{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:01Z","timestamp":1773878401013,"version":"3.50.1"},"reference-count":71,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["420598"],"award-info":[{"award-number":["420598"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"name":"German Academic Scholarship Foundation"},{"name":"Boise Trust of the University of Oxford"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Birch tar is well-documented for its use as an adhesive in the Middle Palaeolithic of Europe, but other uses remain poorly explored. Drawing from recent arguments suggesting multimodal uses of products such as ochre and birch tar, this study tests the antibiotic properties of birch tar produced experimentally with methods reconstructed from Middle Palaeolithic birch tar finds from Europe. Made from the bark of\n                    <jats:italic>Betula pendula<\/jats:italic>\n                    and\n                    <jats:italic>Betula pubescens,<\/jats:italic>\n                    widely documented for the European Late Pleistocene, we produced birch tar samples using an underground pit method, a condensation method, and a modern tin can method. The birch tar samples were tested for antibiotic properties using the modified Kirby-Bauer disc diffusion antibiotic assay. The resulting inhibition zones, ranging from no effect to 10.5\u2009\u00b1\u20090.7\u2009mm with a mean of 7.5\u2009\u00b1\u20090.17\u2009mm, indicate a moderate effect against the Gram-positive\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    , a bacterium widely known for its role in wound infections. We further establish that the efficacy of antibiotic properties is not related to the production method, with all methods showing a degree of variation. This supports a coevolutionary relationship between medicinal and technological use and production of birch tar during the Pleistocene. The antibiotic properties documented in this study are consistent with the use of birch tar as a wound dressing and skin ointment in Mi\u2019kmaq communities in Eastern Canada, and the use of birch tar in Saami communities of Lapland. Arguing from an underexplored angle between experimental archaeology and ethnopharmacology, we suggest that similar to the ethnographic examples, a use of birch tar beyond exclusively technological contexts must be considered for the Middle Palaeolithic.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0343618","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T17:22:21Z","timestamp":1773854541000},"page":"e0343618","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antibacterial properties of experimentally produced birch tar and its medicinal affordances in the Pleistocene"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0210-1040","authenticated-orcid":true,"given":"Tjaark","family":"Siemssen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aderonke","family":"Oludare","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcel","family":"Schemmel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6778-8488","authenticated-orcid":true,"given":"Janos","family":"Puschmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8433-2664","authenticated-orcid":true,"given":"Matthias","family":"Bierenstiel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"issue":"23","key":"pone.0343618.ref001","doi-asserted-by":"crossref","first-page":"6372","DOI":"10.1073\/pnas.1521269113","article-title":"Neandertals revised","volume":"113","author":"W Roebroeks","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"pone.0343618.ref002","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1016\/j.jas.2011.03.001","article-title":"Hafted armatures and multi-component tool design at the Micoquian site of Inden-Altdorf, Germany","volume":"38","author":"AF Pawlik","year":"2011","journal-title":"Journal of Archaeological Science"},{"issue":"6","key":"pone.0343618.ref003","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1007\/s12520-023-01789-2","article-title":"Production method of the K\u00f6nigsaue birch tar documents