| 1. |
- Björklund, Erik, et al.
(författare)
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Admission N-terminal pro-brain natriuretic peptide and its interaction with admission troponin T and ST segment resolution for early risk stratification in ST elevation myocardial infarction
- 2006
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Ingår i: Heart. - : BMJ Publishing Group. - 1468-201X .- 1355-6037. ; 92:6, s. 735-40
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the long term prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) on admission and its prognostic interaction with both admission troponin T (TnT) concentrations and resolution of ST segment elevation in fibrinolytic treated ST elevation myocardial infarction (STEMI). DESIGN AND SETTING: Substudy of the ASSENT (assessment of the safety and efficacy of a new thrombolytic) -2 and ASSENT-PLUS trials. PATIENTS: NT-proBNP and TnT concentrations were determined on admission in 782 patients. According to NT-proBNP concentrations, patients were divided into three groups: normal concentration (for patients < or = 65 years, < or = 184 ng/l and < or = 268 ng/l and for those > 65 years, < or = 269 ng/l and < or = 391 ng/l in men and women, respectively); higher than normal but less than the median concentration (742 ng/l); and above the median concentration. For TnT, a cut off of 0.1 microg/l was used. Of the 782 patients, 456 had ST segment resolution (< 50% or > or = 50%) at 60 minutes calculated from ST monitoring. MAIN OUTCOME MEASURES: All cause one year mortality. RESULTS: One year mortality increased stepwise according to increasing concentrations of NT-proBNP (3.4%, 6.5%, and 23.5%, respectively, p < 0.001). In receiver operating characteristic analysis, NT-proBNP strongly trended to be associated more with mortality than TnT and time to 50% ST resolution (area under the curve 0.81, 95% confidence interval (CI) 0.72 to 0.9, 0.67, 95% CI 0.56 to 0.79, and 0.66, 95% CI 0.56 to 0.77, respectively). In a multivariable analysis adjusted for baseline risk factors and TnT, both raised NT-proBNP and ST resolution < 50% were independently associated with higher one year mortality, whereas raised TnT contributed independently only before information on ST resolution was added to the model. CONCLUSION: Admission NT-proBNP is a strong independent predictor of mortality and gives, together with 50% ST resolution at 60 minutes, important prognostic information even after adjustment for TnT and baseline characteristics in STEMI.
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| 2. |
- Björklund, Erik, et al.
(författare)
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Admission Troponin T and measurement of ST-segment resolution at 60 min improve early risk stratification in ST-elevation myocardial infarction
- 2004
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Ingår i: Eur Heart J. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 25:2, s. 113-20
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The prognostic value of admission troponin T (tnT) levels and the resolution of the ST-segment elevation in ST-elevation myocardial infarction (STEMI) is well established. However, the combination of these two early available markers for predicting risk has not been evaluated. METHODS AND RESULTS: We evaluated 516 patients with fibrinolytic treated STEMI from the ASSENT-2 and ASSENT-PLUS studies, which had both admission tnT and ST-monitoring available. We used a prospectively defined cut-off value of tnT of 0.1microg/l. For ST-segment resolution, a cut-off of 50% measured after 60min was used. Both a tnT >/=0.1microg/l (n=116) and ST-segment resolution <50% (n=301) were related to higher one-year mortality, 13% vs 4% (P<0.001) and 8.4% vs 2.8% (P=0.009), respectively. In a multivariate analysis ST-segment resolution was and tnT showed a strong trend to be independently related to mortality. The combination of both further improved risk stratification. The one-year mortality in the group with elevation of tnT and without ST-segment resolution compared to the group without tnT elevation and with ST-segment resolution was 18.2% vs 2.8% (P<0.001). CONCLUSIONS: Both tnT on admission and ST-segment resolution after 60min are strong predictors of one-year mortality. The combination of both gives additive early information about prognosis and further improves risk stratification.
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| 3. |
- Agemark, Maria, et al.
(författare)
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Reconstitution of water channel function and 2D-crystallization of human aquaporin 8.
- 2012
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Ingår i: Biochimica et Biophysica Acta. - : Elsevier BV. - 0006-3002 .- 0005-2736. ; 1818:3, s. 839-850
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Tidskriftsartikel (refereegranskat)abstract
- Among the thirteen human aquaporins (AQP0-12), the primary structure of AQP8 is unique. By sequence alignment it is evident that mammalian AQP8s form a separate subfamily distinct from the other mammalian aquaporins. The constriction region of the pore determining the solute specificity deviates in AQP8 making it permeable to both ammonia and H(2)O(2) in addition to water. To better understand the selectivity and gating mechanism of aquaporins, high-resolution structures are necessary. So far, the structure of one human aquaporin (HsAQP5) has been solved at atomic resolution. For mammalian aquaporins in general, high-resolution structures are only available for those belonging to the water-specific subfamily (including HsAQP5). Thus, it is of interest to solve structures of other aquaporin subfamily members with different solute specificities. To achieve this the aquaporins need to be overexpressed heterologously and purified. Here we use the methylotrophic yeast Pichia pastoris as a host for the overexpression. A wide screen of different detergents and detergent-lipid combinations resulted in the solubilization of functional human AQP8 protein and in well-ordered 2D crystals. It also became evident that removal of amino acids constituting affinity tags was crucial to achieve highly ordered 2D crystals diffracting to 3Å.
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| 4. |
- Ahlberg, Per, et al.
(författare)
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Developmental plasticity and disparity in early dipnoan (lungfish) dentitions.
- 2006
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Ingår i: Evolution & Development. - 1520-541X .- 1525-142X. ; 8:4, s. 331-349
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Tidskriftsartikel (refereegranskat)abstract
- Although the lungfish (Dipnoi) belong within the Osteichthyes, their dentitions are radically different from other osteichthyans. Lungfish dentitions also show a uniquely high structural disparity during the early evolution of the group, partly owing to the independent variation of odontogenic and odontoclastic processes that are tightly and stereotypically coordinated in other osteichthyans. We present a phylogenetic analysis of early lungfishes incorporating a novel approach to coding these process characters in preference to the resultant adult dental morphology. The results only partially resolve the interrelationships of Devonian dipnoans, but show that the widely discussed hypothesis of separate tooth-plated, dentine-plated, and denticulated lineages is unlikely to be true. The dipnoan status of Diabolepis is corroborated. Lungfish dentitions seem to have undergone extensive and nonparsimonious evolution during the early history of the group, but much of the resulting disparity can be explained by a modest number of evolutionary steps in the underlying developmental processes, those for dental formation (odontogenic) and those for the remodeling of dentine tissue (odontoclastic). Later in lungfish evolution, this disparity was lost as the group settled to a pattern of dental development that is just as stereotypic as, but completely different from, that of other osteichthyans.
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| 5. |
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Ahlberg, Per Erik, 1963-, et al.
