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- Danielsson, Christian, et al.
(författare)
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Exploration of human, rat, and rabbit embryonic cardiomyocytes suggests K-channel block as a common teratogenic mechanism
- 2013
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Ingår i: Cardiovascular Research. - : Oxford University Press (OUP): Policy B. - 0008-6363 .- 1755-3245. ; 97:1, s. 23-32
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Tidskriftsartikel (refereegranskat)abstract
- Several drugs blocking the rapidly activating potassium (K-r) channel cause malformations (including cardiac defects) and embryonic death in animal teratology studies. In humans, these drugs have an established risk for acquired long-QT syndrome and arrhythmia. Recently, associations between cardiac defects and spontaneous abortions have been reported for drugs widely used in pregnancy (e.g. antidepressants), with long-QT syndrome risk. To investigate whether a common embryonic adverse-effect mechanism exists in the human, rat, and rabbit embryos, we made a comparative study of embryonic cardiomyocytes from all three species. less thanbrgreater than less thanbrgreater thanPatch-clamp and quantitative-mRNA measurements of K-r and slowly activating K (K-s) channels were performed on human, rat, and rabbit primary cardiomyocytes and cardiac samples from different embryo-foetal stages. The K-r channel was present when the heart started to beat in all species, but was, in contrast to human and rabbit, lost in rats in late organogenesis. The specific K-r-channel blocker E-4031 prolonged the action potential in a species- and development-dependent fashion, consistent with the observed K-r-channel expression pattern and reported sensitive periods of developmental toxicity. E-4031 also increased the QT interval and induced 2:1 atrio-ventricular block in multi-electrode array electrographic recordings of rat embryos. The K-s channel was expressed in human and rat throughout the embryo-foetal period but not in rabbit. less thanbrgreater than less thanbrgreater thanThis first comparison of mRNA expression, potassium currents, and action-potential characteristics, with and without a specific K-r-channel blocker in human, rat, and rabbit embryos provides evidence of K-r-channel inhibition as a common mechanism for embryonic malformations and death.
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- Danielsson, C, et al.
(författare)
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Is Cardiac Arrhythmia in the Human Embryo a Possible Mechanism for Cardiovascular Defects by I-Kr Blocking Antidepressants? in BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY, vol 91, issue 5, pp 345-345
- 2011
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Ingår i: BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY. - : WILEY-BLACKWELL, COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA. ; , s. 345-345
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Konferensbidrag (refereegranskat)abstract
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- Edfors, Fredrik, et al.
(författare)
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Gene-specific correlation of RNA and protein levels in human cells and tissues
- 2016
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Ingår i: Molecular Systems Biology. - : EMBO. - 1744-4292 .- 1744-4292. ; 12:10
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Tidskriftsartikel (refereegranskat)abstract
- An important issue for molecular biology is to establish whether transcript levels of a given gene can be used as proxies for the corresponding protein levels. Here, we have developed a targeted proteomics approach for a set of human non-secreted proteins based on parallel reaction monitoring to measure, at steady-state conditions, absolute protein copy numbers across human tissues and cell lines and compared these levels with the corresponding mRNA levels using transcriptomics. The study shows that the transcript and protein levels do not correlate well unless a gene-specific RNA-to-protein (RTP) conversion factor independent of the tissue type is introduced, thus significantly enhancing the predictability of protein copy numbers from RNA levels. The results show that the RTP ratio varies significantly with a few hundred copies per mRNA molecule for some genes to several hundred thousands of protein copies per mRNA molecule for others. In conclusion, our data suggest that transcriptome analysis can be used as a tool to predict the protein copy numbers per cell, thus forming an attractive link between the field of genomics and proteomics.
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- Fagerberg, Linn, et al.
(författare)
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Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics
- 2014
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 13:2, s. 397-406
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Tidskriftsartikel (refereegranskat)abstract
- Global classification of the human proteins with regards to spatial expression patterns across organs and tissues is important for studies of human biology and disease. Here, we used a quantitative transcriptomics analysis (RNA-Seq) to classify the tissue-specific expression of genes across a representative set of all major human organs and tissues and combined this analysis with antibody- based profiling of the same tissues. To present the data, we launch a new version of the Human Protein Atlas that integrates RNA and protein expression data corresponding to 80% of the human protein-coding genes with access to the primary data for both the RNA and the protein analysis on an individual gene level. We present a classification of all human protein-coding genes with regards to tissue-specificity and spatial expression pattern. The integrative human expression map can be used as a starting point to explore the molecular constituents of the human body.
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- Skold, A C, et al.
