Role of intron 1 in smooth muscle α-actin transcriptional regulation in activated mesangial cells in vivo

Role of intron 1 in smooth muscle α-actin transcriptional regulation in activated mesangial cells in vivo.BackgroundThe activation of glomerular mesangial cells is one of the early, important features of progressive glomerular disease. Smooth muscle α-actin (SMαA) is an excellent marker of activated mesangial cells. However, the mechanisms of SMαA regulation are only available from in vitro investigation.MethodsWe examined in vivo promoter analysis of the SMαA gene-utilizing transgenic mice harboring different promoter regions of the SMαA gene fused to chloramphenicol acetyl transferase (CAT). CAT activities were tested in primary cultured mesangial cells and in glomerular legions of Habu venom glomerulonephritis.ResultsThe DNA sequence -891 to +3828, which contains exon 1, intron 1, and the first 14bp of exon 2 in addition to the 5′-flanking sequence of the SMαA gene, induced high levels of transcription in activated mesangial cells in in vivo habu venom glomerulonephritis and in cultured mesangial cells derived from transgenic mice. The DNA region -891 to -124 was a positive element in mesangial cells derived from transgenic mice. Deletions (3316 or 137bp) in intron 1 reduced transcription to undetectable levels. The 137bp sequence is highly conserved among several species, containing one CArG box element, which is one of the key motifs for transcriptional activation of contractile-related proteins. In vitro transfection analysis failed to demonstrate these positive effects of intron 1 and region -891 to -124.ConclusionsIn vivo promoter analysis of the SMαA gene provided new information about the transcriptional regulation of SMαA in activated mesangial cells. The DNA region -891 to -124 has a positive effect on SMαA transcription in cultured mesangial cells. The intron 1 region (+1088 to +1224) plays a pivotal role in SMαA transcription in activated mesangial cells in vivo. Further analysis of this conserved region in intron 1, including the CArG motif, will be of great value in understanding the molecular mechanisms of mesangial activation

Serotonin transporter gene polymorphism may be associated with functional dyspepsia in a Japanese population

<p>Abstract</p> <p>Background</p> <p>Although familial clustering of functional dyspepsia (FD) has been reported, the role of genetics in the susceptibility to FD is still not well understood. In the present study, the association between serotonin transporter (SERT) gene (<it>SLC6A4</it>) polymorphism and FD was explored.</p> <p>Methods</p> <p>Subjects were divided into either a postprandial distress syndrome (PDS) group or an epigastric pain syndrome (EPS) group according to the Rome III criteria. The healthy controls were those who had visited a hospital for an annual health check-up. The presence of the <it>SLC6A4 </it>promoter polymorphism, <it>5-hydroxytryptamin transporter gene linked polymorphic region </it>(<it>5-HTTLPR</it>), was then evaluated, and logistic regression analysis was used to test all variables.</p> <p>Results</p> <p>The <it>5-HTTLPR </it>genotype distribution was 448 SS, 174 SL, and 24 LL in controls and 30 SS, 20 SL, and 3 LL in FD subjects. No significant correlation was found between the <it>5-HTTLPR </it>genotype and FD. When the genotypes and subtypes of FD were exploratory evaluated, the SL genotype was significantly associated with PDS [odds ratio (OR) = 2.24, 95% confidence interval (CI); 1.16-4.32, <it>P </it>= 0.034 after Bonferroni correction] compared to the SS genotype adjusted for sex and age. Comparison of the SS genotype with the SL/LL genotype also showed a significant association of genotype with PDS (OR = 2.32, 95% CI; 1.23-4.37, <it>P </it>= 0.009).</p> <p>Conclusion</p> <p>The present results suggest that <it>5-HTTLPR </it>L allele may influence the susceptibility to PDS.</p

A prototypical small-molecule modulator uncouples mitochondria in response to endogenous hydrogen peroxide production

