| 1. |
- Hillier, Ladeana W, et al.
(författare)
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Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
- 2004
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
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Tidskriftsartikel (refereegranskat)abstract
- We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
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| 2. |
- Aleksandrov, D., et al.
(författare)
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Halo excitations in fragmentation of He-6 at 240 MeV/u on carbon and lead targets
- 2000
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Ingår i: Nuclear Physics A. - 0375-9474. ; 669:1-2, s. 51-64
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Tidskriftsartikel (refereegranskat)abstract
- Dissociation of a 240 MeV/u beam of He-6, incident on carbon and lead targets, has been studied in kinematically complete experiments to investigate low-lying excitation modes in the halo nucleus He-6. It is shown that alignment effects characterize the inelastic scattering and allow an unambiguous assignment of the spin of a narrow resonance observed in the excitation energy spectrum. The differential cross sections for the He-6 inelastic scattering on carbon and lead targets were deduced from the measured moments of the two neutrons and the a-particle. An analysis of these distributions shows that quadrupole and, possibly, monopole excitations characterize the hadronic interaction, while the dipole mode is dominating in Coulomb dissociation. Neither theoretically predicted new resonance states in He-6 nor nuclear excitation of a dipole mode were found. Direct evidence has been obtained for strong suppression of Coulornb post-acceleration in direct Coulomb breakup in a lead target.
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| 3. |
- Alvez, Maria Bueno, et al.
(författare)
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Next generation pan-cancer blood proteome profiling using proximity extension assay
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- A comprehensive characterization of blood proteome profiles in cancer patients can contribute to a better understanding of the disease etiology, resulting in earlier diagnosis, risk stratification and better monitoring of the different cancer subtypes. Here, we describe the use of next generation protein profiling to explore the proteome signature in blood across patients representing many of the major cancer types. Plasma profiles of 1463 proteins from more than 1400 cancer patients are measured in minute amounts of blood collected at the time of diagnosis and before treatment. An open access Disease Blood Atlas resource allows the exploration of the individual protein profiles in blood collected from the individual cancer patients. We also present studies in which classification models based on machine learning have been used for the identification of a set of proteins associated with each of the analyzed cancers. The implication for cancer precision medicine of next generation plasma profiling is discussed.
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| 4. |
- Axelsson, Mikael D., et al.
(författare)
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Determination of major and trace elements in sphalerite using laser ablation double focusing sector field ICP-MS
- 2001
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Ingår i: Journal of Geochemical Exploration. - 0375-6742 .- 1879-1689. ; 72:2, s. 81-89
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Tidskriftsartikel (refereegranskat)abstract
- The analytical performance of laser ablation (LA) for the determination of Co, Fe, Cd, Ag, Mn, Cu and S in sphalerite was evaluated using double focusing sector field inductively coupled plasma mass spectrometry (ICP-SFMS). Samples were collected from Zinkgruvan, situated in the south central Sweden. The use of Zn for internal standardisation, together with correction for FeS impurities in sphalerite, allows straightforward quantification without using external methods for the determination of the actual Zn content. LA-ICP-SFMS results were compared with data obtained by conventional pneumatic nebulisation introduction of sample solutions following acid digestion. Good agreement between the two methods was obtained for homogeneously distributed elements. For the majority of the elements under consideration, LA-ICP-SFMS precision was better than 10% RSD.
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| 5. |
- Axelsson, Mikael D., et al.
(författare)
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High spatial resolution analysis of ferromanganese concretions by LA-ICP-MS
- 2002
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Ingår i: Geochemical Transactions. - : Springer Science and Business Media LLC. - 1467-4866. ; 3:5, s. 40-47
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Tidskriftsartikel (refereegranskat)abstract
- A procedure was developed for the determination of element distributions in cross-sections of ferromanganese concretions using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The effects of carrier flow rates, rf forward power, ablation energy, ablation spot size, repetition rate and number of shots per point on analyte intensity were studied. It is shown that different carrier gas flow rates are required in order to obtain maximum sensitivities for different groups of elements, thus complicating the optimisation of ICP parameters. On the contrary, LA parameters have very similar effects on almost all elements studied, thus providing a common optimum parameter set for the entire mass range. However, for selected LA parameters, the use of compromise conditions was necessary in order to compensate for relatively slow data acquisition by ICP-MS and maintain high spatial resolution without sacrificing the multielemental capabilities of the technique. Possible variations in ablation efficiency were corrected for mathematically using the sum of Fe and Mn intensities. Quantification by external calibration against matrix-matched standards was successfully used for more than 50 elements. These standards, in the form of pressed pellets (no binder), were prepared in-house using
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| 6. |
- Axelsson, Mikael D.
