RESUMO
Human culture, biology, and health were shaped dramatically by the onset of agriculture â¼12,000 y B.P. This shift is hypothesized to have resulted in increased individual fitness and population growth as evidenced by archaeological and population genomic data alongside a decline in physiological health as inferred from skeletal remains. Here, we consider osteological and ancient DNA data from the same prehistoric individuals to study human stature variation as a proxy for health across a transition to agriculture. Specifically, we compared "predicted" genetic contributions to height from paleogenomic data and "achieved" adult osteological height estimated from long bone measurements for 167 individuals across Europe spanning the Upper Paleolithic to Iron Age (â¼38,000 to 2,400 B.P.). We found that individuals from the Neolithic were shorter than expected (given their individual polygenic height scores) by an average of −3.82 cm relative to individuals from the Upper Paleolithic and Mesolithic (P = 0.040) and −2.21 cm shorter relative to post-Neolithic individuals (P = 0.068), with osteological vs. expected stature steadily increasing across the Copper (+1.95 cm relative to the Neolithic), Bronze (+2.70 cm), and Iron (+3.27 cm) Ages. These results were attenuated when we additionally accounted for genome-wide genetic ancestry variation: for example, with Neolithic individuals −2.82 cm shorter than expected on average relative to pre-Neolithic individuals (P = 0.120). We also incorporated observations of paleopathological indicators of nonspecific stress that can persist from childhood to adulthood in skeletal remains into our model. Overall, our work highlights the potential of integrating disparate datasets to explore proxies of health in prehistory.
Assuntos
Agricultura , Estatura , Fazendeiros , Saúde , Esqueleto , Adulto , Agricultura/história , Estatura/genética , Criança , DNA Antigo , Europa (Continente) , Fazendeiros/história , Variação Genética , Genômica , Saúde/história , História Antiga , Humanos , Paleopatologia , Esqueleto/anatomia & histologiaRESUMO
BACKGROUND & AIMS: BiTE (bispecific T-cell engager) immune therapy has demonstrated clinical activity in multiple tumor indications, but its influence in the tumor microenvironment remains unclear. CLDN18.2 is overexpressed in solid tumors including gastric cancer (GC) and pancreatic ductal adenocarcinoma (PDAC), both of which are characterized by the presence of immunosuppressive cells, including regulatory T cells (Tregs) and few effector T cells (Teffs). METHODS: We evaluated the activity of AMG 910, a CLDN18.2-targeted half-life extended (HLE) BiTE molecule, in GC and PDAC preclinical models and cocultured Tregs and Teffs in the presence of CLDN18.2-HLE-BiTE. RESULTS: AMG 910 induced potent, specific cytotoxicity in GC and PDAC cell lines. In GSU and SNU-620 GC xenograft models, AMG 910 engaged human CD3+ T cells with tumor cells, resulting in significant antitumor activity. AMG 910 monotherapy, in combination with a programmed death-1 (PD-1) inhibitor, suppressed tumor growth and enhanced survival in an orthotopic Panc4.14 PDAC model. Moreover, Treg infusion enhanced the antitumor efficacy of AMG 910 in the Panc4.14 model. In syngeneic KPC models of PDAC, treatment with a mouse surrogate CLDN18.2-HLE-BiTE (muCLDN18.2-HLE-BiTE) or the combination with an anti-PD-1 antibody significantly inhibited tumor growth. Tregs isolated from mice bearing KPC tumors that were treated with muCLDN18.2-HLE-BiTE showed decreased T cell suppressive activity and enhanced Teff cytotoxic activity, associated with increased production of type I cytokines and expression of Teff gene signatures. CONCLUSIONS: Our data suggest that BiTE molecule treatment converts Treg function from immunosuppressive to immune enhancing, leading to antitumor activity in immunologically "cold" tumors.
