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Cell polarity, the asymmetric distribution of proteins and organelles, is permanently or transiently established in various cell types and plays an important role in many physiological events. EH domain-binding protein 1 like 1 (EHBP1L1) is an adaptor protein that is localized on recycling endosomes and regulates apical-directed transport in polarized epithelial cells. However, the role of EHBP1L1 in non-epithelial cells remains unknown. In this study, Ehbp1l1-/- mice showed impaired erythroblast enucleation. Further analyses showed that nuclear polarization prior to enucleation was impaired in Ehbp1l1-/- erythroblasts. It was also revealed that EHBP1L1 interactors Rab10, Bin1, and dynamin were involved in erythroblast enucleation. In addition, Ehbp1l1-/- erythrocytes exhibited stomatocytic morphology and dehydration. These defects in erythroid cells culminated in early postnatal anemic lethality in Ehbp1l1-/- mice. Moreover, we found the mislocalization of nuclei and mitochondria in the skeletal muscle cells of Ehbp1l1-/- mice, as observed in patients with centronuclear myopathy with genetic mutations in Bin1 or dynamin 2. Taken together, our findings indicate that the Rab8/10-EHBP1L1-Bin1-dynamin axis plays an important role in multiple cell polarity systems in epithelial and non-epithelial cells.

Corticosteroids are stress-related hormones that maintain homeostasis. The most effective corticosteroids are corticosterone (CORT) in rodents and cortisol in primates. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1; EC 1.1.1.146), encoded by Hsd11b1, is a key regulator of the local concentration of CORT/cortisol. Hsd11b1 expression in layer 5 of the primary somatosensory cortex has been shown in adult mice. However, its localization in the entire neocortex, especially during development, has not been fully addressed. Here, we established robust and dynamic expression profiles of Hsd11b1 in the developing mouse neocortex. Hsd11b1 was found mostly in pyramidal neurons. By retrograde tracing, we observed that some Hsd11b1-positive cells were projection neurons, indicating that at least some were excitatory. At postnatal day 0 (P0), Hsd11b1 was expressed in the deep layer of the somatosensory cortex. Then, from P3 to P8, the expression area expanded broadly; it was observed in layers 4 and 5, spanning the whole neocortex, including the primary motor cortex (M1) and the primary visual cortex (V1). The positive region gradually narrowed from P14 onwards and was ultimately limited to layer 5 of the somatosensory cortex at P26 and later. Furthermore, we administered CORT to nursing dams to increase the systemic CORT level of their pups. Here, we observed a reduced number of Hsd11b1-positive cells in the neocortex of these pups. Our observation suggests that Hsd11b1 expression in the developing neocortex is affected by systemic CORT levels. It is possible that stress on mothers influences the neocortical development of their children.

Coordination of skilled movements and motor planning relies on the formation of regionally restricted brain circuits that connect cortex with subcortical areas during embryonic development. Layer 5 neurons that are distributed across most cortical areas innervate the pontine nuclei (basilar pons) by protrusion and extension of collateral branches interstitially along their corticospinal extending axons. Pons-derived chemotropic cues are known to attract extending axons, but molecules that regulate collateral extension to create regionally segregated targeting patterns have not been identified. Here, we discovered thatEphA7andEfnA5are expressed in the cortex and the basilar pons in a region-specific and mutually exclusive manner, and that their repulsive activities are essential for segregating collateral extensions from corticospinal axonal tracts in mice. Specifically,EphA7andEfnA5forward and reverse inhibitory signals direct collateral extension such thatEphA7-positive frontal and occipital cortical areas extend their axon collaterals into theEfnA5-negative rostral part of the basilar pons, whereasEfnA5-positive parietal cortical areas extend their collaterals into theEphA7-negative caudal part of the basilar pons. Together, our results provide a molecular basis that explains how the corticopontine projection connects multimodal cortical outputs to their subcortical targets.SIGNIFICANCE STATEMENTOur findings put forward a model in which region-to-region connections between cortex and subcortical areas are shaped by mutually exclusive molecules to ensure the fidelity of regionally restricted circuitry. This model is distinct from earlier work showing that neuronal circuits within individual cortical modalities form in a topographical manner controlled by a gradient of axon guidance molecules. The principle that a shared molecular program of mutually repulsive signaling instructs regional organization—both within each brain region and between connected brain regions—may well be applicable to other contexts in which information is sorted by converging and diverging neuronal circuits.

