| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)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. |
- Benjamin, Caroline M., et al.
(författare)
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Educational priorities and current involvement in genetic practice: a survey of midwives in the Netherlands, UK and Sweden
- 2009
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Ingår i: Midwifery. - : Elsevier BV. - 1532-3099 .- 0266-6138. ; 25:5, s. 483-499
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Tidskriftsartikel (refereegranskat)abstract
- Objective: to investigate whether practising midwives are adequately prepared to integrate genetic information into their practice. Design: a cross-sectional, postal, structured questionnaire survey was sent to practising midwives. Setting: practising midwives from the Netherlands (NL), Sweden (SE) and the United Kingdom (UK). Participants: 1021 replies were received, achieving a response rate of 62%. Findings: 79% (799/1015) of midwives reported attending courses with some 'genetic content' during their initial training. Sixty-eight per cent (533/784) judged this to have been useful for clinical practice. Variation was seen between countries in the amount of genetic content in post-registration training (SE 87%, NL 44%, UK 17%) and underpinned by genetic knowledge. For eight of the 12 procedures, fewer than 20% of midwives considered themselves to be confident. Differences were apparent between countries. Midwives identified psychosocial, screening and risk assessment aspects of genetic education as being important to them, rather than technical aspects or genetic science. Conclusions: given the low reported confidence with genetic issues in clinical practice, it is essential that this is addressed in terms of the amount, content and targeting of genetic education. This is especially important to ensure the success of national antenatal and baby screening programmes. The results of this study suggest that midwives would welcome further training in genetics, addressing genetic topics most relevant to their clinical practice. (C) 2007 Elsevier Ltd. All rights reserved.
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| 3. |
- Calefato, Jean-Marc, et al.
(författare)
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Assessing educational priorities in genetics for general practitioners and specialists in five countries: factor structure of the Genetic-Educational Priorities (Gen-EP) scale
- 2008
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Ingår i: Genetics in Medicine. - 1098-3600. ; 10:2, s. 99-106
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: A scale assessing primary care physicians' priorities for genetic education (The Gen-EP scale) was developed and tested in five European countries. The objective of this study was to determine its factor structure, to test scaling assumptions and to determine internal consistency. Methods: The sample consisted of 3686 practitioners (general practitioners, gyneco-obstetricians, pediatricians) sampled in France, Germany, the Netherlands, Sweden, and United Kingdom. We first determined the factor structure of the Gen-EP scale (30 items) on the whole sample. Scaling assumptions were then tested on each country using multitrait scaling analysis. Internal consistency was assessed across the five countries. Results: Six factors were identified accounting for 63.3% of the variance of the items. They represented the following priorities for genetic education: "Genetics of Common Diseases"; "Ethical, Legal, and Public Health Issues"; "Approaching Genetic Risk Assessment in Clinical Practice"; "Basic Genetics and Congenital Malformations"; "Techniques and Innovation in Genetics" and "Psychosocial and Counseling Issues." In each country, convergent and discriminant validity were satisfactory. Internal-consistency reliability coefficients (Cronbach's alpha) were all above the acceptable threshold (0.70). Conclusion: The Gen-EP scale could be a helpful instrument in different countries to organize and evaluate the impact of genetic educational programs for primary care providers.
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| 4. |
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| 5. |
- Evangelou, Evangelos, et al.
(författare)
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Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
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Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
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| 6. |
- Frazier-Wood, Alexis C., et al.
(författare)
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Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
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Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
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Tidskriftsartikel (refereegranskat)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
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| 7. |
- Joshi, Peter K, et al.
(författare)
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Directional dominance on stature and cognition in diverse human populations
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
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Tidskriftsartikel (refereegranskat)abstract
- Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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| 8. |
- Julian-Reynier, Claire, et al.
(författare)
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Genetics in clinical practice: general practitioners' educational priorities in European countries
- 2008
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Ingår i: Genetics in Medicine. - 1098-3600. ; 10:2, s. 107-113
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To assess how general practitioners (GPs) from European countries prioritized their genetic educational needs according to their geographic, sociodemographic, and educational characteristics. Methods: Cross-sectional survey, random and total samples of GPs in five European countries (France, Germany, the Netherlands, Sweden, and United Kingdom), mailed questionnaires; Outcome: Genetic Educational Priority Scale (30 items; six subscores). Results: A total 1168 GPs answered. Priorities differed (P < 0.001) but were consistently ranked across the countries. Previous education had a marginal effect on priorities. Women gave higher priorities than men to Genetics of Common Disorders (adjusted odds ratio [ORadj], 2.5; 95% confidence interval [CI], 1.6-3.8), Psychosocial and Counseling Issues (ORadj, 1.6(adj); 95% CI, 1.1-2.5), and Ethical, Legal, and Public Health Issues (ORadj, 1.3; 95% CI, 1.1-1.8), but lower than men to Techniques and Innovation in Genetics (ORadj, 0.7; 95% CI, 0.5-0.9). Older physicians gave higher priorities to Basic Genetics and Congenital Malformations (ORadj, 1.5; 95% CI, 1.1-1.9), and to Techniques and Innovation in Genetics (ORadj: 1.3; 95% CI, 1.0-1.7), compared with their younger colleagues. Conclusions: Expressed genetic educational needs vary according to the countries and sociodemographics. In accordance, training could be more focused on genetics of common disorders and on how to approach genetic risk in clinical practice rather than on ethics, hew technologies, or basic concepts.
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| 9. |
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| 10. |
- Plass, Anne Marie C., et al.
(författare)
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Testing the Children: Do Non-Genetic Health-Care Providers Differ in Their Decision to Advise Genetic Presymptomatic Testing on Minors? A Cross-Sectional Study in Five Countries in the European Union
- 2009
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Ingår i: Genetic Testing and Molecular Biomarkers. - : Mary Ann Liebert Inc. - 1945-0265 .- 1945-0257. ; 13:3, s. 367-376
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Tidskriftsartikel (refereegranskat)abstract
- Background: Within Europe many guidelines exist regarding the genetic testing of minors. Predictive and presymptomatic genetic testing of minors is recommended for disorders for which medical intervention/preventive measures exist, and for which early detection improves future medical health. Aim: This study, which is part of the larger 5th EU-framework "genetic education'' (GenEd) study, aimed to evaluate the self-reported responses of nongenetic health-care providers in five different EU countries (Germany, France, Sweden, the United Kingdom, and the Netherlands) when confronted with a parent requesting presymptomatic testing on a minor child for a treatable disease. Methods: A cross-sectional study design using postal, structured scenario-based questionnaires that were sent to 8129 general practitioners (GPs) and pediatricians, between July 2004 and October 2004, addressing self-reported management of a genetic case for which early medical intervention during childhood is beneficial, involving a minor. Results: Most practitioners agreed on testing the oldest child, aged 12 years (81.5% for GPs and 87.2% for pediatricians), and not testing the youngest child, aged 6 months (72.6% for GPs and 61.3% for pediatricians). After multivariate adjustment there were statistical differences between countries in recommending a genetic test for the child at the age of 8 years. Pediatricians in France (50%) and Germany (58%) would recommend a test, whereas in the United Kingdom (22%), Sweden (30%), and the Netherlands (32%) they would not. Conclusion: Even though presymptomatic genetic testing in minors is recommended for disorders for which medical intervention exists, EU physicians are uncertain at what age starting to do so in young children.
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