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- 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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- Ekanem, Emmanuel, et al.
(author)
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Safety of pulsed field ablation in more than 17,000 patients with atrial fibrillation in the MANIFEST-17K study
- 2024
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In: Nature Medicine. - : NATURE PORTFOLIO. - 1078-8956 .- 1546-170X.
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Journal article (peer-reviewed)abstract
- Pulsed field ablation (PFA) is an emerging technology for the treatment of atrial fibrillation (AF), for which pre-clinical and early-stage clinical data are suggestive of some degree of preferentiality to myocardial tissue ablation without damage to adjacent structures. Here in the MANIFEST-17K study we assessed the safety of PFA by studying the post-approval use of this treatment modality. Of the 116 centers performing post-approval PFA with a pentaspline catheter, data were received from 106 centers (91.4% participation) regarding 17,642 patients undergoing PFA (mean age 64, 34.7% female, 57.8% paroxysmal AF and 35.2% persistent AF). No esophageal complications, pulmonary vein stenosis or persistent phrenic palsy was reported (transient palsy was reported in 0.06% of patients; 11 of 17,642). Major complications, reported for similar to 1% of patients (173 of 17,642), were pericardial tamponade (0.36%; 63 of 17,642) and vascular events (0.30%; 53 of 17,642). Stroke was rare (0.12%; 22 of 17,642) and death was even rarer (0.03%; 5 of 17,642). Unexpected complications of PFA were coronary arterial spasm in 0.14% of patients (25 of 17,642) and hemolysis-related acute renal failure necessitating hemodialysis in 0.03% of patients (5 of 17,642). Taken together, these data indicate that PFA demonstrates a favorable safety profile by avoiding much of the collateral damage seen with conventional thermal ablation. PFA has the potential to be transformative for the management of patients with AF.
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- Garde, E., et al.
(author)
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Life history parameters of narwhals (Monodon monoceros) from Greenland
- 2015
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In: Journal of Mammalogy. - : Oxford University Press (OUP). - 0022-2372 .- 1545-1542. ; 96:4, s. 866-879
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Journal article (peer-reviewed)abstract
- Life history parameters for narwhals (Monodon monoceros) were estimated based on age estimates from aspartic acid racemization of eye lens nuclei. Eyes, reproductive organs, and measures of body lengths were collected from 282 narwhals in East and West Greenland in the years 1993, 2004, and 2007-2010. Age estimates were based on the racemization of L-aspartic acid to D-aspartic acid in the nucleus of the eye lens. The ratio of D- and L-enantiomers was measured using high-performance liquid chromatography. The age equation used, 420.32X - 24.02 center dot year where X is the D/L ratio, was determined from data from Garde et al. (2012). Asymptotic body length was estimated to be 405 +/- 5.8cm for females and 462 +/- 16.2cm for males from East Greenland, and 399 +/- 5.9cm for females and 456 +/- 6.9cm for males from West Greenland. Due to several indeterminant age class estimates, age at sexual maturity was subjectively assessed based on data from reproductive organs and was estimated to be 8-9 years for females and 12-20 years for males. Pregnancy rates for East and West Greenland were estimated to be 0.38-0.42 and 0.38, respectively. Maximum life span expectancy was found to be approximately 100 years. A population projection matrix was parameterized with the data on age structure and fertility rates. The annual rate of increase of narwhals in East Greenland was estimated to be 3.8% while narwhals in West Greenland had a rate of increase at 2.6%.
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- Heide-Jørgensen, Mads Peter, et al.
(author)
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Rate of increase and current abundance of humpback whales in West Greenland.
