Full-length genomic analysis of korean porcine sapelovirus strains.

Porcine sapelovirus (PSV), a species of the genus Sapelovirus within the family Picornaviridae, is associated with diarrhea, pneumonia, severe neurological disorders, and reproductive failure in pigs. However, the structural features of the complete PSV genome remain largely unknown. To analyze the structural features of PSV genomes, the full-length nucleotide sequences of three Korean PSV strains were determined and analyzed using bioinformatic techniques in comparison with other known PSV strains. The Korean PSV genomes ranged from 7,542 to 7,566 nucleotides excluding the 3' poly(A) tail, and showed the typical picornavirus genome organization; 5'untranslated region (UTR)-L-VP4-VP2-VP3-VP1-2A-2B-2C-3A-3B-3C-3D-3'UTR. Three distinct cis-active RNA elements, the internal ribosome entry site (IRES) in the 5'UTR, a cis-replication element (CRE) in the 2C coding region and 3'UTR were identified and their structures were predicted. Interestingly, the structural features of the CRE and 3'UTR were different between PSV strains. The availability of these first complete genome sequences for PSV strains will facilitate future investigations of the molecular pathogenesis and evolutionary characteristics of PSV

Incidence of Bovine Enterovirus, Coronavirus, and Group A Rotavirus, and Concentration of Fecal Coliforms in Midwestern Pasture Streams

The occurrence of bovine enteric pathogens and fecal coliform contamination in streams of 13 Midwestern cow/calf pastures was studied during the 2007-2008 grazing seasons. Water samples (n=812) were collected biweekly at up- and downstream locations on each stream. Incidence of Bovine Enterovirus (BEV), Coronavirus (BCV), and group A Rotavirus (BRV), and concentration of fecal coliforms (FC) were evaluated. The mean incidence of BEV, BCV, and BRV in all samples were 5.42, 1.60, and 0.25%, respectively, over the two grazing seasons. There were farm differences for BEV (P=0.02) and BCV (P=0.01) incidences, but there were no differences (P\u3e0.05) for the incidences of the viruses between samples collected from up- or downstream locations. Cattle presence in the pasture on the day and three days prior to sampling were related (P=0.02, P=0.04), respectively, to BEV, but were not related (P\u3e0.05) to BCV or BRV. However, incidences of BEV, BCV or BRV were not related (P\u3e0.05) to cattle presence seven days prior to sampling. Mean FC were 930 and 938 colony-forming units (CFU)/100ml, respectively, for up- and downstream samples. Differences (P=0.01) were observed between farms for concentration of FC. Preliminary results indicate that the timing and management of grazing may be beneficial in decreasing the incidence of enteric viral pathogens and concentrations of FC in Midwestern pasture streams

Three-dimensional oscillations of twenty one halo coronal mass ejections by multi-spacecraft

We investigate the 3D structure of kinematic oscillations of full halo coronal mass ejections (FHCMEs) using multi-spacecraft coronagraph data from two non-parallel lines of sight. For this, we consider 21 FHCMEs which are simultaneously observed by the Solar and Heliospheric Observatory and the Solar TErrestrial RElations Observatory A or B, from 2010 June to 2012 August when the spacecraft were roughly in quadrature. Using sequences of running difference images, we estimate the instantaneous projected speeds of the FHCMEs at 24 different azimuthal angles in the planes of the sky of those coronagraphs. We find that all these FHCMEs have experienced kinematic oscillations characterized by quasi-periodic variations of the instantaneous projected radial velocity with periods ranging from 24 to 48 min. The oscillations detected in the analyzed events are found to show distinct azimuthal wave modes. Thirteen events (about 62%) are found to oscillate with the azimuthal wave number m = 1. The oscillating directions of the nodes of the m = 1 mode for these FHCMEs are consistent with those of their position angles (or the direction of eruption), with a mean difference of about 23°. The oscillation amplitude is found to correlate well with the projected radial speed of the CME. An estimation of Lorentz accelerations shows that they are dominant over other forces, implying that the magnetic force is responsible for the kinematic oscillations of CMEs. However, we cannot rule out other possibilities: a global layer of enhanced current around the CMEs or the nonlinear nature of its driver, for example the effect of vortex shedding

Epidemiological Characteristics of Novel Influenza A (H1N1) in Antiviral Drug Users in Korea

