| 1. |
- Lindqvist, C. Mårten, et al.
(författare)
-
Deep targeted sequencing in pediatric acute lymphoblastic leukemia unveils distinct mutational patterns between genetic subtypes and novel relapse-associated genes
- 2016
-
Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:39, s. 64071-64088
-
Tidskriftsartikel (refereegranskat)abstract
- To characterize the mutational patterns of acute lymphoblastic leukemia (ALL) we performed deep next generation sequencing of 872 cancer genes in 172 diagnostic and 24 relapse samples from 172 pediatric ALL patients. We found an overall greater mutational burden and more driver mutations in T-cell ALL (T-ALL) patients compared to B-cell precursor ALL (BCP-ALL) patients. In addition, the majority of the mutations in T-ALL had occurred in the original leukemic clone, while most of the mutations in BCP-ALL were subclonal. BCP-ALL patients carrying any of the recurrent translocations ETV6-RUNX1, BCR-ABL or TCF3-PBX1 harbored few mutations in driver genes compared to other BCP-ALL patients. Specifically in BCP-ALL, we identified ATRX as a novel putative driver gene and uncovered an association between somatic mutations in the Notch signaling pathway at ALL diagnosis and increased risk of relapse. Furthermore, we identified EP300, ARID1A and SH2B3 as relapse-associated genes. The genes highlighted in our study were frequently involved in epigenetic regulation, associated with germline susceptibility to ALL, and present in minor subclones at diagnosis that became dominant at relapse. We observed a high degree of clonal heterogeneity and evolution between diagnosis and relapse in both BCP-ALL and T-ALL, which could have implications for the treatment efficiency.
|
|
| 2. |
|
|
| 3. |
- Althini, Sanna, et al.
(författare)
-
Normal Nigrostriatal Innervation but Dopamine Dysfunction in Mice Carrying Hypomorphic Tyrosine Hydroxylase Alleles
- 2003
-
Ingår i: Journal of Neuroscience Research. - : Wiley. - 0360-4012 .- 1097-4547. ; 72:4, s. 444-453
-
Tidskriftsartikel (refereegranskat)abstract
- We investigated the use of the mouse tyrosine hydroxylase (TH) gene to drive knock-in constructs in catecholaminergic neurons. Two targeting constructs representing truncated forms of either of the BMP receptors ALK-2 or BMPR-II preceded by an internal ribosome entry site (IRES) were introduced into the 3' untranslated region of TH. An frt-flanked neomycin-resistance (neo(r)) cassette was placed in the 3' end of the targeting constructs. Mice homozygous for the knock-in alleles showed various degrees of hypokinetic behavior, depending mainly on whether the neo(r) cassette was removed. In situ hybridization and immunohistochemistry showed that TH mRNA and protein were variously down-regulated in these mouse strains. Reduced levels of dopamine and noradrenalin were found in several brain areas. However, number and morphology of neurons in substantia nigra and their projections to striatum appeared normal in the neo(r)-positive TH hypomorphic mice as examined by markers for L-aromatic amino acid decarboxylase and the dopamine transporter. Elimination of the neo(r) cassette from the knock-in alleles partially restored TH and dopamine levels. The present neo(r)-positive TH hypomorphic mice show that nigrostriatal innervation develops independently of TH and should find use as a model for conditions of reduced catecholamine synthesis, as seen in, for example, L-dihydroxyphenylalanine-responsive dystonia/infantile parkinsonism.
|
|
| 4. |
- Andersson, Maria, 1980, et al.
(författare)
-
Enhanced concentrations of dissolved gaseous mercury in the surface waters of the Arctic Ocean
- 2008
-
Ingår i: Marine Chemistry. - : Elsevier BV. - 0304-4203. ; 110:3-4, s. 190-194
-
Tidskriftsartikel (refereegranskat)abstract
- During an almost three months long expedition in the Arctic Ocean, the Beringia 2005, dissolved gaseous mercury (DGM) was measured continuously in the surface water. The DGM concentration was measured using an equilibrium system, i.e. the DGM in the water phase equilibrated with a stream of gas and the gas was thereafter analysed with respect to its mercury content. The DGM concentrations were calculated using the following equation, DGM = Hg eq / k H' where Hg eq is the equilibrated concentration of elemental mercury in the gas phase and k H' is the dimensionless Henry's law constant at desired temperature and salinity. During the expedition several features were observed. For example, enhanced DGM concentration was measured underneath the ice which may indicate that the sea ice acted as a barrier for evasion of mercury from the Arctic Ocean to the atmosphere. Furthermore, elevated DGM concentrations were observed in water that might have originated from river discharge. The gas-exchange of mercury between the ocean and the atmosphere was calculated in the open water and both deposition and evasion were observed. The measurements showed significantly enhanced DGM concentrations, compared to more southern latitudes. © 2008 Elsevier B.V. All rights reserved.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Bergemalm, Daniel, 1977-, et al.
(författare)
-
Systemic Inflammation in Preclinical Ulcerative Colitis
- 2021
-
Ingår i: Gastroenterology. - : AGA Institute. - 0016-5085 .- 1528-0012. ; 161:5, s. 1526-1539.e9
-
Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Preclinical ulcerative colitis is poorly defined. We aimed to characterize the preclinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins.Methods: We obtained plasma samples biobanked from individuals who developed ulcerative colitis later in life (n = 72) and matched healthy controls (n = 140) within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biologic relevance of these findings was validated in an inception cohort of patients with ulcerative colitis (n = 101) and healthy controls (n = 50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of patients with ulcerative colitis (n = 41) and matched healthy controls (n = 37) were explored.Results: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP-1) were up-regulated (P < .05) in preclinical ulcerative colitis compared with controls based on both univariate and multivariable models. Ingenuity Pathway Analyses identified several potential key regulators, including interleukin-1β, tumor necrosis factor, interferon-gamma, oncostatin M, nuclear factor-κB, interleukin-6, and interleukin-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve patients with ulcerative colitis from controls with leave-one-out cross-validation (area under the curve = 0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly up-regulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis.Conclusions: A set of inflammatory proteins are up-regulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be up-regulated already at exposure to genetic and environmental risk factors.
|
|
| 8. |
- Berglund, U. W., et al.
