Effect of 3d element substitution on inter- and intragrain critical temperatures in (bi,pb):2223 system

The inter- and intragrain critical temperatures are differently affected by the natur and concentration of the 3d substituent (Fe,Ni,Zn) for Cu. Decrease of these temperatures is in agreement with the increase in residual resistivity.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Thermoelectric and thermomagnetic effects of (B1.6Pb0.4) Sr2Ca2Cu3Ox thin films

Measurements of resistivity, Nernst, Seebeck and Hall effects of Bi2223 epitaxial thin films for magnetic fields between 0 and 5T and temperature range 5-300 K are reported.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Sox2 Cooperates with Lkb1 Loss in a Mouse Model of Squamous Cell Lung Cancer

Squamous cell carcinoma (SCC) of the lung is the second most common subtype of lung cancer. With limited treatment options, the 5-year survival rate of SCC is only 15%. Although genomic alterations in SCC have been characterized, identifying the alterations that drive SCC is critical for improving treatment strategies. Mouse models of SCC are currently limited. Using lentiviral delivery of Sox2 specifically to the mouse lung, we tested the ability of Sox2 to promote tumorigenesis in multiple tumor suppressor backgrounds. Expression of Sox2, frequently amplified in human SCC, specifically cooperates with loss of Lkb1 to promote squamous lung tumors. Mouse tumors exhibit characteristic histopathology and biomarker expression similar to human SCC. They also mimic human SCCs by activation of therapeutically relevant pathways including STAT and mTOR. This model may be utilized to test the contribution of additional driver alterations in SCC, as well as for preclinical drug discovery

RNA Sequencing of Sessile Serrated Colon Polyps Identifies Differentially Expressed Genes and Immunohistochemical Markers

<div><p>Background</p><p>Sessile serrated adenomas/polyps (SSA/Ps) may account for 20–30% of colon cancers. Although large SSA/Ps are generally recognized phenotypically, small (<1 cm) or dysplastic SSA/Ps are difficult to differentiate from hyperplastic or small adenomatous polyps by endoscopy and histopathology. Our aim was to define the comprehensive gene expression phenotype of SSA/Ps to better define this cancer precursor.</p><p>Results</p><p>RNA sequencing was performed on 5′ capped RNA from seven SSA/Ps collected from patients with the serrated polyposis syndrome (SPS) versus eight controls. Highly expressed genes were analyzed by qPCR in additional SSA/Ps, adenomas and controls. The cellular localization and level of gene products were examined by immunohistochemistry in syndromic and sporadic SSA/Ps, adenomatous and hyperplastic polyps and controls. We identified 1,294 differentially expressed annotated genes, with 106 increased ≥10-fold, in SSA/Ps compared to controls. Comparing these genes with an array dataset for adenomatous polyps identified 30 protein coding genes uniquely expressed ≥10-fold in SSA/Ps. Biological pathways altered in SSA/Ps included mucosal integrity, cell adhesion, and cell development. Marked increased expression of <i>MUC17</i>, the cell junction protein genes <i>VSIG1</i> and <i>GJB5</i>, and the antiapoptotic gene <i>REG4</i> were found in SSA/Ps, relative to controls and adenomas, were verified by qPCR analysis of additional SSA/Ps (n = 21) and adenomas (n = 10). Immunohistochemical staining of syndromic (n≥11) and sporadic SSA/Ps (n≥17), adenomatous (n≥13) and hyperplastic (n≥10) polyps plus controls (n≥16) identified unique expression patterns for VSIG1 and MUC17 in SSA/Ps.</p><p>Conclusion</p><p>A subset of genes and pathways are uniquely increased in SSA/Ps, compared to adenomatous polyps, thus supporting the concept that cancer develops by different pathways in these phenotypically distinct polyps with markedly different gene expression profiles. Immunostaining for a subset of these genes differentiates both syndromic and sporadic SSA/Ps from adenomatous and hyperplastic polyps.</p></div

Demographics of Serrated Polyposis Syndrome Patients.

<p>History and colonoscopy details of patients with serrated polyposis syndrome. Only polyps with the serrated histopathology are reported. None of the patients had colon cancer. FH = Family History.</p

Top 50 gene transcripts increased by RNA sequencing in sessile serrated polyps (SSA/P) in serrated polyposis patients compared to controls.

<p>Fold change is reported for seven right-sided sessile serrated polyps, from five serrated polyposis patients (age 26–62 years, 3 female and 2 male), compared to surrounding uninvolved colon and normal colon from healthy volunteers (controls, n = 8). Fold-change (Fold) and false discovery rate (FDR) for specific gene sequencing reads are provided (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088367#s2" target="_blank">Methods</a>). The fold change and FDR in sex matched adenomatous polyps (AP) (age 55–79 years, three right-sided and four left-sided) with low dysplasia compared to uninvolved colon (n = 7) from a previous microarray study are provided (Sabates-Bellver, et al., 2007). Genes with an asterisk have not been previously reported to be differentially expressed in SSA/Ps. “na” denotes transcripts not analyzed in the microarray study.</p

Differentially expressed genes in sessile serrated adenoma/polyps (SSA/Ps) by RNA sequencing (RNA-seq) and microarray analyses.

