| 1. |
- Sondergaard, Mads T., et al.
(författare)
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Calmodulin mutations causing catecholaminergic polymorphic ventricular tachycardia confer opposing functional and biophysical molecular changes
- 2015
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Ingår i: The FEBS Journal. - : Wiley. - 1742-464X. ; 282:4, s. 803-816
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Tidskriftsartikel (refereegranskat)abstract
- Calmodulin (CaM) is the central mediator of intracellular Ca2+ signalling in cardiomyocytes, where it conveys the intricate Ca2+ transients to the proteins controlling cardiac contraction. We recently linked two separate mutations in CaM (N53I and N97S) to dominantly inherited catecholaminergic polymorphic ventricular tachycardia (CPVT), an arrhythmic disorder in which exercise or acute emotion can lead to syncope and sudden cardiac death. Given the ubiquitous presence of CaM in all eukaryote cells, it is particular intriguing that carriers of either mutation show no additional symptoms. Here, we investigated the effects of the CaM CPVT mutations in a zebrafish animal model. Three-day-old embryos injected with either CaM mRNA showed no detectable pathologies or developmental abnormalities. However, embryos injected with CPVT CaM mRNA displayed increased heart rate compared to wild-type CaM mRNA under -adrenergic stimulation, demonstrating a conserved dominant cardiac specific effect between zebrafish and human carriers of these mutations. Motivated by the highly similar physiological phenotypes, we compared the effects of the N53I and N97S mutations on the biophysical and functional properties of CaM. Surprisingly, the mutations have opposing effects on CaM C-lobe Ca2+ binding affinity and kinetics, and changes to the CaM N-lobe Ca2+ binding are minor and specific to the N53I mutation. Furthermore, both mutations induce differential perturbations to structure and stability towards unfolding. Our results suggest different molecular disease mechanisms for the CPVT (N53I and N97S mutations) and strongly support that cardiac contraction is the physiological process most sensitive to CaM integrity.
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| 2. |
- Beelen, Rob, et al.
(författare)
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Natural-Cause Mortality and Long-Term Exposure to Particle Components : An Analysis of 19 European Cohorts within the Multi-Center ESCAPE Project
- 2015
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 123:6, s. 525-533
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Forskningsöversikt (refereegranskat)abstract
- Background: Studies have shown associations between mortality and long-term exposure to particulate matter air pollution. Few cohort studies have estimated the effects of the elemental composition of particulate matter on mortality. Objectives: Our aim was to study the association between natural-cause mortality and long-term exposure to elemental components of particulate matter. Methods: Mortality and confounder data from 19 European cohort studies were used. Residential exposure to eight a priori-selected components of particulate matter ( PM) was characterized following a strictly standardized protocol. Annual average concentrations of copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc within PM size fractions <= 2.5 mu m (PM2.5) and <= 10 mu m (PM10) were estimated using land-use regression models. Cohort-specific statistical analyses of the associations between mortality and air pollution were conducted using Cox proportional hazards models using a common protocol followed by meta-analysis. Results: The total study population consisted of 291,816 participants, of whom 25,466 died from a natural cause during follow-up (average time of follow-up, 14.3 years). Hazard ratios were positive for almost all elements and statistically significant for PM2.5 sulfur (1.14; 95% CI: 1.06, 1.23 per 200ng/m(3)). In a two-pollutant model, the association with PM2.5 sulfur was robust to adjustment for PM2.5 mass, whereas the association with PM2.5 mass was reduced. Conclusions: Long-term exposure to PM2.5 sulfur was associated with natural-cause mortality. This association was robust to adjustment for other pollutants and PM2.5.
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| 3. |
- Sorensen, Annette, et al.
(författare)
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Identifying and characterizing the most significant beta-glucosidase of the novel species Aspergillus saccharolyticus
- 2012
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Ingår i: Canadian Journal of Microbiology. - 0008-4166. ; 58:9, s. 1035-1046
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Tidskriftsartikel (refereegranskat)abstract
- The newly discovered fungal species Aspergillus saccharolyticus was found to produce a culture broth rich in beta-glucosidase activity. In this present work, the main beta-glucosidase of A. saccharolyticus responsible for the efficient hydrolytic activity was identified, isolated, and characterized. Ion exchange chromatography was used to fractionate the culture broth, yielding fractions with high beta-glucosidase activity and only 1 visible band on an SDS-PAGE gel. Mass spectrometry analysis of this band gave peptide matches to beta-glucosidases from aspergilli. Through a polymerase chain reaction approach using degenerate primers and genome walking, a 2919 bp sequence encoding the 860 amino acid BGL1 polypeptide was determined. BGL1 of A. saccharolyticus has 91% and 82% identity with BGL1 from Aspergillus aculeatus and BGL1 from Aspergillus niger, respectively, both belonging to Glycoside Hydrolase family 3. Homology modeling studies suggested beta-glucosidase activity with preserved retaining mechanism and a wider catalytic pocket compared with other beta-glucosidases. The bgl1 gene was heterologously expressed in Trichoderma reesei QM6a, purified, and characterized by enzyme kinetics studies. The enzyme can hydrolyze cellobiose, p-nitrophenyl-beta-D-glucoside, and cellodextrins. The enzyme showed good thermostability, was stable at 50 degrees C, and at 60 degrees C it had a half-life of approximately 6 h.
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| 4. |
- Weinmayr, Gudrun, et al.