(författare)
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Pelvic claspers confirm chondrichthyan-like internal fertilization in arthrodires
- 2009
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 460:7257, s. 888-889
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Tidskriftsartikel (refereegranskat)abstract
- Recent finds(1,2) demonstrate that internal fertilization and viviparity (live birth) were more widespread in the Placodermi, an extinct group of armoured fishes, than was previously realized. Placoderms represent the sister group of the crown group jawed vertebrates (Gnathostomata)(3,4), making their mode(s) of reproduction potentially informative about primitive gnathostome conditions. An ossified pelvic fin basipterygium discovered in the arthrodire Incisoscutum ritchiei was hypothesized to be identical in males and females, with males presumed to have an additional cartilaginous element or series forming a clasper. Here we report the discovery of a completely ossified pelvic clasper in Incisoscutum ritchiei (WAM 03.3.28) which shows that this interpretation was incorrect: the basipterygium described previously(1) is in fact unique to females. The male clasper is a slender rod attached to a square basal plate that articulates directly with the pelvis. It carries a small cap of dermal bone covered in denticles and small hooks that may be homologous with the much larger dermal component of the ptyctodont clasper.
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| 10. |
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| 11. |
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| 12. |
- Akhtar, Reema, 1986-
(författare)
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What if your world is outside the oyster? : How highly educated and skilled first-generation immigrant entrepreneurs develop opportunities in knowledge-intensive sectors
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the previous decades, immigration has increased significantly from non-EU countries to Western countries including Sweden. Due to different backgrounds, immigrant´s economic integration is even more important for their financial support and the economic growth of the host country. Consequently, the rising unemployment rate poses a threat requiring multiple efforts to integrate immigrants into the labor market. One way immigrants tackle unemployment is by opting for entrepreneurship. However, most prior studies within the field of immigrant entrepreneurship focus mainly on disadvantaged immigrants who face high entry barriers and limit themselves to labor-intensive and low-productive traditional sectors that are not fast-growing nor boost economic growth. This disadvantaged view on immigrants is challenged, and subjected to reassessment, especially in the urban context, due to which I shift the focus to highly educated and skilled first-generation immigrant entrepreneurs from non-EU backgrounds. To understand what facilitates this group of immigrants, I use a consolidated view of opportunity creation and discovery namely opportunity development which is at the core of the entrepreneurship process. Furthermore, opportunities are considered to originate from a business idea making it indisputable that recognition and evaluation of a business idea are vital in their development. Hence I use IPA to analyze data from 30 interviews, cross-checked with secondary data collected through online sources, and contribute with a model, that provides empirical evidence and theoretical perspective within immigrant entrepreneurship literature on how weak and strong social ties, prior work experience, and education of highly educated and skilled first-generation immigrant entrepreneurs influence them to recognize and evaluate business ideas during opportunity development in knowledge-intensive sectors. Results show there was not a specific stage of opportunity development when either of the two social ties was more or less relevant, as knowledge flowed through both that helped bridge social distances. To persevere and overcome their foreign status, immigrants sought out weak social ties to get more acquainted with their host country. While they avoided involving some strong ties directly in business matters, however, they were equally important in providing emotional support and motivation. This resulted in increased self-efficacy in their capabilities and confidence in the feasibility, credibility, and legitimacy of their business ideas that helped overcome fears to make informed assessments, educated investments, and suitable adjustments. Furthermore, some weak ties turned into strong ties with time, such as ex-colleagues and clients who became lifelong friends, business partners, and advisors. Social ties also had a stronger impact when paired with the immigrant´s high human capital from pre-existing sources of specialized knowledge i.e., prior work experience and education as well as new knowledge gained through a systematic search with the help of social ties. Therefore, social ties are a source of new knowledge, while prior work and education are a source of social ties. A marginal number of immigrants felt frustrated with weak ties and as an alternative they relied on social networking websites, to connect with a wider global pool of potential business partners, clients, and skilled people.
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| 13. |
- Alexandersson, Erik, et al.
(författare)
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Transcriptional regulation of aquaporins in accessions of Arabidopsis in response to drought stress.
- 2010
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Ingår i: Plant Journal. - 1365-313X. ; 61, s. 650-660
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Tidskriftsartikel (refereegranskat)abstract
- Summary Aquaporins facilitate water transport over cellular membranes and are therefore believed to play an important role in water homeostasis. In higher plants aquaporin-like proteins, also called major intrinsic proteins (MIPs), are divided into 5 subfamilies. We have previously shown that MIP transcription in Arabidopsis thaliana generally is down-regulated in leaves upon drought stress, apart from two members of the Plasma membrane Intrinsic Protein (PIP) subfamily, AtPIP1;4 and AtPIP2;5, which are up-regulated. In order to assess if this regulation is general or accession-specific we monitored gene expression of all PIPs in five Arabidopsis accessions. Overall drought regulation of PIPs was well conserved for all five accessions tested suggesting a general and fundamental physiological role of this drought response. In addition, significant differences among accessions were identified for transcripts of three PIP genes. Principal component analysis showed that most of the PIP transcriptional variation during drought stress could be explained by one variable linked to leaf water content. Promoter-GUS constructs of AtPIP1;4, AtPIP2;5 and also AtPIP2;6, which is unresponsive to drought stress, had distinct expression patterns concentrated to the base of the leaf petioles and parts of the flowers. The presence of drought stress response elements within the 1.6 kb promoter regions of AtPIP1;4 and AtPIP2;5, was demonstrated by comparing transcription of the promoter reporter construct and the endogenous gene upon drought stress. Analysis by ATTED-II and other web-based bioinformatical tools showed that several of the MIPs down-regulated upon drought are strongly co-expressed, whereas AtPIP1;4, AtPIP2;5 and AtPIP2;6 are not co-expressed.
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| 14. |
- Alexandersson, Erik, et al.
(författare)
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Whole gene family expression and drought stress regulation of aquaporins
- 2005
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Ingår i: Plant Molecular Biology. - : Springer Science and Business Media LLC. - 1573-5028 .- 0167-4412. ; 59:3, s. 469-484
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Tidskriftsartikel (refereegranskat)abstract
- Since many aquaporins (AQPs) act as water channels, they are thought to play an important role in plant water relations. It is therefore of interest to study the expression patterns of AQP isoforms in order to further elucidate their involvement in plant water transport. We have monitored the expression patterns of all 35 Arabidopsis AQPs in leaves, roots and flowers by cDNA microarrays, specially designed for AQPs, and by quantitative real-time reverse transcriptase PCR (Q-RT-PCR). This showed that many AQPs are pre-dominantly expressed in either root or flower organs, whereas no AQP isoform seem to be leaf specific. Looking at the AQP subfamilies, most plasma membrane intrinsic proteins (PIPs) and some tonoplast intrinsic proteins (TIPs) have a high level of expression, while NOD26-like proteins (NIPs) are present at a much lower level. In addition, we show that PIP transcripts are generally down-regulated upon gradual drought stress in leaves, with the exception of AtPIP1;4 and AtPIP2;5, which are up-regulated. AtPIP2;6 and AtSIP1;1 are constitutively expressed and not significantly affected by the drought stress. The transcriptional down-regulation of PIP genes upon drought stress could also be observed on the protein level.
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| 15. |
- Ampah-Korsah, Henry, et al.
(författare)
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Single amino acid substitutions in the selectivity filter render NbXIP1;1α aquaporin water permeable
- 2017
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Ingår i: BMC Plant Biology. - : Springer Science and Business Media LLC. - 1471-2229. ; 17:1, s. 61-61
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Aquaporins (AQPs) are integral membrane proteins that facilitate transport of water and/or other small neutral solutes across membranes in all forms of life. The X Intrinsic Proteins (XIPs) are the most recently recognized and the least characterized aquaporin subfamily in higher plants. XIP1s have been shown to be impermeable to water but permeable to boric acid, glycerol, hydrogen peroxide and urea. However, uncertainty regarding the determinants for selectivity and lack of an activity that is easy to quantify have hindered functional investigations. In an effort to resolve these issues, we set out to introduce water permeability in Nicotiana benthamiana XIP1;1α (NbXIP1;1α), by exchanging amino acid residues of predicted alternative aromatic/arginine (ar/R) selectivity filters of NbXIP1;1α for residues constituting the water permeable ar/R selectivity filter of AtTIP2;1.RESULTS: Here, we present functional results regarding the amino acid substitutions in the putative filters as well as deletions in loops C and D of NbXIP1;1α. In addition, homology models were created based on the high resolution X-ray structure of AtTIP2;1 to rationalize the functional properties of wild-type and mutant NbXIP1;1α. Our results favour Thr 246 rather than Val 242 as the residue at the helix 5 position in the ar/R filter of NbXIP1;1α and indicate that the pore is not occluded by the loops when heterologously expressed in Pichia pastoris. Moreover, our results show that a single amino acid substitution in helix 1 (L79G) or in helix 2 (I102H) is sufficient to render NbXIP1;1α water permeable. Most of the functional results can be rationalized from the models based on a combination of aperture and hydrophobicity of the ar/R filter.CONCLUSION: The water permeable NbXIP1;1α mutants imply that the heterologously expressed proteins are correctly folded and offer means to explore the structural and functional properties of NbXIP1;1α. Our results support that Thr 246 is part of the ar/R filter. Furthermore, we suggest that a salt bridge to an acidic residue in helix 1, conserved among the XIPs in clade B, directs the orientation of the arginine in the ar/R selectivity filter and provides a novel approach to tune the selectivity of AQPs.
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| 16. |
- Ampah-Korsah, Henry, et al.
(författare)
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The aquaporin splice variant NbXIP1;1α is permeable to boric acid and is Phosphorylated in the N-terminal domain
- 2016
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Ingår i: Frontiers in Plant Science. - : Frontiers Media SA. - 1664-462X. ; 7:JUNE2016
-
Tidskriftsartikel (refereegranskat)abstract
- Aquaporins (AQPs) are membrane channel proteins that transport water and uncharged solutes across different membranes in organisms in all kingdoms of life. In plants, the AQPs can be divided into seven different subfamilies and five of these are present in higher plants. The most recently characterized of these subfamilies is the XIP subfamily, which is found in most dicots but not in monocots. In this article, we present data on two different splice variants (α and β) of NbXIP1;1 from Nicotiana benthamiana. We describe the heterologous expression of NbXIP1;1α and β in the yeast Pichia pastoris, the subcellular localization of the protein in this system and the purification of the NbXIP1;1α protein. Furthermore, we investigated the functionality and the substrate specificity of the protein by stopped-flow spectrometry in P. pastoris spheroplasts and with the protein reconstituted in proteoliposomes. The phosphorylation status of the protein and localization of the phosphorylated amino acids were verified by mass spectrometry. Our results show that NbXIP1;1α is located in the plasma membrane when expressed in P. pastoris, that it is not permeable to water but to boric acid and that the protein is phosphorylated at several amino acids in the N-terminal cytoplasmic domain of the protein. A growth assay showed that the yeast cells expressing the N-terminally His-tagged NbXIP1;1α were more sensitive to boric acid as compared to the cells expressing the C-terminally His-tagged isoform. This might suggest that the N-terminal His-tag functionally mimics the phosphorylation of the N-terminal domain and that the N-terminal domain is involved in gating of the channel.
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| 17. |
- Anderberg, Hanna, et al.
(författare)
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Annotation of Selaginella moellendorffii Major Intrinsic Proteins and the Evolution of the Protein Family in Terrestrial Plants.
- 2012
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Ingår i: Frontiers in Plant Science. - : Frontiers Media SA. - 1664-462X. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Major intrinsic proteins (MIPs) also called aquaporins form pores in membranes to facilitate the permeation of water and certain small polar solutes across membranes. MIPs are present in virtually every organism but are uniquely abundant in land plants. To elucidate the evolution and function of MIPs in terrestrial plants, the MIPs encoded in the genome of the spikemoss Selaginella moellendorffii were identified and analyzed. In total 19 MIPs were found in S. moellendorffii belonging to 6 of the 7 MIP subfamilies previously identified in the moss Physcomitrella patens. Only three of the MIPs were classified as members of the conserved water specific plasma membrane intrinsic protein (PIP) subfamily whereas almost half were found to belong to the diverse NOD26-like intrinsic protein (NIP) subfamily permeating various solutes. The small number of PIPs in S. moellendorffii is striking compared to all other land plants and no other species has more NIPs than PIPs. Similar to moss, S. moellendorffii only has one type of tonoplast intrinsic protein (TIP). Based on ESTs from non-angiosperms we conclude that the specialized groups of TIPs present in higher plants are not found in primitive vascular plants but evolved later in a common ancestor of seed plants. We also note that the silicic acid permeable NIP2 group that has been reported from angiosperms appears at the same time. We suggest that the expansion of the number MIP isoforms in higher plants is primarily associated with an increase in the different types of specialized tissues rather than the emergence of vascular tissue per se and that the loss of subfamilies has been possible due to a functional overlap between some subfamilies.
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| 18. |
- Backmark, Anna, 1979, et al.
(författare)
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Affinity tags can reduce merohedral twinning of membrane protein crystals
- 2008
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Ingår i: Acta Crystallographica. Section D: Biological Crystallography. - 1399-0047 .- 0907-4449. ; D64, s. 1183-1186
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Tidskriftsartikel (refereegranskat)abstract
- This work presents a comparison of the crystal packing of three eukaryotic membrane proteins: human aquaporin 1, human aquaporin 5 and a spinach plasma membrane aquaporin. All were purified from expression constructs both with and without affinity tags. With the exception of tagged aquaporin 1, all constructs yielded crystals. Two significant effects of the affinity tags were observed: crystals containing a tag typically diffracted to lower resolution than those from constructs encoding the protein sequence alone and constructs without a tag frequently produced crystals that suffered from merohedral twinning. Twinning is a challenging crystallographic problem that can seriously hinder solution of the structure. Thus, for integral membrane proteins, the addition of an affinity tag may help to disrupt the approximate symmetry of the protein and thereby reduce or avoid merohedral twinning.
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| 19. |
- Barfod, Anders, et al.
(författare)
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In Vitro Selection of RNA Aptamers Directed Against Protein E: A Haemophilus influenzae Adhesin. : a Haemophilus influenzae adhesin
- 2014
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Ingår i: Molecular Biotechnology. - : Springer Science and Business Media LLC. - 1559-0305 .- 1073-6085. ; 56:8, s. 714-725
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Tidskriftsartikel (refereegranskat)abstract
- Protein E (PE) of Haemophilus influenzae is a highly conserved ubiquitous surface protein involved in adhesion to and activation of epithelial cells. The host proteins-vitronectin, laminin, and plasminogen are major targets for PE-dependent interactions with the host. To identify novel inhibitory molecules of PE, we used an in vitro selection method based on systematic evolution of ligands by exponential enrichment known as SELEX in order to select 2'F-modified RNA aptamers that specifically bind to PE. Fourteen selection cycles were performed with decreasing concentrations of PE. Sequencing of clones from the 14th selection round revealed the presence of semiconserved sequence motifs in loop regions of the RNA aptamers. Among these, three aptamers showed the highest affinity to PE in electrophoretic mobility shift assays and in dot blots. These three aptamers also inhibited the interaction of PE with vitronectin as revealed by ELISA. Moreover, pre-treatment of H. influenzae with the aptamers significantly inhibited binding of vitronectin to the bacterial surface. Biacore experiments indicated that one of the aptamers had a higher binding affinity for PE as compared to the other aptamers. Our results show that it is possible to select RNA inhibitors against bacterial adhesins using SELEX in order to inhibit interactions with target proteins.
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| 20. |
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| 21. |
- Bjurman, Christian, 1983, et al.
(författare)
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Decreased admissions and hospital costs with a neutral effect on mortality following lowering of the troponin T cutoff point to the 99th percentile
- 2017
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Ingår i: Cardiology journal. - 1897-5593 .- 1898-018X. ; 24:6, s. 612-622
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Tidskriftsartikel (refereegranskat)abstract
- Background: The implementation of high-sensitivity cardiac troponin T (hs-cTnT) assays and a cutoff based on the 99th cTnT percentile in the evaluation of patients with suspected acute coronary syndrome has not been uniform due to uncertain effects on health benefits and utilization of limited resources.Methods:Clinical and laboratory data from patients with chest pain or dyspnea at the emergency department (ED) were evaluated before (n = 20516) and after (n = 18485) the lowering of the hs-cTnT cutoff point from 40 ng/L to the 99th hs-cTnT percentile of 14 ng/L in February 2012. Myocardial infarction (MI) was diagnosed at the discretion of the attending clinicians responsible for the patient.Results:Following lowering of the hs-cTnT cutoff point fewer ED patients with chest pain or dyspnea as the principal complaint were analyzed with an hs-cTnT sample (81% vs. 72%, p < 0.001). Overall 30-day mortality was unaffected but increased among patients not analyzed with an hs-cTnT sample (5.3% vs. 7.6%, p < 0.001). The MI frequency was unchanged (4.0% vs. 3.9%, p = 0.72) whereas admission rates decreased (51% vs. 45%, p < 0.001) as well as hospital costs. Coronary angiographies were used more frequently (2.8% vs. 3.3%, p = 0.004) but with no corresponding change in coronary interventions.Conclusions:At the participating hospital, lowering of the hs-cTnT cutoff point to the 99th percentile decreased admissions and hospital costs but did not result in any apparent prognostic or treatment benefits for the patients.
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| 22. |
- Bjurman, Christian, 1983, et al.
(författare)
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Small changes in Troponin T levels are common in patients with non-ST-elevation myocardial infarction and are linked to higher mortality
- 2013
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 62:14, s. 1231-1238
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:To examine the extent of change in Troponin T levels in patients with non-ST-elevation myocardial infarction (NSTEMI).BACKGROUND:Changes in cardiac troponin levels are required for the diagnosis of NSTEMI, according to the new universal definition of acute myocardial infarction. A relative change of 20-230 % and an absolute change of 7- 9 ng/L have been suggested as cut-off points.METHOD:In a clinical setting, where a change in cTnT was not mandatory for the diagnosis of NSTEMI, serial samples of cTnT were measured with a high-sensitive cTnT (hs-cTnT) assay, and 37 clinical parameters were evaluated in 1178 patients with a final diagnosis of NSTEMI presenting <24h after symptom onset.RESULTS:After six hours of observation, the relative change in the hs-cTnT level remained <20 % in 26 % and the absolute change <9 ng/L in 12 % of the NSTEMI patients. A relative hs-cTnT change <20% was linked to higher long-term mortality across quartiles (p=0.002) and in multivariate analyses (HR 1.61 (1.17-2.21) p=0.004), whereas 30-day mortality was similar across quartiles of relative hs-cTnT changeCONCLUSION:Because stable hs-TnT levels are common in patients with a clinical diagnosis of NSTEMI in our hospital, a small hs-cTnT change may not be useful to exclude NSTEMI, particularly as these patients show both short-term and long-term mortality at least as high as patients with large changes in hs-cTnT.
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| 23. |
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| 24. |
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| 25. |
- Cervin, Nicholas Tchang, et al.
(författare)
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Strong, Water-Durable, and Wet-Resilient Cellulose Nanofibril-Stabilized Foams from Oven Drying
- 2016
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 8:18, s. 11682-11689
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Tidskriftsartikel (refereegranskat)abstract
- Porous materials from cellulose nanofibrils (CNFs) have been prepared using Pickering foams from aqueous dispersions. Stable wet foams were first produced using surface-modified CNFs as stabilizing particles. To better maintain the homogeneous pore structure of the foam after drying, the foams were dried in an oven on a liquid-filled porous ceramic frit. The cell structure was studied by scanning electron microscopy and liquid porosimetry, the mechanical properties were studied by compression testing, and the liquid absorption capacity was determined both with liquid porosimetry and by soaking in water. By controlling the charge density of the CNFs, it was possible to prepare dry foams with different densities, the lowest density being 6 kg m(-3), that is, a porosity of 99.6%. For a foam with a density of 200 kg m(-3) the compressive Young's modulus was 50 MPa and the energy absorption to 70% strain was 2.3 MJ M-3. The use of chemically modified CNFs made it possible to prepare cross-linked foams with water-durable and wet-resilient properties. These foams absorbed liquid up to 34 times their own weight and were able to release this liquid under compression and to reabsorb the same amount when the pressure was released.
