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1.
J Biotechnol ; 363: 32-39, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36610479

RESUMO

As an easily obtained organic waste, by-product acetic acid could be an appropriate co-substrate with blue algae wastes (increase C/N ratio of substrates) for co-fermentation of PHA production. However, there are still acrylic acid and other chemicals in by-product acetic acid, which could cause severe inhibition for fermenting microorganisms during PHA production process. The current study represented that alkali pretreatment (pH level of 12) is a more favorable method compared with thermal pretreatment (80 â„ƒ for 30 min) for breaking cell walls of blue algae. It seemed that there was no synergistic effect of the combination of thermal and alkali pretreatment methods (temperature of 80 â„ƒ and pH level of 12). Optimal parameters during electro-fenton process for removal of inhibitors in by-product acetic acid were under current of 0.5 A, pH level of 3 and reaction time of 120 min. Both the highest dry weight of PHA and PHA concentration were achieved by applying blue algae and by-product acetic acid (after pretreatment) as co-substrates (mixed ratio of 3:1, stirring speed of 200 r/min, 24 h), indicating that using by-product acetic acid (after pretreatment) as co-substrate could increase C/N ratio and promote PHA production successfully. The current study could offer new insights for improving PHA production by co-fermentation.


Assuntos
Ácido Acético , Poli-Hidroxialcanoatos , Poli-Hidroxialcanoatos/metabolismo , Fermentação , Álcalis , Reatores Biológicos
2.
J Phys Chem A ; 126(16): 2578-2589, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35420816

RESUMO

The extraordinary sensitivity of 129Xe, hyperpolarized by spin-exchange optical pumping, is essential for magnetic resonance imaging and spectroscopy in life and materials sciences. However, fluctuations of the polarization over time still limit the reproducibility and quantification with which the interconnectivity of pore spaces can be analyzed. Here, we present a polarizer that not only produces a continuous stream of hyperpolarized 129Xe but also maintains stable polarization levels on the order of hours, independent of gas flow rates. The polarizer features excellent magnetization production rates of about 70 mL/h and 129Xe polarization values on the order of 40% at moderate system pressures. Key design features include a vertically oriented, large-capacity two-bodied pumping cell and a separate Rb presaturation chamber having its own temperature control, independent of the main pumping cell oven. The separate presaturation chamber allows for precise control of the Rb vapor density by restricting the Rb load and varying the temperature. The polarizer is both compact and transportable─making it easily storable─and adaptable for use in various sample environments. Time-evolved two-dimensional (2D) exchange spectra of 129Xe absorbed in the microporous metal-organic framework CAU-1-AmMe are presented to highlight the quantitative nature of the device.

3.
Waste Manag Res ; 40(6): 836-845, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34286637

RESUMO

An incentives-based residential recycling programme was designed and implemented for improving residential waste sorting in Shanghai city, but showed very limited success in its performance. To identify why, this study systematically analysed each step of implementation using key informant interviews and site observations. Results show that policy intentions were retained in the policy devolution processes from Municipality to District, and then to Street (ward) levels, but the incentives concepts were effectively nullified in the further devolution to community-level governance. The local implementers focused on formal key performance indicators (KPIs) in order to satisfy inspections. However, the KPIs, which had been devised to allow ease of measurement, were found to unintentionally cause divergence from the policy intention of incentivisation of residents. Furthermore, high scores for these KPIs masked the implementation failure. This identification of the effective derailing of a policy via conscientious implementation is worth highlighting for avoidance in other programmes, in recycling or elsewhere.


