Genetic variations in APPL2 are associated with overweight and obesity in a Chinese population with normal glucose tolerance

<p>Abstract</p> <p>Background</p> <p>APPL1 and APPL2 are two adaptor proteins, which can mediate adiponectin signaling via binding to N terminus of adiponectin receptors in muscle cells. Genes encoding adiponectin and adiponectin receptors contribute to insulin resistance and the risk of obesity, and genetic variants of <it>APPL1 </it>are associated with body fat distribution. However, the association between genetic variations of <it>APPL2 </it>and metabolic traits remains unknown. In the current study, we aimed to test the impacts of <it>APPL2 </it>genetic variants on obesity in a Chinese population with normal glucose tolerance.</p> <p>Methods</p> <p>We genotyped six single nucleotide polymorphisms (SNPs) in <it>APPL2 </it>in 1,808 non-diabetic subjects. Overweight and obesity were defined by body mass index (BMI). Obesity-related anthropometric parameters were measured, including height, weight, waist circumference, hip circumference. BMI and waist-hip ratio (WHR) were calculated.</p> <p>Results</p> <p>We found significant evidence of association with overweight/obesity for rs2272495 and rs1107756. rs2272495 C allele and rs1107756 T allele both conferred a higher risk of being overweight and obese (OR 1.218, 95% CI 1.047-1.416, <it>p </it>= 0.011 for rs2272495; OR 1.166, 95% CI 1.014-1.341, <it>p </it>= 0.031 for rs1107756). After adjusting multiple comparisons, only the effect of rs2272495 on overweight/obesity remained to be significant (empirical <it>p </it>= 0.043). Moreover, we investigated the effects of these SNPs on obesity-related quantitative traits in all participants. rs2272495 was associated with BMI (<it>p </it>= 0.015), waist circumference (<it>p </it>= 0.006), hip circumference (<it>p </it>= 0.025) as well as WHR (<it>p </it>= 0.047) under a recessive model. Similar associations were found for rs1107756 except for WHR.</p> <p>Conclusion</p> <p>This study suggests that genetic variations in <it>APPL2 </it>are associated with overweight and obesity in Chinese population with normal glucose tolerance.</p

Lack of association between genetic polymorphisms within DUSP12 - ATF6 locus and glucose metabolism related traits in a Chinese population

<p>Abstract</p> <p>Background</p> <p>Genome-wide linkage studies in multiple ethnic populations found chromosome 1q21-q25 was the strongest and most replicable linkage signal in the human chromosome. Studies in Pima Indian, Caucasians and African Americans identified several SNPs in <it>DUSP12 </it>and <it>ATF6</it>, located in chromosome 1q21-q23, were associated with type 2 diabetes.</p> <p>Methods</p> <p>We selected 19 single nucleotide polymorphisms (SNPs) that could tag 98% of the SNPs with minor allele frequencies over 0.1 within <it>DUSP12-ATF6 </it>region. These SNPs were genotyped in a total of 3,700 Chinese Han subjects comprising 1,892 type 2 diabetes patients and 1,808 controls with normal glucose regulation.</p> <p>Results</p> <p>None of the SNPs and haplotypes showed significant association to type 2 diabetes in our samples. No association between the SNPs and quantitative traits was observed either.</p> <p>Conclusions</p> <p>Our data suggests common SNPs within <it>DUSP12</it>-<it>ATF6 </it>locus may not play a major role in glucose metabolism in the Chinese.</p

Genome structure of cotton revealed by a genome-wide SSR genetic map constructed from a BC1 population between gossypium hirsutum and G. barbadense

<p>Abstract</p> <p>Background</p> <p>Cotton, with a large genome, is an important crop throughout the world. A high-density genetic linkage map is the prerequisite for cotton genetics and breeding. A genetic map based on simple polymerase chain reaction markers will be efficient for marker-assisted breeding in cotton, and markers from transcribed sequences have more chance to target genes related to traits. To construct a genome-wide, functional marker-based genetic linkage map in cotton, we isolated and mapped expressed sequence tag-simple sequence repeats (EST-SSRs) from cotton ESTs derived from the A₁, D₅, (AD)₁, and (AD)₂genome.</p> <p>Results</p> <p>A total of 3177 new EST-SSRs developed in our laboratory and other newly released SSRs were used to enrich our interspecific BC₁genetic linkage map. A total of 547 loci and 911 loci were obtained from our EST-SSRs and the newly released SSRs, respectively. The 1458 loci together with our previously published data were used to construct an updated genetic linkage map. The final map included 2316 loci on the 26 cotton chromosomes, 4418.9 cM in total length and 1.91 cM in average distance between adjacent markers. To our knowledge, this map is one of the three most dense linkage maps in cotton. Twenty-one segregation distortion regions (SDRs) were found in this map; three segregation distorted chromosomes, Chr02, Chr16, and Chr18, were identified with 99.9% of distorted markers segregating toward the heterozygous allele. Functional analysis of SSR sequences showed that 1633 loci of this map (70.6%) were transcribed loci and 1332 loci (57.5%) were translated loci.</p> <p>Conclusions</p> <p>This map lays groundwork for further genetic analyses of important quantitative traits, marker-assisted selection, and genome organization architecture in cotton as well as for comparative genomics between cotton and other species. The segregation distorted chromosomes can be a guide to identify segregation distortion loci in cotton. The annotation of SSR sequences identified frequent and rare gene ontology items on each chromosome, which is helpful to discover functions of cotton chromosomes.</p