Yuichiro Oka, Miyuki Doi, Manabu Taniguchi, Sheena Y X Tiong, Hisanori Akiyama, Takuto Yamamoto, Tokuichi Iguchi, Makoto Sato, Interstitial Axon Collaterals of Callosal Neurons Form Association Projections from the Primary Somatosensory to Motor Cortex in Mice, Cerebral Cortex, 2021;, bhab153, https://doi.org/10.1093/cercor/bhab153., Association projections from cortical pyramidal neurons connect disparate intrahemispheric cortical areas, which are implicated in higher cortical functions. The underlying developmental processes of these association projections, especially the initial phase before reaching the target areas, remain unknown. To visualize developing axons of individual neurons with association projections in the mouse neocortex, we devised a sparse labeling method that combined in utero electroporation and confocal imaging of flattened and optically cleared cortices. Using the promoter of an established callosal neuron marker gene that was expressed in over 80% of L2/3 neurons in the primary somatosensory cortex (S1) that project to the primary motor cortex (M1), we found that an association projection of a single neuron was the longest among the interstitial collaterals that branched out in L5 from the earlier-extended callosal projection. Collaterals to M1 elongated primarily within the cortical gray matter with little branching before reaching the target. Our results suggest that dual-projection neurons in S1 make a significant fraction of the association projections to M1, supporting the directed guidance mechanism in long-range corticocortical circuit formation over random projections followed by specific pruning.

We investigated fibroblast growth factor 12 (FGF12) as a transcript enriched in the inner ear by searching published cDNA library databases. FGF12 is a fibroblast growth factor homologous factor, a subset of the FGF superfamily. To date, its localisation and function in the inner ear have not been determined. Here, we show that FGF12 mRNA is localised in spiral ganglion neurons (SGNs) and the vestibular ganglion. We also show that FGF12 protein is localised in SGNs, the vestibular ganglion, and nerve fibres extending beneath hair cells. Moreover, we investigated FGF12 function in auditory and vestibular systems using Fgf12-knockout (FGF12-KO) mice generated with CRISPR/Cas9 technology. Our results show that the inner ear morphology of FGF12-KO mice is not significantly different compared with wild-type mice. However, FGF12-KO mice exhibited an increased hearing threshold, as measured by the auditory brainstem response, as well as deficits in rotarod and balance beam performance tests. These results suggest that FGF12 is necessary for normal auditory and equilibrium function.

The study of inner ear specific transcripts has revealed novel information about hereditary hearing loss and a mechanism of normal hearing. In this study, by analyzing a published cDNA library, we focused on Epiphycan (Epyc), a member of the small leucine-rich repeat proteoglycan family, whose transcript is enriched in the inner ear. Epyc mRNA was expressed abundantly and specifically in adult mice cochleae and was localized in supporting cells within the organ of Corti of both neonatal and adult mice. To examine the function of Epyc, we generated Epyc knockout (KO) mice using the CRISPR/Cas9 system. Epyc KO mice cochleae exhibited normal morphology. However, measurement of the auditory brain-stem response in Epyc KO mice revealed an elevated hearing threshold above 16 kHz frequency. This study suggests that Epyc is necessary for normal auditory function.

While good ohmic contact formation has been achieved on both p-GaN and n-AlGaN surfaces, the turn-on and operating voltages of AlGaN-based deep-ultraviolet light-emitting diodes (DUV-LEDs) remain very high. We find that this critical problem is mainly caused by the large difference between the annealing temperatures required for ohmic contact formation on the p-GaN and high Al-fraction n-AlGaN surfaces. We studied the effects of the high-temperature annealing treatments required for n-ohmic contact formation on the subsequent p-ohmic contact formation process in DUV-LEDs. The results show that post-annealing treatment at high temperature is necessary to form an ohmic contact on n-Al0.7Ga0.3N, but a treatment temperature of 900°C or more could cause severe degradation of the specific contact resistivity and the bulk resistivity of p-GaN. We conclude that 900°C is the optimum temperature to form an ohmic contact on n-Al0.7Ga0.3N in DUV-LEDs, where p-GaN and n-Al0.7Ga0.3N act as the p- and n-ohmic contact layers, respectively. We also found that the specific contact resistivity of p-GaN can be reduced by an additional low-temperature annealing treatment after the high-temperature annealing step; this effect can be attributed to the enhancement of the hole concentration in the p-GaN surface contact region. Finally, DUV-LEDs that emit at 280 nm were fabricated using four different annealing treatments during processing. A considerable reduction in the series resistance and thereby in the operating voltage was confirmed using the annealing process proposed above, consisting of a high-temperature anneal at 900°C followed by a low-temperature anneal at 500°C for 3 min.

