Effect modification of air pollution on Urinary 8-Hydroxy-2'-Deoxyguanosine by genotypes: an application of the multiple testing procedure to identify significant SNP interactions

<p>Abstract</p> <p>Background</p> <p>Air pollution is associated with adverse human health, but mechanisms through which pollution exerts effects remain to be clarified. One suggested pathway is that pollution causes oxidative stress. If so, oxidative stress-related genotypes may modify the oxidative response defenses to pollution exposure.</p> <p>Methods</p> <p>We explored the potential pathway by examining whether an array of oxidative stress-related genes (twenty single nucleotide polymorphisms, SNPs in nine genes) modified associations of pollutants (organic carbon (OC), ozone and sulfate) with urinary 8-hydroxy-2-deoxygunosine (8-OHdG), a biomarker of oxidative stress among the 320 aging men. We used a Multiple Testing Procedure in R modified by our team to identify the significance of the candidate genes adjusting for <it>a priori </it>covariates.</p> <p>Results</p> <p>We found that glutathione S-tranferase P1 (GSTP1, rs1799811), M1 and catalase (rs2284367) and group-specific component (GC, rs2282679, rs1155563) significantly or marginally significantly modified effects of OC and/or sulfate with larger effects among those carrying the wild type of GSTP1<it/>, catalase, non-wild type of <it>GC </it>and the non-null of GSTM1.</p> <p>Conclusions</p> <p>Polymorphisms of oxidative stress-related genes modified effects of OC and/or sulfate on 8-OHdG, suggesting that effects of OC or sulfate on 8-OHdG and other endpoints may be through the oxidative stress pathway.</p

What's wrong with the murals at the Mogao Grottoes : a near-infrared hyperspectral imaging method

Although a significant amount of work has been performed to preserve the ancient murals in the Mogao Grottoes by Dunhuang Cultural Research, non-contact methods need to be developed to effectively evaluate the degree of flaking of the murals. In this study, we propose to evaluate the flaking by automatically analyzing hyperspectral images that were scanned at the site. Murals with various degrees of flaking were scanned in the 126th cave using a near-infrared (NIR) hyperspectral camera with a spectral range of approximately 900 to 1700 nm. The regions of interest (ROIs) of the murals were manually labeled and grouped into four levels: normal, slight, moderate, and severe. The average spectral data from each ROI and its group label were used to train our classification model. To predict the degree of flaking, we adopted four algorithms: deep belief networks (DBNs), partial least squares regression (PLSR), principal component analysis with a support vector machine (PCA + SVM) and principal component analysis with an artificial neural network (PCA + ANN). The experimental results show the effectiveness of our method. In particular, better results are obtained using DBNs when the training data contain a significant amount of striping noise

Prevalence of overweight and obesity among Chinese Yi nationality: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Overweight and obesity are considered a serious health problem. There are little data on the prevalence of overweight and obesity among the Yi ethnic group in China. This study aimed to investigate the epidemiologic features of overweight/obesity among Chinese Yi nationality.</p> <p>Methods</p> <p>A cross-sectional study, including 1255 subjects aged 20-75 years, was carried out in Liangshan Yi Autonomous Prefecture of Sichuan province from 2007 to 2008. Overweight/overall obesity was defined by World Health Organization (WHO) or the Working Group on Obesity in China.</p> <p>Results</p> <p>Overall, the prevalence of overweight and obesity was 19.0% and 2.9%, respectively, based on the WHO definition, while it was 21.0% and 7.4%, respectively, according to the Working Group on Obesity in China, which is similar to data reported in the 2002 Chinese National Nutrition and Health Survey. Urban residents had a significantly higher prevalence of obesity (WHO criteria: 4.3% vs 1.7% <it>p </it>= 0.008; China criteria: 11.4% vs 3.7%, <it>p </it>< 0.001) and overweight (WHO criteria: 28.9% vs 8.9% <it>p </it>< 0.001; China criteria: 31.2% vs 10.4%, <it>p </it>< 0.001) than that in rural residents. Older age, a family history of obesity, higher income, drinking and urban residence were significantly associated with an increased risk of overweight/obesity.</p> <p>Conclusions</p> <p>The prevalence of overweight/obesity in the Yi nationality is similar to that in Chinese adults 5 years ago. However, urban residents have a much higher prevalence of overweight/obesity than their rural counterparts. Lifestyle and diet patterns associated with socioeconomic status may explain the difference between urban and rural residents. The prevention of overweight/obesity among urban inhabitants deserves more attention in national health education programs.</p

Tissue Microenvironments Define and Get Reinforced by Macrophage Phenotypes in Homeostasis or during Inflammation, Repair and Fibrosis

Current macrophage phenotype classifications are based on distinct in vitro culture conditions that do not adequately mirror complex tissue environments. In vivo monocyte progenitors populate all tissues for immune surveillance which supports the maintenance of homeostasis as well as regaining homeostasis after injury. Here we propose to classify macrophage phenotypes according to prototypical tissue environments, e.g. as they occur during homeostasis as well as during the different phases of (dermal) wound healing. In tissue necrosis and/or infection, damage- and/or pathogen-associated molecular patterns induce proinflammatory macrophages by Toll-like receptors or inflammasomes. Such classically activated macrophages contribute to further tissue inflammation and damage. Apoptotic cells and antiinflammatory cytokines dominate in postinflammatory tissues which induce macrophages to produce more antiinflammatory mediators. Similarly, tumor-associated macrophages also confer immunosuppression in tumor stroma. Insufficient parenchymal healing despite abundant growth factors pushes macrophages to gain a profibrotic phenotype and promote fibrocyte recruitment which both enforce tissue scarring. Ischemic scars are largely devoid of cytokines and growth factors so that fibrolytic macrophages that predominantly secrete proteases digest the excess extracellular matrix. Together, macrophages stabilize their surrounding tissue microenvironments by adapting different phenotypes as feed-forward mechanisms to maintain tissue homeostasis or regain it following injury. Furthermore, macrophage heterogeneity in healthy or injured tissues mirrors spatial and temporal differences in microenvironments during the various stages of tissue injury and repair. Copyright (C) 2012 S. Karger AG, Base

