| 1. |
- Blanco Blanco, Ignacio, et al.
(författare)
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Intravenous Infusions of Purified Alpha-1 Antitripsyn Effectively Controls Symptoms and Reverts Muscle Biopsy Changes in an MZ Alpha-1 Antitripsyn Deficiency and Fibromyalgia Syndrome Patient
- 2010
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Ingår i: Journal of Musculoskeletal Pain. - : Informa UK Limited. - 1540-7012 .- 1058-2452. ; 18:2, s. 167-172
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Tidskriftsartikel (refereegranskat)abstract
- Background: An MZ phenotype alpha-1 antitrypsin [AAT] deficiency and fibromyalgia syndrome [FMS] patient participated in a trial with AAT-intravenous augmentationtherapy [AAT-IV-AT] after failure of conventional therapeutic measures. Three quadricep biopsies were performed at different stages. The first one showed large aggregates of AAT and ubiquitin in myocytes and blood vessels, and moderate muscle atrophy, before AAT-IV-AT. The two remaining biopsies were performed while receiving AAT-IV-AT. Findings: Remarkably good clinical response and histological improvement in the follow-up biopsies. Conclusions: The clinical and histopathological efficacy of AAT-IV-AT evidenced in this patient should open new perspectives of research and management of AAT deficiency and FMS patients.
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| 2. |
- Carraminana, Albert, et al.
(författare)
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Rationale and Study Design for an Individualized Perioperative Open Lung Ventilatory Strategy in Patients on One-Lung Ventilation (iPROVE-OLV)
- 2019
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Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : W B SAUNDERS CO-ELSEVIER INC. - 1053-0770 .- 1532-8422. ; 33:9, s. 2492-2502
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this clinical trial is to examine whether it is possible to reduce postoperative complications using an individualized perioperative ventilatory strategy versus using a standard lung-protective ventilation strategy in patients scheduled for thoracic surgery requiring one-lung ventilation. Design: International, multicenter, prospective, randomized controlled clinical trial. Setting: A network of university hospitals. Participants: The study comprises 1,380 patients scheduled for thoracic surgery. Interventions: The individualized group will receive intraoperative recruitment maneuvers followed by individualized positive end-expiratory pressure (open lung approach) during the intraoperative period plus postoperative ventilatory support with high-flow nasal cannula, whereas the control group will be managed with conventional lung-protective ventilation. Measurements and Main Results: Individual and total number of postoperative complications, including atelectasis, pneumothorax, pleural effusion, pneumonia, acute lung injury; unplanned readmission and reintubation; length of stay and death in the critical care unit and in the hospital will be analyzed for both groups. The authors hypothesize that the intraoperative application of an open lung approach followed by an individual indication of high-flow nasal cannula in the postoperative period will reduce pulmonary complications and length of hospital stay in high-risk surgical patients. (C) 2019 Published by Elsevier Inc.
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| 3. |
- Manni, Giovanni Li, et al.
(författare)
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The OpenMolcas Web : A Community-Driven Approach to Advancing Computational Chemistry
- 2023
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Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 19:20, s. 6933-6991
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Tidskriftsartikel (refereegranskat)abstract
- The developments of the open-source OpenMolcas chemistry software environment since spring 2020 are described, with a focus on novel functionalities accessible in the stable branch of the package or via interfaces with other packages. These developments span a wide range of topics in computational chemistry and are presented in thematic sections: electronic structure theory, electronic spectroscopy simulations, analytic gradients and molecular structure optimizations, ab initio molecular dynamics, and other new features. This report offers an overview of the chemical phenomena and processes OpenMolcas can address, while showing that OpenMolcas is an attractive platform for state-of-the-art atomistic computer simulations.
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| 4. |
- Vialas, Vital, et al.