(författare)
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Multi-element analysis of environmental samples using LA-ICP-MS : method developments with emphasis on calibration strategies
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Analytical applications based on the use of laser ablation-inductively coupled plasma-sector field mass spectrometry (LA-ICP-SFMS) have shown great potential for both quantitative and qualitative determination of elements in a variety of materials, although the weak point is finding a suitable calibration approach. The major focus of this work has, therefore, been internal standardisation and calibration. Methods for quantitative and qualitative analysis of geological (coal, ferromanganese concretions, sulphide minerals) and biological (nail and hair) samples have been developed. For coal, two reference materials were analysed after microwave (MW) treatment with different combinations of HNO3, aqua regia, HF and H2O2. Lithium metaborate (LMB) fusion with and without ashing of samples, as well as LA solid sampling on pressed coal pellets were also evaluated. External calibration for LA-ICP-SFMS was conducted using matrix-matched standard dopeds with standard solutions. This approach resulted in good accuracy for 46 out of 47 elements tested in the coal fly ash reference material. The precision was assessed in this work by replicate analyses of coal samples and was found to be, as average values for all elements, 4-5% and 10-15% relative standard deviation (RSD) for procedures involving digestion and LA sampling, respectively. For ferromanganese concretions, improvement of existing sample preparation schemes was necessary in order to expand the element coverage. The optimised and validated (for about 60 elements) method has the potential to replace the multitude of sample preparation and instrumental analytical techniques previously used to determine specific groups of elements in ferromanganese nodules. By using this improved method, it was possible to successfully quantify more than 50 elements by LA-ICP-SFMS using external calibration against matrix-matched standards. The results also show how different LA parameters affect the isotopic response and RSD. For sulphide minerals, LA-ICP-SFMS analysis was performed directly on polished crystalline sections. In sphalerite, a number of major and trace elements were determined by a ‘single-standard’ method using Zn for internal standardisation, together with correction for FeS impurities in the mineral, allowing straightforward quantification without using external methods for the determination of the actual Zn content. Results obtained by this approach were in good agreement with those from using external calibration. In order to evaluate the possibility to use crystalline sections of sphalerite and four other sulphide minerals as in-house standards, an analytical method was developed for multi-elemental analysis of such samples after preparation based on both MW digestion using different acid mixtures and LMB fusion. The performance of the sample preparation and analysis stages was evaluated using powdered pyrite and galena reference materials. It was found possible to use the selected minerals as matrix-matched standards for the determination of about 20 trace and ultra-trace elements by LA-ICP-SFMS. The second group of matrices concerned in this work comprises hair and nail samples. The first part of this study was focused on method validation for the determination of 71 elements by conventional ICP-SFMS analysis after MW-assisted digestion, with special attention paid to the correction of spectral interferences and to accuracy assessment. In the follow up study, the main concern was to evaluate the capabilities of LA-ICP-SFMS for quantitative multi-elemental analysis of hair and nail samples, emphasising the collection of spatially resolved information. Quantification was performed by means of an in-house, multi-element, matrix-matched standard using 32S+ as internal standard. A major conclusion of this thesis is that each sample type is in many respects unique, and therefore demands careful selection of a suitable calibration protocol, in order to ensure that reliable analytical results are delivered. The developed methods will make it possible to quantitatively analyse samples such as geological thin-sections, single sulphide grains, ferromanganese concretions, fingernails and hair. The results also show that LA-ICP-SFMS potentially can be used for obtaining quantitative analyses with good spatial resolution in a variety of materials.
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| 7. |
- Axelsson, Mikael D.