Hexagonal boron nitride (h-BN) is an attractive wide-bandgap material for application to emitters and detectors operating in the deep ultraviolet (DUV) spectral region. The optical transmittance of h-BN in the DUV region is particularly important for these devices. We report on the deposition of thick h-BN films (&gt, 200 nm) on Al0.7Ga0.3N templates via radio-frequency sputtering, along with the realization of ultrahigh transmittance in the DUV region. The fraction of the gas mixture (Ar/N2) was varied to investigate its effects on the optical transmittance of BN. DUV light transmittance of as high as 94% was achieved at 265 nm. This value could be further enhanced to exceed 98% by a post-annealing treatment at 800 &deg, C in a N2 ambient for 20 min. The phase of the highly DUV&ndash, transparent BN film was determined to be a purely hexagonal structure via Raman spectra measurements. More importantly, these deposition processes were performed at a low temperature (300 &deg, C), which can provide protection from device performance degradation when applied to actual devices.

Hexagonal boron nitride (h-BN) is an attractive wide-bandgap material for application to emitters and detectors operating in the deep ultraviolet (DUV) spectral region. The optical transmittance of h-BN in the DUV region is particularly important for these devices. We report on the deposition of thick h-BN films (>200 nm) on Al0.7Ga0.3N templates via radio-frequency sputtering, along with the realization of ultrahigh transmittance in the DUV region. The fraction of the gas mixture (Ar/N2) was varied to investigate its effects on the optical transmittance of BN. DUV light transmittance of as high as 94% was achieved at 265 nm. This value could be further enhanced to exceed 98% by a post-annealing treatment at 800 °C in a N2 ambient for 20 min. The phase of the highly DUV–transparent BN film was determined to be a purely hexagonal structure via Raman spectra measurements. More importantly, these deposition processes were performed at a low temperature (300 °C), which can provide protection from device performance degradation when applied to actual devices.

The external quantum efficiency (EQE) in electrically injected AlGaN-based deep-ultraviolet light-emitting diodes (DUV-LEDs) is severely limited by their poor current injection efficiency (CIE). We report improvement in the CIE via controlling the relaxation of strains in the p-AlGaN hole injection layer (HIL) and the electron blocking layer (EBL). Simulation results show that an unrelaxed strain in the HIL associated with a relaxed strain in EBL can significantly enhance CIE. Deeper analysis indicates that high hole concentrations can be generated at HIL/EBL interface by strain-induced piezoelectric fields, which can then provide abundant numbers of holes for injection into quantum wells. Two sub-280 nm DUV-LEDs were fabricated with specific designs for different strain relaxations in the p-AlGaN HIL by changing the HIL thickness from 200 to 20 nm. The strain difference was identified using Raman spectroscopy. Electroluminescence measurements demonstrated much higher EQE in the strained-HIL DUV-LEDs. By separating the EQE contributions of three efficiencies, i.e. the CIE, the radiative recombination efficiency and the light extraction efficiency, we found that the EQE enhancement could mainly be attributed to the improved CIE, which agreed well with the simulation results.

