| 21. |
- Martrat, Griselda, et al.
(författare)
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Exploring the link between MORF4L1 and risk of breast cancer
- 2011
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. Methods: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. Results: A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to g-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, P-trend = 0.45 and 0.05, P-2df = 0.51 and 0.14, respectively; and rs10519219, P-trend = 0.92 and 0.72, P-2df = 0.76 and 0.07, respectively. Conclusions: While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers.
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| 22. |
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| 23. |
- Muscarella, Robert, et al.
(författare)
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The global abundance of tree palms
- 2020
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Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 29:9, s. 1495-1514
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Tidskriftsartikel (refereegranskat)abstract
- AimPalms are an iconic, diverse and often abundant component of tropical ecosystems that provide many ecosystem services. Being monocots, tree palms are evolutionarily, morphologically and physiologically distinct from other trees, and these differences have important consequences for ecosystem services (e.g., carbon sequestration and storage) and in terms of responses to climate change. We quantified global patterns of tree palm relative abundance to help improve understanding of tropical forests and reduce uncertainty about these ecosystems under climate change.LocationTropical and subtropical moist forests.Time periodCurrent.Major taxa studiedPalms (Arecaceae).MethodsWe assembled a pantropical dataset of 2,548 forest plots (covering 1,191 ha) and quantified tree palm (i.e., ≥10 cm diameter at breast height) abundance relative to co‐occurring non‐palm trees. We compared the relative abundance of tree palms across biogeographical realms and tested for associations with palaeoclimate stability, current climate, edaphic conditions and metrics of forest structure.ResultsOn average, the relative abundance of tree palms was more than five times larger between Neotropical locations and other biogeographical realms. Tree palms were absent in most locations outside the Neotropics but present in >80% of Neotropical locations. The relative abundance of tree palms was more strongly associated with local conditions (e.g., higher mean annual precipitation, lower soil fertility, shallower water table and lower plot mean wood density) than metrics of long‐term climate stability. Life‐form diversity also influenced the patterns; palm assemblages outside the Neotropics comprise many non‐tree (e.g., climbing) palms. Finally, we show that tree palms can influence estimates of above‐ground biomass, but the magnitude and direction of the effect require additional work.ConclusionsTree palms are not only quintessentially tropical, but they are also overwhelmingly Neotropical. Future work to understand the contributions of tree palms to biomass estimates and carbon cycling will be particularly crucial in Neotropical forests.
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| 24. |
- Norman, Åsa, et al.
(författare)
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"Everyone can take photos." Feasibility and relative validity of phone photography-based assessment of children's diets - a mixed methods study.
- 2020
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Ingår i: Nutrition Journal. - : Springer Science and Business Media LLC. - 1475-2891. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Dietary assessment methods that are user-friendly, simple, yet valid are of interest to both researchers and participants, particularly for use in disadvantaged settings, where language barriers and low levels of education are often present. We tested if parents taking photos of what children ate, using mobile phones, would be a feasible, acceptable method that could still provide information with adequate relative validity.METHODS: We used a mixed-methods design, with parents of 21 5- to 7-year-olds from disadvantaged areas in Sweden. Parents reported all dietary intake, during non-school hours, on three days (two weekdays) using a photo method (PM). The PM consisted of simple instructions and a fiduciary card, but no training, equipment or software. Text messages could be sent if necessary. As a reference method, parents completed three 24-h recalls (24HRs) with an interviewer each following day. The next week, parents completed a 9-item semi-FFQ regarding the preceding week. The outcomes were intakes (in dl) of 9 food groups, categorised as fruits and vegetables, energy-dense sweet/salty foods, and sweet drinks. Agreement with the reference 24HRs was assessed using correlations, median differences and Bland-Altman plots. Parents completed an open-ended questionnaire on barriers and facilitators. Data collectors provided complementary information. Qualitative data was analysed using qualitative manifest analysis.RESULTS: Nineteen parents (90%) provided complete data. The majority (n = 13) spoke Swedish as a second language, few (n = 4) were proficient. Compared to 24HRs, intakes measured by PM correlated well for all categories (Spearman's rho = 0.609-0.845). However, intakes were underreported, significantly so for fruits and vegetables; Bland-Altman plots indicated that the underestimation was fairly constant across intake levels. When the FFQ was compared to the 24HRs, parameters of agreement were generally inferior than for the PM. Parents found the PM a positive experience, primarily facilitated by its simplicity and familiarity. Barriers, mainly related to time and logistics, can inform further methodological refinements.CONCLUSIONS: The PM was an acceptable and feasible way to measure children's diet outside of school hours in this population of parents from disadvantaged areas. While the absolute validity should be evaluated further, this relatively simple method has potential for assessing intakes of well-defined foods at group level.