(författare)
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Multielemental analysis of geological and biological samples using laser ablation ICP-SFMS
- 2000
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The analytical performance of laser ablation (LA) for multielemental determination of geological and biological samples has been investigated. In the present study, LA has been used for sample introduction in inductively coupled plasma sector field mass spectrometry (ICP-SFMS). Although LA can provide semi-quantitative results rapidly and easily, the calibration process still remains the "Achilles heel" of the technique. The major goal of this study has been to investigate the capabilities of LA-ICP-SFMS for qualitative and quantitative analysis of various solid materials. LA was used for analyses of coal were calibration was performed by using coal powder doped with analyte elements. This was done by adding solution standards (including analyte and internal standard elements) to the coal, drying and finally homogenising, followed by pressing tablets. LA results were compared with data obtained by conventional solution nebulisation (SN) after preparation of coal samples using microwave (MW) digestion or fusion. In spite of a relatively poor agreement for elements such as As, Se, Sn, Re, Te, and Tl, accuracy obtained with LA in the present study is otherwise generally superior to previously reported data for LA and slurry nebulisation. For about 50 elements, results obtained with LA fall within 20% of those obtained by SN. The study shows the potential of LA quantification, based on solution-doped powders. However, the necessity of sample grinding and homogenising results in loss of spatial distribution information and makes the approach more vulnerable to sample contamination. The possibilities of sulphide minerals analysis by ICP-SFMS have been investigated. Seven elements (Co, Fe, Cd, Ag, Mn, Cu and S) have been quantitatively determined in sphalerite samples from the Zinkgruvan mine, using Zn as internal standard (IS). A straightforward calibration procedure allows on-line correction for possible Fe impurities at percent levels. Consequently, the use of complimentary techniques for determination of actual Zn content in the samples is avoided. The LA-ICP-SFMS results were compared with data from conventional SN introduction of sample solutions following acid digestion. Good agreement was found between the methods. For homogeneously distributed elements the overall precision for LA was found to be better than 10% RSD. A method for total mineral dissolution of five sulphides (sphalerite, pyrite, galena, pyrrhotite and chalcopyrite) has been developed, followed by multielemental analysis by ICP-SFMS. By performing this mineral characterisation the intention was to determine whether the analysed bulk mineral samples could be used as in-house LA calibration standards. The use of LA was focused towards elucidating whether the observed deviations in results obtained by ICP-SFMS for the two reference material powders used were caused by sample inhomogeneity or by inefficient matrix dissolution. It was found that the reference materials showed lack of accuracy in recommended concentrations for many trace and ultra trace elements, as well as possible inhomogeneity when using 50 mg sample amounts. The sulphide minerals studied appears to be suitable as matrix matched calibration standards for the determination of about 20 trace and ultra trace elements by LA. Laser ablation was also used for analysing element to sulphur ratios in washed human nails. The element ratios were then used to display the effectiveness of the applied washing method applied prior to MW digestion and analysis by ICP-SFMS. Based on the LA analysis, it was found that, even after the applied nail washing procedure, many elements are enriched in the surface of the nail.
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| 8. |
- Axelsson, Mikael D., et al.
(författare)
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Multielemental analysis of Mn–Fe nodules by ICP-MS: optimisation of analytical method
- 2002
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Ingår i: The Analyst. - 0003-2654 .- 1364-5528. ; 127:1, s. 76-82
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Tidskriftsartikel (refereegranskat)abstract
- Two acid digestion procedures (microwave-assisted and room temperature) were developed for the quantitative analysis of ferromanganese nodules by inductively coupled plasma double focusing sector field mass spectrometry (ICP-SFMS). Different compositions of the acid mixture, dilution factors and corrections for spectral interferences were tested. A combination of nitric, hydrochloric and hydrofluoric acids is necessary for complete sample digestion, with lowest acid to sample ratios (v/m) of 15 and 1.5. respectively, for the last two acids. Sample dilution factors higher than 2 X 104 should be used in order to decrease matrix effects and provide robust long-term instrumental operation. In spite of high dilution. method detection limits in the sub-mug g(-1) range were obtained for 54 out of 71 elements tested. due to the high detection capability of ICP-SFMS, as well as the special care taken to ensure the purity of reagents, to clean the instrument sample introduction system and to minimise sample handling. Owing to the presence of unresolved (at the resolution available) spectral interferences, accurate determination of Au, Hg, Os, Pd, Re and Rh is impossible without matrix separation. The accuracy of the entire analytical method was tested by the analysis of two nodule reference materials. The results generated agreed to within +/-2% for about 10, within +/-10% for more than 40 and within +/-20% for about 50 of 53 elements for which certified, recommended or literature values are available. A precision better than 3%, expressed as the between-digestion relative standard deviation (n=4). was obtained for the majority of elements, except in cases limited by low analyte concentrations
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| 9. |
- Gyllensten, Ulf B., et al.
