Paleolithic to Bronze Age Siberians Reveal Connections with First Americans and across Eurasia.

Modern humans have inhabited the Lake Baikal region since the Upper Paleolithic, though the precise history of its peoples over this long time span is still largely unknown. Here, we report genome-wide data from 19 Upper Paleolithic to Early Bronze Age individuals from this Siberian region. An Upper Paleolithic genome shows a direct link with the First Americans by sharing the admixed ancestry that gave rise to all non-Arctic Native Americans. We also demonstrate the formation of Early Neolithic and Bronze Age Baikal populations as the result of prolonged admixture throughout the eighth to sixth millennium BP. Moreover, we detect genetic interactions with western Eurasian steppe populations and reconstruct Yersinia pestis genomes from two Early Bronze Age individuals without western Eurasian ancestry. Overall, our study demonstrates the most deeply divergent connection between Upper Paleolithic Siberians and the First Americans and reveals human and pathogen mobility across Eurasia during the Bronze Age.

Ancient genomes reveal insights into ritual life at Chichén Itzá.

The ancient city of Chichén Itzá in Yucatán, Mexico, was one of the largest and most influential Maya settlements during the Late and Terminal Classic periods (AD 600-1000) and it remains one of the most intensively studied archaeological sites in Mesoamerica1-4. However, many questions about the social and cultural use of its ceremonial spaces, as well as its population's genetic ties to other Mesoamerican groups, remain unanswered2. Here we present genome-wide data obtained from 64 subadult individuals dating to around AD 500-900 that were found in a subterranean mass burial near the Sacred Cenote (sinkhole) in the ceremonial centre of Chichén Itzá. Genetic analyses showed that all analysed individuals were male and several individuals were closely related, including two pairs of monozygotic twins. Twins feature prominently in Mayan and broader Mesoamerican mythology, where they embody qualities of duality among deities and heroes5, but until now they had not been identified in ancient Mayan mortuary contexts. Genetic comparison to present-day people in the region shows genetic continuity with the ancient inhabitants of Chichén Itzá, except at certain genetic loci related to human immunity, including the human leukocyte antigen complex, suggesting signals of adaptation due to infectious diseases introduced to the region during the colonial period.

The demise of the giant ape Gigantopithecus blacki.

The largest ever primate and one of the largest of the southeast Asian megafauna, Gigantopithecus blacki1, persisted in China from about 2.0 million years until the late middle Pleistocene when it became extinct2-4. Its demise is enigmatic considering that it was one of the few Asian great apes to go extinct in the last 2.6 million years, whereas others, including orangutan, survived until the present5. The cause of the disappearance of G. blacki remains unresolved but could shed light on primate resilience and the fate of megafauna in this region6. Here we applied three multidisciplinary analyses-timing, past environments and behaviour-to 22 caves in southern China. We used 157 radiometric ages from six dating techniques to establish a timeline for the demise of G. blacki. We show that from 2.3 million years ago the environment was a mosaic of forests and grasses, providing ideal conditions for thriving G. blacki populations. However, just before and during the extinction window between 295,000 and 215,000 years ago there was enhanced environmental variability from increased seasonality, which caused changes in plant communities and an increase in open forest environments. Although its close relative Pongo weidenreichi managed to adapt its dietary preferences and behaviour to this variability, G. blacki showed signs of chronic stress and dwindling populations. Ultimately its struggle to adapt led to the extinction of the greatest primate to ever inhabit the Earth.

Isotopic and DNA analyses reveal multiscale PPNB mobility and migration across Southeastern Anatolia and the Southern Levant.

Growing reliance on animal and plant domestication in the Near East and beyond during the Pre-Pottery Neolithic B (PPNB) (the ninth to eighth millennium BC) has often been associated with a "revolutionary" social transformation from mobility toward more sedentary lifestyles. We are able to yield nuanced insights into the process of the Neolithization in the Near East based on a bioarchaeological approach integrating isotopic and archaeogenetic analyses on the bone remains recovered from Nevali Çori, a site occupied from the early PPNB in Turkey where some of the earliest evidence of animal and plant domestication emerged, and from Ba'ja, a typical late PPNB site in Jordan. In addition, we present the archaeological sequence of Nevali Çori together with newly generated radiocarbon dates. Our results are based on strontium (87Sr/86Sr), carbon, and oxygen (δ18O and δ13Ccarb) isotopic analyses conducted on 28 human and 29 animal individuals from the site of Nevali Çori. 87Sr/86Sr results indicate mobility and connection with the contemporaneous surrounding sites during the earlier PPNB prior to an apparent decline in this mobility at a time of growing reliance on domesticates. Genome-wide data from six human individuals from Nevali Çori and Ba'ja demonstrate a diverse gene pool at Nevali Çori that supports connectedness within the Fertile Crescent during the earlier phases of Neolithization and evidence of consanguineous union in the PPNB Ba'ja and the Iron Age Nevali Çori.

