| 1. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
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.
|
|
| 2. |
- May, Andrew A., et al.
(författare)
-
Gas-particle partitioning of primary organic aerosol emissions : 3. Biomass burning
- 2013
-
Ingår i: Journal of Geophysical Research: Atmospheres. - : American Geophysical Union (AGU). - 2169-897X. ; 118:19, s. 11327-11338
-
Tidskriftsartikel (refereegranskat)abstract
- Atmospheric organic aerosol concentrations depend in part on the gas-particle partitioning of primary organic aerosol (POA) emissions. Consequently, heating and dilution were used to investigate the volatility of biomass-burning smoke particles from combustion of common North American trees/shrubs/grasses during the third Fire Lab at Missoula Experiment. Fifty to eighty percent of the mass of biomass-burning POA evaporated when isothermally diluted from plume- (~1000 µg m−3) to ambient-like concentrations (~10 µg m−3), while roughly 80% of the POA evaporated upon heating to 100°C in a thermodenuder with a residence time of ~14 sec. Therefore, the majority of the POA emissions were semivolatile. Thermodenuder measurements performed at three different residence times indicated that there were not substantial mass transfer limitations to evaporation (i.e., the mass accommodation coefficient appears to be between 0.1 and 1). An evaporation kinetics model was used to derive volatility distributions and enthalpies of vaporization from the thermodenuder data. A single volatility distribution can be used to represent the measured gas-particle partitioning from the entire set of experiments, including different fuels, organic aerosol concentrations, and thermodenuder residence times. This distribution, derived from the thermodenuder measurements, also predicts the dilution-driven changes in gas-particle partitioning. This volatility distribution and associated emission factors for each fuel studied can be used to update emission inventories and to simulate the gas-particle partitioning of biomass-burning POA emissions in chemical transport models.
|
|
| 3. |
- Brown, Sally, et al.
(författare)
-
Shifting perspectives on coastal impacts and adaptation
- 2014
-
Ingår i: Nature Climate Change. - : Nature Publishing Group. - 1758-678X .- 1758-6798. ; 4:9, s. 752-755
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The Intergovernmental Panel on Climate Change reports reflect evolving attitudes in adapting to sea-level rise by taking a systems approach and recognizing that multiple responses exist to achieve a less hazardous coast.
|
|
| 4. |
- Argüelles, Nancy, et al.
(författare)
-
Design, synthesis, and docking of highly hypolipidemic agents: Schizosaccharomyces pombe as a new model for evaluating α-asarone-based HMG-CoA reductase inhibitors
- 2010
-
Ingår i: Bioorganic and Medicinal Chemistry. - : Elsevier BV. - 0968-0896. ; 18, s. 4238-4248
-
Tidskriftsartikel (refereegranskat)abstract
- A series of α-asarone-based analogues was designed by conducting docking experiments with published crystal structures of human HMG-CoA reductase. Indeed, synthesis and evaluation of this series showed a highly hypocholesterolemic in vivo activity in a murine model, as predicted by previous docking studies. In agreement with this model, the polar groups attached to the benzene ring could play a key role in the enzyme binding and probably also in its biological activity, mimicking the HMG-moiety of the natural substrate. The hypolipidemic action mechanism of these compounds was investigated by developing a simple, efficient, and novel model for determining HMG-CoA reductase inhibition. The partial purification of the enzyme from Schizosaccharomyces pombe allowed for testing of α-asarone- and fibrate-based analogues, resulting in positive and significant inhibitory activity. © 2010 Elsevier Ltd. All rights reserved.
|
|
| 5. |
- García-Diz, Luis, et al.
(författare)
-
Assessing nutritional status of acute intermittent porphyria patients
- 2012
-
Ingår i: European Journal of Clinical Investigation. - : Wiley-Blackwell. - 0014-2972 .- 1365-2362. ; 42:9, s. 943-952
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Acute intermittent porphyria (AIP) is a metabolic disease of haem synthesis, whose haem precursors may accumulate in the body. A well-balanced diet may prevent the symptoms, so that porphyric patients should be monitored closely during therapy for possible complications concerning any progression of acute porphyria. The aim was to evaluate the nutritional status of patients with AIP and to assess their compliance with nutritional recommendations, comparing the findings with a control group and assessing any possible nutritional deficiency.MATERIAL AND METHODS: Sixteen patients with AIP and a control group were evaluated by means of a lifestyle questionnaire, the Nutrition Screening Initiative checklist and a dietary questionnaire. The following diet quality indicators were calculated: animal and vegetal proteins, protein quality index, PUFA/SFA and MUFA + PUFA/SFA ratios, insoluble dietary fibre (DF)/total DF, soluble DF/total DF and insoluble DF/soluble DF ratios, thiamine, riboflavin and niacin density and the vitamin B6/protein ratio.STATISTICAL METHODS: Differences in continuous variables were compared using the unpaired Student's t-test and the chi-square test for nonparametric variables. The odds ratio (OR) of malnutrition was also used.RESULTS: Our patients showed a low intake of carbohydrates, a high lipid intake and very high protein intake, and accompanied by an inadequate intake of zinc, folic acid and tocopherol, increasing the risk of malnutrition for energy, Ca, Fe, Mg, K, folic acid and tocopherols.CONCLUSIONS: The patients with AIP studied individually show an increased risk of malnutrition and, given the potential increase of oxidative stress in patients with porphyria, it is recommended that they should increase their intake of carbohydrates, minerals and antioxidant nutrients.
