Molecular epidemiology and genetic diversity of human astrovirus in South Korea from 2002 to 2007

AbstractThe present study was conducted to survey the prevalence and genotypic distribution of human astrovirus (HAstV) circulating in South Korea. Of 160,027 patients with acute gastroenteritis, 2,057 (1.3%) were positive for HAstV antigen. We determined the genotypes of 187 HAstV strains collected from laboratories across the country. Genetic analysis revealed genotype 1 to be the most prevalent, accounting for 72.19% of the strains, followed by genotypes 8 (9.63%), 6 (6.95%), 4 (6.42%), 2 (3.21%) and 3 (1.60%). Our findings indicate that HAstV is less common but, even so, a potentially important viral agent of gastroenteritis in South Korea, with significant genetic diversity among circulating HAstV strains

Sex differences in body composition affect total airway resistance during puberty

Abstract Background During puberty, changes in body composition due to sex hormones are associated with lung mechanics. However, little is known about the mediation effect of sex differences in body composition during puberty with total airway resistance. Methods We prospectively recruited 620 children (10–12years old) from the general population and conducted a cross-sectional study. This study assessed pubertal status according to the five Tanner stages using a questionnaire, line drawings, and each subjects blood sex hormone profile. Both the impulse oscillation system for total lung mechanics and multifrequency bioelectrical impedance for body composition analyses were conducted. The effects of puberty on body composition and subsequent total lung resistance were evaluated using mediation analysis. Results Among the 503 children enrolled, there were 261 males (51.9%) and 242 females (48.1%). In males, higher testosterone levels corresponded with reduced total lung resistance (β = –0.13, 95% CI = –0.21 to –0.05, p < 0.001), and the proportion of the mediating effect through the muscle-fat ratio was 19% (95% CI = 4 to 59, p = 0.02). In contrast, in females, pubertal status reduced total lung resistance (β = –0.27, 95% CI = –0.58 to –0.05, p = 0.04), however, the proportion of the mediating effect through the body mass index was –51% (95% CI = –244 to –4%, p = 0.04). Conclusion The muscle-fat ratio in adolescent males had a synergistic effect with testosterone on improving total airway resistance, whereas improvements in lung resistance by pubertal status were partially masked by body mass index in adolescent females. In conclusion, body composition changes during puberty between males and females have differing effects on total airway resistance

CSF total tau/α-synuclein ratio improved the diagnostic performance for Alzheimers disease as an indicator of tau phosphorylation

Abstract Background Recently, several studies suggested potential involvements of α-synuclein in Alzheimers disease (AD) pathophysiology. Higher concentrations of α-synuclein were reported in cerebrospinal fluid (CSF) of AD patients with a positive correlation towards CSF tau, indicating its possible role in AD. We analyzed the CSF biomarkers to verify whether α-synuclein could be an additional supported biomarker in AD diagnosis. Methods In this cross-sectional study, CSF samples of 71 early-onset AD, 34 late-onset AD, 11 mild cognitive impairment, 17 subjective cognitive decline, 45 Parkinsons disease, and 32 healthy control (HC) were collected. CSF amyloid-β1-42 (A), total tau (N), and phosphorylated tau181 (T) were measured by commercial ELISA kits, and in-house ELISA kit was developed to quantify α-synuclein. The cognitive assessments and amyloid-PET imaging were also performed. Results CSF α-synuclein manifested a tendency to increase in AD and to decreased in Parkinsons disease compared to HC. The equilibrium states of total tau and α-synuclein concentrations were changed significantly in AD, and the ratio of total tau/α-synuclein (N/αS) was dramatically increased in AD than HC. Remarkably, N/αS revealed a strong positive correlation with tau phosphorylation rate. Also, the combination of N/αS with amyloid-β1-42/phosphorylated tau181ratio had the best diagnosis performance (AUC = 0.956, sensitivity = 96%, specificity = 87%). In concordance analysis, N/αS showed the higher diagnostic agreement with amyloid-β1-42 and amyloid-PET. Analysis of biomarker profiling with N/αS had distinctive characteristics and clustering of each group. Especially, among the group of suspected non-Alzheimers disease pathophysiology, all A−T+N+ patients with N/αS+ were reintegrated into AD. Conclusions The high correlation of α-synuclein with tau and the elevated N/αS in AD supported the involvement of α-synuclein in AD pathophysiology. Importantly, N/αS improved the diagnostic performance, confirming the needs of incorporating α-synuclein as a biomarker for neurodegenerative disorders. The incorporation of a biomarker group [N/αS] could contribute to provide better understanding and diagnosis of neurodegenerative disorders

Strategies to improve the signal and noise performance of active matrix, flatâ panel imagers for diagnostic xâ ray applications

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134928/1/mp8831.pd

Mechanical Properties of Silicon Nanowires

Nanowires have been taken much attention as a nanoscale building block, which can perform the excellent mechanical function as an electromechanical device. Here, we have performed atomic force microscope (AFM)-based nanoindentation experiments of silicon nanowires in order to investigate the mechanical properties of silicon nanowires. It is shown that stiffness of nanowires is well described by Hertz theory and that elastic modulus of silicon nanowires with various diameters from ~100 to ~600 nm is close to that of bulk silicon. This implies that the elastic modulus of silicon nanowires is independent of their diameters if the diameter is larger than 100 nm. This supports that finite size effect (due to surface effect) does not play a role on elastic behavior of silicon nanowires with diameter of >100 nm