A high membrane potential across the mitochondrial inner membrane leads to the production of the reactive oxygen species (ROS) implicated in aging and age-related diseases. A prototypical drug for the correction of this type of mitochondrial dysfunction is presented. MitoDNP-SUM accumulates in mitochondria in response to the membrane potential due to its mitochondria-targeting alkyltriphenylphosphonium (TPP) cation and is uncaged by endogenous hydrogen peroxide to release the mitochondrial uncoupler, 2,4-dinitrophenol (DNP). DNP is known to reduce the high membrane potential responsible for the production of ROS. The approach potentially represents a general method for the delivery of drugs to the mitochondrial matrix through mitochondria targeting and H2O2-induced uncaging

Evidence for suppressed metallicity on the surface of La2-xSrxCuO4 and Nd2-xCexCuO4

Hard X-ray Photoemission spectroscopy (PES) of copper core electronic states, with a probing depth of $\sim$60 \AA, is used to show that the Zhang-Rice singlet feature is present in La$_2$CuO$_4$ but is absent in Nd$_2$CuO$_4$. Hole- and electron doping in La$_{2-x}$Sr$_x$CuO$_4$ (LSCO) and Nd$_{2-x}$Ce$_x$CuO$_4$ (NCCO) result in new well-screened features which are missing in soft X-ray PES. Impurity Anderson model calculations establish metallic screening as its origin, which is strongly suppressed within 15 $\text{\AA}$ of the surface. Complemented with X-ray absorption spectroscopy, the small chemical-potential shift in core levels ($\sim0.2$ eV) are shown to be consistent with modifications of valence and conduction band states spanning the band gap ($\sim1$ eV) upon hole- and electron-doping in LSCO and NCCO.Comment: 4 pages, 4 figure

Novel Variants in the CLCN1, RYR2, and DCTN1 Found in Elderly Japanese Dementia Patients: A Case Series

Dementia has an enormous impact on medical and financial resources in aging societies like Japan. Diagnosis of dementia can be made by physical and mental examinations, imaging tests, and findings of high abnormal proteins in cerebrospinal fluids. In addition, genetic tests can be performed in neurodegenerative diseases such as Alzheimer's disease (AD), frontotemporal dementia (FTD), and Parkinson's disease (PD). In this case series, we presented three cases of dementia with unknown causes who carry novel variants in the genes associated with neurodegenerative diseases. Three patients (Patients 1, 2, and 6) were found by screening 18 dementia patients using a gene panel including 63 genes. The age of onset for Patient 1 was 74 years old, and his father had PD and mother had AD. The age of onset for Patient 2 was 75 years old, and her mother had AD. The age of onset for Patient 6 was 83 years old, and her father, two sisters, and daughter had dementia. The Mini-Mental State Examination produced results of 20, 15, and 22, respectively. The suspected diagnosis by neurological examinations and imaging studies for Patients 1 and 2 was AD, and for Patient 6 was FTD. Patient 1 was treated with donepezil; Patient 2 was treated with donepezil and memantine; and Patient 6 was treated with donepezil, galantamine, and rivastigmine. The three rare variants identified were: CLCN1, encoding a chloride channel, c.2848G>A:p.Glu950Lys (Patient 1); RYR2, encoding a calcium releasing ryanodine receptor, c.13175A>G:p.Lys4392Arg (Patient 2); and DCTN1, encoding a subunit of dynactin, c. 3209G>A:p.Arg1070Gln (Patient 6). The detected variants were interpreted according to the American College of Medical Genetics (ACMG) guidelines. The minor allele frequency for each variant was 0.025%, 0.023%, and 0.0004% in East Asians, respectively. The DCTN1 variant found in Patient 6 might be associated with FTD. Although none of them were previously reported in dementia patients, all variants were classified as variants of unknown significance (VUS). Our report suggests that results of genetic tests in elderly patients with dementia need to be carefully interpreted. Further data accumulation of genotype-phenotype relationships and development of appropriate functional models are warranted