Although the volume overload of pulmonary circulation improves after atrial septal defect (ASD) closure, the increasing left ventricular preload may contribute to mitral regurgitation (MR) deterioration. We aimed to evaluate the impact of MR after transcatheter ASD closure on clinical outcomes in adults. A total of 288 consecutive patients who underwent transcatheter ASD closure were enrolled. Changes in MR were assessed at 1 month after the procedure. The end point was defined as cardiovascular events. After the procedure, MR ameliorated in 3 patients and unchanged in 253, whereas MR deteriorated in 32. During a median follow-up of 24 months, patients with MR deterioration had no cardiovascular events, and the event-free survival rate was not different between patients with MR deterioration and those with MR amelioration or no-change (p = 0.355). Even in patients with MR deterioration, the New York Heart Association functional class improved after the procedure, with no cases of worsening functional class. Multivariate logistic regression analysis showed that MR deterioration was independently related to advanced age and female gender. The degree of enlargement of mitral valve annulus diameter after the procedure was greater in patients with MR deterioration than in those with MR amelioration or no-change, and it was correlated with the degree of MR deterioration. In conclusion, MR deterioration occurs in a minority of adult patients after transcatheter ASD closure; however, it is not linked with adverse outcomes. MR deterioration may be provoked by geometric changes in mitral valve annulus, especially in women with advanced age.

Objective This study evaluated the effect of echocardiographic left ventricular (LV) diastolic dysfunction on acute congestive heart failure after transcatheter atrial septal defect (ASD) closure in elderly patients. Background Although there is concern that LV diastolic dysfunction develops acute congestive heart failure after ASD closure, limited information is available regarding the influence, especially in elderly patients with severe LV diastolic dysfunction. Methods Two hundred consecutive patients older than 60 years were divided into 3 groups according to echocardiographic LV diastolic dysfunction: severe (early diastolic mitral annular velocity [e’]

Although numerous studies have shown an association between a patent foramen ovale (PFO) and cryptogenic cerebrovascular accidents (CVA), there has been no definitive control study that demonstrated the benefit of percutaneous device closure of a PFO compared to medical therapy in patients with CVA. Additionally, few clinical data exist for Japanese patients in this field. We demonstrate the initial experiences in catheter closure of a PFO as secondary prevention of CVA in Japan. Catheter closure of a PFO was attempted in 7 patients who were diagnosed with cryptogenic CVA. Mean age at the procedure was 54 ± 19 years. The presence of spontaneous interatrial right-to-left shunts was demonstrated by transesophageal contrast echocardiography without Valsalva maneuver in all of the patients. Amplatzer Cribriform device (n = 4) or Amplatzer PFO Occluder (n = 3) was used for the procedure and was successfully deployed. Device-related complications were not observed at the time of the procedure or during the follow-up period (mean period of 16 ± 9 months). Catheter closure of a PFO could be safely performed with Amplatzer Cribriform or Amplatzer PFO Occluder. This procedure may contribute to prevention of recurrent cryptogenic CVA in Japanese patients.

Wound healing is often delayed in the patients whose sensory and autonomic innervation is impaired. We hypothesized that existence of neurites in the skin may promote wound healing by inducing differentiation of fibroblasts into myofibroblasts with consequent wound contraction. In the current study, we examined the effect of neurons on differentiation of fibroblasts and contraction of collagen matrix in vitro using a new co-culture model. Neuronal cell line, PC12 cells, of which the neurite outgrowth can be controlled by adding nerve growth factor, was used. Rat dermal fibroblasts were co-cultured with PC12 cells extending neurites or with PC12 cells lacking neurites. Then, differentiation of fibroblasts into myofibroblasts and contraction of the collagen matrix was evaluated. Finally, we examined whether direct or indirect contact with neurites of PC12 cells promoted the differentiation of fibroblasts. Our results showed that fibroblasts co-cultured with PC12 extending neurites differentiated into myofibroblasts more effectively and contracted the collagen matrix stronger than those with PC12 lacking neurites. Direct contact of fibroblasts with neurites promoted more differentiation than indirect contact. In conclusion, direct contact of fibroblasts with neuronal processes is important for differentiation into myofibroblasts and induction of collagen gel contraction, leading to promotion of wound healing.

This study sought to evaluate the usefulness of real-time three-dimensional (3D) transesophageal echocardiography (TEE) to guide the repair of multiple atrial septal defects (ASDs). Of 212 consecutive patients with secundum ASD who were scheduled for transcatheter closure of their ASDs, 27 had multiple ASDs. These patients underwent two-dimensional (2D) transthoracic echocardiography, 2D TEE, and 3D TEE. Overall, 18 patients had two defects, and 9 patients had three or more defects. The latter group included three patients with multi-fenestrated defects. Optimal 3D images were obtained in 93 % of the patients. In patients with two defects, information on the positional relation of the defects was obtained using 2D TEE and 3D TEE in 71 and 94 % of patients, respectively (P = 0.22). The positional relations of the defects could not be evaluated with 2D TEE in patients with three or more defects, whereas it could be evaluated with 3D TEE in all of these patients (0 vs. 100 %, P = 0.008). In all patients, 3D TEE proved superior to 2D TEE for providing sufficient information (96 vs. 48 %, P = 0.002). Procedural success was obtained in 26 patients (96.3 %), without complications. Transcatheter closure of multiple ASDs under 3D TEE guidance is effective and safe. Real-time 3D TEE can provide useful information regarding complex ASD morphology. It can thus contribute to developing a successful treatment strategy, especially in patients with three or more defects.