Liquid marble-derived solid-liquid hybrid superparticles for CO2 capture.

The design of effective CO2 capture materials is an ongoing challenge. Here we report a concept to overcome current limitations associated with both liquid and solid CO2 capture materials by exploiting a solid-liquid hybrid superparticle (SLHSP). The fabrication of SLHSP involves assembly of hydrophobic silica nanoparticles on the liquid marble surface, and co-assembly of hydrophilic silica nanoparticles and tetraethylenepentamine within the interior of the liquid marble. The strong interfacial adsorption force and the strong interactions between amine and silica are identified to be key elements for high robustness. The developed SLHSPs exhibit excellent CO2 sorption capacity, high sorption rate, long-term stability and reduced amine loss in industrially preferred fixed bed setups. The outstanding performances are attributed to the unique structure which hierarchically organizes the liquid and solid at microscales

The AMT1 Arginine Methyltransferase Gene Is Important for Plant Infection and Normal Hyphal Growth in Fusarium graminearum

Arginine methylation of non-histone proteins by protein arginine methyltransferase (PRMT) has been shown to be important for various biological processes from yeast to human. Although PRMT genes are well conserved in fungi, none of them have been functionally characterized in plant pathogenic ascomycetes. In this study, we identified and characterized all of the four predicted PRMT genes in Fusarium graminearum, the causal agent of Fusarium head blight of wheat and barley. Whereas deletion of the other three PRMT genes had no obvious phenotypes, the Δamt1 mutant had pleiotropic defects. AMT1 is a predicted type I PRMT gene that is orthologous to HMT1 in Saccharomyces cerevisiae. The Δamt1 mutant was slightly reduced in vegetative growth but normal in asexual and sexual reproduction. It had increased sensitivities to oxidative and membrane stresses. DON mycotoxin production and virulence on flowering wheat heads also were reduced in the Δamt1 mutant. The introduction of the wild-type AMT1 allele fully complemented the defects of the Δamt1 mutant and Amt1-GFP fusion proteins mainly localized to the nucleus. Hrp1 and Nab2 are two hnRNPs in yeast that are methylated by Hmt1 for nuclear export. In F. graminearum, AMT1 is required for the nuclear export of FgHrp1 but not FgNab2, indicating that yeast and F. graminearum differ in the methylation and nucleo-cytoplasmic transport of hnRNP components. Because AMT2 also is a predicted type I PRMT with limited homology to yeast HMT1, we generated the Δamt1 Δamt2 double mutants. The Δamt1 single and Δamt1 Δamt2 double mutants had similar defects in all the phenotypes assayed, including reduced vegetative growth and virulence. Overall, data from this systematic analysis of PRMT genes suggest that AMT1, like its ortholog in yeast, is the predominant PRMT gene in F. graminearum and plays a role in hyphal growth, stress responses, and plant infection

Landscape Composition and Spatial Prediction of Alveolar Echinococcosis in Southern Ningxia, China

In humans, larvae of the fox tapeworm Echinococcus multilocularis typically infect the liver where metastasis, calcification and necrosis cause the zoonotic disease alveolar echinococcosis (AE). Treatment is difficult. Early detection greatly increases patient life expectancy but under-detection is a problem. Understanding the ecological conditions that elevate AE risk would help identify at-risk communities. Voles and lemmings of the subfamily Arvicolinae are important intermediate hosts in most AE endemic areas, and arvicoline habitat has been proposed as a predictor of AE risk. Using a model of spatial autocorrelation with land cover identified from satellite remote sensing imagery, we identified AE hotspots in southern Ningxia Hui Autonomous Region (NHAR), China. Hotspots were not located near optimal arvicoline habitats. Thus, non-arvicolines provide principal reservoirs in NHAR and the range of ecological conditions sustaining E. multilocularis transmission in China is greater than previously thought. We also show: social factors explain higher prevalence in females than males; dogs increase infection risk; and we argue that water source quality is important via interaction with other environmental variables. Our map of AE prevalence represents the current state-of-the-art regarding the spatial distribution of AE in southern NHAR and provides an important baseline for future monitoring programs there

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease