通級指導教室における コミュニケーションに困難のある児童の支援 1 ―通級による指導の役割と今後の課題―

The framework for children who need special support in school education has changed from “special education” to “special support education” since the revision of the School Education Law in 2007. In the course of this change, “resource room education”, which had not been recognized as part of the formal education system, has been attracting attention as a system that plays a central role in “special needs education.” The aim of this paper is to clarify the role of resource room education and its future issues by sorting out the development and transition of the system for children with both language and developmental disabilities who are taking advantage of resource rooms. Resource room education was initiated in the early 1950s by teachers as extracurricular classes for children with language disabilities who had difficulty in reading or speaking in class. After that, a more systematic “resource room for children with speech and language disorders” was established, but the actual situation was that guidance was not given in a fixed class in the resource room but was instead given at the regular class level. On the other hand, since the Act on Support for Persons with Development Disabilities was enacted in 2005, children with developmental disabilities, such as ADHD （attention-deficit hyperactivity disorder） and LD （learning disabilities）, who had not been recipients of the type of support until then, also began to receive special support education. Today inclusive education has become part of a standard educational system, and the resource room education is a very effective educational system for children with developmental disabilities and other special needs as well as language disorders

通級指導教室における コミュニケーションに困難のある児童の支援 2 ―場面緘黙児の指導事例―

In instructing children with selective mutism in the field of education, it is necessary to conduct a multi-faceted assessment of each child to enhance their power of expression in a way that suits them in terms of their ability, interest, concern, willingness and motivation.In this study, the goal is to assess the effectiveness of instruction by reporting the progress of a case where three teachers, including one of the authors of this paper, were involved in the instruction in a resource room of a child “G”, aged 6, who has selective mutism.G has a level of intellectual development appropriate for her age, but was highly anxious and could not speak in a group. In the resource room, small-group “communication” and “physical exercise” programs were combined with individualized instruction, and were conducted once or twice a week. The instruction entailed physical exercises and painting, which G is good at. Teachers conducted communication skill training by acting in short skits. As a result of yearlong comprehensive instruction, the symptoms of selective mutism declined; G could express her thoughts more actively than before. The instruction seemed to have had some effect. However, at the beginning of the second part of the year, G could no longer attend regular class. Thus those assisting in her recovery have more work to do

Bullous Pemphigoid IgG Induces BP180 Internalization via a Macropinocytic Pathway

Bullous pemphigoid (BP) is an autoimmune blistering skin disease induced by pathogenic autoantibodies against a type II transmembrane protein (BP180, collagen type XVII, or BPAG2). In animal models, BP180 autoantibody-antigen interaction appears insufficient to develop blisters, but involvement of complement and neutrophils is required. However, cultured keratinocytes treated with BP-IgG exhibit a reduction in the adhesive strength and a loss of expression of BP180, suggesting that the autoantibodies directly affect epidermal cell–extracellular matrix integrity. In this study, we explored the consequences of two distinct epithelial cells treated with BP-IgG, particularly the fate of BP180. First, we followed the distribution of green fluorescent protein–tagged BP180 in an epithelial cell line, 804G, and normal human epidermal keratinocytes after autoantibody clustering. After BP-IgG treatment, the adhesive strength of the cells to their substrate was decreased, and BP180 was internalized in both cell types, together with the early endosomal antigen-1. By using various endocytosis inhibitors and a fluid-uptake assay, we demonstrated that BP-IgG–induced BP180 internalization is mediated via a macropinocytic pathway. Moreover, a macropinocytosis inhibitor rescued a BP-IgG–induced reduction in the adhesive strength of the cells from their substrate. The results of this study suggest that BP180 internalization induced by BP-IgG plays an important role in the initiation of disease pathogenesis

Trans-complemented hepatitis C virus particles as a versatile tool for study of virus assembly and infection

AbstractIn this study, we compared the entry processes of trans-complemented hepatitis C virus particles (HCVtcp), cell culture-produced HCV (HCVcc) and HCV pseudoparticles (HCVpp). Anti-CD81 antibody reduced the entry of HCVtcp and HCVcc to almost background levels, and that of HCVpp by approximately 50%. Apolipoprotein E-dependent infection was observed with HCVtcp and HCVcc, but not with HCVpp, suggesting that the HCVtcp system is more relevant as a model of HCV infection than HCVpp. We improved the productivity of HCVtcp by introducing adapted mutations and by deleting sequences not required for replication from the subgenomic replicon construct. Furthermore, blind passage of the HCVtcp in packaging cells resulted in a novel mutation in the NS3 region, N1586D, which contributed to assembly of infectious virus. These results demonstrate that our plasmid-based system for efficient production of HCVtcp is beneficial for studying HCV life cycles, particularly in viral assembly and infection

Neuroprotective effect of 5-aminolevulinic acid against low inorganic phosphate in neuroblastoma SH-SY5Y cells

