| 1. |
- Dolinska, Monika, et al.
(författare)
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Characterization of the bone marrow niche in patients with chronic myeloid leukemia identifies CXCL14 as a new therapeutic option
- 2023
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 142:1, s. 73-89
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Tidskriftsartikel (refereegranskat)abstract
- Although tyrosine kinase inhibitors (TKIs) are effective in treating chronic myeloid leukemia (CML), they often fail to eradicate the leukemia-initiating stem cells (LSCs), causing disease persistence and relapse. Evidence indicates that LSC persistence may be because of bone marrow (BM) niche protection; however, little is known about the underlying mechanisms. Herein, we molecularly and functionally characterize BM niches in patients with CML at diagnosis and reveal the altered niche composition and function in these patients. Long -term culture initiating cell assay showed that the mesenchymal stem cells from patients with CML displayed an enhanced supporting capacity for normal and CML BM CD34+CD38- cells. Molecularly, RNA sequencing detected dysregulated cytokine and growth factor expression in the BM cellular niches of patients with CML. Among them, CXCL14 was lost in the BM cellular niches in contrast to its expression in healthy BM. Restoring CXCL14 significantly inhibited CML LSC maintenance and enhanced their response to imatinib in vitro, and CML engraftment in vivo in NSG-SGM3 mice. Importantly, CXCL14 treatment dramatically inhibited CML engraftment in patient-derived xenografted NSG-SGM3 mice, even to a greater degree than imatinib, and this inhibition persisted in patients with suboptimal TKI response. Mechanistically, CXCL14 upregulated inflammatory cytokine signaling but downregulated mTOR signaling and oxidative phosphorylation in CML LSCs. Together, we have discovered a suppressive role of CXCL14 in CML LSC growth. CXCL14 might offer a treatment option targeting CML LSCs.
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| 2. |
- Johansson, Monika, et al.
(författare)
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Relation between alpha(S1)-casein, genotype, and quality traits of milk from Swedish dairy goats
- 2023
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Ingår i: Journal of Dairy Science. - 0022-0302 .- 1525-3198. ; 106, s. 5582-5592
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Tidskriftsartikel (refereegranskat)abstract
- Locally produced food is becoming popular among Swedish consumers. One product that has increased in popularity is artisan-manufactured goat cheese, and although the dairy goat industry in Sweden is smallscale, production is gradually increasing. In goats, the CSN1S1 gene regulates expression of the protein aS1casein (alpha(S1)-CN), which has been found to be important for cheese yield. Over the years, breeding animals have been imported to Sweden from Norway. Historically, a high frequency of the Norwegian goat population carried a polymorphism at the CSN1S1 gene. This polymorphism, called the Norwegian null allele (D), leads to zero or significantly reduced expression of alpha(S1)-CN. Using milk samples from 75 goats, this study investigated associations between expression of alpha(S1)-CN and genotype at the CSN1S1 gene on milk quality traits from Swedish Landrace goats. Milk samples were grouped according to relative level of alpha(S1)-CN (low: 0-6.9% of total protein; medium-high: 7-25% of total protein) and genotype (DD, DG, DA/AG/AA). While the D allele leads to extremely low expression of alpha(S1)-CN, the G allele is low expressing and the A allele is highly expressing for this protein. Principal component analysis was used to explore the total variation in milk quality traits. To evaluate the effect of different allele groups on milk quality attributes, 1-way ANOVA and Tukey pairwise comparison tests were used. The majority (72%) of all goat milk samples investigated showed relative aS1-CN content of 0% to 6.82% of total protein. The frequency of individuals homozygous for the Norwegian null allele (DD) was 59% in the population of sampled goats, and only 15% carried at least one A allele. A low relative concentration of alpha(S1)-CN was associated with lower total protein, higher pH, and higher relative concentration of beta-casein and levels of free fatty acids. Milk from goats homozygous for the null allele (DD) showed a similar pattern as milk with low relative concentration of alpha(S1)-CN, but total protein was only numerically lower, and somatic cell count and alpha(S2)-CN were higher than for the other genotypes. The associations between levels of alpha(S1)-CN and the investigated genotype at the CSN1S1 gene indicate a need for a national breeding program for Swedish dairy goats.