<p><b>Panel A</b>. RNA-seq analysis identified 1294 genes (875 increased, 419 decreased) that were significantly differentially expressed (fold change ≥1.5, FDR<0.05) in SSA/Ps as compared to control colon biopsies. Differentially expressed genes in SSA/Ps that were found by RNA-seq analysis (red) and those found in a microarray study (green; 101 total, 59 increased, 42 decreased) are shown in the Venn diagram (23). <b>Panel B</b>. Hierarchical clustering of the differentially expressed genes in Panel A. Note: only 782 genes could be compared in the hierarchical clustering analysis because fewer genes were interrogated in the microarray analysis. <b>Panel C</b>. Hierarchical clustering of differentially expressed genes in SSA/Ps identified by RNA-seq analysis and in adenomatous polyps (APs) identified by microarray analysis (24). 136 genes (75 increased, 61 decreased) with a fold change ≥10 and FDR of <0.05 from both datasets were compared. Four distinct clusters are shown, cluster 1 represents genes increased in only SSA/Ps, cluster 2 represents genes increased in both SSA/Ps and APs, cluster 3 represents genes decreased only in APs, and cluster 4 represents genes decreased in both SSA/Ps and APs. Note: the full range of fold change is not reflected in color bar scale, the maximum fold change in RNA-seq analysis was 582-fold (<i>MUC5AC</i>) in SSA/Ps and 208-fold (<i>GCG</i>) in APs by microarray analysis.</p

Immunohistochemical analysis of different serrated and adenomatous polyp types for proteins encoded by genes found to be highly differentially expressed in SSA/Ps.

*<p>The number of polyp or normal colonic specimens that showed positive immunohistochemical staining (IHC) over the total number of independent samples examined are shown. The intensity of IHC staining was scored 0 (none) to 4 (maximal). See Pathologic Classification in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088367#s2" target="_blank">Methods</a> for the criteria used to select polyps for study.</p

Immunostaining for VSIG1, MUC17, CTSE and TFF2 in control colon, SSA/Ps, hyperplastic and adenomatous polyps.

<p>Representative images of immunoperoxidase staining with affinity purified polyclonal antibodies and formalin-fixed, paraffin-embedded biopsies of patient matched and normal control colon (Panel A, n = 15, see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088367#s2" target="_blank">Methods</a>), syndromic SSA/Ps (Panel B, n = 10), sporadic SSA/Ps (Panel C, n = 15), hyperplastic polyps (Panel D, n = 10) and adenomatous polyps (Panel E, n = 10) are shown. Representative immunohistochemical stains for REG4 in control and polyp specimens are provided in Figure S2 in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088367#pone.0088367.s001" target="_blank">File S1</a>.</p

Expression of mucin 17 (<i>MUC17</i>), V-set and immunoglobulin domain containing 1 (<i>VSIG1</i>), gap junction protein, beta 5 (<i>GJB5</i>) and regenerating islet-derived family member 4 (<i>REG4</i>) in SSA/Ps, adenomatous polyps (APs) and controls as measured by RNA-seq analysis.

<p><b>Panel A1</b>. <i>MUC17</i> RNA-seq results. The y-axis represents the number of uniquely mapped sequencing reads per kilobase of transcript length per million total reads (RPKM) mapped to the <i>MUC17</i> locus. The x-axis represents the chromosome (Chr) 7 coordinates and gene structure of the <i>MUC17</i> transcript. Analysis showed an 82-fold increase in <i>MUC17</i> mRNA in SSA/Ps (red, n = 7 polyps) compared to uninvolved colon (patient matched uninvolved, blue, n = 6) and control colon (screening colon without polyps; green, n = 2). The sequencing read length was 50 base pairs. <b>Panel A2</b>. <i>MUC17</i> expression measured by qPCR analysis in SSA/Ps, adenomatous polyps and controls in additional patients. Relative mRNA levels of <i>MUC17</i> in large (>1 cm) and small (<1 cm) SSA/Ps (n = 21), adenomatous polyps (n = 10), uninvolved colon and normal control colon biopsies (n = 10 each) are shown. In small and large SSA/Ps, <i>MUC17</i> expression was increased by 38 and 71-fold, respectively, compared to controls. qPCR results were normalized to β-actin. The average <i>MUC17</i> expression level in uninvolved colon tissue was chosen as the baseline. P-values were calculated using the Mann-Whitney U-test. <b>Panel B1</b>. <i>VSIG1</i> (Chr X) RNA-seq results. A 106-fold increase in expression of <i>VSIG1</i> was found in SSA/Ps as compared to controls. <b>Panel B2</b>. <i>VSIG1</i> qPCR results. In small and large SSA/Ps, <i>VSIG1</i> expression was increased 969 and 1393-fold, respectively. <b>Panel C1</b>. <i>GJB5</i> (Chr 1) RNA-seq results. A 27-fold increase in <i>GJB5</i> mRNA was found in SSA/Ps. <b>Panel C2</b>. <i>GJB5</i> qPCR results. In small and large SSA/Ps, <i>GJB5</i> expression was increased 446 and 523-fold, respectively. <b>Panel D1</b>. <i>REG4</i> (Chr 1) RNA-seq results. An 87-fold increase in <i>REG4</i> mRNA was found in SSA/Ps. <b>Panel D2</b>. <i>REG4</i> qPCR results. In small and large SSA/Ps, <i>REG4</i> mRNA was increased 68 and 116-fold, respectively.</p