| 1. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
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- 2019
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Journal article (peer-reviewed)
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| 3. |
- Kanoni, Stavroula, et al.
(author)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
-
In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Journal article (peer-reviewed)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 4. |
- Richards, Stephen, et al.
(author)
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The genome of the model beetle and pest Tribolium castaneum.
- 2008
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In: Nature. - 1476-4687. ; 452:7190, s. 949-55
-
Journal article (peer-reviewed)abstract
- Tribolium castaneum is a representative of earth’s most numerous eukaryotic order, a powerful model organism for the study of generalized insect development, and also an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved an ability to interact with a diverse chemical environment as evidenced by large expansions in odorant and gustatory receptors, as well as p450 and other detoxification enzymes. Developmental patterns in Tribolium are more representative of other arthropods than those found in Drosophila, a fact represented in gene content and function. For one, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, and some are expressed in the growth zone crucial for axial elongation in short germ development. Systemic RNAi in T. castaneum appears to use mechanisms distinct from those found in C. elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.
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| 5. |
- Haghighi, Mona, et al.
(author)
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A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study
- 2016
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Journal article (peer-reviewed)abstract
- Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
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| 6. |
- Lundgren, Markus, et al.
(author)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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In: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Journal article (peer-reviewed)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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| 7. |
- Soranno, Patricia A., et al.
(author)
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LAGOS-NE : A multi-scaled geospatial and temporal database of lake ecological context and water quality for thousands of U.S. lakes
- 2017
-
In: GigaScience. - : Oxford University Press (OUP). - 2047-217X. ; 6:12, s. 1-22
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Journal article (peer-reviewed)abstract
- Understanding the factors that affect water quality and the ecological services provided by freshwater ecosystems is an urgent global environmental issue. Predicting how water quality will respond to global changes not only requires water quality data, but also information about the ecological context of individual water bodies across broad spatial extents. Because lake water quality is usually sampled in limited geographic regions, often for limited time periods, assessing the environmental controls of water quality requires compilation of many data sets across broad regions and across time into an integrated database. LAGOS-NE accomplishes this goal for lakes in the northeastern-most 17 US states. LAGOS-NE contains data for 51101 lakes and reservoirs larger than 4 ha in 17 lake-rich US states. The database includes 3 datamodules for: lake location and physical characteristics for all lakes; ecological context (i.e., the land use, geologic, climatic, and hydrologic setting of lakes) for all lakes; and in situmeasurements of lake water quality for a subset of the lakes fromthe past 3 decades for approximately 2600–12 000 lakes depending on the variable. The database contains approximately 150000 measures of total phosphorus, 200 000 measures of chlorophyll, and 900 000 measures of Secchi depth. The water quality data were compiled from87 lake water quality data sets fromfederal, state, tribal, and non-profit agencies, university researchers, and citizen scientists. This database is one of the largest andmost comprehensive databases of its type because it includes both in situmeasurements and ecological context data. Because ecological context can be used to study a variety of other questions about lakes, streams, and wetlands, this database can also be used as the foundation for other studies of freshwaters at broad spatial and ecological scales
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| 8. |
- Aglago, Elom K., et al.
(author)
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A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk
- 2023
-
In: Cancer Research. - : American Association For Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 83:15, s. 2572-2583
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Journal article (peer-reviewed)abstract
- Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer.SIGNIFICANCE: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.
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| 9. |
- Amundadottir, Laufey, et al.
(author)
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Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer.
- 2009
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41, s. 986-990
-
Journal article (peer-reviewed)abstract
- We conducted a two-stage genome-wide association study of pancreatic cancer, a cancer with one of the lowest survival rates worldwide. We genotyped 558,542 SNPs in 1,896 individuals with pancreatic cancer and 1,939 controls drawn from 12 prospective cohorts plus one hospital-based case-control study. We conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from eight case-control studies, adjusting for study, sex, ancestry and five principal components. We identified an association between a locus on 9q34 and pancreatic cancer marked by the SNP rs505922 (combined P = 5.37 x 10(-8); multiplicative per-allele odds ratio 1.20; 95% confidence interval 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene. Our results are consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B.
