3,343 research outputs found
Molecular Logic of Spinocerebellar Tract Neuron Diversity and Connectivity
No full textCoordinated motor behaviors depend on feedback communication between peripheral sensory systems and central circuits in the brain and spinal cord. Relay of muscle- and tendon-derived sensory information to the CNS is facilitated by functionally and anatomically diverse groups of spinocerebellar tract neurons (SCTNs), but the molecular logic by which SCTN diversity and connectivity is achieved is poorly understood. We used single-cell RNA sequencing and genetic manipulations to define the mechanisms governing the molecular profile and organization of SCTN subtypes. We found that SCTNs relaying proprioceptive sensory information from limb and axial muscles are generated through segmentally restricted actions of specific Hox genes. Loss of Hox function disrupts SCTN-subtype-specific transcriptional programs, leading to defects in the connections between proprioceptive sensory neurons, SCTNs, and the cerebellum. These results indicate that Hox-dependent genetic programs play essential roles in the assembly of neural circuits necessary for communication between the brain and spinal cord. © 2019 The Author(s)Baek et al. show that Hox-transcription-factor-dependent programs govern the specification and connectivity of spinal interneurons that relay muscle-derived sensory information to the cerebellum. These findings shed light on the development of neural circuits required for proprioception—the perception of body position. © 2019 The Author(s)1
Stopping power of liquid water for carbon ions in the energy range between 1 MeV and 6 MeV
No full textThe stopping power of liquid water was measured for the first time for carbon ions in the energy range between 1 and 6 MeV using the inverted Doppler shift attenuation method. The feasibility study carried out within the scope of the present work shows that this method is well suited for the quantification of the controversial condensed phased effect in the stopping power for heavy ions in the intermediate energy range. The preliminary results of this work indicate that the stopping power of water for carbon ions with energies prevailing in the Bragg-peak region is significantly lower than that of water vapor. In view of the relatively high uncertainty of the present results, a new experiment with uncertainties less than the predicted difference between the stopping powers of both water phases is planned
DS_10.1177_0022034519893656 – Supplemental material for PIN1 Attenuation Improves Midface Hypoplasia in a Mouse Model of Apert Syndrome
No full textSupplemental material, DS_10.1177_0022034519893656 for PIN1 Attenuation Improves Midface Hypoplasia in a Mouse Model of Apert Syndrome by B. Kim, H. Shin, W. Kim, H. Kim, Y. Cho, H. Yoon, J. Baek, K. Woo, Y. Lee and H. Ryoo in Journal of Dental Research</p
PIN1 Attenuation Improves Midface Hypoplasia in a Mouse Model of Apert Syndrome
No full textPremature fusion of the cranial suture and midface hypoplasia are common features of syndromic craniosynostosis caused by mutations in the FGFR2 gene. The only treatment for this condition involves a series of risky surgical procedures designed to correct defects in the craniofacial bones, which must be performed until brain growth has been completed. Several pharmacologic interventions directed at FGFR2 downstream signaling have been tested as potential treatments for premature coronal suture fusion in a mouse model of Apert syndrome. However, there are no published studies that have targeted for the pharmacologic treatment of midface hypoplasia. We used Fgfr2(S252W/+) knock-in mice as a model of Apert syndrome and morphometric analyses to identify causal hypoplastic sites in the midface region. Three-dimensional geometric and linear analyses of Fgfr2(S252W/+) mice at postnatal day 0 demonstrated distinct morphologic variance. The premature fusion of anterior facial bones, such as the maxilla, nasal, and frontal bones, rather than the cranium or cranial base, is the main contributing factor toward the anterior-posterior skull length shortening. The cranial base of the mouse model had a noticeable downward slant around the intersphenoid synchondrosis, which is related to distortion of the airway. Within a skull, the facial shape variance was highly correlated with the cranial base angle change along Fgfr2 S252W mutation-induced craniofacial anomalies. The inhibition of an FGFR2 downstream signaling enzyme, PIN1, via genetic knockdown or use of a PIN1 inhibitor, juglone, attenuated the aforementioned deformities in a mouse model of Apert syndrome. Overall, these results indicate that FGFR2 signaling is a key contributor toward abnormal anterior-posterior dimensional growth in the midface region. Our study suggests a novel therapeutic option for the prevention of craniofacial malformations induced by mutations in the FGFR2 gene.N
Direct Gingival Fibroblast/Osteoblast Transdifferentiation via Epigenetics
No full textAlveolar bone resorption caused by trauma or periodontal diseases has represented a challenge for both dental clinicians and researchers. In this study, we evaluate the osteogenic potential of human gingival fibroblasts (HGFs) through a direct transdifferentiation from HGFs to functional osteoblasts via epigenetic modification and osteogenic signaling with bone morphogenetic protein 2 (BMP2) in vitro and in vivo. HGF treatment with 5-aza-2'-deoxycytidine (5-aza-dC) induced demethylation in the hypermethylated CpG islands of the osteogenic lineage marker genes RUNX2 and ALP, and subsequent BMP2 treatment successfully drove the fibroblasts to the osteoblasts' lineage. Cell morphological changes viewed under microscopy and alkaline phosphatase (ALP) and alizarin red S (ARS) staining confirmed the osteoblastic change mediated by epigenetic modification as did real-time polymerase chain reaction (PCR), methylation-specific PCR (MSP), and chromatin immunoprecipitation (ChIP) assay, which demonstrated the altered methylation patterns in the RUNX2 and ALP promoter regions and their effect on gene expression. Furthermore, micro-computed tomography (CT) analysis of in vivo mouse cell transplantation experiments showed high-density signal in the epigenetically modified HGF group; in addition, a significant amount of bone formation was observed in the transplanted material using hematoxylin and eosin (H&E) staining as well. Collectively, our results indicate that epigenetic modification permits the direct programming of HGFs into functional osteoblasts, suggesting that this approach might open a novel therapeutic avenue in alveolar bone regeneration.OAIID:RECH_ACHV_DSTSH_NO:T201719919RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A000241CITE_RATE:5.38DEPT_NM:치의학과EMAIL:[email protected]_YN:YN
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