Assuntos
Motivação , Gerenciamento de Resíduos , China , Cidades , Políticas , Reciclagem/métodos , Gerenciamento de Resíduos/métodos
4.
J Environ Manage ; 303: 114092, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34836675

RESUMO

Although food loss and waste (FL&W) is high on China's national policy agenda, there is still little scientific information published about how much FL&W exists in China, what its impacts are, and what needs to be done to reduce it. Furthermore, what is known about FL&W across the various hotspots of China's food supply chain is not accessible in one place due to the tendency of scholars to focus on one part of the food chain depending on their disciplinary backgrounds, thereby making it difficult to obtain a 'comprehensive whole supply chain perspective'. Thus, this review provides an interdisciplinary collation of what is already known about FL&W in China. A systematic review of both English and Chinese databases followed PRISMA guidelines further complemented with a qualitative content analysis process uncovered 57 articles. The view revealed confounding factors such as an inconsistency of the definitions and calculation methods used to measure FL&W, and research gaps such as a lack of focus on the behavioral factors pertaining to waste, and the limited range of social innovations studied to reduce it. Thus, this review will help in the development of research agendas designed to advance efforts in this field.


Assuntos
Abastecimento de Alimentos , Alimentos , China , Bases de Dados Factuais , Políticas
5.
PLoS One ; 16(5): e0252525, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34048505

RESUMO

BACKGROUND: Weight loss after bariatric surgery varies widely between individuals, partly due to genetic differences. In addition, genetic determinants of abdominal obesity have been shown to attenuate weight loss after dietary intervention with special attention paid to the rs1358980-T risk allele in the VEGFA locus. Here we aimed to test if updated genetic risk scores (GRSs) for adiposity measures and the rs1358980-T risk allele are linked with weight loss following gastric bypass surgery. METHODS: Five hundred seventy six patients with morbid obesity underwent Roux-en-Y gastric bypass. A GRS for BMI and a GRS for waist-hip-ratio adjusted for BMI (proxy for abdominal obesity), respectively, were constructed. All patients were genotyped for the rs1358980-T risk allele. Associations between the genetic determinants and weight loss after bariatric surgery were evaluated. RESULTS: The GRS for BMI was not associated with weight loss (ß = -2.0 kg/100 risk alleles, 95% CI -7.5 to 3.3, p = 0.45). Even though the GRS for abdominal obesity was associated with an attenuated weight loss response adjusted for age, sex and center (ß = -14.6 kg/100 risk alleles, 95% CI -25.4 to -3.8, p = 0.008), it was not significantly associated with weight loss after adjustment for baseline BMI (ß = -7.9 kg/100 risk alleles, 95% CI -17.5 to 1.6, p = 0.11). Similarly, the rs1358980-T risk allele was not significantly associated with weight loss (ß = -0.8 kg/risk allele, 95% CI -2.2 to 0.6, p = 0.25). DISCUSSION: GRSs for adiposity derived from large meta-analyses and the rs1358980-T risk allele in the VEGFA locus did not predict weight loss after gastric bypass surgery. The association between a GRS for abdominal obesity and the response to bariatric surgery may be dependent on the association between the GRS and baseline BMI.


Assuntos
Obesidade Abdominal/genética , Redução de Peso/genética , Adulto , Alelos , Cirurgia Bariátrica , Índice de Massa Corporal , Feminino , Marcadores Genéticos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal/patologia , Fator A de Crescimento do Endotélio Vascular/genética , Relação Cintura-Quadril
6.
Front Psychol ; 12: 618956, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33679533

RESUMO

Most research in environmental psychology is conducted in individualistic countries and focuses on factors pertaining to individuals. It is yet unclear whether these findings also apply to more collectivistic countries, in which group factors might play a prominent role. In the current paper, we test the individual-focused value-identity-behaviour pathway, in which personal biospheric values relate to pro-environmental actions via environmental self-identity, in an individualistic and a collectivistic country. Furthermore, we test in both countries whether a new group-focused pathway also exists, in which group values relate to pro-environmental behaviour via environmental group identity, particularly in collectivistic countries. Questionnaire studies were conducted among Dutch (N = 161) and Chinese (N = 168) students. Our results indicated that personal biospheric values, mostly via environmental self-identity, predict pro-environmental behaviour in both countries. We also found initial support for our newly proposed value-identity-behaviour pathway at the group level, particularly in China. Yet, in both countries, the association between group-level variables and pro-environmental behaviour was weaker than for personal-level variables, and partly overlapped with personal-level variables. Our findings show the relevance of personal- and group-level factors in understanding pro-environmental behaviour in both individualistic and collectivistic countries, which has strong theoretical and practical implications, particularly for developing international strategies to promote pro-environmental actions across the world.

