NFATc1 regulates the transcription of DNA damage-induced apoptosis suppressor

AbstractDNA damage induced apoptosis suppressor (DDIAS), or human Noxin (hNoxin), is strongly expressed in lung cancers. DDIAS knockdown induced apoptosis in non-small cell lung carcinoma A549 cells in response to DNA damage, indicating DDIAS as a potential therapeutic target in lung cancer. To understand the transcriptional regulation of DDIAS, we determined the transcription start site, promoter region, and transcription factor. We found that DDIAS transcription begins at nucleotide 212 upstream of the DDIAS translation start site. We cloned the DDIAS promoter region and identified NFAT2 as a major transcription factor (Im et al., 2016 [1]). We demonstrated that NFATc1 regulates DDIAS expression in both pancreatic cancer Panc-1 cells and lung cancer cells

Transparent graphene films with a tunable piezoresistive response

We demonstrate a graphene-coated polymer film as a transparent piezoresistive strain sensor. Strain sensitivity was tuned by controlling the thickness and density of the graphene layer as well as the adhesion force between graphene and the substrate. Chemically reducing the graphene oxide, thereby maximizing its adhesion to the substrate, while minimizing the coating density and thickness resulted in excellent transparency and high gauge factors. The fabrication method presented allows design optimization of transparent, high-performance, and sensitivity-tunable piezoresistive sensors, which can make inroads into such applications as wide-area strain sensors, self-sensing flexible electronics, and intelligent structural health monitoring.close0

Recessive C10orf2 mutations in a family with infantile-onset spinocerebellar ataxia, sensorimotor polyneuropathy, and myopathy

Recessive mutations in chromosome 10 open reading frame 2 (C10orf2) are relevant in infantile-onset spinocerebellar ataxia (IOSCA). In this study, we investigated the causative mutation in a Korean family with combined phenotypes of IOSCA, sensorimotor polyneuropathy, and myopathy. We investigated recessive mutations in a Korean family with two individuals affected by IOSCA. Causative mutations were investigated using whole exome sequencing. Electrophysiological analyses and muscle and nerve biopsies were performed, along with magnetic resonance imaging (MRI) of the brain and lower extremities. Compound heterozygous mutations c.1460C>T and c.1485-1G>A in C10orf2 were identified as causative of IOSCA. Skeletal muscle showed mitochondrial DNA (mtDNA) deletions. Both patients showed a period of normal development until 12–15 months, followed by ataxia, athetosis, hearing loss, and intellectual disability. Electrophysiological findings indicated motor and sensory polyneuropathies. Muscle biopsy revealed variations in the size and shape of myofibers with scattered, small, and angulated degenerating myofibers containing abnormal mitochondria; these observations are consistent with myopathy and may be the result of mtDNA deletions. Sural nerve biopsy revealed an axonal neuropathy. High-signal-intensity lesions in the middle cerebellar peduncles were correlated with clinical severity, and MRI of the lower legs was compatible with the hypothesis of length-dependent axonal degeneration. We identified novel compound heterozygous mutations of the C10orf2 gene as the cause of IOSCA with sensorimotor polyneuropathy and myopathy. Signs of motor neuropathy and myopathy were discovered for the first time in IOSCA patients with C10orf2 mutations. These results suggest that the clinical spectrum of IOSCA caused by C10orf2 mutations may be more variable than previously reported. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10048-014-0405-1) contains supplementary material, which is available to authorized users