(författare)
-
Validation and development of MTH1 inhibitors for treatment of cancer
- 2016
-
Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 27:12, s. 2275-2283
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Previously, we showed cancer cells rely on the MTH1 protein to prevent incorporation of otherwise deadly oxidised nucleotides into DNA and we developed MTH1 inhibitors which selectively kill cancer cells. Recently, several new and potent inhibitors of MTH1 were demonstrated to be non-toxic to cancer cells, challenging the utility of MTH1 inhibition as a target for cancer treatment. Material and methods: Human cancer cell lines were exposed in vitro to MTH1 inhibitors or depleted of MTH1 by siRNA or shRNA. 8-oxodG was measured by immunostaining and modified comet assay. Thermal Proteome profiling, proteomics, cellular thermal shift assays, kinase and CEREP panel were used for target engagement, mode of action and selectivity investigations of MTH1 inhibitors. Effect of MTH1 inhibition on tumour growth was explored in BRAF V600E-mutated malignant melanoma patient derived xenograft and human colon cancer SW480 and HCT116 xenograft models. Results: Here, we demonstrate that recently described MTH1 inhibitors, which fail to kill cancer cells, also fail to introduce the toxic oxidized nucleotides into DNA. We also describe a new MTH1 inhibitor TH1579, (Karonudib), an analogue of TH588, which is a potent, selective MTH1 inhibitor with good oral availability and demonstrates excellent pharmacokinetic and anti-cancer properties in vivo. Conclusion: We demonstrate that in order to kill cancer cells MTH1 inhibitors must also introduce oxidized nucleotides into DNA. Furthermore, we describe TH1579 as a best-in-class MTH1 inhibitor, which we expect to be useful in order to further validate the MTH1 inhibitor concept.
|
|
| 9. |
- Bergqvist, Jonas, et al.
(författare)
-
Sub-glass transition annealing enhances polymer solar cell performance
- 2014
-
Ingår i: Journal of Materials Chemistry A. - : Royal Society of Chemistry. - 2050-7488. ; 2:17, s. 6146-6152
-
Tidskriftsartikel (refereegranskat)abstract
- Thermal annealing of non-crystalline polymer: fullerene blends typically results in a drastic decrease in solar cell performance. In particular aggressive annealing above the glass transition temperature results in a detrimental coarsening of the blend nanostructure. We demonstrate that mild annealing below the glass transition temperature is a viable avenue to control the nanostructure of a non-crystalline thiophene-quinoxaline copolymer: fullerene blend. Direct imaging methods indicate that coarsening of the blend nanostructure can be avoided. However, a combination of absorption and luminescence spectroscopy reveals that local changes in the polymer conformation as well as limited fullerene aggregation are permitted to occur. As a result, we are able to optimise the solar cell performance evenly across different positions of the coated area, which is a necessary criterion for large-scale, high throughput production.
|
|
| 10. |
- Bergqvist, Jonas, et al.
(författare)
-
Time-resolved morphology formation of solution cast polymer : fullerene blends revealed by in-situ photoluminescence spectroscopy
- 2015
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The nanoscale morphology of the photo-active layer in organic solar cells is critical for device efficiency. The photoactive layer is cast from solution and during drying both the polymer and the fullerene self-assemble to form a blend. Here, we introduce in-situ spectroscopic photoluminescence (PL) combined with laser reflectometry to monitor the drying process of an amorphous polymer:fullerene blend. When casting only the pristine components (polymer or PCBM only), the strength of PL emission is proportional to the solid content of the drying solution, and both kinetics reveal a rapid aggregation onset at the final stage of film drying. On the contrary, when casting polymer:fullerene blends, the strength of PL emission is proportional to the wet film thickness and reveals polymer/fullerene charge transfer (CT) already at the earliest stages of film drying, i.e. in dilute solutions. The proposed method allows to detect polymer/fullerene phase separation during film casting – from a reduction in the PL quenching rate as the film dries. Poor solvents lead to phase separation already at early stages of film drying (low solid content), resulting in a coarse final morphology as confirmed by atomic force microscopy (AFM). We therefore anticipate that the proposed method will be an important tool in the future development of processing inks, not only for solution-cast polymer:fullerene solar cells but also for organic heterojunctions in general.
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Carstens, Adam, 1975-, et al.
(författare)
-
The Gut Microbiota in Collagenous Colitis Shares Characteristics With Inflammatory Bowel Disease-Associated Dysbiosis
- 2019
-
Ingår i: Clinical and Translational Gastroenterology. - : Nature Publishing Group. - 2155-384X. ; 10:7
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: In inflammatory bowel disease (IBD), an aberrant immune response to gut microbiota is important, but the role of the microbiota in collagenous colitis (CC) is largely unknown. We aimed to characterize the microbiota of patients with CC compared with that of healthy control and patients with IBD.METHODS: Fecal samples were collected from patients with CC (n = 29), age- and sex-matched healthy controls (n = 29), patients with Crohn's disease (n = 32), and patients with ulcerative colitis (n = 32). Sequence data were obtained by 454 sequencing of 16S rRNA gene amplicons, and the obtained sequences were subsequently taxonomically classified.RESULTS: Analysis of similarity statistics showed a segregation between patients with CC and healthy controls with increasing taxonomic resolution, becoming significant comparing operational taxonomic unit data (P = 0.006). CC had a lower abundance of 10 different taxa. Taxa-specific analyses revealed a consistent lower abundance of several operational taxonomic units belonging to the Ruminococcaceae family in patients with CC, q < 0.05 after false discovery rate correction. Loss of these taxa was seen in patients with CC with active disease and/or corticosteroid treatment only and resembled the findings in patients with IBD.DISCUSSION: CC is associated with a specific fecal microbiome seen primarily in patients with active disease or ongoing corticosteroid treatment, whereas the microbiome of CC patients in remission resembled that of healthy controls. Notably, the shift in key taxa, including the Ruminococcaceae family, was also observed in IBD. There may be common mechanisms in the pathogenesis of CC and IBD.
|
|
| 14. |
- Claesson, Åsa, et al.
(författare)
-
lntegrated Optical Fiber Sensors in Additive Manufactured Metal Components for Smart Manufacturing Applications
- 2019
-
Ingår i: Smart Systems Integration; 13th International Conference and Exhibition on Integration Issues of Miniaturized Systems.
-
Konferensbidrag (refereegranskat)abstract
- This work combines fiber optic sensors with additive manufacturing to enable integration of temperature and strain sensors in metal components. In this paper, we present a fiber optic sensor network integrated in press hardening tools to monitor the contact between the tool and the metal sheet during forming operation. The tools are manufactured through metal powder bed fusion using laser melting processes (PBF-SLM), after which the tools are prepared for sensor integration. A demonstrator press hardening tool with integrated fiber optic sensors was heated using an electric heat foil and the sensor measurements was compared to a thermal simulation model. The sensor technology is based on Fiber Bragg Gratings (FBGs), integrated at several positions along the optical fiber. FBGs are in-fiber sensors that are multiplexed. lt is possible to place hundreds of FBG sensors along one single fiber, thus allowing for quasidistributed sensing of temperature or strain. The optical fiber itself can be less than 100 micrometer in diameter, allowing for sensing at several points in a minimally invasive way, when integrated in a tool or component.
|
|
| 15. |
- Diaz de Zerio Mendaza, Amaia, 1986, et al.
