Canine respiratory coronavirus employs caveolin-1-mediated pathway for internalization to HRT-18G cells

Canine respiratory coronavirus (CRCoV), identified in 2003, is a member of the Coronaviridae family. The virus is a betacoronavirus and a close relative of human coronavirus OC43 and bovine coronavirus. Here, we examined entry of CRCoV into human rectal tumor cells (HRT-18G cell line) by analyzing co-localization of single virus particles with cellular markers in the presence or absence of chemical inhibitors of pathways potentially involved in virus entry. We also targeted these pathways using siRNA. The results show that the virus hijacks caveolin-dependent endocytosis to enter cells via endocytic internalization

No Evidence of Murine Leukemia Virus-Related Viruses in Live Attenuated Human Vaccines

The association of xenotropic murine leukemia virus (MLV)-related virus (XMRV) in prostate cancer and chronic fatigue syndrome reported in previous studies remains controversial as these results have been questioned by recent data. Nonetheless, concerns have been raised regarding contamination of human vaccines as a possible source of introduction of XMRV and MLV into human populations. To address this possibility, we tested eight live attenuated human vaccines using generic PCR for XMRV and MLV sequences. Viral metagenomics using deep sequencing was also done to identify the possibility of other adventitious agents.All eight live attenuated vaccines, including Japanese encephalitis virus (JEV) (SA-14-14-2), varicella (Varivax), measles, mumps, and rubella (MMR-II), measles (Attenuvax), rubella (Meruvax-II), rotavirus (Rotateq and Rotarix), and yellow fever virus were negative for XMRV and highly related MLV sequences. However, residual hamster DNA, but not RNA, containing novel endogenous gammaretrovirus sequences was detected in the JEV vaccine using PCR. Metagenomics analysis did not detect any adventitious viral sequences of public health concern. Intracisternal A particle sequences closest to those present in Syrian hamsters and not mice were also detected in the JEV SA-14-14-2 vaccine. Combined, these results are consistent with the production of the JEV vaccine in Syrian hamster cells.We found no evidence of XMRV and MLV in eight live attenuated human vaccines further supporting the safety of these vaccines. Our findings suggest that vaccines are an unlikely source of XMRV and MLV exposure in humans and are consistent with the mounting evidence on the absence of these viruses in humans

4D treatment planning for scanned ion beams

At Gesellschaft für Schwerionenforschung (GSI) more than 330 patients have been treated with scanned carbon ion beams in a pilot project. To date, only stationary tumors have been treated. In the presence of motion, scanned ion beam therapy is not yet possible because of interplay effects between scanned beam and target motion which can cause severe mis-dosage. We have started a project to treat tumors that are subject to respiratory motion. A prototype beam application system for target tracking with the scanned pencil beam has been developed and commissioned

MAGGnet: an international network to foster mitigation of agricultural greenhouse gases.

Research networks provide a framework for review, synthesis and systematic testing of theories by multiple scientists across international borders critical for addressing global-scale issues. In 2012, a GHG research network referred to as MAGGnet (Managing Agricultural Greenhouse Gases Network) was established within the Croplands Research Group of the Global Research Alliance on Agricultural Greenhouse Gases (GRA). With involvement from 46 alliance member countries, MAGGnet seeks to provide a platform for the inventory and analysis of agricultural GHG mitigation research throughout the world. To date, metadata from 315 experimental studies in 20 countries have been compiled using a standardized spreadsheet. Most studies were completed (74%) and conducted within a 1-3-year duration (68%). Soil carbon and nitrous oxide emissions were measured in over 80% of the studies. Among plant variables, grain yield was assessed across studies most frequently (56%), followed by stover (35%) and root (9%) biomass. MAGGnet has contributed to modeling efforts and has spurred other research groups in the GRA to collect experimental site metadata using an adapted spreadsheet. With continued growth and investment, MAGGnet will leverage limited-resource investments by any one country to produce an inclusive, globally shared meta-database focused on the science of GHG mitigation

2-Aminophenoxazine-3-one and 2-amino-4,4α-dihydro-4α,7-dimethyl-3H-phenoxazine-3-one cause cellular apoptosis by reducing higher intracellular pH in cancer cells

We examined intracellular pH (pHi) of ten cancer cell lines derived from different organs and two normal cell lines including human embryonic lung fibroblast cells (HEL) and human umbilical vein endothelial cells (HUVEC) in vitro, and found that pHi of most of these cancer cells was evidently higher (pH 7.5 to 7.7) than that of normal cells (7.32 and 7.44 for HEL and HUVEC, respectively) and that of primary leukemic cells and erythrocytes hitherto reported (≤7.2). Higher pHi in these cancer cells could be related to the Warburg effect in cancer cells with enhanced glycolytic metabolism. Since reversal of the Warburg effect may perturb intracellular homeostasis in cancer cells, we looked for compounds that cause extensive reduction of pHi, a major regulator of the glycolytic pathway and its associated metabolic pathway. We found that phenoxazine compounds, 2-aminophenoxazine-3-one (Phx-3) and 2-amino-4,4α-dihydro-4α,7-dimethyl-3H-phenoxazine-3-one (Phx-1) caused a rapid and drastic dose-dependent decrease of pHi in ten different cancer cells within 30 min, though the extent of the decrease of pHi was significantly larger for Phx-3 (ΔpHi = 0.6 pH units or more for 100 µM Phx-3) than for Phx-1 (ΔpHi = 0.1 pH units or more for 100 µM Phx-1). This rapid and drastic decrease of pHi in a variety of cancer cells caused by Phx-3 and Phx-1 possibly perturbed their intracellular homeostasis, and extensively affected the subsequent cell death, because these phenoxazines exerted dose-dependent proapoptotic and cytotoxic effects on these cells during 72 h incubation, confirming a causal relationship between ΔpHi and cytotoxic effects due to Phx-3 and Phx-1. Phx-3 and Phx-1 also reduced pHi of normal cells including HEL and HUVEC, although they exerted less proapoptotic and cytotoxic effects on these cells than on cancer cells. Drugs such as Phx-3 and Phx-1 that reduce pHi and thereby induce cellular apoptosis might serve as benevolent anticancer drugs

West Nile virus and its emergence in the United States of America

Zoonotic West Nile virus (WNV) circulates in natural transmission cycles involving certain mosquitoes and birds, horses, humans, and a range of other vertebrates are incidental hosts. Clinical infections in humans can range in severity from uncomplicated WNV fever to fatal meningoencephalitis. Since its introduction to the Western Hemisphere in 1999, WNV had spread across North America, Central and South America and the Caribbean, although the vast majority of severe human cases have occurred in the United States of America (USA) and Canada. By 2002–2003, the WNV outbreaks have involved thousands of patients causing severe neurologic disease (meningoencephalitis and poliomyelitis-like syndrome) and hundreds of associated fatalities in USA. The purpose of this review is to present recent information on the epidemiology and pathogenicity of WNV since its emergence in North America

The elements of human cyclin D1 promoter and regulation involved

Cyclin D1 is a cell cycle machine, a sensor of extracellular signals and plays an important role in G1-S phase progression. The human cyclin D1 promoter contains multiple transcription factor binding sites such as AP-1, NF-қB, E2F, Oct-1, and so on. The extracellular signals functions through the signal transduction pathways converging at the binding sites to active or inhibit the promoter activity and regulate the cell cycle progression. Different signal transduction pathways regulate the promoter at different time to get the correct cell cycle switch. Disorder regulation or special extracellular stimuli can result in cell cycle out of control through the promoter activity regulation. Epigenetic modifications such as DNA methylation and histone acetylation may involved in cyclin D1 transcriptional regulation