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| 25. |
- Oddo, Dominic, et al.
(författare)
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Characterization of a Set of Small Planets with TESS and CHEOPS and an Analysis of Photometric Performance
- 2023
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 165:3
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Tidskriftsartikel (refereegranskat)abstract
- The radius valley carries implications for how the atmospheres of small planets form and evolve, but this feature is visible only with highly precise characterizations of many small planets. We present the characterization of nine planets and one planet candidate with both NASA TESS and ESA CHEOPS observations, which adds to the overall population of planets bordering the radius valley. While five of our planets—TOI 118 b, TOI 262 b, TOI 455 b, TOI 560 b, and TOI 562 b—have already been published, we vet and validate transit signals as planetary using follow-up observations for four new TESS planets, including TOI 198 b, TOI 244 b, TOI 444 b, and TOI 470 b. While a three times increase in primary mirror size should mean that one CHEOPS transit yields an equivalent model uncertainty in transit depth as about nine TESS transits in the case that the star is equally as bright in both bands, we find that our CHEOPS transits typically yield uncertainties equivalent to between two and 12 TESS transits, averaging 5.9 equivalent transits. Therefore, we find that while our fits to CHEOPS transits provide overall lower uncertainties on transit depth and better precision relative to fits to TESS transits, our uncertainties for these fits do not always match expected predictions given photon-limited noise. We find no correlations between number of equivalent transits and any physical parameters, indicating that this behavior is not strictly systematic, but rather might be due to other factors such as in-transit gaps during CHEOPS visits or nonhomogeneous detrending of CHEOPS light curves.
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| 26. |
- Porsbjerg, Celeste M., et al.
(författare)
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Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma
- 2024
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: To date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials.Aim: To elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life.Methods: This was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers.Results: Overall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in FEV1 for both anti-IgE and anti-IL5/5R, with a trend for antiI-IL4R alpha. Mean FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/mu L), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and - anti- IL4R alpha, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4R alpha, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic FEV1 increase (adjusted R-2: 0.751), compared to BEC (adjusted R-2: 0.747) or FeNO alone (adjusted R-2: 0.743) (p=0.005 and <0.001, respectively); however, this prediction was not improved by the addition of IgE.Conclusions: The ability of higher baseline BEC, FeNO and their combination to predict biologic-associated lung function improvement may encourage earlier intervention in patients with impaired lung function or at risk of accelerated lung function decline.
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| 27. |
- Reveiz, Ludovic, et al.
(författare)
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Prioritization strategies in clinical practice guidelines development : a pilot study
- 2010
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Ingår i: Health Research Policy and Systems. - : BioMed Central. - 1478-4505. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Few methodological studies address the prioritization of clinical topics for the development of Clinical Practice Guidelines (CPGs). The aim of this study was to validate a methodology for Priority Determination of Topics (PDT) of CPGs.METHODS AND RESULTS: Firstly, we developed an instrument for PDT with 41 criteria that were grouped under 10 domains, based on a comprehensive systematic search. Secondly, we performed a survey of stakeholders involved in CPGs development, and end users of guidelines, using the instrument. Thirdly, a pilot testing of the PDT procedure was performed in order to choose 10 guideline topics among 34 proposed projects; using a multi-criteria analysis approach, we validated a mechanism that followed five stages: determination of the composition of groups, item/domain scoring, weights determination, quality of the information used to support judgments, and finally, topic selection. Participants first scored the importance of each domain, after which four different weighting procedures were calculated (including the survey results). The process of weighting was determined by correlating the data between them. We also reported the quality of evidence used for PDT. Finally, we provided a qualitative analysis of the process. The main domains used to support judgement, having higher quality scores and weightings, were feasibility, disease burden, implementation and information needs. Other important domains such as user preferences, adverse events, potential for health promotion, social effects, and economic impact had lower relevance for clinicians. Criteria for prioritization were mainly judged through professional experience, while good quality information was only used in 15% of cases.CONCLUSION: The main advantages of the proposed methodology are supported by the use of a systematic approach to identify, score and weight guideline topics selection, limiting or exposing the influence of personal biases. However, the methodology was complex and included a number of quantitative and qualitative approaches reflecting the difficulties of the prioritization process.
