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- 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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- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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- 2019
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Tidskriftsartikel (refereegranskat)
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- Chen, Chao-Ying, et al.
(författare)
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Problematic Use of Internet Associates with Poor Quality of Life via Psychological Distress in Invididuals with ADHD
- 2024
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Ingår i: Psychology Research and Behavior Management. - : Dove Medical Press. - 1179-1578. ; 17, s. 443-455
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Tidskriftsartikel (refereegranskat)abstract
- Background: Problematic use of internet (PUI) may have negative impacts on psychological distress and quality of life (QoL). This situation might be more profound in people with attention-deficit/hyperactivity disorder (ADHD) due to poorer behavioral control and regulatory capacity. However, there is little evidence regarding mediated effects in the associations between PUI, psychological distress, and QoL in people with ADHD. Aims: To investigate mediating effects of psychological distress in the associations of problematic smartphone use (PSPU), problematic use of social media (PUSM), and problematic gaming (PG) with QoL in individuals with ADHD. Methods and Procedures: PUI behaviors of participants with ADHD (n = 99) were assessed using the Smartphone ApplicationBased Addiction Scale, Bergen Social Media Addiction Scale, and Internet Gaming Disorder-Short Form. Psychological distress was assessed using the Depression, Anxiety, Stress Scale and QoL using the Kid-KINDL. Outcomes and Results: Psychological distress mediated the associations between PUI and different domains of QoL, except for selfesteem QoL. There were also positively direct effects between PG and physical QoL, PUSM and friends' QoL, and PSPU and physical QoL. Conclusions and Implications: PUI may associate with poor QoL in people with ADHD via psychological distress. Programs on reducing PUI for people with ADHD are needed.
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| 8. |
- Lee, Kuan-Ying, et al.
(författare)
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Exploring mediational roles for self-stigma in associations between types of problematic use of internet and psychological distress in youth with ADHD
- 2023
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Ingår i: Research in Developmental Disabilities. - : Elsevier. - 0891-4222 .- 1873-3379. ; 133
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several studies have linked the problematic use of the Internet (PUI) to psychological distress. Youth with attention deficit hyperactivity disorder (ADHD) are considered a particular disadvantaged population with a high risk of developing PUI, psychological distress, and self-stigma. Nonetheless, the interrelationships of PUI, self-stigma, and psychological distress in ad-olescents with ADHD are not well understood.Aims: This study investigated whether self-stigma mediates relationships between different forms of PUI, such as problematic gaming (PG), problematic social media use (PSMU), problematic smartphone use (PSPU), and psychological distress (i.e., depression, anxiety, and stress), in children with ADHD.Methods and procedures: We recruited 100 youth with ADHD (mean age=10.80 [SD=3.07] years; 84 boys) from psychiatric outpatient clinics in Taiwan. All participants were assessed for PUI (via Internet Gaming Disorder-Short Form for PG, Bergan Social Medica Addiction Scale for PSMU, and Smartphone Application-Based Addiction Scale for PSPU), self-stigma (via Self-Stigma Short -Scale), and psychological distress (via Depression, Anxiety, Stress Scale).Outcomes and results: The results of path and bootstrapping analyses indicated that self-stigma mediated the associations between PSMU and PSPU, but not PG, and depression, anxiety, and stress.Conclusions and implications: This study expands the extant literature by revealing that self-stigma mediates the association between specific forms of PUI and psychological distress in adolescents with ADHD. Interventions aimed at reducing self-stigma and PUI, particularly PSMU and PSPU, may help decrease psychological distress among adolescents with ADHD.
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| 9. |
- Pakpour, Amir H., et al.
(författare)
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The relationship between children's overweight and quality of life : A comparison of Sizing Me Up, PedsQL and Kid-KINDL
- 2019
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Ingår i: International Journal of Clinical and Health Psychology. - : Elsevier. - 1697-2600 .- 2174-0852. ; 19:1, s. 49-56
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Tidskriftsartikel (refereegranskat)abstract
- Background/Objective: Overweight and obese children are likely to encounter negative impact on psychological well-being and quality of life (QoL). Hence, for overweight and obese children, measuring QoL could go beyond simply assessing objective medical parameters and cover their physical health, psychological well-being, and social interaction. Generic (Kid-KINDL and Pediatric Quality of Life Inventory [PedsQL]) and weight-related (Sizing Me Up) measures are two major types of QoL measurement instruments; however, little is known about the differences between them.Method: We recruited 569 3rd to 6th graders from eleven schools in Southern Taiwan. In addition to the three QoL questionnaires, the Child Depression Inventory and Rosenberg Self-Esteem Scale were applied.Results: Depression had significantly negative associations with all three QoL questionnaires. Self-esteem was only associated with Kid-KINDL. Body mass index had a significantly stronger relationship with Sizing Me Up than its relationships with PedsQL and Kid-KINDL. In other words, the items related to body size concerns in Size Me Up significantly contributed to impaired overweight/obese children's QoL.Conclusions: The study further identified the characters and strength of these QoL measures for better suggestions on evaluating physical and psychological issues for overweight/obese children.
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- Tung, Serene En Hui, et al.
(författare)
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Internet-Related Instruments (Bergen Social Media Addiction Scale, Smartphone Application-Based Addiction Scale, Internet Gaming Disorder Scale-Short Form, and Nomophobia Questionnaire) and Their Associations with Distress among Malaysian University Students
- 2022
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Ingår i: Healthcare. - : MDPI. - 2227-9032. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- The present study evaluated the psychometric properties of four instruments related to internet use, namely the Bergen Social Media Addiction Scale (BSMAS), Smartphone Application-Based Addiction Scale (SABAS), (nine-item) Internet Gaming Disorder Scale Short Form (IGDS9-SF), and Nomophobia Questionnaire (NMPQ) as well as their associations with psychological distress among Malaysian university students. A total of 380 Malaysian university students (71.6% females, mean age 24.0 years) were recruited through convenience sampling and completed an online survey including questions concerning socio-demographic background, social media addiction, smartphone addiction, internet gaming disorder, and nomophobia. Confirmatory factor analysis and Rasch analysis were applied to evaluate the psychometric properties of the instruments and Cronbach's alpha value and McDonald's omega value were used to confirm the internal consistency reliability of the instruments. The unidimensional structure was confirmed for the BSMAS, SABAS, and IGDS9-SF while the four-factor structure was confirmed for NMPQ. All instruments showed good internal consistency reliability. Promising validity and reliability were confirmed for BSMAS, SABAS, IGDS9-SF, and NMPQ. Therefore, they are useful to assess different types of problematic internet use among university students in Malaysia. Furthermore, a significant association was observed between internet use and psychological distress. The present study is the first to investigate the validity and reliability of BSMAS, SABAS, IGDS9-SF, and NMPQ among Malaysian university students using rigorous psychometric testing methods (i.e., Rasch analysis).
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