The role of GRK6 in animal models of Parkinson's Disease and L-DOPA treatment

G protein-coupled Receptor Kinase 6 (GRK6) belongs to a family of kinases that phosphorylate GPCRs. GRK6 levels were found to be altered in Parkinson's Disease (PD) and D2 dopamine receptors are supersensitive in mice lacking GRK6 (GRK6-KO mice). To understand how GRK6 modulates the behavioral manifestations of dopamine deficiency and responses to L-DOPA, we used three approaches to model PD in GRK6-KO mice: 1) the cataleptic response to haloperidol; 2) introducing GRK6 mutation to an acute model of absolute dopamine deficiency, DDD mice; 3) hemiparkinsonian 6-OHDA model. Furthermore, dopamine-related striatal signaling was analyzed by assessing the phosphorylation of AKT/GSK3β and ERK1/2. GRK6 deficiency reduced cataleptic behavior, potentiated the acute effect of L-DOPA in DDD mice, reduced rotational behavior in hemi-parkinsonian mice, and reduced abnormal involuntary movements induced by chronic L-DOPA. These data indicate that approaches to regulate GRK6 activity could be useful in modulating both therapeutic and side-effects of L-DOPA

Less than 5 Netrin-1 molecules initiate attraction but 200 Sema3A molecules are necessary for repulsion

Guidance molecules, such as Sema3A or Netrin-1, induce growth cone (GC) repulsion or attraction. In order to determine the speed of action and efficiency of these guidance cues we developed an experimental procedure to deliver controlled amounts of these molecules. Lipid vesicles encapsulating 10-10 4 molecules of Sema3A or Netrin-1 were manipulated with high spatial and temporal resolution by optical tweezers and their photolysis triggered by laser pulses. Guidance molecules released from the vesicles diffused and reached the GC membrane in a few seconds. Following their arrival, GCs retracted or grew in 20-120 s. By determining the number of guidance molecules trapped inside vesicles and estimating the fraction of guidance molecules reaching the GC, we show that the arrival of less than 5 Netrin-1 molecules on the GC membrane is sufficient to induce growth. In contrast, the arrival of about 200 Sema3A molecules is necessary to induce filopodia repulsion

Reciprocal Interaction between Macrophages and T cells Stimulates IFN-γ and MCP-1 Production in Ang II-induced Cardiac Inflammation and Fibrosis

Background: The inflammatory response plays a critical role in hypertension-induced cardiac remodeling. We aimed to study how interaction among inflammatory cells causes inflammatory responses in the process of hypertensive cardiac fibrosis. Methodology/Principal Findings: Infusion of angiotensin II (Ang II, 1500 ng/kg/min) in mice rapidly induced the expression of interferon c (IFN-c) and leukocytes infiltration into the heart. To determine the role of IFN-c on cardiac inflammation and remodeling, both wild-type (WT) and IFN-c-knockout (KO) mice were infused Ang II for 7 days, and were found an equal blood pressure increase. However, knockout of IFN-c prevented Ang II-induced: 1) infiltration of macrophages and T cells into cardiac tissue; 2) expression of tumor necrosis factor a and monocyte chemoattractant protein 1 (MCP-1), and 3) cardiac fibrosis, including the expression of a-smooth muscle actin and collagen I (all p,0.05). Cultured T cells or macrophages alone expressed very low level of IFN-c, however, co-culture of T cells and macrophages increased IFN-c expression by 19.860.95 folds (vs. WT macrophage, p,0.001) and 20.9 6 2.09 folds (vs. WT T cells, p,0.001). In vitro co-culture studies using T cells and macrophages from WT or IFN-c KO mice demonstrated that T cells were primary source for IFN-c production. Co-culture of WT macrophages with WT T cells, but not with IFN-c-knockout T cells, increased IFN-c production (p,0.01). Moreover, IFN-c produced by T cells amplified MCP-1 expression in macrophages and stimulated macrophag

Importance of incomplete lineage sorting and introgression in the origin of shared genetic variation between two closely related pines with overlapping distributions

Genetic variation shared between closely related species may be due to retention of ancestral polymorphisms because of incomplete lineage sorting (ILS) and/or introgression following secondary contact. It is challenging to distinguish ILS and introgression because they generate similar patterns of shared genetic diversity, but this is nonetheless essential for inferring accurately the history of species with overlapping distributions. To address this issue, we sequenced 33 independent intron loci across the genome of two closely related pine species (Pinus massoniana Lamb. and Pinus hwangshanensis Hisa) from Southeast China. Population structure analyses revealed that the species showed slightly more admixture in parapatric populations than in allopatric populations. Levels of interspecific differentiation were lower in parapatry than in allopatry. Approximate Bayesian computation suggested that the most likely speciation scenario explaining this pattern was a long period of isolation followed by a secondary contact. Ecological niche modeling suggested that a gradual range expansion of P. hwangshanensis during the Pleistocene climatic oscillations could have been the cause of the overlap. Our study therefore suggests that secondary introgression, rather than ILS, explains most of the shared nuclear genomic variation between these two species and demonstrates the complementarity of population genetics and ecological niche modeling in understanding gene flow history. Finally, we discuss the importance of contrasting results from markers with different dynamics of migration, namely nuclear, chloroplast and mitochondrial DNA