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- Santangelo, James S., et al.
(författare)
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Global urban environmental change drives adaptation in white clover
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
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Tidskriftsartikel (refereegranskat)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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| 3. |
- Iacopetta, B, et al.
(författare)
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Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study.
- 2006
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Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. - : Elsevier BV. - 0923-7534. ; 17:5, s. 842-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (< or=20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity. MATERIALS AND METHODS: TP53 mutations within a large, international database of CRC (n = 3583) were classified according to functional status for transactivation. RESULTS: Inactive TP53 mutations were found in 29% of all CRCs and were more frequent in rectal (32%) than proximal colon (22%) tumours (P < 0.001). Higher frequencies of inactive TP53 mutations were also seen in advanced stage tumours (P = 0.0003) and in tumours with the poor prognostic features of vascular (P = 0.006) and lymphatic invasion (P = 0.002). Inactive TP53 mutations were associated with significantly worse outcome only in patients with Dukes' stage D tumours (RR = 1.71, 95%CI 1.25-2.33, P < 0.001). Patients with Dukes' C stage tumours appeared to gain a survival benefit from 5-fluorouracil-based chemotherapy regardless of TP53 functional status for transactivation ability. CONCLUSIONS: Mutations that inactivate the transactivational ability of TP53 are more frequent in advanced CRC and are associated with worse prognosis in this stage of disease.
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| 4. |
- Lindemalm, C, et al.
(författare)
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Associations Between Asthma and Sensitization to Pet or Pollen Allergens in Young Swedish Twins - The STOPPA Study
- 2017
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Ingår i: Twin research and human genetics : the official journal of the International Society for Twin Studies. - : Cambridge University Press (CUP). - 1832-4274. ; 20:5, s. 380-388
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Tidskriftsartikel (refereegranskat)abstract
- Background: An association between childhood asthma and IgE sensitization has been established, but our understanding of the genetic and environmental contribution to it is incomplete. Our aim was to estimate the associations and dose-response relationship between asthma and sensitization to airborne allergens in Swedish 9- to 14-year-old twins. Additionally, we aimed to explore the importance of familial confounding from shared genes and environment using co-twin controls.Methods: In the STOPPA cohort, 752 same-sex twin children were screened with Phadiatop® (Thermo Fisher Scientific; Pharmacia, Uppsala, Sweden); if positive further analysis of IgE antibodies to airborne allergens of pets (cat, horse, dog), pollens (birch, timothy, mugwort), mites, and mold were performed. The associations between asthma and airborne allergens were assessed with generalized estimating equations. The co-twin control analysis was performed by conditional logistic regression.Results: Children with positive Phadiatop® had more than doubled odds of asthma (OR 2.53, 95% CI [1.74, 3.70]). Sensitization to pet allergens was associated with increased odds of asthma; for example, cat OR 4.15 (95% CI [2.67, 6.45]), with similar estimates for pollens; for example, birch OR 3.22 (95% CI [2.12, 4.91]). Associations persisted with sensitization as a categorical variable and for trend, indicating a dose-response relationship. Results remained in the co-twin analyses; for example, cat OR 4.75 (95% CI [1.62, 14.0]) and birch OR 5.00 (95% CI [1.45, 17.3]).Conclusion: The association between childhood asthma and sensitization to airborne allergens remains in co-twin analyses, indicating they are not due to confounding from shared environmental or genetic factors.
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| 7. |
- Ullemar, V., et al.
(författare)
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Predictors of Adolescents' Consent to Use Health Records for Research and Results from Data Collection in a Swedish Twin Cohort
- 2015
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Ingår i: Twin Research and Human Genetics. - Stockholm : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 18:3, s. 256-265
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Non-random selection into a study population due to differences between consenters and non-consenters may introduce participation bias. Past investigations of factors predicting consent to collection of medical health records for research imply that age, sex, health status, and education are of importance for participation, but disagree on the direction of effects. Very little is known about influences on consent from adolescents. Methods: Two cohorts of Swedish 15-year-old twins (total n = 4,611) previously invited to the Child and Adolescent Twin Study in Sweden (CATSS) responded to a questionnaire with information on sex, individual's health, height, weight, and parental factors. The questionnaire included a question for consent to collection of medical health records. Predictors for consent were analyzed using logistic regression. Additionally, regional differences in the collection of health records of consenters were evaluated. Results: Males were significantly less likely to consent compared to females (OR 0.74, 95% CI 0.64-0.85). The twin siblings' decision to consent was strongly associated with consent (OR 10.9, 95% CI 8.76-13.5), and individuals whose parents had responded to the original CATSS study were more likely to consent to record collection at age 15 (OR 2.2, 95% CI 1.81-2.75). Results of the subsequent collection of consenters' medical health records varied between geographical regions of Sweden. Conclusion: We identified several predictors for adolescents' consent to collection of their medical health records. Further selection was introduced through the subsequent record collection. Whether this will induce participation bias in future studies depends on the research questions' relationship to the identified predictors.