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| 10. |
- Bouras, Emmanouil, et al.
(author)
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Genome-wide interaction analysis of folate for colorectal cancer risk
- 2023
-
In: American Journal of Clinical Nutrition. - : Elsevier. - 0002-9165 .- 1938-3207. ; 118:5, s. 881-891
-
Journal article (peer-reviewed)abstract
- Background: Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate's role in CRC.Objectives: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk.Methods: We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO).Results: Inverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate.Conclusions: Variation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant omics data are warranted to validate this finding.
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| 11. |
- Dixon-Suen, Suzanne C, et al.
(author)
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Physical activity, sedentary time and breast cancer risk : a Mendelian randomisation study
- 2022
-
In: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 56:20, s. 1157-1170
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.METHODS: We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.RESULTS: Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).CONCLUSION: Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.
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| 12. |
- Hagger, Martin S., et al.
(author)
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A Multilab Preregistered Replication of the Ego-Depletion Effect
- 2016
-
In: Perspectives on Psychological Science. - : Sage Publications. - 1745-6916 .- 1745-6924. ; 11:4, s. 546-573
-
Journal article (peer-reviewed)abstract
- Good self-control has been linked to adaptive outcomes such as better health, cohesive personal relationships, success in the workplace and at school, and less susceptibility to crime and addictions. In contrast, self-control failure is linked to maladaptive outcomes. Understanding the mechanisms by which self-control predicts behavior may assist in promoting better regulation and outcomes. A popular approach to understanding self-control is the strength or resource depletion model. Self-control is conceptualized as a limited resource that becomes depleted after a period of exertion resulting in self-control failure. The model has typically been tested using a sequential-task experimental paradigm, in which people completing an initial self-control task have reduced self-control capacity and poorer performance on a subsequent task, a state known as ego depletion. Although a meta-analysis of ego-depletion experiments found a medium-sized effect, subsequent meta-analyses have questioned the size and existence of the effect and identified instances of possible bias. The analyses served as a catalyst for the current Registered Replication Report of the ego-depletion effect. Multiple laboratories (k = 23, total N = 2,141) conducted replications of a standardized ego-depletion protocol based on a sequential-task paradigm by Sripada et al. Meta-analysis of the studies revealed that the size of the ego-depletion effect was small with 95% confidence intervals (CIs) that encompassed zero (d = 0.04, 95% CI [-0.07, 0.15]. We discuss implications of the findings for the ego-depletion effect and the resource depletion model of self-control.
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| 13. |
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| 14. |
- Hornborg, Alf, et al.
(author)
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Money, value, and entropy
- 2023
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In: Handbook of inequality and the environment. - 9781800881129
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Book chapter (peer-reviewed)
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| 15. |
- Johnston, Jennifer J., et al.
(author)
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Molecular Analysis Expands the Spectrum of Phenotypes Associated with GLI3 Mutations
- 2010
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In: Human Mutation. - : Hindawi Limited. - 1059-7794. ; 31:10, s. 1142-1154
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Journal article (peer-reviewed)abstract
- A range of phenotypes including Greig cephalopolysyndactyly and Pallister-Hall syndromes (GCPS, PHS) are caused by pathogenic mutation of the GLI3 gene. To characterize the clinical variability of GLI3 mutations, we present a subset of a cohort of 174 probands referred for GLI3 analysis. Eighty-one probands with typical GCPS or PHS were previously reported, and we report the remaining 93 probands here. This includes 19 probands (12 mutations) who fulfilled clinical criteria for GCPS or PHS, 48 probands (16 mutations) with features of GCPS or PHS but who did not meet the clinical criteria (sub-GCPS and sub-PHS), 21 probands (6 mutations) with features of PHS or GCPS and oral-facial- digital syndrome, and 5 probands (1 mutation) with nonsyndromic polydactyly. These data support previously identified genotype-phenotype correlations and demonstrate a more variable degree of severity than previously recognized. The finding of GLI3 mutations in patients with features of oral-facial-digital syndrome supports the observation that GLI3 interacts with cilia. We conclude that the phenotypic spectrum of GLI3 mutations is broader than that encompassed by the clinical diagnostic criteria, but the genotype-phenotype correlation persists. Individuals with features of either GCPS or PHS should be screened for mutations in GLI3 even if they do not fulfill clinical criteria. Hum Mutat 31:1142-1154, 2010. (C) 2010 Wiley-Liss, Inc.
