Genome and Transcriptome Analysis of the Food-Yeast Candida utilis

The industrially important food-yeast Candida utilis is a Crabtree effect-negative yeast used to produce valuable chemicals and recombinant proteins. In the present study, we conducted whole genome sequencing and phylogenetic analysis of C. utilis, which showed that this yeast diverged long before the formation of the CUG and Saccharomyces/Kluyveromyces clades. In addition, we performed comparative genome and transcriptome analyses using next-generation sequencing, which resulted in the identification of genes important for characteristic phenotypes of C. utilis such as those involved in nitrate assimilation, in addition to the gene encoding the functional hexose transporter. We also found that an antisense transcript of the alcohol dehydrogenase gene, which in silico analysis did not predict to be a functional gene, was transcribed in the stationary-phase, suggesting a novel system of repression of ethanol production. These findings should facilitate the development of more sophisticated systems for the production of useful reagents using C. utilis

Effect of structural defects on anomalous ultrasound propagation in solids during second-order phase transitions

The effect of structural defects on the critical ultrasound attenuation and ultrasound velocity dispersion in Ising-like three-dimensional systems is studied. A field-theoretical description of the dynamic effects of acoustic-wave propagation in solids during phase transitions is performed with allowance for both fluctuation and relaxation attenuation mechanisms. The temperature and frequency dependences of the scaling functions of the attenuation coefficient and the ultrasound velocity dispersion are calculated in a two-loop approximation for pure and structurally disordered systems, and their asymptotic behavior in hydrodynamic and critical regions is separated. As compared to a pure system, the presence of structural defects in it is shown to cause a stronger increase in the sound attenuation coefficient and the sound velocity dispersion even in the hydrodynamic region as the critical temperature is reached. As compared to pure analogs, structurally disordered systems should exhibit stronger temperature and frequency dependences of the acoustic characteristics in the critical region.Comment: 7 RevTeX pages, 4 figure

Adaptive Response in Mice Exposed to 900 MHz Radiofrequency Fields: Primary DNA Damage

The phenomenon of adaptive response (AR) in animal and human cells exposed to ionizing radiation is well documented in scientific literature. We have examined whether such AR could be induced in mice exposed to non-ionizing radiofrequency fields (RF) used for wireless communications. Mice were pre-exposed to 900 MHz RF at 120 µW/cm2 power density for 4 hours/day for 1, 3, 5, 7 and 14 days and then subjected to an acute dose of 3 Gy γ-radiation. The primary DNA damage in the form of alkali labile base damage and single strand breaks in the DNA of peripheral blood leukocytes was determined using the alkaline comet assay. The results indicated that the extent of damage in mice which were pre-exposed to RF for 1 day and then subjected to γ-radiation was similar and not significantly different from those exposed to γ-radiation alone. However, mice which were pre-exposed to RF for 3, 5, 7 and 14 days showed progressively decreased damage and was significantly different from those exposed to γ-radiation alone. Thus, the data indicated that RF pre-exposure is capable of inducing AR and suggested that the pre-exposure for more than 4 hours for 1 day is necessary to elicit such AR

Tumor-promoting functions of transforming growth factor-β in progression of cancer

Transforming growth factor-β (TGF-β) elicits both tumor-suppressive and tumor-promoting functions during cancer progression. Here, we describe the tumor-promoting functions of TGF-β and how these functions play a role in cancer progression. Normal epithelial cells undergo epithelial-mesenchymal transition (EMT) through the action of TGF-β, while treatment with TGF-β and fibroblast growth factor (FGF)-2 results in transdifferentiation into activated fibroblastic cells that are highly migratory, thereby facilitating cancer invasion and metastasis. TGF-β also induces EMT in tumor cells, which can be regulated by oncogenic and anti-oncogenic signals. In addition to EMT promotion, invasion and metastasis of cancer are facilitated by TGF-β through other mechanisms, such as regulation of cell survival, angiogenesis, and vascular integrity, and interaction with the tumor microenvironment. TGF-β also plays a critical role in regulating the cancer-initiating properties of certain types of cells, including glioma-initiating cells. These findings thus may be useful for establishing treatment strategies for advanced cancer by inhibiting TGF-β signaling