cumulative culture in Neanderthals","volume":"15","author":"P Schmidt","year":"2023","journal-title":"Archaeol Anthropol Sci"},{"issue":"44","key":"pone.0343618.ref004","doi-asserted-by":"crossref","first-page":"22081","DOI":"10.1073\/pnas.1907828116","article-title":"Middle Paleolithic complex technology and a Neandertal tar-backed tool from the Dutch North Sea","volume":"116","author":"MJLT Niekus","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"9","key":"pone.0343618.ref005","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1016\/j.jas.2006.01.006","article-title":"A new Palaeolithic discovery: tar-hafted stone tools in a European Mid-Pleistocene bone-bearing bed","volume":"33","author":"PPA Mazza","year":"2006","journal-title":"Journal of Archaeological Science"},{"key":"pone.0343618.ref006","doi-asserted-by":"crossref","first-page":"109025","DOI":"10.1016\/j.quascirev.2024.109025","article-title":"A Neanderthal\u2019s specialised burning structure compatible with tar obtention","volume":"346","author":"J Ochando","year":"2024","journal-title":"Quaternary Science Reviews"},{"issue":"3","key":"pone.0343618.ref007","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1179\/eja.2001.4.3.385","article-title":"High-tech in the middle Palaeolithic: Neandertal-manufactured pitch identified","volume":"4","author":"J Koller","year":"2001","journal-title":"Eur J Archaeol"},{"issue":"6","key":"pone.0343618.ref008","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0213473","article-title":"Hafting of Middle Paleolithic tools in Latium (central Italy): New data from Fossellone and Sant\u2019Agostino caves","volume":"14","author":"I Degano","year":"2019","journal-title":"PLoS One"},{"issue":"10","key":"pone.0343618.ref009","doi-asserted-by":"crossref","first-page":"3722","DOI":"10.1016\/j.jas.2013.03.018","article-title":"A multi-analytical methodology of lithic residue analysis applied to Paleolithic tools from Hummal, Syria","volume":"40","author":"GF Monnier","year":"2013","journal-title":"Journal of Archaeological Science"},{"issue":"9","key":"pone.0343618.ref010","doi-asserted-by":"crossref","first-page":"3506","DOI":"10.1016\/j.jas.2012.12.026","article-title":"First molecular identification of a hafting adhesive in the Late Howiesons Poort at Diepkloof Rock Shelter (Western Cape, South Africa)","volume":"40","author":"A Charri\u00e9-Duhaut","year":"2013","journal-title":"Journal of Archaeological Science"},{"issue":"318","key":"pone.0343618.ref011","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1017\/S0003598X00097623","article-title":"Middle Palaeolithic bitumen use at Umm el Tlel around 70 000 BP","volume":"82","author":"E Bo\u00ebda","year":"2008","journal-title":"Antiquity"},{"issue":"40","key":"pone.0343618.ref012","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2209592119","article-title":"Archaeological adhesives made from Podocarpus document innovative potential in the African Middle Stone Age","volume":"119","author":"P Schmidt","year":"2022","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0343618.ref013","doi-asserted-by":"crossref","first-page":"103578","DOI":"10.1016\/j.jhevol.2024.103578","article-title":"Adhesive technology based on biomass tar documents engineering capabilities in the African Middle Stone Age","volume":"194","author":"P Schmidt","year":"2024","journal-title":"J Hum Evol"},{"issue":"8","key":"pone.0343618.ref014","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.adl0822","article-title":"Ochre-based compound adhesives at the Mousterian type-site document complex cognition and high investment","volume":"10","author":"P Schmidt","year":"2024","journal-title":"Sci Adv"},{"issue":"1","key":"pone.0343618.ref015","first-page":"57","article-title":"Direct evidence for the use of ochre in the hafting technology of Middle Stone Age tools from Sibudu Cave","volume":"18","author":"M Lombard","year":"2006","journal-title":"Southern African Humanities"},{"issue":"9","key":"pone.0343618.ref016","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0136090","article-title":"Evaluating