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| 16. |
- Lynch, Sean R., et al.
(author)
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A comparison of physical properties, screening procedures and a human efficacy trial for predicting the bioavailability of commercial elemental iron powders used for food fortification
- 2007
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In: INTERNATIONAL JOURNAL FOR VITAMIN AND NUTRITION RESEARCH. - : Hogrefe Publishing Group. - 0300-9831 .- 1664-2821. ; 77:2, s. 107-124
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Journal article (peer-reviewed)abstract
- Elemental iron powders are widely used to fortify staple foods. Experimental evidence indicates that there is considerable variation in the bioavailability of different products. For some powders, it may be too low to permit a significant impact on iron status. This study was designed to evaluate possible approaches to screening commercial iron powders for predicted bioavailability, to identify products that have the potential to improve iron status, and to ascertain whether bioavailability is related to the method of manufacture. Nine commercial iron powders were allocated to one of five types based on the production process; carbonyl, electrolytic, hydrogen-reduced (H-reduced), carbon monoxide-reduced (CO-reduced), and other reduced. Structure by scanning electron microscopy and physical properties (pycnometric and apparent density, particle size distribution, Fisher subsieve size, and surface area) were determined on all samples. Selected samples (one or more of each type depending on the cost of the assay) were then subjected to five screening procedures that have previously been advocated for predicting bioavailability in humans - dissolution rate in 0.1 mol/L HCl, dialyzability and Caco-2 cell iron uptake, both after simulated in vitro gastrointestinal digestion, relative bioavailability (RBV) with respect to ferrous sulfate by the AOAC rat hemoglobin repletion method, and plasma iron tolerance tests in human volunteers. The results for particle size distribution, surface area, Fisher subsieve size, dissolution rate in 0.1 mol/L HCl, and RBV in rats were significantly correlated and consistent for powders of the same type. However, values for different powder types were significantly different. There was no correlation between either dialyzability or Caco-2 cell uptake and the predicted bioavailability estimates based on the physical properties, dissolution rates, RBV in rats, or human efficacy data. Although human plasma iron tolerance tests were in general agreement with the other measures of predicted bioavailability, they did not provide information that would have improved the precision of bioavailability estimates based on physical properties, dissolution in HCl and/or RBV in rats. Our observations indicate that the dissolution rate in 0.1 mol/L HCl under standardized conditions is highly predictive of potential bioavailability and that it would be the most practical approach to developing a reliable and sensitive screening procedure for predicting and monitoring the bioavailability of commercial elemental iron powder products. Some, but not all, of the carbonyl and electrolytic iron powders had the highest predicted bioavailability values. The predicted bioavailability for the reduced iron products was lower and variable, with the lowest values being recorded for the carbon monoxide and other reduced iron products. Two powder types were selected for a human efficacy trial, electrolytic (because it is the iron powder type recommended by WHO) and hydrogen-reduced (because of its widespread use). Electrolytic/A131 and H-reduced/AC-325 had relative efficacies compared with ferrous sulfate monohydrate of 77% and 49%, respectively, based on the change in body iron stores in Thai women with low iron stores, who received an additional 12 mg iron per day, six days per week for 35 weeks in wheat-based snacks. We conclude that there is significant variability in the bioavailability of the commercial iron powders that we evaluated (those used for food fortification at the time that our studies were initiated), and that bioavailability is related in part to production method. The bioavailability of some carbonyl and electrolytic iron powders may be adequate for effective food fortification. The reduced iron powders that we tested are unlikely to have an adequate impact on iron nutrition at the fortification levels currently employed, although preliminary analysis of a new H-reduced product indicates that it may be possible to improve the bioavailability of individual powders of this type of product. We did find significant differences among products in both the electrolytic and carbonyl categories. Therefore, all products should be screened rigorously.