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| 3. |
- Langton, Maud, et al.
(författare)
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Gelation of faba bean proteins - Effect of extraction method, pH and NaCl
- 2020
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Ingår i: Food Hydrocolloids. - : Elsevier BV. - 0268-005X .- 1873-7137. ; 103
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Tidskriftsartikel (refereegranskat)abstract
- The effect of extraction method, pH and NaCl addition on rheological properties and microstructure of heat-induced faba bean protein gels was evaluated. Gels formed at pH 7 (no NaCl) of alkaline-extracted protein had the densest and finest network structure and highest stress and strain at fracture. The high density of nodes and small pores in the protein network could contribute to those mechanical properties. In contrast, storage modulus (G′) and Young's modulus were lowest for protein gels at pH 7. The gels formed at pH 5 had high G′ and Young's modulus, whereas stress and strain at fracture were lower, especially for gels formed from alkaline-extracted protein. Gels formed at pH 5 with 2% NaCl had two types of internal gel network, caused by a change in solubility of 7S globulins. When the protein powder was dissolved in water, particle size was dependent on the extraction method, with alkaline extraction giving much larger protein particles than soaked extraction.
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| 4. |
- Abulaiti, Yiming, et al.
(författare)
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Measurement of the centrality dependence of the charged-particle pseudorapidity distribution in proton-lead collisions at root s(NN)=5.02 TeV with the ATLAS detector
- 2016
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 76:4
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Tidskriftsartikel (refereegranskat)abstract
- The centrality dependence of the mean charged-particle multiplicity as a function of pseudorapidity is measured in approximately 1 mu b(-1) of proton-lead collisions at a nucleon-nucleon centre-of-mass energy of root s(NN) = 5.02 TeV using the ATLAS detector at the Large Hadron Collider. Charged particles with absolute pseudorapidity less than 2.7 are reconstructed using the ATLAS pixel detector. The p + Pb collision centrality is characterised by the total transverse energy measured in the Pb-going direction of the forward calorimeter. The charged-particle pseudorapidity distributions are found to vary strongly with centrality, with an increasing asymmetry between the proton-going and Pb-going directions as the collisions become more central. Three different estimations of the number of nucleons participating in the p + Pb collision have been carried out using the Glauber model as well as two Glauber-Gribov inspired extensions to the Glauber model. Charged-particle multiplicities per participant pair are found to vary differently for these three models, highlighting the importance of including colour fluctuations in nucleon-nucleon collisions in the modelling of the initial state of p + Pb collisions.
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| 5. |
- Andersson Odén, Tomas, 1952, et al.
(författare)
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Kriskommunikation 2.0. Allmänhet, medier och myndigheter i det digitala medielandskapet
- 2016
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Hur uppfattar allmänheten nyhetsmediernas rapportering och myndigheternas kriskommunikation? Och hur kriskommunicerar allmänheten själv i de sociala mediernas tidevarv? Det är frågor som ställt i denna bok, där kriskommunikationen i samband med fem dramatiska svenska händelser jämförs och analyseras, med medborgarnas kommunikationsbehov som utgångspunkt. Boken vänder sig till kommunikatörer i offentlig tjänst, till mediemedarbetare, samt till forskare och andra med intresse av kriskommunikation. Boken utgör slutrapport från projektet Kriskommunikation 2.0, som finansierats av Myndighten för samhällsskydd och beredskap (MSB)
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| 6. |
- Antonson, Maria, et al.
