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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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- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 4. |
- Guntram, Lisa, 1981-, et al.
(författare)
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Feminist Approaches to Using Other People’s Words : Two Examples
- 2018
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Ingår i: SAGE Research Methods Cases Part 2. - 1 Oliver's Yard, 55 City Road, London EC1Y 1SP United Kingdom : Sage Publications. - 9781526443236
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Bokkapitel (refereegranskat)abstract
- This research methods case discusses how we use other people’s words—often collected through interviews—when informed by feminist methodology and theory. It presents different approaches to interview material (narrative analysis, discourse analysis, and conversation analysis) and considers how these epistemological approaches create “facts” (often called ontology) from “data.” We end by discussing how our use of interview material created different knowledge through the concept of onto-epistemology. We hope students will be left with an understanding of how one’s own positionality always affects what one sees in material. Using feminist methods and theories (and hoping students see the difficulties in drawing a strong distinction between methods and theories), we problematize a positivist understanding of qualitative research.
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- Krifors, Anders, et al.
(författare)
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Influenza-associated invasive aspergillosis in patients admitted to the intensive care unit in Sweden : a prospective multicentre cohort study
- 2024
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Ingår i: Infectious Diseases. - : Taylor & Francis. - 2374-4235 .- 2374-4243. ; 56:2, s. 110-115
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The purpose of this study was to prospectively investigate the incidence of influenza-associated pulmonary aspergillosis (IAPA) in influenza patients admitted to intensive care units in Sweden.METHODS: The study included consecutive adult patients with PCR-verified influenza A or B in 12 Swedish intensive care units (ICUs) over four influenza seasons (2019-2023). Patients were screened using serum galactomannan and β-d-glucan tests and fungal culture of a respiratory sample at inclusion and weekly during the ICU stay. Bronchoalveolar lavage was performed if clinically feasible. IAPA was classified according to recently proposed case definitions.RESULTS: The cohort included 55 patients; 42% were female, and the median age was 59 (IQR 48-71) years. All patients had at least one galactomannan test, β-d-glucan test and respiratory culture performed. Bronchoalveolar lavage was performed in 24 (44%) of the patients. Five (9%, 95% CI 3.8% - 20.4%) patients were classified as probable IAPA, of which four lacked classical risk factors. The overall ICU mortality was significantly higher among IAPA patients than non-IAPA patients (60% vs 8%, p = 0.01).CONCLUSIONS: The study represents the first prospective investigation of IAPA incidence. The 9% incidence of IAPA confirms the increased risk of invasive pulmonary aspergillosis among influenza patients admitted to the ICU. Therefore, it appears reasonable to implement a screening protocol for the early diagnosis and treatment of IAPA in influenza patients receiving intensive care.TRIAL REGISTRATION: ClinicalTrials.gov NCT04172610, registered November 21, 2019.
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- Lindén, Lisa, 1985-
(författare)
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Communicating Care : The Contradictions of HPV Vaccination Campaigns
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Denna avhandling undersöker tre statligt finansierade kampanjer mot human papillomvirus (HPV) i Sverige. Författaren visar att kampanjerna innehåller och artikulerar olika former av omsorg som inte är begränsade till att endast uppmana människor att ”ta hand om sig själva” eller ”bry sig om andra”. Istället studeras omsorg som något mångfasetterat och kontextuellt, och som något som innefattar såväl mänskliga som icke-mänskliga komponenter. I studien fokuserar författaren på hur aktörer möjliggör och problematiserar olika former av omsorg. Dessa aktörer inkluderar yrkesverksamma inom landsting som försöker kommunicera omsorg till tjejer och deras anhöriga, men också olika materiella ting, såsom en ”HPV-app”, en Facebook-kampanjsida och en vaccinationshusvagn.Kampanjmedia, intervjuer och textbaserade cancerberättelser analyseras med hjälp av teoretiska perspektiv från fältet feministiska teknik- och vetenskapsstudier (STS). Studien är situerad till forskning kring omsorgspolitik inom teknik och vetenskap, och bidrar till diskussioner om tidsmässiga dimensioner av omsorg. I kampanjmaterialet som studeras dominerar ett fokus på omsorg som något som skall göras nu för att möjliggöra en hälsosam och lycklig framtid. Genom att använda sig av ett ”etiskt-politiskt” ställningstagande, och en analytisk ansats, där fokus ligger på att synliggöra marginella, frånvarande och alternativa omsorgsformer problematiserar författaren sådana ”snabba” framtidsorienterade omsorgsvisioner enligt vilka omsorg ses som något som skall göras omedelbart i preventivt syfte. Detta görs genom ett synliggörande av ”långsammare” och sammanflätade ”omsorgstemporaliteter” som öppnar upp för osäkerheter, tveksamheter, obestämdheter samt för olika känslouttryck, och som möjliggör mer omsorgsfulla praktiker.
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