Presynaptically Released Cbln1 Induces Dynamic Axonal Structural Changes by Interacting with GluD2 during Cerebellar Synapse Formation

SummaryDifferentiation of pre- and postsynaptic sites is coordinated by reciprocal interaction across synaptic clefts. At parallel fiber (PF)-Purkinje cell (PC) synapses, dendritic spines are autonomously formed without PF influence. However, little is known about how presynaptic structural changes are induced and how they lead to differentiation of mature synapses. Here, we show that Cbln1 released from PFs induces dynamic structural changes in PFs by a mechanism that depends on postsynaptic glutamate receptor delta2 (GluD2) and presynaptic neurexin (Nrx). Time-lapse imaging in organotypic culture and ultrastructural analyses in vivo revealed that Nrx-Cbln1-GluD2 signaling induces PF protrusions that often formed circular structures and encapsulated PC spines. Such structural changes in PFs were associated with the accumulation of synaptic vesicles and GluD2, leading to formation of mature synapses. Thus, PF protrusions triggered by Nrx-Cbln1-GluD2 signaling may promote bidirectional maturation of PF-PC synapses by a positive feedback mechanism

複雑先天性心疾患患者における心房細動の病因 : より良い治療戦略のために

Background: The demographics of patients with congenital heart disease (CHD) and atrial fibrillation (AF) differ significantly from the general population. The etiology and treatment strategy for AF in CHD patients have been investigated but are to date inconclusive. Methods: To determine the etiology of AF in CHD and to seek a better treatment strategy, we retrospectively evaluated the atrial overload in 42 complex CHD cases with normal atrial arrangements and AF (age 25; range, 9-66 years) and the impact of a reduction in the atrial overload on the atrial rhythm. Results: Cardiac defect diagnoses varied, with 17% of the patients having a persistent left superior vena cava (PLSVC). In regard to the volume overload, the frequencies of an overload in the right atrium (RA), left atrium (LA), or both, were 50 %, 23%, and 10%, respectively (p = 0.015). Other sustained supraventricular tachycardias were observed in 29 patients (69%) before and after the onset of AF. Among these 29 patients, 26 had intra-atrial reentrant tachycardia. Fifteen patients (36%), 10 of whom had chronic AF, died during the follow-up including 3 with arrhythmias and 10 because of heart failure. Fourteen (33%) patients had no AF at the last follow-up due to medical interventions, 8 of which underwent solely an RA-sided catheter ablation and/or surgical RA overload reduction. Conclusions: AF in complex CHD with a normal atrial arrangement correlates with a higher RA-sided overload than an LA-sided and exhibits a high incidence of PLSVCs, high comorbidity of intra-atrial reentrant tachycardias, and high mortality rate. In a substantial number of patients, RA-sided interventions were effective in controlling AF. To effectively manage AF in complex CHD it is essential to understand each individual's hemodynamics and consider hemodynamic interventions.博士（医学）・甲第853号・令和4年9月28日© 2020 Published by Elsevier Ltd on behalf of Japanese College of Cardiology

Age-related changes in a patient with Pelizaeus-Merzbacher disease by repeated 1H-MRS

Purpose: In this report, we describe a patient with Pelizaeus-Merzbacher disease (PMD) who underwent repeated evaluations by 1H-Magnetic resonance spectroscopy (MRS). Subject: The patient was given a definitive diagnosis of PMD based on genetic testing, which showed overlap of the proteolipid protein 1 (PLP1) gene. The control subjects for 1H-MRS consisted of healthy age-matched children. Methods: All measurements were performed with a clinical 3-tesla magnetic resonance imaging (MRI) system. For 1H-MRS, the center of a voxel was positioned in the right parietal lobe. 1H-MRS was performed when the patient was 2, 6, 14, and 25 months old. Results: The concentration of GABA in early childhood (2 months 1.72 mM, 6 months 2.15 mM) was increased compared with that in normal controls. However, his GABA concentration was normalized at 14 and 25 months. The concentrations of Ins were increased after 6 months. No remarkable changes were seen in the concentration of Cho at any time. Conclusion These results suggest that the changes in metabolite concentrations during growth may reflect the pathological state of PMD. Furthermore, the lack of a change in the Cho concentration may be useful for differentiating PMD from other demyelinating diseases