(författare)
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Andningsvårdande behandling vid buk- och thoraxkirurgi
- 2010
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Ingår i: Fysioterapi. - 1653-5804. ; :2, s. 36-40
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Tidskriftsartikel (refereegranskat)abstract
- Sedan snart hundra år arbetar sjukgymnaster för att minska risken för postoperativa lungkomplikationer hos patienter som skall opereras i bröstkorg och buk. Klinisk erfarenhet visar att sjukgymnastisk andningsvård är viktig men vad vet vi idag om effekten av olika insatser? Vilka insatser bör man i första hand välja? Författarna till denna artikel har utarbetat Riktlinjer för andningsvårdande behandling inom sjukgymnastik för patienter som genomgår buk- och thoraxkirurgi. Målet med riktlinjearbetet har varit att utvärdera och sammanställa befintlig evidens för andningsvårdande behandlingsmetoder inom sjukgymnastik som används i samband med buk- och thoraxkirurgiska ingrepp. Den samlade evidensen i kombination med expertgruppens kommentarer har resulterat i kliniska behandlingsrekommendationer. Dessa riktar sig till kliniskt verksamma sjukgymnaster som arbetar med buk- och thoraxkirurgiska patienter. Förhoppningen är att den aktuella och systematiskt sammanställda kunskapen ska bidra till diskussioner på enskilda arbetsplatser och att behandlingsrekommendationerna kan anpassa till lokala förhållanden. Denna artikel är en sammanfattning av riktlinjerna som finns att hämta på Sjukgymnastförbundets hemsida under Profession. I riktlinjedokumentet återfinns också en fullständig referenslista
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| 7. |
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| 8. |
- Barclay, Victoria K. H., et al.
(författare)
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Acidic transformation of nordiazepam can affect recovery estimate during trace analysis of diazepam and nordiazepam in environmental water samples by liquid chromatography-tandem mass spectrometry
- 2019
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Ingår i: Analytical and Bioanalytical Chemistry. - : SPRINGER HEIDELBERG. - 1618-2642 .- 1618-2650. ; 411:17, s. 3919-3928
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Tidskriftsartikel (refereegranskat)abstract
- In this study, a special interest was focused on the stability of diazepam and nordiazepam in aqueous samples at acidic and neutral pH. The aim of the study was to isolate and illustrate one of the many possible sources of error that can be encountered when developing and validating analytical methods. This can be of particular importance when developing multi-analyte methods where there is limited time to scrutinize the behavior of each analyte. A method was developed for the analysis of the benzodiazepines diazepam and nordiazepam in treated wastewater. The samples were extracted by solid phase extraction, using SPEC C18AR cartridges, and analyzed by the use of liquid chromatography, with a C18 stationary phase, coupled to tandem mass spectrometry. Environmental water samples are often acidified during storage to reduce the microbial degradation of the target compounds and to preserve the sample. In some cases, the samples are acidified before extraction. In this study, it was found that a chemical equilibrium between nordiazepam and a transformation product could cause inaccurately high extraction recovery values when the samples were stored at low sample pH. The stability of nordiazepam was shown to be low at pH3. Within 12days, 20% of the initial concentration of nordiazepam was transformed. Interestingly, the transformed nordiazepam was shown to be regenerated and reformed to nordiazepam during sample handling. At a sample pH of 7, diazepam and nordiazepam were stable for 12days. It was concluded that great care must be taken when acidifying water samples containing nordiazepam during storage or extraction. The storage and the extraction should be conducted at neutral pH if no internal standard is used to compensate for degradation and conversion of nordiazepam. The developed method was validated in treated wastewater and applied for the quantification of diazepam and nordiazepam in treated wastewater samples.
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| 9. |
- Barclay, Victoria K.H., et al.
