| 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. |
- Beecham, Ashley H, et al.
(författare)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 3. |
- Bellenguez, Celine, et al.
(författare)
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Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:3, s. 141-328
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Tidskriftsartikel (refereegranskat)abstract
- Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 x 10(-11); odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28-1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes.
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| 4. |
- Stubbins, Aron, et al.
(författare)
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Biogeochemical interpretations of colored dissolved organic matter optical signatures (invited)
- 2014
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The optical properties of colored dissolved organic matter (CDOM) in surface waters are visible from space and observable throughout the water column in real time using in situ sensors. Due to their ease of measurement, CDOM optical properties are used as proxies for the quantity, quality and processing of dissolved organic matter (DOM) in natural waters. This talk will focus upon the use of these optical signatures to provide insight into the cycling of DOM. Examples will include the use of color to estimate quantitative fluxes and the molecular composition of organics in natural waters.
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| 5. |
- Bjelosevic, Haris, et al.
(författare)
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Platinum(II) and gold(I) complexes based on 1,1 '-bis(diphenylphosphino)metallocene derivatives: Synthesis, characterization and biological activity of the gold complexes
- 2012
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Ingår i: Journal of Organometallic Chemistry. - : Elsevier BV. - 0022-328X. ; 720, s. 52-59
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Tidskriftsartikel (refereegranskat)abstract
- The synthesis of series of 1,2,1' substituted bis(diphenylphosphino)- ruthenocenyl (1-4) and ferrocenyl cis-platinum(II) (5-7) and gold(I) (8-12) complexes are described. Crystal structures of 2 and 4, as well as 5, 6 and 10 confirm the molecular geometry of these ligands and their metal complexes. Preliminary investigation of four gold complexes as potential anticancer, antiHIV and antimalaria showed at least one gold compound that has excellent activity towards one of these diseases. The three gold(I) complexes, {1- [1-(dimethylamino)ethyl]-1 ,2-bis(diphenylphosphino)ruthenocene-kappa P-2,P'}bis[chlorogold(I)] (8) (IC50 = 1.40 mu M), {1-[1-(acetoxyethyl)-1',2-bis(diphenylphosphino)ferrocene-kappa P-2,P']bis[chlorogold(1)] (9) (IC50 = 0.51 mu M), {1-[1-(3-carboxypropanamido)ethyl]-1',2-bis(diphenylphosphino)-ruthenocene kappa P-2,P'} bis[chlorogold(I)] (12) (IC50 = 1.784 mu M), have the best activities against cancer, HIV and malaria respectively. (C) 2012 Elsevier B.V. All rights reserved.
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| 6. |
- Brown, William R A, et al.
(författare)
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A Geographically Diverse Collection of Schizosaccharomyces pombe Isolates Shows Limited Phenotypic Variation but Extensive Karyotypic Diversity.
- 2011
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Ingår i: G3 (Bethesda, Md.). - : Oxford University Press (OUP). - 2160-1836. ; 1:7, s. 615-26
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Tidskriftsartikel (refereegranskat)abstract
- The fission yeast Schizosaccharomyces pombe has been widely used to study eukaryotic cell biology, but almost all of this work has used derivatives of a single strain. We have studied 81 independent natural isolates and 3 designated laboratory strains of Schizosaccharomyces pombe. Schizosaccharomyces pombe varies significantly in size but shows only limited variation in proliferation in different environments compared with Saccharomyces cerevisiae. Nucleotide diversity, π, at a near neutral site, the central core of the centromere of chromosome II is approximately 0.7%. Approximately 20% of the isolates showed karyotypic rearrangements as detected by pulsed field gel electrophoresis and filter hybridization analysis. One translocation, found in 6 different isolates, including the type strain, has a geographically widespread distribution and a unique haplotype and may be a marker of an incipient speciation event. All of the other translocations are unique. Exploitation of this karyotypic diversity may cast new light on both the biology of telomeres and centromeres and on isolating mechanisms in single-celled eukaryotes.
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| 7. |
- Chenouard, Nicolas, et al.
(författare)
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Objective comparison of particle tracking methods
- 2014
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Ingår i: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 11:3, s. 281-U247
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Tidskriftsartikel (refereegranskat)abstract
- Particle tracking is of key importance for quantitative analysis of intracellular dynamic processes from time-lapse microscopy image data. Because manually detecting and following large numbers of individual particles is not feasible, automated computational methods have been developed for these tasks by many groups. Aiming to perform an objective comparison of methods, we gathered the community and organized an open competition in which participating teams applied their own methods independently to a commonly defined data set including diverse scenarios. Performance was assessed using commonly defined measures. Although no single method performed best across all scenarios, the results revealed clear differences between the various approaches, leading to notable practical conclusions for users and developers.
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| 8. |
- Hilmi, nathalie, et al.
(författare)
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Towards improved socio-economic assessments of ocean acidification’s impacts
- 2013
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Ingår i: Marine Biology. - : Springer Science and Business Media LLC. - 0025-3162 .- 1432-1793. ; 160:8, s. 1773-1787
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Forskningsöversikt (refereegranskat)abstract
- Ocean acidification is increasingly recognized as a component of global change that could have a wide range of impacts on marine organisms, the ecosystems they live in, and the goods and services they provide humankind. Assessment of these potential socio-economic impacts requires integrated efforts between biologists, chemists, oceanographers, economists and social scientists. But because ocean acidification is a new research area, significant knowledge gaps are preventing economists from estimating its welfare impacts. For instance, economic data on the impact of ocean acidification on significant markets such as fisheries, aquaculture and tourism are very limited (if not non-existent), and non-market valuation studies on this topic are not yet available. Our paper summarizes the current understanding of future OA impacts and sets out what further information is required for economists to assess socio-economic impacts of ocean acidification. Our aim is to provide clear directions for multidisciplinary collaborative research.
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| 9. |
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| 10. |
- Rockey, William M., et al.
(författare)
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Rational truncation of an RNA aptamer to prostate-specific membrane antigen using computational structural modeling
- 2011
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Ingår i: Nucleic Acid Therapeutics. - : Mary Ann Liebert. - 2159-3337 .- 2159-3345. ; 21:5, s. 299-314
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Tidskriftsartikel (refereegranskat)abstract
- RNA aptamers represent an emerging class of pharmaceuticals with great potential for targeted cancer diagnostics and therapy. Several RNA aptamers that bind cancer cell-surface antigens with high affinity and specificity have been described. However, their clinical potential has yet to be realized. A significant obstacle to the clinical adoption of RNA aptamers is the high cost of manufacturing long RNA sequences through chemical synthesis. Therapeutic aptamers are often truncated postselection by using a trial-and-error process, which is time consuming and inefficient. Here, we used a rational truncation approach guided by RNA structural prediction and protein/RNA docking algorithms that enabled us to substantially truncateA9, an RNA aptamer to prostate-specific membrane antigen (PSMA),with great potential for targeted therapeutics. This truncated PSMA aptamer (A9L; 41mer) retains binding activity, functionality, and is amenable to large-scale chemical synthesis for future clinical applications. In addition, the modeled RNA tertiary structure and protein/RNA docking predictions revealed key nucleotides within the aptamer critical for binding to PSMA and inhibiting its enzymatic activity. Finally, this work highlights the utility of existing RNA structural prediction and protein docking techniques that may be generally applicable to developing RNA aptamers optimized for therapeutic use. © 2011 Mary Ann Liebert, Inc.
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