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| 26. |
- Chen, Donglei, 1985-
(författare)
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The Origin of Tooth Replacement : Three-dimensional Synchrotron Histology Visualizes the Dental Development of Silurian Stem Osteichthyans
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mechanisms of tooth replacement distribute incongruently among extant gnathostomes (jawed vertebrates): a permanent tooth-generating dental lamina exists in chondrichthyans (cartilaginous fish) and tetrapods but not teleosts, whereas tooth shedding by basal hard tissue resorption occurs in tetrapods and teleosts but not chondrichthyans. Theories about the evolution of tooth development have been biased towards the chondrichthyan conveyor-belt replacement, since there has been no fossil evidence for the origin of osteichthyan (bony fish and tetrapods) tooth replacement until now. 3D virtual dissections with submicron-scale resolution, based on propagation phase contrast synchrotron microtomography (PPC-SRµCT), reveal the growth history of the dentitions of Andreolepis and Lophosteus, 423-Myr-old Silurian stem osteichthyans close to the common ancestor of tetrapods and teleosts. Their marginal jawbones and “tooth cushions” (possible homologues of coronoids) shed teeth by in situ cyclic basal resorption, the earliest examples of osteichthyan-style tooth replacement. The replacement cycles were site-autonomic, and occurred in broad irregular multi-row tooth fields, including at sites separated from the margin of the bone by intervening teeth, showing that the production of replacement teeth did not occur in a single deep dental lamina, but in pockets associated with each tooth, as in many teleosts. It suggests that the functionally and anatomically similar laminae of chondrichthyans and tetrapods are convergent. The marginal jaw bones of both genera carry an initial non-shedding dentition arranged in alternate transverse files, labial to the shedding tooth field, overgrown by later dermal ornament and probably not belonging to the oral domain, but bearing in vivo biting damage showing that they functioned as teeth. The most lingual of these odontodes have been resorbed apically and are overlain by shedding teeth. The first-generation teeth on the tooth cushions display basal resorption in Andreolepis, but semi-basal resorption in Lophosteus. The latter leaves a basal dentine ring from each tooth, implying only odontoclasts are involved in the semi-basal resorption, which is probably the first step towards evolving a site-specific resorption. The polarized displacement of each generation of resorption surfaces reflects the fact that the cyclic replacement, as well as the sequential addition of tooth sites, is closely related to bone growth. Resorption surfaces and growth arrest surfaces also record the life history and the replacement rate. These data provide unique insights into the origin of osteichthyan tooth replacement.
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| 27. |
- Damman, Peter, et al.
(författare)
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Invasive strategies and outcomes for non-ST-segment elevation acute coronary syndromes : a twelve-year experience from SWEDEHEART.
- 2016
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Ingår i: EuroIntervention. - 1774-024X .- 1969-6213. ; 12:9, s. 1108-1116
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Despite recommendations in recent guidelines for a routine invasive strategy for non-ST-segment elevation acute coronary syndrome (NSTE-ACS), long-term data on the implementation of treatment strategies in clinical practice are not available. Our aim was to provide long-term data on the implementation of a routine invasive strategy in NSTE-ACS in clinical practice.METHODS AND RESULTS: In the SWEDEHEART registry, data from 204,092 consecutive NSTE-ACS patients admitted between 1996 and 2007 were recorded. The use of the routine invasive strategy, retrospectively defined as coronary angiography (and subsequent revascularisation) within three days after admission, increased from 3.8% in the period 1996-1998 to 37.4% in the period 2005-2007. The largest absolute increase in the use of this strategy was observed in low-risk patients, while a similar relative increase was observed in all risk categories. The use of the selective invasive strategy, defined as coronary angiography later than three days after admission or none at all, decreased from 96.2% in the period 1996-1998 to 62.5% in the period 2005-2007. In the total population, there was a gradual decrease in three-year all-cause mortality, from 29.1% in the period 1996-1998 to 23.9% in the period 2005-2007.CONCLUSIONS: There has been an increase in the use of a routine invasive strategy in NSTE-ACS patients over the course of 12 years in Sweden. There was a decrease in three-year mortality over the same time course.
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| 28. |
- Dellborg, Mikael, 1954, et al.
(författare)
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Efficacy and safety with ticagrelor in patients with prior myocardial infarction in the approved European label: insights from PEGASUS-TIMI 54.
- 2019
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Ingår i: European heart journal. Cardiovascular pharmacotherapy. - : Oxford University Press (OUP). - 2055-6845 .- 2055-6837. ; 5:4, s. 200-206
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Tidskriftsartikel (refereegranskat)abstract
- In PEGASUS-TIMI 54, ticagrelor significantly reduced the risk of the composite of major adverse cardiovascular (CV) events by 15-16% in stable patients with a prior myocardial infarction (MI) 1-3years earlier. We report the efficacy and safety in the subpopulation recommended for treatment in the European (EU) label, i.e. treatment with 60mg b.i.d. initiated up to 2years from the MI, or within 1 year after stopping previous adenosine diphosphate receptor inhibitor treatment.Of the 21162 patients enrolled in PEGASUS-TIMI 54, 10779 patients were included in the primary analysis for this study, randomized to ticagrelor 60mg (n=5388) or matching placebo (n=5391). The cumulative proportions of patients with events at 36months were calculated by the Kaplan-Meier (KM) method. The composite of CV death, MI, or stroke occurred less frequently in the ticagrelor group (7.9% KM rate vs. 9.6%), hazard ratio (HR) 0.80 [95% confidence interval (CI) 0.70-0.91; P=0.001]. Ticagrelor also reduced the risk of all-cause mortality, HR 0.80 (0.67-0.96; P=0.018). Thrombolysis in myocardial infarction major bleeding was more frequent in the ticagrelor group 2.5% vs. 1.1%; HR 2.36 (1.65-3.39; P<0.001). The corresponding HR for fatal or intracranial bleeding was 1.17 (0.68-2.01; P=0.58).In PEGASUS-TIMI 54, treatment with ticagrelor 60mg as recommended in the EU label, was associated with a relative risk reduction of 20% in CV death, MI, or stroke. Thrombolysis in myocardial infarction major bleeding was increased, but fatal or intracranial bleeding was similar to placebo. There appears to be a favourable benefit-risk ratio for long-term ticagrelor 60mg in this population.http://www.clinicaltrials.gov NCT01225562.
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| 29. |
- Digas, Georgios, 1963, et al.
(författare)
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Inducible Displacements of the Cup and the Femoral Head During Active Range of Motion: Dynamic RSA Studies of Cemented Total Hip Replacements
- 2013
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Ingår i: Journal of Orthopaedic Research. - : Wiley. - 0736-0266. ; 31:11, s. 1686-1693
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated changes in position of the femoral head relative to the cup and of the cup relative to the pelvis in total hip replacement patients during hip motion 2 years postoperatively. Two patient groups with nine patients in each group were studied. Hip motions, translations of the femoral head center, and cup displacements were recorded with dynamic radiostereometric examination (RSA, 2exposures/s) during abduction in Group 1 and with use of static RSA exposures at increasing flexion of the hip in Group 2. Conventional radiographic examinations were used to evaluate any radiolucent lines around the cups at 2 years. During active abduction the femoral head center moved medially (median 0.04mm) and the cup tilted anteriorly (median 0.09mm). Increments in radiolucent lines at 2 years correlated to medial femoral head penetration, posterior tilt, and retroversion of the cup at 20 degrees of abduction. The extension of radiolucent lines at 2 years showed a positive correlation with proximal inducible displacement of the cup and posterior translation of the femoral head center at maximum hip flexion. Our observations may be of value in understanding the pathogenesis of the loosening process and may be used to facilitate the development of prosthetic designs that optimize hip kinematics. (c) 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1686-1693, 2013
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| 30. |
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| 31. |
- Docherty, Kieran F., et al.
