Ectopic Expression of Vaccinia Virus E3 and K3 Cannot Rescue Ectromelia Virus Replication in Rabbit RK13 Cells

Citation: Hand, E. S., Haller, S. L., Peng, C., Rothenburg, S., & Hersperger, A. R. (2015). Ectopic Expression of Vaccinia Virus E3 and K3 Cannot Rescue Ectromelia Virus Replication in Rabbit RK13 Cells. Plos One, 10(3), 15. doi:10.1371/journal.pone.0119189As a group, poxviruses have been shown to infect a wide variety of animal species. However, there is individual variability in the range of species able to be productively infected. In this study, we observed that ectromelia virus (ECTV) does not replicate efficiently in cultured rabbit RK13 cells. Conversely, vaccinia virus (VACV) replicates well in these cells. Upon infection of RK13 cells, the replication cycle of ECTV is abortive in nature, resulting in a greatly reduced ability to spread among cells in culture. We observed ample levels of early gene expression but reduced detection of virus factories and severely blunted production of enveloped virus at the cell surface. This work focused on two important host range genes, named E3L and K3L, in VACV. Both VACV and ECTV express a functional protein product from the E3L gene, but only VACV contains an intact K3L gene. To better understand the discrepancy in replication capacity of these viruses, we examined the ability of ECTV to replicate in wild-type RK13 cells compared to cells that constitutively express E3 and K3 from VACV. The role these proteins play in the ability of VACV to replicate in RK13 cells was also analyzed to determine their individual contribution to viral replication and PKR activation. Since E3L and K3L are two relevant host range genes, we hypothesized that expression of one or both of them may have a positive impact on the ability of ECTV to replicate in RK13 cells. Using various methods to assess virus growth, we did not detect any significant differences with respect to the replication of ECTV between wild-type RK13 compared to versions of this cell line that stably expressed VACV E3 alone or in combination with K3. Therefore, there remain unanswered questions related to the factors that limit the host range of ECTV

Study of TLR3, TLR4 and TLR9 in breast carcinomas and their association with metastasis

<p>Abstract</p> <p>Background</p> <p>Toll-like receptors (TLRs) have garnered an extraordinary amount of interest in cancer research due to their role in tumor progression. By activating the production of several biological factors, TLRs induce type I interferons and other cytokines, which drive an inflammatory response and activate the adaptive immune system. The aim of this study was to investigate the expression and clinical relevance of TLR3, 4 and 9 in breast cancer.</p> <p>Methods</p> <p>The expression levels of TLR3, TLR4 and TLR9 were analyzed on tumors from 74 patients with breast cancer. The analysis was performed by immunohistochemistry.</p> <p>Results</p> <p>Samples of carcinomas with recurrence exhibited a significant increase in the mRNA levels of TLR3, TLR4 and TLR9. Tumors showed high expression of TLRs expression levels by cancer cells, especially TLR4 and 9. Nevertheless, a significant percentage of tumors also showed TLR4 expression by mononuclear inflammatory cells (21.6%) and TLR9 expression by fibroblast-like cells (57.5%). Tumors with high TLR3 expression by tumor cell or with high TLR4 expression by mononuclear inflammatory cells were significantly associated with higher probability of metastasis. However, tumours with high TLR9 expression by fibroblast-like cells were associated with low probability of metastasis.</p> <p>Conclusions</p> <p>The expression levels of TLR3, TLR4 and TLR9 have clinical interest as indicators of tumor aggressiveness in breast cancer. TLRs may represent therapeutic targets in breast cancer.</p

Varieties of living things: Life at the intersection of lineage and metabolism

publication-status: Publishedtypes: Articl

FCC-ee: The Lepton Collider: Future Circular Collider Conceptual Design Report Volume 2

In response to the 2013 Update of the European Strategy for Particle Physics, the Future Circular Collider (FCC) study was launched, as an international collaboration hosted by CERN. This study covers a highest-luminosity high-energy lepton collider (FCC-ee) and an energy-frontier hadron collider (FCC-hh), which could, successively, be installed in the same 100 km tunnel. The scientific capabilities of the integrated FCC programme would serve the worldwide community throughout the 21st century. The FCC study also investigates an LHC energy upgrade, using FCC-hh technology. This document constitutes the second volume of the FCC Conceptual Design Report, devoted to the electron-positron collider FCC-ee. After summarizing the physics discovery opportunities, it presents the accelerator design, performance reach, a staged operation scenario, the underlying technologies, civil engineering, technical infrastructure, and an implementation plan. FCC-ee can be built with today’s technology. Most of the FCC-ee infrastructure could be reused for FCC-hh. Combining concepts from past and present lepton colliders and adding a few novel elements, the FCC-ee design promises outstandingly high luminosity. This will make the FCC-ee a unique precision instrument to study the heaviest known particles (Z, W and H bosons and the top quark), offering great direct and indirect sensitivity to new physics

Quantifying the burden of disease due to premature mortality in Hong Kong using standard expected years of life lost

Plaß D, Chau PY, Thach T, et al. Quantifying the burden of disease due to premature mortality in Hong Kong using standard expected years of life lost. BMC Public Health. 2013;13(1): 863.Background To complement available information on mortality in a population Standard Expected Years of Life Lost (SEYLL), an indicator of premature mortality, is increasingly used to calculate the mortality-associated disease burden. SEYLL consider the age at death and therefore allow a more accurate view on mortality patterns as compared to routinely used measures (e.g. death counts). This study provides a comprehensive assessment of disease and injury SEYLL for Hong Kong in 2010. Methods To estimate the SEYLL, life-expectancy at birth was set according to the 2004 Global Burden of Disease study at 82.5 and 80 years for females and males, respectively. Cause of death data for 2010 were corrected for misclassification of cardiovascular and cancer causes. In addition to the baseline estimates, scenario analyses were performed using alternative assumptions on life-expectancy (Hong Kong standard life-expectancy), time-discounting and age-weighting. To estimate a trend of premature mortality a time-series analysis from 2001 to 2010 was conducted. Results In 2010 524,706.5 years were lost due to premature death in Hong Kong with 58.3% of the SEYLL attributable to male deaths. The three overall leading single causes of SEYLL were “trachea, bronchus and lung cancers”, “ischaemic heart disease” and “lower respiratory infections” together accounting for about 29% of the overall SEYLL. Further, self-inflicted injuries (5.6%; ranked 5) and liver cancer (4.9%; ranked 7) were identified as important causes not adequately captured by classical mortality measures. Scenario analyses highlighted that by using a 3% time-discount rate and non-uniform age-weights the SEYLL dropped by 51.6%. Using Hong Kong’s standard life-expectancy values resulted in an overall increase of SEYLL by 10.8% as compared to the baseline SEYLL. Time-series analysis indicates an overall increase of SEYLL by 6.4%. In particular, group I (communicable, maternal, perinatal and nutritional) conditions showed highest increases with SEYLL-rates per 100,000 in 2010 being 1.4 times higher than 2001. Conclusions The study stresses the mortality impact of diseases and injuries that occur in earlier stages of life and thus presents the SEYLL measure as a more sensitive indicator compared to classical mortality indicators. SEYLL provide useful additional information and supplement available death statistics