Use of N,N -dimethyl- p -phenylenediamine to Evaluate the Oxidative Status of Human Plasma

Oxidative stress has been clearly implicated in human disease by a growing body of scientific evidences. There is no ideal method for the measurement of this parameter. A possible strategy would be to measure simultaneously several biomarkers representing damage to different cellular components or, alternatively, a method able to evaluate the hydroperoxides, intermediate products of oxidation originating from different classes of molecules, such as lipids, peptides, amino acids, etc. can be used. We are introducing a simple, rapid and inexpensive assay to measure the oxidative status of human plasma. It is based on the properties of N, N -dimethyl- p -phenylenediamine (DMPD), a compound able to produce a fairly long-lived radical cation. The absorbance at 505 nm of a DMPD solution in the presence of plasma, which is proportional to the amount of hydroperoxyl compounds, is related to the oxidative status of the sample and could be expressed as hydrogen peroxide equivalents (HPE). This assay was not influenced by freezing-thawing and storage time of the plasma samples. The assay can be automated, performed in a kinetic mode, and used for routine analyses. The DMPD assay alone or in combination with analytical methods for assessing antioxidant capacity is suggested as a reliable tool to obtain information in pathologies related to oxidative stress.     

Temporal variability is a personalized feature of the human microbiome

Background

It is now apparent that the complex microbial communities found on and in the human body vary across individuals. What has largely been missing from previous studies is an understanding of how these communities vary over time within individuals. To the extent to which it has been considered, it is often assumed that temporal variability is negligible for healthy adults. Here we address this gap in understanding by profiling the forehead, gut (fecal), palm, and tongue microbial communities in 85 adults, weekly over 3 months.

Results

We found that skin (forehead and palm) varied most in the number of taxa present, whereas gut and tongue communities varied more in the relative abundances of taxa. Within each body habitat, there was a wide range of temporal variability across the study population, with some individuals harboring more variable communities than others. The best predictor of these differences in variability across individuals was microbial diversity; individuals with more diverse gut or tongue communities were more stable in composition than individuals with less diverse communities.

Conclusions

Longitudinal sampling of a relatively large number of individuals allowed us to observe high levels of temporal variability in both diversity and community structure in all body habitats studied. These findings suggest that temporal dynamics may need to be considered when attempting to link changes in microbiome structure to changes in health status. Furthermore, our findings show that, not only is the composition of an individual’s microbiome highly personalized, but their degree of temporal variability is also a personalized feature.

Electronic supplementary material

The online version of this article (doi:10.1186/s13059-014-0531-y) contains supplementary material, which is available to authorized users.     

The Personal Human Oral Microbiome Obscures the Effects of Treatment on Periodontal Disease

Periodontitis is a progressive disease of the periodontium with a complex, polymicrobial etiology. Recent Next-Generation Sequencing (NGS) studies of the microbial diversity associated with periodontitis have revealed strong, community-level differences in bacterial assemblages associated with healthy or diseased periodontal sites. In this study, we used NGS approaches to characterize changes in periodontal pocket bacterial diversity after standard periodontal treatment. Despite consistent changes in the abundance of certain taxa in individuals whose condition improved with treatment, post-treatment samples retained the highest similarity to pre-treatment samples from the same individual. Deeper phylogenetic analysis of periodontal pathogen-containing genera Prevotella and Fusobacterium found both unexpected diversity and differential treatment response among species. Our results highlight how understanding interpersonal variability among microbiomes is necessary for determining how polymicrobial diseases respond to treatment and disturbance.     

Deconvolution of pigment and physiologically related photochemical reflectance index variability at the canopy scale over an entire growing season

The sensitivity of the photochemical reflectance index (PRI) to leaf pigmentation and its impacts on its potential as a proxy for light‐use efficiency (LUE) have recently been shown to be problematic at the leaf scale. Most leaf‐to‐leaf and seasonal variability can be explained by such a confounding effect. This study relies on the analysis of PRI light curves that were generated at the canopy scale under natural conditions to derive a precise deconvolution of pigment‐related and physiologically related variability in the PRI. These sources of variability were explained by measured or estimated physiologically relevant variables, such as soil water content, that can be used as indicators of water availability and canopy chlorophyll content. The PRI mainly reflected the variability in the pigment content of the canopy. However, the corrected PRI, which was obtained by subtracting the pigment‐related seasonal variability from the PRI measurement, was highly correlated with the upscaled LUE measurements. Moreover, the sensitivity of the PRI to the leaf pigment content may mask the PRI versus LUE relationship or result in an artificial relationship that reflects the relationship of chlorophyll versus LUE, depending on the species phenology.     

