Association between ultraviolet radiation,skin sun sensitivity and risk of pancreatic cancer

Background: Ecological studies showing an inverse association between pancreatic cancer incidence and mortality and levels of ultraviolet radiation (UVR), suggest that higher levels of sun exposure may reduce risks of pancreatic cancer but there has been only one individual-level study that examined this issue. We aimed to examine the association between pancreatic cancer and markers of exposure to solar UVR, namely skin type, treatment of skin lesions, ambient UVR and time outdoors on work days. Methods: We used data from an Australian case-control study. Location at birth, residential location during adulthood, outdoors work, history of skin lesion treatment and sensitivity of the skin to the sun were obtained by questionnaire. We limited the analyses to Caucasians who answered the questionnaire about UVR (controls = 589/711 recruited; cases = 496/705 recruited). We used NASA's Total Ozone Mapping Spectrometer to estimate ambient UVR. Results: Being born in or living in areas of higher ambient UVR (compared to lower ambient UVR) was associated with about 30–40% lower risk of pancreatic cancer. People with fair skin colour had 47% lower risk of pancreatic cancer than those with dark skin colour (95% CI 0.37–0.75). There was some suggestion of increased risk with increased average number of hours spent outside at work. Conclusions: This study suggests that people with light skin colour or those born or living in areas of high ambient UVR have lower risk of pancreatic cancer. Our analysis supports an association between UVR and pancreatic cancer, possibly mediated through production of vitamin D.     

Sperm Associated Antigen 9 Plays an Important Role in Bladder Transitional Cell Carcinoma

Background

Majority of bladder cancer deaths are caused due to transitional cell carcinoma (TCC) which is the most prevalent and chemoresistant malignancy of urinary bladder. Therefore, we analyzed the role of Sperm associated antigen 9 (SPAG9) in bladder TCC.

Methodology and Findings

We examined SPAG9 expression and humoral response in 125 bladder TCC patients. Four bladder cancer cell lines were assessed for SPAG9 expression. In addition, we investigated the effect of SPAG9 ablation on cellular proliferation, cell cycle, migration and invasion in UM-UC-3 bladder cancer cells by employing gene silencing approach. Our SPAG9 gene and protein expression analysis revealed SPAG9 expression in 81% of bladder TCC tissue specimens. High SPAG9 expression (>60% SPAG9 positive cells) was found to be significantly associated with superficial non-muscle invasive stage (P = 0.042) and low grade tumors (P = 0.002) suggesting SPAG9 putative role in early spread and tumorigenesis. Humoral response against SPAG9 was observed in 95% of patients found positive for SPAG9 expression. All four bladder cancer cell lines revealed SPAG9 expression. In addition, SPAG9 gene silencing in UM-UC-3 cells resulted in induction of G₀–G₁ arrest characterized by up-regulation of p16 and p21 and consequent down-regulation of cyclin E, cyclin D and cyclin B, CDK4 and CDK1. Further, SPAG9 gene silencing also resulted in reduction in cellular growth, and migration and invasion ability of cancer cells in vitro.

Conclusions

Collectively, our data in clinical specimens indicated that SPAG9 is potential biomarker and therapeutic target for bladder TCC.     

Lead induced antioxidant defense system in pigeon pea and its impact on yield and quality of seeds

Toxic effects of lead (>0.2 mM Pb) were measured in pigeon pea (Cajanus cajan Mill) cv. UPAS grown in sand culture as reduction in growth, yield, and quality of seeds. Leaves containing >38 μg g⁻¹ Pb showed oxidative damage as decrease in chlorophyll content and induction of antioxidants such as carotenoids, proline, and non-protein thiol contents with enhanced activities of SOD and peroxidase. At excess (>0.2 mM) Pb, accumulation of >1,000 μg Pb g⁻¹ root tissue was associated with increase in non-protein thiol content. It is concluded that inhibition in root-to-shoot translocation of Pb and induction in the level of proline, chloroplast pigments, and non-protein thiols and activities of antioxidant enzymes SOD and peroxidase at <0.2 mM Pb could have protected the pigeon pea plants from the deleterious effects of Pb. However, excess Pb at >0.2 mM showed a decline in yield, boldness, and quality of seeds despite the expression of an additional band each of Cu–Zn SOD and peroxidase isoform. The threshold of toxicity and toxicity values in pigeon pea leaves of plants exhibiting 10 and 33% yield depression at 27 days after metal supply were 27 and 56 μg Pb g⁻¹, respectively.     

