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1.
Methamphetamine (MA) is an illegal stimulant drug of abuse with serious negative health consequences. The neurochemical effects of MA have been partially characterized, with a traditional focus on classical neurotransmitter systems. However, these directions have not yet led to novel drug treatments for MA abuse or toxicity. As an alternative approach, we describe here the first application of metabolomics to investigate the neurochemical consequences of MA exposure in the rodent brain. We examined single exposures at 3 mg/kg and repeated exposures at 3 mg/kg over 5 days in eight common inbred mouse strains. Brain tissue samples were assayed using high-throughput gas and liquid chromatography mass spectrometry, yielding quantitative data on >300 unique metabolites. Association testing and false discovery rate control yielded several metabolome-wide significant associations with acute MA exposure, including compounds such as lactate (p = 4.4 × 10?5, q = 0.013), tryptophan (p = 7.0 × 10?4, q = 0.035) and 2-hydroxyglutarate (p = 1.1 × 10?4, q = 0.022). Secondary analyses of MA-induced increase in locomotor activity showed associations with energy metabolites such as succinate (p = 3.8 × 10?7). Associations specific to repeated (5 day) MA exposure included phosphocholine (p = 4.0 × 10?4, q = 0.087) and ergothioneine (p = 3.0 × 10?4, q = 0.087). Our data appear to confirm and extend existing models of MA action in the brain, whereby an initial increase in energy metabolism, coupled with an increase in behavioral locomotion, gives way to disruption of mitochondria and phospholipid pathways and increased endogenous antioxidant response. Our study demonstrates the power of comprehensive MS-based metabolomics to identify drug-induced changes to brain metabolism and to develop neurochemical models of drug effects.  相似文献   

2.
Genome-wide association studies (GWAS) of obesity measures have identified associations with single nucleotide polymorphisms (SNPs). However, no large-scale evaluation of gene-environment interactions has been performed. We conducted a search of gene-environment (G × E) interactions in post-menopausal African-American and Hispanic women from the Women’s Health Initiative SNP Health Association Resource GWAS study. Single SNP linear regression on body mass index (BMI) and waist-to-hip circumference ratio (WHR) adjusted for multidimensional-scaling-derived axes of ancestry and age was run in race-stratified data with 871,512 SNPs available from African-Americans (N = 8,203) and 786,776 SNPs from Hispanics (N = 3,484). Tests of G × E interaction at all SNPs for recreational physical activity (m h/week), dietary energy intake (kcal/day), alcohol intake (categorical), cigarette smoking years, and cigarette smoking (ever vs. never) were run in African-Americans and Hispanics adjusted for ancestry and age at interview, followed by meta-analysis of G × E interaction terms. The strongest evidence for concordant G × E interactions in African-Americans and Hispanics was for smoking and marker rs10133840 (Q statistic P = 0.70, beta = ?0.01, P = 3.81 × 10?7) with BMI as the outcome. The strongest evidence for G × E interaction within a cohort was in African-Americans with WHR as outcome for dietary energy intake and rs9557704 (SNP × kcal = ?0.04, P = 2.17 × 10?7). No results exceeded the Bonferroni-corrected statistical significance threshold.  相似文献   

3.
Recent genome-wide association studies of the adult human metabolome have identified genetic variants associated with relative levels of several acylcarnitines, which are important clinical correlates for chronic conditions such as type 2 diabetes and obesity. We have previously shown that these same metabolite levels are highly heritable at birth; however, no studies to our knowledge have examined genetic associations with these metabolites measured at birth. Here, we examine, in 743 newborns, 58 single nucleotide polymorphisms (SNPs) in 11 candidate genes previously associated with differing relative levels of short-chain acylcarnitines in adults. Six SNPs (rs2066938, rs3916, rs3794215, rs555404, rs558314, rs1799958) in the short-chain acyl-CoA dehydrogenase gene (ACADS) were associated with neonatal C4 levels. Most significant was the G allele of rs2066938, which was associated with significantly higher levels of C4 (P = 1.5 × 10?29). This SNP explains 25 % of the variation in neonatal C4 levels, which is similar to the variation previously reported in adult C4 levels. There were also significant (P < 1 × 10?4) associations between neonatal levels of C5-OH and SNPs in the solute carrier family 22 genes (SLC22A4 and SLC22A5) and the 3-methylcrotonyl-CoA carboxylase 1 gene (MCCC1). We have replicated, in newborns, SNP associations between metabolic traits and the ACADS and SLC22A4 genes observed in adults. This research has important implications not only for the identification of rare inborn errors of metabolism but also for personalized medicine and early detection of later life risks for chronic conditions.  相似文献   