Host-associated and free-living phage communities differ profoundly in phylogenetic composition

Phylogenetic profiling has been widely used for comparing bacterial communities, but has so far been impossible to apply to viruses because of the lack of a single marker gene analogous to 16S rRNA. Here we developed a reference tree approach for matching viral sequences and applied it to the largest viral datasets available. The resulting technique, Shotgun UniFrac, was used to compare host-associated and non-host-associated phage communities (130 total metagenomes), and revealed a profound split similar to that found with bacterial communities. This new informatics approach complements analysis of bacterial communities and promises to provide new insights into viral community dynamics, such as top-down versus bottom-up control of bacterial communities by viruses in a range of systems.     

Helicobacter pylori seropositivity and risk of lung cancer

Lung cancer is the leading cause of cancer mortality worldwide. Helicobacter pylori (H. pylori) is a risk factor for distal stomach cancer, and a few small studies have suggested that H. pylori may be a potential risk factor for lung cancer. To test this hypothesis, we conducted a study of 350 lung adenocarcinoma cases, 350 squamous cell carcinoma cases, and 700 controls nested within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) cohort of male Finnish smokers. Controls were one-to-one matched by age and date of baseline serum draw. Using enzyme-linked immunosorbent assays to detect immunoglobulin G antibodies against H. pylori whole-cell and cytotoxin-associated gene (CagA) antigens, we calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations between H. pylori seropositivity and lung cancer risk using conditional logistic regression. H. pylori seropositivity was detected in 79.7% of cases and 78.5% of controls. After adjusting for pack-years and cigarettes smoked per day, H. pylori seropositivity was not associated with either adenocarcinoma (OR: 1.1, 95% CI: 0.75-1.6) or squamous cell carcinoma (OR: 1.1, 95% CI: 0.77-1.7). Results were similar for CagA-negative and CagA-positive H. pylori seropositivity. Despite earlier small studies suggesting that H. pylori may contribute to lung carcinogenesis, H. pylori seropositivity does not appear to be associated with lung cancer.     

Large-scale pathway-based analysis of bladder cancer genome-wide association data from five studies of European background

Pathway analysis of genome-wide association studies (GWAS) offer a unique opportunity to collectively evaluate genetic variants with effects that are too small to be detected individually. We applied a pathway analysis to a bladder cancer GWAS containing data from 3,532 cases and 5,120 controls of European background (n = 5 studies). Thirteen hundred and ninety-nine pathways were drawn from five publicly available resources (Biocarta, Kegg, NCI-PID, HumanCyc, and Reactome), and we constructed 22 additional candidate pathways previously hypothesized to be related to bladder cancer. In total, 1421 pathways, 5647 genes and ∼90,000 SNPs were included in our study. Logistic regression model adjusting for age, sex, study, DNA source, and smoking status was used to assess the marginal trend effect of SNPs on bladder cancer risk. Two complementary pathway-based methods (gene-set enrichment analysis [GSEA], and adapted rank-truncated product [ARTP]) were used to assess the enrichment of association signals within each pathway. Eighteen pathways were detected by either GSEA or ARTP at P≤0.01. To minimize false positives, we used the I² statistic to identify SNPs displaying heterogeneous effects across the five studies. After removing these SNPs, seven pathways (‘Aromatic amine metabolism’ [P_GSEA = 0.0100, P_ARTP = 0.0020], ‘NAD biosynthesis’ [P_GSEA = 0.0018, P_ARTP = 0.0086], ‘NAD salvage’ [P_ARTP = 0.0068], ‘Clathrin derived vesicle budding’ [P_ARTP = 0.0018], ‘Lysosome vesicle biogenesis’ [P_GSEA = 0.0023, P_ARTP<0.00012], ’Retrograde neurotrophin signaling’ [P_GSEA = 0.00840], and ‘Mitotic metaphase/anaphase transition’ [P_GSEA = 0.0040]) remained. These pathways seem to belong to three fundamental cellular processes (metabolic detoxification, mitosis, and clathrin-mediated vesicles). Identification of the aromatic amine metabolism pathway provides support for the ability of this approach to identify pathways with established relevance to bladder carcinogenesis.     