Repeated stressful events are associated with the onset of major depressive disorder (MDD). We previously showed oligodendrocyte (OL)-specific activation of the serum/glucocorticoid-regulated kinase (SGK)1 cascade, increased expression of axon-myelin adhesion molecules and elaboration of the oligodendrocytic arbor in the corpus callosum of chronically stressed mice. In the current study, we demonstrate that the nodes and paranodes of Ranvier in the corpus callosum were narrower in these mice. Chronic stress also led to diffuse redistribution of Caspr and Kv 1.1 and decreased the activity in white matter, suggesting a link between morphological changes in OLs and inhibition of axonal activity. OL primary cultures subjected to chronic stress resulted in SGK1 activation and translocation to the nucleus, where it inhibited the transcription of metabotropic glutamate receptors (mGluRs). Furthermore, the cAMP level and membrane potential of OLs were reduced by chronic stress exposure. We showed by diffusion tensor imaging that the corpus callosum of patients with MDD exhibited reduced fractional anisotropy, reflecting compromised white matter integrity possibly caused by axonal damage. Our findings suggest that chronic stress disrupts the organization of the nodes of Ranvier by suppressing mGluR activation in OLs and that specific white matter abnormalities are closely associated with MDD onset.

Background Although it has been demonstrated that cardiac remodeling and exercise capacity improve after transcatheter closure of atrial septal defect (ASD), little is known about long-term benefits in middle-aged and elderly patients with a reduction in cardiopulmonary function. Objectives To evaluate long-term extent and time course of improvements in cardiac remodeling and exercise capacity in those patients. Methods: Twenty ASD patients ≥ 40 years of age with a reduction in cardiopulmonary function (predicted peak oxygen uptake [VO2] 12 months after the procedure. Results At 1 month after the procedure, significant decreases in right ventricular (RV) end-diastolic diameter (38.2 ± 4.4 to 31.9 ± 4.4 mm; P < 0.001) and RV/left ventricular end-diastolic diameter ratio (0.95 ± 0.17 to 0.71 ± 0.13; P < 0.001) occurred, and they were maintained during the follow-up period. Normal RV size was achieved in 11 of 18 patients with RV enlargement. Predicted peak VO2 did not change at 1 month and 3 months, but it improved significantly after 6 months (53.6 ± 6.5 to 62.1 ± 12.6%; P < 0.01). Sixteen of the 20 patients showed improved predicted peak VO2. Conclusions Cardiac remodeling and exercise capacity could be improved over the long-term period after transcatheter closure of ASD in middle-aged and elderly patients with a reduction in cardiopulmonary function. There were differences in the time course of improvement between cardiac remodeling and exercise capacity in those patients. (J Interven Cardiol 2013;26:195–199)

The aim of this study was to demonstrate the feasibility and usefulness of addition of the right parasternal approach to the conventional left parasternal and apical approaches using two-dimensional (2D) and three-dimensional (3D) transthoracic echocardiography (TTE) for morphologic evaluation in cases of transcatheter closure of atrial septal defects (ASDs).In 112 consecutive patients with ASDs, the morphology of the defects was evaluated for transcatheter closure in the right parasternal view in addition to the conventional left views using 2D and 3D TTE. Measurements of the maximal ASD diameter and detection of deficient rim obtained on 2D TTE were compared with those obtained by 2D transesophageal echocardiography. The shapes and locations of ASDs visualized by 3D TTE were compared with those visualized by 3D transesophageal echocardiography.In 88 patients (80.0%), optimal images from the right parasternal approach for morphologic evaluation of ASDs were obtained. Although there was a significant difference in maximal ASD diameter obtained only in the conventional left approach compared with transesophageal echocardiographic measurements (P.05), when the right parasternal approach was applied, a significant difference was not found (P = .18), and the diagnostic concordance of the rim deficiency was improved from 85.2% to 90.9%. Three-dimensional TTE from the right parasternal approach improved visualization of the shape and location of ASDs from 65.5% to 74.5%.Additional use of the right parasternal approach enables detailed morphologic evaluation for transcatheter closure of ASDs. In patients with suboptimal images on 3D TTE in the left conventional approach, additional 3D TTE in the right parasternal approach can improve the feasibility of obtaining optimal 3D images to evaluate the shapes and locations of ASDs.

