Association between urinary biomarkers of total sugars intake and measures of obesity in a cross-sectional study

Obesity is an important modifiable risk factor for chronic diseases. While there is increasing focus on the role of dietary sugars, there remains a paucity of data establishing the association between sugar intake and obesity in the general public. The objective of this study was to investigate associations of estimated sugar intake with odds for obesity in a representative sample of English adults. We used data from 434 participants of the 2005 Health Survey of England. Biomarkers for total sugar intake were measured in 24 h urine samples and used to estimate intake. Linear and logistic regression analyses were used to investigate associations between biomarker-based estimated intake and measures of obesity (body mass intake (BMI), waist circumference and waist-to-hip ratio) and obesity risk, respectively. Estimated sugar intake was significantly associated with BMI, waist circumference and waist-to-hip ratio; these associations remained significant after adjustment for estimated protein intake as a marker of non-sugar energy intake. Estimated sugar intake was also associated with increased odds for obesity based on BMI (OR 1.02; 95%CI 1.00-1.04 per 10g), waist-circumference (1.03; 1.01-1.05) and waist-to-hip ratio (1.04; 1.02-1.06); all OR estimates remained significant after adjusting for estimated protein intake. Our results strongly support positive associations between total sugar intake, measures of obesity and likelihood of being obese. It is the first time that such an association has been shown in a nationally-representative sample of the general population using a validated biomarker. This biomarker could be used to monitor the efficacy of public health interventions to reduce sugar intake

The MeerKAT international GHz tiered extragalactic exploration (MIGHTEE) survey

The MIGHTEE large survey project will survey four of the most well-studied extragalactic deep fields, totalling 20 square degrees to µJy sensitivity at Giga-Hertz frequencies, as well as an ultra-deep image of a single ∼1 deg2 MeerKAT pointing. The observations will provide radio continuum, spectral line and polarisation information. As such, MIGHTEE, along with the excellent multi-wavelength data already available in these deep fields, will allow a range of science to be achieved. Specifically, MIGHTEE is designed to significantly enhance our understanding of, (i) the evolution of AGN and star-formation activity over cosmic time, as a function of stellar mass and environment, free of dust obscuration; (ii) the evolution of neutral hydrogen in the Universe and how this neutral gas eventually turns into stars after moving through the molecular phase, and how efficiently this can fuel AGN activity; (iii) the properties of cosmic magnetic fields and how they evolve in clusters, filaments and galaxies. MIGHTEE will reach similar depth to the planned SKA all-sky survey, and thus will provide a pilot to the cosmology experiments that will be carried out by the SKA over a much larger survey volume

The discovery of a z = 0.7092 OH megamaser with the MIGHTEE survey

We present the discovery of the most distant OH megamaser (OHM) to be observed in the main lines, using data from the MeerKAT International Giga-Hertz Tiered Extragalactic Exploration (MIGHTEE) survey. At a newly measured redshift of z = 0.7092, the system has strong emission in both the 1665 MHz (L ≈ 2500 L⊙) and 1667 MHz (L ≈ 4.5 × 104 L⊙) transitions, with both narrow and broad components. We interpret the broad line as a high-velocity-dispersion component of the 1667 MHz transition, with velocity v ∼ 330 km s−1 with respect to the systemic velocity. The host galaxy has a stellar mass of M⋆ = 2.95 × 1010 M⊙ and a star formation rate of SFR = 371 M⊙ yr−1, placing it ∼1.5 dex above the main sequence for star-forming galaxies at this redshift, and can be classified as an ultraluminous infrared galaxy. Alongside the optical imaging data, which exhibit evidence for a tidal tail, this suggests that the OHM arises from a system that is currently undergoing a merger, which is stimulating star formation and providing the necessary conditions for pumping the OH molecule to saturation. The OHM is likely to be lensed, with a magnification factor of ∼2.5, and perhaps more if the maser emitting region is compact and suitably offset relative to the centroid of its host galaxy’s optical light. This discovery demonstrates that spectral line mapping with the new generation of radio interferometers may provide important information on the cosmic merger history of galaxies

Effects of Parasitism and Morphology on Squirrelpox Virus Seroprevalence in Grey Squirrels (Sciurus carolinensis)

