El Diario de Pontevedra : periódico liberal: Ano LI Número 15301 - 1937 novembro 2

Fig. S1. Viability of FaDu and Cal27 cells at low concentrations of methylglyoxal. Assessment of the cytotoxic effect of MG at low concentration in a colony-forming assay. (TIFF 92 kb

Perfiles paleokarsticos en el techo de la unidad intermedia del mioceno de la cuenca de Madrid

An intra-Vallesian (Upper Miocene) paleokarst developed at the top of the Intermediate Miocene Unit in the continental Madrid basin is recognized. This paleokarst is a early shallow, tabular-shaped karst that shows a marked control by the depositional facies pattern and lithologies. By integrating morphological, petrological and geochemica1 data, three hydrogeological or environmental zones have been established throughout the paleokarstic profiles: (i) a vadose zone, characterized by vertically elongated caves and discontinuous speleothems and vadose cements (ii) a 3-7 m thick water table fringe, characterized by the wide development of stratiform breccia bodies, the superimposition of both vadose and phreatic features, and the lowest Fe and Mn contents in host-rock carbonates; and (iii) a phreatic zone characterized by an increase of 6I3C values and the predominance of phreatic cementation. The paleogeographic reconstruction for the intra-Vallesian paleokarst using paleokarstic profiles reveals relative topographic highs to the north and topographic lows to the south drawing the paleokarst landscape.<br><br>En el techo de la Unidad Intermedia del Mioceno de la Cuenca de Madrid se ha desarrollado un paleokarst temprano, somero y de forma tabular que muestra un marcado control litol&#243;gico y del dispositivo de facies deposicionales en su g&#233;nesis. Integrando criterios geomorfol&#243;gicos, petrogr&#225;ficos y geoqu&#237;micos se ha establecido una zonaci&#243;n hidrogeol&#243;gica en los perfiles paleok&#225;rsticos estudiados, diferenci&#225;ndose: (i) una zona vadosa caracterizada por la existencia de cavidades alargadas en la vertical tapizadas discontinuamente por espeleotemas y otros cementos vadosos; (ii) una franja de oscilaci&#243;n del nivel fre&#225;tico de unos 3-7 metros de espesor, caracterizado por el desarrollo extensivo de cuerpos brechoides estratiformes, la yuxtaposici&#243;n de cementos vadosos y fre&#225;ticos y los contenidos m&#225;s bajos en Fe y Mn en el material encajante, y (iii) una zona fre&#225;tica caracterizada por un aumento en los valores de 613C y el predominio de la cementaci&#243;n fre&#225;tica. La correlaci&#243;n de los perfiles paleok&#225;rticos revela una paleogeograf&#237;a para el techo de la Unidad Intermedia con un paisaje topogr&#225;ficamente descendente de norte a sur en la cuenca para el Vallesiense

Additional file 7: of Glyoxalase 1 expression is associated with an unfavorable prognosis of oropharyngeal squamous cell carcinoma

Table S5. Univariate analysis of distinct risk factors for progression-free and disease-specific survival. (DOCX 72 kb

Veldaangeleenthede en beweging van wild in die Kalahari - Gemsbokpark

Veldaangeleenthede en beweging van wild in die Kalahari - Gemsbokpar

Schematic overview of the mechanism suggested for UV-induced NMSC development in <i>Mastomys coucha</i>.

<p><b>A)</b> MnPV infects basal epithelial cells of the skin of young animals via small injuries. <b>B)</b> MnPV genome is amplified in stratified skin layers (pink and red nuclei) and new virions are released. <b>C)</b> UVB irradiation of the skin. <b>D)</b> UVB-irradiated skin is hyperproliferative, favoring viral replication and virion formation. UVB-induced photoproducts, e.g. in <i>Trp53</i>, occur in keratinocytes (altered nuclei). In uninfected cells, damages are repaired. In infected cells, MnPV-E6/E7 reduce chromosomal stability and inhibit DNA repair. Mutations can accumulate and altered cells become neoplastic. <b>E)</b> Neoplastic squamous cells (light blue) start forming a well-differentiated keratinizing SCC, still representing a permissive system that allows viral replication and formation of virions. <b>F)</b> When neoplastic squamous cells accumulate further mutations (dark blue), a spindle cell phenotype is acquired, forming a poorly differentiated SCC that may become ulcerated. MnPV cannot replicate in dedifferentiated cells and the viral DNA is subsequently lost.</p

Molecular analyses of tumor-bearing animals.