(författare)
-
Neat C60:C70 buckminsterfullerene mixtures enhance polymer solar cell performance
- 2014
-
Ingår i: Journal of Materials Chemistry A. - : Royal Society of Chemistry (RSC). - 2050-7488 .- 2050-7496. ; 2:35, s. 14354-14359
-
Tidskriftsartikel (refereegranskat)abstract
- We demonstrate that bulk-heterojunction blends based on neat, unsubstituted buckminsterfullerenes (C60, C70) and a thiophene–quinoxaline copolymer (TQ1) can be readily processed from solution. Atomic force and transmission electron microscopy as well as photoluminescence spectroscopy reveal that thin films with a fine-grained nanostructure can be spin-coated, which display a good photovoltaic performance. Replacement of substituted fullerenes with C60 or C70 only results in a small drop in open-circuit voltage from 0.9 V to about 0.8 V. Thus, a power conversion efficiency of up to 2.9% can be maintained if C70 is used as the acceptor material. Further improvement in photovoltaic performance to 3.6% is achieved, accompanied by a high internal quantum efficiency of 75%, if a 1 : 1 C60:C70 mixture is used as the acceptor material, due to its improved solubility in ortho-dichlorobenzene.
|
|
| 16. |
- Enoksson, Helen, et al.
(författare)
-
Studier i en främmande skolkultur
- 2019
-
Ingår i: Didaktisk utvecklingsdialog. - Lund : Studentlitteratur AB. - 9789144125749 ; , s. 49-66
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 17. |
|
|
| 18. |
- Feng, Xinbin, et al.
(författare)
-
On-line speciation of mercury in flue gas
- 1999
-
Ingår i: Book of Abstract. 5th International Conference on Mercury as a Global Pollutant, Rio de Janeiro, Brazil, 1999.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)
|
|
| 19. |
- Feng, Xinbin, et al.
(författare)
-
On-line Speciation of Mercury in the Flue Gases
- 1999
-
Ingår i: Proceedings of A&WM Mercury in the Environment Specialty Conference, Air & Waste Management Association, Minneapolis, MN. USA.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)
|
|
| 20. |
- Fletcher, Erika A. K., et al.
(författare)
-
Extracorporeal human whole blood in motion, as a tool to predict first-infusion reactions and mechanism-of-action of immunotherapeutics
- 2018
-
Ingår i: International Immunopharmacology. - : Elsevier BV. - 1567-5769 .- 1878-1705. ; 54, s. 1-11
-
Tidskriftsartikel (refereegranskat)abstract
- First infusion reactions along with severe anaphylactic responses can occur as a result of systemic administration of therapeutic antibodies. The underlying mechanisms by which monoclonal antibodies induce cytokine release syndrome (CRS) can involve direct agonistic effects via the drug target, or a combination of target-engagement along with innate receptor interactions. Despite the wide variety of pathways and cells that can play a role in CRS, many currently used assays are devoid of one or more components that must be present for these responses to occur. One assay that has not been assessed for its capacity to predict CRS is the modified Chandler loop model. Herein we evaluate a plethora of commercially available monoclonal antibodies to evaluate the modified Chandler loop model's potential in CRS prediction. We demonstrate that in a 4-hour loop assay, both the superagonistic antibodies, anti-CD3 (OKT3) and anti-CD28 (ANC28.1), display a clear cytokine response with a mixed adaptive/innate cytokine source. OKT3 induce TNFα and IFN-γ release in 20 out of 23 donors tested, whereas ANC28.1 induce TNF-α, IL-2 and IFN-γ release in all donors tested (n = 18–22). On the other hand, non-agonistic antibodies associated with no or low infusion reactions in the clinic, namely cetuximab and natalizumab, neither induce cytokine release nor cause false positive responses. A TGN1412-like antibody also display a clear cytokine release with an adaptive cytokine profile (IFN-γ and IL-2) and all donors (n = 9) induce a distinct IL-2 response. Additionally, the value of an intact complement system in the assay is highlighted by the possibility to dissect out the mechanism-of-action of alemtuzumab and rituximab. The loop assay can either complement lymph node-like assays or stand-alone to investigate drug/blood interactions during preclinical development, or for individual safety screening prior to first-in-man clinical trial.
|
|
| 21. |
- Fletcher, Erika, et al.
(författare)
-
Extracorporeal human whole blood in motion, as a tool to predict first-infusion reactions and mechanisms-of-action of immunotherapeutics : CRS prediction in human whole blood
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- First infusion reactions along with severeanaphylactic responses can occur as a result of systemic administration oftherapeutic antibodies. The underlying mechanisms by which monoclonal antibodiesinduce cytokine release syndrome (CRS) can involve direct agonistic effects viathe drug target, or a combination of target-engagement along with innatereceptor interactions. Despite the wide variety of pathways and cells that canplay a role in CRS, many currently used assays are devoid of one or morecomponents that must be present for these responses to occur. To date, oneassay that has not been used for studying CRS is the Chandler loop model. Thismodel is commonly used to study surface/blood interface interactions and has alsobeen used to study the instant blood-mediated inflammatory reaction (IBMIR). Herein we use a modified Chandler loopmodel with a heparin conjugate lining the inner surface of the loops to studyCRS. This allows for an assay harboring immune cells, intact cascade systemsalong with endogenous antibodies. Here, we evaluated a plethora of commerciallyavailable monoclonal antibodies to assess the capacity of the Chandler loopmodel for CRS prediction. We demonstrated that in a 4-hour loop assay both thesuperagonistic antibodies, anti-CD3 (OKT3) and anti-CD28 (ANC28.1), displayed aclear cytokine response with a mixed adaptive/innate cytokine source. OKT3 induced TNFα and IFN-g release in 20 out of23 donors tested, whereas ANC28.1 induced TNF-α, IL-2 and IFN-g release in all donors tested (n=18-22). On theother hand, non-agonistic antibodies associated with no or low infusionreactions in the clinic, namely cetuximab and natalizumab, neither induced cytokinerelease nor caused false positive responses. A TGN1412-like antibody alsodisplayed a clear cytokine release with an adaptive cytokine profile (IFN-g and IL-2) and all donors (n=9) inducing adistinct IL-2 response. Additionally, the value of an intact complement systemin the assay was highlighted by the possibility to dissect out themechanism-of-action (MOA) of alemtuzumab and rituximab. The loop assay can eithercomplement lymph node-like assays or stand-alone to investigate drug/bloodinteractions during preclinical development, or for individual safety screeningprior to a first-in-man clinical trial.
|
|
| 22. |
- Flygare, Jonas, 1988, et al.