本学教育学科・短大幼児教育学科2016年夏期短期海外研修 プログラム改善の成果と課題

本研究の目的は本学教育学科・幼児教育学科2016 年夏期短期海外研修プログラム改善の成果と課題を明らかにすることである。2015 年度の夏期短期海外研修の成果と課題は金子ら（2015）によって明らかにされた。その結果を元に2016 年度のプログラムに改善を加えた。主な改善点は，レーニア山旅行中止，小学校のサマーキャンプへの参加，学びの振り返りの時間を持つなどである。改善の結果，学生がどのように評価しているかを調査した。調査は質問紙法（2015 年度，2016 年度の結果比較）と添乗員のプログラム記録比較と引率者・同行者の観察によって行った。その結果，昨年度に比べて研修の満足度が高くなったり，楽しかったことに教育施設の訪問を挙げる学生が増えてきたりなどプラスの効果が見られた

本学教育学科・短大幼児教育学科2015年夏期短期海外研修の成果と課題

武庫川女子大学文学部教育学科・短大幼児教育学科は，米国ワシントン州にある St. Martin’s University と友好的な関係を結んでいて，8 月に実施される 3 週間の研修プログラムに毎年 20 人から 30 人の学生が参加している。本研究の目的は，2015年に行われた研修プログラムの成果と課題を明らかにする事である。研究の目的を達成するために，参加学生対象の事前，事後のアンケート結果，事前指導を行った担当者の指導内容と所見，引率助手と海外研修担当助手の指導内容と所見から，研修の成果と課題を明らかにした。その結果，学生はこの研修に髙い満足度を示し，異なる文化や英語でのコミュニケーションについて大きな学びをしていることから，この研修は大きな成果をあげている事がわかった。今後の課題としては，研修プログラムに休日や振り返りを入れる必要があること，そのために不要な内容を削除すること，健康上の問題が発生した場合の対処や事前指導をより効果的なものにするための改善などが必要である事が明らかになった

The G-Protein β3 subunit 825 TT genotype is associated with epigastric pain syndrome-like dyspepsia

<p>Abstract</p> <p>Background</p> <p>Although familial clustering of functional dyspepsia (FD) has been reported, the role of genetics in the susceptibility to FD is still not well understood. Several reports indicate an association between FD and G-protein β3 (GNB3) subunit gene polymorphism (C825T); however, these studies had small sample sizes and the findings are inconclusive. In the present study we clarified the association between GNB3 gene polymorphism and dyspepsia in a large population of Japanese subjects who visited a hospital for annual health check-up.</p> <p>Methods</p> <p>Subjects with significant upper gastrointestinal findings were excluded. Subjects with dyspeptic symptoms were divided into either a postprandial distress syndrome (PDS) group or an epigastric pain syndrome (EPS) group according to the Rome III criteria. The presence of the GNB3 C825T polymorphism was then evaluated and logistic regression analysis was used to test all variables.</p> <p>Results</p> <p>The GNB3 genotype distribution in subjects without dyspepsia was 191 CC (25.1%), 368 TC (48.4%), and 202 TT (26.5%) and 17 CC (25.0%), 29 TC (42.6%), and 22 TT (32.4%) in subjects with dyspepsia. No significant correlation was found between the GNB3 825TT genotype and dyspepsia. However, the TT genotype was significantly associated with subjects with EPS-like symptoms (odds ratio (OR) = 2.00, 95% confidence interval (CI); 1.07-3.76) compared to the CT/CC genotype adjusted for gender and age. No significant correlation was found between GNB3 polymorphism and PDS-like symptoms (OR = 0.68, 95% CI; 0.31-1.51). With the exclusion of subjects with both EPS- and PDS-like symptoms, only the TT genotype was significantly associated with EPS-like symptoms (OR = 2.73, 95% CI; 1.23-5.91).</p> <p>Conclusion</p> <p>The homozygous GNB3 825T allele influences the susceptibility to EPS-like dyspepsia.</p

Mathematical Modeling of the Role of Mitochondrial Fusion and Fission in Mitochondrial DNA Maintenance

10.1371/journal.pone.0076230PLOS ONE8101-1