Twinning superlattices in indium phosphide nanowires

Here, we show that we control the crystal structure of indium phosphide (InP) nanowires by impurity dopants. We have found that zinc decreases the activation barrier for 2D nucleation growth of zinc-blende InP and therefore promotes the InP nanowires to crystallise in the zinc blende, instead of the commonly found wurtzite crystal structure. More importantly, we demonstrate that we can, by controlling the crystal structure, induce twinning superlattices with long-range order in InP nanowires. We can tune the spacing of the superlattices by the wire diameter and the zinc concentration and present a model based on the cross-sectional shape of the zinc-blende InP nanowires to quantitatively explain the formation of the periodic twinning.Comment: 18 pages, 4 figure

The Role of Osteopontin (OPN/SPP1) Haplotypes in the Susceptibility to Crohn's Disease

Osteopontin represents a multifunctional molecule playing a pivotal role in chronic inflammatory and autoimmune diseases. Its expression is increased in inflammatory bowel disease (IBD). The aim of our study was to analyze the association of osteopontin (OPN/SPP1) gene variants in a large cohort of IBD patients. Genomic DNA from 2819 Caucasian individuals (n = 841 patients with Crohn's disease (CD), n = 473 patients with ulcerative colitis (UC), and n = 1505 healthy unrelated controls) was analyzed for nine OPN SNPs (rs2728127, rs2853744, rs11730582, rs11739060, rs28357094, rs4754 = p.Asp80Asp, rs1126616 = p.Ala236Ala, rs1126772 and rs9138). Considering the important role of osteopontin in Th17-mediated diseases, we performed analysis for epistasis with IBD-associated IL23R variants and analyzed serum levels of the Th17 cytokine IL-22. For four OPN SNPs (rs4754, rs1126616, rs1126772 and rs9138), we observed significantly different distributions between male and female CD patients. rs4754 was protective in male CD patients (p = 0.0004, OR = 0.69). None of the other investigated OPN SNPs was associated with CD or UC susceptibility. However, several OPN haplotypes showed significant associations with CD susceptibility. The strongest association was found for a haplotype consisting of the 8 OPN SNPs rs2728127-rs2853744-rs11730582-rs11439060-rs28357094-rs112661-rs1126772-rs9138 (omnibus p-value = 2.07×10⁻⁸). Overall, the mean IL-22 secretion in the combined group of OPN minor allele carriers with CD was significantly lower than that of CD patients with OPN wildtype alleles (p = 3.66×10⁻⁵). There was evidence for weak epistasis between the OPN SNP rs28357094 with the IL23R SNP rs10489629 (p = 4.18×10⁻²) and between OPN SNP rs1126616 and IL23R SNP rs2201841 (p = 4.18×10⁻²) but none of these associations remained significant after Bonferroni correction. Our study identified OPN haplotypes as modifiers of CD susceptibility, while the combined effects of certain OPN variants may modulate IL-22 secretion

Analysis of IL12B Gene Variants in Inflammatory Bowel Disease

IL12B encodes the p40 subunit of IL-12, which is also part of IL-23. Recent genome-wide association studies identified IL12B and IL23R as susceptibility genes for inflammatory bowel disease (IBD). However, the phenotypic effects and potential gene-gene interactions of IL12B variants are largely unknow

The value of age and medical history for predicting colorectal cancer and adenomas in people referred for colonoscopy

<p>Abstract</p> <p>Background</p> <p>Colonoscopy is an invasive and costly procedure with a risk of serious complications. It would therefore be useful to prioritise colonoscopies by identifying people at higher risk of either cancer or premalignant adenomas. The aim of this study is to assess a model that identifies people with colorectal cancer, advanced, large and small adenomas.</p> <p>Methods</p> <p>Patients seen by gastroenterologists and colorectal surgeons between April 2004 and December 2006 completed a validated, structured self-administered questionnaire prior to colonoscopy. Information was collected on symptoms, demographics and medical history. Multinomial logistic regression was used to simultaneously assess factors associated with findings on colonoscopy of cancer, advanced adenomas and adenomas sized 6 -9 mm, and ≤ 5 mm. The area under the curve of ROC curve was used to assess the incremental gain of adding demographic variables, medical history and symptoms (in that order) to a base model that included only age.</p> <p>Results</p> <p>Sociodemographic variables, medical history and symptoms (from 8,204 patients) jointly provide good discrimination between colorectal cancer and no abnormality (AUC 0.83), but discriminate less well between adenomas and no abnormality (AUC advanced adenoma 0.70; other adenomas 0.67). Age is the dominant risk factor for cancer and adenomas of all sizes. Having a colonoscopy within the last 10 years confers protection for cancers and advanced adenomas.</p> <p>Conclusions</p> <p>Our models provide guidance about which factors can assist in identifying people at higher risk of disease using easily elicited information. This would allow colonoscopy to be prioritised for those for whom it would be of most benefit.</p

rs1004819 Is the Main Disease-Associated IL23R Variant in German Crohn's Disease Patients: Combined Analysis of IL23R, CARD15, and OCTN1/2 Variants