- 2012
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In: Journal of Cetacean Research and Management. - 1561-0713. ; 12, s. 1-14
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Journal article (peer-reviewed)abstract
- Aerial line transect surveys of the density of humpback whales (Megaptera novaeangliae) conducted off West Greenland eight times between 1984 and 2007 were used to estimate the rate of increase on the summer feeding ground. Only surveys in 1993, 2005 and 2007 had enough sightings to construct independent density estimates, whereas the surveys in 1984–85 and 1987–89 had to be merged and treated as two surveys. The annual rate of increase was 9.4% yr–1 (SE = 0.01) between 1984 and 2007. This rate of increase is higher than the increase estimated at the breeding grounds in the West Indies, but is of the same magnitude as the observed rate of increase at other feeding grounds in the North Atlantic. A matrix model based on observed life history parameters revealed that the theoretical growth rate of a humpback whale population ranged between 1 and 11%. This confirms that the observed growth in West Greenland is within the plausible values. The survey in 2007 was used to make a fully corrected abundance estimate including corrections for whales that were submerged during the passage of the survey plane. The line transect estimate for 2007 was 1,020 (CV = 0.35). When the estimate was corrected for perception bias with mark-recapture distance sampling (MRDS) methods, the abundance increased to 1,505 (0.49). A correction for availability bias was developed based on time-depth-recorder information on the time spent at the surface (0–4m). However, used directly this correction leads to a positively-biased abundance estimate and instead a correction was developed for the non-instantaneous visual sighting process in an aircraft. The resulting estimate for 2007 was 3,272 (CV = 0.50) for the MRDS analysis. An alternative strip census estimate deploying a strip width of 300m resulted in 995 (0.33) whales. Correction for perception bias resulted in 991 (0.35) whales and corrected for the same availability bias as for the MRDS method resulted in a fully corrected estimate of 2,154 (0.36) humpback whales in West Greenland in 2007.
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- Hoeft, Birgit, et al.
(author)
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Polymorphisms in fatty acid metabolism-related genes are associated with colorectal cancer risk
- 2010
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In: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 31:3, s. 466-472
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Journal article (peer-reviewed)abstract
- Colorectal cancer (CRC) is the third most common malignant tumor and the fourth leading cause of cancer death worldwide. The crucial role of fatty acids for a number of important biological processes suggests a more in-depth analysis of inter-individual differences in fatty acid metabolizing genes as contributing factor to colon carcinogenesis. We examined the association between genetic variability in 43 fatty acid metabolism-related genes and colorectal risk in 1225 CRC cases and 2032 controls participating in the European Prospective Investigation into Cancer and Nutrition study. Three hundred and ninety two single-nucleotide polymorphisms were selected using pairwise tagging with an r(2) cutoff of 0.8 and a minor allele frequency of > 5%. Conditional logistic regression models were used to estimate odds ratios and corresponding 95% confidence intervals. Haplotype analysis was performed using a generalized linear model framework. On the genotype level, hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD), phospholipase A2 group VI (PLA2G6) and transient receptor potential vanilloid 3 were associated with higher risk for CRC, whereas prostaglandin E receptor 2 (PTGER2) was associated with lower CRC risk. A significant inverse association (P < 0.006) was found for PTGER2 GGG haplotype, whereas HPGD AGGAG and PLA2G3 CT haplotypes were significantly (P < 0.001 and P = 0.003, respectively) associated with higher risk of CRC. Based on these data, we present for the first time the association of HPGD variants with CRC risk. Our results support the key role of prostanoid signaling in colon carcinogenesis and suggest a relevance of genetic variation in fatty acid metabolism-related genes and CRC risk.
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| 9. |
- Munthe, John, et al.
(author)
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Klimatförändringen och miljömål
- 2016
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Reports (other academic/artistic)abstract
- Forskningsprogrammet CLEO, Climate change and Environmental Objectives, startades 2010 efter en utlysning från Naturvårdsverket där man efterfrågade forskning med en övergripande målsättning att få: * En analys och kvantifiering av hur förändringar i klimatet, såsom temperatur, nederbörd och avrinning, påverkar förutsättningarna att nå de miljömål som påverkas av långväga transporterade luftföroreningar * En beskrivning och analys av synergier och målkonflikter av åtgärder, både nationellt och internationellt, för att minska utsläpp av växthusgaser och andra luftföroreningar för att nå uppsatta miljömål. * Förbättrad kunskap om grundläggande processer för att ta fram tillförlitliga prognoser och scenarier för utvecklingen mot miljömålen, förbättrade indata till existerande modeller samt bättre sammanlänkning av modeller för klimat, luft och ekosystem. Programmet har fokuserat på miljömålen Frisk luft, Bara Naturlig Försurning, Ingen övergödning och i viss mån Giftfri miljö. Då målsättningen var att ta fram resultat som är relevanta för pågående arbete med miljömålen och för långsiktiga överväganden så har CLEO arbetat med framtidsscenarier som både fokuserat på en relativt nära framtid (2030), och i vissa avseenden ett längre tidsperspektiv (2100). This report is only available in Swedish. English summary is available in the report.
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