| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Carén, Helena, 1979, et al.
(författare)
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High-resolution array copy number analyses for detection of deletion, gain, amplification and copy-neutral LOH in primary neuroblastoma tumors; Four cases of homozygous deletions of the CDKN2A gene.
- 2008
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Neuroblastoma is a very heterogeneous pediatric tumor of the sympathetic nervous system showing clinically significant patterns of genetic alterations. Favorable tumors usually have near-triploid karyotypes with few structural rearrangements. Aggressive stage 4 tumors often have near-diploid or near-tetraploid karyotypes and structural rearrangements. Whole genome approaches for analysis of genome-wide copy number have been used to analyze chromosomal abnormalities in tumor samples. We have used array-based copy number analysis using oligonucleotide single nucleotide polymorphisms (SNP) arrays to analyze the chromosomal structure of a large number of neuroblastoma tumors of different clinical and biological subsets. Results Ninety-two neuroblastoma tumors were analyzed with 50 K and/or 250 K SNP arrays from Affymetrix, using CNAG3.0 software. Thirty percent of the tumors harbored 1p deletion, 22% deletion of 11q, 26% had MYCN amplification and 45% 17q gain. Most of the tumors with 1p deletion were found among those with MYCN amplification. Loss of 11q was most commonly seen in tumors without MYCN amplification. In the case of MYCN amplification, two types were identified. One type displayed simple continuous amplicons; the other type harbored more complex rearrangements. MYCN was the only common gene in all cases with amplification. Complex amplification on chromosome 12 was detected in two tumors and three different overlapping regions of amplification were identified. Two regions with homozygous deletions, four cases with CDKN2A deletions in 9p and one case with deletion on 3p (the gene RBMS3) were also detected in the tumors. Conclusion SNP arrays provide useful tools for high-resolution characterization of significant chromosomal rearrangements in neuroblastoma tumors. The mapping arrays from Affymetrix provide both copy number and allele-specific information at a resolution of 10–12 kb. Chromosome 9p, especially the gene CDKN2A, is subject to homozygous (four cases) and heterozygous deletions (five cases) in neuroblastoma tumors.
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| 3. |
- van den Berg, Martin, et al.
(författare)
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Polybrominated Dibenzo-p-Dioxins, Dibenzofurans, and Biphenyls : Inclusion in the Toxicity Equivalency Factor Concept for Dioxin-Like Compounds
- 2013
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Ingår i: Toxicological Sciences. - Oxfors, United Kingdom : Oxford University Press. - 1096-6080 .- 1096-0929. ; 133:2, s. 197-208
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Forskningsöversikt (refereegranskat)abstract
- In 2011 a joint World Health Organization (WHO) and United Nations Environment Programme (UNEP) expert consultation took place, during which the possible inclusion of brominated analogues of the dioxin-like compounds in the WHO Toxicity Equivalency Factor (TEF) scheme were evaluated. The expert panel concluded that polybrominated dibenzo-p-dioxins (PBDDs), dibenzofurans (PBDFs), and some dioxin-like biphenyls (dl-PBBs) may contribute significantly in daily human background exposure to the total dioxin toxic equivalencies (TEQs). These compounds are also commonly found in the aquatic environment. Available data for fish toxicity were evaluated for possible inclusion in the WHO-UNEP TEF scheme (Van den Berg et al., 1998). Because of the limited database it was decided not to derive specific WHO-UNEP TEFs for fish, but for ecotoxicological risk assessment the use of specific relative effect potencies (REPs) from fish embryo assays is recommended. Based on the limited mammalian REP database for these brominated compounds, it was concluded that sufficient differentiation from the present TEF values of the chlorinated analogues (Van den Berg et al., 2005) was not possible. However, the REPs for PBDDs, PBDFs, and non-ortho dl-PBBs in mammals closely follow those of the chlorinated analogues, at least within one order of magnitude. Therefore, the use of similar interim TEF values for brominated and chlorinated congeners for human risk assessment is recommended, pending more detailed information in the future.
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| 4. |
- Ekeberg, Tomas, 1983-, et al.