7.
Int J Obes (Lond) ; 45(1): 66-76, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32921795

RESUMO

OBJECTIVES: To determine the prevalence of Melanocortin-4 Receptor (MC4R) mutations in a cohort of children and adolescents with overweight or obesity and to determine whether treatment responses differed between carriers and noncarriers. METHODS: Using target region capture sequencing, an MC4R mutation screen was performed in 1261 Danish children and adolescents enrolled at a tertiary multidisciplinary childhood obesity treatment center. Measurements of anthropometrics, blood pressure, fasting blood biochemistry including lipid and hormone levels, and dual-energy X-ray absorptiometry were performed at baseline and throughout treatment. RESULTS: Of 1209 children and adolescents that met all criteria to be included in the described analyses, 30 (2.5%) carried damaging or unresolved MC4R mutations. At baseline, mutation carriers exhibited higher concentrations of plasma thyroid-stimulating hormone (p = 0.003), and lower concentrations of plasma thyroxine (p = 0.010) compared to noncarriers. After a median of 1 year of treatment (range 0.5-4.0 years), body mass index (BMI) standard deviation score (SDS) was reduced in noncarriers but not in carriers, and this difference in treatment response was statistically significant (p = 0.005). Furthermore, HDL cholesterol was reduced in carriers, a response significantly different from that of noncarriers (p = 0.017). CONCLUSION: Among Danish children and adolescents with overweight or obesity entering a tertiary lifestyle intervention, 2.5% carried damaging or unresolved MC4R mutations. In contrast to noncarriers, carriers of damaging or unresolved MC4R mutations failed to reduce their BMI SDS during obesity treatment, indicating a need for personalized treatment based on the MC4R genotype.


Assuntos
Obesidade Pediátrica , Receptor Tipo 4 de Melanocortina/genética , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Dinamarca , Humanos , Estilo de Vida , Mutação/genética , Obesidade Pediátrica/sangue , Obesidade Pediátrica/epidemiologia , Obesidade Pediátrica/genética , Obesidade Pediátrica/terapia , Tireotropina/sangue , Tiroxina/sangue , Adulto Jovem
8.
Clim Change ; 163(1): 63-82, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33281250

RESUMO

In recent decades, greater acknowledgement has been given to climate change as a cultural phenomenon. This paper takes a cultural lens to the topic of climate change, in which climate-relevant understandings are grounded in wider cultural, political and material contexts. We approach climate-relevant accounts at the level of the everyday, understood as a theoretically problematic and politically contested space This is in contrast to simply being the backdrop to mundane, repetitive actions contributing to environmental degradation and the site of mitigative actions. Taking discourse as a form of practice in which fragments of cultural knowledge are drawn on to construct our environmental problems, we investigate citizens' accounts of climate-relevant issues in three culturally diverse emerging economies: Brazil, South Africa and China. These settings are important because greenhouse gas (GHG) emissions are predicted to significantly increase in these countries in the future. We conducted semi-structured interviews with a range of citizens in each country using a narrative approach to contextualise climate-relevant issues as part of people's lifestyle narratives. Participants overwhelmingly framed their accounts in the context of locally-salient issues, and few accounts explicitly referred to the phenomenon of climate change. Instead, elements of climate changes were conflated with other environmental issues and related to a wide range of cultural assumptions that influenced understandings and implied particular ways of responding to environmental problems. We conclude that climate change scholars should address locally relevant understandings and develop dialogues that can wider meanings that construct climate-relevant issues in vernacular ways at the local level.

9.
Waste Manag ; 108: 183-188, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32361534

RESUMO

The distance of recycling bins from households is often considered important by practitioners, but published evidence for this uses only indirect and self-reported data. This study aims to provide such evidence by obtaining a clean test using measured distances in a walled community with 1200 households with the same building types, local governance, recycling and waste arrangements. The number of deposits each month of food waste for recycling at a designated site are logged via smart-cards allocated per household. The number of days per month that each household deposits showed a highly significant - but small - negative correlation with distance of the bin: fewer householders participate if further away, accounting for 3% of the variation. Surprisingly, there is no variation with distance among those who do participate: their recycling frequency does not vary. This second result is not consistent with the first in terms of cost/benefit concepts assumed by government planners, nor with the static theories of behaviour currently used in waste management research. We recommend that recycling practitioners note the smallness of the contribution of distance to recycling performance, and not overrate it. And we recommend that researchers make better use of non-static models (which model different stages towards behaviour change), which our second result appears to call for.


Assuntos
Eliminação de Resíduos , Gerenciamento de Resíduos , Características da Família , Alimentos , Reciclagem
10.
Clin Genet ; 97(6): 902-907, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32087029

RESUMO

Silver-Russell syndrome (SRS) is an imprinting disorder characterized by prenatal and postnatal growth retardation, relative macrocephaly, feeding difficulties and body asymmetry. Recently, upd(20)mat has been identified in few patients with SRS-like features, suggestive of a new imprinting disorder characterized by prenatal and postnatal growth failure. Here, we describe two male patients with upd(20) and feeding difficulties, prenatal and postnatal growth retardation and normal cognitive development. During pregnancy, confined placental mosaicism for trisomy 20 was detected in one of the patients but was not investigated further until identification of upd(20)mat in the neonatal period. To evaluate whether upd(20)mat should be part of the first trier genetic diagnostic in patients with growth retardation, we screened a large cohort of patients (n = 673) referred to our laboratories for SRS-testing without detecting any upd(20). Our results, along with the existing evidence, indicate that upd(20)mat is a very rare cause of growth retardation, but should be followed up when confined placental mosaicism for trisomy 20 mosaicism is observed during pregnancy.


Assuntos
Impressão Genômica/genética , Síndrome de Silver-Russell/genética , Trissomia/genética , Dissomia Uniparental/genética , Adolescente , Criança , Pré-Escolar , Cromossomos Humanos Par 20/genética , Cromossomos Humanos Par 20/fisiologia , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mosaicismo , Fenótipo , Placenta/metabolismo , Placenta/patologia , Gravidez , Síndrome de Silver-Russell/patologia , Dissomia Uniparental/patologia
11.
Sci Total Environ ; 711: 135045, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31818601

RESUMO

Sustainable development is a global aim, aided in its application by the use of social, environmental and economic indicators for monitoring, planning, and assessment. However, several significant weaknesses are reported which reveal the need for improvement of the social indicators such as problems of being difficult to localize; to measure, and to be complete; being less commonly used; and thus, leading to assessments which are unbalanced across the three domains. Here we demonstrate that a values-based approach called WeValue InSitu, previously known to reliably 'crystallize' local shared values, can be successfully used as a bolt-on process to produce localized social indicators for direct insertion into the SuRF-UK process. SuRF-UK is a widely used decision-support framework for sustainable remediation of brownfield sites, and we apply it here to a hypothetical scenario analysis for a real community in villages near a derelict Salt Lake in Nigeria. Results show the WeValue InSitu approach resolves the reported challenges of localized social indicators, does not introduce any new issues, and in addition provides a route for wider participation and auditability. The study shows that a mechanism of red-flag boundaries may need to be introduced into SuRF-UK to allow veto of unacceptable breaches of social issues by proposed scenarios.