The IL23R gene has been identified as a susceptibility gene for inflammatory bowel disease (IBD) in the North American population. The aim of our study was to test this association in a large German IBD cohort and to elucidate potential interactions with other IBD genes as well as phenotypic consequences of IL23R variants. Genomic DNA from 2670 Caucasian individuals including 833 patients with Crohn's disease (CD), 456 patients with ulcerative colitis (UC), and 1381 healthy unrelated controls was analyzed for 10 IL23R SNPs. Genotyping included the NOD2 variants p.Arg702Trp, p.Gly908Arg, and p.Leu1007fsX1008 and polymorphisms in SLC22A4/OCTN1 (1672 C-->T) and SLC22A5/OCTN2 (-207 G-->C). All IL23R gene variants analyzed displayed highly significant associations with CD. The strongest association was found for the SNP rs1004819 [P = 1.92x10(-11); OR 1.56; 95 % CI (1.37-1.78)]. 93.2% of the rs1004819 TT homozygous carriers as compared to 78% of CC wildtype carriers had ileal involvement [P = 0.004; OR 4.24; CI (1.46-12.34)]. The coding SNP rs11209026 (p.Arg381Gln) was protective for CD [P = 8.04x10(-8); OR 0.43; CI (0.31-0.59)]. Similar, but weaker associations were found in UC. There was no evidence for epistasis between the IL23R gene and the CD susceptibility genes CARD15 and SLC22A4/5. IL23R is an IBD susceptibility gene, but has no epistatic interaction with CARD15 and SLC22A4/5. rs1004819 is the major IL23R variant associated with CD in the German population, while the p.Arg381Gln IL23R variant is a protective marker for CD and UC

Gene Expression Profiles from Formalin Fixed Paraffin Embedded Breast Cancer Tissue Are Largely Comparable to Fresh Frozen Matched Tissue

BACKGROUND AND METHODS: Formalin Fixed Paraffin Embedded (FFPE) samples represent a valuable resource for cancer research. However, the discovery and development of new cancer biomarkers often requires fresh frozen (FF) samples. Recently, the Whole Genome (WG) DASL (cDNA-mediated Annealing, Selection, extension and Ligation) assay was specifically developed to profile FFPE tissue. However, a thorough comparison of data generated from FFPE RNA and Fresh Frozen (FF) RNA using this platform is lacking. To this end we profiled, in duplicate, 20 FFPE tissues and 20 matched FF tissues and evaluated the concordance of the DASL results from FFPE and matched FF material. METHODOLOGY AND PRINCIPAL FINDINGS: We show that after proper normalization, all FFPE and FF pairs exhibit a high level of similarity (Pearson correlation >0.7), significantly larger than the similarity between non-paired samples. Interestingly, the probes showing the highest correlation had a higher percentage G/C content and were enriched for cell cycle genes. Predictions of gene expression signatures developed on frozen material (Intrinsic subtype, Genomic Grade Index, 70 gene signature) showed a high level of concordance between FFPE and FF matched pairs. Interestingly, predictions based on a 60 gene DASL list (best match with the 70 gene signature) showed very high concordance with the MammaPrint® results. CONCLUSIONS AND SIGNIFICANCE: We demonstrate that data generated from FFPE material with the DASL assay, if properly processed, are comparable to data extracted from the FF counterpart. Specifically, gene expression profiles for a known set of prognostic genes for a specific disease are highly comparable between two conditions. This opens up the possibility of using both FFPE and FF material in gene expressions analyses, leading to a vast increase in the potential resources available for cancer research

The diagnostic value of ultrasonography-derived edema of the temporal artery wall in giant cell arteritis: a second meta-analysis

<p>Abstract</p> <p>Background</p> <p>Ultrasonography of temporal arteries is not commonly used in the approach of patients with suspected giant cell arteritis (GCA) in clinical practice. A meta-analysis of primary studies available through April 2004 concluded that ultrasonography could indeed be helpful in diagnosing GCA. We specifically re-examined the diagnostic value of the ultrasonography-derived halo sign, a dark hypoechoic circumferential thickening around the artery lumen, indicating vasculitic wall edema, in GCA.</p> <p>Methods</p> <p>Original, prospective studies in patients with suspected GCA that examined ultrasonography findings of temporal arteries using the ACR 1990 classification criteria for GCA as reference standard, published through 2009, were identified. Only eight studies involving 575 patients, 204 of whom received the final diagnosis of GCA, fulfilled technical quality criteria for ultrasound. Weighted sensitivity and specificity estimates of the halo sign were assessed, their possible heterogeneity was investigated and pooled diagnostic odds ratio was determined.</p> <p>Results</p> <p>Unilateral halo sign achieved an overall sensitivity of 68% (95% CI, 0.61-0.74) and specificity of 91% (95% CI, 0.88-0.94) for GCA. The values of inconsistency coefficient (I²) of both sensitivity and specificity of the halo sign, showed significant heterogeneity concerning the results between studies. Pooled diagnostic odds ratio, expressing how much greater the odds of having GCA are for patients with halo sign than for those without, was 34 (95% CI, 8.21-138.23). Diagnostic odds ratio was further increased to 65 (95% CI, 17.86-236.82) when bilateral halo signs were present (sensitivity/specificity of 43% and 100%, respectively). In both cases, it was found that DOR was constant across studies.</p> <p>Conclusion</p> <p>Temporal artery edema demonstrated as halo sign should be always looked for in ultrasonography when GCA is suspected. Providing that currently accepted technical quality criteria are fulfilled, halo sign's sensitivity and specificity are comparable to those of autoantibodies used as diagnostic tests in rheumatology. Validation of revised GCA classification criteria which will include the halo sign may be warranted.</p