(författare)
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Next Generation Plasma Proteomics Identifies High-Precision Biomarker Candidates for Ovarian Cancer
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:7
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Ovarian cancer is the eighth most common cancer among women and has a 5-year survival of only 30-50%. The survival is close to 90% for patients in stage I but only 20% for patients in stage IV. The presently available biomarkers have insufficient sensitivity and specificity for early detection and there is an urgent need to identify novel biomarkers. The aim of our study was to broadly measure protein biomarkers to find tests for the early detection of ovarian cancer. We found that combinations of 4-7 protein biomarkers can provide highly accurate detection of early- and late-stage ovarian cancer compared to benign conditions. The performance of the tests was then validated in a second independent cohort. Background: Ovarian cancer is the eighth most common cancer among women and has a 5-year survival of only 30-50%. The survival is close to 90% for patients in stage I but only 20% for patients in stage IV. The presently available biomarkers have insufficient sensitivity and specificity for early detection and there is an urgent need to identify novel biomarkers. Methods: We employed the Explore PEA technology for high-precision analysis of 1463 plasma proteins and conducted a discovery and replication study using two clinical cohorts of previously untreated patients with benign or malignant ovarian tumours (N = 111 and N = 37). Results: The discovery analysis identified 32 proteins that had significantly higher levels in malignant cases as compared to benign diagnoses, and for 28 of these, the association was replicated in the second cohort. Multivariate modelling identified three highly accurate models based on 4 to 7 proteins each for separating benign tumours from early-stage and/or late-stage ovarian cancers, all with AUCs above 0.96 in the replication cohort. We also developed a model for separating the early-stage from the late-stage achieving an AUC of 0.81 in the replication cohort. These models were based on eleven proteins in total (ALPP, CXCL8, DPY30, IL6, IL12, KRT19, PAEP, TSPAN1, SIGLEC5, VTCN1, and WFDC2), notably without MUCIN-16. The majority of the associated proteins have been connected to ovarian cancer but not identified as potential biomarkers. Conclusions: The results show the ability of using high-precision proteomics for the identification of novel plasma protein biomarker candidates for the early detection of ovarian cancer.
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| 10. |
- Herold, Nikolas, et al.
(författare)
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Targeting SAMHD1 with the Vpx protein to improve cytarabine therapy for hematological malignancies
- 2017
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 23:2, s. 256-263
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Tidskriftsartikel (refereegranskat)abstract
- The cytostatic deoxycytidine analog cytarabine (ara-C) is the most active agent available against acute myelogenous leukemia (AML). Together with anthracyclines, ara-C forms the backbone of AML treatment for children and adults'. In AML, both the cytotoxicity of ara-C in vitro and the clinical response to ara-C therapy are correlated with the ability of AML blasts to accumulate the active metabolite ara-C triphosphate (ara-CTP)(2-5), which causes DNA damage through perturbation of DNA synthesis(6). Differences in expression levels of known transporters or metabolic enzymes relevant to ara-C only partially account for patient-specific differential ara-CTP accumulation in AML blasts and response to ara-C treatment(7-9). Here we demonstrate that the deoxynucleoside triphosphate (dNTP) triphosphohydrolase SAM domain and HD domain 1 (SAMHD1) promotes the detoxification of intracellular ara-CTP pools. Recombinant SAMHD1 exhibited ara-CTPase activity in vitro, and cells in which SAMHD1 expression was transiently reduced by treatment with the simian immunodeficiency virus (SIV) protein Vpx were dramatically more sensitive to ara-C-induced cytotoxicity. CRISPR-Cas9-mediated disruption of the gene encoding SAMHD1 sensitized cells to ara-C, and this sensitivity could be abrogated by ectopic expression of wild-type (WT), but not dNTPase-deficient, SAMHD1. Mouse models of AML lacking SAMHD1 were hypersensitive to ara-C, and treatment ex vivo with Vpx sensitized primary patient derived AML blasts to ara-C. Finally, we identified SAMHD1 as a risk factor in cohorts of both pediatric and adult patients with de novo AML who received ara-C treatment. Thus, SAMHD1 expression levels dictate patient sensitivity to ara-C, providing proof-of-concept that the targeting of SAMHD1 by Vpx could be an attractive therapeutic strategy for potentiating ara-C efficacy in hematological malignancies.
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