The impact of hypoxia on oncolytic virotherapy

The hypoxic tumor microenvironment plays significant roles in tumor cell metabolism and survival, tumor growth, and progression. Hypoxia modulates target genes in target cells mainly through an oxygen-sensing signaling pathway mediated by hypoxia-inducible factor of transcription factors. As a result, hypoxic tumor cells are resistant to conventional therapeutics such as radiation and chemotherapy. Oncolytic virotherapy may be a promising novel therapeutic for hypoxic cancer. Some oncolytic viruses are better adapted than others to the hypoxic tumor environment. Replication of adenoviruses from both groups B and C is inhibited, yet replication of herpes simplex virus is enhanced. Hypoxia seems to exert little or no effect on the replication of other oncolytic viruses. Vaccinia virus displayed increased cytotoxicity in some hypoxic cancer cells even though viral protein synthesis and transgene expression were not affected. Vesicular stomatitis virus replicated to similar levels in both hypoxic and normoxic conditions, and is effective for killing hypoxic cancer cells. However, vesicular stomatitis virus and reovirus, but not encephalomyocarditis virus, are sensitive to elevated levels of hypoxia-inducible factor-1α in renal cancer cells with the loss of von Hippel-Lindau tumor suppressor protein, because elevated hypoxia-inducible factor activity confers dramatically enhanced resistance to cytotoxicity mediated by vesicular stomatitis virus or reovirus. A variety of hypoxia-selective and tumor-type-specific oncolytic adenoviruses, generated by incorporating hypoxia-responsive elements into synthetic promoters to control essential genes for viral replication or therapeutic genes, have been shown to be safe and efficacious. Hypoxic tumor-homing macrophages can function effectively as carrier cells to deliver an oncolytic adenovirus to the hypoxic/necrotic areas of the tumor. It is envisioned that further improved oncolytic viruses will be highly effective against hypoxic tumor, especially when combined with other therapeutic regimens such as immunotherapy, radiation therapy, and/or chemotherapy. © 2011 Guo

Study on the triphenyl tetrazolium chloride– dehydrogenase activity (TTC-DHA) method in determination of bioactivity for treating tomato paste wastewater

A quick analysis of the sludge activity method based on triphenyltetrazolium chloride-dehydrogenase activity (TTC-DHA) was developed to change the rule and status of the biological activity of the activated sludge in tomato paste wastewater treatment. The results indicate that dehydrogenase activity (DHA) can effectively facilitate the biochemical reaction of tomato paste wastewater treatment upon analysis of the influences of various DHA and kinetic factors. The biological activity of the activated sludge by TTC-DHA was changed to become applicable to aeration and wastewater treatment operation and management.Key words: Tomato paste wastewater, TTC-DHA, bioactivity, active sludge

Homeobox gene Rhox5 is regulated by epigenetic mechanisms in cancer and stem cells and promotes cancer growth

<p>Abstract</p> <p>Background</p> <p>Homeobox genes murine <it>Rhox5 </it>and human <it>RHOXF1 </it>are expressed in early embryonic stages and then mostly restricted to germline tissues in normal adult, yet they are aberrantly expressed in cancer cells <it>in vitro </it>and <it>in vivo </it>. Here we study the epigenetic regulation and potential functions of <it>Rhox5 </it>gene.</p> <p>Findings</p> <p>In <it>Rhox5 </it>-silenced or extremely low expresser cells, we observed low levels of active histone epigenetic marks (H3ac, H4ac and H3K4me2) and high levels of repressive mark H3K9me2 along with DNA hypermethylation in the promoter. In <it>Rhox5 </it>low expresser cells, we typically observed modest levels of both active and repressive histone marks along with moderate DNA methylation. In <it>Rhox5 </it>highly expressed CT26 cancer cells, we observed DNA hypomethylation along with high levels of both active and repressive histone marks. Epigenetic drugs (retinoic acid and MS-275) induced F9 cell differentiation with enhanced <it>Rhox5 </it>expression and dynamic changes of epigenetic marks. Finally, <it>Rhox5 </it>knockdown by small hairpin RNA (shRNA) in CT26 colon cancer decreased cell proliferation and migration <it>in vitro </it>and tumor growth <it>in vivo </it>.</p> <p>Conclusions</p> <p>Both DNA methylation and histone methylation/acetylation play key roles in modulating <it>Rhox5 </it>expression in various cell types. The stem cell-like "bivalent domain", an epigenetic feature originally identified in key differentiation genes within stem cells, exists in the <it>Rhox5 </it>gene promoter in not only embryonic stem cells but also cancer cells, cancer stem cells, and differentiated Sertoli cells. As <it>Ras </it>signaling-dependent <it>Rhox5 </it>expression promotes tumor growth, <it>Rhox5 </it>may be an ideal target for therapeutic intervention in cancer.</p

Analysis of genetic diversity and construction of core collection of local mulberry varieties from Shanxi Province based on ISSR marker