A Case Report of Sweet’s Syndrome with Parotitis

Sweet’s syndrome is characterized by clinical symptoms, physical features, and pathologicfindings which include fever, neutrophilia, tender erythematous skin lesions, and a diffuseinfiltrate of mature neutrophils. This is a report of our experience of Sweet’s syndrome withparotitis. A 57-year-old man initially presented with tender swelling on the right cheeksimilar to parotitis. His symptoms relapsed despite the use of an oral antibiotic agent for 3weeks. He additionally presented with erythematous papules and plaques on the perioculararea and dorsum of both hands. Histiopathologic findings on punch biopsy of the rightdorsum of the hand showed superficial perivenular histiocytic infiltration without vasculitis.We confirmed this as histiocytoid Sweet’s syndrome and used systemic corticosteroid. Afterinitiation of treatment with systemic corticosteroids, there was a prompt recovery from boththe dermatosis-releated symptoms and skin lesions. Sweet’s syndrome should be consideredin patients with therapy-refractory parotitis and unclear infiltrated nodules. We present aconfusing case who initially appeared to have parotitis but turned out to have histiocytoidSweet’s syndrome

Therapeutic genome editing for Charcot-marie-tooth disease type 1a

Charcot-Marie-Tooth 1A (CMT1A) is the most common inherited neuropathy without a known therapy, which is caused by a 1.4 Mb duplication on human chromosome 17, which includes the gene encoding the peripheral myelin protein of 22 kDa (PMP22). Overexpressed PMP22 protein from its gene duplication is thought to cause demyelination and subsequently axonal degeneration in the peripheral nervous system (PNS). Here, we targeted regulatory region of human PMP22 to normalize overexpressed PMP22 level in C22 mice, a mouse model of CMT1A harboring multi copies of human PMP22. Direct local intraneural delivery of CRISPR/Cas9 designed to target TATA-box of PMP22 before the onset of disease, downregulates gene expression of PMP22 and preserves both myelin and axons. Notably, the same approach was effective in partial rescue of demyelination even after the onset of disease. Collectively, our data present a potential therapeutic efficacy of CRISPR/Cas9-mediated targeting of regulatory region of PMP22 to treat CMT1A. Please click Additional Files below to see the full abstract

Psychometric Properties of the Hypomania Checklist-32 in Korean Patients with Mood Disorders

OBJECTIVE The aim of this study was to examine the validity of the Korean version of the Hypomania Checklist-32, second revision (HCL-32-R2) in mood disorder patients. METHODS A total of 454 patients who diagnosed as mood disorder according to Structured Clinical Interview for DSM-IV Axis I Disorders, clinician version (SCID-CV) (bipolar disorder [BD] I, n=190; BD-II, n=72; and major depressive disorder [MDD], n=192) completed the Korean module of the HCL-32-R2 (KHCL-32-R2). RESULTS The KHCL-32-R2 showed a three-factorial structure (eigenvalue ＞2) that accounted for 43.26% of the total variance. Factor 1 was labeled "active/elated" and included 16 items; factor 2, "irritable/distractible" and included 9 items; and factor 3 was labeled "risk-taking/indulging" and included 9 items. A score of 16 or more on the KHCL-32-R2 total scale score distinguished between BD and MDD, which yielded a sensitivity of 70% and a specificity of 70%. MDD and BD-II also could be differentiated at a cut-off of 15 with maximized sensitivity (0.67) and specificity (0.66). Cronbach's alpha of KHCL-32-R2 and its subsets (factors 1, 2, and 3) were 0.91, 0.89, 0.81 and 0.79, respectively. Correlations between KHCL-32-R2 and Montgomery- Asberg Depression Rating Scale, Young Mania Rating Scale and Korean version of Mood Disorder Questionnaire were -0.66 (p=0.41), -0.14 (p=0.9), and 0.61 (p＜0.001), respectively. CONCLUSION The KHCL-32-R2 may be a useful tool in distinguishing between bipolar and depressive patients in clinical settings

Periprocedural Myocardial Infarction After Retrograde Approach for Chronic Total Occlusion of Coronary Artery: Demonstrated by Cardiac Magnetic Resonance Imaging

A retrograde approach through the collateral channels was recently proposed as one of the most promising current techniques for percutaneous coronary intervention of chronic total occlusion in coronary arteries (CTO). This report describes the case of a 68-year-old man in whom CTO was successfully crossed with a wire by the retrograde approach using septal collateral, but the patient suffered from a complication with septal myocardial infarction demonstrated by cardiac magnetic resonance imaging