Assuntos
Anticorpos Biespecíficos , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Animais , Camundongos , Linfócitos T Reguladores/metabolismo , Anticorpos Biespecíficos/genética , Anticorpos Biespecíficos/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Moléculas de Adesão Celular , Carcinoma Ductal Pancreático/tratamento farmacológico , Imunidade , Microambiente Tumoral , ClaudinasRESUMO
Neanderthals are commonly depicted as leading dangerous lives and permanently struggling for survival. This view largely relies on the high incidences of trauma that have been reported1,2 and have variously been attributed to violent social behaviour3,4, highly mobile hunter-gatherer lifestyles2 or attacks by carnivores5. The described Neanderthal pattern of predominantly cranial injuries is further thought to reflect violent encounters with large prey mammals, resulting from the use of close-range hunting weapons1. These interpretations directly shape our understanding of Neanderthal lifestyles, health and hunting abilities, yet mainly rest on descriptive, case-based evidence. Quantitative, population-level studies of traumatic injuries are rare. Here we reassess the hypothesis of higher cranial trauma prevalence among Neanderthals using a population-level approach-accounting for preservation bias and other contextual data-and an exhaustive fossil database. We show that Neanderthals and early Upper Palaeolithic anatomically modern humans exhibit similar overall incidences of cranial trauma, which are higher for males in both taxa, consistent with patterns shown by later populations of modern humans. Beyond these similarities, we observed species-specific, age-related variation in trauma prevalence, suggesting that there were differences in the timing of injuries during life or that there was a differential mortality risk of trauma survivors in the two groups. Finally, our results highlight the importance of preservation bias in studies of trauma prevalence.
Assuntos
Lesões Encefálicas Traumáticas/história , Fósseis , Homem de Neandertal , Crânio/patologia , Adulto , Determinação da Idade pelo Esqueleto , Animais , Lesões Encefálicas Traumáticas/epidemiologia , Lesões Encefálicas Traumáticas/patologia , Criança , Feminino , História Antiga , Humanos , Incidência , Estilo de Vida/história , Masculino , Prevalência , Determinação do Sexo pelo Esqueleto , Incerteza , Violência/história , Adulto JovemRESUMO
Recent genomic data have revealed multiple interactions between Neanderthals and modern humans, but there is currently little genetic evidence regarding Neanderthal behaviour, diet, or disease. Here we describe the shotgun-sequencing of ancient DNA from five specimens of Neanderthal calcified dental plaque (calculus) and the characterization of regional differences in Neanderthal ecology. At Spy cave, Belgium, Neanderthal diet was heavily meat based and included woolly rhinoceros and wild sheep (mouflon), characteristic of a steppe environment. In contrast, no meat was detected in the diet of Neanderthals from El Sidrón cave, Spain, and dietary components of mushrooms, pine nuts, and moss reflected forest gathering. Differences in diet were also linked to an overall shift in the oral bacterial community (microbiota) and suggested that meat consumption contributed to substantial variation within Neanderthal microbiota. Evidence for self-medication was detected in an El Sidrón Neanderthal with a dental abscess and a chronic gastrointestinal pathogen (Enterocytozoon bieneusi). Metagenomic data from this individual also contained a nearly complete genome of the archaeal commensal Methanobrevibacter oralis (10.2× depth of coverage)-the oldest draft microbial genome generated to date, at around 48,000 years old. DNA preserved within dental calculus represents a notable source of information about the behaviour and health of ancient hominin specimens, as well as a unique system that is useful for the study of long-term microbial evolution.