Genetic diversity of 73 local mulberry varieties from Shanxi Province were screened using ISSR markers, with l5 primers combinations selected for their reproducibility and polymorphism. 129 bands were amplified, of which 115 bands showed polymorphism and the ratio of polymorphism bands was 89.15%. Nei’s genetic similarity coefficients ranged from 0.5891 to 0.9457 with an average of 0.7674. The observed number of alleles of each loci, effective number of alleles of each loci, Nei’s gene diversity, Shannon’s information index were 1.8915, 1.4771, 0.2780 and 0.4197, respectively. Clustering results showed that the 73 varieties could be divided into three different groups and nine subgroups. By using stepwise clustering and random methods and the modified heuristic algorithm, 21 core collections were constructed and the ratio of core collection was 28.77%. The result of t-test to the parameters (the number effective of alleles, Nei's genetic diversity index and Shannon's information index) showed that there was not significant difference between the core collection and initial sample with the exception of the number of observed alleles, that is, the core collection could well represent the initial sample.Key words: Mulberry, germplasm resource, genetic diversity, ISSR, cluster analysis, core collection

Numerical simulation of solitary wave propagation over a steady current

YesA two-dimensional numerical model is developed to study the propagation of a solitary wave in the presence of a steady current flow. The numerical model is based on the Reynolds-averaged Navier-Stokes (RANS) equations with a k-ε turbulence closure scheme and an internal wave-maker method. To capture the air-water interface, the volume of fluid (VOF) method is used in the numerical simulation. The current flow is initialized by imposing a steady inlet velocity on one computational domain end and a constant pressure outlet on the other end. The desired wave is generated by an internal wave-maker. The propagation of a solitary wave travelling with a following/opposing current is simulated. The effects of the current velocity on the solitary wave motion are investigated. The results show that the solitary wave has a smaller wave height, larger wave width and higher travelling speed after interacting with a following current. Contrariwise, the solitary wave becomes higher with a smaller wave width and lower travelling speed with an opposing current. The regression equations for predicting the wave height, wave width and travelling speed of the resulting solitary wave are for practical engineering applications. The impacts of current flow on the induced velocity and the turbulent kinetic energy (TKE) of a solitary wave are also investigated.National Natural Science Foundation of China Grant #51209083, #51137002 and #41176073, the Natural Science Foundation of Jiangsu Province (China) Grant #BK2011026, the 111 Project under Grant No. B12032, the Fundamental Research Funds for the Central University, China (2013B31614), and the Carnegie Trust for Scottish Universitie

A promising new class of high-temperature alloys: Eutectic high-entropy alloys

High-entropy alloys (HEAs) can have either high strength or high ductility, and a simultaneous achievement of both still constitutes a tough challenge. The inferior castability and compositional segregation of HEAs are also obstacles for their technological applications. To tackle these problems, here we proposed a novel strategy to design HEAs using the eutectic alloy concept, i.e. to achieve a microstructure composed of alternating soft fcc and hard bcc phases. As a manifestation of this concept, an AlCoCrFeNi 2.1 (atomic portion) eutectic high-entropy alloy (EHEA) was designed. The as-cast EHEA possessed a fine lamellar fcc/B2 microstructure, and showed an unprecedented combination of high tensile ductility and high fracture strength at room temperature. The excellent mechanical properties could be kept up to 700°C. This new alloy design strategy can be readily adapted to large-scale industrial production of HEAs with simultaneous high fracture strength and high ductility

Experimental entanglement verification and quantification via uncertainty relations

We report on experimental studies on entanglement quantification and verification based on uncertainty relations for systems consisting of two qubits. The new proposed measure is shown to be invariant under local unitary transformations, by which entanglement quantification is implemented for two-qubit pure states. The nonlocal uncertainty relations for two-qubit pure states are also used for entanglement verification which serves as a basic proposition and promise to be a good choice for verification of multipartite entanglement.Comment: 5 pages, 3 figures and 2 table

Genetic Polymorphisms in Caveolin-1 Associate with Breast Cancer Risk in Chinese Han Population

Caveolin-1(CAV-1) was demonstrated to be a tumor suppressor gene and be implicated in the development of breast cancer (BC). Numerous potentially functional polymorphisms in CAV-1 have been identified, but their effects on BC were not clear. This case-control study aims to evaluate the relationship between CAV-1 polymorphisms and BC risk. 560 BC patients and 583 healthy controls were enrolled in the present study, all from Chinese Han population. We detected 3 single nucleotide polymorphisms (rs3807987, rs1997623, and rs7804372) in CAV-1 using the Sequenom MassARRAY method. The association between CAV-1genotypes and BC risk was assessed in six genetic models by calculating the odds ratio (OR) and 95% confidence intervals (95% CIs) with χ2-test. The CAV-1rs3807987 polymorphism was observed to increase the risk of BC And the A allele of rs3807987 relates to a larger tumor size (≥2cm) and lower incidence of PR-positive BC while the AA genotype of rs7804372 associates with a higher ER and Her-2 positive rate among BC patients. In addition, Ars1997623Grs3807987Trs7804372 haplotype was linked to a decreased risk of BC (OR =0.64, 95%CI=0.44-0.93), whereas Crs1997623Ars3807987Trs7804372 haplotype was related to an increased BC risk (OR =1.74, 95%CI=1.04-2.92). Our study suggests that CAV-1 rs3807987 can increase the BC risk among Chinese Han women. And the rs3807987 and rs7804372 in CAV-1 may serve as predictors for prognosis of BC