(författare)
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A multicentric study to evaluate the use of relative retention times in targeted proteomics
- 2017
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919. ; 152, s. 138-149
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Tidskriftsartikel (refereegranskat)abstract
- Despite the maturity reached by targeted proteomic strategies, reliable and standardized protocols are urgently needed to enhance reproducibility among different laboratories and analytical platforms, facilitating a more widespread use in biomedical research. To achieve this goal, the use of dimensionless relative retention times (iRT), defined on the basis of peptide standard retention times (RT), has lately emerged as a powerful tool. The robustness, reproducibility and utility of this strategy were examined for the first time in a multicentric setting, involving 28 laboratories that included 24 of the Spanish network of proteomics laboratories (ProteoRed-ISCIII). According to the results obtained in this study, dimensionless retention time values (iRTs) demonstrated to be a useful tool for transferring and sharing peptide retention times across different chromatographic set-ups both intra- and inter-laboratories. iRT values also showed very low variability over long time periods. Furthermore, parallel quantitative analyses showed a high reproducibility despite the variety of experimental strategies used, either MRM (multiple reaction monitoring) or pseudoMRM, and the diversity of analytical platforms employed. Biological significance From the very beginning of proteomics as an analytical science there has been a growing interest in developing standardized methods and experimental procedures in order to ensure the highest quality and reproducibility of the results. In this regard, the recent (2012) introduction of the dimensionless retention time concept has been a significant advance. In our multicentric (28 laboratories) study we explore the usefulness of this concept in the context of a targeted proteomics experiment, demonstrating that dimensionless retention time values is a useful tool for transferring and sharing peptide retention times across different chromatographic set-ups.
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| 5. |
- Antoniou, Antonis C., et al.
(författare)
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A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:10, s. 885-892
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Tidskriftsartikel (refereegranskat)abstract
- Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P-trend = 2.3 x 10(-9) to Ptrend = 3.9 x 10(-7)), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75-0.92, P-trend = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P-trend = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (Ptrend = 1 x 10(-7) to Ptrend = 8 x 10(-5); rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P-trend = 1.1 x 10(-7)).
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| 6. |
- Antoniou, Antonis C., et al.
(författare)
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Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers
- 2011
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:16, s. 3304-3321
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Tidskriftsartikel (refereegranskat)abstract
- Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [ hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
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| 7. |
- Blanco, Ignacio, et al.
(författare)
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Estimates of the prevalence and number of Fibromyalgia syndrome patients and their alpha-1 antitrypsin phenotypic distribution in ten countries
- 2007
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Ingår i: Journal of Musculoskeletal Pain. - 1540-7012. ; 15:4, s. 41540-41540
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Forskningsöversikt (refereegranskat)abstract
- Objectives: During the last few years, clinical, epidemiological, and pathological evidence has suggested that inherited alpha-1 antitrypsin [AAT] deficiency might play a role in the development of the fibromyalgia syndrome [FMS], probably because of the loss of AAT anti-inflammatory efficacy. The objective of this study was to estimate the prevalence and number of FMS patients, and their AAT phenotypic distribution worldwide. Methods: A critical review selecting reliable studies on the subject. Results: Studies on AAT gene frequencies and FMS prevalence were retrieved for ten countries worldwide, namely Canada, the United States of America [USA], Denmark, Finland, Germany, Italy, the Netherlands, Spain, Sweden, and Pakistan. The severe deficiency Z allele was found in all these countries, with very high frequencies in Denmark and Sweden [23 and 27 per 1,000, respectively], high frequencies in Italy and Spain [16 and 17], intermediate frequencies in Germany, the Netherlands, Canada, and the USA [10 to 14], and a low frequency in Pakistan [nine per 1,000]. The calculated prevalence of AAT deficiency and the number of FMS patients with AAT deficiency were 1/10 and 25,408 in Canada, 1/11 and 478,681 in the US, 1/9 and 3,124 in Denmark, 1/36 and 726 in Finland, 1/16 and 48,523 in Germany, 1/13 and 84,876 in Italy, 1115 and 9,639 in the Netherlands, 1/4 and 114,359 in Spain, 1/11 and 9,065 in Sweden, and 1/25 and 85.965 in Pakistan. Our calculations predict that AAT deficiency would remain undetected in around nine percent of FMS patients, with about eight percent of them carrying moderate deficiency phenotypes [MS, SS, and MZ], and less than one percent with severe deficiency phenotypes [SZ and ZZ]. Conclusions: Therefore, AAT phenotype characterization should be recommended in FMS patients and the possible efficacy of AAT replacement therapy in severe deficiency FMS patients should warrant further Studies.
