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1.
Bull Entomol Res ; 112(4): 451-457, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35199630

RESUMO

Aphidophagous hoverflies (Diptera, Syrphidae, Syrphinae) are common flower visitors and aphid predators in a range of flowering plants, including fruit crops. Here, we investigate whether aphid prey DNA can be detected in the gut contents of hoverfly larvae from a commercial strawberry field as a proof of concept that a molecular approach can be used to measure agricultural biocontrol. We used high-throughput sequencing (HTS) to target insect DNA and compared the resulting data to reference databases containing aphid and hoverfly DNA sequences. We explored what impact incorporating wildflowers within polythene-clad tunnels may have on aphid DNA detection rates in hoverfly larvae. In a randomized block experiment, coriander (Coriandrum sativum), field forget-me-not (Myosotis arvensis) and corn mint (Mentha arvensis) plants were inserted in rows of strawberries. Their effect on aphid DNA detection rates was assessed. Aphid DNA was found in 55 of 149 specimens (37%) validating the method in principle for measuring agricultural services provided by hoverflies. Interestingly, detection rates were higher near plots with forget-me-not than plots with coriander, though detection rates in control plots did not differ significantly from either wildflower species. These findings confirm that hoverflies predate aphids in UK strawberry fields, and that HTS is a viable method of identifying aphid DNA in predatory hoverflies. We comment on the need for further method development to narrow down identifications of both predator and prey. We furthermore provide some evidence that there is an effect of intercropping strawberry crops with wildflowers which may affect aphid consumption in hoverfly larvae.


Assuntos
Afídeos , Dípteros , Animais , Produtos Agrícolas , DNA , Larva , Comportamento Predatório
2.
PLoS Genet ; 8(12): e1003095, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23284290

RESUMO

Sensitivity to pain varies considerably between individuals and is known to be heritable. Increased sensitivity to experimental pain is a risk factor for developing chronic pain, a common and debilitating but poorly understood symptom. To understand mechanisms underlying pain sensitivity and to search for rare gene variants (MAF<5%) influencing pain sensitivity, we explored the genetic variation in individuals' responses to experimental pain. Quantitative sensory testing to heat pain was performed in 2,500 volunteers from TwinsUK (TUK): exome sequencing to a depth of 70× was carried out on DNA from singletons at the high and low ends of the heat pain sensitivity distribution in two separate subsamples. Thus in TUK1, 101 pain-sensitive and 102 pain-insensitive were examined, while in TUK2 there were 114 and 96 individuals respectively. A combination of methods was used to test the association between rare variants and pain sensitivity, and the function of the genes identified was explored using network analysis. Using causal reasoning analysis on the genes with different patterns of SNVs by pain sensitivity status, we observed a significant enrichment of variants in genes of the angiotensin pathway (Bonferroni corrected p = 3.8×10(-4)). This pathway is already implicated in animal models and human studies of pain, supporting the notion that it may provide fruitful new targets in pain management. The approach of sequencing extreme exome variation in normal individuals has provided important insights into gene networks mediating pain sensitivity in humans and will be applicable to other common complex traits.


Assuntos
Angiotensinas , Exoma/genética , Redes Reguladoras de Genes , Dor , Adulto , Angiotensinas/genética , Angiotensinas/metabolismo , Sequência de Bases , Regulação da Expressão Gênica , Predisposição Genética para Doença , Temperatura Alta , Humanos , Masculino , Dor/genética , Dor/fisiopatologia , Limiar da Dor , Sensibilidade e Especificidade , Análise de Sequência de DNA , Transdução de Sinais
3.
Ann Neurol ; 73(1): 16-31, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23381943

RESUMO

OBJECTIVE: End-stage coagulation and the structure/function of fibrin are implicated in the pathogenesis of ischemic stroke. We explored whether genetic variants associated with end-stage coagulation in healthy volunteers account for the genetic predisposition to ischemic stroke and examined their influence on stroke subtype. METHODS: Common genetic variants identified through genome-wide association studies of coagulation factors and fibrin structure/function in healthy twins (n = 2,100, Stage 1) were examined in ischemic stroke (n = 4,200 cases) using 2 independent samples of European ancestry (Stage 2). A third clinical collection having stroke subtyping (total 8,900 cases, 55,000 controls) was used for replication (Stage 3). RESULTS: Stage 1 identified 524 single nucleotide polymorphisms (SNPs) from 23 linkage disequilibrium blocks having significant association (p < 5 × 10(-8)) with 1 or more coagulation/fibrin phenotypes. The most striking associations included SNP rs5985 with factor XIII activity (p = 2.6 × 10(-186)), rs10665 with FVII (p = 2.4 × 10(-47)), and rs505922 in the ABO gene with both von Willebrand factor (p = 4.7 × 10(-57)) and factor VIII (p = 1.2 × 10(-36)). In Stage 2, the 23 independent SNPs were examined in stroke cases/noncases using MOnica Risk, Genetics, Archiving and Monograph (MORGAM) and Wellcome Trust Case Control Consortium 2 collections. SNP rs505922 was nominally associated with ischemic stroke (odds ratio = 0.94, 95% confidence interval = 0.88-0.99, p = 0.023). Independent replication in Meta-Stroke confirmed the rs505922 association with stroke, beta (standard error, SE) = 0.066 (0.02), p = 0.001, a finding specific to large-vessel and cardioembolic stroke (p = 0.001 and p = < 0.001, respectively) but not seen with small-vessel stroke (p = 0.811). INTERPRETATION: ABO gene variants are associated with large-vessel and cardioembolic stroke but not small-vessel disease. This work sheds light on the different pathogenic mechanisms underpinning stroke subtype.


Assuntos
Sistema ABO de Grupos Sanguíneos/genética , Coagulação Sanguínea/genética , Isquemia Encefálica/genética , Loci Gênicos/genética , Estudo de Associação Genômica Ampla , Acidente Vascular Cerebral/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiologia , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Variação Genética/genética , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Adulto Jovem
4.
Eur J Drug Metab Pharmacokinet ; 38(1): 63-7, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22945461

RESUMO

Atypical cytochrome P450 3A4 (CYP3A4) enzyme activity-induced and inhibited-is thought to be the driver of numerous poor or adverse therapeutic responses to up to 50 % of all commonly prescribed drugs. We carried out a genome-wide association study to identify common genetic variants associated with variation in induced CYP3A4 activity. A total of 310 twins were included in this study. Each participant had already completed a 14 days course of St John's Wort to induce CYP3A4, which was quantified through the metabolic ratio of exogenous 3-hydroxyquinine to quinine. We failed to detect any genome-wide significant associations (P < 1 × 10(-8)) with variation in induced CYP3A4 activity although several genomic regions were highlighted which may play minor roles. We report the first GWAS of variation in induced CYP3A4 activity and our preliminary results indicate a complex genetic architecture underpinning induced CYP3A4 enzyme activity.


Assuntos
Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Fígado/enzimologia , Gêmeos/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/urina , Biotransformação , Citocromo P-450 CYP3A/biossíntese , Indução Enzimática , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Hidroxilação , Hypericum , Fígado/efeitos dos fármacos , Pessoa de Meia-Idade , Fenótipo , Preparações de Plantas/farmacologia , Quinidina/análogos & derivados , Quinidina/urina , Quinina/urina , Especificidade por Substrato
5.
Pharmacogenet Genomics ; 21(10): 642-51, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21750469

RESUMO

AIM: The cytochrome P450 3A4 (CYP3A4) enzyme is implicated in the metabolism of more than 50% of all prescribed medications and its activity - including induced or inhibited activity - is deemed to be a crucial determinant of interindividual variability in drug disposition, poor therapeutic efficacy, and adverse response to medication. METHODS: We used the classical twin model in conjunction with an induction experiment to uncover the relative contribution of genetic and environmental factors to interindividual variation in induced CYP3A4 activity. A total of 367 healthy twins participated in the study. Each volunteer was administered a potent inducer of CYP3A4 (St John's Wort) for 14 days and the activity of CYP3A4 was quantified through the metabolism of the exogenously administered probe drug quinine sulfate. RESULTS: Baseline and induced CYP3A4 activity were highly variable with a seven-fold and 11-fold difference among our population, respectively. Alcohol consumption, BMI, and smoking were significantly associated with induced CYP3A4 activity, collectively explaining 20% of the variation (P<1×10(-4)). The narrow-sense heritability of induced CYP3A4 activity was estimated at 66%, whereas the remainder of the variation was attributed to unique environmental factors. CONCLUSION: To our knowledge, this is the first genetic epidemiological study of induced CYP3A4 activity. Our results motivate further research to identify common and rarer genetic variants that underpin the heritable component of variation in induced CYP3A4 activity.


Assuntos
Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Hypericum , Extratos Vegetais/farmacologia , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/genética , Consumo de Bebidas Alcoólicas/metabolismo , Biomarcadores Farmacológicos , Índice de Massa Corporal , Feminino , Humanos , Pessoa de Meia-Idade , Modelos Genéticos , Extratos Vegetais/administração & dosagem , Quinidina/análogos & derivados , Quinidina/urina , Quinina/farmacologia , Quinina/urina , Fumar/genética , Fumar/metabolismo , Inquéritos e Questionários
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