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| 17. |
- Minelli, Caterina, et al.
(author)
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Versailles project on advanced materials and standards (VAMAS) interlaboratory study on measuring the number concentration of colloidal gold nanoparticles
- 2022
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In: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3372 .- 2040-3364. ; 14, s. 4690-4704
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Journal article (peer-reviewed)abstract
- We describe the outcome of a large international interlaboratory study of the measurement of particle number concentration of colloidal nanoparticles, project 10 of the technical working area 34, "Nanoparticle Populations" of the Versailles Project on Advanced Materials and Standards (VAMAS). A total of 50 laboratories delivered results for the number concentration of 30 nm gold colloidal nanoparticles measured using particle tracking analysis (PTA), single particle inductively coupled plasma mass spectrometry (spICP-MS), ultraviolet-visible (UV-Vis) light spectroscopy, centrifugal liquid sedimentation (CLS) and small angle X-ray scattering (SAXS). The study provides quantitative data to evaluate the repeatability of these methods and their reproducibility in the measurement of number concentration of model nanoparticle systems following a common measurement protocol. We find that the population-averaging methods of SAXS, CLS and UV-Vis have high measurement repeatability and reproducibility, with between-labs variability of 2.6%, 11% and 1.4% respectively. However, results may be significantly biased for reasons including inaccurate material properties whose values are used to compute the number concentration. Particle-counting method results are less reproducibile than population-averaging methods, with measured between-labs variability of 68% and 46% for PTA and spICP-MS respectively. This study provides the stakeholder community with important comparative data to underpin measurement reproducibility and method validation for number concentration of nanoparticles.
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| 18. |
- Papadimitriou, Nikos, et al.
(author)
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Physical activity and risks of breast and colorectal cancer : a Mendelian randomisation analysis
- 2020
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- Physical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies; however, it is unknown if these associations are causal or confounded. In two-sample Mendelian randomisation analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27 to 0.98, P-value=0.04) and colorectal cancer (OR: 0.66, 95% CI: 0.48 to 0.90, P-value=0.01). We found similar magnitude inverse associations for estrogen positive (ER+ve) breast cancer and for colon cancer. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers. Physical activity has been linked to lower risks of colorectal and breast cancer. Here, the authors present a Mendelian randomisation analysis supporting a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer.
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| 19. |
- Petersen, Gloria M, et al.
(author)
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A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:3, s. 224-228
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Journal article (peer-reviewed)abstract
- We conducted a genome-wide association study of pancreatic cancer in 3,851 affected individuals (cases) and 3,934 unaffected controls drawn from 12 prospective cohort studies and 8 case-control studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry and five principal components, we identified eight SNPs that map to three loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Two correlated SNPs, rs9543325 (P = 3.27 x 10(-11), per-allele odds ratio (OR) 1.26, 95% CI 1.18-1.35) and rs9564966 (P = 5.86 x 10(-8), per-allele OR 1.21, 95% CI 1.13-1.30), map to a nongenic region on chromosome 13q22.1. Five SNPs on 1q32.1 map to NR5A2, and the strongest signal was at rs3790844 (P = 2.45 x 10(-10), per-allele OR 0.77, 95% CI 0.71-0.84). A single SNP, rs401681 (P = 3.66 x 10(-7), per-allele OR 1.19, 95% CI 1.11-1.27), maps to the CLPTM1L-TERT locus on 5p15.33, which is associated with multiple cancers. Our study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies.