(författare)
-
Design trade-offs in feed systems for ultra-wideband VLBI observations
- 2018
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Due to the advanced capability of today’s ultra-wideband feed systems and low-noise amplifiers, interesting upgrades for future VLBI receiver and tele- scope design should be considered. Multiple input pa- rameters need to be taken into account for optimal sensitivity and applications of the future astronomical and geodetic observational systems. In this paper we present an overview of some trade-offs for wideband systems between SEFD, bandwidth and telescope re- flector optics. We evaluate receiver bandwidths from 3.5:1 to 10.3:1 bandwidth within the frequency range 1.5-24 GHz in different configurations. Due to poten- tial RFI-pollution of the lower frequencies we present potential feed upgrades for the most common reflector geometries ofVGOS and EVN telescopes that mitigate this problem. The results of this work is relevant for fu- ture VLBI stations and telescope design in general. Keywords
|
|
| 23. |
- Flygare, Jonas, 1988, et al.
(författare)
-
Ultra-wideband feed systems for the EVN and SKA - evaluated for VGOS
- 2018
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The design of the Square Kilometre Array (SKA) project for radio astronomy is now materializing at a rapid speed; the EU Horizon 2020 RadioNet project BRoad-bAND (BRAND) has the ambition to deliver a decade bandwidth receiver for EVN. The ultra-wideband quad-ridge flared horn (QRFH) feed systems developed for these projects show good performance within the geodetic VLBI Global Observing System (VGOS) frame due to the overlapping frequency bands and reflector geometries. We estimate, through simulation, system equivalent flux density (SEFD) of the two feed systems in the VGOS reflector and compare the it to the existing system installed on one of the 13.2 m diameter reflectors of the Onsala twin telescope (OTT). The two frequency bands analyzed cover 1.5−15.5 GHz and 4.6−24 GHz. Both systems show SEFD better than 1000 Jy over large parts of resp. frequency band - comparable to the 3−18 GHz feed systems. For the SKA QRFH over 4.6−24 GHz, the water vapor absorption line at 22 GHz is within the operational band, therefore we study the application of water-vapor radiometry in line-of-sight of the telescope.
|
|
| 24. |
- Forsström, Stefan, 1984-, et al.
(författare)
-
Surveying and identifying the communication platforms of the internet of things
- 2018
-
Ingår i: 2018 Global Internet of Things Summit, GIoTS 2018. - : IEEE. - 9781538664513
-
Konferensbidrag (refereegranskat)abstract
- Research and industry invest time and resources in producing Internet of Things-based services, and the concept of Internet of Things platforms is climbing in the hype cycle for emerging technologies. Consequently, there is a vast number of enabling technologies, making it difficult to find the most suitable platform. The aim and goal of this article is to list and identify the currently available communication platforms for the Internet of Things. In this workwe surveyed the area and found over 128 different platforms for communication of data between things and services, out of which 42 fulfilled our listed basic requirements for being an IoT communication platform.
|
|
| 25. |
|
|
| 26. |
- Grännö, O., et al.
(författare)
-
Preclinical protein signatures in blood predict Crohn's disease and Ulcerative colitis several years before the diagnosis
- 2024
-
Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 18:Suppl. 1, s. I660-I661
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: We aimed to identify protein signatures predictive of a future diagnosis of inflammatory bowel disease (IBD).Methods: We conducted a case-control study, nested within large population-based cohorts with biorepositories. Samples were obtained from individuals who later in life were diagnosed with IBD (preclinical cases) and compared with age and sex-matched individuals who remained free from IBD during follow-up (controls). Using proximity extension assays (Olink, Uppsala), we measured 176 proteins. We applied regularized logistic regression to identify protein signatures of preclinical disease in serum from the discovery cohort (n=312). Their performance was validated in an external preclinical cohort (n=222). The biological relevance of identified proteins was further assessed in an inception cohort (n=144). Finally, we used an IBD twin cohort (n=327) to examine the impact of genetic and shared environmental factors on identified proteins.Results: We identified 34 proteins associated with preclinical Crohn’s disease (CD) in the discovery cohort (Pfalse discovery rate <0.10), with 9 confirmed in the validation cohort (Pfalse discovery rate <0.05). For preclinical ulcerative colitis (UC), 45 proteins were identified and 12 validated (Fig. 1A-B). In the discovery cohort, a signature of 29 proteins differentiated preclinical CD cases from controls with an AUC of 0.85 (Fig. 1G). Its performance was confirmed when applied to the preclinical validation cohort (AUC=0.84, Fig. 1H). Moreover, the signature had excellent capacity to differentiate newly diagnosed CD from healthy controls in the inception cohort (AUC = 0.99, Fig. 1I). The preclinical UC signature had a significant, but albeit lower, predictive capacity in the discovery (AUC=0.77), validation (AUC=0.67) and inception cohort (AUC=0.90, Fig. 1G-I).15 of 17 proteins associated with preclinical IBD demonstrated significantly higher intra-pair correlation coefficients in healthy monozygotic- compared to dizygotic twin pairs, indicating an influence from genetic factors on the regulation of these protein markers. The preclinical signature for CD demonstrated an AUC of 0.87 when comparing twins with preclinical CD (n=10) to matched external healthy twins. However, its predictive capacity was lower when comparing preclinical CD twins with their healthy twin siblings (AUC=0.58), i.e., when accounting for genetic and shared environmental factors. The difference in AUC estimates in the twin cohort was not significant (P=0.07).
|
|
| 27. |
|
|
| 28. |
- Gårdfeldt, Katarina, 1959, et al.