4.
Gene–environment interactions need to be studied to better understand the obesity. We aimed at determining whether genetic susceptibility to obesity associates with diet intake levels and whether diet intakes modify the genetic susceptibility. In 29,480 subjects of the population-based Malmö Diet and Cancer Study (MDCS), we first assessed association between 16 genome-wide association studies identified obesity-related single-nucleotide polymorphisms (SNPs) with body mass index (BMI) and associated traits. We then conducted association analyses between a genetic risk score (GRS) comprising of 13 replicated SNPs and the individual SNPs, and relative dietary intakes of fat, carbohydrates, protein, fiber and total energy intake, as well as interaction analyses on BMI and associated traits among 26,107 nondiabetic MDCS participants. GRS associated strongly with increased BMI (P = 3.6 × 10?34), fat mass (P = 6.3 × 10?28) and fat-free mass (P = 1.3 × 10?24). Higher GRS associated with lower total energy intake (P = 0.001) and higher intake of fiber (P = 2.3 × 10?4). No significant interactions were observed between GRS and the studied dietary intakes on BMI or related traits. Of the individual SNPs, after correcting for multiple comparisons, NEGR1 rs2815752 associated with diet intakes and BDNF rs4923461 showed interaction with protein intake on BMI. In conclusion, our study does not provide evidence for a major role for macronutrient-, fiber- or total energy intake levels in modifying genetic susceptibility to obesity measured as GRS. However, our data suggest that the number of risk alleles as well as some of the individual obesity loci may have a role in regulation of food and energy intake and that some individual loci may interact with diet.  相似文献   

5.
Genome-wide association (GWA) studies have identified many candidate genes that are associated with blood lipid and lipoprotein concentrations. In this study, we want to know whether the results from European for lipid-related single-nucleotide polymorphisms (SNPs) are generalizable to Chinese children. We genotyped seven SNPs in Chinese school-age children (n = 3,503) and assessed the associations of these SNPs with lipids profiles and dyslipidemia. After false discovery rate correction, of the seven SNPs, six (rs2144300, p ~ 9.30 × 10?3; rs1260333, p ~ 6.20 × 10?11; rs1260326, p ~ 8.73 × 10?11; rs10105606, p ~ 0.010; rs1748195, p ~ 0.016 and rs964184, p ~ 2.33 × 10?13) showed strong association with triglycerides. Three SNPs (rs1260333, p ~ 3.30 × 10?3; rs1260326, p ~ 4.39 × 10?3 and rs2954029, p ~ 6.36 × 10?4) showed strong association with total cholesterol. Two SNPs (rs10105606, p ~ 6.66 × 10?4 and rs1748195, p ~ 2.55 × 10?3) showed strong association with high density lipoprotein cholesterol. Four SNPs (rs1260333, p ~ 0.017; rs1260326, p ~ 0.013; rs2954029, p ~ 1.09 × 10?3 and rs964184, p ~ 5.51 × 10?3) showed strong association with low density lipoprotein cholesterol. There were significant associations between rs1260333 (OR is 0.82, 95 % CI 0.74–0.92, p ~ 3.96 × 10?4), rs1260326 (OR is 0.82, 95 % CI 0.74–0.92, p ~ 5.31 × 10?4), and rs964184 (OR is 1.36, 95 % CI 1.20–1.55, p ~ 1.89 × 10?6) and dyslipidemia. These SNPs generated strong combined effects on lipid profiles and dyslipidemia. Our study demonstrates that SNPs associated with lipids from European GWA studies also play roles in Chinese children, which broadened the understanding of lipids metabolism.  相似文献   