Isotope analysis of human dental calculus δ13 CO3 2- : Investigating a potential new proxy for sugar consumption.

RATIONALE: Dental calculus (mineralised dental plaque) is composed primarily of hydroxyapatite. We hypothesise that the carbonate component of dental calculus will reflect the isotopic composition of ingested simple carbohydrates. Therefore, dental calculus carbonates may be an indicator for sugar consumption, and an alternative to bone carbonate in isotopic palaeodiet studies. METHODS: We utilised Fourier transform infrared attenuated total reflectance analysis to characterise the composition and crystallisation of bone and dental calculus before isotope analysis of carbonate. Using a Sercon 20-22 mass spectrometer coupled with a Sercon GSL sample preparation system and an IsoPrime 100 dual inlet mass spectrometer plus Multiprep device to measure carbon, we tested the potential of dental calculus carbonate to identify C4 resources in diet through analysis of δ13 C values in paired bone, calculus and teeth mineral samples. RESULTS: The modern population shows higher δ13 C values in all three tissue carbonates compared to both archaeological populations. Clear differences in dental calculus δ13 C values are observed between the modern and archaeological individuals suggesting potential for utilising dental calculus in isotope palaeodiet studies. The offset between dental calculus and either bone or enamel carbonate δ13 C values is large and consistent in direction, with no consistent offset between the δ13 C values for the three tissues per individual. CONCLUSIONS: Our results support dental calculus carbonate as a new biomaterial to identify C4 sugar through isotope analysis. Greater carbon fractionation in the mouth is likely due to the complex formation of dental calculus as a mineralized biofilm, which results in consistently high δ13 C values compared to bone and enamel.

Correction to: Imaging of Bronchial Pathology in Antibody Deficiency: Data from the European Chest CT Group.

In the original version of this article unfortunately two authors were missing: Dr. Jürgen Weidemann and Dr. Daniel Berthold. The correct list of authors is presented above.

Imaging of Bronchial Pathology in Antibody Deficiency: Data from the European Chest CT Group.

Studies of chest computed tomography (CT) in patients with primary antibody deficiency syndromes (ADS) suggest a broad range of bronchial pathology. However, there are as yet no multicentre studies to assess the variety of bronchial pathology in this patient group. One of the underlying reasons is the lack of a consensus methodology, a prerequisite to jointly document chest CT findings. We aimed to establish an international platform for the evaluation of bronchial pathology as assessed by chest CT and to describe the range of bronchial pathologies in patients with antibody deficiency. Ffteen immunodeficiency centres from 9 countries evaluated chest CT scans of patients with ADS using a predefined list of potential findings including an extent score for bronchiectasis. Data of 282 patients with ADS were collected. Patients with common variable immunodeficiency disorders (CVID) comprised the largest subgroup (232 patients, 82.3%). Eighty percent of CVID patients had radiological evidence of bronchial pathology including bronchiectasis in 61%, bronchial wall thickening in 44% and mucus plugging in 29%. Bronchiectasis was detected in 44% of CVID patients aged less than 20 years. Cough was a better predictor for bronchiectasis than spirometry values. Delay of diagnosis as well as duration of disease correlated positively with presence of bronchiectasis. The use of consensus diagnostic criteria and a pre-defined list of bronchial pathologies allows for comparison of chest CT data in multicentre studies. Our data suggest a high prevalence of bronchial pathology in CVID due to late diagnosis or duration of disease.

Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency disorders.

