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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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| 2. |
- Conde, Lucia, et al.
(författare)
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Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:8, s. 661-664
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Tidskriftsartikel (refereegranskat)abstract
- To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 x 10(-29) and rs7755224, combined P = 2.00 x 10(-19); r(2) = 1.0), supporting the idea that major histocompatibility complex genetic variation influences follicular lymphoma susceptibility. We also found confirmatory evidence of a previously reported association between chronic lymphocytic leukemia/small lymphocytic lymphoma and rs735665 (combined P = 4.24 x 10(-9)).
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| 5. |
- Klepsch, Mirjam, 1983-, et al.
(författare)
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Escherichia coli Peptide Binding Protein OppA Has a Preference for Positively Charged Peptides
- 2011
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 414:1, s. 75-85
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Tidskriftsartikel (refereegranskat)abstract
- The Escherichia coli peptide binding protein OppA is an essential component of the oligopeptide transporter Opp. Based on studies on its orthologue from Salmonella typhimurium, it has been proposed that OppA binds peptides between two and five amino acids long, with no apparent sequence selectivity. Here, we studied peptide binding to E. coli OppA directly and show that the protein has an unexpected preference for basic peptides. OppA was expressed in the periplasm, where it bound to available peptides. The protein was purified in complex with tightly bound peptides. The crystal structure (up to 2.0 angstrom) of OppA liganded with the peptides indicated that the protein has a preference for peptides containing a lysine. Mass spectrometry analysis of the bound peptides showed that peptides between two and five amino acids long bind to the protein and indeed hinted at a preference for positively charged peptides. The preference of OppA for peptides with basic residues, in particular lysines, was corroborated by binding studies with peptides of defined sequence using isothermal titration calorimetry and intrinsic protein fluorescence titration. The protein bound tripeptides and tetrapeptides containing positively charged residues with high affinity, whereas related peptides without lysines/arginines were bound with low affinity. A structure of OppA in an open conformation in the absence of ligands was also determined to 2.0 angstrom, revealing that the initial binding site displays a negative surface charge, consistent with the observed preference for positively charged peptides. Taken together, E. coli OppA appears to have a preference for basic peptides.
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| 6. |
- Low, Nicola, et al.
(författare)
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Chlamydia control activities in Europe : cross-sectional survey
- 2012
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Ingår i: European Journal of Public Health. - : Oxford University Press (OUP). - 1101-1262 .- 1464-360X. ; 22:4, s. 556-561
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chlamydia is the most commonly reported bacterial sexually transmitted infection in Europe. The objective of the Screening for Chlamydia in Europe (SCREen) project was to describe current and planned chlamydia control activities in Europe.METHODS: The authors sent a questionnaire asking about different aspects of chlamydia epidemiology and control to public health and clinical experts in each country in 2007. The principles of sexually transmitted infection control were used to develop a typology comprising five categories of chlamydia control activities. Each country was assigned to a category, based on responses to the questionnaire.RESULTS: Experts in 29 of 33 (88%) invited countries responded. Thirteen of 29 countries (45%) had no current chlamydia control activities. Six countries in this group stated that there were plans to introduce chlamydia screening programmes. There were five countries (17%) with case management guidelines only. Three countries (10%) also recommended case finding amongst partners of diagnosed chlamydia cases or people with another sexually transmitted infection. Six countries (21%) further specified groups of asymptomatic people eligible for opportunistic chlamydia testing. Two countries (7%) reported a chlamydia screening programme. There was no consistent association between the per capita gross domestic product of a country and the intensity of chlamydia control activities (P = 0.816).CONCLUSION: A newly developed classification system allowed the breadth of ongoing national chlamydia control activities to be described and categorized. Chlamydia control strategies should ensure that clinical guidelines to optimize chlamydia diagnosis and case management have been implemented before considering the appropriateness of screening programmes.
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| 7. |
- Moles, Angela T, et al.
(författare)
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Correlations between physical and chemical defences in plants : tradeoffs, syndromes, or just many different ways to skin a herbivorous cat?
- 2013
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Ingår i: New Phytologist. - : Wiley-Blackwell. - 0028-646X .- 1469-8137. ; 198:1, s. 252-263
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Tidskriftsartikel (refereegranskat)abstract
- Most plant species have a range of traits that deter herbivores. However, understanding of how different defences are related to one another is surprisingly weak. Many authors argue that defence traits trade off against one another, while others argue that they form coordinated defence syndromes. We collected a dataset of unprecedented taxonomic and geographic scope (261 species spanning 80 families, from 75 sites across the globe) to investigate relationships among four chemical and six physical defences. Five of the 45 pairwise correlations between defence traits were significant and three of these were tradeoffs. The relationship between species' overall chemical and physical defence levels was marginally nonsignificant (P=0.08), and remained nonsignificant after accounting for phylogeny, growth form and abundance. Neither categorical principal component analysis (PCA) nor hierarchical cluster analysis supported the idea that species displayed defence syndromes. Our results do not support arguments for tradeoffs or for coordinated defence syndromes. Rather, plants display a range of combinations of defence traits. We suggest this lack of consistent defence syndromes may be adaptive, resulting from selective pressure to deploy a different combination of defences to coexisting species.
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| 8. |
- Moles, A. T., et al.
(författare)
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Putting plant resistance traits on the map : A test of the idea that plants are better defended at lower latitudes
- 2011
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Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 191:3, s. 777-788
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Tidskriftsartikel (refereegranskat)abstract
- It has long been believed that plant species from the tropics have higher levels of traits associated with resistance to herbivores than do species from higher latitudes. A meta-analysis recently showed that the published literature does not support this theory. However, the idea has never been tested using data gathered with consistent methods from a wide range of latitudes. • We quantified the relationship between latitude and a broad range of chemical and physical traits across 301 species from 75 sites world-wide. • Six putative resistance traits, including tannins, the concentration of lipids (an indicator of oils, waxes and resins), and leaf toughness were greater in high-latitude species. Six traits, including cyanide production and the presence of spines, were unrelated to latitude. Only ash content (an indicator of inorganic substances such as calcium oxalates and phytoliths) and the properties of species with delayed greening were higher in the tropics. • Our results do not support the hypothesis that tropical plants have higher levels of resistance traits than do plants from higher latitudes. If anything, plants have higher resistance toward the poles. The greater resistance traits of high-latitude species might be explained by the greater cost of losing a given amount of leaf tissue in low-productivity environments. © 2011 New Phytologist Trust.
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