(författare)
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Effect of Dapagliflozin on Outpatient Worsening of Patients With Heart Failure and Reduced Ejection Fraction : A Prespecified Analysis of DAPA- HF.
- 2020
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Ingår i: Circulation. ; 142:17, s. 1623-1632
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), dapagliflozin, added to guideline-recommended therapies, reduced the risk of mortality and heart failure (HF) hospitalization. We examined the frequency and significance of episodes of outpatient HF worsening, requiring the augmentation of oral therapy, and the effects of dapagliflozin on these additional events. METHODS: Patients in New York Heart Association functional class II to IV, with a left ventricular ejection fraction
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| 32. |
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| 33. |
- Dowdy, Lauren, et al.
(författare)
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Early repolarization: friend or foe?
- 2003
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Ingår i: The American journal of medicine. - 0002-9343. ; 115:3, s. 237-40
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Tidskriftsartikel (refereegranskat)
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| 34. |
- Florio, Marilina, et al.
(författare)
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Characterization of the Aquaporin-9 Inhibitor RG100204 In Vitro and in db/db Mice
- 2022
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 11:19
-
Tidskriftsartikel (refereegranskat)abstract
- Aquaporin-9 (AQP9) is a facilitator of glycerol and other small neutral solute transmembrane diffusion. Identification of specific inhibitors for aquaporin family proteins has been difficult, due to high sequence similarity between the 13 human isoforms, and due to the limited channel surface areas that permit inhibitor binding. The few AQP9 inhibitor molecules described to date were not suitable for in vivo experiments. We now describe the characterization of a new small molecule AQP9 inhibitor, RG100204 in cell-based calcein-quenching assays, and by stopped-flow light-scattering recordings of AQP9 permeability in proteoliposomes. Moreover, we investigated the effects of RG100204 on glycerol metabolism in mice. In cell-based assays, RG100204 blocked AQP9 water permeability and glycerol permeability with similar, high potency (~5 × 10 -8 M). AQP9 channel blocking by RG100204 was confirmed in proteoliposomes. After oral gavage of db/db mice with RG100204, a dose-dependent elevation of plasma glycerol was observed. A blood glucose-lowering effect was not statistically significant. These experiments establish RG100204 as a direct blocker of the AQP9 channel, and suggest its use as an experimental tool for in vivo experiments on AQP9 function.
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| 35. |
- Floyd, James S, et al.
(författare)
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Effects of ischemic preconditioning and arterial collateral flow on ST-segment elevation and QRS complex prolongation in a canine model of acute coronary occlusion.
- 2009
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Ingår i: Journal of electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 42:1, s. 19-26
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: During acute myocardial infarction, both ST elevation and QRS distortion on the initial electrocardiogram (ECG) have been correlated with poorer prognosis. Studies in dogs and humans suggest that these ECG markers provide information about myocardial protection from both collateral blood flow and ischemic preconditioning. METHODS: In a protocol designed to precondition the heart with ischemia, we examined both ST-segment elevation and QRS complex prolongation in lead II of the ECG in 23 mongrel dogs during the first and fourth episode of 5 minutes of left circumflex artery occlusion. Myocardial collateral flow was measured during each of these episodes by injection of radioactive microspheres 2.5 minutes into the episode of ischemia. RESULTS: During ischemia, the degree of elevation of the ST segments was reduced markedly in hearts preconditioned with ischemia and/or in hearts with the greatest amounts of collateral arterial flow. During the first episode of ischemia, the ST segments increased to a similar extent in severe and moderate ischemia, but less in hearts in which the ischemia was mild. However, marked QRS prolongation was present only in hearts with severe ischemia, and decreased when the hearts were preconditioned. In addition, large ischemic beds exhibited the most marked QRS prolongation, whereas small but even severely ischemic beds showed little or no change in QRS duration. CONCLUSION: Both ST elevation and QRS prolongation are reduced by the presence of collateral flow and ischemic preconditioning. The QRS complex merits further study as an important marker of the degree of myocardial protection during human acute myocardial ischemia/infarction.
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| 36. |
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| 37. |
- Guthrie, James, et al.
(författare)
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Intangibles and the transparent enterprise : new strands of knowledge
- 2003
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Ingår i: Journal of Intellectual Capital. - : Emerald Group Publishing Limited. - 1469-1930 .- 1758-7468. ; 4:4, s. 429-440
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Tidskriftsartikel (refereegranskat)abstract
- Examines the new challenges that have been posed by the information society and the new demands posed on management. The term “knowledge-based economy” has become universal, the rules of business are being rewitten and the industrial era enterprise models are no longer adequate to meet the dynamic condition of a changing world market. Companies have become aware of the importance of managing the external communication since this issue is considered important for the company's ability to generate value. Various studies of investors and analysts' request for information indicate a substantial difference between the amount of information found in companies' annual reports and the type of information demanded by the market. The articles in this special edition of Journal of Intellectual Capital represent main current research activities into the area of intellectual capital (IC) in Europe and also Australia. The articles represent the wide scope of research that is being carried out in the expansive field of the measurement, analysis and management of IC.
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| 38. |
- Hallén, Jonas, et al.
(författare)
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Influence of ST-segment recovery on infarct size and ejection fraction in patients with ST-segment elevation myocardial infarction receiving primary percutaneous coronary intervention.
- 2010
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Ingår i: The American journal of cardiology. - : Elsevier BV. - 1879-1913 .- 0002-9149. ; 105:9, s. 1223-8
-
Tidskriftsartikel (refereegranskat)abstract
- In patients with ST-segment elevation myocardial infarction treated with fibrinolytics, electrocardiogram-derived measures of ST-segment recovery guide therapy decisions and predict infarct size. The comprehension of these relationships in patients undergoing mechanical reperfusion is limited. We studied 144 patients treated with primary percutaneous coronary intervention. We aimed to define the association between infarct size as determined by cardiac magnetic resonance imaging and different metrics of ST-segment recovery. Electrocardiograms were assessed at baseline and 90 minutes after primary percutaneous coronary intervention. Three methods for calculating and categorizing ST-segment recovery were used: (1) summed ST-segment deviation (STD) resolution analyzed in 3 categories (> or = 70%, > or = 30% to <70%, and <30%); (2) single-lead STD resolution analyzed in the same 3 categories; (3) worst-lead residual STD analyzed in 3 categories (<1 mm, 1 to <2 mm, and > or = 2 mm). Infarct size and ejection fraction were assessed at 4 months by cardiac magnetic resonance imaging. All 3 ST-segment recovery algorithms predicted the final infarct size and cardiac function. Worst-lead residual STD performed the same as, or better than, the more complex methods and identified large subgroups at either end of the risk spectrum (median infarct size from the lowest to highest risk category (percentage of left ventricle: 7.7% [interquartile range 10.8], 13.1% [interquartile range 13.6]; 24.6% [interquartile range 21.1]); with adjusted odds ratios for infarct size greater than the median (reference <1 mm): 1 to <2 mm, odds ratio 2.3 (95% confidence interval 0.8 to 5.9); > or = 2 mm, odds ratio 6.3 (95% confidence interval 1.7 to 23.7; c-index 0.781). In conclusion, an electrocardiogram obtained early after primary percutaneous coronary intervention analyzed by a simple algorithm provided prognostic information on the final infarct size and cardiac function.
