The IDENTIFY study: the investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer - a multicentre observational study

Objective To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation. Patients and Methods This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries. Results Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3–34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1–30.2), UTUC (n = 128) 1.14% (95% CI 0.77–1.52), renal cancer (n = 107) 1.05% (95% CI 0.80–1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32–2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03–1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90–4.15; P < 0.001), male sex 1.30 (95% CI 1.14–1.50; P < 0.001), and smoking 2.70 (95% CI 2.30–3.18; P < 0.001). Conclusions A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer

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Not AvailableCodon is the basic unit for biological message transmission during synthesis of proteins in an organism. Codon Usage Bias is preferential usage among synonymous codons, in an organisms. This preferential use of a synonymous codon was found not only among species but also occurs among genes within the same genome of a species. This variation of codon usage patterns are controlled by natural processes such as mutation, drift and pressure. In this study, we have used computational as well as statistical techniques for finding codon usage bias and codon context pattern of Salinibacter ruber (extreme halophilic), Chromohalobacter salexigens (moderate halophilic) and Rhizobium etli (nonhalophilic). In addition to this, compositional variation in translated amino acid frequency, effective number of codons and optimal codons were also studied. A plot of ENc versus GC3s suggests that both mutation bias and translational selection contribute to these differences of codon bias. However, mutation bias is the driving force of the synonymous codon usage patterns in halophilic bacteria (Salinibacter ruber and Chromohalobacter salexigens) and translational selection seems to affect codon usage pattern in non-halophilic bacteria (Rhizobium etli). Correspondence analysis of Relative Synonymous Codon Usage revealed different clusters of genes varying in numbers in the bacteria under study. Moreover, codon context pattern was also seen variable in these bacteria. These results clearly indicate the variation in the codon usage pattern in these bacterial genomes.Not Availabl

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Not AvailableThe degeneracy of the genetic code allows for multiple codons to encode the same amino acid. However, alternative codons and amino acids are used unevenly among genes, a phenomenon termed codon-usage bias. Genes regulating amino acid biosynthesis of Salinibacter ruber, an extremely halophilic bacterium were studied in order to determine the synonymous codon usage patterns. Factors responsible for codon usage variation among the genes were investigated using codon usage indices and multi-variate statistical approach. Overall codon usage data analysis indicated that codons ending in G and/or C were predominant among the genes. Multi-variate statistical analysis showed that there was a single major trend in the codon usage variation among the genes, which had a strong positive correlation (r = 0.93, P < 0.01) with (G + C) content of the genes. Further, correlation analysis indicated that genes with higher expression level and showing a greater degree of codon usage bias were GC-rich and preferred codons with C or G nucleotides at the third position. A set of thirteen codons were identified through Chi-square test as optimal codons, which were preferred in highly expressed genes. It could be concluded that mutational bias had a profound effect on codon usage pattern. In addition, translational selections also operated with a proper balance, making the genes translationally more efficient. The frequency of these codons appeared to be correlated with the level of gene expression and might be a useful indicator in the case of genes (or open-reading-frames) whose expression levels are unknown.Not Availabl

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Not AvailableCodon is the basic unit for biological message transmission during synthesis of proteins in an organism. Codon Usage Bias is preferential usage among synonymous codons, in an organisms. This preferential use of a synonymous codon was found not only among species but also occurs among genes within the same genome of a species. This variation of codon usage patterns are controlled by natural processes such as mutation, drift and pressure. In this study, we have used computational as well as statistical techniques for finding codon usage bias and codon context pattern of Salinibacter ruber (extreme halophilic), Chromohalobacter salexigens (moderate halophilic) and Rhizobium etli (nonhalophilic). In addition to this, compositional variation in translated amino acid frequency, effective number of codons and optimal codons were also studied. A plot of ENc versus GC3s suggests that both mutation bias and translational selection contribute to these differences of codon bias. However, mutation bias is the driving force of the synonymous codon usage patterns in halophilic bacteria (Salinibacter ruber and Chromohalobacter salexigens) and translational selection seems to affect codon usage pattern in non-halophilic bacteria (Rhizobium etli). Correspondence analysis of Relative Synonymous Codon Usage revealed different clusters of genes varying in numbers in the bacteria under study. Moreover, codon context pattern was also seen variable in these bacteria. These results clearly indicate the variation in the codon usage pattern in these bacterial genomes.Not Availabl