Common Variable Immunodeficiency Disorders (CVIDs) are the most prevalent cause of primary antibody failure. CVIDs are highly variable and a genetic causes have been identified in <5% of patients. Here, we performed whole genome sequencing (WGS) of 34 CVID patients (94% sporadic) and combined them with transcriptomic profiling (RNA-sequencing of B cells) from three patients and three healthy controls. We identified variants in CVID disease genes TNFRSF13B, TNFRSF13C, LRBA and NLRP12 and enrichment of variants in known and novel disease pathways. The pathways identified include B-cell receptor signalling, non-homologous end-joining, regulation of apoptosis, T cell regulation and ICOS signalling. Our data confirm the polygenic nature of CVID and suggest individual-specific aetiologies in many cases. Together our data show that WGS in combination with RNA-sequencing allows for a better understanding of CVIDs and the identification of novel disease associated pathways.

Antibody deficiency secondary to chronic lymphocytic leukemia: Should patients be treated with prophylactic replacement immunoglobulin?

Hypogammaglobulinemia is a common finding in chronic lymphocytic leukemia (CLL). Its incidence increases with disease duration and stage such that it is present in up to 85 % of patients at some point in their disease course. It is therefore important to monitor patients for the development of an antibody deficiency. However, not all patients with antibody deficiency secondary to CLL are symptomatic with bacterial infections. In addition patients are susceptible to viral, fungal and opportunistic infections as a result of iatrogenic immunosuppression and through a variety of disease-related mechanisms, which affect cellular immunity and phagocytes. Published guidelines suggest that patients with a history of recurrent bacterial infections and a documented failure of antibody production should be treated with antibiotic prophylaxis in the first instance, with replacement immunoglobulin reserved for those who continue to suffer with significant bacterial infections. Here we present a review of the existing literature in order to provide a practical approach, based on best available evidence, to the investigation, monitoring and treatment of patients with antibody failure secondary to CLL; and we highlight areas in which further studies are needed.

Patients with non-Jo-1 anti-tRNA-synthetase autoantibodies have worse survival than Jo-1 positive patients.

OBJECTIVE: To compare the cumulative survival and event free survival in patients with Jo-1 versus non-Jo-1 anti-tRNA synthetase autoantibodies (anti-synAb). METHODS: Anti-synAb positive patients initially evaluated from 1985 to 2009 were included regardless of the connective tissue disease (CTD) diagnosis. Clinical data were extracted from a prospectively collected database and chart review. Survival between Jo-1 and non-Jo-1 was compared by log rank and Cox proportional hazards methods. RESULTS: 202 patients possessed anti-synAb: 122 Jo-1 and 80 non-Jo-1 (35 PL-12; 25 PL-7; 9 EJ; 6 KS; 5 OJ). The diagnoses at first visit for Jo-1 and non-Jo-1 patients were myositis in 83% and 40.0%, overlap or undifferentiated CTD in 17% and 47.5%, and systemic sclerosis in 0% and 12.5%, respectively (p<0.001). The median delay in diagnosis was 0.4 years in Jo-1 patients versus 1.0 year in non-Jo-1 patients (p<0.001). The most common causes of death in the overall cohort were pulmonary fibrosis in 49% and pulmonary hypertension in 11%. The 5- and 10-year unadjusted cumulative survival was 90% and 70% for Jo-1 patients, and 75% and 47% for non-Jo-1 patients (p<0.005). The hazard ratio (HR) of non-Jo-1 patients compared with Jo-1 patients was 1.9 (p=0.01) for cumulative and 1.9 (p=0.008) for event free survival from diagnosis. Age at first diagnosis and diagnosis delay but not gender, ethnicity and CTD diagnosis influenced survival. CONCLUSIONS: Non-Jo-1 anti-synAb positive patients have decreased survival compared with Jo-1 patients. The difference in survival may be partly attributable to a delay in diagnosis in the non-Jo-1 patients.

Unravelling social status in the first medieval military order of the Iberian Peninsula using isotope analysis.

Medieval Iberia witnessed the complex negotiation of religious, social, and economic identities, including the formation of religious orders that played a major role in border disputes and conflicts. While archival records provide insights into the compositions of these orders, there have been few direct dietary or osteoarchaeological studies to date. Here, we analysed 25 individuals discovered at the Zorita de los Canes Castle church cemetery, Guadalajara, Spain, where members of one of the first religious orders, the Order of Calatrava knights, were buried between the 12th to 15th centuries CE. Stable carbon (δ13C) and nitrogen (δ15N) isotope analyses of bone collagen reveal dietary patterns typical of the Medieval social elite, with the Bayesian R model, 'Simmr' suggesting a diet rich in poultry and marine fish in this inland population. Social comparisons and statistical analyses further support the idea that the order predominantly comprised the lower nobility and urban elite in agreement with historical sources. Our study suggests that while the cemetery primarily served the order's elite, the presence of individuals with diverse dietary patterns may indicate complexities of temporal use or wider social interaction of the medieval military order.