6.
Uterine fibroid (UFs) affect 77 % of women by menopause and account for $9.4 billion in healthcare costs each year. Although UFs are heritable, genetic risk is poorly understood. The first genome-wide association study (GWAS) of UFs was recently performed in a Japanese population, with reported genome-wide significance for single nucleotide polymorphisms (SNPs) across three chromosomal regions. We tested these SNPs for association with UFs in US cohorts. Women were enrolled in the Right from the Start (RFTS) cohort and the BioVU DNA repository. UF status in both cohorts was determined by pelvic imaging. We tested 65 candidate and haplotype-tagging SNPs for association with UFs presence using logistic regression in RFTS and the top three GWAS-associated SNPs in BioVU. We also combined association results from both cohorts using meta-analysis. 1,086 European American (EA) cases and 1,549 controls were examined. Two SNP associations replicated [blocked early in transport 1 homolog (BET1L) rs2280543, RFTS–BioVU meta-odds ratio (OR) = 0.67 95 % confidence interval (CI) 0.38–0.96, Q = 0.70, I = 0, p = 6.9 × 10?3; trinucleotide repeat containing 6B (TNRC6B) rs12484776, RFTS–BioVU meta-OR = 1.21, 95 % CI 1.07–1.35, Q = 0.24, I = 28.37, p = 8.7 × 10?3). Meta-analyses combining evidence from RFTS, BioVU, and prior GWAS showed little heterogeneity in effect sizes across studies, with meta-p values between 7.45 × 10?8 and 3.89 × 10?9, which were stronger than prior GWAS and supported associations observed for all previously identified loci. These data suggest common variants increase risk for UF in both EA and Japanese populations. However, further research is needed to assess the role of these genes across other racial groups.  相似文献   

7.
Human height is a complex genetic trait with high heritability but discovery efforts in Asian populations are limited. We carried out a meta-analysis of genome-wide association studies (GWAS) for height in 6,534 subjects with in silico replication of 1,881 subjects in Han Chinese. We identified three novel loci reaching the genome-wide significance threshold (P < 5 × 10?8), which mapped in or near ZNF638 (rs12612930, P = 2.02 × 10?10), MAML2 (rs11021504, P = 7.81 × 10?9), and C18orf12 (rs11082671, P = 1.87 × 10?8). We also confirmed two loci previously reported in European populations including CS (rs3816804, P = 2.63 × 10?9) and CYP19A1 (rs3751599, P = 4.80 × 10?10). In addition, we provided evidence supporting 35 SNPs identified by previous GWAS (P < 0.05). Our study provides new insights into the genetic determination of biological regulation of human height.  相似文献   

8.
Drying of garlic slices in thin-layer have been studied with Infrared (IR) at 0.075, 0.15, 0.225 and 0.3 W cm?2 radiation intensity and 0.75 and 1.25 m s?1 air flow velocity. The results showed increasing in drying rate and decreasing at the time of drying with decreasing air flow velocity and increasing IR radiation intensity. The effective moisture diffusivity (Deff) was obtained using Fick’s diffusion equation and its mean values ranged between 5.83×10?11 and 7.66×10?10 m2 s?1 for all investigated conditions. In addition, a third-order polynomial equation linking the effective moisture diffusivity and moisture content was found. Average activation energy increased with the decrease of IR radiation and increase of air flow velocity. Thirteen different mathematical models were verified with non-linear regression analysis for describing the garlic drying process. Modified Henderson and Pabis model presented the best prediction of the drying of garlic slices.  相似文献   

9.
Twenty local isolates of entomopathogenic fungi were determined for control of the larvae and adults of Culex quinquefasciatus. In a laboratory experiment, a Penicillium sp. CM-010 caused 100 % mortality of third-instar larvae within 2 h using a conidial suspension of 1 × 106 conidia ml?1. Its LC50 was 3 × 105 conidia ml?1, and the lethal time (LT50) was 1.06 h. Cloning and sequencing of its internal transcribed spacer region indicated that this Penicillium species is Penicillium citrinum (100 % identity in 434 bp). Mortality of the adult was highest with Aspergillus flavus CM-011 followed with Metarhizium anisopliae CKM-048 from 1 × 109 conidia ml?1. P. citrinum CM-010 at 1 × 106 conidia ml?1 killed 100 % larvae within 2 h while Bacillus thuringiensis var. israelensis at 5 ITU ml?1 required 24 h. This P. citrinum CM-010 also greatly reduced survival of C. quinquefasciatus larvae in an unreplicated field test. Light and transmission electron micrographs showed that the fungal conidia were ingested by the larvae and deposited in the gut. The metabolite patulin was produced by P. citrinum CM-010 instead of citrinin.  相似文献   

10.
C-reactive protein (CRP) is a heritable biomarker of systemic inflammation and a predictor of cardiovascular disease (CVD). Large-scale genetic association studies for CRP have largely focused on individuals of European descent. We sought to uncover novel genetic variants for CRP in a multiethnic sample using the ITMAT Broad-CARe (IBC) array, a custom 50,000 SNP gene-centric array having dense coverage of over 2,000 candidate CVD genes. We performed analyses on 7,570 African Americans (AA) from the Candidate gene Association Resource (CARe) study and race-combined meta-analyses that included 29,939 additional individuals of European descent from CARe, the Women’s Health Initiative (WHI) and KORA studies. We observed array-wide significance (p < 2.2 × 10?6) for four loci in AA, three of which have been reported previously in individuals of European descent (IL6R, p = 2.0 × 10?6; CRP, p = 4.2 × 10?71; APOE, p = 1.6 × 10?6). The fourth significant locus, CD36 (p = 1.6 × 10?6), was observed at a functional variant (rs3211938) that is extremely rare in individuals of European descent. We replicated the CD36 finding (p = 1.8 × 10?5) in an independent sample of 8,041 AA women from WHI; a meta-analysis combining the CARe and WHI AA results at rs3211938 reached genome-wide significance (p = 1.5 × 10?10). In the race-combined meta-analyses, 13 loci reached significance, including ten (CRP, TOMM40/APOE/APOC1, HNF1A, LEPR, GCKR, IL6R, IL1RN, NLRP3, HNF4A and BAZ1B/BCL7B) previously associated with CRP, and one (ARNTL) previously reported to be nominally associated with CRP. Two novel loci were also detected (RPS6KB1, p = 2.0 × 10?6; CD36, p = 1.4 × 10?6). These results highlight both shared and unique genetic risk factors for CRP in AA compared to populations of European descent.  相似文献   

11.
Bone and muscle, two major tissue types of musculoskeletal system, have strong genetic determination. Abnormality in bone and/or muscle may cause musculoskeletal diseases such as osteoporosis and sarcopenia. Bone size phenotypes (BSPs), such as hip bone size (HBS), appendicular bone size (ABS), are genetically correlated with body lean mass (mainly muscle mass). However, the specific genes shared by these phenotypes are largely unknown. In this study, we aimed to identify the specific genes with pleiotropic effects on BSPs and appendicular lean mass (ALM). We performed a bivariate genome-wide association study (GWAS) by analyzing ~690,000 SNPs in 1,627 unrelated Han Chinese adults (802 males and 825 females) followed by a replication study in 2,286 unrelated US Caucasians (558 males and 1,728 females). We identified 14 interesting single nucleotide polymorphisms (SNPs) that may contribute to variation of both BSPs and ALM, with p values <10?6 in discovery stage. Among them, the association of three SNPs (rs2507838, rs7116722, and rs11826261) in/near GLYAT (glycine-N-acyltransferase) gene was replicated in US Caucasians, with p values ranging from 1.89 × 10?3 to 3.71 × 10?4 for ALM–ABS, from 5.14 × 10?3 to 1.11 × 10?2 for ALM–HBS, respectively. Meta-analyses yielded stronger association signals for rs2507838, rs7116722, and rs11826261, with pooled p values of 1.68 × 10?8, 7.94 × 10?8, 6.80 × 10?8 for ALB–ABS and 1.22 × 10?4, 9.85 × 10?5, 3.96 × 10?4 for ALM–HBS, respectively. Haplotype allele ATA based on these three SNPs was also associated with ALM–HBS and ALM–ABS in both discovery and replication samples. Interestingly, GLYAT was previously found to be essential to glucose metabolism and energy metabolism, suggesting the gene’s dual role in both bone development and muscle growth. Our findings, together with the prior biological evidence, suggest the importance of GLYAT gene in co-regulation of bone phenotypes and body lean mass.  相似文献   

