Increased susceptibility of Cantagalo virus to the antiviral effect of ST-246®

AbstractCantagalo virus (CTGV) is the etiologic agent of a pustular disease in dairy cows and dairy workers in Brazil with important economical and occupational impacts. Nevertheless, no antiviral therapy is currently available. ST-246 is a potent inhibitor of orthopoxvirus egress from cells and has proved its efficacy in cell culture and in animal models. In this work, we evaluated the effect of ST-246 on CTGV replication. Plaque reduction assays indicated that CTGV is 6–38 times more susceptible to the drug than VACV-WR and cowpox virus, respectively, with an EC50 of 0.0086μM and a selective index of >11,600. The analysis of β-gal activity expressed by recombinant viruses in the presence of ST-246 confirmed these results. In addition, ST-246 had a greater effect on the reduction of CTGV spread in comet tail assays and on the production of extracellular virus relative to VACV-WR. Infection of mice with CTGV by tail scarification generated primary lesions at the site of scarification that appeared less severe than those induced by VACV-WR. Animals infected with CTGV and treated with ST-246 at 100mg/kg for 5days did not develop primary lesions and virus yields were inhibited by nearly 98%. In contrast, primary lesions induced by VACV-WR were not affected by ST-246. The analysis of F13 (p37) protein from CTGV revealed a unique substitution in residue 217 (D217N) not found in other orthopoxviruses. Construction of recombinant VACV-WR containing the D217N polymorphism did not lead to an increase in the susceptibility to ST-246. Therefore, it is still unknown why CTGV is more susceptible to the antiviral effects of ST-246 compared to VACV-WR. Nonetheless, our data demonstrates that ST-246 is a potent inhibitor of CTGV replication that should be further evaluated as a promising anti-CTGV therapy

Low expression of galectin-3 is associated with poor survival in node-positive breast cancers and mesenchymal phenotype in breast cancer stem cells

Background Galectin-3 (Gal3) plays diverse roles in cancer initiation, progression, and drug resistance depending on tumor type characteristics that are also associated with cancer stem cells (CSCs). Recurrence of breast carcinomas may be attributed to the presence of breast CSCs (BCSCs). BCSCs exist in mesenchymal-like or epithelial-like states and the transition between these states endows BCSCs with the capacity for tumor progression. The discovery of a feedback loop with galectins during epithelial-to-mesenchymal transition (EMT) prompted us to investigate its role in breast cancer stemness. Method To elucidate the role of Gal3 in BCSCs, we performed various in vitro and in vivo studies such as sphere-formation assays, Western blotting, flow cytometric apoptosis assays, and limited dilution xenotransplant models. Histological staining for Gal3 in tissue microarrays of breast cancer patients was performed to analyze the relationship of clinical outcome and Gal3 expression. Results Here, we show in a cohort of 87 node-positive breast cancer patients treated with doxorubicin-based chemotherapy that low Gal3 was associated with increased lymphovascular invasion and reduced overall survival. Analysis of in vitro BCSC models demonstrated that Gal3 knockdown by small hairpin RNA (shRNA) interference in epithelial-like mammary spheres leads to EMT, increased sphere-formation ability, drug-resistance, and heightened aldefluor activity. Furthermore, Gal3negative BCSCs were associated with enhanced tumorigenicity in orthotopic mouse models. Conclusions Thus, in at least some breast cancers, loss of Gal3 might be associated with EMT and cancer stemness-associated traits, predicts poor response to chemotherapy, and poor prognosis

Patient-Reported Outcome questionnaires for hip arthroscopy: a systematic review of the psychometric evidence

Abstract Background Hip arthroscopies are often used in the treatment of intra-articular hip injuries. Patient-reported outcomes (PRO) are an important parameter in evaluating treatment. It is unclear which PRO questionnaires are specifically available for hip arthroscopy patients. The aim of this systematic review was to investigate which PRO questionnaires are valid and reliable in the evaluation of patients undergoing hip arthroscopy. Methods A search was conducted in Pubmed, Medline, CINAHL, the Cochrane Library, Pedro, EMBASE and Web of Science from 1931 to October 2010. Studies assessing the quality of PRO questionnaires in the evaluation of patients undergoing hip arthroscopy were included. The quality of the questionnaires was evaluated by the psychometric properties of the outcome measures. The quality of the articles investigating the questionnaires was assessed by the COSMIN list. Results Five articles identified three questionnaires; the Modified Harris Hip Score (MHHS), the Nonarthritic Hip Score (NAHS) and the Hip Outcome Score (HOS). The NAHS scored best on the content validity, whereas the HOS scored best on agreement, internal consistency, reliability and responsiveness. The quality of the articles describing the HOS scored highest. The NAHS is the best quality questionnaire. The articles describing the HOS are the best quality articles. Conclusions This systematic review shows that there is no conclusive evidence for the use of a single patient-reported outcome questionnaire in the evaluation of patients undergoing hip arthroscopy. Based on available psychometric evidence we recommend using a combination of the NAHS and the HOS for patients undergoing hip arthroscopy.</p