Glioblastoma—a moving target

The slow development of effective treatment of glioblastoma is contrasted by the rapidly advancing research on the molecular mechanisms underlying the disease. Amplification and overexpression of receptor tyrosine kinases, particularly EGFR and PDGFRA, are complemented by mutations in the PI3K, RB1, and p53 signaling pathways. In addition to finding effective means to target these pathways, we may take advantage of the recent understanding of the hierarchical structure of tumor cell populations, where the progressive expansion of the tumor relies on a minor subpopulation of glioma stem cells, or glioma-initiating cells. Finding ways to reprogram these cells and block their self-renewal is one of the most important topics for future research

Effect of CD26/dipeptidyl peptidase IV on Jurkat sensitivity to G2/M arrest induced by topoisomerase II inhibitors

CD26/dipeptidyl peptidase IV (DPPIV) is a surface antigen with multiple functions, including a role in T-cell activation and the development of certain human cancers. We previously demonstrated that CD26/DPPIV enhanced sensitivity of Jurkat cells to doxorubicin. We now show that expression of CD26/DPPIV enhanced sensitivity of CD26 Jurkat transfectants to G2–M arrest mediated by the antineoplastic agent etoposide. The increased sensitivity to etoposide-induced G2–M arrest was associated with disruption of cell cycle-related events, including hyperphosphorylation of p34cdc2 kinase, change in cdc25C expression and phosphorylation, and alteration in cyclin B1 expression. CD26/DPPIV-associated enhancement of doxorubicin and etoposide-induced G2–M arrest was also observed in serum-free media, suggesting an effect of CD26 on cell-derived processes rather than serum-derived factors. Importantly, our work elucidated a potential mechanism for the enhanced susceptibility of CD26-expressing Jurkat cells to the topoisomerase II inhibitors by demonstrating that CD26/DPPIV surface expression was associated with increased topoisomerase II α levels and enhanced enzyme activity. Besides being the first to show a functional association between the multifaceted molecule CD26 and the key cellular protein topoisomerase II α, our studies provide additional evidence of a potential role for CD26 in the treatment of selected malignancies

The SOX2 response program in glioblastoma multiforme: an integrated ChIP-seq, expression microarray, and microRNA analysis

<p>Abstract</p> <p>Background</p> <p><it>SOX2 </it>is a key gene implicated in maintaining the stemness of embryonic and adult stem cells. <it>SOX2 </it>appears to re-activate in several human cancers including glioblastoma multiforme (GBM), however, the detailed response program of <it>SOX2 </it>in GBM has not yet been defined.</p> <p>Results</p> <p>We show that knockdown of the <it>SOX2 </it>gene in LN229 GBM cells reduces cell proliferation and colony formation. We then comprehensively characterize the <it>SOX2 </it>response program by an integrated analysis using several advanced genomic technologies including ChIP-seq, microarray profiling, and microRNA sequencing. Using ChIP-seq technology, we identified 4883 <it>SOX2 </it>binding regions in the GBM cancer genome. <it>SOX2 </it>binding regions contain the consensus sequence wwTGnwTw that occurred 3931 instances in 2312 <it>SOX2 </it>binding regions. Microarray analysis identified 489 genes whose expression altered in response to <it>SOX2 </it>knockdown. Interesting findings include that <it>SOX2 </it>regulates the expression of SOX family proteins <it>SOX1 </it>and <it>SOX18</it>, and that <it>SOX2 </it>down regulates <it>BEX1 </it>(brain expressed X-linked 1) and <it>BEX2 </it>(brain expressed X-linked 2), two genes with tumor suppressor activity in GBM. Using next generation sequencing, we identified 105 precursor microRNAs (corresponding to 95 mature miRNAs) regulated by <it>SOX2</it>, including down regulation of miR-143, -145, -253-5p and miR-452. We also show that miR-145 and <it>SOX2 </it>form a double negative feedback loop in GBM cells, potentially creating a bistable system in GBM cells.</p> <p>Conclusions</p> <p>We present an integrated dataset of ChIP-seq, expression microarrays and microRNA sequencing representing the <it>SOX2 </it>response program in LN229 GBM cells. The insights gained from our integrated analysis further our understanding of the potential actions of <it>SOX2 </it>in carcinogenesis and serves as a useful resource for the research community.</p