Diets, stress, and disease in the Etruscan society: Isotope analysis and infantile skeletal palaeopathology from Pontecagnano (Campania, southern Italy, 730-580 BCE).

Susceptibility to morbidity and mortality is increased in early life, yet proactive measures, such as breastfeeding and weaning practices, can be taken through specific investments from parents and wider society. The extent to which such biosocialcultural investment was achieved within 1st millennium BCE Etruscan society, of whom little written sources are available, is unkown. This research investigates life histories in non-adults and adults from Pontecagnano (southern Italy, 730-580 BCE) in order to track cross-sectional and longitudinal breastfeeding and weaning patterns and to characterize the diet more broadly. Stable carbon and nitrogen isotope analysis of incrementally-sampled deciduous and permanent dentine (n = 15), bulk bone collagen (n = 38), and tooth enamel bioapatite (n = 21) reveal the diet was largely based on C3 staple crops with marginal contributions of animal protein. Millet was found to play a role for maternal diet and trajectories of breastfeeding and feeding for some infants and children at the site. The combination of multiple isotope systems and tissues demonstrates exclusive breastfeeding was pursued until 0.6 years, followed by progressive introduction of proteanocius supplementary foods during weaning that lasted between approximately 0.7 and 2.6 years. The combination of biochemical data with macroscopic skeletal lesions of infantile metabolic diseases and physiological stress markers showed high δ15Ndentine in the months prior to death consistent with the isotopic pattern of opposing covariance.

Disparities in Retinal Vein Occlusion Presentation and Initiation of Anti-VEGF Therapy: An Academy IRIS® Registry Analysis.

OBJECTIVE: Investigate disparities in retinal vein occlusion (RVO) presentation and initiation of anti-VEGF treatment. DESIGN: Retrospective cohort study. SUBJECTS: Patients in the American Academy of Ophthalmology IRIS® (Intelligent Research in Sight) Registry database (2015-2021) with branch or central RVO and macular edema (ME). METHODS: The association of demographic characteristics and presenting visual acuity (VA) with anti-VEGF treatment initiation were quantified using multivariable logistic regression. MAIN OUTCOME MEASURES: Treatment with ≥ 1 anti-VEGF injection within 12 months after RVO diagnosis. RESULTS: A total of 304 558 eligible patients with RVO and ME were identified. Age at presentation varied by race, ethnicity, sex, and RVO type (all P values < 0.001). Within the first year after RVO presentation, 192 602 (63.2%) patients received ≥ 1 anti-VEGF injection. In a multivariable regression model adjusting for relevant covariates, female (vs. male) patients had lower odds of receiving injections (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.93-0.96; P < 0.0001) as did Black/African American (vs. White) patients (OR, 0.90; 95% CI, 0.88-0.92; P < 0.0001) and Asian (vs. White) patients (OR, 0.95; 95% CI, 0.91-0.99; P = 0.02), whereas older patients (vs. patients aged < 51 years) had higher odds (61-70 years: OR, 1.20; 95% CI, 1.16-1.24; 71-80 years: OR, 1.20; 95% CI, 1.16-1.24; > 80 years: OR, 1.15; 95% CI, 1.11-1.18; all P values < 0.0001). Hispanic (vs. non-Hispanic) patients had a small increased odds of treatment initiation (OR, 1.08; 95% CI, 1.04-1.11; P < 0.0001). Results were similar in the subset of 226 143 patients with VA data. In this subset, patients with presenting VA < 20/40 to 20/200 were most frequently treated in the first year after diagnosis (∼ 70%) and patients with light perception/no light perception (LP-NLP) vision or VA of 20/20 or better were treated least frequently (36.9% and 41.9%, respectively). CONCLUSIONS: In this large national clinical registry, 37% of RVO patients with ME had no anti-VEGF treatment documented in the first year after diagnosis. Black/African American, Asian, and female patients and patients with VA of LP-NLP were least likely to receive treatment. Awareness of this undertreatment and these disparities highlight the need for initiatives to ensure all RVO patients receive timely anti-VEGF injections for optimized visual outcomes. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Multi-isotope reconstruction of Late Pleistocene large-herbivore biogeography and mobility patterns in Central Europe.