12.
The aim of this study was to carry out a bioaccessibility-based risk assessment of polycyclic aromatic hydrocarbons (PAHs) in soils from sites of different anthropogenic activities in Lagos, Nigeria. Using an in vitro gastrointestinal model—Fed Organic Estimation Human Simulation Test method (FOREShT), the concentration of bioaccessible 16 priority US Environmental Protection Agency (USEPA) PAHs in soils were determined. Total concentration of 16 priority USEPA PAHs was also determined. The concentration range was 702–253,922 ng g?1 and 92–760 ng g?1 for total and bioaccessible PAHs, respectively. For persons involved with activities at these sites no health risks were observed, based on bioaccessibility values of PAHs. Mean daily intake of PAHs from these soils were below the oral mean daily intake threshold for PAHs in food. Also, overall estimated theoretical cancer risk (2.5 × 10?09, 6.5 × 10?07, 5.5 × 10?10, 2.7 × 10?09, 6.5 × 10?10, 9.5 × 10?10, 2.0 × 10?09, and 4.1 × 10?07 for the eight sites based on their bioaccessible concentration) for exposure to PAHs in surface soils were below the health guidelines for extreme (1 × 10?04) and normal (1 × 10?06) exposures.  相似文献   

13.
The patterns of use of marine and freshwater habitats by the tropical anguillid eels Anguilla marmorata and A. bicolor pacifica were examined by analysing the otolith strontium (Sr) and calcium (Ca) concentrations of yellow (immature) and silver (mature) stage eels collected in Vietnamese waters. In A. marmorata, the change in the Sr:Ca ratios outside the high Sr:Ca core was generally divided into three patterns: (1) typical catadromous life history pattern; (2) constant residence in brackish water; and (3) habitat shifting between sea and brackish waters with no freshwater life. In A. bicolor pacifica, no eels had a general life history as freshwater residents. The eels were also divided into three patterns: (1) constant residence in sea water; (2) constantly living in brackish water; and (3) habitat shifting from brackish to sea water with no freshwater residence. The mean Sr:Ca ratio value after recruitment to coastal waters ranged from 1.73 to 5.67 × 10?3 (mean 3.2 × 10?3) in A. marmorata and from 2.53 to 6.32 × 10?3 (mean 4.3 × 10?3) in A. bicolor pacifica. The wide range of otolith Sr:Ca ratios in both species indicated that the habitat use of these tropical eels was facultative among fresh, brackish, and marine waters during their growth phases after recruitment to coastal areas. Tropical eel species may have the same behavioural plasticity as temperate anguillid species regarding whether to enter freshwater or to remain in estuarine and marine environments.  相似文献   

14.
Leprosy is caused by infection with Mycobacterium leprae and is classified clinically into paucibacillary (PB) or multibacillary (MB) subtypes based on the number of skin lesions and the bacillary index detected in skin smears. We previously identified a major PB susceptibility locus on chromosome region 10p13 in Vietnamese families by linkage analysis. In the current study, we conducted high-density association mapping of the 9.5 Mb linkage peak on chromosome region 10p13 covering 39 genes. Using leprosy per se and leprosy subtypes as phenotypes, we employed 294 nuclear families (303 leprosy cases, 63 % MB, 37 % PB) as a discovery sample and 192 nuclear families (192 cases, 55 % MB, 45 % PB) as a replication sample. Replicated significant association signals were revealed in the genes for cubilin (CUBN) and nebulette (NEBL). In the combined sample, the C allele (frequency 0.26) at CUBN SNP rs10904831 showed association [p = 1 × 10?5; OR 0.52 (0.38–0.7)] with MB leprosy only. Likewise, allele T (frequency 0.42) at NEBL SNP rs11012461 showed association [p = 4.2 × 10?5; OR 2.51 (1.6–4)] with MB leprosy only. These associations remained valid for the CUBN signal when taking into account the effective number of tests performed (type I error significance threshold = 2.4 × 10?5). We used the results of our analyses to propose a new model for the genetic control of polarization of clinical leprosy.  相似文献   