|
|
| 6. |
- Guallar, Eliseo, et al.
(författare)
-
Excess risk attributable to traditional cardiovascular risk factors in clinical practice settings across Europe : The EURIKA Study
- 2011
-
Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 18:11
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundPhysicians involved in primary prevention are key players in CVD risk control strategies, but the expected reduction in CVD risk that would be obtained if all patients attending primary care had their risk factors controlled according to current guidelines is unknown. The objective of this study was to estimate the excess risk attributable, firstly, to the presence of CVD risk factors and, secondly, to the lack of control of these risk factors in primary prevention care across Europe.MethodsCross-sectional study using data from the European Study on Cardiovascular Risk Prevention and Management in Daily Practice (EURIKA), which involved primary care and outpatient clinics involved in primary prevention from 12 European countries between May 2009 and January 2010. We enrolled 7,434 patients over 50 years old with at least one cardiovascular risk factor but without CVD and calculated their 10-year risk of CVD death according to the SCORE equation, modified to take diabetes risk into account.ResultsThe average 10-year risk of CVD death in study participants (N = 7,434) was 8.2%. Hypertension, hyperlipidemia, smoking, and diabetes were responsible for 32.7 (95% confidence interval 32.0-33.4), 15.1 (14.8-15.4), 10.4 (9.9-11.0), and 16.4% (15.6-17.2) of CVD risk, respectively. The four risk factors accounted for 57.7% (57.0-58.4) of CVD risk, representing a 10-year excess risk of CVD death of 5.66% (5.47-5.85). Lack of control of hypertension, hyperlipidemia, smoking, and diabetes were responsible for 8.8 (8.3-9.3), 10.6 (10.3-10.9), 10.4 (9.9-11.0), and 3.1% (2.8-3.4) of CVD risk, respectively. Lack of control of the four risk factors accounted for 29.2% (28.5-29.8) of CVD risk, representing a 10-year excess risk of CVD death of 3.12% (2.97-3.27).ConclusionsLack of control of CVD risk factors was responsible for almost 30% of the risk of CVD death among patients participating in the EURIKA Study.
|
|
| 7. |
- Jimenez-Saez, Fernando, et al.
(författare)
-
Evaluating research efficiency within National R&D Programmes
- 2011
-
Ingår i: Research Policy. - : Elsevier BV. - 0048-7333. ; 40:2, s. 230-241
-
Tidskriftsartikel (refereegranskat)abstract
- Relying on efficiency analysis, we evaluate to what extent policy makers have been able to promote the establishment of consolidated and comprehensive research groups to contribute to the implementation of a successful innovation system for the Spanish food technology sector, oriented to the production of knowledge based on an application model. Using data envelopment analysis techniques that allow calculation of a generalized version of the traditional distance function model for productive efficiency, we find pervasive levels of inefficiency and a typology of different research strategies. Among these, in contrast to what has been assumed, established groups do not play the pre-eminent benchmarking role; rather, partially oriented, specialized and "shooting star" groups are the most common patterns. These results correspond with an infant innovation system, where the fostering of higher levels of efficiency and the promotion of the desired research patterns are ongoing. (C) 2010 Elsevier B.V. All rights reserved.
|
|
| 8. |
- Rodríguez-Artalejo, Fernando, et al.
(författare)
-
Rationale and methods of the European Study on Cardiovascular Risk Prevention and Management in Daily Practice (EURIKA)
- 2010
-
Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- The EURIKA study aims to assess the status of primary prevention of cardiovascular disease (CVD) acrossEurope. Specifically, it will determine the degree of control of cardiovascular risk factors in current clinical practice in relation to the European guidelines on cardiovascular prevention. It will also assess physicians' knowledge and attitudes about CVD prevention as well as the barriers impeding effective risk factor management in clinical practice.
|
|