12.
Front Psychol ; 10: 788, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31214064

RESUMO

Responding to serious environmental problems, requires urgent and fundamental shifts in our day-to-day lifestyles. This paper employs a qualitative, cross-cultural approach to explore people's subjective self-reflections on their experiences of pro-environmental behavioral spillover in three countries; Brazil, China, and Denmark. Behavioral spillover is an appealing yet elusive phenomenon, but offers a potential way of encouraging wider, voluntary lifestyle shifts beyond the scope of single behavior change interventions. Behavioral spillover theory proposes that engaging in one pro-environmental action can catalyze the performance of others. To date, evidence for the phenomenon has been mixed, and the causal processes governing relationships between behaviors appear complex, inconsistent and only partly understood. This paper addresses a gap in the literature by investigating accounts of behavioral spillover in three diverse cultural settings using qualitative semi-structured interviews. The analysis shows that while around half of participants overall who were questioned recalled spillover effects, the other half had not consciously experienced spillover. There were few significant differences across cultures, though some forms of spillover effects were reported more in some cultures than others. More environmentally engaged participants across all three countries were significantly more likely to experience spillover than those who were less engaged. Accounts of within-domain spillovers were most commonly reported, mainly comprising waste, resource conservation and consumption-related actions. Accounts of between-domain spillover were very rare. Recollection of contextual and interpersonal spillover effects also emerged from the interviews. Our findings suggest that more conscious behavioral spillover pathways may be limited to those with pre-existing environmental values. Behavioral spillover may comprise multiple pathways incorporating conscious and unconscious processes. We conclude that targeting behavioral catalysts that generate more socially diffuse spillover effects could offer more potential than conventional spillover involving a single individual.

13.
Obes Surg ; 29(8): 2554-2561, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31001758

RESUMO

BACKGROUND: The weight loss after bariatric surgery shows considerable individual variation. Twin studies of response to dietary interventions and studies of bariatric surgery patients suggest that genetic differences may play a role. This study aimed to examine the effect of three genetic risk scores on the inter-individual variation in excess body mass index loss (EBMIL) after Roux-en-Y gastric bypass. Furthermore, we searched among known adiposity-related single nucleotide polymorphisms (SNPs) for genetic determinants of the inter-individual variation in EBMIL. METHODS: Patients with morbid obesity underwent Roux-en-Y gastric bypass and were genotyped (n = 577). Two genetic risk scores for weight loss after bariatric surgery and a genetic risk score for body mass index were calculated. Associations between the genetic risk scores and EBMIL were evaluated. Lasso regression was performed on 126 SNPs known to be associated with adiposity. RESULTS: The average EBMIL was 76.9% (range 21.7-149.2%). EBMIL was 81.1% (SD 20.6) and 73.9% (SD 21.7) in the high and low tertile groups of a genetic risk score for weight loss. Patients with a low genetic risk score for body mass index (in the lowest 5% percentile) had an EBMIL of 68.8% (SD 20.6, p = 0.018). Thirteen adiposity-related SNPs were identified to associate with EBMIL through lasso regression. DISCUSSION: A genetic risk score was associated with EBMIL after bariatric surgery, but may not yet be applicable to clinical practice. Patients genetically predisposed to low body mass index had lower weight loss after bariatric surgery.


Assuntos
Cirurgia Bariátrica , Obesidade Mórbida/genética , Obesidade Mórbida/cirurgia , Redução de Peso/genética , Adiposidade/genética , Adulto , Variação Biológica da População/genética , Índice de Massa Corporal , Dinamarca , Feminino , Derivação Gástrica , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Resultado do Tratamento
14.
Sci Total Environ ; 652: 810-821, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30380488