TNFRSF1B +676 T>G polymorphism predicts survival of non-Small cell lung cancer patients treated with chemoradiotherapy

<p>Abstract</p> <p>Background</p> <p>The dysregulation of gene expression in the TNF-TNFR superfamily has been involved in various human cancers including non-small cell lung cancer (NSCLC). Furthermore, functional polymorphisms in <it>TNF-α </it>and <it>TNFRSF1B </it>genes that alter gene expression are likely to be associated with risk and clinical outcomes of cancers. However, few reported studies have investigated the association between potentially functional SNPs in both <it>TNF-α </it>and <it>TNFRSF1B </it>and prognosis of NSCLC patients treated with chemoradiotherapy.</p> <p>Methods</p> <p>We genotyped five potentially functional polymorphisms of <it>TNF-α </it>and <it>TNFRSF1B </it>genes [<it>TNF-α </it>-308 G>A (rs1800629) and -1031 T>C (rs1799964); <it>TNFRSF1B </it>+676 T>G (rs1061622), -1709A>T(rs652625) and +1663A>G (rs1061624)] in 225 NSCLC patients treated with chemoradiotherapy or radiotherapy alone. Kaplan-Meier survival analysis, log-rank tests and Cox proportional hazard models were used to evaluate associations between these variants and NSCLC overall survival (OS).</p> <p>Results</p> <p>We found that the <it>TNFRSF1B </it>+676 GG genotype was associated with a significantly better OS of NSCLC (GG <it>vs. </it>TT: adjusted HR = 0.38, 95% CI = 0.15-0.94; GG <it>vs. </it>GT/TT: adjusted HR = 0.35, 95% CI = 0.14-0.88). Further stepwise multivariate Cox regression analysis showed that the <it>TNFRSF1B </it>+676 GG was an independent prognosis predictor in this NSCLC cohort (GG <it>vs. </it>GT/TT: HR = 0.35, 95% CI = 0.14-0.85), in the presence of node status (N_2-3<it>vs. </it>N_0-1: HR = 1.60, 95% CI = 1.09-2.35) and tumor stage (T_3-4<it>vs. </it>T_0-2: HR = 1.48, 95% CI = 1.08-2.03).</p> <p>Conclusions</p> <p>Although the exact biological function for this SNP remains to be explored, our findings suggest a possible role of <it>TNFRSF1B </it>+676 T>G (rs1061622) in the prognosis of NSCLC. Further large and functional studies are needed to confirm our findings.</p

Interaction of Crohn's Disease Susceptibility Genes in an Australian Paediatric Cohort

Genetic susceptibility is an important contributor to the pathogenesis of Crohn's disease (CD). We investigated multiple CD susceptibility genes in an Australian paediatric onset CD cohort. Newly diagnosed paediatric onset CD patients (n = 72) and controls (n = 98) were genotyped for 34 single nucleotide polymorphisms (SNPs) in 18 genetic loci. Gene-gene interaction analysis, gene-disease phenotype analysis and genetic risk profiling were performed for all SNPs and all genes. Of the 34 SNPs analysed, four polymorphisms on three genes (NOD2, IL23R, and region 3p21) were significantly associated with CD status (p<0.05). All three CD specific paediatric polymorphisms on PSMG1 and TNFRSF6B showed a trend of association with p<0.1. An additive gene-gene interaction involving TLR4, PSMG1, TNFRSF6B and IRGM was identified with CD. Genes involved in microbial processing (TLR4, PSMG1, NOD2) were significantly associated either at the individual level or in gene-gene interactive roles. Colonic disease was significantly associated with disease SNP rs7517847 (IL23R) (p<0.05) and colonic and ileal/colonic disease was significantly associated with disease SNP rs125221868 (IBD5) and SLC22A4 & SLC22A4/5 variants (p<0.05). We were able to demonstrate genetic association of several genes to CD in a paediatric onset cohort. Several of the observed associations have not been reported previously in association with paediatric CD patients. Our findings demonstrate that CD genetic susceptibility in paediatric patients presents as a complex interaction between numerous genes