(författare)
-
Evasion of Mercury from coastal and open waters of the Atlantic ocean and the Mediterranean sea
- 2003
-
Ingår i: Atmospheric Environment. - 1352-2310 .- 1873-2844. ; 37:Suppl 1
-
Tidskriftsartikel (refereegranskat)abstract
- Dissolved gaseous mercury (DGM) was measured in coastal Atlantic seawater and in the Mediterranean Sea. The Atlantic measurements were performed during September 1999 at the Mace Head Atmospheric Research Station, situated on the Irish west coast. The measurements in the Mediterranean Sea were made along a 6000 km cruise path from 14 July to 9 August 2000 in the framework of the Med-Oceanor project. Total gaseous mercury (TGM) concentrations in air were continuously measured with a 5 min time resolution using an automated mercury analyser (Tekran 2537A) during both expeditions. Paired TGM and DGM samples from all campaigns showed that the surface water was supersaturated with elemental mercury. The mercury evasion was estimated using a gas exchange model (J. Geophys. Res. 97 (1992) 7373), which uses salinity, wind speed and water temperature as independent parameters. The predicted average mercury evasion from the coastal Atlantic water was 2.7 ng m−2 h−1 implying that the concentration of TGM in the Atlantic air is enhanced by mercury evasion from the sea. Measurements in different regions of the Mediterranean Sea showed spatial variations in DGM concentrations. The highest DGM concentration (90 pg l−1) was observed at a location in the Strait of Sicily (37°16N 11°52E). The mercury evasion in the eastern sector of the Mediterranean Sea (area: 32–36°N, 17–28°E) was generally higher (7.9 ng m−2 h−1) than that observed in the Tyrrhenian Sea (4.2 ng m−2 h−1) or in the western sector (2.5 ng m−2 h−1) (areas: 38–42°N, 8–13°E and 38–41°N, 7–8°E, respectively). Estimations of mercury evasion were also made at Mediterranean coastal sites using a dynamic chamber technique. In addition, a newly developed method making continuous in situ DGM measurements possible was tested.
|
|
| 29. |
- Hamann, Maike, et al.
(författare)
-
Inequality and the biosphere
- 2018
-
Ingår i: Annual Review of Environment and Resources. - : Annual Reviews. - 1543-5938 .- 1545-2050. ; 43, s. 61-83
-
Forskningsöversikt (refereegranskat)abstract
- Rising inequalities and accelerating global environmental change pose two of the most pressing challenges of the twenty-first century. To explore how these phenomena are linked, we apply a social-ecological systems perspective and review the literature to identify six different types of interactions (or "pathways") between inequality and the biosphere. We find that most of the research so far has only considered one-directional effects of inequality on the biosphere, or vice versa. However, given the potential for complex dynamics between socioeconomic and environmental factors within social-ecological systems, we highlight examples from the literature that illustrate the importance of cross-scale interactions and feedback loops between inequality and the biosphere. This review draws on diverse disciplines to advance a systemic understanding of the linkages between inequality and the biosphere, specifically recognizing cross-scale feedbacks and the multidimensional nature of inequality.
|
|
| 30. |
- Håkanson, Christina, et al.
(författare)
-
Firms and Skills The Evolution of Worker Sorting
- 2021
-
Ingår i: The Journal of human resources. - 0022-166X .- 1548-8004. ; 56:2, s. 512-538
-
Tidskriftsartikel (refereegranskat)abstract
- We document a significant increase in the sorting of workers by cognitive and noncognitive skills across Swedish firms during 1986–2008. During this period, worker skill differences between firms increased, while within-firm skill differences fell. A significant fraction of the increase in the between-firm differences in cognitive skill is due to high-skilled workers moving into the information and communications technology (ICT) sector. Within-firm skill differences fell in all major industries, but particularly in the manufacturing sector. Combined with steeper firm-level skill gradients, the increase in sorting can account for 45 percent of the increase in between-firm wage dispersion during our period of study.
|
|
| 31. |
- Höckertin, Chatrine, 1964-
(författare)
-
Organisational characteristics and psychosocial working conditions in different forms of ownership
- 2007
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main aim of this thesis has been to compare psychosocial working conditions in workplaces with different forms of ownership, i.e. public, private and cooperative. A second aim has been to study how organisational characteristics of relevance for psychosocial working conditions (in terms of management control strategies and prerequisites for management) are manifested in these ownership forms. The empirical data is based on structured interviews with managers at 60 workplaces within the service sector and on a questionnaire to all employees working in the participating workplaces, resulting in a set of 1384 individuals. An additional seven interviews with first-line managers within geriatric care were also conducted for the last study. The results show that employees in cooperatives perceived that they had better opportunities to influence decisions concerning the workplace as a whole, although there were also results showing advantages for public and private employees. Regarding opportunities for employees to influence their own work situation, there were no differences between the ownership forms. Differences were found in the prerequisites for first-line geriatric care managers. As a result of an earlier organisational change, the public managers were now further away from the strategic level and had to focus on daily, operative work tasks, while simultaneously also being responsible for keeping within the budget. The private managers, on the other hand, having group leaders to deal with the daily work concerning personnel and operations, could focus more on strategic work related to financial results in terms of planning and follow-up of the budget. One conclusion is that there are certain differences in both psychosocial working conditions and organisational characteristics between the ownership forms, but when the comparisons were restricted to only one type of service, in this case the provision of care, it is rather the similarities within the care organisations, regardless of ownership form, that are most pronounced.
|
|
| 32. |
- Juzenas, Simonas, et al.
(författare)
-
Depletion of erythropoietic miR-486-5p and miR-451a improves detectability of rare microRNAs in peripheral blood-derived small RNA sequencing libraries
- 2020
-
Ingår i: NAR Genomics and Bioinformatics. - Oxford, UK : Oxford University Press. - 2631-9268. ; 2:1
-
Tidskriftsartikel (refereegranskat)abstract
- Erythroid-specific miR-451a and miR-486-5p are two of the most dominant microRNAs (miRNAs) in human peripheral blood. In small RNA sequencing libraries, their overabundance reduces diversity as well as complexity and consequently causes negative effects such as missing detectability and inaccurate quantification of low abundant miRNAs. Here we present a simple, cost-effective and easy to implement hybridization-based method to deplete these two erythropoietic miRNAs from blood-derived RNA samples. By utilization of blocking oligonucleotides, this method provides a highly efficient and specific depletion of miR-486-5p and miR-451a, which leads to a considerable increase of measured expression as well as detectability of low abundant miRNA species. The blocking oligos are compatible with common 5′ ligation-dependent small RNA library preparation protocols, including commercially available kits, such as Illumina TruSeq and Perkin Elmer NEXTflex. Furthermore, the here described method and oligo design principle can be easily adapted to target many other miRNA molecules, depending on context and research question.
|
|
| 33. |
- Juzenas, Simonas, et al.