(författare)
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Observation of a single protein by ultrafast X-ray diffraction
- 2024
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Ingår i: Light. - : Springer Nature. - 2095-5545 .- 2047-7538. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- The idea of using ultrashort X-ray pulses to obtain images of single proteins frozen in time has fascinated and inspired many. It was one of the arguments for building X-ray free-electron lasers. According to theory, the extremely intense pulses provide sufficient signal to dispense with using crystals as an amplifier, and the ultrashort pulse duration permits capturing the diffraction data before the sample inevitably explodes. This was first demonstrated on biological samples a decade ago on the giant mimivirus. Since then, a large collaboration has been pushing the limit of the smallest sample that can be imaged. The ability to capture snapshots on the timescale of atomic vibrations, while keeping the sample at room temperature, may allow probing the entire conformational phase space of macromolecules. Here we show the first observation of an X-ray diffraction pattern from a single protein, that of Escherichia coli GroEL which at 14 nm in diameter is the smallest biological sample ever imaged by X-rays, and demonstrate that the concept of diffraction before destruction extends to single proteins. From the pattern, it is possible to determine the approximate orientation of the protein. Our experiment demonstrates the feasibility of ultrafast imaging of single proteins, opening the way to single-molecule time-resolved studies on the femtosecond timescale.
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| 5. |
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| 6. |
- Rose, Linda M, 1963-
(författare)
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RAMP: Ett nytt riskhanteringsverktyg – Risk Assessment and Management tool for manual handling Proactively – : Slutrapport i projektet ”Utveckling, implementering och spridning av belastningsergonomiskt bedömningsverktyg och åtgärdsprocess” (Dnr 090168)
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I denna rapport beskrivs riskhanteringsmetoden RAMP – Risk Assessment and Management tool for manual handling Proactively – och dess utveckling som gjorts i projektet ”Utveckling, implementering och spridning av belastningsergonomiskt bedömningsverktyg och åtgärds-process”. Projektets mål har varit att utveckla en fritt tillgänglig metod för riskhantering för arbete med manuell hantering. Metoden ska kunna användas för att bedöma risken att utveckla belastningsbesvär och stötta det systematiska arbetsmiljöarbetet genom att ge en struktur för förbättringsåtgärder och utarbetande av handlingsplaner. Syftet är att användningen av verktyget ska bidra att arbetsmiljöförbättrande åtgärder genomförs, vilket förväntas leda till positiva hälsoeffekter.Projektet har genomförts som ett samarbetsprojekt med interaktiv metodologisk ansats mellan forskare vid KTH Skolan för Teknik och hälsa, Enheten för Ergonomi, och personer som aktivt deltagit i projektet i egenskap av professionella yrkesverksamma med olika roller på de medverkande företagen Arla Foods, Scania CV AB, Svenskt Butikskött AB och Mikael Loods Åkeri AB – exempelvis operatör, logistiker, chef, VD, skyddsombud, produktionstekniker, ergonom, och global arbetsmiljösmordnare. Till projektet har en referensgrupp och en expertgrupp varit knutna. Projektet har finansierats av i huvudsak Afa Försäkring och de medverkande företagen.Bland metoderna om används i projektet finns litteraturgenomgång, iterativ prototyp-utveckling, användartester och utvärdering av prototyper, work-shops, intervjuer och enkäter. RAMP baseras på vetenskapliga studier, svensk arbetsmiljölagstiftning, ergonomistandarder, andra bedömningsmetoder, expertbedömningar av projektets expertgrupp, erfarenheter och expertbedömningar från personer verksamma i industrin inom bland annat företagshälsovård, ledning och produktion, användartester samt referensgruppens feed-back.I rapporten presenteras RAMP-verktyget som består av fyra moduler: RAMP I - en checklista för screening av belastningsergonomiska riskfaktorer; RAMP II – som möjliggör en fördjupad analys; en Resultatmodul där resultatet kan presenteras på olika detaljnivå och med olika omfattning och en Åtgärdsmodul som ger stöd för det systematiska arbetsmiljöarbetet med bland annat åtgärdsförslag och en mall för att utforma handlingsplaner för att minska riskerna.En prototyp av RAMP har utvärderades i ett examensarbete genom validitets- och reliabilitets- och användbarhetsstudier. Utvärderingen visar på hög repeterbarhet av bedömningar genomförda av icke-experter samt att överensstämmelsen var hög mellan experter och icke-experter. Användbarhetsstudien visade att RAMP uppleveds som ganska lätt att använda och tidseffektiv.Digitaliseringen av RAMP förväntas bli klar under hösten 2014. RAMP kommer därefter att göras fritt tillgänglig via KTH STHs hemsida och en implementeringsstudie av metoden sker på de medverkande företagen. Metoden kommer att spridas enligt projektets kommunikationsplan som beskrivs i rapporten.
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| 7. |
- Bergman, Åke, et al.