the Photoprotective Effects of Ochre on Human Skin by In Vivo SPF Assessment: Implications for Human Evolution, Adaptation and Dispersal","volume":"10","author":"RF Rifkin","year":"2015","journal-title":"PLoS One"},{"issue":"4","key":"pone.0343618.ref017","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s13752-018-0306-x","article-title":"Cultural Exaptation and Cultural Neural Reuse: A Mechanism for the Emergence of Modern Culture and Behavior","volume":"13","author":"F d\u2019Errico","year":"2018","journal-title":"Biol Theory"},{"key":"pone.0343618.ref018","article-title":"Birch bark glue and its potential use in Neanderthal clothing: A pilot study","volume":"4","author":"PH Baker","year":"2021","journal-title":"EXARC Journal"},{"issue":"1","key":"pone.0343618.ref019","first-page":"18","article-title":"Midge-infested wetlands and the coevolution of birch tar use in Late Pleistocene Neanderthals","volume":"39","author":"T Siemssen","year":"2024","journal-title":"Archaeological Review from Cambridge"},{"issue":"2","key":"pone.0343618.ref020","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1017\/S0959774322000300","article-title":"Material and Sensory Experiences of Mesolithic Resinous Substances","volume":"33","author":"A Little","year":"2022","journal-title":"CAJ"},{"key":"pone.0343618.ref021","unstructured":"Itkonen and Minn. The Lapps in Finland up to 1945. Helsinki, 1948."},{"key":"pone.0343618.ref022","volume-title":"The Yakut: An Experiment in Ethnographic Research","author":"W Sieroszewski","year":"1993"},{"key":"pone.0343618.ref023","first-page":"3","article-title":"Maskwio\u2019min: A birch bark antibiotic","volume":"116","author":"M Bierenstiel","year":"2018","journal-title":"Green Teacher"},{"key":"pone.0343618.ref024","doi-asserted-by":"crossref","first-page":"105309","DOI":"10.1016\/j.jas.2020.105309","article-title":"Management systems of adhesive materials throughout the Neolithic in the North-West Mediterranean","volume":"126","author":"M Rageot","year":"2021","journal-title":"Journal of Archaeological Science"},{"issue":"3","key":"pone.0343618.ref025","doi-asserted-by":"crossref","DOI":"10.1007\/s00107-025-02255-7","article-title":"Comparison of the properties of birch bark tar obtained by the double-clay pot method and the laboratory method","volume":"83","author":"M Bartkowiak","year":"2025","journal-title":"Eur J Wood Prod"},{"key":"pone.0343618.ref026","unstructured":"Kaliaperumal R, Oludare A, Zuieva V, Young T, Bierenstiel M. Assessment of the antibacterial activity of Maskwio\u2019mi, an L\u2019nu (Mi\u2019kmaq) skin medicine made from birch bark, against Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae."},{"key":"pone.0343618.ref027","doi-asserted-by":"crossref","first-page":"115922","DOI":"10.1016\/j.marpolbul.2023.115922","article-title":"Characterization of bacterial biofilms developed on the biodegradable polylactide and polycaprolactone polymers containing birch tar in an aquatic environment","volume":"199","author":"A Richert","year":"2024","journal-title":"Mar Pollut Bull"},{"key":"pone.0343618.ref028","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-18860-7","volume-title":"Theory and Practice in the Bioarchaeology of Care","author":"L Tilley","year":"2015"},{"issue":"3","key":"pone.0343618.ref029","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1080\/00438243.2018.1433060","article-title":"Calculated or caring? Neanderthal healthcare in social context","volume":"50","author":"P Spikins","year":"2018","journal-title":"World Archaeology"},{"key":"pone.0343618.ref030","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.quascirev.2018.08.011","article-title":"Living to fight another day: The ecological and evolutionary significance of Neanderthal healthcare","volume":"217","author":"P Spikins","year":"2019","journal-title":"Quaternary Science Reviews"},{"key":"pone.0343618.ref031","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/B978-0-12-821428-2.00004-4","article-title":"The use of plants by Neanderthals as food, medicine, and raw materials","author":"K