RESUMO

Brownfield regeneration to soft reuse such as recreation and amenity has become increasingly common due to the demand for the potential environmental, social and economic benefits that it can deliver. This has led in turn to an increased demand for improved tools to support decision-making for this style of regeneration: tools which are simple to use, based on robust scientific principles and preferably which can ultimately link to quantitative or semi-quantitative cost-benefit analyses. This work presents an approach to assessing and comparing different scenarios for brownfield regeneration to soft reuse and other end-points. A "sustainability linkages" approach, based on sustainability assessment criteria produced by the UK Sustainable Remediation Forum (SuRF-UK), is developed and used in a refined qualitative sustainability assessment, and applied to develop a conceptual site model of sustainability, for a specific case study site (Port Sunlight River Park, U.K., a public leisure park established and maintained on a capped and managed former landfill site). Ranking, on an ex post basis, highlighted the clear sustainability advantages that the establishment of the Port Sunlight River Park has compared with a hypothetical non-development scenario. The conceptual site model provides a clearer basis for understanding cause and effect for benefits and disbenefits and a rationale for grouping individual effects based on their ease of valuation, providing a road map for cost-benefit assessments by (1) being able to match specific linkages to the most appropriate means of valuation, and (2) transparently connecting the sustainability assessment and cost benefit assessment processes.

18.
Nat Commun ; 8: 14977, 2017 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-28443625

RESUMO

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.


Assuntos
Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Obesidade/genética , Locos de Características Quantitativas/genética , Fumar/genética , Adiposidade/genética , Adulto , Distribuição da Gordura Corporal , Índice de Massa Corporal , Epistasia Genética , Humanos , Fenótipo , Polimorfismo de Nucleotídeo Único , Circunferência da Cintura/genética , Relação Cintura-Quadril
19.
PLoS Genet ; 13(4): e1006528, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28448500

RESUMO

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.


Assuntos
Adiposidade/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Exercício Físico , Obesidade/genética , Adiposidade/fisiologia , Índice de Massa Corporal , Epigenômica , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Obesidade/fisiopatologia , Circunferência da Cintura , Relação Cintura-Quadril
20.
J Med Genet ; 54(3): 166-175, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27627987

RESUMO

BACKGROUND: Levels of serum thyroid-stimulating hormone (TSH) indicate thyroid function, because thyroid hormone negatively controls TSH release. Genetic variants in the vascular endothelial growth factor A (VEGFA) gene are associated with TSH levels. The aim of this study was to characterise the association of VEGFA variants with TSH in a Danish cohort and to identify and characterise functional variants. METHODS: We performed an association study of the VEGFA locus for circulating TSH levels in 8445 Danish individuals. Lead variants were tested for allele-specific effects in vitro using luciferase reporter and gel-shift assays. RESULTS: Four SNPs in VEGFA were associated with circulating TSH (rs9472138, rs881858, rs943080 and rs4711751). For rs881858, the presence of each G-allele was associated with a corresponding decrease in TSH levels of 2.3% (p=8.4×10-9) and an increase in circulating free T4 levels (p=0.0014). The SNP rs881858 is located in a binding site for CHOP (C/EBP homology protein) and c/EBPß (ccaat enhancer binding protein ß). Reporter-gene analysis showed increased basal enhancer activity of the rs881858 A-allele versus the G-allele (34.5±9.9% (average±SEM), p=0.0012), while co-expression of CHOP effectively suppressed the rs881858 A-allele activity. The A-allele showed stronger binding to CHOP in gel-shift assays. CONCLUSIONS: VEGF is an important angiogenic signal required for tissue expansion. We show that VEGFA variation giving allele-specific response to transcription factors with overlapping binding sites associate closely with circulating TSH levels. Because CHOP is induced by several types of intracellular stress, this indicates that cellular stress could be involved in the normal or pathophysiological response of the thyroid to TSH. TRIAL REGISTRATION NUMBER: NCT00289237, NCT00316667; Results.


Assuntos
Isquemia Miocárdica/genética , Tireotropina/sangue , Fator de Transcrição CHOP/genética , Fator A de Crescimento do Endotélio Vascular/genética , Dinamarca , Elementos Facilitadores Genéticos , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/sangue , Isquemia Miocárdica/patologia , Polimorfismo de Nucleotídeo Único , Ligação Proteica/genética , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Tireotropina/deficiência , Tireotropina/genética
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