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| 8. |
- Blanco, Ignacio, et al.
(författare)
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Low plasma levels of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF alpha), and vascular endothelial growth factor (VEGF) in patients with alpha1-antitrypsin deficiency-related fibromyalgia
- 2010
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Ingår i: Clinical Rheumatology. - : Springer Science and Business Media LLC. - 1434-9949 .- 0770-3198. ; 29:2, s. 189-197
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Tidskriftsartikel (refereegranskat)abstract
- Abnormalities in blood inflammatory markers have been associated with clinical manifestations and the pathogenesis of the fibromyalgia syndrome (FMS); a relationship between inherited alpha1-antitrypsin deficiency (AATD) and FMS has also been recently raised. In this study, plasma levels of inflammatory markers in FMS patients with and without AATD have been investigated. Blood samples from 138 age-matched females (79 FMS) and 59 general population (GP), with normal MM [n = 82 (59.4%)] and with MS, MZ, SZ, and ZZ AATD genotypes [n = 56 (40.6%)], were analyzed by ELISA for monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF alpha), soluble TNF alpha receptors I and II, interleukin-8, and vascular endothelial growth factor (VEGF). Plasma levels of MCP-1, VEGF, and TNF alpha were significantly lower in FMS and GP subjects with AATD compared with those with normal MM-AAT genotypes. Moreover, plasma levels of MCP-1, VEGF, and TNF alpha were lower in AATD subjects with FMS than in those without FMS (P = 0.000, 0.000, and 0.046, respectively). No statistical differences were found for the other substances measured. Furthermore, a logistic regression model based on plasma MCP-1 cutoff value of a parts per thousand currency sign130 pg/ml allowed us to discriminate between FMS and GP subjects with a sensitivity of about 93% and a specificity of 79%. Low plasma levels of MCP-1, VEGF, and TNF alpha are related to AATD, although more markedly in FMS patients. Thus, hypotheses considering FMS as an inflammatory condition related to high plasma levels of inflammatory biomarkers cannot be supported.
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| 9. |
- Bolton, Kelly L., et al.
(författare)
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Association Between BRCA1 and BRCA2 Mutations and Survival in Women With Invasive Epithelial Ovarian Cancer
- 2012
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Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598. ; 307:4, s. 382-390
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Tidskriftsartikel (refereegranskat)abstract
- Context Approximately 10% of women with invasive epithelial ovarian cancer (EOC) carry deleterious germline mutations in BRCA1 or BRCA2. A recent article suggested that BRCA2-related EOC was associated with an improved prognosis, but the effect of BRCA1 remains unclear. Objective To characterize the survival of BRCA carriers with EOC compared with noncarriers and to determine whether BRCA1 and BRCA2 carriers show similar survival patterns. Design, Setting, and Participants A pooled analysis of 26 observational studies on the survival of women with ovarian cancer, which included data from 1213 EOC cases with pathogenic germline mutations in BRCA1 (n=909) or BRCA2 (n=304) and from 2666 noncarriers recruited and followed up at variable times between 1987 and 2010 (the median year of diagnosis was 1998). Main Outcome Measure Five-year overall mortality. Results The 5-year overall survival was 36% (95% CI, 34%-38%) for noncarriers, 44% (95% CI, 40%-48%) for BRCA1 carriers, and 52% (95% CI, 46%-58%) for BRCA2 carriers. After adjusting for study and year of diagnosis, BRCA1 and BRCA2 mutation carriers showed a more favorable survival than noncarriers (for BRCA1: hazard ratio [HR], 0.78; 95% CI, 0.68-0.89; P<.001; and for BRCA2: HR, 0.61; 95% CI, 0.50-0.76; P<.001). These survival differences remained after additional adjustment for stage, grade, histology, and age at diagnosis (for BRCA1: HR, 0.73; 95% CI, 0.64-0.84; P<.001; and for BRCA2: HR, 0.49; 95% CI, 0.39-0.61; P<.001). The BRCA1 HR estimate was significantly different from the HR estimated in the adjusted model (P for heterogeneity=.003). Conclusion Among patients with invasive EOC, having a germline mutation in BRCA1 or BRCA2 was associated with improved 5-year overall survival. BRCA2 carriers had the best prognosis. JAMA. 2012;307(4):382-390
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| 10. |
- Candido-dos-Reis, Francisco J, et al.