Expression analysis of genes responsible for amino acid biosynthesis in halophilic bacterium <i style="mso-bidi-font-style:normal">Salinibacter ruber</i>

177-185The degeneracy of the genetic code allows for multiple codons to encode the same amino acid. However, alternative codons and amino acids are used unevenly among genes, a phenomenon termed codon-usage bias. Genes regulating amino acid biosynthesis of Salinibacter ruber, an extremely halophilic bacterium were studied in order to determine the synonymous codon usage patterns. Factors responsible for codon usage variation among the genes were investigated using codon usage indices and multi-variate statistical approach. Overall codon usage data analysis indicated that codons ending in G and/or C were predominant among the genes. Multi-variate statistical analysis showed that there was a single major trend in the codon usage variation among the genes, which had a strong positive correlation (r = 0.93, P<0.01) with (G + C) content of the genes. Further, correlation analysis indicated that genes with higher expression level and showing a greater degree of codon usage bias were GC-rich and preferred codons with C or G nucleotides at the third position. A set of thirteen codons were identified through Chi-square test as optimal codons, which were preferred in highly expressed genes. It could be concluded that mutational bias had a profound effect on codon usage pattern. In addition, translational selections also operated with a proper balance, making the genes translationally more efficient. The frequency of these codons appeared to be correlated with the level of gene expression and might be a useful indicator in the case of genes (or open-reading-frames) whose expression levels are unknown. </span

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Not AvailableBacteria from genus Rhizobium have ability to fix atmospheric nitrogen in symbiosis with leguminous plants resulting in formation of root nodules. They act as an alternate source of nitrogenous fertilizers. The study of codon usage patterns of Rhizobium species is gaining increasing attention over the times. In the present study three strains of Rhizobium namely Sinorhizobium meliloti 1021, Bradyrhizobium japonicum USDA110 and Rhizobium tropici CIAT899 whose complete genome sequence are available were retrieved from NCBI for the analysis of codon usage. The overall codon usage analysis showed that codons ending with G and C are preferred more in the rhizobium genome than codon ending with A and T. ENc plot revealed that compositional constraints along with translational selection are the major cause of codon usage bias. Correspondence analysis (COA) showed that the variation in codon usage is accounted mainly by the first two axes. From the Pearson correlation analysis significant correlation was identified among the first axis of COA and Codon adaptation index (CAI) and other factors of codon usage bias. 17 optimal codons were identified that were shared among these three strains.Not Availabl

Molecular Docking and Isothermal calorimetry experiments.

<p>(<b>A</b>) <b>Docking modes of l-serine with MtSerB2</b>. l-serine was docked against the binding sites predicted in the ACTI and ACTII domains respectively. Interactions of l-serine with ACTI (<i>top</i>) and ACTII (<i>bottom</i>) domains are shown here. Key interacting residues are labeled in <i>black</i> and shown in stick representation while the rest of the site is shown in cartoon representation. l-serine is depicted in ball- and-stick representation. (<b>B</b>) <b>ITC experiments involving interactions of l-serine with MtSerB2</b>. Titration of l-serine (300 µM) into MtSerB2 solution (30 µM). The experiments were performed in 50 mM sodium phosphate buffer, pH 7.4, and 50 mM NaCl and 2 mM β mercaptoethanol at 25°C. The cell volume was 1.43 ml while the injection volume was 6 µl.</p

Determination of K_m and K_cat values for l-phosphoserine.

<p>Michaelis-Menten plots calculated using l-phosphoserine as the substrate, for (<b>A</b>) MtSerB2 and (<b>B</b>) PSPD respectively. Inset shows double-reciprocal plots of the initial velocities (1/Vo) against the reciprocal of l-phosphoserine phosphate. The experiment was performed in triplicate and the values represent their average.</p

Size exclusion chromatography experiments involving MtSerB2, its mutants and l-serine.

<p>(<b>A</b>) <b>Wildtype SerB2</b> (<b>B</b>) <b>D341N</b> (<b>C</b>) <b>G18A</b> (D) <b>G108A</b>. Chromatogram in the absence of l-serine is in <i>black</i>, whereas the chromatogram in the presence of of l-serine, and MtSerB2 and its mutants, are shown in grey. Wild-type MtSerB2 and D341N show a shift to the tetrameric/higher order oligomeric forms in the presence of ∼0.8 molar ratio of l-serine.</p