A chronology for the earliest human burials at Cuchipuy, central Chile

Cuchipuy is an archaeological site within the ancient Laguna de Tagua Tagua area (O’Higgins Region, central Chile; known for containing the remains of extinct fauna), with evidence for cultural activity spanning most of the Holocene, including over 50 human burials. The bulk of chronometric work at Cuchipuy was carried out in the 1980s, where a discrepancy within the radiocarbon dating results raised questions on the antiquity of the oldest funerary deposits (Stratum 4). Given the importance of both the site and area in prehistoric studies, this analysis aimed to reassess the chronology of Stratum 4 through the production of new radiocarbon dates on human remains and the application of Bayesian modelling. When combined with previously published ages, results place the commencement of Stratum 4 at 7320–7160 cal BP, within the early-mid Holocene. This is later than previous conclusions based on the discrepant dataset, refuting a temporal connection to Paleoindian deposits within the region. In addition, stable light isotope results suggest that human diet during the period was diverse, relying on both terrestrial and freshwater aquatic resources. This pattern changes with later populations, however, where the isotopic signal reflects the consumption of mainly terrestrial resources

Dental malocclusions are not just about small and weak bones: assessing the morphology of the mandible with cross-section analysis and geometric morphometrics

© 2019, The Author(s).Objectives: Dental malocclusions in modern populations would be the result of small and weak jaws developing under low masticatory loads. We assess the validity of this by characterising the external and internal morphology of mandibles affected by class II and III malocclusions and comparing them with those from individuals with different masticatory load patterns. Materials and methods: CTs from up to 118 individuals exerting intensive, medium and low masticatory loads with harmonic occlusion, and from class II and III individuals, were used to compare their external shape using geometric morphometrics, as well as their internal amount and distribution of cortical bone. Results: The low-load groups (harmonic, class II and III occlusion) are externally more gracile than the intense and medium load groups. But more relevant in shape variation is a marked allometric pattern, which differentiates class II (small) and III (large) mandibles. Despite gracility, the re

Structural surfaceomics reveals an AML-specific conformation of integrin β2 as a CAR T cellular therapy target

Safely expanding indications for cellular therapies has been challenging given a lack of highly cancer-specific surface markers. Here we explore the hypothesis that tumor cells express cancer-specific surface protein conformations that are invisible to standard target discovery pipelines evaluating gene or protein expression, and these conformations can be identified and immunotherapeutically targeted. We term this strategy integrating cross-linking mass spectrometry with glycoprotein surface capture 'structural surfaceomics'. As a proof of principle, we apply this technology to acute myeloid leukemia (AML), a hematologic malignancy with dismal outcomes and no known optimal immunotherapy target. We identify the activated conformation of integrin β2 as a structurally defined, widely expressed AML-specific target. We develop and characterize recombinant antibodies to this protein conformation and show that chimeric antigen receptor T cells eliminate AML cells and patient-derived xenografts without notable toxicity toward normal hematopoietic cells. Our findings validate an AML conformation-specific target antigen and demonstrate a tool kit for applying these strategies more broadly