(författare)
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Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer
- 2015
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 21:3, s. 7-652
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To analyze the effect of germline mutations in BRCA1 and BRCA2 on mortality in patients with ovarian cancer up to 10 years after diagnosis.EXPERIMENTAL DESIGN: We used unpublished survival time data for 2,242 patients from two case-control studies and extended survival time data for 4,314 patients from previously reported studies. All participants had been screened for deleterious germline mutations in BRCA1 and BRCA2. Survival time was analyzed for the combined data using Cox proportional hazard models with BRCA1 and BRCA2 as time-varying covariates. Competing risks were analyzed using Fine and Gray model.RESULTS: The combined 10-year overall survival rate was 30% [95% confidence interval (CI), 28%-31%] for non-carriers, 25% (95% CI, 22%-28%) for BRCA1 carriers, and 35% (95% CI, 30%-41%) for BRCA2 carriers. The HR for BRCA1 was 0.53 at time zero and increased over time becoming greater than one at 4.8 years. For BRCA2, the HR was 0.42 at time zero and increased over time (predicted to become greater than 1 at 10.5 years). The results were similar when restricted to 3,202 patients with high-grade serous tumors and to ovarian cancer-specific mortality.CONCLUSIONS: BRCA1/2 mutations are associated with better short-term survival, but this advantage decreases over time and in BRCA1 carriers is eventually reversed. This may have important implications for therapy of both primary and relapsed disease and for analysis of long-term survival in clinical trials of new agents, particularly those that are effective in BRCA1/2 mutation carriers.
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| 11. |
- Ding, Yuan C, et al.
(författare)
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A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers
- 2012
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 21:8, s. 1362-1370
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers.METHODS: IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers.RESULTS: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P(difference), 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03).CONCLUSION: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers.Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers.
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| 12. |
- Dorn, Reinhold J., et al.
(författare)
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CRIRES+ on sky : High spectral resolution at infrared wavelength enabling better science at the ESO VLT
- 2022
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Ingår i: Ground-Based And Airborne Instrumentation For Astronomy IX. - : SPIE - International Society for Optical Engineering. - 9781510653504 - 9781510653498
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Konferensbidrag (refereegranskat)abstract
- CRIRES+ extended the capabilities of CRIRES, the CRyogenic InfraRed Echelle Spectrograph. It transformed this VLT instrument into a cross-dispersed spectrograph to increase the wavelength range that is covered simultaneously by a factor of ten. In addition, a new detector focal plane array of three Hawaii 2RG detectors with a 5.3 mu m cut-off wavelength replaced the existing detectors. Amongst many other improvements a new spectropolarimetric unit was added and the calibration system has been enhanced. The instrument was installed at the VLT on Unit Telescope 3 beginning of 2020 and successfully commissioned and verified for science operations during 2021, partly remote from Europe due to the pandemic. The instrument was subsequently offered to the community from October 2021 onwards. This article describes the performance and capabilities of this development and presents on sky results.
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| 13. |
- Gaudet, Mia M., et al.
(författare)
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Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer
- 2010
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 6:10
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Tidskriftsartikel (refereegranskat)abstract
- The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (, 40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (lambda) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values, 10 25 and 39 SNPs had p-values<10(-4). These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, p = 3: 8 x 10(-5)) and for rs311499 was 0.72 (95% CI 0.61-0.85, p = 6: 6 x 10(-5)). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, p = 1: 2 x 10(-8)). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer.
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| 14. |
- Islar, Mine, et al.
