Copy number loss of (src homology 2 domain containing)-transforming protein 2 (SHC2) gene: discordant loss in monozygotic twins and frequent loss in patients with multiple system atrophy

<p>Abstract</p> <p>Background</p> <p>Multiple system atrophy (MSA) is a sporadic disease. Its pathogenesis may involve multiple genetic and nongenetic factors, but its etiology remains largely unknown. We hypothesized that the genome of a patient with MSA would demonstrate copy number variations (CNVs) in the genes or genomic regions of interest. To identify genomic alterations increasing the risk for MSA, we examined a pair of monozygotic (MZ) twins discordant for the MSA phenotype and 32 patients with MSA.</p> <p>Results</p> <p>By whole-genome CNV analysis using a combination of CNV beadchip and comparative genomic hybridization (CGH)-based CNV microarrays followed by region-targeting, high-density, custom-made oligonucleotide tiling microarray analysis, we identified disease-specific copy number loss of the (Src homology 2 domain containing)-transforming protein 2 (<it>SHC2</it>) gene in the distal 350-kb subtelomeric region of 19p13.3 in the affected MZ twin and 10 of the 31 patients with MSA but not in 2 independent control populations (<it>p </it>= 1.04 × 10^-8, odds ratio = 89.8, Pearson's chi-square test).</p> <p>Conclusions</p> <p>Copy number loss of <it>SHC2 </it>strongly indicates a causal link to MSA. CNV analysis of phenotypically discordant MZ twins is a powerful tool for identifying disease-predisposing loci. Our results would enable the identification of novel diagnostic measure, therapeutic targets and better understanding of the etiology of MSA.</p

「学科間プロジェクト」のカリキュラム開発に関する実践的研究/「有馬温泉ゆけむり大学」を事例として

本研究では、「有馬温泉ゆけむり大学」を実践的なデザイン教育の場として研究を行った。すなわち、「学科間プロジェクト」の教育的効果を再考するために、本イベントの「Tシャツ」、「チラシ」デザイン、及び有志学生による「神戸芸工大雑貨屋さん」、「浴衣DEファッションショー」を開催した。その他イベントとして、「有馬温泉クリスマスツリープロジェクト」のワークショップ、「有馬節分会」の「チラシ」デザインを行った。また、武蔵野美術大学・群馬県立女子大学・立命館アジア太平洋大学に出向き、聞き取り調査を行った。研究の結果、「有馬温泉ゆけむり大学」に参加した学生は、他の学科及び学年を超えた交流の機会ができた。また、特に大阪音楽大学・近畿大学・武庫川女子大学の学生たち及び有馬温泉のスタッフとも交流ができたことは、大変貴重な経験となり、様々な教育効果が期待できる。したがって、「学科間プロジェクト」のカリキュラム開発のための基礎資料を得ることができた。In this studies, we studied that the "Arima Onsen Yukemuri University" was for design practical education. That is, in order to rethink the educational effect of "Interdepartmental Project", of this event "T-shirt", "Flyer" design, and by volunteer students "Kobe Design University Zakkaya san", "Yukata DE Fashion show" were held. As other events, workshop of "Arima Onsen Christmas tree project" , "Flyer" design for "Arima Setsubun E".In addition, visited to Musashino Art University, Gunma Prefectural Women\u27s University, Ritsumeikan Asia Pacific University, which were investigated.Results of the studies, students who participated in the "Arima Onsen Yukemuri University" was able opportunity of exchange beyond the school year and other departments. In addition, it becomes a very valuable experience, that the staff of Arima Onsen and students of Osaka College of Music, Kinki University, Mukogawa Women\u27s University also could exchange in particular can be expected to be teaching a variety of effects. Therefore, it was possible to obtain the basic data for curriculum development "Interdepartmental Project"

Breastfeeding information in midwifery textbooks in Japan: content analysis with evaluation standards based on Delphi method.

The purpose of this study was to evaluate breastfeeding information in midwifery textbooks. Evaluation standards were developed in order to perform content analysis. A 3-round Delphi method using a panel of 32 midwives resulted in 36 evaluation items from the original 38 draft items based on 4 major international guidelines and statements on breastfeeding. Subsequently, breastfeeding descriptions in 4 midwifery textbooks most frequently used in Japan were examined using a 4-point scale (A, accurate and sufficient description; B, accurate but insufficient description; C, no description; and D, inaccurate or inconsistent description). Among the evaluation items, 40% were rated as A, 25% as C, 21% as B, and 15% as D across the 4 textbooks. In conclusion, a substantial proportion of breastfeeding information in these textbooks was found to be inaccurate, inconsistent, or insufficient in content

Whole-exome sequencing and digital PCR identified a novel compound heterozygous mutation in the NPHP1 gene in a case of Joubert syndrome and related disorders

Abstract Background Joubert syndrome and related disorders (JSRD) is a clinically and genetically heterogeneous condition with autosomal recessive or X-linked inheritance, which share a distinctive neuroradiological hallmark, the so-called molar tooth sign. JSRD is classified into six clinical subtypes based on associated variable multiorgan involvement. To date, 21 causative genes have been identified in JSRD, which makes genetic diagnosis difficult. Case presentation We report here a case of a 28-year-old Japanese woman diagnosed with JS with oculorenal defects with a novel compound heterozygous mutation (p.Ser219*/deletion) in the NPHP1 gene. Whole-exome sequencing (WES) of the patient identified the novel nonsense mutation in an apparently homozygous state. However, it was absent in her mother and heterozygous in her father. A read depth-based copy number variation (CNV) detection algorithm using WES data of the family predicted a large heterozygous deletion mutation in the patient and her mother, which was validated by digital polymerase chain reaction, indicating that the patient was compound heterozygous for the paternal nonsense mutation and the maternal deletion mutation spanning the site of the single nucleotide change. Conclusion It should be noted that analytical pipelines that focus purely on sequence information cannot distinguish homozygosity from hemizygosity because of its inability to detect large deletions. The ability to detect CNVs in addition to single nucleotide variants and small insertion/deletions makes WES an attractive diagnostic tool for genetically heterogeneous disorders