Interpretations of Late Pleistocene hominin adaptative capacities by archaeologists have focused heavily on their exploitation of certain prey and documented contemporary behaviours for these species. However, we cannot assume that animal prey-taxa ecology and ethology were the same in the past as in the present, or were constant over archaeological timescales. Sequential isotope analysis of herbivore teeth has emerged as a particularly powerful method of directly reconstructing diet, ecology and mobility patterns on sub-annual scales. Here, we apply 87Sr/86Sr isotope analysis, in combination with δ18O and δ13C isotope analysis, to sequentially sampled tooth enamel of prevalent herbivore species that populated Europe during the Last Glacial Period, including Rangifer tarandus, Equus sp. and Mammuthus primigenius. Our samples come from two open-air archaeological sites in Central Germany, Königsaue and Breitenbach, associated with Middle Palaeolithic and early Upper Palaeolithic cultures, respectively. We identify potential inter- and intra-species differences in range size and movement through time, contextualised through insights into diet and the wider environment. However, homogeneous bioavailable 87Sr/86Sr across large parts of the study region prevented the identification of specific migration routes. Finally, we discuss the possible influence of large-herbivore behaviour on hominin hunting decisions at the two sites.

Biomolecular evidence for changing millet reliance in Late Bronze Age central Germany.

The Bronze Age of Central Europe was a period of major social, economic, political and ideological change. The arrival of millet is often seen as part of wider Bronze Age connectivity, yet understanding of the subsistence regimes underpinning this dynamic period remains poor for this region, in large part due to a dominance of cremation funerary rites, which hinder biomolecular studies. Here, we apply stable isotope analysis, radiocarbon dating and archaeobotanical analysis to two Late Bronze Age (LBA) sites, Esperstedt and Kuckenburg, in central Germany, where human remains were inhumed rather than cremated. We find that people buried at these sites did not consume millet before the Middle Bronze Age (MBA) (ca. 1600 BCE). However, by the early LBA (ca. 1300-1050 BCE) people consumed millet, often in substantial quantities. This consumption appears to have subsequently diminished or ceased around 1050-800 BCE, despite charred millet grains still being found in the archaeological deposits from this period. The arrival of millet in this region, followed by a surge in consumption spanning two centuries, indicates a complex interplay of cultural and economic factors, as well as a potential use of millet to buffer changes in aridity in a region increasingly prone to crop failure in the face of climate change today.

Earliest known funerary rites in Wallacea after the last glacial maximum.

The insular region of Wallacea has become a focal point for studying Pleistocene human ecological and cultural adaptations in island environments, however, little is understood about early burial traditions during the Pleistocene. Here we investigate maritime interactions and burial practices at Ratu Mali 2, an elevated coastal cave site on the small island of Kisar in the Lesser Sunda Islands of eastern Indonesia dated to 15,500-3700 cal. BP. This multidisciplinary study demonstrates extreme marine dietary adaptations, engagement with an extensive exchange network across open seas, and early mortuary practices. A flexed male and a female, interred in a single grave with abundant shellfish and obsidian at Ratu Mali 2 by 14.7 ka are the oldest known human burials in Wallacea with established funerary rites. These findings highlight the impressive flexibility of our species in marginal environments and provide insight into the earliest known ritualised treatment of the dead in Wallacea.

A clinical and serologic comparison of African American and Caucasian patients with systemic sclerosis.