(författare)
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Diverse values of nature for sustainability
- 2022
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 620, s. 813-823
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Tidskriftsartikel (refereegranskat)abstract
- Twenty-five years since foundational publications on valuing ecosystem services for human well-being1,2, addressing the global biodiversity crisis3 still implies confronting barriers to incorporating nature’s diverse values into decision-making. These barriers include powerful interests supported by current norms and legal rules such as property rights, which determine whose values and which values of nature are acted on. A better understanding of how and why nature is (under)valued is more urgent than ever4. Notwithstanding agreements to incorporate nature’s values into actions, including the Kunming-Montreal Global Biodiversity Framework (GBF)5 and the UN Sustainable Development Goals6, predominant environmental and development policies still prioritize a subset of values, particularly those linked to markets, and ignore other ways people relate to and benefit from nature7. Arguably, a ‘values crisis’ underpins the intertwined crises of biodiversity loss and climate change8, pandemic emergence9 and socio-environmental injustices10. On the basis of more than 50,000 scientific publications, policy documents and Indigenous and local knowledge sources, the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES) assessed knowledge on nature’s diverse values and valuation methods to gain insights into their role in policymaking and fuller integration into decisions7,11. Applying this evidence, combinations of values-centred approaches are proposed to improve valuation and address barriers to uptake, ultimately leveraging transformative changes towards more just (that is, fair treatment of people and nature, including inter- and intragenerational equity) and sustainable futures.
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| 15. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 16. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 17. |
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| 18. |
- 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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| 19. |
- Maxwell, Christopher A., et al.
(författare)
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Interplay between BRCA1 and RHAMM Regulates Epithelial Apicobasal Polarization and May Influence Risk of Breast Cancer
- 2011
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Ingår i: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885 .- 1544-9173. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio ((w)HR) = 1.09 (95% CI 1.02-1.16), p(trend) = 0.017; and n = 3,965, (w)HR = 1.04 (95% CI 0.94-1.16), p(trend) = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM.
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| 20. |
- Moreno, Noelia, et al.
(författare)
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Rabbit hemorrhagic disease virus capsid, a versatile platform for foreign B-cell epitope display inducing protective humoral immune responses
- 2016
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 6:31844
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Tidskriftsartikel (refereegranskat)abstract
- Virus-like particles (VLPs), comprised of viral structural proteins devoid of genetic material, are tunable nanoparticles that can be chemically or genetically engineered, to be used as platforms for multimeric display of foreign antigens. Here, we report the engineering of chimeric VLPs, derived from rabbit hemorrhagic disease virus (RHDV) for presentation of foreign B-cell antigens to the immune system. The RHDV capsid comprises 180 copies of a single capsid subunit (VP60). To evaluate the ability of chimeric RHDV VLPs to elicit protective humoral responses against foreign antigens, we tested two B-cell epitopes: a novel neutralizing B-cell epitope, derived from feline calicivirus capsid protein, and a well characterized B-cell epitope from the extracellular domain of influenza A virus M2 protein (M2e). We generated sets of chimeric RHDV VLPs by insertion of the foreign B-cell epitopes at three different locations within VP60 protein (which involved different levels of surface accessibility) and in different copy numbers per site. The immunogenic potential of the chimeric VLPs was analyzed in the mouse model. The results presented here indicated that chimeric RHDV VLPs elicit potent protective humoral responses against displayed foreign B-cell epitopes, demonstrated by both, in vitro neutralization and in vivo protection against a lethal challenge.
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| 21. |
- Osorio, Ana, et al.
(författare)
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DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
- 2014
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7×10-3) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8×10-3). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
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| 22. |
- Quétel, C. R., et al.
