Miracle-dz/UniFAR-FTUs huggingface dataset:
VP‐1 quasispecies in human infection with polyomavirus BK

Polyomavirus BK is a recognized cause of nephropathy and hemorrhagic cystitis in kidney or allogeneic hematopoietic stem cell transplant recipients. This study explored a role of genetic variations in capsid protein VP‐1 gene as a factor in viral pathogenesis. VP‐1 was amplified from 7 healthy subjects with viruria, 7 transplant patients with viruria, and 11 patients with viremia or nephropathy. PCR products were cloned and a total of 558 clonal sequences were subjected to phylogenetic analysis using standard methods. VP‐1 quasispecies were found in 25/25 and coinfection with different genotypes in 12/25 subjects. Genotype II was found as an unexpected minority species in 5/25 individuals. Recombinant strains of uncertain biologic significance, which frequently contained genotype II and IV sequences were identified in 9/25 subjects. Viremia/nephropathy group was characterized by (a) greater sequence complexity in whole VP‐1 versus BC loop and BC loop compared to the HI loop, (b) greater intra‐strain genetic diversity in the BC loop compared to whole VP‐1 protein and HI loop, (c) more non‐synonymous substitutions (dN) in the BC loop compared to whole VP‐1 and HI loop, (e) fewer synonymous substitutions (dS) compared to healthy‐viruria group, and (f) selection pressure (dN/dS >1.0) exerted on VP‐1. In conclusion, this study documents frequent occurrence of quasispecies in a host DNA polymerase dependent virus, which is theoretically expected to show high replication fidelity. Quasispecies occur even in healthy subjects with viruria, but evolutionary selection pressure directed at the viral capsid protein (VP‐1) is seen only in patients with viremia or nephropathy. J. Med. Virol. 84:152–161, 2011. © 2011 Wiley Periodicals, Inc.
cDNA Microarray Gene Expression Profiling of Hedgehog Signaling Pathway Inhibition in Human Colon Cancer Cells

Background Hedgehog (HH) signaling plays a critical role in normal cellular processes, in normal mammalian gastrointestinal development and differentiation, and in oncogenesis and maintenance of the malignant phenotype in a variety of human cancers. Increasing evidence further implicates the involvement of HH signaling in oncogenesis and metastatic behavior of colon cancers. However, genomic approaches to elucidate the role of HH signaling in cancers in general are lacking, and data derived on HH signaling in colon cancer is extremely limited. Methodology/Principal Findings To identify unique downstream targets of the GLI genes, the transcriptional regulators of HH signaling, in the context of colon carcinoma, we employed a small molecule inhibitor of both GLI1 and GLI2, GANT61, in two human colon cancer cell lines, HT29 and GC3/c1. Cell cycle analysis demonstrated accumulation of GANT61-treated cells at the G1/S boundary. cDNA microarray gene expression profiling of 18,401 genes identified Differentially Expressed Genes (DEGs) both common and unique to HT29 and GC3/c1. Analyses using GenomeStudio (statistics), Matlab (heat map), Ingenuity (canonical pathway analysis), or by qRT-PCR, identified p21Cip1 (CDKN1A) and p15Ink4b (CDKN2B), which play a role in the G1/S checkpoint, as up-regulated genes at the G1/S boundary. Genes that determine further cell cycle progression at G1/S including E2F2, CYCLIN E2 (CCNE2), CDC25A and CDK2, and genes that regulate passage of cells through G2/M (CYCLIN A2 [CCNA2], CDC25C, CYCLIN B2 [CCNB2], CDC20 and CDC2 [CDK1], were down-regulated. In addition, novel genes involved in stress response, DNA damage response, DNA replication and DNA repair were identified following inhibition of HH signaling. Conclusions/Significance This study identifies genes that are involved in HH-dependent cellular proliferation in colon cancer cells, and following its inhibition, genes that regulate cell cycle progression and events downstream of the G1/S boundary.
Molecular genetic maps in wild emmer wheat, Triticum dicoccoides: genome-wide coverage, massive negative interference, and putative quasi-linkage.

