Gene expression profile of cervical and skin tissues from human papillomavirus type 16 E6 transgenic mice

<p>Abstract</p> <p>Background</p> <p>Although K14E6 transgenic mice develop spontaneous tumors of the skin epithelium, no spontaneous reproductive tract malignancies arise, unless the transgenic mice were treated chronically with 17β-estradiol. These findings suggest that E6 performs critical functions in normal adult cervix and skin, highlighting the need to define E6-controlled transcriptional programs in these tissues.</p> <p>Methods</p> <p>We evaluated the expression profile of 14,000 genes in skin or cervix from young K14E6 transgenic mice compared with nontransgenic. To identify differentially expressed genes a linear model was implemented using R and the LIMMA package. Two criteria were used to select the set of relevant genes. First a set of genes with a Log-odds ≥ 3 were selected. Then, a hierarchical search of genes was based on Log Fold Changes.</p> <p>Results</p> <p>Microarray analysis identified a total of 676 and 1154 genes that were significantly up and down-regulated, respectively, in skin from K14E6 transgenic mice. On the other hand, in the cervix from K14E6 transgenic mice we found that only 97 and 252 genes were significantly up and down-regulated, respectively. One of the most affected processes in the skin from K14E6 transgenic mice was the cell cycle. We also found that skin from transgenic mice showed down-regulation of pro-apoptotic genes and genes related to the immune response. In the cervix of K14E6 transgenic mice, we could not find affected any gene related to the cell cycle and apoptosis pathways but did observe alterations in the expression of immune response genes. Pathways such as angiogenesis, cell junction and epidermis development, also were altered in their gene expression profiles in both tissues.</p> <p>Conclusion</p> <p>Expression of the HPV16 E6 oncoprotein in our model alters expression of genes that fell into several functional groups providing insights into pathways by which E6 deregulate cell cycle progression, apoptosis, the host resistance to infection and immune function, providing new opportunities for early diagnostic markers and therapeutic drug targets.</p

<it>In situ</it> molecular identification of the Influenza A (H1N1) 2009 Neuraminidase in patients with severe and fatal infections during a pandemic in Mexico City

Abstract Background In April 2009, public health surveillance detected an increased number of influenza-like illnesses in Mexico City’s hospitals. The etiological agent was subsequently determined to be a spread of a worldwide novel influenza A (H1N1) triple reassortant. The purpose of the present study was to demonstrate that molecular detection of pandemic influenza A (H1N1) 2009 strains is possible in archival material such as paraffin-embedded lung samples. Methods In order to detect A (H1N1) virus sequences in archived biological samples, eight paraffin-embedded lung samples from patients who died of pneumonia and respiratory failure were tested for influenza A (H1N1) Neuraminidase (NA) RNA using in situ RT-PCR. Results We detected NA transcripts in 100% of the previously diagnosed A (H1N1)-positive samples as a cytoplasmic signal. No expression was detected by in situ RT-PCR in two Influenza-like Illness A (H1N1)-negative patients using standard protocols nor in a non-related cervical cell line. In situ relative transcription levels correlated with those obtained when in vitro RT-PCR assays were performed. Partial sequences of the NA gene from A (H1N1)-positive patients were obtained by the in situ RT-PCR-sequencing method. Sequence analysis showed 98% similarity with influenza viruses reported previously in other places. Conclusions We have successfully amplified specific influenza A (H1N1) NA sequences using stored clinical material; results suggest that this strategy could be useful when clinical RNA samples are quantity limited, or when poor quality is obtained. Here, we provide a very sensitive method that specifically detects the neuraminidase viral RNA in lung samples from patients who died from pneumonia caused by Influenza A (H1N1) outbreak in Mexico City.</p

RAE-1 ligands for the NKG2D receptor are regulated by E2F transcription factors, which control cell cycle entry

The NKG2D stimulatory receptor expressed by natural killer cells and T cell subsets recognizes cell surface ligands that are induced on transformed and infected cells and facilitate immune rejection of tumor cells. We demonstrate that expression of retinoic acid early inducible gene 1 (RAE-1) family NKG2D ligands in cancer cell lines and proliferating normal cells is coupled directly to cell cycle regulation. Raet1 genes are directly transcriptionally activated by E2F family transcription factors, which play a central role in regulating cell cycle entry. Induction of RAE-1 occurred in primary cell cultures, embryonic brain cells in vivo, and cells in healing skin wounds and, accordingly, wound healing was delayed in mice lacking NKG2D. Transcriptional activation by E2Fs is likely coordinated with posttranscriptional regulation by other stress responses. These findings suggest that cellular proliferation, as occurs in cancer cells but also other pathological conditions, is a key signal tied to immune reactions mediated by NKG2D-bearing lymphocytes

Nanoscale Mechanical Softening of Morphotropic BiFeO 3

Mechanical switching can be used to form phase-transformed areas in mixed-phase bismuth ferrite thin films, which might be exploited to yield various soft elastic areas with greatly reduced Young's modulus on the nanoscale. Due to the mechanically susceptible nature of morphotropic phase boundaries in multiferroics, combined elastic control of electronic, magnetic, and ferroelectric properties becomes possible. (Figure Presented)

Relaxor-ferroelectric thin film heterostructure with large imprint for high energy-storage performance at low operating voltage

Excellent energy storage performance in combination with a low operating voltage is a very important factor for pulse-power dielectric capacitor devices to achieve miniaturization and integration. Here the heterostructure of the relaxor ferroelectric Pb0.9La0.1(Zr0.52Ti0.48)O3 (PL), with a slim hysteresis loop, on the normal ferroelectric Pb(Zr0.52Ti0.48)0.99Nb0.01O3 (PN), causing a large voltage imprint, is shown to improve the energy-storage performance. A large recoverable energy-storage density of 43.5 J/cm3 and a high energy-storage efficiency of 84.1%, under an electric field of 2450 kV/cm (i.e. a 49 V voltage bias), are obtained in the 180 nm PL/20 nm PN thin film heterostructure. Due to the small total film thickness the excellent energy-storage properties are obtained at a low operating voltage of 49 V. Moreover, the PL/PN heterostructure also exhibits an excellent charge-discharge endurance up to 1010 cycles and good thermal stability in a wide temperature range from room temperature to 200 °C. These performances show that these heterostructures form a promising design for high-temperature pulse-power capacitors, with superior energy-storage performance at low operating voltages