(författare)
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A novel abbreviation standard for organobromine, organochlorine and organophosphorus flame retardants and some characteristics of the chemicals
- 2012
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 49, s. 57-82
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Forskningsöversikt (refereegranskat)abstract
- Ever since the interest in organic environmental contaminants first emerged 50 years ago, there has been a need to present discussion of such chemicals and their transformation products using simple abbreviations so as to avoid the repetitive use of long chemical names. As the number of chemicals of concern has increased, the number of abbreviations has also increased dramatically, sometimes resulting in the use of different abbreviations for the same chemical. In this article, we propose abbreviations for flame retardants (FRs) substituted with bromine or chlorine atoms or including a functional group containing phosphorus, i.e. BFRs, CFRs and PFRs, respectively. Due to the large number of halogenated and organophosphorus FRs, it has become increasingly important to develop a strategy for abbreviating the chemical names of FRs. In this paper, a two step procedure is proposed for deriving practical abbreviations (PRABs) for the chemicals discussed. In the first step, structural abbreviations (STABs) are developed using specific STAB criteria based on the FR structure. However, since several of the derived STABs are complicated and long, we propose instead the use of PRABs. These are, commonly, an extract of the most essential part of the STAB, while also considering abbreviations previously used in the literature. We indicate how these can be used to develop an abbreviation that can be generally accepted by scientists and other professionals involved in FR related work. Tables with PRABs and STABs for BFRs, CFRs and PERs are presented, including CAS (Chemical Abstract Service) numbers, notes of abbreviations that have been used previously, CA (Chemical Abstract) name, common names and trade names, as well as some fundamental physicochemical constants.
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| 8. |
- Pattaro, Cristian, et al.
(författare)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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| 9. |
- Van den Berg, Martin, et al.
(författare)
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The 2005 World Health Organization reevaluation of human and mammalian toxic equivalency factors for dioxins and dioxin-like compounds
- 2006
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Ingår i: Toxicological Sciences. - : Oxford University Press. - 1096-6080 .- 1096-0929. ; 93:2, s. 223-241
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Tidskriftsartikel (refereegranskat)abstract
- In June 2005, a World Health Organization (WHO)-International Programme on Chemical Safety expert meeting was held in Geneva during which the toxic equivalency factors (TEFs) for dioxin-like compounds, including some polychlorinated biphenyls (PCBs), were reevaluated. For this reevaluation process, the refined TEF database recently published by Haws et al. (2006, Toxicol. Sci. 89, 4-30) was used as a starting point. Decisions about a TEF value were made based on a combination of unweighted relative effect potency (REP) distributions from this database, expert judgment, and point estimates. Previous TEFs were assigned in increments of 0.01, 0.05, 0.1, etc., but for this reevaluation, it was decided to use half order of magnitude increments on a logarithmic scale of 0.03, 0.1, 0.3, etc. Changes were decided by the expert panel for 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) (TEF = 0.3), 1,2,3,7,8-pentachlorodibenzofuran (PeCDF) (TEF = 0.03), octachlorodibenzo-p-dioxin and octachlorodibenzofuran (TEFs = 0.0003), 3,4,4',5-tetrachlorbiphenyl (PCB 81) (TEF = 0.0003), 3,3',4,4',5,5'-hexachlorobiphenyl (PCB 169) (TEF = 0.03), and a single TEF value (0.00003) for all relevant mono-ortho-substituted PCBs. Additivity, an important prerequisite of the TEF concept was again confirmed by results from recent in vivo mixture studies. Some experimental evidence shows that non-dioxin-like aryl hydrocarbon receptor agonists/antagonists are able to impact the overall toxic potency of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds, and this needs to be investigated further. Certain individual and groups of compounds were identified for possible future inclusion in the TEF concept, including 3,4,4'-TCB (PCB 37), polybrominated dibenzo-p-dioxins and dibenzofurans, mixed polyhalogenated dibenzo-p-dioxins and dibenzofurans, polyhalogenated naphthalenes, and polybrominated biphenyls. Concern was expressed about direct application of the TEF/total toxic equivalency (TEQ) approach to abiotic matrices, such as soil, sediment, etc., for direct application in human risk assessment. This is problematic as the present TEF scheme and TEQ methodology are primarily intended for estimating exposure and risks via oral ingestion (e.g., by dietary intake). A number of future approaches to determine alternative or additional TEFs were also identified. These included the use of a probabilistic methodology to determine TEFs that better describe the associated levels of uncertainty and "systemic" TEFs for blood and adipose tissue and TEQ for body burden.
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| 10. |
- Zuntini, Alexandre R., et al.
(författare)
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Phylogenomics and the rise of the angiosperms
- 2024
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Ingår i: NATURE. - 0028-0836 .- 1476-4687. ; 629, s. 843-850
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Tidskriftsartikel (refereegranskat)abstract
- Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods(1,2). A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome(3,4). Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins(5-7). However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes(8). This 15-fold increase in genus-level sampling relative to comparable nuclear studies(9) provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade.
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