The main objectives of the study reported here were to construct a molecular map of wild emmer wheat, Triticum dicoccoides, to characterize the marker-related anatomy of the genome, and to evaluate segregation and recombination patterns upon crossing T. dicoccoides with its domesticated descendant Triticum durum (cultivar Langdon). The total map length exceeded 3000 cM and possibly covered the entire tetraploid genome (AABB). Clusters of molecular markers were observed on most of the 14 chromosomes. AFLP (amplified fragment length polymorphism) markers manifested a random distribution among homologous groups, but not among genomes and chromosomes. Genetic differentiation between T. dicoccoides and T. durum was attributed mainly to the B genome as revealed by AFLP markers. The segregation-distorted markers were mainly clustered on 4A, 5A, and 5B chromosomes. Homeoalleles, differentially conferring the vigor of gametes, might be responsible for the distortion on 5A and 5B chromosomes. Quasilinkage, deviation from free recombination between markers of nonhomologous chromosomes, was discovered. Massive negative interference was observed in most of the chromosomes (an excess of double crossovers in adjacent intervals relative to the expected rates on the assumption of no interference). The general pattern of distribution of islands of negative interference included near-centromeric location, spanning the centromere, and median/subterminal location. [An appendix describing the molecular marker loci is available as an online supplement at http://www.genome. org. ]
Nanostructured composites as electrochemical catalysts for Li-air batteries

Advanced energy conversion and storage systems are drawing tremendous research attention as the energy demand for portable electronics and electric vehicle (EV) applications continues to increase. Although lithium (Li) ion batteries are currently used for various applications, including EVs, these batteries are still unable to fulfill the ultimate driving range requirements. Li-air batteries are an attractive alternative due to their extremely high theoretical energy density; however some technical hurdles remain, including insufficient cycle stability, low energy efficiency and poor rate capability. These challenges are directly related to the sluggish oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), which are the two main reactions that govern the discharge and charge processes, respectively. Therefore, the development of a highly efficient bi-functional catalyst active towards both ORR and OER is a significantly important research area to commercialize Li-air batteries. In the first part of this study, a facile method which utilizes one-step rapid heating is introduced to synthesize reduced graphene oxide with heterogeneously doped nitrogen atoms (NRGO), with the morphology and nitrogen doping investigated by electron microscopy and x-ray photoelectron spectroscopy, respectively. Electrochemical half-cell experiments show that NRGO has comparable ORR activity to that of state-of-the-art commercial Pt/C catalysts. Next, by combining NRGO synthesized via the facile method with La0.5Sr0. 5Co0.8Fe0. 2O3 perovskite oxide with a porous rod morphology prepared by electrospinning (LSCF-PR), a novel composite catalyst (LSCF-PR/NRGO) is created. Electrochemical testing of the LSCF-PR/NRGO composite in alkaline medium shows that it has excellent ORR and OER activities, verifying the effectiveness of the composite for bi-functional activity. These results highlight the importance of morphology on the catalytic activity for metal-air battery applications. Next in the study, one-dimensional carbon nanotube-based composite catalysts have been investigated such as ethylene diamine (EDA)-based nitrogen-doped carbon nanotubes (NCNT) synthesized on RGO, prepared by chemical vapor deposition (CVD). The NCNT/RGO composites exhibit ORR performance similar to that of commercial Pt/C catalysts, with much superior OER activity. Last in the study, a one-pot facile synthetic is developed to prepare advanced bi-functional composite catalysts (op-LN), which combine NCNT and perovskite oxide La0.5Sr0. 5Co0.8Fe0. 2O3 nanoparticles (LSCF-NP). Electron microscopy confirms that NCNTs are densely grown on the metal oxide. Half-cell experiments show that the synergy of combining LSCF-NP with NCNT yields good bi-functionality towards both ORR and OER, attributed to the synergistic effects arising from the two component species. op-LN has been evaluated in a practical rechargeable Li-air battery and demonstrated superior charge and discharge performance and cycle stability compared to those of LSCF-NP, NCNT and Pt/C. Based on the…
On the Amalgamation Property for Various Algebraic Logics

We show that a natural class of representable algebras (of logic) has the super amalgamation property. Applications of this results are given. In particular, questions originally posed by Tarski, Henkin, Monk and Pigozzi are answered. Several techniques for failure of various forms of the amalgamation property are appropriately modified, proving new results. Answers to open questions in the recent paper [18] are summarized in tabular form at the end of the paper. Mathematics Subject Classification: Primary 03G15. Secondary 03C05, 03C40
Rotavirus genome replication: Some assembly required