PiT-1 (encoded by SLC20A1) and PiT-2 (encoded by SLC20A2) are type-III sodium-dependent phosphate cotransporters (NaPiTs). Recently, SLC20A2 mutations have been found in patients with idiopathic basal ganglia calcification (IBGC), and were predicted to bring about an inability to transport Pi from the extracellular environment. Here we investigated the effect of low Pi loading on the human neuroblastoma SH-SY5Y and the human glioblastoma A172 cell lines. The results show a different sensitivity to low Pi loading and differential regulation of type-III NaPiTs in these cells. We also examined whether 5-aminolevulinic acid (5-ALA) inhibited low Pi loading-induced neurotoxicity in SH-SY5Y cells. Concomitant application of 5-ALA with low Pi loading markedly attenuated low Pi-induced cell death and mitochondrial dysfunction via the induction of HO-1 by p38 MAPK. The findings provide us with novel viewpoints to understand the pathophysiology of IBGC, and give a new insight into the clinical prevention and treatment of IBGC

Single-cell transcriptomics of human cholesteatoma identifies an activin A-producing osteoclastogenic fibroblast subset inducing bone destruction

Cholesteatoma, which potentially results from tympanic membrane retraction, is characterized by intractable local bone erosion and subsequent hearing loss and brain abscess formation. However, the pathophysiological mechanisms underlying bone destruction remain elusive. Here, we performed a single-cell RNA sequencing analysis on human cholesteatoma samples and identify a pathogenic fibroblast subset characterized by abundant expression of inhibin βA. We demonstrate that activin A, a homodimer of inhibin βA, promotes osteoclast differentiation. Furthermore, the deletion of inhibin βA /activin A in these fibroblasts results in decreased osteoclast differentiation in a murine model of cholesteatoma. Moreover, follistatin, an antagonist of activin A, reduces osteoclastogenesis and resultant bone erosion in cholesteatoma. Collectively, these findings indicate that unique activin A-producing fibroblasts present in human cholesteatoma tissues are accountable for bone destruction via the induction of local osteoclastogenesis, suggesting a potential therapeutic target.Shimizu K., Kikuta J., Ohta Y., et al. Single-cell transcriptomics of human cholesteatoma identifies an activin A-producing osteoclastogenic fibroblast subset inducing bone destruction. Nature Communications 14, 4417 (2023); https://doi.org/10.1038/s41467-023-40094-3

Physiological and Ultrastructural Studies on the Origin of Activator Calcium in Body Wall Muscles of Spoon Worms

To examine the origin of activator Ca and its translocation during contraction in body wall muscles (BWM) of spoon worms, Urechis unicinctus , physiological and ultrastructural studies, including cytochemistry, were performed. The potassium (K-) contracture tension was significantly reduced by the removal of external Ca, and by the application of Mn, La and verapamil. On the other hand, caffeine induced a prolonged contraction. The removal of Ca and Mg from the external solution, and the rapid cooling caused an irregular or oscillatory contraction. These results suggested that, in BWM fibers, the activator Ca is supplied partially from both external solution and intracellular Ca-accumulating structures. Ultrastructural observations revealed that the muscle fibers contain a relatively large amount of sarcoplasmic reticulum (SR). The fractional volume of the SR relative to the fiber volume was 2~5% in all fibers of three muscle layers. To demonstrate the Ca localization, the muscle fibers were fixed by pyroantimonate (PA) methods at resting and contracting states. In the resting fibers, the PA precipitates were exclusively localized in the SR and the inner surface of plasma membrane. On the other hand, in the contracting fibers, they were diffusely distributed in the central regions of myoplasm, and had disappeared from the SR and plasma membrane. X-ray microanalysis revealed that the PA precipitates contain Ca. With the results of physiological experiments, these results indicate that the activator Ca originates not only from the external solution, but also from the intracellular Ca-accumulating structures, the SR and the inner surface of plasma membrane.Full-Length Pape

Decoding the view expectation during learned maze navigation from human fronto-parietal network

脳活動から予測したシーンを解読 －予測の間違い「思い込み」も明るみに－. 京都大学プレスリリース. 2015-12-04.Humans use external cues and prior knowledge about the environment to monitor their positions during spatial navigation. View expectation is essential for correlating scene views with a cognitive map. To determine how the brain performs view expectation during spatial navigation, we applied a multiple parallel decoding technique to functional magnetic resonance imaging (fMRI) when human participants performed scene choice tasks in learned maze navigation environments. We decoded participants’ view expectation from fMRI signals in parietal and medial prefrontal cortices, whereas activity patterns in occipital cortex represented various types of external cues. The decoder’s output reflected participants’ expectations even when they were wrong, corresponding to subjective beliefs opposed to objective reality. Thus, view expectation is subjectively represented in human brain, and the fronto-parietal network is involved in integrating external cues and prior knowledge during spatial navigation