Soon after the first novel influenza A (H1N1) death was documented in Korea on August 15, 2009, prompt treatment with antiviral drugs was recommended when an infection was suspected. Free antiviral drugs were distributed to patients who met the case definition in the treatment guidelines, and patients prescribed the antiviral drugs were included in the Antiviral Drug Surveillance System (ADSS). A total of 2,825,821 patients were reported to the ADSS from September 1 to December 31, 2009. Odds ratios were calculated to compare the risks of severe diseases, as indicated by general hospital admissions or intensive care unit (ICU) admissions according to demographic characteristics, underlying medical conditions, and behavioral factors. Approximately 6% of the total population received antiviral drugs during the study period. Of these, 2,709,611 (95.9%) were outpatients, 114,840 (4.06%) were hospitalized, and 1,370 (0.05%) were admitted to the ICU. Children aged 0-9 yr accounted for 33.94% of all reported cases, whereas only 3.89% of the patients were ≥ 60 yr. The estimated incidence of novel influenza A (H1N1) during the pandemic was 5.68/100 of all reported cases. Mortality due to influenza A (H1N1) during the pandemic was 0.33/100,000, with the highest mortality of 1.31/100,000 for patients aged ≥ 60 years. Severe pandemic H1N1 influenza was associated with the presence of one or more underlying medical conditions in elderly aged ≥ 60 years and with lower economic status. Moreover, influenza A (H1N1) appeared to be age-specific in terms of mortality. Although the incidence and admission rates of influenza A (H1N1) were higher in younger age groups, fatal cases were much more likely to occur in the elderly (≥60 years). In contrast to earlier influenza A (H1N1) reports, the risks of a severe outcome were elevated among those who were underweight (body mass index < 18.5 kg/m 2)

β-catenin activation down-regulates cell-cell junction-related genes and induces epithelial-to-mesenchymal transition in colorectal cancers

WNT signaling activation in colorectal cancers (CRCs) occurs through APC inactivation or β-catenin mutations. Both processes promote β-catenin nuclear accumulation, which up-regulates epithelial-to-mesenchymal transition (EMT). We investigated β-catenin localization, transcriptome, and phenotypic differences of HCT116 cells containing a wild-type (HCT116-WT) or mutant β-catenin allele (HCT116-MT), or parental cells with both WT and mutant alleles (HCT116-P). We then analyzed β-catenin expression and associated phenotypes in CRC tissues. Wild-type β-catenin showed membranous localization, whereas mutant showed nuclear localization; both nuclear and non-nuclear localization were observed in HCT116-P. Microarray analysis revealed down-regulation of Claudin-7 and E-cadherin in HCT116-MT vs. HCT116-WT. Claudin-7 was also down-regulated in HCT116-P vs. HCT116-WT without E-cadherin dysregulation. We found that ZEB1 is a critical EMT factor for mutant β-catenin-mediated loss of E-cadherin and Claudin-7 in HCT116-P and HCT116-MT cells. We also demonstrated that E-cadherin binds to both WT and mutant β-catenin, and loss of E-cadherin releases β-catenin from the cell membrane and leads to its degradation. Alteration of Claudin-7, as well as both Claudin-7 and E-cadherin respectively caused tight junction (TJ) impairment in HCT116-P, and dual loss of TJs and adherens junctions (AJs) in HCT116-MT. TJ loss increased cell motility, and subsequent AJ loss further up-regulated that. Immunohistochemistry analysis of 101 CRCs revealed high (14.9%), low (52.5%), and undetectable (32.6%) β-catenin nuclear expression, and high β-catenin nuclear expression was significantly correlated with overall survival of CRC patients (P = 0.009). Our findings suggest that β-catenin activation induces EMT progression by modifying cell-cell junctions, and thereby contributes to CRC aggressiveness

Round Cell Variant of Myxoid Liposarcoma in a Japanese Macaque (Macaca fuscata)

