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1.
Arch Oral Biol ; 89: 1-8, 2018 May.
Article in English | MEDLINE | ID: mdl-29407634

ABSTRACT

OBJECTIVES: This paper studies A. probatocephalus teeth and investigates the mechanical properties and chemical composition of the enameloid and dentin. DESIGN: Nanoindentation tests with a max load of 1000 µN and X-ray Energy Dispersive Spectroscopy (EDS) were performed along the diameter of the polished sample. Microstructural analysis of the dentin tubules was performed from SEM images. RESULTS: From nanoindentation testing, the dentin of the sheepshead teeth has a nanoindentation hardness of 0.89 ±â€¯0.21 (mean ±â€¯S.D.) GPa and a reduced Young's modulus of 23.29 ±â€¯5.30 GPa. The enameloid of A. probatocephalus has a hardness of 4.36 ±â€¯0.44 GPa and a mean reduced Young's modulus of 98.14 ±â€¯6.91 GPa. Additionally, nanoindentation tests showed that the enameloid's hardness and modulus increased closer to the surface of the tooth. X-ray Energy Dispersive Spectroscopy (EDS) data further suggests that the gradient may be a result of the wt% fluoride within the enameloid, where an increase in fluoride results in an increase in reduced Young's modulus and hardness. CONCLUSION: The microstructural characterization of the number density and area of the dentin tubules were used to address the porosity effect in the dentin to achieve the experimentally validated microhardness. The mechanical properties of the sheepshead teeth were also compared with previous nanoindentation tests from other aquatic species. The sheepshead teeth exhibit a greater reduced Young's modulus and hardness compared to shark and piranha teeth.


Subject(s)
Dentin/chemistry , Dentin/ultrastructure , Fishes/anatomy & histology , Tooth/chemistry , Tooth/ultrastructure , Animals , Biomechanical Phenomena , Dental Enamel/chemistry , Dental Enamel/diagnostic imaging , Dental Enamel/drug effects , Dental Stress Analysis , Dentin/diagnostic imaging , Dentin/drug effects , Elastic Modulus , Fluorides/pharmacology , Hardness , Stress, Mechanical , Tooth/diagnostic imaging , Tooth/drug effects
2.
Oncogene ; 33(20): 2665-73, 2014 May 15.
Article in English | MEDLINE | ID: mdl-23752194

ABSTRACT

Non-small-cell lung carcinoma (NSCLC) is among the deadliest of human cancers. The CDKN2A locus, which houses the INK4a and ARF tumor suppressor genes, is frequently altered in NSCLC. However, the specific role of ARF in pulmonary tumorigenesis remains unclear. KRAS and other oncogenes induce the expression of ARF, thus stabilizing p53 activity and arresting cell proliferation. To address the role of ARF in Kras-driven NSCLC, we compared the susceptibility of NIH/Ola strain wild-type and Arf-knockout mice to urethane-induced lung carcinogenesis. Lung tumor size, malignancy and associated morbidity were significantly increased in Arf(-/-) compared with Arf(+/+) animals at 25 weeks after induction. Pulmonary tumors from Arf-knockout mice exhibited increased cell proliferation and DNA damage compared with wild-type mice. A subgroup of tumors in Arf(-/-) animals presented as dedifferentiated and metastatic, with many characteristics of pulmonary sarcomatoid carcinoma, a neoplasm previously undocumented in mouse models. Our finding of a role for ARF in NSCLC is consistent with the observation that benign adenomas from Arf(+/+) mice robustly expressed ARF, while ARF expression was markedly reduced in malignant adenocarcinomas. ARF expression also frequently colocalized with the expression of p21(CIP1), a transcriptional target of p53, arguing that ARF induces the p53 checkpoint to arrest cell proliferation in vivo. Taken together, these findings demonstrate that induction of ARF is an early response in lung tumorigenesis that mounts a strong barrier against tumor growth and malignant progression.


Subject(s)
Carcinoma, Non-Small-Cell Lung/pathology , Cyclin-Dependent Kinase Inhibitor p16/physiology , Lung Neoplasms/pathology , Animals , Cell Proliferation , Cyclin-Dependent Kinase Inhibitor p16/genetics , DNA Damage/physiology , Disease Progression , Genes, ras , Mice , Mice, Knockout , Mutation , Neoplasm Invasiveness , Neoplasm Metastasis , Tumor Suppressor Protein p53/metabolism
3.
Acta Biomater ; 9(2): 5289-96, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23149253

ABSTRACT

During recent decades, research on biological systems such as abalone shell and fish armor has revealed that these biological systems employ carefully arranged hierarchical multilayered structures to achieve properties of high strength, high ductility and light weight. Knowledge of such structures may enable pathways to design bio-inspired materials for various applications. This study was conducted to investigate the spatial distribution of structure, chemical composition and mechanical properties in mineralized fish scales of the species Atractosteus spatula. Microindentation tests were conducted, and cracking patterns and damage sites in the scales were examined to investigate the underlying protective mechanisms of fish scales under impact and penetration loads. A difference in nanomechanical properties was observed, with a thinner, stiffer and harder outer layer (indentation modulus ∼69 GPa and hardness ∼3.3 GPa) on a more compliant and thicker inner layer (indentation modulus ∼14.3 GPa and hardness ∼0.5 GPa). High-resolution scanning electron microscopy imaging of a fracture surface revealed that the outer layer contained oriented nanorods embedded in a matrix, and that the nanostructure of the inner layer contained fiber-like structures organized in a complex layered pattern. Damage patterns formed during microindentation show complex deformation mechanisms. Images of cracks identify growth through the outer layer, then deflection along the interface before growing and arresting in the inner layer. High-magnification images of the crack tip in the inner layer show void-linking and fiber-bridging exhibiting inelastic behavior. The observed difference in mechanical properties and unique nanostructures of different layers may have contributed to the resistance of fish scales to failure by impact and penetration loading.


Subject(s)
Animal Structures/anatomy & histology , Animal Structures/physiology , Fishes/anatomy & histology , Animal Structures/diagnostic imaging , Animal Structures/ultrastructure , Animals , Biomechanical Phenomena/physiology , Elastic Modulus/physiology , Hardness , Nanotechnology , Spectrometry, X-Ray Emission , Spectroscopy, Fourier Transform Infrared , Stress, Mechanical , X-Ray Microtomography
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