Research Spotlight

Crawford, J., Liu, S. and Tao, F. (2021). “A Multidisciplinary Approach to Simultaneously Monitoring Real-Time Neuronal Activity and Pain Behaviors During Optogenetic Stimulation of Brain Neurons in Freely Moving Mice.” J Pain Res 14: 3503-3509.

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BACKGROUND: Highlighted by the current opioid epidemic, identifying novel therapies to treat chronic trigeminal neuropathic pain is a critical need. To develop these treatments, it is necessary to have viable targets in the brain to act on. Historically, neural tracing studies have been extremely useful in determining connections between brain areas but do not provide information about the functionality of these connections. Combining optogenetics and behavioral observation allows researchers to determine whether a particular brain area is involved in the regulation of such behavior. The addition of multi-channel electrophysiological recording provides information on real-time neuronal activity in the specific neuronal pathway. METHODS: Male C57/BL/6J mice (8-week-old) underwent either chronic constriction injury of infraorbital nerve (CCI-ION) or a sham surgery and were injected with either channelrhodopsin (ChR2) or a control virus in the hypothalamic A11 nucleus. Two weeks after CCI-ION, they were tested in real-time place preference (RTPP), while neuronal activity in the spinal trigeminal nucleus caudalis (Sp5C) was recorded. RESULTS: Optogenetic excitation of the A11 neurons results in more time spent in the stimulation chamber during RTPP testing. Additionally, stimulation of the A11 results in a greater number of neuronal activity increase in the Sp5C in animals with the injection of AAV carrying ChR2 compared to animals injected with a control virus or that underwent a sham surgery. CONCLUSION: In vivo multi-channel electrophysiological recording, optogenetic stimulation, and behavioral observation can be combined in a mouse model of chronic trigeminal neuropathic pain to validate brain areas involved in the modulation of such pain.

Zandinejad, A. and Revilla-León, M. (2021). “Additively Manufactured Dental Crown with Color Gradient and Graded Structure: A Technique Report.” J Prosthodont 30(9): 822-825.

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To assess the feasibility of manufacturing a dental crown with internal color gradient and graded structure design using additive manufacturing technology, a mandibular first molar was prepared and a monolayer dental crown with 1.5 mm uniform thickness was designed in a dental software (STL(C1) ). The monolayer crown design was sliced into multiple layers of 0.1 mm thickness and a design for a multilayer crown was obtained (STL(C2) ). A multilayer crown was manufactured with gradient color and graded structure using a material jetting printer. Different materials with different colors and properties were used and mixed in different ratios during manufacturing to achieve the prospected design. The feasibility of manufacturing such a crown was reported. This report confirms that multilayer dental crowns with internal gradient color and graded structure are possible when using a multimaterial jetting printer.

Kaplan, F.S., Groppe, J.C., Xu, M., Towler, O.W., Grunvald, E., Kalunian, K., Kallish, S., Al Mukaddam, M., Pignolo, R.J. and Shore, E.M. (2021). “An ACVR1(R375P) pathogenic variant in two families with mild fibrodysplasia ossificans progressiva.” Am J Med Genet A Dec 2. [Epub ahead of print].

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Genetic variants are vital in informing clinical phenotypes, aiding physical diagnosis, guiding genetic counseling, understanding the molecular basis of disease, and potentially stimulating drug development. Here we describe two families with an ultrarare ACVR1 gain-of-function pathogenic variant (codon 375, Arginine > Proline; ACVR1(R375P) ) responsible for a mild nonclassic fibrodysplasia ossificans progressiva (FOP) phenotype. Both families include people with the ultrarare ACVR1(R375P) variant who exhibit features of FOP while other individuals currently do not express any clinical signs of FOP. Thus, the mild ACVR1(R375P) variant greatly expands the scope and understanding of this rare disorder.

Aminoshariae, A., Azarpazhooh, A., Diogenes, A.R., Fouad, A.F., Glickman, G.N., He, J., Kishen, A., Letra, A.M., Levin, L., Roda, R.S., Setzer, F.C., Tay, F.R. and Hargreaves, K.M. (2021). “Insights into the December 2021 Issue of the JOE.” J Endod 47(12): 1817-1819.

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Welcome to the December 2021 issue of the JOE. Here, we share some of our favorite articles that are published in this issue of the Journal. We hope you look forward to reading these and other articles in the JOE.[No abstract; excerpt from article].

Pandya, M. and Diekwisch, T.G.H. (2021). “Amelogenesis: Transformation of a protein-mineral matrix into tooth enamel.” J Struct Biol 213(4): 107809.

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During enamel formation, the organic enamel protein matrix interacts with calcium phosphate minerals to form elongated, parallel, and bundled enamel apatite crystals of extraordinary hardness and biomechanical resilience. The enamel protein matrix consists of unique enamel proteins such as amelogenin, ameloblastin, and enamelin, which are secreted by highly specialized cells called ameloblasts. The ameloblasts also facilitate calcium and phosphate ion transport toward the enamel layer. Within ameloblasts, enamel proteins are transported as a polygonal matrix with 5 nm subunits in secretory vesicles. Upon expulsion from the ameloblasts, the enamel protein matrix is re-organized into 20 nm subunit compartments. Enamel matrix subunit compartment assembly and expansion coincide with C-terminal cleavage by the MMP20 enamel protease and N-terminal amelogenin self-assembly. Upon enamel crystal precipitation, the enamel protein phase is reconfigured to surround the elongating enamel crystals and facilitate their elongation in C-axis direction. At this stage of development, and upon further amelogenin cleavage, central and polyproline-rich fragments of the amelogenin molecule associate with the growing mineral crystals through a process termed “shedding”, while hexagonal apatite crystals fuse in longitudinal direction. Enamel protein sheath-coated enamel “dahlite” crystals continue to elongate until a dense bundle of parallel apatite crystals is formed, while the enamel matrix is continuously degraded by proteolytic enzymes. Together, these insights portrait enamel mineral nucleation and growth as a complex and dynamic set of interactions between enamel proteins and mineral ions that facilitate regularly seeded apatite growth and parallel enamel crystal elongation.