Objectives: To evaluate the efficacy and safety of transcatheter closure of atrial septal defects (ASD) in patients over 70 years of age. Background: Transcatheter closure of ASD is an established procedure in children and young adults, but the benefits of this procedure in geriatric patients are still unclear. Methods: Between 2005 and 2010, 430 patients with ASD underwent transcatheter closure in our hospital. Among those patients, 30 consecutive patients older than 70 years of age were prospectively evaluated. Results: Mean age at procedure was 75.8 ± 3.8 years (range: 70–85 years). Mean Qp/Qs was 2.4 ± 0.7 and mean ASD diameter was 20.3 ± 6.4 mm. Nine patients (30%) had a history of hospitalization due to heart failure. ASD closure was successfully performed in 28 patients (93%) without significant complications. During the follow-up period (mean period of 19.1 ± 11.3 months), New York Heart Association (NYHA) functional class was significantly improved in 20 patients (74%). Significant improvements of plasma BNP level, resting heart rate, and systolic pulmonary artery pressure were also observed. Improvement of tricuspid regurgitation was observed in 11 of 17 patients with moderate or severe regurgitation during the follow-up period. Conversely, worsening of mitral regurgitation was observed in 10 of the 27 patients. Conclusion: Transcatheter closure of ASD in geriatric patients can be performed safely. This procedure contributes to significant improvement of symptoms and positive cardiac remodeling. Long-term follow-up is mandatory, especially for patients with mitral regurgitation. © 2012 Wiley Periodicals, Inc.

Nowadays transcatheter closure has become the standard treatment for an atrial septal defect (ASD). Since morphologic variation of ASD is common, imaging modalities with high diagnostic ability continue to be required. Meanwhile, experts are required to visualize high-quality images with advanced imaging modalities. Echocardiography plays a pivotal role in patient selection for treatment, recently introduced 3D echocardiography is a promising modality to provide comprehensible en face images of ASD, especially in patients with a complex-shaped ASD. In addition, cardiac MRI and computed tomography can provide complementary information. Transesophageal echocardiography and intracardiac echocardiography can provide images of excellent quality for guidance of the procedure. In this review, we discuss the role of imaging for transcatheter ASD closure, focusing on echocardiography.

Coronary sinus defect is a rare type of atrial septal defect. We report two patients who had a coronary sinus atrial septal defect without persistent left superior caval vein, where the orifice of the coronary sinus was closed using the Amplatzer Septal Occluder. The procedure was successful, without any complications including conduction disturbance.

Dental caries in early childhood is a significant public health problem, among which nursing caries is known to be caused by inappropriate nursing habits. The aim of the present study was to investigate lifestyle factors related to nursing caries. We examined 2,506 Japanese children aged 18 months, as a part of public health examinations conducted by the Municipal Public Health Center in 2008. Questionnaires were also administered to their guardians, which focused on nutritional and dental health conditions. Statistical analyses were then performed to determine significant nutritional and dental health factors associated with nursing caries. There were 117 children (4.7% of total) identified with dental caries, of whom 18 (0.7% of total cohort, 15.3% of children with dental caries) were designated as the nursing caries group. Statistical analyses revealed that breastfeeding was the most important factor as compared to children without nursing caries ( P =0.0002; odds ratio, 6.373). Our results showed that inappropriate breastfeeding is one of the most important factors related to both onset and exacerbation of nursing caries, and conclude that parents should be informed of appropriate breastfeeding practices by dentists for their prevention.