Hardy","year":"2022","journal-title":"Updating Neanderthals. Elsevier"},{"key":"pone.0343618.ref032","first-page":"8927654","article-title":"Evidence for the Paleoethnobotany of the Neanderthal: A Review of the Literature","volume":"2016","author":"GP Shipley","year":"2016","journal-title":"Scientifica (Cairo)"},{"issue":"8","key":"pone.0343618.ref033","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1007\/s00114-012-0942-0","article-title":"Neanderthal medics? Evidence for food, cooking, and medicinal plants entrapped in dental calculus","volume":"99","author":"K Hardy","year":"2012","journal-title":"Naturwissenschaften"},{"issue":"3","key":"pone.0343618.ref034","first-page":"183","article-title":"A differential diagnostics of the right shoulder girdle deformity in the Shanidar I Neanderthal","volume":"26","author":"J Lietava","year":"1988","journal-title":"Anthropologie"},{"issue":"36","key":"pone.0343618.ref035","doi-asserted-by":"crossref","first-page":"17707","DOI":"10.1073\/pnas.1911137116","article-title":"Birch tar production does not prove Neanderthal behavioral complexity","volume":"116","author":"P Schmidt","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pone.0343618.ref036","doi-asserted-by":"crossref","first-page":"8033","DOI":"10.1038\/s41598-017-08106-7","article-title":"Experimental methods for the Palaeolithic dry distillation of birch bark: implications for the origin and development of Neandertal adhesive technology","volume":"7","author":"PRB Kozowyk","year":"2017","journal-title":"Sci Rep"},{"issue":"2","key":"pone.0343618.ref037","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1586\/edm.10.6","article-title":"Staphylococcus colonization of the skin and antimicrobial peptides","volume":"5","author":"M Otto","year":"2010","journal-title":"Expert Rev Dermatol"},{"key":"pone.0343618.ref038","volume-title":"Microbiology: A Laboratory Manual","author":"JG Cappuccino","year":"2008"},{"key":"pone.0343618.ref039","article-title":"Performance standards for antimicrobial susceptibility testing","volume-title":"Clinical and Laboratory Standards Institute (CLSI)","year":"2017"},{"issue":"6","key":"pone.0343618.ref040","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.3390\/molecules25061340","article-title":"Resistance of Gram-Negative Bacteria to Current Antibacterial Agents and Approaches to Resolve It","volume":"25","author":"Z Breijyeh","year":"2020","journal-title":"Molecules"},{"issue":"1","key":"pone.0343618.ref041","article-title":"Maskwio\u2019mi (Birch Bark Extract): A Case Study Exploring The Use Of A Traditional L\u2019nu Medicine On Skin Conditions","volume":"5","author":"L O\u2019Donnell","year":"2024","journal-title":"WCC"},{"issue":"6","key":"pone.0343618.ref042","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1542\/pir.2017-0224","article-title":"Staphylococcus aureus","volume":"39","author":"DS Ondusko","year":"2018","journal-title":"Pediatr Rev"},{"issue":"9","key":"pone.0343618.ref043","article-title":"Skin Infections Caused by Staphylococcus aureus","volume":"100","author":"P Del Giudice","year":"2020","journal-title":"Acta Derm Venereol"},{"issue":"4","key":"pone.0343618.ref044","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1139\/cjc-2023-0166","article-title":"Qualitative and Quantitative Analysis of Cresols Found in Maskwio\u2019mi (Birch Bark Extract)","volume":"102","author":"V Lyczywek","year":"2024","journal-title":"Canadian Journal of Chemistry"},{"key":"pone.0343618.ref045","author":"V Zuieva","year":"2025"},{"issue":"1","key":"pone.0343618.ref046","doi-asserted-by":"crossref","DOI":"10.1002\/mbo3.944","article-title":"Antimicrobial activity and chemical composition of white birch (Betula papyrifera Marshall) bark extracts","volume":"9","author":"D Blondeau","year":"2020","journal-title":"Microbiologyopen"},{"issue":"1","key":"pone.0343618.ref047","doi-asserted-by":"crossref","first-page":"268","DOI":"10.3390\/ijms23010268","article-title":"The Role of Birch Tar in Changing the Physicochemical and Biocidal Properties of Polylactide-Based