1 Virginia Tech Carilion School of Medicine and Research Institute, Roanoke, Virginia, United States of America, 2 Translational Biology, Medicine, and Health Graduate Program, Virginia-Maryland College of Veterinary Medicine, Blacksburg, Virginia, United States of America, 3 Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, Virginia, United States of America
Functional analysis of Normalized Difference Vegetation Index curves reveals overwinter mule deer survival is driven by both spring and autumn phenology

Large herbivore populations respond strongly to remotely sensed measures of primary productivity. Whereas most studies in seasonal environments have focused on the effects of spring plant phenology on juvenile survival, recent studies demonstrated that autumn nutrition also plays a crucial role. We tested for both direct and indirect (through body mass) effects of spring and autumn phenology on winter survival of 2315 mule deer fawns across a wide range of environmental conditions in Idaho, USA. We first performed a functional analysis that identified spring and autumn as the key periods for structuring the among-population and among-year variation of primary production (approximated from 1 km Advanced Very High Resolution Radiometer Normalized Difference Vegetation Index (NDVI)) along the growing season. A path analysis showed that early winter precipitation and direct and indirect effects of spring and autumn NDVI functional components accounted for 45% of observed variation in overwinter survival. The effect size of autumn phenology on body mass was about twice that of spring phenology, while direct effects of phenology on survival were similar between spring and autumn. We demonstrate that the effects of plant phenology vary across ecosystems, and that in semi-arid systems, autumn may be more important than spring for overwinter survival.
NY-ESO-1 Expression and Immunogenicity in Malignant and Benign Breast Tumors

NY-ESO-1 is a cancer/testis antigen expressed in normal adult tissues solely in the testicular germ cells of normal adults and in various cancers. It induces specific humoral and cellular immunity in patients with NY-ESO-1-expressing cancer. The aim of this study was to determine the frequency of NY-ESO-1 mRNA and protein expression in malignant and benign breast tumors. NY-ESO-1 mRNA expression was detected by conventional reverse transcription-PCR and real-time PCR, and that of the protein expression by immunohistochemistry and Western blot analysis. Expression of NY-ESO-1 mRNA was detected in 37 of 88 (42%) cancer specimens, whereas that of the NY-ESO-1 protein was detected only in 1 mRNA-positive specimen. In the latter case, expression level of NY-ESO-1 mRNA relative to that in the testis was relatively high (75% of testicular expression) and to the other among breast cancer specimens. In benign breast lesions, 21 of 31 (68%) specimens expressed low levels of NY-ESO-1 mRNA. In 1 case of fibroadenoma, NY-ESO-1 mRNA was 8% of the testicular level, and protein was detected by Western blot analysis. Only 1 breast cancer patient had detectable antibody at time of surgery, which disappeared within 2 years. Tumor specimen from this patient was both NY-ESO-1 mRNA and protein positive, and NY-ESO-1-specific CD8 T cells were detected in this patient by IFN-γ enzyme-linked immunospot assay using NY-ESO-1 recombinant adeno and vaccinia virus. A higher rate of NY-ESO-1 expression was noted in breast cancer with high histological grade and negative hormone receptor status, suggesting NY-ESO-1 as a potential tumor antigen for immunotherapy in patients with breast cancer and poor prognosis.
Histologic Activity of Childhood Chronic Hepatitis B Related to Viremia Levels, Genotypes, Mutations, and Epidemiologic Factors

Background Despite high viral load, children with chronic hepatitis B virus (HBV) infection may lack significant biochemical signs of liver dysfunction. Failure to develop abnormal liver chemistriesis is probably due to immunologic hyporeactivity. Despite the absence of biochemical abnormalities in these patients, there is still a risk for long-term complications. The pathogenic importance of viral load and genetic variability is less well studied in children than in adults. Methods We evaluated viremia levels, genotypes, and mutations related to histologic evidence of liver damage in 71 HBV carriers, aged 2 to 18 years, all of non-Swedish origin. Results None of the of 22 children who were hepatitis B e antigen (HBeAg) negative had severe liver disease or had HBV DNA levels greater than 104.6 copies/mL (mean 103.2); 3 (14%) of them had increased alanine aminotransferase (ALT). The 49 HBeAg-positive children had a mean HBV DNA level of 108.0 copies/mL, and increased ALT was seen in 28 (55%). Core promoter mutations (at nt 1764) or precore mutations (at codon 1, 2, or 28) were rare; they were seen in four and one HBeAg-positive children, and in four and nine HBeAg-negative children, respectively, without association to liver damage. C-1858 was associated with more liver inflammation. Genotype did not significantly influence liver damage. Children with horizontal transmission had a faster rate of seroconversion and more inflammation of the liver. Conclusions Severe HBeAg-negative hepatitis with high HBV DNA levels and mutations in the core promoter or precore regions seems to be less common in children than in adults. C-1858 strains may be more pathogenic, but this requires further study. Epidemiologic factors influence the course of infection.
Photoemission study of the electronic structure of CrCl3 and RuCl3 compounds.