15.
Glycolysis and Krebs cycle intermediates were incubated with Eu3+-tetracycline and separated using capillary electrophoresis utilizing post-column laser-induced luminescence detection in a sheath flow cuvette. 3-phopshoglycerate, phosphoenolpyruvate, adenosine diphosphate, phosphate, citrate and oxaloacetate were detected at a concentration of 100 μM or lower. When all these detected metabolites were contained within the same sample it was found that they interfered with one another. Of all the metabolites, oxaloacetate showed the highest detectability. The system was found to yield a linear response for oxaloacetate from 50 nM to 10 μM. The injected volume of sample was 400 pL. This corresponds to 2 × 10?17 mol of injected oxaloacetate from the 50 nM sample. As an application, the system was used to assay the enzyme aspartate aminotransferase, for whom oxaloacetate is a product. After a 1 h incubation period, 1.2 × 10?13 M (3.3 μU/mL) enzyme was sufficient to form a detectable product signal. Extension of this incubation to 18 h permitted the detection of the activity of 1.2 × 10?14 M (330 nU/mL) enzyme. This is the equivalent of 4.8 ymoles (2.9 molecules) of enzyme in the 400 pL injection volume. The enzyme’s catalytic rate was determined to be 240 s?1 under the conditions used. In a second application, homogenates of Drosophila melanogaster were analyzed for metabolites, providing several peaks, including one which had the same retention time as citrate.  相似文献   

16.
We estimated the grazing impact of the heterotrophic flagellate Collodictyon triciliatum on the harmful, bloom-forming cyanobacterium Microcystis aeruginosa in an experimental pond during a Microcystis bloom from summer to winter in 2010. For these experiments, we calculated the grazing rates from the digestion rate of C. triciliatum and its food vacuole contents. During the study period, M. aeruginosa exhibited one bloom event with a maximum density of 1.1 × 105 cells ml?1. The cell density of C. triciliatum fluctuated from below the detection limit to 291 cells ml?1. The number of M. aeruginosa cells ingested by C. triciliatum food vacuoles ranged between 0.4 and 10.8 cells flagellate?1, and the digestion rate of C. triciliatum at 25 °C was 0.73 % cell contents min?1. The grazing rate of C. triciliatum on the M. aeruginosa prey was 0.2–6.9 cells flagellate?1 h?1, and its grazing impact was 0.0–25.3 % standing stock day?1. The functional response of C. triciliatum to the M. aeruginosa prey followed the Michaelis–Menten model of significance (r 2 = 0.873, p < 0.001) in our experimental systems, in which the prey concentration varied from 1.0 × 104 to 2.1 × 106 cells ml?1. The maximum grazing rate was 6.2 prey cells grazer?1 h?1, and the half-saturation constant was 1.2 × 105 cells ml?1. We present evidence that C. triciliatum grazing explained the remarkable decrease in M. aeruginosa cell density in the pond. The present study is the first demonstration of the high potential of protistan grazing on M. aeruginosa to reduce cyanobacterial blooms.  相似文献   

17.
Spirodela polyrrhiza, a fast-growing duckweed with high starch and low lignin content, shows promise as a feedstock for bioenergy. Abscisic acid (ABA) is a biological hormone that controls plant growth and stress response. The effects of different ABA concentrations (0, 1.0 × 10?5, 1.0 × 10?4, 1.0 × 10?3, 1.0 × 10?2, and 1.0 × 10?1 mg/L) on duckweed biomass growth, carbon dioxide fixation, formation of photosynthetic pigments (Chlorophyll a (Chla), Chlorophyll b (Chlb), and carotenoids), the activities of soluble starch synthase (SSS) and starch branching enzyme (SBE), and the starch content of biomass were investigated in this study. ABA at concentrations lower than 1.0 × 10?3 mg/L promoted carbon dioxide fixation, whereas it inhibited carbon dioxide fixation at concentrations over 1.0 × 10?3 mg/L. ABA enhanced SSS and SBE activities at concentrations lower than 1.0 × 10?2 mg/L. ABA treatment increased the content of Chla, Chlb, and carotenoids and resulted in the enhancement of starch content. Chla content gradually increased with the increasing concentration of ABA (1.0 × 10?5 to 1.0 × 10?2 mg/L). After culturing for 10 days, starch content in 1.0 × 10?2 mg/L ABA medium reached 35.3% of dry weight (DW), which was the highest level in this study. This suggests that there is a great potential to develop a technology to increase starch accumulation in duckweed which can be used as an alternative to corn, sugarcane, or other food crops as a starch source.  相似文献   