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| 28. |
- Saénz-de la O, Diana, et al.
(författare)
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Antioxidant and drought‑acclimation responses in UV‑B‑exposed transgenic Nicotiana tabacum displaying constitutive overproduction of H2O2
- 2023
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Ingår i: Photochemical and Photobiological Sciences. - : Springer. - 1474-905X .- 1474-9092. ; 22:10, s. 2373-2387
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Tidskriftsartikel (refereegranskat)abstract
- Hydrogen peroxide (H2O2) is an important molecule that regulates antioxidant responses that are crucial for plant stress resistance. Exposure to low levels of ultraviolet-B radiation (UV-B, 280–315 nm) can also activate antioxidant defenses and acclimation responses. However, how H2O2 and UV-B interact to promote stress acclimation remains poorly understood. In this work, a transgenic model of Nicotiana tabacum cv Xanthi nc, with elevated Mn-superoxide dismutase (Mn-SOD)activity, was used to study the interaction between the constitutive overproduction of H2O2 and a 14-day UV-B treatment (1.75 kJ m−2 d−1 biologically effective UV-B). Subsequently, these plants were subjected to a 7-day moderate drought treatment to evaluate the impact on drought resistance of H2O2- and UV-dependent stimulation of the plants' antioxidant system. The UV-B treatment enhanced H2O2 levels and altered the antioxidant status by increasing the epidermal flavonol index, Trolox Equivalent Antioxidant Capacity, and catalase, peroxidase and phenylalanine ammonia lyase activities in the leaves. UV-B also retarded growth and suppressed acclimation responses in highly H2O2-overproducing transgenic plants. Plants not exposed to UV-B had a higher drought resistance in the form of higher relative water content of leaves. Our data associate the interaction between Mn-SOD transgene overexpression and the UV-B treatment with a stress response. Finally, we propose a hormetic biphasic drought resistance response curve as a function of leaf H2O2 content in N. tabacum cv Xanthi.
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| 29. |
- Sáenz-de la, O. Diana, et al.
(författare)
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Ultraviolet-B exposure and exogenous hydrogen peroxide application lead to cross-tolerance toward drought in Nicotiana tabacum L.
- 2021
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Ingår i: Physiologia Plantarum. - : Blackwell Publishing. - 0031-9317 .- 1399-3054. ; 173:3, s. 666-679
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Tidskriftsartikel (refereegranskat)abstract
- Acclimation of plants to water deficit involves biochemical and physiological adjustments. Here, we studied how UV‐B exposure and exogenously applied hydrogen peroxide (H2O2) potentiates drought tolerance in tobacco (Nicotiana tabacum L. cv. xanthi nc). Separate and combined applications for 14 days of 1.75 kJ m−2 day−1 UV‐B radiation and 0.2 mM H2O2 were assessed. Both factors, individually and combined, resulted in inhibition of growth. Furthermore, the combined treatment led to the most compacted plants. UV‐B‐ and UV‐B+H2O2‐treated plants increased total antioxidant capacity and foliar epidermal flavonol index. H2O2‐ and UV‐B+H2O2‐pre‐treated plants showed cross‐tolerance to a subsequent 7‐day moderate drought treatment, which was assessed as the absence of negative impact on growth, leaf wilting, and leaf relative water content (RWC). Plant responses to the pre‐treatment were notably different: (1) H2O2 increased the activity of catalase (CAT, EC 1.11.1.6), phenylalanine ammonia lyase (PAL; EC 4.3.1.5) and peroxidase activities (POD, EC 1.11.1.7), and (2) the combined treatment induced epidermal flavonols which were key to drought tolerance. We report synergistic effects of UV‐B and H2O2 on transcription accumulation of UV RESISTANCE LOCUS 8, NAC DOMAIN PROTEIN 13 (NAC13), and BRI1‐EMS‐SUPPRESSOR 1 (BES1). Our data demonstrate a pre‐treatment‐dependent response to drought for NAC13, BES1 and CHALCONE SYNTHASE transcript accumulation. This study highlights the potential of combining UV‐B and H2O2 to improve drought tolerance which could become a useful tool to reduce water use.
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| 30. |
- 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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