(författare)
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Chiral analysis of metoprolol and two of its metabolites, alpha‑hydroxymetoprolol and deaminated metoprolol, in wastewater using liquid chromatography-tandem mass spectrometry
- 2012
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Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1269:SI, s. 208-217
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Tidskriftsartikel (refereegranskat)abstract
- A LC–MS/MS method for the chiral separation of metoprolol and two of its main metabolites, α-hydroxymetoprolol (α-OH-Met) and deaminated metoprolol (COOH-Met), in environmental water samples has been developed. The target bases, metoprolol and α-OH-Met, as well as the acidic metabolite (COOH-Met) were extracted from water samples by a solid phase extraction method employing Oasis HLB cartridges. The extraction recoveries were ≥73% for all compounds in surface water. Four different types of chiral stationary phases were investigated for the separation of the eight stereoisomers of metoprolol and its metabolites, Chiralcel OD-H, Chirobiotic V, Chiral AGP and Chiral CBH. In the final method, the enantiomers of metoprolol and four stereoisomers of α-OH-Met were separated using Chiral CBH, the enantiomers of COOH-Met were separated employing Chiral AGP. The analytes were detected in SRM mode by triple quadrupole mass spectrometry. The method was applied for the chiral analysis of the analytes in treated wastewater samples from Uppsala, Sweden. The enantiomers and diastereoisomers of α-OH-Met were detected and analyzed in the samples. The concentrations of the three first eluting stereoisomers of α-OH-Met were between 54 and 61 pM. Interestingly, the last eluting stereoisomer was found to be present at a concentration of 151 pM at the same sampling occasion. This is, to the best of the authors’ knowledge, the first time the stereoisomers of α-OH-Met have been detected in wastewater samples. The enantiomers of metoprolol were determined to be 1.77 and 1.86 nM in the same matrix. The enantiomers of COOH-Met were not detected above the method detection limit (42 pM) in treated wastewater samples. The developed LC–MS/MS methods were validated in wastewater samples.
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| 10. |
- Barclay, Victoria K.H.
(författare)
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Development of LC-MS/MS Methods for the Analysis of Chiral and Achiral Pharmaceuticals and Metabolites in Aqueous Environmental Matrices
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis describes the development of liquid chromatography tandem mass spectrometry (LC-MS/MS) methods for the trace analysis of active pharmaceutical ingredients (APIs) and their metabolites in aqueous environmental matrices. The research was focused on the development of chiral LC-MS/MS methods for the analysis of fluoxetine and metoprolol, as well as their chiral metabolites in environmental water samples. A method was also developed for the achiral compounds, diazepam and nordiazepam. The LC-MS/MS methods were validated by the use of the isotope-labeled compounds. As these isotope-labeled compounds were not found in the wastewater samples, the validation could be assessed at trace level concentrations in the actual matrices in which the analytes were detected. The analytes were extracted from the water samples using solid phase extraction methods. Different types of solid phase extraction sorbents were evaluated. Fluoxetine and norfluoxetine were extracted through the use of a mixed mode polymeric based extraction sorbent. A hydrophilic and lipophilic balanced sorbent was employed for the simultaneous extraction of metoprolol and its metabolites, the base α-hydroxymetoprolol and the acidic metabolite deaminated metoprolol. Moreover, silica based C18 extraction discs were applied for the sample preparation of diazepam and nordiazepam. The chromatographic separations were conducted in reversed phase LC with MS compatible mobile phases. The enantiomers of fluoxetine and norfluoxetine were simultaneously separated using the chiral stationary phase (CSP), α1-acid glycoprotein (AGP). The Chiral AGP column was also applied for the separation of the enantiomers of deaminated metoprolol. For the simultaneous separation of the metoprolol enantiomers and the four stereoisomers of α-hydroxymetoprolol, the cellobiohydrolase (CBH) protein based CSP was used. An octadecyl silica based LC column was applied for the separation of diazepam and nordiazepam. The analytes were detected by the use of tandem quadrupole mass spectrometry operating in selective reactive monitoring mode. High resolution MS, employing a quadrupole time-of-flight (QqTOF) mass analyzer, was utilized for the identification of an unknown compound in wastewater samples. The APIs and their metabolites, as well as their respective enantiomers, were quantified in raw and treated wastewater from Uppsala, Sweden along with surface water from the River Fyris in Uppsala.
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