Assuntos
DNA Antigo/análise , Cálculos Dentários/química , Dieta/história , Preferências Alimentares , Saúde/história , Homem de Neandertal/microbiologia , Homem de Neandertal/psicologia , Animais , Bélgica , Carnivoridade , Cavernas , Enterocytozoon/genética , Enterocytozoon/isolamento & purificação , Genoma Bacteriano/genética , História Antiga , Humanos , Intestinos/microbiologia , Carne/história , Methanobrevibacter/genética , Methanobrevibacter/isolamento & purificação , Boca/microbiologia , Pan troglodytes/microbiologia , Penicillium/química , Perissodáctilos , Ovinos , Espanha , Estômago/microbiologia , Simbiose , Fatores de Tempo , Vegetarianos/históriaRESUMO
Pathogens and associated outbreaks of infectious disease exert selective pressure on human populations, and any changes in allele frequencies that result may be especially evident for genes involved in immunity. In this regard, the 1346-1353 Yersinia pestis-caused Black Death pandemic, with continued plague outbreaks spanning several hundred years, is one of the most devastating recorded in human history. To investigate the potential impact of Y. pestis on human immunity genes, we extracted DNA from 36 plague victims buried in a mass grave in Ellwangen, Germany in the 16th century. We targeted 488 immune-related genes, including HLA, using a novel in-solution hybridization capture approach. In comparison with 50 modern native inhabitants of Ellwangen, we find differences in allele frequencies for variants of the innate immunity proteins Ficolin-2 and NLRP14 at sites involved in determining specificity. We also observed that HLA-DRB1*13 is more than twice as frequent in the modern population, whereas HLA-B alleles encoding an isoleucine at position 80 (I-80+), HLA C*06:02 and HLA-DPB1 alleles encoding histidine at position 9 are half as frequent in the modern population. Simulations show that natural selection has likely driven these allele frequency changes. Thus, our data suggest that allele frequencies of HLA genes involved in innate and adaptive immunity responsible for extracellular and intracellular responses to pathogenic bacteria, such as Y. pestis, could have been affected by the historical epidemics that occurred in Europe.
Assuntos
Peste , Yersinia pestis , DNA , Genômica , Humanos , Pandemias/história , Peste/genética , Yersinia pestis/genéticaRESUMO
We generated genome-wide data from 69 Europeans who lived between 8,000-3,000 years ago by enriching ancient DNA libraries for a target set of almost 400,000 polymorphisms. Enrichment of these positions decreases the sequencing required for genome-wide ancient DNA analysis by a median of around 250-fold, allowing us to study an order of magnitude more individuals than previous studies and to obtain new insights about the past. We show that the populations of Western and Far Eastern Europe followed opposite trajectories between 8,000-5,000 years ago. At the beginning of the Neolithic period in Europe, â¼8,000-7,000 years ago, closely related groups of early farmers appeared in Germany, Hungary and Spain, different from indigenous hunter-gatherers, whereas Russia was inhabited by a distinctive population of hunter-gatherers with high affinity to a â¼24,000-year-old Siberian. By â¼6,000-5,000 years ago, farmers throughout much of Europe had more hunter-gatherer ancestry than their predecessors, but in Russia, the Yamnaya steppe herders of this time were descended not only from the preceding eastern European hunter-gatherers, but also from a population of Near Eastern ancestry. Western and Eastern Europe came into contact â¼4,500 years ago, as the Late Neolithic Corded Ware people from Germany traced â¼75% of their ancestry to the Yamnaya, documenting a massive migration into the heartland of Europe from its eastern periphery. This steppe ancestry persisted in all sampled central Europeans until at least â¼3,000 years ago, and is ubiquitous in present-day Europeans. These results provide support for a steppe origin of at least some of the Indo-European languages of Europe.
Assuntos
Evolução Cultural/história , Pradaria , Migração Humana/história , Idioma/história , Europa (Continente)/etnologia , Genoma Humano/genética , História Antiga , Humanos , Masculino , Polimorfismo Genético/genética , Dinâmica Populacional , Federação RussaRESUMO
OBJECTIVES: This study characterizes patterns of cranial trauma prevalence in a large sample of Upper Paleolithic (UP) fossil specimens (40,000-10,000 BP). MATERIALS AND METHODS: Our sample comprised 234 individual crania (specimens), representing 1,285 cranial bones (skeletal elements), from 101 Eurasian UP sites. We used generalized linear mixed models (GLMMs) to assess trauma prevalence in relation to age-at-death, sex, anatomical distribution, and between pre- and post-Last Glacial Maximum (LGM) samples, while accounting for skeletal preservation. RESULTS: Models predicted a mean cranial trauma prevalence of 0.07 (95% CI 0.003-0.19) at the level of skeletal elements, and of 0.26 (95% CI 0.08-0.48) at the level of specimens, each when 76-100% complete. Trauma prevalence increased with skeletal preservation. Across specimen and skeletal element datasets, trauma prevalence tended to be higher for males, and was consistently higher in the old age group. We found no time-specific trauma prevalence patterns for the two sexes or age cohorts when comparing samples from before and after the LGM. Samples showed higher trauma prevalence in the vault than in the face, with vault remains being affected predominantly in males. DISCUSSION: Cranial trauma prevalence in UP humans falls within the variation described for Mesolithic and Neolithic samples. According to our current dataset, UP males and females were exposed to slightly different injury risks and trauma distributions, potentially due to different activities or behaviors, yet both sexes exhibit more trauma among the old. Environmental stressors associated with climatic changes of the LGM are not reflected in cranial trauma prevalence. To analyze trauma in incomplete skeletal remains we propose GLMMs as an informative alternative to crude frequency calculations.
Assuntos
Traumatismos Craniocerebrais/epidemiologia , Crânio/lesões , Adolescente , Adulto , Criança , Traumatismos Craniocerebrais/patologia , Europa (Continente) , Feminino , Fósseis , Humanos , Masculino , Modelos Estatísticos , Paleopatologia , Prevalência , Crânio/patologia , Adulto JovemRESUMO
We sequenced the genomes of a â¼7,000-year-old farmer from Germany and eight â¼8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians, who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations' deep relationships and show that early European farmers had â¼44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages.
Assuntos
Genoma Humano/genética , População Branca/classificação , População Branca/genética , Agricultura/história , Ásia/etnologia , Europa (Continente) , História Antiga , Humanos , Dinâmica Populacional , Análise de Componente Principal , Recursos HumanosRESUMO
Throughout history, humans have been afflicted by parasitic worms, and eggs are readily detected in archaeological deposits. This study integrated parasitological and ancient DNA methods with a large sample set dating between Neolithic and Early Modern periods to explore the utility of molecular archaeoparasitology as a new approach to study the past. Molecular analyses provided unequivocal species-level parasite identification and revealed location-specific epidemiological signatures. Faecal-oral transmitted nematodes (Ascaris lumbricoides and Trichuris trichiura) were ubiquitous across time and space. By contrast, high numbers of food-associated cestodes (Diphyllobothrium latum and Taenia saginata) were restricted to medieval Lübeck. The presence of these cestodes and changes in their prevalence at approximately 1300 CE indicate substantial alterations in diet or parasite availability. Trichuris trichiura ITS-1 sequences grouped into two clades; one ubiquitous and one restricted to medieval Lübeck and Bristol. The high sequence diversity of T.tITS-1 detected in Lübeck is consistent with its importance as a Hanseatic trading centre. Collectively, these results introduce molecular archaeoparasitology as an artefact-independent source of historical evidence.
Assuntos
Evolução Cultural , Fezes/parasitologia , Helmintos/fisiologia , Tricuríase/história , Animais , Arqueologia , Cidades/epidemiologia , DNA Antigo/análise , Variação Genética , Alemanha/epidemiologia , Helmintos/classificação , História do Século XV , História do Século XVI , História do Século XVII , História Antiga , História Medieval , Humanos , Contagem de Ovos de Parasitas , Parasitologia , Tricuríase/epidemiologia , Tricuríase/parasitologia , Trichuris/genética , Trichuris/fisiologiaRESUMO
OBJECTIVES: The purpose of this study was to put forth a precise landmark-based technique for reconstructing the three-dimensional shape of human entheseal surfaces, to investigate whether the shape of human entheses is related to their size. The effects of age-at-death and bone length on entheseal shapes were also assessed. MATERIALS AND METHODS: The sample comprised high-definition three-dimensional models of three right hand entheseal surfaces, which correspond to 45 male adult individuals of known age. For each enthesis, a particular landmark configuration was introduced, whose precision was tested both within and between observers. The effect of three-dimensional size, age-at-death, and bone length on shape was investigated through shape regression. RESULTS: The method presented high intra-observer and inter-observer repeatability. All entheses showed significant allometry, with the area of opponens pollicis demonstrating the most substantial relationship. This was particularly due to variation related to its proximal elongated ridge. The effect of age-at-death and bone length on entheses was limited. DISCUSSION: The introduced methodology can set a reliable basis for further research on the factors affecting entheseal shape. Using both size and shape, variables can provide further information on entheseal variation and its biomechanical implications. The low entheseal variation by age verifies that specimens under 50 years of age are not substantially affected by age-related changes. The lack of correlation between entheseal shape and bone length or age implies that other factors may regulate entheseal surfaces. Future research should focus on multivariate shape patterns among entheses and their association with occupation.
Assuntos
Pontos de Referência Anatômicos/anatomia & histologia , Antropometria/métodos , Mãos/anatomia & histologia , Imageamento Tridimensional/métodos , Sistema Musculoesquelético/anatomia & histologia , Adulto , Pontos de Referência Anatômicos/diagnóstico por imagem , Pontos de Referência Anatômicos/fisiologia , Antropologia Física/normas , Mãos/diagnóstico por imagem , Mãos/fisiologia , Humanos , Imageamento Tridimensional/normas , Masculino , Sistema Musculoesquelético/diagnóstico por imagem , Sistema Musculoesquelético/patologia , Análise de Regressão , Reprodutibilidade dos TestesRESUMO
To optimize chiral separation conditions and to improve the knowledge of enantioseparation, it is important to know the binding constants K between analytes and cyclodextrins and the electrophoretic mobilities of the temporarily formed analyte-cyclodextrin-complexes. K values for complexes between eight phenethylamine enantiomers, namely ephedrine, pseudoephedrine, methylephedrine and norephedrine, and four different ß-cyclodextrin derivatives were determined by affinity capillary electrophoresis. The binding constants were calculated from the electrophoretic mobility values of the phenethylamine enantiomers at increasing concentrations of cyclodextrins in running buffer. Three different linear plotting methods (x-reciprocal, y-reciprocal, double reciprocal) and nonlinear regression were used for the determination of binding constants with ß-cyclodextrin, (2-hydroxypropyl)-ß-cyclodextrin, methyl-ß-cyclodextrin and 6-O-α-maltosyl-ß-cyclodextrin. The cyclodextrin concentration in a 50 mM phosphate buffer pH 3.0 was varied from 0 to 12 mM. To investigate the influence of the binding constant values on the enantioseparation the observed electrophoretic selectivities were compared with the obtained K values and the calculated enantiomer-cyclodextrin-complex mobilities. The different electrophoretic mobilities of the temporarily formed complexes were crucial factors for the migration order and enantioseparation of ephedrine derivatives. To verify the apparent binding constants determined by capillary electrophoresis, a titration process using ephedrine enantiomers and ß-cyclodextrin was carried out. Furthermore, the isothermal titration calorimetry measurements gave information about the thermal properties of the complexes.
Assuntos
Eletroforese Capilar/métodos , Fenetilaminas/química , beta-Ciclodextrinas/química , Calorimetria , Ensaio de Desvio de Mobilidade Eletroforética , Estereoisomerismo , TermodinâmicaRESUMO
OBJECTIVES: In anthropological sciences, entheses are widely utilized as occupational stress markers. However, the reaction of entheseal surfaces to mechanical loading is not well understood. Furthermore, previous studies on entheses relied on the individuals' occupation-at-death. Past research by one of us has identified two patterns among hand entheses, proposing that they reflect two synergistic muscle groups. Here, we investigate the association between these patterns and habitual manual activity using an extensively documented skeletal sample and a three-dimensional system of quantification. MATERIALS AND METHODS: The hand bones utilized belong to 45 individuals from mid-19th century Basel. These were male adults (18 to 48 years old) who were not directly related, showed no manual pathological conditions, and whose occupational activities during their lifetime were clearly documented and could be evaluated according to historical sources. The patterns of entheses were explored using principal component analysis on both raw and size-adjusted variables. The influence of age-at-death, body mass, and bone length was assessed through correlation tests. RESULTS: The analysis showed that the previously proposed patterns of entheses are present in our sample. Individuals with the same or comparable occupations presented similar entheseal patterns. These results were not considerably affected by entheseal overall size, age-at-death, body mass, or bone length. DISCUSSION: Individuals involved in intense manual labor during their lifetime presented a distinctive pattern of hand entheses, consistent with the application of high grip force. By contrast, individuals with less strenuous and/or highly mechanized occupations showed an entheseal pattern related to the thumb intrinsic muscles.