X-ray and ultraviolet photoelectron spectra of the valence band and core levels of ${\mathrm{CrCl}}_{3}$ and \ensuremath{\alpha}-${\mathrm{RuCl}}_{3}$ crystals have been performed in order to study their electronic structure. It is found that the 3d and 4d states of the transition metal and the 3p states of the chlorine contribute to the valence-band structure. The valence band consists of overlapping Cr 3d and Cl 3p states in ${\mathrm{CrCl}}_{3}$, while a narrow Ru 4d band is separated by 2--2.5 eV from the top of the Cl 3p valence states in ${\mathrm{RuCl}}_{3}$. Photoemission, photoconductivity, and optical spectra indicate that in ${\mathrm{CrCl}}_{3}$ and ${\mathrm{RuCl}}_{3}$ the energy gap involves d-d Coulomb and exchange interactions on the transition-metal atom. On this basis, the main 3d- and 4d-emission structures are assigned to unscreened 3${\mathit{d}}^{2}$ and 4${\mathit{d}}^{4}$ hole states within the framework of the Mott-Hubbard model.
Methodological variation in antibiotic synergy tests against enterococci

Thirty-two human isolates of enterococci were tested for antibiotic synergy by using penicillin and one of six aminoglycosides. Three methods were used: synergy screen, microdilution checkerboard, and time-kill curves. The synergy screen accurately predicted synergy for gentamicin-penicillin combinations, and this synergy was later confirmed by time-kill curves. The microdilution checkerboard method suffered from inherent variation, and agreement with time-kill curves ranged from 92% (twofold reduction in minimum inhibitory concentration) to 4.2% (fourfold reduction in minimum inhibitory concentration). We suggest that enterococci be screened for synergy (i.e., presence or absence of high-level resistance) by using the criterion of growth or no growth in the presence of 2,000 microgram of an aminoglycoside per ml. The microdilution checkerboard test for synergy is not recommended.
Pre-conditioning induces the precocious differentiation of neonatal astrocytes to enhance their neuroprotective properties

Hypoxic preconditioning reprogrammes the brain's response to subsequent H/I (hypoxia–ischaemia) injury by enhancing neuroprotective mechanisms. Given that astrocytes normally support neuronal survival and function, the purpose of the present study was to test the hypothesis that a hypoxic preconditioning stimulus would activate an adaptive astrocytic response. We analysed several functional parameters 24 h after exposing rat pups to 3 h of systemic hypoxia (8% O2). Hypoxia increased neocortical astrocyte maturation as evidenced by the loss of GFAP (glial fibrillary acidic protein)-positive cells with radial morphologies and the acquisition of multipolar GFAP-positive cells. Interestingly, many of these astrocytes had nuclear S100B. Accompanying their differentiation, there was increased expression of GFAP, GS (glutamine synthetase), EAAT-1 (excitatory amino acid transporter-1; also known as GLAST), MCT-1 (monocarboxylate transporter-1) and ceruloplasmin. A subsequent H/I insult did not result in any further astrocyte activation. Some responses were cell autonomous, as levels of GS and MCT-1 increased subsequent to hypoxia in cultured forebrain astrocytes. In contrast, the expression of GFAP, GLAST and ceruloplasmin remained unaltered. Additional experiments utilized astrocytes exposed to exogenous dbcAMP (dibutyryl-cAMP), which mimicked several aspects of the preconditioning response, to determine whether activated astrocytes could protect neurons from subsequent excitotoxic injury. dbcAMP treatment increased GS and glutamate transporter expression and function, and as hypothesized, protected neurons from glutamate excitotoxicity. Taken altogether, these results indicate that a preconditioning stimulus causes the precocious differentiation of astrocytes and increases the acquisition of multiple astrocytic functions that will contribute to the neuroprotection conferred by a sublethal preconditioning stress.
The Impact of Competition on Management Quality: Evidence from Public Hospitals

