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

Unilateral Hypofunction of the Masseter Leads to Molecular and 3D Morphometric Signs of Atrophy in Ipsilateral Agonist Masticatory Muscles in Adult Mice

Mice are commonly used to study mandibular dynamics due to their similarity in chewing cycle patterns with humans. Adult mice treated unilaterally with botulinum toxin type A (BoNTA) in the masseter exhibit atrophy of this muscle characterized by an increase in the gene expression of atrophy-related molecular markers, and a reduction in both muscle fiber diameter and muscle mass at 14d. However, the impact of this muscle imbalance on the non-treated masticatory muscles remains unexplored. Here, we hypothesize that the unilateral masseter hypofunction leads to molecular and 3D morphometric signs of atrophy of the masseter and its agonist masticatory muscles in adult mice. Twenty-three 8-week-old male BALB/c mice received a single injection of BoNTA in the right masseter, whereas the left masseter received the same volume of saline solution (control side). Animals were euthanized at 2d, 7d, and 14d, and the masticatory muscles were analyzed for mRNA expression. Five heads were harvested at 14d, fixed, stained with a contrast-enhanced agent, and scanned using X-ray microtomography. The three-dimensional morphometric parameters (the volume and thickness) from muscles in situ were obtained. Atrogin-1/MAFbx, MuRF-1, and Myogenin mRNA gene expression were significantly increased at 2 and 7d for both the masseter and temporalis from the BoNTA side. For medial pterygoid, increased mRNA gene expression was found at 7d for Atrogin-1/MAFbx and at 2d–7d for Myogenin. Both the volume and thickness of the masseter, temporalis, and medial pterygoid muscles from the BoNTA side were significantly reduced at 14d. In contrast, the lateral pterygoid from the BoNTA side showed a significant increase in volume at 14d. Therefore, the unilateral hypofunction of the masseter leads to molecular and morphological signs of atrophy in both the BoNTA-injected muscle and its agonistic non-injected masticatory muscles. The generalized effect on the mouse masticatory apparatus when one of its components is intervened suggests the need for more clinical studies to determine the safety of BoNTA usage in clinical dentistry

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