18.
Maximum number of alcoholic drinks consumed in a 24-h period (maxdrinks) is a heritable (>50 %) trait and is strongly correlated with vulnerability to excessive alcohol consumption and subsequent alcohol dependence (AD). Several genome-wide association studies (GWAS) have studied alcohol dependence, but few have concentrated on excessive alcohol consumption. We performed two GWAS using maxdrinks as an excessive alcohol consumption phenotype: one in 118 extended families (N = 2,322) selected from the Collaborative Study on the Genetics of Alcoholism (COGA), and the other in a case–control sample (N = 2,593) derived from the Study of Addiction: Genes and Environment (SAGE). The strongest association in the COGA families was detected with rs9523562 (p = 2.1 × 10?6) located in an intergenic region on chromosome 13q31.1; the strongest association in the SAGE dataset was with rs67666182 (p = 7.1 × 10?7), located in an intergenic region on chromosome 8. We also performed a meta-analysis with these two GWAS and demonstrated evidence of association in both datasets for the LMO1 (p = 7.2 × 10?7) and PLCL1 genes (p = 4.1 × 10?6) with maxdrinks. A variant in AUTS2 and variants in INADL, C15orf32 and HIP1 that were associated with measures of alcohol consumption in a meta-analysis of GWAS studies and a GWAS of alcohol consumption factor score also showed nominal association in the current meta-analysis. The present study has identified several loci that warrant further examination in independent samples. Among the top SNPs in each of the dataset (p ≤ 10?4) far more showed the same direction of effect in the other dataset than would be expected by chance (p = 2 × 10?3, 3 × 10?6), suggesting that there are true signals among these top SNPs, even though no SNP reached genome-wide levels of significance.  相似文献   

19.
Efforts to increase the productivity of microalgal cultures have been focused on the improvement of photobioreactors, but little attention has been paid to the nutritional requirements of microalgae in order to improve culture media formulation. In this study, the main goal was obtaining a high productivity for Tetraselmis suecica (Chlorophyta) in semicontinuous culture by adding magnesium (Mg), silicon (Si), and strontium (Sr) at concentrations from 0.01 to 10 mM; at the time, the effect on steady-state cell density, biochemical composition, and antioxidant activity of T. suecica was evaluated. Because productivity is higher in high-density cultures, the work was focused many times to cell density. Mg (3 mM) and Sr (0.1 mM) added separately reached the highest steady-state cell density (7.0?×?106?±?0.4 cells mL?1) in comparison to control (4.2?±?0.1 cells mL?1), but simultaneous addition had a synergic effect, achieving 8.7?×?106?±?0.6 cells mL?1. Silicon (3 mM) significantly affected the steady-state cell density, reaching 6.0?±?0.3 cells mL?1 and increased the cell ash-free dry weight, reaching 127?±?7.9 pg cell?1 in comparison to control (102.7?±?5.0 pg cell?1), resulting in an ash-free dry weight productivity of 0.75?±?0.07 g?L?1 day?1. The highest fatty acids content and antioxidant activity, measured by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) method were obtained with Sr 10 mM. Sr treatments showed a high correlation (R 2?=?0.98) between DPPH inhibition and polyphenolic content, explaining its high antioxidant activity. Therefore, the addition of Mg, Si, and Sr to culture medium of T. suecica is recommended to achieve high steady-state cell density in semicontinuous cultures.  相似文献   

20.
Turbulence can affect predator–prey interactions. The effect of turbulence on the feeding efficiency of an ambush predator was tested with laboratory experiments. The experiments were conducted in 100-L aquaria in which ten individuals of fourth instar Chaoborus flavicans larvae were placed as predators. Two prey densities (3 and 10 ind. of Daphnia pulex L?1) and two durations (30 and 120 min) were tested in a nonturbulent treatment and five different turbulence levels [average root-mean-square (RMS) velocities ranging from 0 to 7.3 cm s?1, corresponding dissipation rates from 7.2 × 10?7 to 1.3 × 10?3 m2 s?3]. We hypothesized that the feeding rate of C. flavicans would be enhanced by turbulence due to increasing encounter rates up to a turbulence level above which a disturbance in post-encounter processes would lead to reduced feeding efficiency. However, the results showed no significant increase in the feeding rate of C. flavicans at intermediate turbulence. At high turbulence we found the expected significant negative response in the feeding rate of Chaoborus larvae. The feeding rate declined below the rates at nonturbulent and intermediate turbulence conditions as the average RMS velocity exceeded 3.1 cm s?1 (dissipation rate 9.9 × 10?5 m2 s?3, respectively).  相似文献   

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