(författare)
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Methylmercury in tuna: demonstrating measurement capabilities and evaluating comparability of results worldwide from the CCQM P-39 comparison
- 2005
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Ingår i: Journal of Analytical Atomic Spectrometry. - : Royal Society of Chemistry (RSC). - 0267-9477 .- 1364-5544. ; 20, s. 1058-66
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Tidskriftsartikel (refereegranskat)abstract
- Six metrology institutes (NMIs) representing at the Comité International des Poids et Mesures (CIPM) 4 Member States of the Metre Convention and 2 international organisations, and 8 expert laboratories selected outside CIPM have compared their capabilities to quantitatively measure methylmercury (MeHg) in a prepared tuna material containing approximately 4.3 mg kg–1 Hg. This comparison was the object of the CIPM–Comité Consultatif pour la Quantité de Matière (CCQM) Pilot Study 39, organised by the Institute for Reference Materials and Measurements (IRMM), from the European Commission—Joint Research Centre. Beside the test material itself, a bottle of the BCR-464 tuna Certified Reference Material (CRM) and an ampoule of IRMM-670, a 202Hg isotope enriched MeHg candidate isotopic CRM, were distributed to all participants, who were free to apply the measurement strategy of their choice. Four, including 1 NMI, relied on external calibration or the method of standard additions, whereas the other 10 implemented an isotope dilution mass spectrometry (IDMS) approach and chose to use the IRMM-670 for their measurements. Alkaline digestion at room temperature (with manual shaking) or high temperature (under sonication, oven or hot plate conditions) was employed by most participants, with hydrochloric acid leaching the second most popular choice. Alkylation (4 phenylations, 4 ethylations and 3 propylations) in the aqueous phase was preferred by a large majority over butylation by the Grignard reaction. All participants were requested to estimate the uncertainty associated with their results and 9 out of 14 stated relative combined uncertainties below 6%(k= 2). Despite this apparent consensus, the perception of which factor caused the largest contribution to this estimation differed among participants because of the differences in the analytical methodologies deployed but also because of wide differences of the concepts of uncertainty estimation. The mixture mode(MM) median, calculated also from the measurement uncertainties stated by the participants, was 1.967 ± 0.204 × 10–5 mol kg–1(95% confidence). Twelve of the results were re-grouped within a range of less than 0.3 × 10–5 mol kg–1(MM median = 1.967 ± 0.162 × 10–5 mol kg–1, 95% confidence): they nearly all (1 exception) overlapped with each other within k= 2 stated uncertainties. For the other 2 results the uncertainty seemed to have been particularly underestimated as they lay, respectively, at more than 20% above and less than –40% below the overall average. The relative standard deviation of the results of 9 laboratories out of the 10 that applied IDMS was about 2.6%. It can be assumed from the degree of equivalence shown by 12 out of 14 study participants that, at present, laboratories worldwide are potentially able to supply accurate results for MeHg in fish-type matrices (containing about 2 × 10–5 mol kg–1) within ±10% uncertainty. This encouraging outcome permitted scheduling of a follow-up CCQM-K43 key comparison for a lower MeHg content level in salmon tissues.
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| 23. |
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| 24. |
- Sitkauskiene, Brigita, et al.
(författare)
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Screening for alpha1-antitrypsin deficiency in Lithuanian patients with COPD
- 2008
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 102:11, s. 1654-1658
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alphal-antitrypsin (AAT) deficiency is an under-diagnosed condition in patients with chronic obstructive pulmonary disease (COPD). The objective of the present screening was to estimate the AAT gene frequency and prevalence and to identify AAT deficiency cases in a large cohort of Lithuanian patients with COPD. Methods: A nationwide program of AAT deficiency was conducted in 1167 COPD patients, defined according to the GOLD criteria. Patients were collected from outpatient clinics in five different Lithuanian regions (Kaunas, Vilnius, Siauliai, Klaipeda and Alytus). AAT serum concentrations were measured by nephelometry; PI-phenotypes characterized by isoelectric-focusing. Results: Mean age and FEV1 were 62.0 (10.3) and 54.7% (10.9), respectively. Ninety-one AAT deficiency genotypes (40 MZ, 39 MS, 1 SS, 3 SZ and 8 ZZ) were identified. Catculated PI*S and PI*Z frequencies, expressed in per 1000, were 18.8 (95% CI: 13.9-25) and 25.3 (95% CI: 19.4-32.7), respectively. The calculated AAT gene prevalence (Hardy-Weinberg principle) was: 1/1.09 for MM, 1/28 for MS, 1/2814 for SS, 1/20 for MZ, 1/1049 for SZ and 1/1565 for ZZ. Calculated Odds ratio (OR) for PI*Z in COPD vs. Lithuanian healthy people was of 1.87 (P = 0.004). Conclusion: The OR for each genotypic class demonstrated a significant increase of MZ, SZ and ZZ genotypes in COPD patients. The results of the present study, with a significant number of ZZ individuals detected, support the general concept of targeted screening for AAT deficiency in countries like Lithuania, with a large population of COPD patients and tow awareness among care-givers about this genetic condition. (C) 2008 Elsevier Ltd. All rights reserved.
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