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| 39. |
- Hallén, Jonas, et al.
(författare)
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Optimal time-point of ST-segment assessment for risk-stratification following primary percutaneous coronary intervention.
- 2010
-
Ingår i: The American journal of cardiology. - : Elsevier BV. - 1879-1913 .- 0002-9149. ; 105:11, s. 1648-1649
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Tidskriftsartikel (refereegranskat)abstract
- Refers to:Predictive Value of ST Resolution Analysis Performed Immediately Versus at Ninety Minutes After Primary Percutaneous Coronary Intervention, The American Journal of Cardiology, Volume 105, Issue 4, 15 February 2010, Pages 467-474, Saurabh Kumar, Gopal Sivagangabalan, Calvin Hsieh, Alisdair D.S. Ryding, Arun Narayan, Hera Chan, David C. Burgess, Andrew T.L. Ong, Norman Sadick, Pramesh Kovoor
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| 40. |
- Hammarsten, Ola, et al.
(författare)
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Troponin T percentiles from a random population sample, emergency room patients and patients with myocardial infarction
- 2012
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 1530-8561 .- 0009-9147. ; 58:3, s. 628-637
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: High-sensitivity cardiac troponin T (cTnT) assays detect small clinically important myocardial infarctions (MI) but also yield higher rates of false-positive results owing to increased concentrations sometimes present in patients without MI. Better understanding is needed of factors influencing the 99th percentile of cTnT concentrations across populations and the frequency of changes in cTnT concentrations >20% often used in combination with increased cTnT concentrations for diagnosis of MI. METHODS: cTnT percentiles were determined by use of the Elecsys® hscTnT immunoassay (Modular® Analytics E170) in a random population sample, in emergency room (ER) patients, and in patients with non–ST-elevation MI (NSTEMI). Changes in cTnT concentrations were determined in hospitalized patients without MI. RESULTS: The 99th cTnT percentile in a random population sample (median age, 65 years) was 24 ng/L. In ER patients <65 years old without obvious conditions that increase cTnT, the 99th cTnT percentile was 12 ng/L with little age dependence, whereas in those >65 years old it was 82 ng/L and highly age dependent. In hospitalized patients without MI the 97.5th percentile for change in the cTnT concentration was 51%–67%. cTnT remained below the 99th percentile (12 ng/L) in 1% of patients with NSTEMI until 8.5 h after symptom onset and 6 h after ER arrival. CONCLUSIONS: Age >65 years was the dominant factor associated with increased cTnT in ER patients. This age association was more prominent in ER patients than in a random population sample. Changes in serial cTnT concentrations >20% were common in hospitalized patients without MI.
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| 41. |
- Hedfalk, Kristina, et al.
(författare)
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Aquaporin gating
- 2006
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Ingår i: Current Opinion in Structural Biology. - : Elsevier BV. - 1879-033X .- 0959-440X. ; 16, s. 447-456
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Forskningsöversikt (refereegranskat)abstract
- An acceleration in the rate at which new aquaporin structures are determined means that structural models are now available for mammalian AQP0, AQP1, AQP2 and AQP4, bacterial GlpF, AqpM and AQPZ, and the plant SoPIP2;1. With an apparent consensus emerging concerning the mechanism of selective water transport and proton extrusion, emphasis has shifted towards the issues of substrate selectivity and the mechanisms of aquaporin regulation. In particular, recently determined structures of plant SoPIP2;1, sheep and bovine AQP0, and Escherichia coli AQPZ provide new insights into the underlying structural mechanisms by which water transport rates are regulated in diverse organisms. From these results, two distinct pictures of 'capping' and 'pinching' have emerged to describe aquaporin gating.
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| 42. |
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| 43. |
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| 44. |
- Hellebö Johanson, Else, 1969, et al.
(författare)
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Early alterations in the postprandial VLDL1 apoB-100 and apoB-48 metabolism in men with strong heredity for type 2 diabetes
- 2004
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Ingår i: J Intern Med. - 0954-6820. ; 255:2, s. 273-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To study the postprandial triglyceride-rich lipoprotein (TRL) metabolism, specifically the concentrations of very low-density lipoproteins (VLDL); from intestine (apoB-48) and liver (apoB-100), in men with normal fasting triglycerides but at increased risk of developing type 2 diabetes. DESIGN: Cross-sectional study. SUBJECTS AND SETTINGS: Sixteen healthy men with at least two first-degree relatives with type 2 diabetes were individually matched with 16 control subjects without known diabetes heredity for: age, body mass index, and fasting triglyceride level. They underwent an 8-h meal tolerance test (919 kcal, 51 g fat) during which lipoproteins were separated by density gradient ultracentrifugation. They were characterized by euglycaemic hyperinsulinaemic clamp, peak VO2, 7-day diet registration and computed tomography. RESULTS: The relatives were, as expected, more insulin resistant than the controls and had increased concentration of postprandial VLDL1 particles (49% higher for VLDL1 apoB-48, P = 0.04 and 21% higher for VLDL1 apoB-100, P = 0.048). The elevation was related to insulin sensitivity, but not to lifestyle and body composition. Moreover, the concentration of postprandial triglycerides in VLDL1 fraction was inversely related to low-density lipoprotein (LDL) size in both relatives (rs = -0.60, P = 0.03) and controls (rs = -0.72, P = 0.004). There were no differences in the concentration of triglycerides or apoB-48 and apoB-100 particles in the other fractions (plasma, chylomicron or VLDL2). CONCLUSION: Increased postprandial concentration of TRLs in the VLDL1 fraction seems to be present at an early stage in the development of diabetes and probably contributes to the excess risk of future coronary events in insulin-resistant men.
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| 45. |
- Hellebö Johanson, Else, 1969, et al.