Sediment accumulation predicts the distribution of a unionid mussel (Elliptio complanata) in nearshore areas of a Canadian Shield lake

1. The importance of native freshwater mussels for ecosystem processes depends on their density, size distribution and activity. In lakes, many of the factors that affect mussels (fish hosts, habitat, food) could be directly or indirectly related to wind‐driven physical processes. 2. We tested whether the abundance and size of Elliptio complanata in the shallow, nearshore areas of a medium‐sized lake were related to site exposure, substratum type and fish distribution. To disentangle some of the correlated variables known to affect mussel distribution, we used paired exposed and sheltered sampling sites along the 7‐km fetch of the lake basin. 3. The distribution of sediment characteristics in nearshore areas was highly predictable. The mean depth of accumulated soft sediments decreased with increasing fetch at wind‐exposed sites, but increased with increasing fetch at sheltered sites. Sediments were deeper along the main shoreline than around islands. Deeper sediments tended to be finer and higher in silt content and organic fraction. 4. The density and proportion of juvenile mussels along the main shoreline varied in a unimodal way with sediment depth. These results suggest that wind‐driven physical forces affect the transport of young juveniles to sediment depositional areas and create sediment conditions that influence their growth and survival. In contrast, the proportion of juvenile mussels around islands was not related to sediment characteristics, but decreased with remoteness of the island, suggesting that the distribution of juvenile mussels may be limited by fish movements. These results are tentative since they do not include buried juvenile mussels. 5. We also found a unimodal relationship between total mussel density (juveniles and adults) and sediment depth but, in contrast to the relationship for juveniles only, it applied to all sites with soft sediments, including islands. We conclude that factors related to sediment depth affect the growth and survival of adult mussels around islands and that these factors are strong enough to modify the pattern of distribution established via dispersal during earlier life stages. 6. The mean shell length of adults at different sites within the lake basin ranged from 60 to 85 mm. Mussel shell length decreased with increasing fetch at sites exposed to the prevalent winds, but was relatively constant on the sheltered side of peninsulas and islands. The size of unionid mussels in different parts of the lake seems to be determined both by their exposure to physical forces and by sediments. 7. The local distribution of E. complanata is determined, directly and indirectly, by wind‐driven forces. These processes are likely to be important for other benthic organisms affected by similar habitat conditions (e.g. sediment characteristics, physical disturbance).     

Mood Disorders and Risk of Lung Cancer in the EAGLE Case-Control Study and in the U.S. Veterans Affairs Inpatient Cohort

Background

Mood disorders may affect lung cancer risk. We evaluated this hypothesis in two large studies.

Methodology/Principal Findings

We examined 1,939 lung cancer cases and 2,102 controls from the Environment And Genetics in Lung cancer Etiology (EAGLE) case-control study conducted in Italy (2002–2005), and 82,945 inpatients with a lung cancer diagnosis and 3,586,299 person-years without a lung cancer diagnosis in the U.S. Veterans Affairs Inpatient Cohort (VA study), composed of veterans with a VA hospital admission (1969–1996). In EAGLE, we calculated odds ratios (ORs) and 95% confidence intervals (CI), with extensive adjustment for tobacco smoking and multiple lifestyle factors. In the VA study, we estimated lung cancer relative risks (RRs) and 95% CIs with time-dependent Poisson regression, adjusting for attained age, calendar year, hospital visits, time within the study, and related previous medical diagnoses. In EAGLE, we found decreased lung cancer risk in subjects with a personal history of mood disorders (OR: 0.59, 95% CI: 0.44–0.79, based on 121 lung cancer incident cases and 192 controls) and family history of mood disorders (OR: 0.62, 95% CI: 0.50–0.77, based on 223 lung cancer cases and 345 controls). The VA study analyses yielded similar results (RR: 0.74, 95% CI: 0.71–0.77, based on 2,304 incident lung cancer cases and 177,267 non-cancer person-years) in men with discharge diagnoses for mood disorders. History of mood disorders was associated with nicotine dependence, alcohol and substance use and psychometric scales of depressive and anxiety symptoms in controls for these studies.

Conclusions/Significance

The consistent finding of a relationship between mood disorders and lung cancer risk across two large studies calls for further research into the complex interplay of risk factors associated with these two widespread and debilitating diseases. Although we adjusted for smoking effects in EAGLE, residual confounding of the results by smoking cannot be ruled out.