Wound-dressing materials with antibacterial activity from electrospun polyurethane-dextran nanofiber mats containing ciprofloxacin HCl

Dextran is a versatile biomacromolecule for preparing electrospun nanofibrous membranes by blending with either water-soluble bioactive agents or hydrophobic biodegradable polymers for biomedical applications. In this study, an antibacterial electrospun scaffold was prepared by electrospinning of a solution composed of dextran, polyurethane (PU) and ciprofloxacin HCl (CipHCl) drug. The obtained nanofiber mats have good morphology. The mats were characterized by various analytical techniques. The interaction parameters between fibroblasts and the PU-dextran and PU-dextran-drug scaffolds such as viability, proliferation, and attachment were investigated. The results indicated that the cells interacted favorably with the scaffolds especially the drug-containing one. Moreover, the composite mat showed good bactericidal activity against both of Gram-positive and Gram-negative bacteria. Overall, our results conclude that the introduced scaffold might be an ideal biomaterial for wound dressing applications.     

Gauging triple stores with actual biological data

Background

Identity by descent (IBD) has played a fundamental role in the discovery of genetic loci underlying human diseases. Both pedigree-based and population-based linkage analyses rely on estimating recent IBD, and evidence of ancient IBD can be used to detect population structure in genetic association studies. Various methods for detecting IBD, including those implemented in the soft- ware programs fastIBD and GERMLINE, have been developed in the past several years using population genotype data from microarray platforms. Now, next-generation DNA sequencing data is becoming increasingly available, enabling the comprehensive analysis of genomes, in- cluding identifying rare variants. These sequencing data may provide an opportunity to detect IBD with higher resolution than previously possible, potentially enabling the detection of disease causing loci that were previously undetectable with sparser genetic data.

Results

Here, we investigate how different levels of variant coverage in sequencing and microarray genotype data influences the resolution at which IBD can be detected. This includes microarray genotype data from the WTCCC study, denser genotype data from the HapMap Project, low coverage sequencing data from the 1000 Genomes Project, and deep coverage complete genome data from our own projects. With high power (78%), we can detect segments of length 0.4 cM or larger using fastIBD and GERMLINE in sequencing data. This compares to similar power to detect segments of length 1.0 cM or higher with microarray genotype data. We find that GERMLINE has slightly higher power than fastIBD for detecting IBD segments using sequencing data, but also has a much higher false positive rate.

Conclusion

We further quantify the effect of variant density, conditional on genetic map length, on the power to resolve IBD segments. These investigations into IBD resolution may help guide the design of future next generation sequencing studies that utilize IBD, including family-based association studies, association studies in admixed populations, and homozygosity mapping studies.     

The importance of exposure rate on odds ratios by cigarette smoking and alcohol consumption for esophageal adenocarcinoma and squamous cell carcinoma in the Barrett's Esophagus and Esophageal Adenocarcinoma Consortium

Background: Cigarette smoking is associated with esophageal adenocarcinoma (EAC), esophagogastric junctional adenocarcinoma (EGJA) and esophageal squamous cell carcinoma (ESCC), and alcohol consumption with ESCC. However, no analyses have examined how delivery rate modifies the strength of odds ratio (OR) trends with total exposure, i.e., the impact on the OR for a fixed total exposure of high exposure rate for short duration compared with low exposure rate for long duration. Methods: The authors pooled data from 12 case–control studies from the Barrett's Esophagus and Esophageal Adenocarcinoma Consortium (BEACON), including 1242 (EAC), 1263 (EGJA) and 954 (ESCC) cases and 7053 controls, modeled joint ORs for cumulative exposure and exposure rate for cigarette smoking and alcohol consumption, and evaluated effect modification by sex, body mass index (BMI), age and self-reported acid reflux. Results: For smoking, all sites exhibited inverse delivery rate effects, whereby ORs with pack-years increased, but trends weakened with increasing cigarettes/day. None of the examined factors modified associations, except for ESCC where younger ages at diagnosis enhanced smoking effects (P < 0.01). For EAC and EGJA, ORs with drink-years exhibited inverse associations in <5 drinks/day consumers and no association in heavier consumers. For ESCC, ORs with drink-years increased, with trends strengthening with greater drinks/day. There was no significant effect modification, except for EAC and EGJA where acid reflux mitigated the inverse associations (P = 0.02). For ESCC, younger ages at diagnosis enhanced drinking-related ORs (P < 0.01). Conclusions: Patterns of ORs by pack-years and drink-years, delivery rate effects and effect modifiers revealed common as well as distinct etiologic elements for these diseases.     