Assuntos
Ossos da Mão/patologia , Fenômenos Fisiológicos Musculoesqueléticos , Ocupações/história , Adolescente , Adulto , Antropologia Física , Feminino , Ossos da Mão/diagnóstico por imagem , História do Século XIX , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Ocupações/estatística & dados numéricos , Análise de Componente Principal , Suíça , Adulto JovemRESUMO
OBJECTIVE: The annual turnover rate of trabecular bone by far exceeds that of cortical bone and, therefore, is very sensitive to its daily loading regime. Here we test the hypothesis that the study of the trabecular bone architecture of the human humerus is able to differentiate between different habitual manual activities. MATERIALS AND METHODS: For this purpose, we compared the trabecular architecture of the humeral head in a Neolithic population to that of a sample of contemporary Europeans using micro-computed tomography (microCT). We defined in each specimen a spherical volume of interest with a diameter of 57.5 ± 2.5% of the maximal diameter of the humeral head to metrically analyze the bulk of humeral head trabecular architecture. We subsequently quantified the trabecular architectures in the VOIs, measuring seven standard 3D-morphometric parameters, and used univariate and multivariate statistical analyses for comparisons within and between populations. RESULTS: Univariate statistical analysis showed significant differences in a combination of 3D-morphometric parameters. A principal components analysis of the 3D-morphometrics of the trabecular architectures separated the Neolithic from the contemporary samples on the basis of differences in their gross trabecular architecture, including differences in the bone volume fraction (BV/TV), the number of trabeculae per unit length (Tb N), and the distance between trabeculae (Tb Sp). DISCUSSION: We interpret the significant differences found in the humeral trabecular bone of the Neolithic and the contemporary group as likely reflecting the distinct manual working routines. The trabecular bone configuration in the Neolithic sample shows presumably functional signatures of prehistoric subsistence techniques and activity levels.
Assuntos
Adaptação Fisiológica/fisiologia , Cabeça do Úmero/diagnóstico por imagem , Cabeça do Úmero/patologia , Adolescente , Adulto , Análise de Variância , Antropologia Física , Fenômenos Biomecânicos/fisiologia , Feminino , Atividades Humanas , Humanos , Masculino , Análise de Componente Principal , Microtomografia por Raio-X , Adulto JovemRESUMO
OBJECTIVES: Straight next to a segment of the outer ditch of the Late Neolithic Michelsberg Culture earthwork of Bruchsal-Aue in SW-Germany (ca. 4250-3650 calBC), a multiple burial of eight individuals (two male adults and six children) plus a subsequent child burial was excavated. In this study, we applied a multidisciplinary approach to elucidate interpersonal relationships and life histories within this collective. MATERIALS AND METHODS: To determine the identity of this collective, we performed aDNA analyses in addition to osteological examination using HVR I plus Y-chromosomal and autosomal STR profiling to find evidence for kinship relations. Strontium isotopic analyses were used to reconsider migrational behavior. To find evidence for a specific social affiliation, the individual diet was reconstructed by performing nitrogen and carbon isotopic analyses. Furthermore, radiocarbon-dating was carried out to integrate the burial context into an absolute timeframe. Two nearby single burials were included in the analyses for comparison. RESULTS: Because of a shared HVR I haplotype, three pairs of individuals were most likely linked by kinship, and statistical testing on autosomal STR profiles shows a high probability for the pair of two men being brothers. Although it cannot be excluded, isotopic data gave no clear proof for migration. A rather poor health status is indicated by skeletal stress markers even though the isotope data attest to a diet rich in meat and fish. DISCUSSION: Although clear kinship relations among the infants remain unconfirmed, a relationship could also be indicated by the positioning of the bodies in the burial pit. Whereas a common cause of death might have been the presupposition for their special treatment, interpersonal relationships were likely the decisive factor for the multiple burial.