<p><b>A)</b> Viral load in tissue samples from UV-irradiated and control animals from the MnPV-infected colony analyzed by qPCR and normalized to a plasmid standard. Samples were grouped according to their origin as indicated (ctrl skin: skin from unirradiated animals; ui skin/UV skin: unirradiated or UV-irradiated skin from irradiated animals; KSCC/nKSCC: UV-induced SCCs; non-UV tumor: tumors from non-UV sites of irradiated animals and spontaneous tumors from unirradiated animals). UV^+/- indicates whether the animal was UV-exposed or not (Kruskal-Wallis test, *p<0.05, ***p<0.001, ^nsp>0.05). <b>B)</b> Southern blot analysis of unirradiated and UV-irradiated skins, a KSCC and a non-UV tumor. DNA was digested with ApaI (no cleavage site in MnPV), XbaI (one site) or XhoI (two sites) as indicated (Form I: supercoiled; Form II: relaxed circular; Form III: linear form of MnPV). <b>C)</b> Semi-quantitative RT-PCR for the most abundant MnPV <i>E1^E4</i> transcript in non-UV tumors and UV-induced SCCs or the control <i>GAPDH</i>. <b>D)</b> Semi-quantitative RT-PCR for MnPV <i>E6</i>, <i>E7</i> and <i>L1</i> transcripts in non-UV tumors and UV-induced SCCs or the control <i>GAPDH</i>.</p

Transactivating capacity of <i>Mastomys</i> p53 in the presence of MnPV E6.

<p><b>A)</b> The capacity of p53 to transactivate a p53-responsive firefly luciferase gene measured in H1299 cells transfected with reporter plasmids and expression vectors for <i>Mastomys</i> p53 and MnPV E6 or human p53 and HPV16 E6 as a control. Transactivation activity was measured by luminescence (RLU, relative light units). Cells transfected only with p53 served as control and their RLU levels were arbitrarily set to 1 (Mean ± SEM; n = 7; 1way-ANOVA, ***p<0.0001). <b>B)</b> Western blots showing protein levels of p53 and E6 in the lysates of the transactivation assay. Actin served as an internal loading control.</p

Dedifferentiation correlates with positive p53 staining.

<p>Consecutive sections of a poorly differentiated nKSCC were stained with antibodies against E-cadherin, vimentin, pan-Cytokeratin and p53. DAPI was used as nuclear counter stain. Note that in this tumor, only mutation R266C could be detected (Scale bars: 100 μm).</p

Study design and tumor development.

<p><b>A)</b><i>Mastomys coucha</i> as a model for cutaneous papillomavirus infection. In the study, naturally MnPV-infected animals (MnPV⁺) as well as virus-free control animals (MnPV^-) were irradiated three times per week with UVB. The starting dose of 150 mJ/cm² was increased weekly by 50 mJ/cm² until the desired final dose was reached (450, 600 or 800 mJ/cm², respectively). Black arrows indicate an increase of the dose, gray arrows the subsequent application of this dose. The irradiation was continued until the animals were sacrificed or died. <b>B)</b> Kaplan-Meier curves demonstrating the percentage of irradiated virus-infected (MnPV⁺, UV⁺), virus-free (MnPV^-, UV⁺) and unirradiated virus-infected (MnPV⁺, UV^-) tumor-bearing animals. <b>C)</b> Two examples of spontaneous skin lesions arising in naturally infected animals. <b>D)</b> Examples of UV-induced keratinizing SCCs (KSCC) with similarities to human keratoacanthomas. <b>E)</b> Examples of UV-induced non-keratinizing SCCs (nKSCC) (C, D and E: scale bars: 10 mm). <b>F)</b> Number of KSCCs and nKSCCs in correlation with the final UV doses. Note that KSCCs preferentially appeared at the lowest dose, nKSCCs preferentially at higher doses (Mean ± SEM; animal numbers: see <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006723#ppat.1006723.t001" target="_blank">Table 1</a>; av: average number of tumors).</p

p21^WAF1 and Ki-67 levels in the skin of wild-type and K14 HPV38 E6/E7-Tg mice after UVB irradiation.

<p>Wild-type and Tg animals were irradiated up to 5 times as described in Materials and <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002125#s4" target="_blank">Methods</a>. 24 hours after the last irradiation, mice were sacrificed and skin tissue was analyzed by immuno-histochemistry. (A) Representative Ki-67 and p21^WAF1 immunostainings of skin from wild-type and Tg mice non-exposed (0×) or four time (4×) exposed to UVB. (B) Quantification of p21^WAF1 and Ki-67-positive cells in skin of wild-type and Tg mice before and after UVB irradiation. The percentage of p21^WAF1 and Ki-67-positive cells in the epidermis was determined as described in the legend of <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002125#ppat-1002125-g003" target="_blank">Figure 3</a>. The differences between the percentages of p21^WAF1 or Ki-67-positive cells in the HPV38 E6/E7 Tg mice (lines 183 and 187) versus the FVB/N non-Tg mice are statistically significant (* = <i>p</i><0.05, ** = <i>p</i><0,001) as determined by Student's t-test.</p