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| 20. |
- Raval, Aparna, et al.
(author)
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Downregulation of death-associated protein kinase 1 (DAPK1) in chronic lymphocytic leukemia
- 2007
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In: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 129:5, s. 879-890
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Journal article (peer-reviewed)abstract
- The heritability of B cell chronic lymphocytic leukemia (CLL) is relatively high; however, no predisposing mutation has been convincingly identified. We show that loss or reduced expression of death-associated protein kinase 1 (DAPK1) underlies cases of heritable predisposition to CLL and the majority of sporadic CLL. Epigenetic silencing of DAPK1 by promoter methylation occurs in almost all sporadic CLL cases. Furthermore, we defined a disease haplotype, which segregates with the CLL phenotype in a large family. DAPK1 expression of the CLL allele is downregulated by 75% in germline cells due to increased HOXB7 binding. In the blood cells from affected family members, promoter methylation results in additional loss of DAPK1 expression. Thus, reduced expression of DAPK1 can result from germline predisposition, as well as epigenetic or somatic events causing or contributing to the CLL phenotype.
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| 21. |
- Werren, John H, et al.
(author)
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Functional and evolutionary insights from the genomes of three parasitoid Nasonia species.
- 2010
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 327:5963, s. 343-8
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Journal article (peer-reviewed)abstract
- We report here genome sequences and comparative analyses of three closely related parasitoid wasps: Nasonia vitripennis, N. giraulti, and N. longicornis. Parasitoids are important regulators of arthropod populations, including major agricultural pests and disease vectors, and Nasonia is an emerging genetic model, particularly for evolutionary and developmental genetics. Key findings include the identification of a functional DNA methylation tool kit; hymenopteran-specific genes including diverse venoms; lateral gene transfers among Pox viruses, Wolbachia, and Nasonia; and the rapid evolution of genes involved in nuclear-mitochondrial interactions that are implicated in speciation. Newly developed genome resources advance Nasonia for genetic research, accelerate mapping and cloning of quantitative trait loci, and will ultimately provide tools and knowledge for further increasing the utility of parasitoids as pest insect-control agents.
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| 22. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 23. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 24. |
- Agin, Sol, 1989-
(author)
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Communicating climate action : Combining action repertoires and linguistic repertoires in social movement message construction
- 2022
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Doctoral thesis (other academic/artistic)abstract
- The climate crisis is one of the largest global challenges that humanity has ever faced. Despite the scientific consensus on the threat, action is not occurring on the pace or level needed to stave off the consequences. As climate change is made up by complex and conjoined causes and effects, the issue is also riddled with communicative challenges which those calling for action need to tackle. Climate change communication research has, however, mainly focus on how traditional news media frame the climate change issue and overlooks climate activist and movement groups. This despite these actors being key for shifting public perceptions and public opinion. Although research on other communication actors exist, it is far from extensive and the research field overlooks the publics perceptions of the sender in relation to the construction of climate messages. Through survey data and an experiment, this doctoral thesis explores the public’s inclination towards different protest action repertoires and addresses the research gap in the climate movement message construction. Herein, the actions and words of three subgroups within the larger environmental movement is considered as one part of a larger message whole. The groups chosen action repertoires are viewed as part of the activists’ performed message and the linguistic communication styles created by lexical choices related to emotional appeals are part of the activists’ verbal/textual message. The results indicate that there is much to be gained from adhering to an alignment between lexical choices and action repertoires. Alignment may be key for understanding why some movement subgroups are successful in inspiring certain actions whilst others inspire other actions. Communication-action alignment is a way to approach the interconnectedness of actions and words for complex and abstract issues that require message recipients to construct consonant mental models to break potential cognitive dissonance.
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| 25. |
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