla and the bones of the lower legs. In a further four cases, leprosy infection is suspected but other infections cannot be excluded. The morphologically diagnosed possible leprosy case significantly modifies our knowledge about the timescale and geographic spread of this specific infectious disease. However, it is not possible to determine the potential connections between the cases of possible leprosy and the special burial circumstances.

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          Genetic analyses from ancient DNA.

          About 20 years ago, DNA sequences were separately described from the quagga (a type of zebra) and an ancient Egyptian individual. What made these DNA sequences exceptional was that they were derived from 140- and 2400-year-old specimens. However, ancient DNA research, defined broadly as the retrieval of DNA sequences from museum specimens, archaeological finds, fossil remains, and other unusual sources of DNA, only really became feasible with the advent of techniques for the enzymatic amplification of specific DNA sequences. Today, reports of analyses of specimens hundreds, thousands, and even millions of years old are almost commonplace. But can all these results be believed? In this paper, we critically assess the state of ancient DNA research. In particular, we discuss the precautions and criteria necessary to ascertain to the greatest extent possible that results represent authentic ancient DNA sequences. We also highlight some significant results and areas of promising future research.
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            Genome-wide comparison of medieval and modern Mycobacterium leprae.

            Leprosy was endemic in Europe until the Middle Ages. Using DNA array capture, we have obtained genome sequences of Mycobacterium leprae from skeletons of five medieval leprosy cases from the United Kingdom, Sweden, and Denmark. In one case, the DNA was so well preserved that full de novo assembly of the ancient bacterial genome could be achieved through shotgun sequencing alone. The ancient M. leprae sequences were compared with those of 11 modern strains, representing diverse genotypes and geographic origins. The comparisons revealed remarkable genomic conservation during the past 1000 years, a European origin for leprosy in the Americas, and the presence of an M. leprae genotype in medieval Europe now commonly associated with the Middle East. The exceptional preservation of M. leprae biomarkers, both DNA and mycolic acids, in ancient skeletons has major implications for palaeomicrobiology and human pathogen evolution.
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              Age estimation from the rib by phase analysis: white females.

              Metamorphosis at the sternal extremity of the rib has already been established as a reliable indicator of age at death. Using a sample of white males, it was shown that an accurate estimation of age can be made by direct examination of the bone itself. However, because of sexual differences in hormonal production and dimorphism in the skeleton, the present study was carried out to develop an appropriate standard for age determination from the sternal rib in white females. The sample consisted of 86 ribs of known age, sex, and race. Observations were made at the costochondral junction with special attention to pit formation (its shape and depth), changes in the walls and rim surrounding it, and overall bone density and texture. Based on changes in these areas, the ribs were separated into nine phases (0 through 8). The most rapid metamorphosis occurred in Phases 1 through 4 (mean ages 14-28) with changes noticeable at 3 to 4 year intervals. After mean age 28, this process slowed, considerably expanding the interval between phases to 10 to 15 years. The female ribs showed both earlier initial pit formation and a different morphologic pattern of aging as compared with males. Statistical analysis revealed that the features chosen to delineate the phases are valid predictors of age. This study has shown that the sternal rib can provide an accurate estimation of age in females spanning a mean age of 14 to 76 years.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: SoftwareRole: VisualizationRole: Writing – original draft
                Role: InvestigationRole: MethodologyRole: SoftwareRole: VisualizationRole: Writing – original draft
                Role: Data curationRole: Formal analysisRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: SupervisionRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SupervisionRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                12 October 2017
                2017
                : 12
                : 10
                : e0185966
                Affiliations
                [1 ] Institute of Archaeology, Research Centre for the Humanities, Hungarian Academy of Sciences, Budapest, Hungary
                [2 ] Retired associate professor, University of Szeged, Szeged, Hungary
                [3 ] Health Centre, Kaposvár University, Kaposvár, Hungary
                [4 ] Department of Biological Anthropology, Institute of Biology, Faculty of Science, Eötvös Loránd University, Budapest, Hungary
                [5 ] Department of Archaeological Excavations and Artefact Processing, Hungarian National Museum, Budapest, Hungary
                [6 ] Centre for Clinical Microbiology, Royal Free Campus, University College London, London, United Kingdom
                Hebrew University, ISRAEL
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-3604-1125
                Article
                PONE-D-16-46490
                10.1371/journal.pone.0185966
                5638319
                29023477
                8231eefa-25ec-4683-8569-ba8bb68e8f06
                © 2017 Köhler et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 23 November 2016
                : 24 September 2017
                Page count
                Figures: 6, Tables: 7, Pages: 25
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100003825, Magyar Tudományos Akadémia;
                Award ID: Bolyai Research Fellowship. http://old.mta.hu/data/cikk/13/65/84/cikk_136584/BolyaiJanosKutatoiOsztondij-2015.pdf
                Award Recipient :
                Tamás Hajdu was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences. Covering the open access publication charges for this article was provided by the Open Access Fund of the Hungarian Academy of Sciences.
                Categories
                Research Article
                Medicine and Health Sciences
                Infectious Diseases
                Bacterial Diseases
                Leprosy
                Medicine and Health Sciences
                Tropical Diseases
                Neglected Tropical Diseases
                Leprosy
                Biology and Life Sciences
                Genetics
                Molecular Genetics
                Biology and Life Sciences
                Molecular Biology
                Molecular Genetics
                Biology and Life Sciences
                Anatomy
                Musculoskeletal System
                Skeleton
                Tibia
                Medicine and Health Sciences
                Anatomy
                Musculoskeletal System
                Skeleton
                Tibia
                Social Sciences
                Archaeology
                Biology and Life Sciences
                Anatomy
                Musculoskeletal System
                Skeleton
                Skull
                Medicine and Health Sciences
                Anatomy
                Musculoskeletal System
                Skeleton
                Skull
                Biology and Life Sciences
                Organisms
                Bacteria
                Actinobacteria
                Mycobacterium Leprae
                Biology and Life Sciences
                Anatomy
                Bone
                Medicine and Health Sciences
                Anatomy
                Bone
                Biology and Life Sciences
                Anatomy
                Biological Tissue
                Connective Tissue
                Bone
                Medicine and Health Sciences
                Anatomy
                Biological Tissue
                Connective Tissue
                Bone
                Biology and Life Sciences
                Molecular Biology
                Molecular Biology Techniques
                Artificial Gene Amplification and Extension
                Polymerase Chain Reaction
                Research and Analysis Methods
                Molecular Biology Techniques
                Artificial Gene Amplification and Extension
                Polymerase Chain Reaction
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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