(författare)
-
Detailed transcriptional landscape of peripheral blood points to increased neutrophil activation in treatment-naïve inflammatory bowel disease
- 2022
-
Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 16:7, s. 1097-1109
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is a chronic relapsing disorder of the gastrointestinal tract, which generally manifests as Crohn's disease (CD) or ulcerative colitis (UC). These subtypes are heterogeneous in terms of disease location and histological features, while sharing common clinical presentation, genetic associations and thus, common immune regulatory pathways.METHODS: Using miRNA and mRNA coupled transcriptome profiling and systems biology approaches, we report a comprehensive analysis of blood transcriptomes from treatment-naïve (n=110) and treatment-exposed (n=177) IBD patients as well as symptomatic- (n=65) and healthy controls (n=95).RESULTS: Broadly, the peripheral blood transcriptomes of CD and UC patients were similar. However, there was an extensive gene deregulation in the blood of IBD patients, while only a slight deregulation in symptomatic controls, when compared with healthy controls. The deregulated mRNAs and miRNAs are mainly involved in the innate immunity and are especially enriched in neutrophil activation-related pathways. Oxidative phosphorylation and neutrophil activation-related modules were found to be differentially co-expressed among treatment-naïve IBD as compared to healthy controls. In the deregulated neutrophil activation-related co-expression module, the IL1B was identified as the central gene. The co-expression levels among IL1B and chemosensing receptor (CXCR1/2 and FPR1/2) genes were reduced in the blood of IBD patients when compared with healthy controls.CONCLUSIONS: Immune dysregulation seen in peripheral blood transcriptomes of treatment-naïve IBD patients is mainly driven by neutrophil activation.
|
|
| 34. |
- Juzenas, S., et al.
(författare)
-
Sequencing-based hematopoietic miRNA landscape reveals common and distinct features of autoimmune inflammatory phenotypes
- 2019
-
Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 13:Suppl. 1, s. S614-S614
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: MiRNAs represent a class of small non-coding RNAs which are involved in regulation of protein-coding gene expression. Being implicated in various processes such as development and regu-latory circuits of cells, miRNAs also play an important role in the etiology of a variety of diseases. Imbalance of the regulatory pro-cesses within immune system development and response may lead to disturbed production of pro-inflammatory cytokines and over-reactivity of the immune cells, thus causing relapsing inflamma-tion, a characteristic feature of inflammatory bowel disease (IBD). Recent studies of colonic miRNAs employed NGS for the distinction between CD, UC and healthy controls, or among different CD sub-types. However, NGS-based profiles of blood-circulating miRNAs have thus far not been investigated in the context of IBD together with other immune-mediated diseases, including ankylosing spon-dylitis, psoriasis, systemic lupus erythematosus, rheumatoid arthritis and sarcoidosis, as well as non-immune hemolytic-uremic syndrome.Methods: Study participants were recruited in Germany and Sweden, where peripheral blood samples (PAXgene) as well as phenotypical and clinical information (such as treatment status, dis-ease activity and location) was collected. Small RNA transcriptomes of 680 individuals (Figure 1) were sequenced using Illumina NGS platform. Small RNA-seq data preprocessing and quantification were performed using cutadapt and miraligner (ref. miRBase v22), respectively. Differential expression analysis (DESeq2) and correla-tion (Spearman) analysis have been performed to identify disease activity-, trait- and treatment-specific miRNA signatures. These sig-natures were then utilized in a machine-learning approach to build classification models for IBD diagnostics.Results: The results of multiple pairwise differential expression anal-yses among different immune-mediated inflammatory conditions and healthy controls revealed inflammation-specific as well and dis-ease-specific deregulation of miRNAs. Correlation analysis identified miRNAs positively and negatively correlated with IBD activity. The preliminary results of machine learning classifiers based on miRNA profiles showed that median Matthews correlation coefficient for all model types showed remarkable predictive performance estimated as being 1.00 (median over main diagnoses), as well as ranging from 0.68 to 0.76 (median over CD location) and from 0.69 to 0.77 (median over UC extent).Conclusions: Immune-mediated inflammatory diseases share com-mon and distinct differentially expressed miRNAs, which have a potential to be used in the diagnostics of IBD, including the evalua-tion of the disease activity.
|
|
| 35. |
|
|
| 36. |
- Keita, Åsa, et al.
(författare)
-
Gut barrier dysfunction : a primary defect in twins with Crohn's disease predominantly caused by genetic predisposition
- 2018
-
Ingår i: Journal of Crohn's & Colitis. - : Elsevier. - 1873-9946 .- 1876-4479. ; 12:10, s. 1200-1209
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aims: The aetiology of Crohn's disease is poorly understood. By investigating twin pairs discordant for Crohn's disease we aimed to assess if the dysregulated barrier represents a cause or a consequence of inflammation and to evaluate the impact of genetic predisposition on barrier function.Methods: Ileal biopsies from 15 twin pairs discordant for Crohn's disease (monozygotic n=9, dizygotic n=6) and 10 external controls were mounted in Ussing chambers to assess paracellular permeability to51Chromium (Cr)-EDTA and trancellular passage to non-pathogenic E. coli K-12. Experiments were performed with and without provocation with acetylsalicylic acid. Immunofluorescence and ELISA were used to quantify the expression level of tight junction proteins.Results: Healthy co-twins and affected twins displayed increased 51Cr-EDTA permeability at 120 min both with Acetylsalicylic acid (p<0.001) and without (p<0.001) when compared to controls. A significant increase in 51Cr-EDTA flux was seen already at 20 minutes in healthy monozygotic co-twins compared to controls (p≤0.05) when stratified by zygosity, but not in healthy dizygotic co-twins. No difference in E. coli passage was observed between groups. Immunofluorescence of the tight junction proteins claudin-5 and tricellulin showed lower levels in healthy co-twins (p<0.05) and affected twins (p<0.05) compared to external controls, while ELISA only showed lower tricellulin in Crohn's disease twins (p<0.05).Conclusion: Our results suggest that barrier dysfunction is a primary defect in Crohn's disease, since changes were predominantly seen in healthy monozygotic co-twins. Passage of E. coli seems to be a consequence of inflammation rather than representing a primary defect.
|
|
| 37. |
- Kidd-Ljunggren, Karin, et al.
(författare)
-
High levels of hepatitis B virus DNA in body fluids from chronic carriers.
- 2006
-
Ingår i: Journal of Hospital Infection. - : Elsevier BV. - 0195-6701. ; 64:4, s. 352-357
-
Tidskriftsartikel (refereegranskat)abstract
- infection with hepatitis B virus (HBV) is a major global health problem. Transmission is mainly blood-borne, although the route of infection during horizontal transmission in childhood is unclear. Nosocomial outbreaks of HBV have been widely reported, but have mainly focused on blood-borne transmission. There is Limited knowledge of the viral Load Levels in other body fluids. In the present study, chronic HBV carriers were tested for the presence of HBV DNA in serum, saliva, nasopharyngeal fluid, urine and tears by means of qualitative and quantitative polymerase chain reaction (PCR) methods. Twenty-five patients who were positive for HBV DNA with both PCRs were included. Low titres in real-time PCR corresponded with weak bands in the qualitative assay. HBV DNA was found in two urine samples, 10 saliva samples, five nasopharyngeal, swabs and in tear fluid from four patients. One highly viraemic HBeAg-positive carrier with serum HBV DNA Levels of 7 x 10(9) genome copies had high copy numbers detected in both saliva and nasopharyngeal fluid. These results demonstrate that highly viraemic HBV carriers may have high titres of HBV DNA in other body fluids. This has particular importance for infection control programmes and regulations, underlining the importance of aiming towards regular HBV DNA testing and thus infectivity assessment of chronic carriers in order to prevent transmission. (c) 2006 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.
|
|
| 38. |
- Larsson, Jonas Larsson, 1981-, et al.