Neurotrophin receptor p75 (p75NTR) knockout mice (p75(−/−) mice) provide a good animal model of progressive-onset hearing loss.1 Cell loss of the spiral ganglion neurons (SGNs) and hair cell degeneration at the basal turn of the cochlea are seen in p75(−/−) mice from 3 months of age. Furthermore, from 3 to 6 months of age, the hearing thresholds of p75(−/−) mice are gradually raised; and after 6 months of age, the mice mostly exhibit hearing loss.1 Several previous reports have indicated that electroacupuncture (EA) stimulation may improve subjective symptoms of tinnitus or hearing loss.2 ,3 However, the molecular mechanisms underlying the therapeutic effect of EA stimulation for hearing loss remain unclear. Thus, to determine whether EA stimulation is useful for the prevention of hearing loss, we used a p75(−/−) mouse model of progressive-onset hearing loss. The Ting Gong (SI19; Small Intestine 19) and the Yifeng (TE17; Triple Energiser meridian 17) are …

Summary Background Hyperkeratosis and acanthosis occur in inflamed skin. Proliferation and differentiation of keratinocytes are important processes during epidermal repair after inflammation. Neuropsin and its human homologue kallikrein-related peptidase 8 (KLK8) have been reported to be involved in epidermal proliferation and differentiation, but the involved molecular mechanisms are obscure. Objectives To explore the molecular mechanism of KLK8/neuropsin-induced hyperkeratosis and acanthosis in inflamed skin. Methods The molecular mechanism involved in KLK8/neuropsin-induced hyperkeratosis and acanthosis in inflamed skin was investigated both in vivo and in vitro using neuropsin knockout mice and KLK8 knockdown human keratinocytes. Neuropsin-related genes were identified by differential gene display. The localization and functional relationship of the molecules affected downstream of KLK8/neuropsin in normal and inflamed skin were analysed by in situ hybridization and immunohistochemistry. Results Hyperkeratosis and acanthosis in sodium lauryl sulphate-stimulated skin were markedly inhibited in neuropsin knockout mice. Knockdown of KLK8/neuropsin increased transcription factor activator protein-2α (AP-2α) expression and decreased keratin 10 expression in human keratinocytes and mouse skin, respectively. AP-2α has been reported to inhibit epidermal proliferation and keratin 10 expression. Distributional analysis showed that KLK8/neuropsin was expressed in the stratum spinosum, AP-2α was expressed in the stratum basale and the lower part of the stratum spinosum, and keratin 10 was expressed throughout the stratum spinosum. Conclusions The above findings suggest the following mechanism of events underlying KLK8/neuropsin-induced hyperkeratosis: (i) skin inflammation increases KLK8/neuropsin expression in the stratum spinosum; (ii) the released KLK8/neuropsin inhibits AP-2α expression in the cells of the stratum basale and stratum spinosum; (iii) the decrease in AP-2α results in cell proliferation in the stratum basale and cell differentiation in the stratum spinosum, with an increase in keratin 10 expression.

Background The aim of this study was to demonstrate the utility of real-time three-dimensional (3D) transesophageal echocardiography (RT3D-TEE) using a matrix array 3D transesophageal echocardiographic probe for morphologic evaluation and guidance of transcatheter closure of atrial septal defects (ASDs). Methods Forty-eight consecutive patients scheduled for the intervention were included. Two-dimensional (2D) transesophageal echocardiography (2D-TEE) and RT3D-TEE were performed before and during the procedures. Measurements of maximal ASD diameter and surrounding rims obtained on RT3D-TEE were compared with those obtained on 2D-TEE. Results In 46 patients (96%), optimal 3D images for the morphologic evaluation of ASDs were obtained. RT3D-TEE facilitated the evaluation of ASD morphology and surrounding rims and was able to provide intraprocedural information clearly. A Bland-Altman plot showed a mean maximal diameter difference of −0.12 mm between the means (95% limits of agreement, −2.2 to 2.5 mm). Conclusion RT3D-TEE is a clinically useful, complementary option to 2D-TEE for evaluation of ASD morphology and for interventional guidance.