Films","volume":"23","author":"A Richert","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"23","key":"pone.0343618.ref048","doi-asserted-by":"crossref","first-page":"4244","DOI":"10.3390\/foods12234244","article-title":"Polycaprolactone-Based Films Incorporated with Birch Tar-Thermal, Physicochemical, Antibacterial, and Biodegradable Properties","volume":"12","author":"A Richert","year":"2023","journal-title":"Foods"},{"key":"pone.0343618.ref049","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.micres.2016.12.003","article-title":"Phytochemicals for human disease: An update on plant-derived compounds antibacterial activity","volume":"196","author":"R Barbieri","year":"2017","journal-title":"Microbiol Res"},{"issue":"1","key":"pone.0343618.ref050","doi-asserted-by":"crossref","first-page":"130","DOI":"10.3390\/antibiotics12010130","article-title":"Antioxidative and Antimicrobial Evaluation of Bark Extracts from Common European Trees in Light of Dermal Applications","volume":"12","author":"S H\u00e4sler Gunnarsdottir","year":"2023","journal-title":"Antibiotics (Basel)"},{"issue":"9","key":"pone.0343618.ref051","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1007\/s00217-021-03796-w","article-title":"In vitro antioxidant and antibacterial activities with polyphenolic profiling of wild cherry, the European larch and sweet chestnut tree bark","volume":"247","author":"C Agarwal","year":"2021","journal-title":"Eur Food Res Technol"},{"key":"pone.0343618.ref052","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.fbio.2015.03.002","article-title":"Antimicrobial efficacy of plant phenolic compounds against Salmonella and Escherichia Coli","volume":"11","author":"H Cetin-Karaca","year":"2015","journal-title":"Food Bioscience"},{"issue":"6","key":"pone.0343618.ref053","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1046\/j.1472-765X.2003.01427.x","article-title":"Activity of natural antimicrobial compounds against Escherichia coli and Salmonella enterica serovar Typhimurium","volume":"37","author":"NA Olasupo","year":"2003","journal-title":"Lett Appl Microbiol"},{"issue":"1","key":"pone.0343618.ref054","doi-asserted-by":"crossref","first-page":"13","DOI":"10.2137\/145960610791015096","article-title":"Effects of birch tar oils on soil organisms and plants","volume":"19","author":"M Hagner","year":"2008","journal-title":"AFSci"},{"key":"pone.0343618.ref055","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1080\/14786419.2012.695364","article-title":"Antimicrobial and antioxidant properties of Betula aetnensis Rafin. (Betulaceae) leaves extract","volume":"27","author":"R Acquaviva","year":"2013","journal-title":"Nat Prod Res"},{"issue":"9","key":"pone.0343618.ref056","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.3390\/molecules27092817","article-title":"Antimicrobial Activity and Wound-Healing Capacity of Birch, Beech and Larch Bark Extracts","volume":"27","author":"S Emrich","year":"2022","journal-title":"Molecules"},{"issue":"6","key":"pone.0343618.ref057","doi-asserted-by":"crossref","first-page":"800","DOI":"10.3109\/13880209.2014.942867","article-title":"Antimicrobial activity of natural products from the flora of Northern Ontario, Canada","volume":"53","author":"J Vandal","year":"2015","journal-title":"Pharm Biol"},{"issue":"02","key":"pone.0343618.ref058","doi-asserted-by":"crossref","first-page":"49","DOI":"10.4236\/aa.2012.22006","article-title":"Genotoxicity Assessment of Birch-Bark Tar\u2014A Most Versatile Prehistoric Adhesive","volume":"02","author":"A Baumgartner","year":"2012","journal-title":"AA"},{"issue":"7","key":"pone.0343618.ref059","doi-asserted-by":"crossref","first-page":"3944","DOI":"10.3390\/ijerph19073944","article-title":"Characteristics and Influencing Factors of Polycyclic Aromatic Hydrocarbons Emitted from Open Burning and Stove Burning of Biomass: A Brief Review","volume":"19","author":"H Zhang","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"pone.0343618.ref060","first-page":"1","article-title":"Polycyclic aromatic hydrocarbons in food-opinion of the Panel on Contaminants