In this paper we examine the causal impact of competition on management quality. We analyze the hospital sector where geographic proximity is a key determinant of competition, and English public hospitals where political competition can be used to construct instrumental variables for market structure. Since almost all major English hospitals are government run, closing hospitals in areas where the governing party has a small majority is rare due to fear of electoral punishment. We find that management quality - measured using a new survey tool - is strongly correlated with financial and clinical outcomes such as survival rates from emergency heart attack admissions (AMI). More importantly, we find that higher competition (as indicated by a greater number of neighboring hospitals) is positively correlated with increased management quality, and this relationship strengthens when we instrument the number of local hospitals with local political competition. Adding another rival hospital increases the index of management quality by one third of a standard deviation and leads to a 10.7% reduction in heart-attack mortality rates.
Stock Market Linkages in Emerging Markets: Implications for International Portfolio Diversification

This paper examines stock market linkages of a group of Pacific-Basin countries with U.S. and Japan by estimating the multivariate cointegration model in both the autoregressive and moving average forms over the period 1980-1998. Recursive estimation helps identify the evolution of the linkages. The results for the 1980s indicate that the relaxation of foreign ownership restrictions was not sufficient to attract foreign investors' attention and that other factors must have affected the portfolio diversification decision. The results of the 1990s suggest that the relaxation of the restrictions might have strengthened international market interrelations. Country Funds have provided access to highly regulated capital markets.
A novel Crumbs3 isoform regulates cell division and ciliogenesis via importin β interactions

The Crumbs family of apical transmembrane proteins regulates apicobasal polarity via protein interactions with a conserved C-terminal sequence, ERLI. However, one of the mammalian Crumbs proteins, Crumbs3 (CRB3) has an alternate splice form with a novel C-terminal sequence ending in CLPI (CRB3-CLPI). We report that CRB3-CLPI localizes to the cilia membrane and a membrane compartment at the mitotic spindle poles. Knockdown of CRB3-CLPI leads to both a loss of cilia and a multinuclear phenotype associated with centrosomal and spindle abnormalities. Using protein purification, we find that CRB3-CLPI interacts with importin β-1 in a Ran-regulated fashion. Importin β-1 colocalizes with CRB3-CLPI during mitosis, and a dominant-negative form of importin β-1 closely phenocopies CRB3-CLPI knockdown. Knockdown of importin β-1 blocks targeting of CRB3-CLPI to the spindle poles. Our data suggest an expanded role for Crumbs proteins in polarized membrane targeting and cell division via unique interactions with importin proteins.
Biological Activity of N-Hydroxyethyl-4-aza-2,3-didehydropodophyllotoxin Derivatives upon Colorectal Adenocarcinoma Cells

Etoposide is a chemotherapy drug derived from the natural lignin podophyllotoxin. Our novel generated Aza-podophyllotoxin compounds (AZP 8a & AZP 9a) are analogues of podophyllotoxin and were previously screened for anti-cancer activity through the NCI 60 cell line screening panel showing activity on various cell types including colon cancer. This study expands the toxicological screening by studying apoptosis and various hallmark events as part of the mechanism of action of these compounds on colon cancer cells. The COLO 205 cell line was selected and exposed to AZP to determine the IC50 doses at 24 hours treatment. Apoptosis hallmark events such as migration of phosphatidylserine (PS) to the cell membrane, DNA fragmentation, cell cycle effects, mitochondrial membrane permeabilization and caspase activation were included. Experiments were performed in triplicates for all tested compounds including AZP 8a, AZP 9a, camptothecin as positive control and vehicle as negative control. Our results present contrasting apoptotic activity between the experimental compounds. Compound 8a presented migration of PS (annexin V assay), DNA fragmentation and cell cycle arrest at S phase. Compound 9a presented PS migration with fragmented DNA, cell cycle arrest at S phase, mitochondrial membrane permeabilization and activation of caspase 3, 8 and 9. Compound 8a without the oxygen atoms in ring A appears to cause effects similarly to autophagy as induced by etoposide, a cancer drug analogue of our heterocyclic compounds. Compound 9a with the oxygen atoms in expanded ring A presented induction of cell death following activation of a classical apoptosis pathway. Our results suggest that minor structural differences among these AZP can account for the difference in biological response and cancer cell toxicity.