Assuntos
Osso e Ossos/química , Cromossomos Humanos Y/genética , DNA Mitocondrial/genética , Repetições de Microssatélites/genética , Adulto , Antropologia Física , Arqueologia , Criança , Pré-Escolar , DNA Mitocondrial/análise , Feminino , Alemanha , Humanos , Lactente , Isótopos/análise , Masculino , Pessoa de Meia-IdadeRESUMO
Community differentiation is a fundamental topic of the social sciences, and its prehistoric origins in Europe are typically assumed to lie among the complex, densely populated societies that developed millennia after their Neolithic predecessors. Here we present the earliest, statistically significant evidence for such differentiation among the first farmers of Neolithic Europe. By using strontium isotopic data from more than 300 early Neolithic human skeletons, we find significantly less variance in geographic signatures among males than we find among females, and less variance among burials with ground stone adzes than burials without such adzes. From this, in context with other available evidence, we infer differential land use in early Neolithic central Europe within a patrilocal kinship system.
Assuntos
Agricultura , Família , Europa (Continente) , Feminino , Geografia , História Antiga , Humanos , MasculinoRESUMO
The rules and structure of human culture impact health as much as genetics or environment. To study these relationships, we combine ancient DNA (n = 230), skeletal metrics (n = 391), palaeopathology (n = 606) and dietary stable isotopes (n = 873) to analyse stature variation in Early Neolithic Europeans from North Central, South Central, Balkan and Mediterranean regions. In North Central Europe, stable isotopes and linear enamel hypoplasias indicate high environmental stress across sexes, but female stature is low, despite polygenic scores identical to males, and suggests that cultural factors preferentially supported male recovery from stress. In Mediterranean populations, sexual dimorphism is reduced, indicating male vulnerability to stress and no strong cultural preference for males. Our analysis indicates that biological effects of sex-specific inequities can be linked to cultural influences at least as early as 7,000 yr ago, and culture, more than environment or genetics, drove height disparities in Early Neolithic Europe.
Assuntos
Genética Populacional , Caracteres Sexuais , Feminino , Masculino , Humanos , DNA Mitocondrial , Europa (Continente) , IsótoposRESUMO
In the focus the pathological changes (stomatitis, sinusitis maxillaris among others) and indications of deficiency (cribra orbitalia, cribra cranii, cribra humeri, cribra fibularis, e.g.) among the 20 subadult individuals from the settlement burials of Lauchheim "Mittelhofen" were analysed and compared to the grownups (adultus-senilis) of the same population. The pathological indications of deficiency appear in similar frequencies as in the grownup individuals. Therefore, exogenous factors leading to the morphological changes must also be considered and the criterion of age at death is not be significant. Only cribra femoris (synonymously often called Allen's fossa or Fossa alleni) tend to occur more frequently in subadults. 85.7% of subadults exhibit cribra femoris compared to 55% of grownup individuals.
Assuntos
Sepultamento , HumanosRESUMO
For the Early Iron Age western Hallstatt culture, which includes the site of Magdalenenberg in southwest Germany, it has been proposed that people were mobile and maintained far reaching social and trading networks throughout Europe. We tested this hypothesis by analyzing multiple isotopes (strontium, oxygen, sulfur, carbon, and nitrogen) of the preserved skeletons from the Magdalenenberg elite cemetery to determine diets and to look for evidence of mobility. The analysis of carbon, nitrogen, and sulfur isotope ratios in collagen of humans (n = 50) and associated domestic fauna (n = 10) indicates a terrestrial-based diet. There was a heterogeneous range of isotope values in both strontium (0.70725 to 0.71923, n = 76) and oxygen (13.4 to 18.5, n = 78) measured in tooth enamel. Although many of the individuals had values consistent with being from Hallstatt culture sites within southwest Germany, some individuals likely originated from further afield. Possible areas include the Alps of Switzerland and Austria or even locations in Italy. Our study strongly supports the assumption of far reaching social and economic networks in the western Hallstatt culture.