Rho GTPase and cAMP/protein kinase A signaling mediates myocilin-induced alterations in cultured human trabecular meshwork cells

Myocilin is a gene linked to the most common form of glaucoma, a major blinding disease. The trabecular meshwork (TM), a specialized eye tissue, is believed to be involved, at least in part, in the development of glaucoma. The myocilin expression is known to be up-regulated by glucocorticoids in TM cells, and an altered myocilin level may be the culprit in conditions such as corticosteroid glaucoma. Wild type myocilin, when transfected into cultured human TM cells, induced a dramatic loss of actin stress fibers and focal adhesions. Myocilin transfectants displayed a heightened sensitivity to trypsin. Adhesion to fibronectin, collagens, and vitronectin was compromised. The fibronectin deposition and the levels of fibronectin protein and mRNA were also reduced in myocilin transfectants. The fibronectin deposition could be restored by treatment with lysophosphatidic acid, a Rho stimulator. Assays further revealed that upon myocilin overexpression, the activity of RhoA was diminished, whereas the cAMP level and the protein kinase A (PKA) activity were augmented. Myocilin protein did not affect actin polymerization. The collapse of actin stress fibers and increased trypsin sensitivity from myocilin transfection could be reverted by co-expression of constitutively active RhoA or by treatment with PKA inhibitor H-89. The PKA activity, however, was not modified by co-expression of either constitutively active or dominant negative RhoA. These results demonstrate that myocilin has a de-adhesive activity and triggers signaling events. cAMP/PKA activation and the downstream Rho inhibition are possible mechanisms by which myocilin in overabundance may lead to TM cell or tissue damage.     

Characterization and phylogenetic analysis of ectoine biosynthesis genes from <Emphasis Type="Italic">Bacillus halodurans</Emphasis>

Ectoine, a cyclic tetrahydropyrimidine (2-methyl-1,4,5,6-tetrahydropyrimidine-4-carboxylic acid), is a natural compound, which serves as a protective substance in many bacterial cells. In this study, the putative ectABC gene cluster from Bacillus halodurans was heterologously expressed in E. coli and the production of ectoine was confirmed by HPLC analysis. The activity of the enzymes coded by the ectA, B and C genes were found to be higher in induced transgenic cells compared to the uninduced cells. Phylogenetic analysis revealed sequence identities ranging from 36–73% for ectA gene, 55–81% for ectB gene and 55–80% for ectC gene indicating that the enzymes are evolutionarily well conserved.     

Isolation and characterization of Dechlorospirillum anomalous strain JB116 from a sewage treatment plant

The dissimilatory perchlorate reducers mainly belong to two monophyletic groups, viz. Dechloromonas and Azospira in the beta subclass of Proteobacteria. The present study describes isolation and genetic characterization of Dechlorospirillum anomalous strain JB116 that belongs to alpha subclass of Proteobacteria. The strain JB116 was isolated under facultative anaerobic conditions on a growth medium containing sodium perchlorate and sodium acetate as electron (e(-)) acceptor and e(-) donor, respectively. The strain is a spirillum shaped, dissimilatory perchlorate and nitrate reducer that prefers nitrate to perchlorate. It grows heterotrophically with acetate at temperatures between 25-35 degrees C, NaCl concentrations between 0-0.5% and pH of 7-7.8. The strain JB116 is the second only representative strain within D. anomalous that shares 99% 16S rDNA sequence similarity with the type strain D. anomalous strain WD.     

Molecular fingerprinting of Salmonella enterica subsp. enterica Typhimurium and Salmonella enterica subsp. enterica derby isolated from tropical seafood in South India

Salmonella enterica subsp. enterica Typhimurium and Salmonella enterica subsp. enterica Derby strains isolated from different seafood were genotyped by PCR-ribotyping and ERIC-PCR assays. This study has ascertained the genetic relatedness among serovars prevalent in tropical seafood. PCR-ribotyping exhibited genetic variation in both Salmonella serovars, and ribotype profile (II) was most predominant, which was observed in 10/18 of Salmonella enterica subsp. enterica Typhimurium and 7/17 Salmonella enterica subsp. enterica Derby isolates. Cluster analysis of ERIC-PCR for Salmonella enterica subsp. enterica Typhimurium strains exhibited nine different banding patterns and four strains showed >95% genetic homology within the cluster pairs. ERIC-PCR produced more genetic variations in Salmonella enterica subsp. enterica Typhimurium; nevertheless, both methods were found to be comparable for Salmonella enterica subsp. enterica Derby isolates. Discrimination index of PCR-ribotyping for Salmonella enterica subsp. enterica Typhimurium isolates was obtained at 0.674 and index value 0.714 was observed for Salmonella enterica subsp. enterica Derby strains. Molecular fingerprinting investigation highlighted the hypothesis of diverse routes of Salmonella contamination in seafood as multiple clones of Salmonella enterica subsp. enterica Typhimurium and Salmonella enterica subsp. enterica Derby were detected in same or different seafood throughout the study period.