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| 3. |
- 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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- 2019
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Huang, Wen-Yi, et al.
(författare)
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Effectiveness of using calligraphic activity to treat people with schizophrenia : a randomized controlled trial in Southern Taiwan
- 2022
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Ingår i: THERAPEUTIC ADVANCES IN CHRONIC DISEASE. - : Sage Publications. - 2040-6223 .- 2040-6231. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prior research has shown preliminary evidence that calligraphy activity improves various body functions and decreases severity of psychotic symptoms in individuals with schizophrenia. However, major limitations of earlier studies include small and heterogeneous samples. The current large-scale randomized controlled trial examined effects of calligraphy activity on cognition (including attention), emotions, psychotic symptoms, quality of life, and mood in people with schizophrenia. Methods: One-hundred-and-fifty patients with schizophrenia were randomly allocated to the treatment group (receiving calligraphy activity) or the control group (receiving general activity), both of which lasted for 24weeks (70 minutes per session; one session per week). Assessments were conducted at pretest, posttest, and three-month follow-up. The Montreal Cognitive Assessment, Chu's Attention Test, Depression, Anxiety, and Stress Scale, Positive and Negative Syndrome Scale, World Health Questionnaire on the Quality of Life-Brief Form, and Visual Analogue Scale were used. Results: Improved cognition and attention were found in both groups, although no group effects were shown. The treatment group appeared to show lower severity of positive symptoms at follow-up than posttest, whereas the control group appeared to show the opposite pattern. Improved mood was found in the treatment group. Conclusion: This study provides evidence regarding effects of calligraphy activity on increasing cognition and potentially decreasing severity of positive symptoms in patients with schizophrenia. Calligraphy activity can be incorporated in clinical occupational therapy and may be provided to supplement medication treatment.
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| 7. |
- 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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| 8. |
- Adare, A., et al.
(författare)
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Inclusive double-helicity asymmetries in neutral-pion and eta-meson production in + collisions at root s=200 GeV
- 2014
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Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 90:1
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Tidskriftsartikel (refereegranskat)abstract
- Results are presented from data recorded in 2009 by the PHENIX experiment at the Relativistic Heavy Ion Collider for the double-longitudinal spin asymmetry, A(LL), for pi(0) and eta production in root s = 200 GeV polarized p + p collisions. Comparison of the pi(0) results with different theory expectations based on fits of other published data showed a preference for small positive values of gluon polarization, Delta G, in the proton in the probed Bjorken x range. The effect of adding the new 2009 pi(0) data to a recent global analysis of polarized scattering data is also shown, resulting in a best fit Delta G(DSSV)([0.05,0.2]) = 0.06(-0.15)(+0.11) in the range 0.05 < x < 0.2, with the uncertainty at Delta chi(2) = 9 when considering only statistical experimental uncertainties. Shifting the PHENIX data points by their systematic uncertainty leads to a variation of the best-fit value of Delta G(DSSV)([0.05,0.2]) between 0.02 and 0.12, demonstrating the need for full treatment of the experimental systematic uncertainties in future global analyses.
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| 9. |
- Adare, A., et al.
(författare)
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Measurements of Elliptic and Triangular Flow in High-Multiplicity He-3 + Au Collisions at root s(NN)=200 GeV
- 2015
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Ingår i: Physical Review Letters. - 1079-7114. ; 115:14
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Tidskriftsartikel (refereegranskat)abstract
- We present the first measurement of elliptic (v(2)) and triangular (v(3)) flow in high-multiplicity He-3 + Au collisions at root s(NN) = 200 GeV. Two-particle correlations, where the particles have a large separation in pseudorapidity, are compared in He-3 + Au and in p + p collisions and indicate that collective effects dominate the second and third Fourier components for the correlations observed in the He-3 + Au system. The collective behavior is quantified in terms of elliptic v(2) and triangular v(3) anisotropy coefficients measured with respect to their corresponding event planes. The v(2) values are comparable to those previously measured in d + Au collisions at the same nucleon-nucleon center-of-mass energy. Comparisons with various theoretical predictions are made, including to models where the hot spots created by the impact of the three He-3 nucleons on the Au nucleus expand hydrodynamically to generate the triangular flow. The agreement of these models with data may indicate the formation of low-viscosity quark-gluon plasma even in these small collision systems.
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| 10. |
- Adare, A., et al.
(författare)
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phi meson production in d plus Au collisions at root s(NN)=200 GeV
- 2015
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 92:4
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Tidskriftsartikel (refereegranskat)abstract
- The PHENIX Collaboration has measured phi meson production in d + Au collisions at root s(NN) = 200 GeV using the dimuon and dielectron decay channels. The phi meson is measured in the forward (backward) d-going (Au-going) direction, 1.2 < y < 2.2 (-2.2 < y < -1.2) in the transverse-momentum (pT) range from 1-7 GeV/c and at midrapidity vertical bar y vertical bar < 0.35 in the p(T) range below 7 GeV/c. The phi meson invariant yields and nuclear-modification factors as a function of p(T), rapidity, and centrality are reported. An enhancement of phi meson production is observed in the Au-going direction, while suppression is seen in the d-going direction, and no modification is observed at midrapidity relative to the yield in p + p collisions scaled by the number of binary collisions. Similar behavior was previously observed for inclusive charged hadrons and open heavy flavor, indicating similar cold-nuclear-matter effects.
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