The Drosophila pericentrin-like protein has been shown to be essential for the formation of the sensory cilia of chemosensory and mechanosensory neurons by mutant analysis in flies, while the in vivo function of pericentrin, a well-studied mammalian centrosomal protein related to microcephalic primordial dwarfism, has been unclear. To determine whether pericentrin is required for ciliogenesis in mammals, we generated and analyzed mice with a hypomorphic mutation of Pcnt encoding the mouse pericentrin. Immunofluorescence analysis demonstrated that olfactory cilia of chemosensory neurons in the nasal olfactory epithelium were malformed in the homozygous mutant mice. On the other hand, the assembly of motile and primary cilia of non-neuronal epithelial cells and the formation of sperm flagella were not affected in the Pcnt-mutant mice. The defective assembly of olfactory cilia in the mutant was apparent from birth. The mutant animals displayed reduced olfactory performance in agreement with the compromised assembly of olfactory cilia. Our findings suggest that pericentrin is essential for the assembly of chemosensory cilia of olfactory receptor neurons, but it is not globally required for cilia formation in mammals.

The intracavity absorption spectra of water vapor in the atmosphere were observed in situ using a multimode unidirectional traveling-wave ring dye laser. Water vapor lines with absolute absorption coefficients of 10-7 to 10-9 cm-1 were measured with uncertainties of a few percents and their values were consistent with those in the HITRAN database within 10%. The sensitivity of the present apparatus was estimated to be 1 ×10-10 cm-1.

The influence of deficient rims surrounding atrial septal defects (ASDs) in patients undergoing transcatheter closure has yet to be clarified. The aim of this study was to assess the influence of a deficient surrounding rim on the procedural success and clinical outcome of transcatheter ASD closure using an Amplatzer septal occluder.A total of 474 patients (mean age, 46 ± 22 years) with ostium secundum ASDs measuring ≤40 mm in diameter who had undergone attempted transcatheter closure using Amplatzer septal occluders from September 2007 to August 2013 were assessed. A comprehensive transesophageal echocardiographic examination was done to assess the morphologic characteristics of the defects in all patients. Subjects were classified into three groups by the extent and location of rim deficiency (5 mm): patients without deficient rims (sufficient group, n = 101), patients with single deficient rims, (single group, n = 338), and patients with multiple rim deficiencies (multiple group, n = 35).There was a significant difference in the maximal defect diameter among the sufficient, single, and multiple groups (15 ± 6, 18 ± 6, and 29 ± 7 mm, respectively, P .001). Transcatheter closure was successfully accomplished in 463 patients (98%). The prevalence of procedural success differed significantly among the sufficient, single, and multiple groups (100%, 98%, and 86%, respectively, P .001). There was no significant difference in the occurrence of cardiovascular events among the three groups during a mean follow-up period of 25 ± 19 months (P = .926, log-rank test).In patients with ASDs with multiple rim deficiencies as determined by transesophageal echocardiography, successful transcatheter ASD closure using Amplatzer septal occluders is more difficult to accomplish. However, if closure is successful, rim deficiencies rarely affect intermediate-term outcomes.

We studied on various p-electrode patterns to solve current crowding problem in AlGaN-based deep-ultraviolet light-emitting diode. Simulation results of optimized p-electrode pattern showed a uniform current density distribution and improved performance of light output power.

Light extraction efficiency (LEE) in deep-ultraviolet light emitting diodes with AlN substrate was investigated using Ray Tracing method. The results showed that LEE was dramatically improved by optimizing the sidewalls angle and AlN thickness.

Cell positioning and neuronal network formation are crucial for proper brain function. Disrupted-in-Schizophrenia 1 (DISC1) is anterogradely transported to the neurite tips, together with Lis1, and functions in neurite extension via suppression of GSK3β activity. Then, transported Lis1 is retrogradely transported and functions in cell migration. Here, we show that DISC1-binding zinc finger protein (DBZ), together with DISC1, regulates mouse cortical cell positioning and neurite developmentin vivo. DBZ hindered Ndel1 phosphorylation at threonine 219 and serine 251. DBZ depletion or expression of a double-phosphorylated mimetic form of Ndel1 impaired the transport of Lis1 and DISC1 to the neurite tips and hampered microtubule elongation. Moreover, application of DISC1 or a GSK3β inhibitor rescued the impairments caused by DBZ insufficiency or double-phosphorylated Ndel1 expression. We concluded that DBZ controls cell positioning and neurite development by interfering with Ndel1 from disproportionate phosphorylation, which is critical for appropriate anterograde transport of the DISC1-complex.