Assuntos
Osso e Ossos/química , Isótopos de Oxigênio/análise , Isótopos de Estrôncio/análise , Dente/química , População Branca/estatística & dados numéricos , Adolescente , Adulto , Animais , Antropologia Física , Bovinos , Cemitérios , Criança , Pré-Escolar , Colágeno/química , Colágeno/isolamento & purificação , Dieta/história , Emigração e Imigração/história , Feminino , Alemanha , Cabras , História Antiga , Humanos , Lactente , Modelos Lineares , Masculino , OvinosRESUMO
BACKGROUND: The pathogen landscape in the Early European Middle Ages remains largely unexplored. Here, we perform a systematic pathogen screening of the rural community Lauchheim "Mittelhofen," in present-day Germany, dated to the Merovingian period, between fifth and eighth century CE. Skeletal remains of individuals were subjected to an ancient DNA metagenomic analysis. Genomes of the detected pathogens were reconstructed and analyzed phylogenetically. RESULTS: Over 30% of the individuals exhibit molecular signs of infection with hepatitis B virus (HBV), parvovirus B19, variola virus (VARV), and Mycobacterium leprae. Seven double and one triple infection were detected. We reconstructed four HBV genomes and one genome each of B19, VARV, and M. leprae. All HBV genomes are of genotype D4 which is rare in Europe today. The VARV strain exhibits a unique pattern of gene loss indicating that viruses with different gene compositions were circulating in the Early Middle Ages. The M. leprae strain clustered in branch 3 together with the oldest to-date genome from the UK. CONCLUSIONS: The high burden of infectious disease, together with osteological markers of physiological stress, reflect a poor health status of the community. This could have been an indirect result of the climate decline in Europe at the time, caused by the Late Antique Little Ice Age (LALIA). Our findings suggest that LALIA may have created an ecological context in which persistent outbreaks set the stage for major epidemics of severe diseases such as leprosy and smallpox hundreds of years later.
Assuntos
Coinfecção , Hanseníase , Pessoa de Meia-Idade , Humanos , Filogenia , Mycobacterium leprae/genética , Hanseníase/epidemiologia , Hanseníase/história , Hanseníase/microbiologia , DNA AntigoRESUMO
AMG 596 is a bispecific T-cell engager (BiTE) immuno-oncology therapy in clinical development for treatment of glioblastoma multiforme (GBM), the most common primary brain tumor in adults with limited therapeutic options. AMG 596 is composed of two single-chain variable fragments that simultaneously bind to the tumor-specific antigen, EGFR variant III (EGFRvIII), on GBM cells and to CD3 on T cells, thereby activating T cells to proliferate and secrete cytotoxic substances that induce lysis of the bound tumor cell. T-cell-redirected lysis by AMG 596 is very potent; in vitro studies revealed EC50 values in the low picomolar range, and in vivo studies showed that AMG 596 treatment significantly increased the overall survival of mice bearing EGFRvIII-expressing orthotopic tumors. In addition, AMG 596 activity is highly specific; no AMG 596-induced T-cell activity can be observed in assays with EGFRvIII-negative GBM cells, and no signs of toxicity and activity were observed in cynomolgus monkeys, which lack expression of EGFRvIII on normal tissues. With EGFRvIII-expressing GBM cells, we showed shedding of EGFRvIII-containing membrane vesicles, followed by vesicle uptake and EGFRvIII cell surface presentation by EGFRvIII noncoding GBM cells. Cell membrane presentation of EGFRvIII following microvesicle transfer allows engagement by AMG 596, resulting in T-cell activation and T-cell-dependent lysis of GBM cells. Together, these data show a compelling preclinical efficacy and safety profile of AMG 596, supporting its development as a novel immunotherapy for treatment of GBM.