A 5-year-old, female, Japanese Macaque (Macaca fuscata) was diagnosed with round cell variant of myxoid liposarcoma. At necropsy, multifocal to coalescing, reddish tan to white nodules, ranging from 0.5 to 1 cm in diameter, were noted throughout the omentum and retroperitoneum. Similar neoplastic nodules were also present in diaphragm, abdominal wall, and on hepatic capsule. Microscopically, neoplastic masses consisted of round to polyhedral cells, which had round, often eccentric nuclei and abundant eosinophilic granular and microvacuolated cytoplasm; Oil red O staining demonstrated large numbers of lipid droplets in the cytoplasm. Ultrastructurally, the cytoplasm of the tumor cells was packed with occasional lipid vacuoles and numerous enlarged mitochondria. Immunohistochemistry revealed tumor cells were positive for vimentin, while negative to cytokeratin, actin, and Factor VIII–related antigen. To the authors' knowledge, this is the first report of round-cell variant of myxoid liposarcoma in nonhuman primate.This study was supported through Brain Korea 21 Program for Veterinary Science

Hα Reverberation Mapping of the Intermediate-mass Active Galactic Nucleus in NGC 4395

We present the results of a high-cadence spectroscopic and imaging monitoring campaign of the active galactic nucleus (AGN) of NGC 4395. High signal-to-noise-ratio spectra were obtained at the Gemini-N 8 m telescope using the GMOS integral field spectrograph (IFS) on 2019 March 7 and at the Keck I 10 m telescope using the Low-Resolution Imaging Spectrometer with slit masks on 2019 March 3 and April 2. Photometric data were obtained with a number of 1 m-class telescopes during the same nights. The narrow-line region (NLR) is spatially resolved; therefore, its variable contributions to the slit spectra make the standard procedure of relative flux calibration impractical. We demonstrate that spatially resolved data from the IFS can be effectively used to correct the slit-mask spectral light curves. While we obtained no reliable lag owing to the lack of a strong variability pattern in the light curves, we constrain the broad-line time lag to be less than 3 hr, consistent with the photometric lag of ∼80 minutes reported by Woo et al. By exploiting the high-quality spectra, we measure the second moment of the broad component of the Hα emission line to be 586 ± 19 km s−1, superseding the lower value reported by Woo et al. Combining the revised line dispersion and the photometric time lag, we update the black hole mass to (1.7 ± 0.3) × 104 M⊙

Hemorheology and Microvascular Disorders

The present review presents basic concepts of blood rheology related to vascular diseases. Blood flow in large arteries is dominated by inertial forces exhibited at high flow velocities, while viscous forces (i.e., blood rheology) play an almost negligible role. When high flow velocity is compromised by sudden deceleration as at a bifurcation, endothelial cell dysfunction can occur along the outer wall of the bifurcation, initiating inflammatory gene expression and, through mechanotransduction, the cascade of events associated with atherosclerosis. In sharp contrast, the flow of blood in microvessels is dominated by viscous shear forces since the inertial forces are negligible due to low flow velocities. Shear stress is a critical parameter in microvascular flow, and a force-balance approach is proposed for determining microvascular shear stress, accounting for the low Reynolds numbers and the dominance of viscous forces over inertial forces. Accordingly, when the attractive forces between erythrocytes (represented by the yield stress of blood) are greater than the shear force produced by microvascular flow, tissue perfusion itself cannot be sustained, leading to capillary loss. The yield stress parameter is presented as a diagnostic candidate for future clinical research, specifically, as a fluid dynamic biomarker for microvascular disorders. The relation between the yield stress and diastolic blood viscosity (DBV) is described using the Casson model for viscosity, from which one may be able determine thresholds of DBV where the risk of microvascular disorders is high

Structure and mechanism of activity-based inhibition of the EGF-Receptor by Mig6

Mig6 is a feedback inhibitor that directly binds, inhibits and drives internalization of ErbB-family receptors. Mig6 selectivity targets activated receptors. Here we find that the EGF receptor phosphorylates Mig6 on Tyr394, and that this phosphorylation is primed by prior phosphorylation of an adjacent residue, Tyr395, by Src. Crystal structures of human EGFR–Mig6 complexes reveal the structural basis for enhanced phosphorylation of primed Mig6 and show how Mig6 rearranges after phosphorylation by EGFR to effectively irreversibly inhibit the same receptor that catalyzed its phosphorylation. This dual phosphorylation site allows Mig6 to inactivate EGFR in a manner that requires activation of the target receptor and can be modulated by Src. Loss of Mig6 is a driving event in human cancer; analysis of 1057 gliomas reveals frequent focal deletions of ERRFI, the gene that encodes Mig6, in EGFR-amplified glioblastomas