(författare)
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Translational Research: Electrophysiological Development in the Embryonic Heart of Rats, Rabbits, and Humans in BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY, vol 91, issue 5, pp 357-357
- 2011
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Ingår i: BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY. - : WILEY-BLACKWELL, COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA. ; , s. 357-357
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Konferensbidrag (refereegranskat)abstract
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- Uhlén, Mathias, et al.
(författare)
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The human secretome
- 2019
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Ingår i: Science Signaling. - : American Association for the Advancement of Science (AAAS). - 1945-0877 .- 1937-9145. ; 12:609
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Tidskriftsartikel (refereegranskat)abstract
- The proteins secreted by human cells (collectively referred to as the secretome) are important not only for the basic understanding of human biology but also for the identification of potential targets for future diagnostics and therapies. Here, we present a comprehensive analysis of proteins predicted to be secreted in human cells, which provides information about their final localization in the human body, including the proteins actively secreted to peripheral blood. The analysis suggests that a large number of the proteins of the secretome are not secreted out of the cell, but instead are retained intracellularly, whereas another large group of proteins were identified that are predicted to be retained locally at the tissue of expression and not secreted into the blood. Proteins detected in the human blood by mass spectrometry-based proteomics and antibody-based immuno-assays are also presented with estimates of their concentrations in the blood. The results are presented in an updated version 19 of the Human Protein Atlas in which each gene encoding a secretome protein is annotated to provide an open-access knowledge resource of the human secretome, including body-wide expression data, spatial localization data down to the single-cell and subcellular levels, and data about the presence of proteins that are detectable in the blood.
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- Alt Murphy, Margit, 1970, et al.
(författare)
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Acceleration based activity metrics during subacute inpatient stroke rehabilitation
- 2016
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Ingår i: Procedia Technology, Biosensors 2016, 25-27 May, Göteborg, Sweden..
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- People after stroke have difficulties to reach sufficient physical activity level during their rehabilitation and particularly outside the therapy time. We aim to quantify activity levels and investigate differences in motor activity in weekdays and weekends in a subacute stage after stroke. Data from multiple three-axis accelerometers was collected during two 48h sessions in 11 patients. The activity level and symmetry indices were sensitive to variations in weekend and weekdays. This information is valuable in rehabilitation planning and management and enables identification of those in risk of low physical activity and inactivity.
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| 10. |
- Andersson, Stefan, et al.
(författare)
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Metod- och kvalitetsbeskrivning för geografiskt fördelade emissioner till luft (submission 2019)
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Sverige rapporterar årligen nationella utsläpp till luft till UNFCCC (FN:s klimatkonvention) och CLRTAP (UNECE:s konvention om gränsöverskridande luftföroreningar), så kallade submissioner. Förutom emissioner på nationell nivå finns även behov av data med högre geografisk upplösning. För regional uppföljning av miljömålen behövs emissioner på kommun- och länsnivå.Detta dokument utgör en metod- och kvalitetsbeskrivning av geografiskt fördelade emissioner för åren 1990, 2000, 2005 samt 2010-2017, rapporterade i submission 2019. Emissionerna presenteras i 55 olika sektorer uppdelade på nio huvudsektorer. Huvudsektorerna är El och fjärrvärme, Egen uppvärmning av bostäder och lokaler, Industri (energi och processer), Transporter, Arbetsmaskiner, Produktanvändning (inkl. lösningsmedel), Jordbruk, Avfall (inkl. avlopp) samt Utrikes transporter.Den geografiska fördelningen utförs huvudsakligen enligt konceptet ”topdown”. Detta innebär att emissioner bryts ner från en nationell totalemission för att uppnå en högre rumslig upplösning på lokal nivå. Nedbrytningen till högre rumslig upplösning kräver en geografisk begränsning av emissionerna och statistik på regional nivå. Metoden för geografisk fördelning tillåter för vissa utsläppskällor en hög rumslig upplösning (t.ex. för vägtrafik och industriprocesser). För flera sektorer är emellertid resultaten otillförlitliga om de ska studeras med högre upplösning än kommunnivå (i vissa fall även länsnivå).Arbetet med geografisk fördelning av Sveriges utsläpp till luft är sedan 2007 ett årligt projekt. Projektet har ett långsiktigt perspektiv med målsättningen att stegvis förbättra kvaliteten på geografiskt upplösta emissionsdata.Resultaten för alla sektorer presenteras med samma geografiska upplösning även om kvaliteten varierar. På grund av detta krävs det att användare av dessa emissionsdata går igenom kvalitetsbeskrivningen och bedömer om osäkerheterna är acceptabla för den aktuella tillämpningen.
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