(författare)
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No acute effect of nateglinide on postprandial lipid and lipoprotein responses in subjects at risk for type 2 diabetes
- 2005
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Ingår i: Diabetes Metab Res Rev. - : Wiley. - 1520-7552. ; 21:4, s. 376-81
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To study the acute effect of nateglinide, an insulinotropic agent, on the postprandial triglyceride and lipoprotein responses in subjects at risk for type 2 diabetes. METHODS: Six women and 10 men, with at least one first-degree relative with type 2 diabetes were included (Age: 48 +/- 7 years, BMI: 27.5 +/- 2.8 kg m(-2), P-triglycerides: 1.3 +/- 0.4 mmol L(-1), P-cholesterol: 5.4 +/- 0.6 mmol L(-1), B-glucose: 4.6 +/- 0.3 mmol L(-1)). They each had two 8-h meal tolerance tests with either nateglinide or placebo given 10 min prior to the meals in randomized order. Lipoprotein fractions were separated by density gradient ultracentrifugation. First-phase insulin secretion was assessed by an intravenous glucose tolerance test (300 mg kg(-1) body weight) and insulin sensitivity by a hyperinsulinaemic euglycaemic clamp (40 mU m(-2) min(-1)). RESULTS: The 1-h insulin levels during the meal tolerance test were significantly higher with nateglinide (577 +/- 81 vs 376 +/- 58 pmol L(-1), p < 0.001), as well as the response during the first two hours (IAUC: 41 243 +/- 5844 vs 29 956 +/- 4662 pmol L(-1) min, p < 0.01). Accordingly, nateglinide lowered the 8-h postprandial glucose response by around 60% compared to placebo (p < 0.001). In contrast, no significant lowering was seen in the excursion of postprandial triglycerides in total plasma or lipoprotein fractions. Consistently, the concentration of exogenous (apoB-48) and endogenous (apoB-100) lipoproteins was not reduced by nateglinide. CONCLUSIONS: Acute administration of nateglinide reduces, as expected, the postprandial glucose concentration, but no reduction in triglyceride or lipoprotein responses are seen in subjects at risk for type 2 diabetes.
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| 46. |
- Herlitz, Johan, 1949, et al.
(författare)
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Prehospital ECG
- 2010
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Ingår i: Comprehensive Electrocardiology. - : Springer. - 1848820453 - 9781848820470
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 47. |
- Horsefield, Rob, 1977, et al.
(författare)
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High-resolution x-ray structure of human aquaporin 5
- 2008
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 105:36, s. 13327-13332
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Tidskriftsartikel (refereegranskat)abstract
- Human aquaporin 5 (HsAQP5)facilitates the transport of water across plasma membranes and has been identified within cells of the stomach, duodenum, pancreas, airways, lungs, salivary glands, sweat glands, eyes, lacrimal glands, and the inner ear. AQP5, like AQP2, is subject to posttranslational regulation by phosphorylation, at which point it is trafficked between intracellular storage compartments and the plasma membrane. Details concerning the molecular mechanism of membrane trafficking are unknown. Here we report the x-ray structure of HsAQP5 to 2.0-angstrom resolution and highlight structural similarities and differences relative to other eukaryotic aquaporins. A lipid occludes the putative central pore, preventing the passage of gas or ions through the center of the tetramer. Multiple consensus phosphorylation sites are observed in the structure and their potential regulatory role is discussed. We postulate that a change in the conformation of the C terminus may arise from the phosphorylation of AQP5 and thereby signal trafficking.
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| 48. |
- Jelen, Sabina, et al.
(författare)
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Aquaporin-9 Protein Is the Primary Route of Hepatocyte Glycerol Uptake for Glycerol Gluconeogenesis in Mice
- 2011
-
Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 286:52, s. 44319-44325
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Tidskriftsartikel (refereegranskat)abstract
- It has been hypothesized that aquaporin-9 (AQP9) is part of the unknown route of hepatocyte glycerol uptake. In a previous study, leptin receptor-deficient wild-type mice became diabetic and suffered from fasting hyperglycemia whereas isogenic AQP9(-/-) knock-out mice remained normoglycemic. The reason for this improvement in AQP9(-/-) mice was not established before. Here, we show increased glucose output (by 123% +/- 36% S. E.) in primary hepatocyte culture when 0.5 mM extracellular glycerol was added. This increase depended on AQP9 because it was absent in AQP9(-/-) cells. Likewise, the increase was abolished by 25 mu M HTS13286 (IC(50) similar to 2 mu M), a novel AQP9 inhibitor, which we identified in a small molecule library screen. Similarly, AQP9 deletion or chemical inhibition eliminated glycerol-enhanced glucose output in perfused liver preparations. The following control experiments suggested inhibitor specificity to AQP9: (i) HTS13286 affected solute permeability in cell lines expressing AQP9, but not in cell lines expressing AQPs 3, 7, or 8. (ii) HTS13286 did not influence lactate-and pyruvate-dependent hepatocyte glucose output. (iii) HTS13286 did not affect glycerol kinase activity. Our experiments establish AQP9 as the primary route of hepatocyte glycerol uptake for gluconeogenesis and thereby explain the previously observed, alleviated diabetes in leptin receptor-deficient AQP9(-/-) mice.
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| 49. |
- Jernberg, Tomas, et al.
(författare)
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Association Between Adoption of Evidence-Based Treatment and Survival for Patients With ST-Elevation Myocardial Infarction
- 2011
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 305:16, s. 1677-1684
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Tidskriftsartikel (refereegranskat)abstract
- Context Only limited information is available on the speed of implementation of new evidence-based and guideline-recommended treatments and its association with survival in real life health care of patients with ST-elevation myocardial infarction (STEMI). Objective To describe the adoption of new treatments and the related chances of short-and long-term survival in consecutive patients with STEMI in a single country over a 12-year period. Design, Setting, and Participants The Register of Information and Knowledge about Swedish Heart Intensive Care Admission (RIKS-HIA) records baseline characteristics, treatments, and outcome of consecutive patients with acute coronary syndrome admitted to almost all hospitals in Sweden. This study includes 61 238 patients with a first-time diagnosis of STEMI between 1996 and 2007. Main Outcome Measures Estimated and crude proportions of patients treated with different medications and invasive procedures and mortality over time. Results Of evidence based-treatments, reperfusion increased from 66% (95%, confidence interval [CI], 52%-79%) to 79% (95% CI, 69%-89%; P<.001), primary percutaneous coronary intervention from 12% (95% CI, 11%-14%) to 61% (95% CI, 45%-77%; P<.001), and revascularization from 10% (96% CI, 6%-14%) to 84% (95% CI, 73%-95%; P<.001). The use of aspirin, clopidogrel, beta-blockers, statins, and angiotensin-converting enzyme (ACE) inhibitors all increased: clopidogrel from 0% to 82% (95% CI, 69%-95%; P<.001), statins from 23% (95% CI, 12%-33%) to 83% (95% CI, 75%-91%; P<.001), and ACE inhibitor or angiotensin II receptor blockers from 39% (95% CI, 26%-52%) to 69% (95% CI, 58%-70%; P<.001). The estimated in-hospital, 30-day and 1-year mortality decreased from 12.5% (95% CI, 4.3%-20.6%) to 7.2% (95% CI, 1.7%-12.6%; P<.001); from 15.0% (95% CI, 6.2%-23.7%) to 8.6% (95% CI, 2.7%-14.5%; P<.001); and from 21.0% (95% CI, 11.0%-30.9%) to 13.3% (95% CI, 6.0%-20.4%; P<.001), respectively. After adjustment, there was still a consistent trend with lower standardized mortality over the years. The 12-year survival analyses showed that the decrease of mortality was sustained over time. Conclusion In a Swedish registry of patients with STEMI, between 1996 and 2007, there was an increase in the prevalence of evidence-based treatments. During this same time, there was a decrease in 30-day and 1-year mortality that was sustained during long-term follow-up.
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| 50. |
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