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| 8. |
- Abend, M., et al.
(författare)
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RENEB Inter-Laboratory Comparison 2021 : The Gene Expression Assay
- 2023
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 199:6, s. 598-615
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Tidskriftsartikel (refereegranskat)abstract
- Early and high-throughput individual dose estimates are essential following large-scale radiation exposure events. In the context of the Running the European Network for Biodosimetry and Physical Dosimetry (RENEB) 2021 exercise, gene expression assays were conducted and their corresponding performance for dose-assessment is presented in this publication. Three blinded, coded whole blood samples from healthy donors were exposed to 0, 1.2 and 3.5 Gy X-ray doses (240 kVp, 1 Gy/min) using the X-ray source Yxlon. These exposures correspond to clinically relevant groups of unexposed, low dose (no severe acute health effects expected) and high dose exposed individuals (requiring early intensive medical health care). Samples were sent to eight teams for dose estimation and identification of clinically relevant groups. For quantitative reverse transcription polymerase chain reaction (qRT-PCR) and microarray analyses, samples were lysed, stored at 20°C and shipped on wet ice. RNA isolations and assays were run in each laboratory according to locally established protocols. The time-to-result for both rough early and more precise later reports has been documented where possible. Accuracy of dose estimates was calculated as the difference between estimated and reference doses for all doses (summed absolute difference, SAD) and by determining the number of correctly reported dose estimates that were defined as ±0.5 Gy for reference doses <2.5 Gy and ±1.0 Gy for reference doses >3 Gy, as recommended for triage dosimetry. We also examined the allocation of dose estimates to clinically/diagnostically relevant exposure groups. Altogether, 105 dose estimates were reported by the eight teams, and the earliest report times on dose categories and estimates were 5 h and 9 h, respectively. The coefficient of variation for 85% of all 436 qRT-PCR measurements did not exceed 10%. One team reported dose estimates that systematically deviated several-fold from reported dose estimates, and these outliers were excluded from further analysis. Teams employing a combination of several genes generated about two-times lower median SADs (0.8 Gy) compared to dose estimates based on single genes only (1.7 Gy). When considering the uncertainty intervals for triage dosimetry, dose estimates of all teams together were correctly reported in 100% of the 0 Gy, 50% of the 1.2 Gy and 50% of the 3.5 Gy exposed samples. The order of dose estimates (from lowest to highest) corresponding to three dose categories (unexposed, low dose and highest exposure) were correctly reported by all teams and all chosen genes or gene combinations. Furthermore, if teams reported no exposure or an exposure >3.5 Gy, it was always correctly allocated to the unexposed and the highly exposed group, while low exposed (1.2 Gy) samples sometimes could not be discriminated from highly (3.5 Gy) exposed samples. All teams used FDXR and 78.1% of correct dose estimates used FDXR as one of the predictors. Still, the accuracy of reported dose estimates based on FDXR differed considerably among teams with one team's SAD (0.5 Gy) being comparable to the dose accuracy employing a combination of genes. Using the workflow of this reference team, we performed additional experiments after the exercise on residual RNA and cDNA sent by six teams to the reference team. All samples were processed similarly with the intention to improve the accuracy of dose estimates when employing the same workflow. Re-evaluated dose estimates improved for half of the samples and worsened for the others. In conclusion, this inter-laboratory comparison exercise enabled (1) identification of technical problems and corrections in preparations for future events, (2) confirmed the early and high-throughput capabilities of gene expression, (3) emphasized different biodosimetry approaches using either only FDXR or a gene combination, (4) indicated some improvements in dose estimation with FDXR when employing a similar methodology, which requires further research for the final conclusion and (5) underlined the applicability of gene expression for identification of unexposed and highly exposed samples, supporting medical management in radiological or nuclear scenarios.
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