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| 2. |
- 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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| 3. |
- Sampson, Joshua N., et al.
(author)
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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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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Journal article (peer-reviewed)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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| 4. |
- Zeng, Jinyan, et al.
(author)
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Trois lettres d'amour
- 2024
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In: Nouvelles de Chine. - 9782350747491 ; , s. 113-122
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Book chapter (pop. science, debate, etc.)
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| 5. |
- Qu, Luo-Yuan, et al.
(author)
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Color Erasure Detectors Enable Chromatic Interferometry
- 2019
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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 123:24
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Journal article (peer-reviewed)abstract
- By engineering and manipulating quantum entanglement between incoming photons and experimental apparatus, we construct single-photon detectors which cannot distinguish between photons of very different wavelengths. These color-erasure detectors enable a new kind of intensity interferometry, with potential applications in microscopy and astronomy. We demonstrate chromatic interferometry experimentally, observing robust interference using both coherent and incoherent photon sources.
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| 6. |
- Wang, Zhaoming, et al.
(author)
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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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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Journal article (peer-reviewed)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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| 7. |
- Czolkos, Ilja, 1980, et al.
(author)
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Flow control of thermotropic lipid monolayers
- 2011
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In: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-6848 .- 1744-683X. ; 7:15, s. 6926-6933
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Journal article (peer-reviewed)abstract
- There is an increasing interest in using liquid crystalline media as mobile phases in two-dimensional nanofluidic systems. Their small-scale, reduced dimensionality, and plentiful opportunities for functionalisation render such phases advantageous. However, flow control has been difficult to achieve, as the wetting processes which drive area expansion are not dynamically controllable. Here, we report on temperature-controlled monolayer spreading of 1,2-dielaidoyl-sn-glycero-3-phosphoethanolamine (DEPE) on the hydrophobic substrates SU-8, and Teflon AF (amorphous fluoropolymer). The gel/liquid phase transition of DEPE at T(c) similar to 38 degrees C is exploited to toggle spreading of a molecular lipid film on SU-8. We observed that on Teflon AF, DEPE monolayer spreading occurs even below T(c), and exhibits strongly accelerated spreading above the phase transition temperature. Our results demonstrate that switching DEPE monolayer spreading on and off, or, alternatively, switching between fast and slow area expansion, is a feasible approach towards establishing control over lipid film flow in two-dimensional fluidic systems. We also present a chip-based device integrating a patterned surface for 2D-microfluidics and on-chip heating.
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| 8. |
- Davies, John R., et al.
(author)
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An inherited variant in the gene coding for vitamin D-binding protein and survival from cutaneous melanoma: a BioGenoMEL study
- 2014
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In: Pigment Cell & Melanoma Research. - : Wiley. - 1755-148X .- 1755-1471. ; 27:2, s. 234-243
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Journal article (peer-reviewed)abstract
- An association between low serum vitamin D levels and poorer melanoma survival has been reported. We have studied inheritance of a polymorphism of the GC gene, rs2282679, coding for the vitamin D-binding protein, which is associated with lower serum levels of vitamin D, in a meta-analysis of 3137 melanoma patients. The aim was to investigate evidence for a causal relationship between vitamin D and outcome (Mendelian randomization). The variant was not associated with reduced overall survival (OS) in the UK cohort, per-allele hazard ratio (HR) for death 1.23 (95% confidence interval (CI) 0.93, 1.64). In the smaller cohorts, HR in OS analysis was 1.07 (95% CI 0.88, 1.3) and for all cohorts combined, HR for OS was 1.09 (95% CI 0.93, 1.29). There was evidence of increased melanoma-specific deaths in the seven cohorts for which these data were available. The lack of unequivocal findings despite the large sample size illustrates the difficulties of implementing Mendelian randomization.
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| 9. |
- Davies, John R, et al.
(author)
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Inherited variation in the PARP1 gene and survival from melanoma
- 2014
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 135:7, s. 1625-1633
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Journal article (peer-reviewed)abstract
- We report the association of an inherited variant located upstream of the poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) gene (rs2249844), with survival in 11 BioGenoMEL melanoma cohorts. The gene encodes a protein involved in a number of cellular processes including single-strand DNA repair. Survival analysis was conducted for each cohort using proportional hazards regression adjusting for factors known to be associated with survival. Survival was measured as overall survival (OS) and, where available, melanoma-specific survival (MSS). Results were combined using random effects meta-analysis. Evidence for a role of the PARP1 protein in melanoma ulceration and survival was investigated by testing gene expression levels taken from formalin-fixed paraffin-embedded tumors. A significant association was seen for inheritance of the rarer variant of PARP1, rs2249844 with OS (hazard ratio (HR) = 1.16 per allele, 95% confidence interval (CI) 1.04-1.28, p=0.005, eleven cohorts) and MSS (HR=1.20 per allele, 95% CI 1.01-1.39, p=0.03, eight cohorts). We report bioinformatic data supportive of a functional effect for rs2249844. Higher levels of PARP1 gene expression in tumors were shown to be associated with tumor ulceration and poorer OS. What's new? Although staging systems predict outcome fairly well for melanoma, survival still varies among individual patients. In this meta-analysis, the authors found that inheritance of a rare genetic variant of PARP1 was associated with improved survival of melanoma patients. Increased expression of PARP1 has been associated with poorer outcome, and depletion of PARP1 may reduce both melanoma growth and angiogenesis. The identification of this and other germline variants that affect survival may help to identify key biological pathways active in host/tumor interactions, which may lead to the discovery of new therapeutic targets for treating advanced melanoma. Epidemiology
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| 10. |
- Feng, Cun-Feng, et al.
(author)
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Effects of average degree of network on an order-disorder transition in opinion dynamics
- 2010
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In: Chinese Physics B. - : IOPScience. - 1674-1056. ; 19:6, s. 060203-
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Journal article (peer-reviewed)abstract
- We have investigated the influence of the average degree (k) of network on the location of an order-disorder transition in opinion dynamics. For this purpose, a variant of majority rule (VMR) model is applied to Watts–Strogatz (WS) small-world networks and Barabási–Albert (BA) scale-free networks which may describe some non-trivial properties of social systems. Using Monte Carlo simulations, we find that the order–disorder transition point of the VMR model is greatly affected by the average degree (k) of the networks; a larger value of (k) results in a more ordered state of the system. Comparing WS networks with BA networks, we find WS networks have better orderliness than BA networks when the average degree (k) is small. With the increase of (k), BA networks have a more ordered state. By implementing finite-size scaling analysis, we also obtain critical exponents β/ν, γ/ν and 1/ν for several values of average degree (k). Our results may be helpful to understand structural effects on order–disorder phase transition in the context of the majority rule model.
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