Invasive species have been cited as major causes of population extinctions in several animal and plant classes worldwide. The North American grey squirrel (Sciurus carolinensis) has a major detrimental effect on native red squirrel (Sciurus vulgaris) populations across Britain and Ireland, in part because it can be a reservoir host for the deadly squirrelpox virus (SQPV). Whilst various researchers have investigated the epizootiology of SQPV disease in grey squirrels and have modelled the consequent effects on red squirrel populations, less work has examined morphological and physiological characteristics that might make individual grey squirrels more susceptible to contracting SQPV. The current study investigated the putative relationships between morphology, parasitism, and SQPV exposure in grey squirrels. We found geographical, sex, and morphological differences in SQPV seroprevalence. In particular, larger animals, those with wide zygomatic arch widths (ZAW), males with large testes, and individuals with concurrent nematode and/or coccidial infections had an increased seroprevalence of SQPV. In addition, males with larger spleens, particularly those with narrow ZAW, were more likely to be exposed to SQPV. Overall these results show that there is variation in SQPV seroprevalence in grey squirrels and that, consequently, certain individual, or populations of, grey squirrels might be more responsible for transmitting SQPV to native red squirrel populations

Abstract 3421: Comparing gene expression of matched FFPE colorectal cancer samples measured by Nanostring nCounter® platform and Affymetrix GeneChip® Human Transcriptome Array platform

Abstract OBJECTIVE: Due to the lack of clinically annotated fresh frozen tumor samples, defining molecular features that can predict the recurrence of colorectal cancer (CRC) for stage II or stage III patients remains challenging in cancer research. Most available clinical samples are Formalin Fixed and Paraffin Embedded (FFPE). Nanostring nCounter® and Affymetrix GeneChip® Human Transcriptome Array (HTA) are two latest platforms that enable gene expression profiling of FFPE samples. In this study, we evaluated these two platforms for validating the prognostic gene expression signature based on FFPE-derived CRC samples. METHODS: We designed a custom nCounter® codeset based on elements from multiple published prognostic gene signatures for CRC based on frozen tissues and used this platform to measure the gene expression of FFPE-derived CRC tissues passing strict quality control measures. Then, we measured the gene expression of 42 matched FFPE-derived samples on the HTA platform. Gene expression data for matched CRC samples measured by the two platforms were compared. Finally, we compared the previously published prognostic subtype assignments based on gene expression data measured by the two platforms. RESULTS: In total, 42 pairs of matched CRC samples including 31 pairs of technical replicates and 11 pairs of biological replicates measured by both platforms passed the quality control. Our results showed moderate positive correlation of gene expression between matched samples measured by both platforms, which is not correlated with the RNA quality. When comparing the gene expression of patients with metastatic recurrence to that of patients with no recurrence over a 7.4-year mean follow up, we identified 5 differentially expressed genes (SYT17, LRIG1, PTPRJ, BSG, PTEN) in common (p &amp;lt; 0.05) based on both platforms. Subtype analysis assigned Zhu et al.'s subtypes (Zhu, J. et al., PLOS One 2013) to 29 pairs of matched technical replicates measured by both platforms with posterior probability greater than 50%. Overall, we found that the gene expression patterns visualized in the HTA dataset were more consistent within defined subtypes as compared to those of the nCounter dataset and the HTA-based assignments are better supported by the corresponding survival estimates. CONCLUSION: We found a moderate positive correlation between matched samples across both HTA and nCounter platforms, however the gene-by-gene correlations were weak. Both platforms support 5 potential biomarkers of poor prognosis. Discovery of CRC subtypes was more definitive using data from the HTA platform as compared to the nCounter® platform. Further comparisons of matched FFPE-derived CRC tissues across these platforms can lead to the discovery of additional prognostic biomarkers and increased confidence in the optimal platform for expanded clinical trial studies. Citation Format: Jing Zhu, Natasha G. Deane, Keeli B. Lewis, Mary K. Washington, Xi Chen, Robert D. Beauchamp. Comparing gene expression of matched FFPE colorectal cancer samples measured by Nanostring nCounter® platform and Affymetrix GeneChip® Human Transcriptome Array platform. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3421. doi:10.1158/1538-7445.AM2015-3421</jats:p

Colorectal cancer gene expression profiling using nanostring nCounter analysis

3555 Background: A more accurate method of identifying stage 2 and 3 colorectal cancer (CRC) patients at highest risk for recurrence after surgical resection is needed. Gene expression signatures utilizing microarray-derived gene expression data from fresh frozen primary CRCs to predict risk of recurrence have been developed by us and others. Advances in technology platforms for gene expression measurements and their applicability to formalin-fixed, paraffin-embedded (FFPE) specimens offer new opportunity to develop clinically useful diagnostics based on molecular profiles. Methods: 58 patient FFPE samples of all stages stored from 1-12 years were collected from the Vanderbilt GI SPORE Translational Pathology and Imaging Core and annotated with appropriate clinicopathologic data. 414 genes were selected from our 34-gene prognostic classifier and other published CRC gene signatures, as well as gene elements associated with intestinal stem cell biology and epithelial-to-mesenchymal transition (EMT). RNA was extracted from the tumors, and gene expression analysis was completed using the nCounterplatform. Results: Quality of extracted RNA from tumor blocks was similar among the tumors and adequate for analysis. No significant differences were seen in signal strength (p=0.94, Kruskal-Wallis test) or intra-class variation (correlation coefficient = 0.99) across material extracted from new and old blocks. Fold change values for the 70 most highly differentially expressed genes on the nCounter platform correlated well with Affymetrix U133 plus 2 microarray (R2=0.819). Genes associated with EMT clustered according to prognosis, with poorer prognoses seen in patients with high TWIST expression or low E-cadherin and SMAD4 expression. There was a trend toward better survival outcomes with high expression of E-cadherin and SMAD4 (p=0.072, log-rank test). Conclusions: This preliminary study demonstrates the feasibility of this approach to determine gene expression patterns in FFPE tumor tissue samples. Our data suggest that this approach may be applied to identify clinically applicable prognostic gene expression profiles that may be validated in archived patient samples that are well annotated with patient outcome data