(författare)
-
From Roll to Bag : D5.2 Final Product Construction Report
- 2016
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This is the final product construction report for the From Roll to Bag project. The purpose of this report is to present the implementation of the new pattern technology to selected products and to present the modularity for consumer selection. For fulfilling the tasks (5.1 and 5.2) two garments where chosen, one jacket and one shirt, and customization options regarding fit, model, colour and function were developed for each of them. This includes implementation of novel pattern technology to products, graphics, a product architecture with customisation options and initial production tests to verify perfect fit in production and later in use. The more challenging part was to guarantee manufacturability as the patterns require automated manufacturing equipment due to their detailed construction and the pattern matching. Such equipment includes a cutter with a scanner that identifies the outline of the printed pattern and cuts accoringly. If garments with less detailed graphics are considered for production, pre-dyed fabrics can be used and that requires less investments in manufacturing equipment. Such set up would miss one point of the project but in the tradeoff between investment cost and product price point it may be a viable solution. The garments and customization modules are also fit for production but in order to achieve a detailed production evaluation with exact production times and material consumption a long run of products is needed. Considerations about customer’s experiences in this type value chains are also discussed.
|
|
| 39. |
- Levinsen, Mette, et al.
(författare)
-
Pharmacogenetically Based Dosing of Thiopurines in Childhood Acute Lymphoblastic Leukemia: Influence on Cure Rates and Risk of Second Cancer
- 2014
-
Ingår i: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 61:5, s. 797-802
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundPrevious studies have indicated that patients with thiopurine methyltransferase (TPMT) low activity (TPMTLA) have reduced risk of relapse but increased risk of second malignant neoplasm (SMN) compared to patients with TPMT wild-type (TPMTWT) when treated with 6MP maintenance therapy starting doses of 75 mg/m2/day. To reduce SMN risk, 6MP starting doses were reduced to 50 mg/m2/day for patients with TPMT heterozygosity in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2000 protocol.ProcedureWe explored the pattern of SMN and relapse in the NOPHO ALL2000 protocol (n = 674) and NOPHO ALL92 protocol (n = 601) in relation to TPMT pheno- and/or genotype.ResultsThe overall risk of any event did not differ significantly between the two protocols. However, in event pattern analyses considering only the patients with TPMTLA who experienced relapse or SMN, the risk of SMN versus leukemia relapse was significantly lower in the ALL2000 cohort for patients with a 6MP starting dose <75 mg/m2/day when compared to the patients in ALL92 (relapse (n = 11) and SMN (n = 0) in ALL2000 versus relapse (n = 5) and SMN (n = 4) in ALL92, P = 0.03). Furthermore, the 8-year cumulative incidence of relapse for patients with TPMTLA was significantly higher in the ALL2000 compared to the ALL92 cohort (19.7% (11.6–33.3%) vs. 6.7% (2.9–15.5%), P = 0.03).ConclusionThis study indicates that reducing 6MP starting dose for patients with TPMTLA may reduce SMN risk but lead to a relapse risk similar to that of patients with TPMTWT.
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
- Lindblad, Sverker, 1946, et al.
(författare)
-
School lockdown? Comparative analyses of responses to the COVID-19 pandemic in European countries
- 2021
-
Ingår i: European Educational Research Journal. - : SAGE Publications. - 1474-9041. ; 20:5, s. 564-583
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of this article is to analyse how education and schooling took part in handling the early phase of the COVID-19 pandemic in eight European countries (Denmark, Finland, Germany, Greece, Italy, Norway, Poland and Sweden). The focus is on primary education and on decisions to close schools, or not. Our research was informed by assemblage theory in order to analyse how different components interacted in developing societal responses to mitigate the pandemic. The research was designed as a comparative case study of practical reasoning in diverse contexts. Data sources were the mass media and statements from governments and authorities. Our analyses showed that decisions to close schools, or not, were based on two alternative discourses on schooling. Closing primary schools was a preventive measure underlined by discourses of schools as places for infection. Keeping primary schools open was underlined by a discourse in which schools were conceived of as a place for social supportive measures and caring. Furthermore, the closing alternative was often combined with attempts to replace school practices by distance learning or computerized instruction. Legal constitutions and lawmaking were of significant importance in selecting discourses and the relative impact of different components, mostly political or medical, in responding to the pandemic.
|
|
| 43. |
- Lindqvist, Camilla, et al.
(författare)
-
Fullerene mixtures enhance the thermal stability of a non-crystalline polymer solar cell blend
- 2014
-
Ingår i: Applied Physics Letters. - : American Institute of Physics (AIP). - 0003-6951 .- 1077-3118. ; 104:15, s. 153301-
-
Tidskriftsartikel (refereegranskat)abstract
- Printing of polymer: fullerene solar cells at high speed requires annealing at temperatures up to 140 degrees C. However, bulk-heterojunction blends that comprise a non-crystalline donor polymer often suffer from insufficient thermal stability and hence rapidly coarsen upon annealing above the glass transition temperature of the blend. In addition, micrometer-sized fullerene crystals grow, which are detrimental for the solar cell performance. In this manuscript, we present a strategy to limit fullerene crystallization, which is based on the use of fullerene mixtures of the two most common derivatives, PC61BM and PC71BM, as the acceptor material. Blends of this fullerene mixture and a non-crystalline thiophene-quinoxaline copolymer display considerably enhanced thermal stability and largely retain their photovoltaic performance upon annealing at elevated temperatures as high as 170 degrees C.
|
|
| 44. |
- Lindqvist, Camilla, 1985, et al.
