Methanethiol, dimethyl sulfide and acetone over biologically productive waters in the southwest Pacific Ocean

Atmospheric methanethiol (MeSHa), dimethyl sulfide (DMSa) and acetone (acetonea) were measured over biologically productive frontal waters in the remote southwest Pacific Ocean in summertime 2012 during the Surface Ocean Aerosol Production (SOAP) voyage. MeSHa mixing ratios varied from below the detection limit (<10ppt) up to 65ppt and were 3%–36% of parallel DMSa mixing ratios. MeSHa and DMSa were correlated over the voyage(R2=0.3,slope=0.07)with a stronger correlation over a coccolithophore-dominated phytoplankton bloom (R2= 0.5, slope 0.13). The diurnal cycle for MeSHa shows similar behaviour to DMSa with mixing ratios varying by a factor of ∼2 according to time of day with the minimum levels of both MeSHa and DMSa occurring at around 16:00LT (local time, all times in this paper are in local time). A positive flux of MeSH out of the ocean was calculated for three different nights and ranged from 3.5 to 5.8µmolm−2 d−1, corresponding to 14%–24% of the DMS flux (MeSH/(MeSH+DMS)). Spearman rank correlations with ocean biogeochemical parameters showed a moderate to-strong positive, highly significant relationship between both MeSHa and DMSa with seawater DMS (DMSsw) and a moderate correlation with total dimethylsulfoniopropionate (total DMSP). A positive correlation of acetonea with water temperature and negative correlation with nutrient concentrations are consistent with reports of acetone production in warmer subtropical waters. Positive correlations of acetonea with cryptophyte and eukaryotic phytoplankton numbers, and high-molecular-weight sugars and chromophoric dissolved organic matter (CDOM), suggest an organic source. This work points to a significant ocean source of MeSH, highlighting the need for further studies into the distribution and fate of MeSH, and it suggests links between atmospheric acetone levels and biogeochemistry over the midlatitude ocean. In addition, an intercalibration of DMSa at ambient levels using three independently calibrated instruments showed ∼15%–25% higher mixing ratios from an atmospheric pressure ionisation chemical ionisation mass spectrometer (mesoCIMS) compared to a gas chromatograph with a sulfurchemiluminescencedetector(GC-SCD)and proton transfer reaction mass spectrometer (PTR-MS). Some differences were attributed to the DMSa gradient above the sea surface and differing approaches of integrated versus discrete measurements. Remaining discrepancies were likely due to different calibrationscales,suggesting that further investigation of the stability and/or absolute calibration of DMSstandards used at sea is warranted

Cimetidine in colorectal cancer – are the effects immunological or adhesion-mediated?

British Journal of Cancer (2002) 86, 159–160. DOI: 10.1038/sj/bjc/6600097 www.bjcancer.co

Crowdsourcing for translational research: analysis of biomarker expression using cancer microarrays

Background: Academic pathology suffers from an acute and growing lack of workforce resource. This especially impacts on translational elements of clinical trials, which can require detailed analysis of thousands of tissue samples. We tested whether crowdsourcing – enlisting help from the public – is a sufficiently accurate method to score such samples. Methods: We developed a novel online interface to train and test lay participants on cancer detection and immunohistochemistry scoring in tissue microarrays. Lay participants initially performed cancer detection on lung cancer images stained for CD8, and we measured how extending a basic tutorial by annotated example images and feedback-based training affected cancer detection accuracy. We then applied this tutorial to additional cancer types and immunohistochemistry markers – bladder/ki67, lung/EGFR, and oesophageal/CD8 – to establish accuracy compared with experts. Using this optimised tutorial, we then tested lay participants’ accuracy on immunohistochemistry scoring of lung/EGFR and bladder/p53 samples. Results: We observed that for cancer detection, annotated example images and feedback-based training both improved accuracy compared with a basic tutorial only. Using this optimised tutorial, we demonstrate highly accurate (>0.90 area under curve) detection of cancer in samples stained with nuclear, cytoplasmic and membrane cell markers. We also observed high Spearman correlations between lay participants and experts for immunohistochemistry scoring (0.91 (0.78, 0.96) and 0.97 (0.91, 0.99) for lung/EGFR and bladder/p53 samples, respectively). Conclusions: These results establish crowdsourcing as a promising method to screen large data sets for biomarkers in cancer pathology research across a range of cancers and immunohistochemical stains

Physical and mental health comorbidity is common in people with multiple sclerosis: nationally representative cross-sectional population database analysis

&lt;b&gt;Background&lt;/b&gt; Comorbidity in Multiple Sclerosis (MS) is associated with worse health and higher mortality. This study aims to describe clinician recorded comorbidities in people with MS. &lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; 39 comorbidities in 3826 people with MS aged ≥25 years were compared against 1,268,859 controls. Results were analysed by age, gender, and socioeconomic status, with unadjusted and adjusted Odds Ratios (ORs) calculated using logistic regression. &lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; People with MS were more likely to have one (OR 2.44; 95% CI 2.26-2.64), two (OR 1.49; 95% CI 1.38-1.62), three (OR 1.86; 95% CI 1.69-2.04), four or more (OR 1.61; 95% CI 1.47-1.77) non-MS chronic conditions than controls, and greater mental health comorbidity (OR 2.94; 95% CI 2.75-3.14), which increased as the number of physical comorbidities rose. Cardiovascular conditions, including atrial fibrillation (OR 0.49; 95% CI 0.36-0.67), chronic kidney disease (OR 0.51; 95% CI 0.40-0.65), heart failure (OR 0.62; 95% CI 0.45-0.85), coronary heart disease (OR 0.64; 95% CI 0.52-0.71), and hypertension (OR 0.65; 95% CI 0.59-0.72) were significantly less common in people with MS. &lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion&lt;/b&gt; People with MS have excess multiple chronic conditions, with associated increased mental health comorbidity. The low recorded cardiovascular comorbidity warrants further investigation

Somatic mutant clones colonize the human esophagus with age.