Heterologous co-chaperone recognition

Streptococcus intermedius DnaK complements the temperature-sensitive phenotype of an Escherichia coli dnaK null mutant, only if co-chaperones DnaJ and GrpE are co-expressed. Therefore, we examined whether S. intermedius DnaK and E. coli DnaK could recognize heterologous co-chaperones in vitro. The addition of heterologous GrpE to DnaK and DnaJ partially stimulated ATPase activity, and almost completely stimulated the luciferase refolding activity. Addition of heterologous DnaJ to GrpE and DnaK also stimulated ATPase activity but significant luciferase refolding activity was not observed. Moreover, E. coli DnaJ had a negative effect on the luciferase refolding activity of the S. intermedius DnaK chaperone system. In E. coli chaperone mutants, with the exception of E. coli DnaJ higher expression of the heterologous co-chaperones partially or almost completely complemented the temperature-sensitive-phenotype. These results indicated that all heterologous co-chaperones could at least partially recognize DnaK of a distantly related species. A region of the ATPase domain that is present in the DnaK of gram-negative bacteria is absent in the DnaK of gram-positive bacteria. This region is believed to be important for the recognition of co-chaperones from gram-negative bacteria. However, insertion of this segment into the S. intermedius DnaK failed to increase its ability to recognize E. coli co-chaperones. This implied that this region might be unnecessary or insufficient for the recognition of E. coli co-chaperones. Therefore, our data suggested that a basic structural similarity is conserved among the components of the S. intermedius and E. coli DnaK chaperone systems, which allow weak associations between heterologous components

Environmental history of Japanese eel, Anguilla japonica collected in Miyako Bay, northeastern Japan

The environmental history in combination with age of the Japanese eel, Anguilla japonica, collected in Miyako Bay along the Sanriku Coast of Japan, was examined using the otolith microstructure and analysis of strontium (Sr) and calcium (Ca) concentrations with wavelength dispersive X-ray spectrometry by an electron microprobe. The line analysis of Sr : Ca ratios along the life history transect of each otolith showed a peak (ca 12-17×10^) between the core and elver mark, which corresponded to the period of their leptocephalus and early glass eel stages in the ocean. The mean Sr : Ca ratios from the elver mark to the otolith edge indicated that there were eels with several general categories of migratory history, that included sea eels that never entered freshwater (average Sr : Ca ratios, >6.0×10^) and others that had entered freshwater for brief periods, but returned to the estuary or bay. This evidence of the occurrence of sea eels indicates that Japanese eels in this northern area do not necessarily migrate into freshwater rivers during recruitment as glass eels at the beginning of their growth phase, and even those that do enter freshwater may later return to the marine environment

An experimental study of use of absorbable plate in combination with self-setting α-tricalcium phosphate for orthognathic surgery

金沢大学医薬保健研究域医学系Objective: The purpose of this study was to histologically and immunohistochemically evaluate bone formation using both self-setting α-tricalcium phosphate (α-TCP; Biopex) and absorbable plate (Super Fixsorb-MX) in rabbit cranium bone. Study design: Twelve adult male Japanese white rabbits (12-16 wk, 2.5-3.0 kg) were used. The surgical defects were made in the nasal bone of a rabbit, and Biopex was implanted in the left side and no material in the right side. Two-hole absorbable plate and 2 screws (Super Fixsorb-MX) were fixed across the defect in each side. The rabbits were killed at 1, 4, 12, and 24 weeks after surgery, and formalin-fixed specimens were embedded in acrylic resin. The specimens were stained with hematoxylin and eosin. For immunohistochemical analysis, the specimens were treated with bone morphogenetic protein 2 (BMP-2) antibodies. Finally, these were evaluated microscopically. Results: New bone formation was observed in the region of absorbable plate and nasal membrane after >4 weeks. The area of new bone with Biopex was significantly larger than that of the control side after 1, 4, and 12 weeks (P < .05). The number of BMP-2stained cells in the experimental side was significantly larger than in the control side after 4 and 12 weeks (P < .05). Conclusion: This study suggests that the use of absorbable plate (Super Fixsorb-MX) in combination with Biopex could be useful and that both of Super Fixsorb-MX and Biopex could provide adequate bone regeneration. © 2010 Mosby, Inc

Long-term prognostic value of cardiac autonomic nervous activity in postoperative patients with congenital heart disease

Background: Abnormal cardiac autonomic nervous activity (CANA) is not uncommon in postoperative patients with congenital heart disease (CHD). Methods and results: We attempted to clarify the prognostic value of the CANA variables in postoperative CHD patients and prospectively evaluated the CANA variables in 292 consecutive biventricular and 91 Fontan repair patients. The CANA variables included the heart rate variability, arterial baroreflex sensitivity (BRS), washout ratio of the myocardial metaiodobenzylguanidine scintigraphy, and plasma norepinephrine level. With a follow-up of 10 ± 2 years, 98 total events that required hospitalization, including 13 deaths and 48 unscheduled cardiac events (UCEs), occurred. In all the CHD patients, all the CANA indices predicted the total events and UCEs. Of those, the NE level (p = 0.0004) and BRS (p = 0.0373) predicted the mortality. In a multivariate analysis, the BRS was an independent CANA-predictor for the total events (p = 0.007). In the biventricular patients, the plasma NE level, heart rate variability, and BRS predicted the total events and UCEs and the BRS was the only independent CANA-predictor for the total events (p = 0.0329). In the Fontan patients, the plasma NE level was the only predictor for the UCEs (p = 0.0242) and no other CANA variables were independent predictors of the total events or UCEs. Conclusions: All CANA variables, especially the BRS, were useful predictors for future clinical events in biventricular CHD patients, whereas no CANA variables, except for the plasma NE level, predicted future clinical events in the Fontan patients