OBJECTIVE: Epidemiology studies suggest that systemic sclerosis (SSc) is more common, occurs at a younger age, and is more severe in African Americans than Caucasians. However, the scleroderma autoantibody profile is very different between these 2 ethnic groups. This study was undertaken to examine the demographic and disease features, frequency and severity of internal organ system involvement, and survival in African American patients compared to Caucasian patients with SSc, giving particular attention to their serum autoantibody profiles. METHODS: Demographic features, clinical characteristics, autoantibody profile, organ involvement, and survival were studied in consecutive African American and Caucasian patients with SSc whose visits were recorded between 1972 and 2007 as part of the Pittsburgh Scleroderma Database. The Medsger Severity Score for SSc was used to determine the severity of disease. RESULTS: African American patients were more likely to have anti-topoisomerase I (anti-topo I), anti-U1 RNP, and anti-U3 RNP autoantibodies. In comparing African American and Caucasian patients with these antibodies, pulmonary fibrosis was found to be more frequent and more severe, and the rate of survival was decreased, in African American patients with anti-topo I antibodies compared to Caucasian patients with anti-topo I. Pulmonary fibrosis was also more severe in the anti-U1 RNP-positive patients, but this was not associated with a difference in survival between African Americans and Caucasians. Anti-U3 RNP was associated with more severe gastrointestinal involvement in African Americans compared to Caucasians. CONCLUSION: African Americans with SSc have more severe disease complications compared to Caucasians with SSc, and this is associated with both the type of autoantibody present and the severity of interstitial lung disease. Thus, it is hoped that early aggressive intervention in African Americans with interstitial lung disease will improve outcomes.

Human interactions with tropical environments over the last 14,000 years at Iho Eleru, Nigeria.

The Ihò Eléérú (or Iho Eleru) rock shelter, located in Southwest Nigeria, is the only site from which Pleistocene-age hominin fossils have been recovered in western Africa. Excavations at Iho Eleru revealed regular human occupations ranging from the Later Stone Age (LSA) to the present day. Here, we present chronometric, archaeobotanical, and paleoenvironmental findings, which include the taxonomic, taphonomic, and isotopic analyses of what is the only Pleistocene faunal assemblage documented in western Africa. Our results indicate that the local landscape surrounding Iho Eleru, although situated within a regional open-canopy biome, was forested throughout the past human occupation of the site. At a regional scale, a shift from forest- to savanna-dominated ecotonal environment occurred during a mid-Holocene warm event 6,000 years ago, with a subsequent modern reforestation of the landscape. Locally, no environmental shift was observable, placing Iho Eleru in a persistent forested "island" during the period of occupation.

Isotopic and proteomic evidence for communal stability at Pre-Pottery Neolithic Jericho in the Southern Levant.

As one of the key, long-term occupied sites in the Southern Levant, Jericho was one of the most important early Neolithic centres to witness social and economic changes associated with the domestication of plants and animals. This study applies strontium (87Sr/86Sr), oxygen (δ18O) and carbon (δ13C) isotope analyses to the enamel of 52 human teeth from Pre-Pottery Neolithic (PPN) layers of Jericho to directly study human diet and mobility and investigate the degree of consolidation and the flexibility of social organization of Jericho society in the PPN period. The results indicate only two non-local individuals out of the 44 sampled inhabitants identified by strontium isotope analysis and are consistent with the presence of a largely sedentary community at PPN Jericho with no evidence for large-scale migration. We also construct strontium spatial baselines (87Sr/86Sr map) with local 87Sr/86Sr signatures for the sites across the Southern Levant based on systematic compilation and analysis of available data. In addition, we apply proteomic analysis of sex-specific amelogenin peptides in tooth enamel for sex estimation of the sampled individuals (n = 44), the results of which showed a sex-biased ratio (more male than female detected in this sample pool) in Jericho society during the PPN period, which may be due to the limited sample size or selective ritual practices like particular burial zones used for specific groups. We also pretreated a batch of human bone samples recovered from PPNB Jericho for stable carbon and nitrogen isotope analyses for dietary investigations. However, the extracted collagen showed poor preservation and no valid δ13C or δ15N data were obtained.

Interdisciplinary evidence for early domestic horse exploitation in southern Patagonia.

The introduction of domestic horses transformed Indigenous societies across the grasslands of Argentina, leading to the emergence of specialized horse cultures across the Southern Cone. However, the dynamics of this introduction are poorly chronicled by historic records. Here, we apply archaeozoological and biomolecular techniques to horse remains from the site of Chorrillo Grande 1 in southern Argentina. Osteological and taphonomic analyses suggest that horses were pastorally managed and used for food by Aónikenk/Tehuelche hunter-gatherers before the onset of permanent European settlement, as early as the mid-17th century. DNA-based sex identifications suggest consumption of both male and female horses, while ceramic residue also shows use of guanaco products. Sequential isotope analyses on horse dentition reveal an origin in southern Patagonia and movement of these animals between the Río Coig and Río Gallegos basins. These results reinforce emerging evidence for rapid Indigenous-mediated dispersal of horses in the Americas and demonstrate that horses catalyzed rapid economic and social transformations.