The extent to which cells in normal tissues accumulate mutations throughout life is poorly understood. Some mutant cells expand into clones that can be detected by genome sequencing. We mapped mutant clones in normal esophageal epithelium from nine donors (age range, 20 to 75 years). Somatic mutations accumulated with age and were caused mainly by intrinsic mutational processes. We found strong positive selection of clones carrying mutations in 14 cancer genes, with tens to hundreds of clones per square centimeter. In middle-aged and elderly donors, clones with cancer-associated mutations covered much of the epithelium, with NOTCH1 and TP53 mutations affecting 12 to 80% and 2 to 37% of cells, respectively. Unexpectedly, the prevalence of NOTCH1 mutations in normal esophagus was several times higher than in esophageal cancers. These findings have implications for our understanding of cancer and aging.Wellcome Trust Cancer Research U

Gastric emptying following Finney pyloroplasty and vagotomy

Gastric emptying was evaluated in a series of unanesthetized dogs in the intact state, following Finney pyloroplasty, and with the addition of vagotomy. Sodium chromate labeled test meals of glucose, trisodium citrate, and trisodium citrate-fat were used. Finney pyloroplasty resulted in a trend for delayed emptying of fat from the stomach. The trisodium citrate test meal increased the levels of gastric secretion after pyloroplasty.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44373/1/10620_2005_Article_BF02239291.pd

Multiple organism algorithm for finding ultraconserved elements

<p>Abstract</p> <p>Background</p> <p>Ultraconserved elements are nucleotide or protein sequences with 100% identity (no mismatches, insertions, or deletions) in the same organism or between two or more organisms. Studies indicate that these conserved regions are associated with micro RNAs, mRNA processing, development and transcription regulation. The identification and characterization of these elements among genomes is necessary for the further understanding of their functionality.</p> <p>Results</p> <p>We describe an algorithm and provide freely available software which can find all of the ultraconserved sequences between genomes of multiple organisms. Our algorithm takes a combinatorial approach that finds all sequences without requiring the genomes to be aligned. The algorithm is significantly faster than BLAST and is designed to handle very large genomes efficiently. We ran our algorithm on several large comparative analyses to evaluate its effectiveness; one compared 17 vertebrate genomes where we find 123 ultraconserved elements longer than 40 bps shared by all of the organisms, and another compared the human body louse, <it>Pediculus humanus humanus</it>, against itself and select insects to find thousands of non-coding, potentially functional sequences.</p> <p>Conclusion</p> <p>Whole genome comparative analysis for multiple organisms is both feasible and desirable in our search for biological knowledge. We argue that bioinformatic programs should be forward thinking by assuming analysis on multiple (and possibly large) genomes in the design and implementation of algorithms. Our algorithm shows how a compromise design with a trade-off of disk space versus memory space allows for efficient computation while only requiring modest computer resources, and at the same time providing benefits not available with other software.</p

The impact of pesticide suicide on the geographic distribution of suicide in Taiwan: a spatial analysis

<p>Abstract</p> <p>Background</p> <p>Pesticide self-poisoning is the most commonly used suicide method worldwide, but few studies have investigated the national epidemiology of pesticide suicide in countries where it is a major public health problem. This study aims to investigate geographic variations in pesticide suicide and their impact on the spatial distribution of suicide in Taiwan.</p> <p>Methods</p> <p>Smoothed standardized mortality ratios for pesticide suicide (2002-2009) were mapped across Taiwan's 358 districts (median population aged 15 or above = 27 000), and their associations with the size of agricultural workforce were investigated using Bayesian hierarchical models.</p> <p>Results</p> <p>In 2002-2009 pesticide poisoning was the third most common suicide method in Taiwan, accounting for 13.6% (4913/36 110) of all suicides. Rates were higher in agricultural East and Central Taiwan and lower in major cities. Almost half (47%) of all pesticide suicides occurred in areas where only 13% of Taiwan's population lived. The geographic distribution of overall suicides was more similar to that of pesticide suicides than non-pesticide suicides. Rural-urban differences in suicide were mostly due to pesticide suicide. Areas where a higher proportion of people worked in agriculture showed higher pesticide suicide rates (adjusted rate ratio [ARR] per standard deviation increase in the proportion of agricultural workers = 1.58, 95% Credible Interval [CrI] 1.44-1.74) and overall suicide rates (ARR = 1.06, 95% CrI 1.03-1.10) but lower non-pesticide suicide rates (ARR = 0.91, 95% CrI 0.87-0.95).</p> <p>Conclusion</p> <p>Easy access to pesticides appears to influence the geographic distribution of suicide in Taiwan, highlighting the potential benefits of targeted prevention strategies such as restricting access to highly toxic pesticides.</p

WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear Β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector Β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.Peer reviewe

Molecular analysis of representative Streptococcus gordonii Spp phase variants reveals no differences in the glucosyltransferase structural gene, gtfG

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73398/1/j.1399-302X.1997.tb00622.x.pd