Imaging Isomers on a Biological Surface:A Review

Mass spectrometry imaging is an imaging technology that allows the localization and identification of molecules on (biological) sample surfaces. Obtaining the localization of a compound in tissue is of great value in biological research. Yet, the identification of compounds remains a challenge. Mass spectrometry alone, even with high-mass resolution, cannot always distinguish between the subtle structural differences of isomeric compounds. This review discusses recent advances in mass spectrometry imaging of lipids, steroid hormones, amino acids and proteins that allow imaging with isomeric resolution. These improvements in detailed identification can give new insights into the local biological activity of isomers

TGF-β and Physiological Root Resorption of Deciduous Teeth

The present study was performed to examine how transforming growth factor β (TGF-β) in root-surrounding tissues on deciduous teeth regulates the differentiation induction into odontoclasts during physiological root resorption. We prepared root-surrounding tissues with (R) or without (N) physiological root resorption scraped off at three regions (R1–R3 or N1–N3) from the cervical area to the apical area of the tooth and measured both TGF-β and the tartrate-resistant acid phosphatase (TRAP) activities. The TGF-β activity level was increased in N1–N3, whereas the TRAP activity was increased in R2 and R3. In vitro experiments for the receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-mediated osteoclast differentiation revealed that proteins from N1–N3 and R1–R3 enhanced the TRAP activity in RAW264 cells. A genetic study indicated that the mRNA levels of TGF-β1 in N1 and N2 were significantly increased, and corresponded with levels of osteoprotegerin (OPG). In contrast, the expression level of RANKL was increased in R2 and R3. Our findings suggest that TGF-β is closely related to the regulation of OPG induction and RANKL-mediated odontoclast differentiation depending on the timing of RANKL and OPG mRNA expression in the root-surrounding tissues of deciduous teeth during physiological root resorption

Dose-Dependent Effect of Intravenous Administration of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Neonatal Stroke Mice

Neonatal brain injury induced by stroke causes significant disability, including cerebral palsy, and there is no effective therapy for stroke. Recently, mesenchymal stem cells (MSCs) have emerged as a promising tool for stem cell-based therapies. In this study, we examined the safety and efficacy of intravenously administered human umbilical cord-derived MSCs (UC-MSCs) in neonatal stroke mice. Pups underwent permanent middle cerebral artery occlusion at postnatal day 12 (P12), and low-dose (1 × 104) or high-dose (1 × 105) UC-MSCs were administered intravenously 48 h after the insult (P14). To evaluate the effect of the UC-MSC treatment, neurological behavior and cerebral blood flow were measured, and neuroanatomical analysis was performed at P28. To investigate the mechanisms of intravenously injected UC-MSCs, systemic blood flowmetry, in vivo imaging and human brain-derived neurotrophic factor (BDNF) measurements were performed. Functional disability was significantly improved in the high-dose UC-MSC group when compared with the vehicle group, but cerebral blood flow and cerebral hemispheric volume were not restored by UC-MSC therapy. The level of exogenous human BDNF was elevated only in the cerebrospinal fluid of one pup 24 h after UC-MSC injection, and in vivo imaging revealed that most UC-MSCs were trapped in the lungs and disappeared in a week without migration toward the brain or other organs. We found that systemic blood flow was stable over the 10 min after cell administration and that there were no differences in mortality among the groups. Immunohistopathological assessment showed that the percent area of Iba1-positive staining in the peri-infarct cortex was significantly reduced with the high-dose UC-MSC treatment compared with the vehicle treatment. These results suggest that intravenous administration of UC-MSCs is safe for a mouse model of neonatal stroke and improves dysfunction after middle cerebral artery occlusion by modulating the microglial reaction in the peri-infarct cortex

Relationship between facial skin problems with a focus on inflammatory cytokines and the presence of Malassezia in 1-month-old infants

Abstract Infantile skin problems not only cause temporary pain and discomfort, but also have a long-term impact on health. Hence, the purpose of this cross-sectional study was to clarify the relationship between inflammatory cytokines and Malassezia fungal facial skin problems in infants. Ninety-six 1-month-old infants were examined. Facial skin problems and the presence of inflammatory cytokines in the forehead skin were assessed using the infant facial skin visual assessment tool (IFSAT) and the skin blotting method, respectively. Malassezia, a fungal commensal, was detected using forehead skin swabs, and its percentage in the total fungal population was analyzed. Infants with positive interleukin-8 signals were more likely to have severe facial skin problems (p = 0.006) and forehead papules (p = 0.043). No significant association between IFSAT scores and Malassezia was found, but infants with forehead dryness had a lower percentage of M. arunalokei in the total fungal population (p = 0.006). No significant association was observed between inflammatory cytokines and Malassezia in the study participants. Longitudinal studies on the development of facial skin problems in infants are warranted to investigate the involvement of interleukin-8 and devise preventive strategies in the future