in the Food Chain","volume":"724","author":"EFSA European Food Safety Authority","year":"2008","journal-title":"EFSA Journal"},{"issue":"4","key":"pone.0343618.ref061","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S0944-7113(98)80072-X","article-title":"Efficacy of plant extracts and oils as mosquito repellents","volume":"5","author":"W Thorsell","year":"1998","journal-title":"Phytomedicine"},{"issue":"14","key":"pone.0343618.ref062","doi-asserted-by":"crossref","first-page":"2884","DOI":"10.1002\/esp.5219","article-title":"Eemian landscape response to climatic shifts and evidence for northerly Neanderthal occupation at a palaeolake margin in northern Germany","volume":"46","author":"M Hein","year":"2021","journal-title":"Earth Surf Processes Landf"},{"key":"pone.0343618.ref063","first-page":"71","article-title":"Das M\u00fcckenthermometer - Subfossile Zuckm\u00fcckenlarven aus dem Pal\u00e4osee von Lichenberg als Anzeiger von Klima- und Umweltver\u00e4nderungen am \u00dcbergang von Kalt- zu Warmzeiten","volume":"20","author":"S Rigterink","year":"2023","journal-title":"Hannoversches Wendland"},{"issue":"2","key":"pone.0343618.ref064","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2018.08.034","article-title":"Evidence that RNA Viruses Drove Adaptive Introgression between Neanderthals and Modern Humans","volume":"175","author":"D Enard","year":"2018","journal-title":"Cell"},{"issue":"1812","key":"pone.0343618.ref065","doi-asserted-by":"crossref","first-page":"20190575","DOI":"10.1098\/rstb.2019.0575","article-title":"Ancient RNA virus epidemics through the lens of recent adaptation in human genomes","volume":"375","author":"D Enard","year":"2020","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"issue":"1","key":"pone.0343618.ref066","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1186\/s13059-016-1098-6","article-title":"Adaptively introgressed Neandertal haplotype at the OAS locus functionally impacts innate immune responses in humans","volume":"17","author":"AJ Sams","year":"2016","journal-title":"Genome Biol"},{"issue":"4","key":"pone.0343618.ref067","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1038\/s41591-021-01281-1","article-title":"A Neanderthal OAS1 isoform protects individuals of European ancestry against COVID-19 susceptibility and severity","volume":"27","author":"S Zhou","year":"2021","journal-title":"Nat Med"},{"issue":"3","key":"pone.0343618.ref068","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1002\/ajpa.22985","article-title":"Neanderthal genomics suggests a pleistocene time frame for the first epidemiologic transition","volume":"160","author":"CJ Houldcroft","year":"2016","journal-title":"Am J Phys Anthropol"},{"issue":"7650","key":"pone.0343618.ref069","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nature21674","article-title":"Neanderthal behaviour, diet, and disease inferred from ancient DNA in dental calculus","volume":"544","author":"LS Weyrich","year":"2017","journal-title":"Nature"},{"issue":"10","key":"pone.0343618.ref070","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0186684","article-title":"External auditory exostoses and hearing loss in the Shanidar 1 Neandertal","volume":"12","author":"E Trinkaus","year":"2017","journal-title":"PLoS One"},{"issue":"26","key":"pone.0343618.ref071","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.adn9310","article-title":"The child who lived: Down syndrome among Neanderthals?","volume":"10","author":"M Conde-Valverde","year":"2024","journal-title":"Sci Adv"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0343618","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T17:22:30Z","timestamp":1773854550000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0343618"}},"subtitle":[],"editor":[{"given":"Branislav T.","family":"\u0160iler","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,3,18]]},"references-count":71,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3,18]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0343618","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,18]]}}}