Statistical models.

<p>Statistical models used to determine the effects of various morphological features as well as parasitism and sex on SQPV exposure. All models used a binomial distribution and log link function. Abbreviations are denoted as follows: BM = Body mass, SPL = Spleen mass, TES = Mass of testes, ZAW = Zygomatic arch width, SEA = Season, COX = Coccidial burden, NEM = Nematode burden, ECT = Ectoparasite burden, SEX = Sex, “*” = interaction, NS = No significance (p>0.05 for all effects in minimal model).</p

Claudin-1 regulates cellular transformation and metastatic behavior in colon cancer

Disruption of the cell-cell junction with concomitant changes in the expression of junctional proteins is a hallmark of cancer cell invasion and metastasis. The role of adherent junction proteins has been studied extensively in cancer, but the roles of tight junction (TJ) proteins are less well understood. Claudins are recently identified members of the tetraspanin family of proteins, which are integral to the structure and function of TJs. Recent studies show changes in expression/cellular localization of claudins during tumorigenesis; however, a causal relationship between claudin expression/localization and cancer has not been established. Here, we report an increased expression of claudin-1 in human primary colon carcinoma and metastasis and in cell lines derived from primary and metastatic tumors. We also report frequent nuclear localization of claudin-1 in these samples. Genetic manipulations of claudin-1 expression in colon cancer cell lines induced changes in cellular phenotype, with structural and functional changes in markers of epithelial-mesenchymal transition. Furthermore, we demonstrate that changes in claudin-1 expression have significant effects on growth of xenografted tumors and metastasis in athymic mice. We further provide data suggesting that the regulation of E-cadherin expression and β-catenin/Tcf signaling is a possible mechanism underlying claudin-1–dependent changes

Linking patient outcome to high throughput protein expression data identifies novel regulators of colorectal adenocarcinoma aggressiveness [v1; ref status: indexed, http://f1000r.es/5ad]

A key question in cancer systems biology is how to use molecular data to predict the biological behavior of tumors from individual patients. While genomics data have been heavily used, protein signaling data are more directly connected to biological phenotype and might predict cancer phenotypes such as invasion, metastasis, and patient survival. In this study, we mined publicly available data for colorectal adenocarcinoma from the Cancer Genome Atlas and identified protein expression and signaling changes that are statistically associated with patient outcome. Our analysis identified a number of known and potentially new regulators of colorectal cancer. High levels of insulin growth factor binding protein 2 (IGFBP2) were associated with both recurrence and death, and this was validated by immunohistochemical staining of a tissue microarray for a secondary patient dataset. Interestingly, GATA binding protein 3 (GATA3) was the protein most frequently associated with death in our analysis, and GATA3 expression was significantly decreased in tumor samples from stage I-II deceased patients. Experimental studies using engineered colon cancer cell lines show that exogenous expression of GATA3 decreases three-dimensional colony growth and invasiveness of colon cancer cells but does not affect two-dimensional proliferation. These findings suggest that protein data are useful for biomarker discovery and identify GATA3 as a regulator of colorectal cancer  aggressiveness

(A) Distribution of sampling locations across various forests in N.I. (B) Percentage of specimens (± S.E.) found to be positive for squirrelpox virus within each location. Forest locations are denoted as: PG – Portglenone; GF – Gosford; DM – Drum Manor; DB – Drumbanagher; LG – Loughgall; BR – Belvoir; LF – Larchfield; DN – Derrynoyd; LN – Lissan; TM – Tollymore.

<p>(A) Distribution of sampling locations across various forests in N.I. (B) Percentage of specimens (± S.E.) found to be positive for squirrelpox virus within each location. Forest locations are denoted as: PG – Portglenone; GF – Gosford; DM – Drum Manor; DB – Drumbanagher; LG – Loughgall; BR – Belvoir; LF – Larchfield; DN – Derrynoyd; LN – Lissan; TM – Tollymore.</p