Regulation of Adipose Tissue Stromal Cells Behaviors by Endogenic Oct4 Expression Control

BACKGROUND: To clarify the role of the POU domain transcription factor Oct4 in Adipose Tissue Stromal Cells (ATSCs), we investigated the regulation of Oct4 expression and other embryonic genes in fully differentiated cells, in addition to identifying expression at the gene and protein levels. The ATSCs and several immature cells were routinely expressing Oct4 protein before and after differentiating into specific lineages. METHODOLOGY/PRINCIPAL FINDINGS AND CONCLUSIONS: Here, we demonstrated the role of Oct4 in ATSCs on cell proliferation and differentiation. Exogenous Oct4 improves adult ATSCs cell proliferation and differentiation potencies through epigenetic reprogramming of stemness genes such as Oct4, Nanog, Sox2, and Rex1. Oct4 directly or indirectly induces ATSCs reprogramming along with the activation of JAK/STAT3 and ERK1/2. Exogenic Oct4 introduced a transdifferentiation priority into the neural lineage than mesodermal lineage. Global gene expression analysis results showed that Oct4 regulated target genes which could be characterized as differentially regulated genes such as pluripotency markers NANOG, SOX2, and KLF4 and markers of undifferentiated stem cells FOXD1, CDC2, and EPHB1. The negatively regulated genes included FAS, TNFR, COL6A1, JAM2, FOXQ1, FOXO1, NESTIN, SMAD3, SLIT3, DKK1, WNT5A, BMP1, and GLIS3 which are implicated in differentiation processes as well as a number of novel genes. Finally we have demonstrated the therapeutic utility of Oct4/ATSCs were introduced into the mouse traumatic brain, engrafted cells was more effectively induces regeneration activity with high therapeutic modality than that of control ATSCs. Engrafted Oct4/ATSCs efficiently migrated and transdifferentiated into action potential carrying, functionally neurons in the hippocampus and promoting the amelioration of lesion cavities

Genotype-phenotype analysis of von Hippel-Lindau syndrome in Korean families: HIF-α binding site missense mutations elevate age-specific risk for CNS hemangioblastoma

BACKGROUND: von Hippel-Lindau (VHL) disease is a rare hereditary tumor syndrome caused by VHL gene mutations that is characterized by heterogeneous phenotypes such as benign/malignant tumors of the central nervous system, retina, kidney, adrenal gland, and pancreas. The genotype-phenotype correlation has not been well characterized in the Korean population so far. Therefore, this study aimed to evaluate the VHL mutation spectrum and genotype-phenotype correlations in Korean VHL patients. METHODS: Thirteen unrelated subjects with VHL mutations were included. Direct sequencing and multiplex ligation-dependent probe amplification were performed. Consequently, the clinical manifestations and family histories of the subjects were evaluated. RESULTS: We identified 10 different VHL mutations. The c.160_161delAT frameshift mutation was novel. Missense mutations clustered in 2 domains (α domain in exon 1; β domain in exon 3). The most frequently observed mutation was c.208G > A (p.Glu70Lys). Milder phenotypes were observed in subjects with de novo mutations. Age-specific risk for CNS hemangioblastoma was significantly higher in subjects carrying missense mutations within the HIF-α binding site (P < 0.05). CONCLUSIONS: This study provides insight into the genotype-phenotype correlation in that amino acid substitutions in the HIF-α binding site may predispose patients to age-related risks of CNS hemangioblastoma

Ell3 Enhances Differentiation of Mouse Embryonic Stem Cells by Regulating Epithelial-Mesenchymal Transition and Apoptosis

Ell3 is a testis-specific RNA polymerase II elongation factor whose cellular function is not clear. The present study shows that Ell3 is activated during the differentiation of mouse embryonic stem cells (mESCs). Furthermore, Ell3 plays a critical role in stimulating lineage differentiation of mESCs by promoting epithelial-mesenchymal transition (EMT) and suppressing apoptosis. Mouse ESCs engineered to stably express Ell3 were rapidly differentiated compared with control cells either under spontaneous differentiation or neural lineage-specific differentiation conditions. Gene expression profile and quantitative RT-PCR analysis showed that the expression of EMT markers, such as Zeb1 and Zeb2, two major genes that regulate EMT, was upregulated in Ell3-overexpressing mESCs. Remarkably, knockdown of Zeb1 attenuated the enhanced differentiation capacity of Ell3-overexpressing mESCs, which indicates that Ell3 plays a role in the induction of mESC differentiation by inducing EMT. In contrast to Ell3-overexpressing mESCs, Ell3-knock down mESCs could not differentiate under differentiation conditions and, instead, underwent caspase-dependent apoptosis. In addition, apoptosis of differentiating Ell3-knock out mESCs was associated with enhanced expression of p53. The present results suggest that Ell3 promotes the differentiation of mESCs by activating the expression of EMT-related genes and by suppressing p53 expression