Taking Ownership: Our Pledge to Educate All of Detroit's Children

Excellent Schools Detroit represents a broad and diverse cross section of Detroit's education, government, civic and community, parent, organized labor, and philanthropic leaders who are committed to ensuring that all Detroit children receive the great education they deserve. This citywide education plan reflects months of discussions and deliberations by coalition members, as well as a series of six community meetings in November and December, youth focus groups, small group discussions with multiple stakeholders, and other outreach efforts. We appreciate the thoughtful recommendations from the many Detroiters who are as passionate as we are about the need to prepare all students for college, careers, and life in the 21st century

Galaxy Zoo and ALFALFA: Atomic Gas and the Regulation of Star Formation in Barred Disc Galaxies

We study the observed correlation between atomic gas content and the likelihood of hosting a large scale bar in a sample of 2090 disc galaxies. Such a test has never been done before on this scale. We use data on morphologies from the Galaxy Zoo project and information on the galaxies' HI content from the ALFALFA blind HI survey. Our main result is that the bar fraction is significantly lower among gas rich disc galaxies than gas poor ones. This is not explained by known trends for more massive (stellar) and redder disc galaxies to host more bars and have lower gas fractions: we still see at fixed stellar mass a residual correlation between gas content and bar fraction. We discuss three possible causal explanations: (1) bars in disc galaxies cause atomic gas to be used up more quickly, (2) increasing the atomic gas content in a disc galaxy inhibits bar formation, and (3) bar fraction and gas content are both driven by correlation with environmental effects (e.g. tidal triggering of bars, combined with strangulation removing gas). All three explanations are consistent with the observed correlations. In addition our observations suggest bars may reduce or halt star formation in the outer parts of discs by holding back the infall of external gas beyond bar co-rotation, reddening the global colours of barred disc galaxies. This suggests that secular evolution driven by the exchange of angular momentum between stars in the bar, and gas in the disc, acts as a feedback mechanism to regulate star formation in intermediate mass disc galaxies.Comment: 16 pages, 10 figures. In press at MNRAS. v2 contains corrections found in proof

Ultraviolet Signatures of Tidal Interaction in the Giant Spiral Galaxy, M101

We present new evidence for tidal interactions having occurred in the disk of M101 in the last 10^8 - 10^9 years. Recent imaging of the far-ultraviolet emission from M101 by the Shuttle-borne Ultraviolet Imaging Telescope (UIT) reveals with unprecedented clarity a disk-wide pattern of multiple linear arm segments (``crooked arms''). The deep FUV image also shows a faint outer spiral arm with a (``curly tail'') feature that appears to loop around the supergiant HII region NGC 5471 - linking this outlying starburst with the rest of the galaxy. These FUV-bright features most likely trace hot O & B-type stars along with scattered light from associated nebular dust. Counterparts of the outermost ``crooked arms'' are evident in maps at visible wavelengths and in the 21-cm line of HI. The inner-disk FUV arms are most closely associated with H$\alpha$ knots and the outer (downstream) sides of CO arms. Comparisons of the ``crooked arm'' and ``curly tail'' morphologies with dynamical simulations yield the greatest similitude, when the non- axisymmetric forcing comes from a combination of ``external interactions'' with one or more companion galaxies and ``internal perturbations'' from massive objects orbiting within the disk. We speculate that NGC 5471 represents one of these ``massive disturbers'' within the disk, whose formation followed from a tidal interaction between M101 and a smaller galaxy.Comment: Paper format (latex); length of paper (8); 4 gif figure files; uses aas2pp4.sty AASTeX macro file; to be published in Part I of the Astrophysical Journa