(författare)
-
Fullerene Nucleating Agents: A Route Towards Thermally Stable Photovoltaic Blends
- 2014
-
Ingår i: Advanced Energy Materials. - : Wiley. - 1614-6840 .- 1614-6832. ; 4:9, s. 1301437-
-
Tidskriftsartikel (refereegranskat)abstract
- The bulk-heterojunction nanostructure of non-crystalline polymer: fullerene blends has the tendency to rapidly coarsen when heated above its glass transition temperature, which represents an important degradation mechanism. We demonstrate that fullerene nucleating agents can be used to thermally arrest the nanostructure of photovoltaic blends that comprise a non-crystalline thiophene-quinoxaline copolymer and the widely used fullerene derivative [6,6]-phenyl-C-61-butyric acid methyl ester (PCBM). To this end, C-60 fullerene is employed to efficiently nucleate PCBM crystallization. Sub-micrometer-sized fullerene crystals are formed when as little as 2 wt% C-60 with respect to PCBM is added to the blend. These reach an average size of only 200 nanometers upon introduction of more than 8 wt% C-60. Solar cells based on C-60-nucleated blends indicate significantly improved thermal stability of the bulk-heterojunction nanostructure even after annealing at an elevated temperature of 130 degrees C, which lies above the glass transition temperature of the blend. Moreover, we find that various other compounds, including C-70 fullerene, single-walled carbon nanotubes, and sodium benzoate, as well as a number of commercial nucleating agents-commonly used to clarify isotactic polypropylene-permit to control crystallization of the fullerene phase.
|
|
| 45. |
|
|
| 46. |
- Lindqvist, C Mårten, et al.
(författare)
-
The Mutational Landscape in Pediatric Acute Lymphoblastic Leukemia Deciphered by Whole Genome Sequencing
- 2015
-
Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 36:1, s. 118-128
-
Tidskriftsartikel (refereegranskat)abstract
- Genomic characterization of pediatric acute lymphoblastic leukemia (ALL) has identified distinct patterns of genes and pathways altered in patients with well-defined genetic aberrations. To extend the spectrum of known somatic variants in ALL, we performed whole genome and transcriptome sequencing of three B-cell precursor patients, of which one carried the t(12;21)ETV6-RUNX1 translocation and two lacked a known primary genetic aberration, and one T-ALL patient. We found that each patient had a unique genome, with a combination of well-known and previously undetected genomic aberrations. By targeted sequencing in 168 patients, we identified KMT2D and KIF1B as novel putative driver genes. We also identified a putative regulatory non-coding variant that coincided with overexpression of the growth factor MDK. Our results contribute to an increased understanding of the biological mechanisms that lead to ALL and suggest that regulatory variants may be more important for cancer development than recognized to date. The heterogeneity of the genetic aberrations in ALL renders whole genome sequencing particularly well suited for analysis of somatic variants in both research and diagnostic applications.
|
|
| 47. |
|
|
| 48. |
- Lindqvist, Maria, et al.
(författare)
-
Genetic relatedness of multi-resistant methicillin-susceptible Staphylococcus aureus in southeast Sweden
- 2014
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: A high exchange of patients occurs between the hospitals in southeast Sweden, resulting in a possible transmission of nosocomial pathogens. The objective of this study was to investigate the incidence and possible genetic relatedness of multi-resistant methicillinsusceptible Staphylococcus aureus (MSSA) in the region in general, and in particular the possible persistence and transmission of the ECT-R clone (t002) showing resistance to erythromycin, clindamycin and tobramycin previously found in Östergötland County.Methods: Three groups of S. aureus isolates with different antibiotic resistance profiles, including the ECT-R profile, were collected from the three County Councils in southeast Sweden and investigated with spa typing, real-time PCR targeting the staphylococcal cassette chromosome (SCC) mec right extremity junction (MREJ), and microarray.Results: All isolates with the ECT-R resistance profile (n = 12) from Östergötland County and two additional isolates with another antibiotic resistance profile were designated spa type t002, MREJ type ii, and were clustered in the same clonal cluster (CC) (i.e. CC5) by the microarray result, indicating the persistence of the ECT-R clone. In addition, 60 % of the isolates belonged to CC15 from newborns, with 94 % sharing spa type t084, indicating interhospital transmission.Conclusions: The persistence of the ECT-R clone and the possible transmission of the t084 strain indicate that there is still an insufficiency in the maintenance of basic hygiene guidelines. The ECT-R clone probably possesses mechanisms of virulence and transmission that make it so successful.
|
|
| 49. |
- Lindqvist, Markus, et al.
(författare)
-
Plasma glycosylphosphatidylinositol phospholipase D (GPI-PLD) and abdominal aortic aneurysm.
- 2012
-
Ingår i: International Journal of Clinical and Experimental Medicine. - 1940-5901. ; 5:4, s. 306-9
-
Tidskriftsartikel (refereegranskat)abstract
- Recent reviews state that a circulating biomarker predicting aortic rupture risk would be a powerful tool to stratify patients with small screen-detected abdominal aortic aneurysm (AAA). In a current proteomic pilot-study elevated levels of the enzyme Glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) was shown in patients with small AAA compared with controls without aneurysm. In the present study we investigated the impact of plasma GPI-PLD as a biomarker in patients with AAA in relation to aneurysm size, and rupture. Plasma GPI-PLD was measured in patients with AAA (nonruptured, n=78 and ruptured, n=55) and controls without aneurysm (n=41) matched by age, sex and smoking habit. The plasma GPI-PLD levels were significantly lower in patients with ruptured compared nonruptured AAA which we interpreted as a result of hemodilution due to hemorrhage in patients with ruptured AAA. The plasma GPI-PLD levels were similar in patients with nonruptured AAA compared to the controls without aneurysm. Furthermore, there was no correlation between plasma GPI-PLD and aneurysm size in the group of patients with nonruptured AAA. In conclusion, the present study fails to show a connection between GPI-PLD and AAA. However, the definite role of GPI-PLD as a predictive marker needs to be further clarified in a follow-up cohort study.
|
|
| 50. |
- Lindqvist, Markus, et al.
(författare)
-
Soluble urokinase plasminogen activator receptor in patients with abdominal aortic aneurysm
- 2012
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 130:3, s. 511-513
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: In the present study we investigated the impact of soluble urokinase plasminogen activator receptor (suPAR) as a biomarker in patients with abdominal aortic aneurysm (AAA) in relation to conventional inflammatory markers, aneurysm size, and rupture. Methods: suPAR and conventional inflammatory markers were measured in 119 patients with AAA and 36 controls without aneurysm matched by age, gender and smoking habit. Results: The results support earlier studies suggesting a state of activated inflammatory response in patients with nonruptured AAA as expressed by elevated CRP and IL-6 compared with the controls. In contrast, suPAR showed similar levels in patients with nonruptured AAA compared with the controls. Unexpectedly, all follow-up patients (n = 16) have significant (p<0.001) elevated suPAR levels three years postoperatively compared preoperatively. Conclusions: suPAR does not seem to be a useful biomarker in the AAA disease. The role of the postoperative elevation of suPAR needs to be further elucidated. (C) 2012 Elsevier Ltd. All rights reserved.
|
|