(författare)
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Particulate matter air pollution components and incidence of cancers of the stomach and the upper aerodigestive tract in the European Study of Cohorts of Air Pollution Effects (ESCAPE)
- 2018
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 120, s. 163-171
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Previous analysis from the large European multicentre ESCAPE study showed an association of ambient particulate matter < 2.5 mu m (PM2.5) air pollution exposure at residence with the incidence of gastric cancer. It is unclear which components of PM are most relevant for gastric and also upper aerodigestive tract (UADT) cancer and some of them may not be strongly correlated with PM mass. We evaluated the association between long-term exposure to elemental components of PM2.5 and PM10 and gastric and UADT cancer incidence in European adults.Methods: Baseline addresses of individuals were geocoded and exposure was assessed by land-use regression models for copper (Cu), iron (Fe) and zinc (Zn) representing non-tailpipe traffic emissions; sulphur (S) indicating long-range transport; nickel (Ni) and vanadium (V) for mixed oil-burning and industry; silicon (Si) for crustal material and potassium (K) for biomass burning. Cox regression models with adjustment for potential confounders were used for cohort-specific analyses. Combined estimates were determined with random effects meta-analyses.Results: Ten cohorts in six countries contributed data on 227,044 individuals with an average follow-up of 14.9 years with 633 incident cases of gastric cancer and 763 of UADT cancer. The combined hazard ratio (HR) for an increase of 200 ng/m(3) of PM2.5_S was 1.92 (95%-confidence interval (95%-CI) 1.13; 3.27) for gastric cancer, with no indication of heterogeneity between cohorts (I-2= 0%), and 1.63 (95%-CI 0.88; 3.01) for PM2.5_Zn (I-2= 70%). For the other elements in PM2.5 and all elements in PM10 including PM10_S, non-significant HRs between 0.78 and 1.21 with mostly wide CIs were seen. No association was found between any of the elements and UADT cancer. The HR for PM2.5_S and gastric cancer was robust to adjustment for additional factors, including diet, and restriction to study participants with stable addresses over follow-up resulted in slightly higher effect estimates with a decrease in precision. In a two-pollutant model, the effect estimate for total PM2.5 decreased whereas that for PM2.5_S was robust.Conclusion: This large multicentre cohort study shows a robust association between gastric cancer and long-term exposure to PM2.5 S but not PM10 S, suggesting that S in PM2.5 or correlated air pollutants may contribute to the risk of gastric cancer.
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| 5. |
- Holmstrup, Martin, et al.
(författare)
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Cold acclimation and lipid composition in the earthworm Dendrobaena octaedra
- 2007
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Ingår i: Comparative Biochemistry and Physiology A. - : Elsevier BV. - 1531-4332. ; 147:4, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated the lipid chemistry during cold acclimation in the freeze tolerant earthworm Dendrobaena octaedra. The dominant phospholipid fatty acids (PLFA) of D. octaedra were 20:4, 20:5 and 20:1 (50% of total PLFA) followed by 18:0, 18:1 and 18:2 omega 6,9 (25% of total PLFA). The ability to tolerate freezing in this species was acquired after acclimation at low temperature for 2-4 weeks. During this period one particular membrane PLFA, 18:2 omega 6,9, increased significantly and there was a good correlation between the proportion of this PLFA and the survival of freezing. The composition of neutral lipid fatty acids (NLFA), most likely representing storage lipids (triacylglycerides), also changed during cold acclimation so that the overall degree of unsaturation increased. Using a common-garden experiment approach, we compared lipid composition of three genetically different populations (Denmark, Finland and Greenland) that differed in their freeze tolerance. Inter-populational differences and differences due to cold acclimation in overall fatty acid composition were evident in both PLFAs and NLFAs. Specifically, the PLFAs, 20:4 and 20:5, were considerably more represented in worms from Greenland, and this contributed to a higher U1 of PLFAs in this population. (c) 2007 Elsevier Inc. All rights reserved.
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| 6. |
- Li, Kefei, et al.
(författare)
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Long-term field exposure of structural concretes in marine environment: state-of-the-art review by RILEM TC 289-DCM
- 2022
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Ingår i: Materials and Structures/Materiaux et Constructions. - : Springer Science and Business Media LLC. - 1359-5997. ; 55:7
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Tidskriftsartikel (refereegranskat)abstract
- This paper reviews the technical aspects related to the long-term field exposure practice in marine environments, based on the return of experiences of major marine exposure sites in world-wide scope. The long-term exposure practice helps both the research on durability mechanisms of structural concretes under real environments and the calibration of durability models to support the life-cycle management of concrete structures. The presentation of the field exposure data can be categorized into the information relevant to exposure sites, the data related to the exposed materials and specimens, the information of environmental actions, and the data related to the performance of materials. A standardized presentation of these data can help the efficiency of data sharing and exploitation. The exploitation of exposure data employs various models to represent the chloride ingress and the induced corrosion risk of the embedded steel bars. There are needs for models addressing the strong environment-material interactions, and simple yet reliable durability indicators for engineering use. The design and operation of exposure stations need the careful choice of exposure sites and specimens, the appropriate scheme for monitoring and inspection of exposed specimens, the systematic recording and management of exposure data, and the regular maintenance of exposure facilities. The support of exposure data for life-cycle management is demonstrated through the durability planning of a real project case. The good practice of long-term field exposure is summarized in the end.
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