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1.	Hess, Timo, et al. (författare) Dissecting the genetic heterogeneity of gastric cancer 2023 Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 92 Tidskriftsartikel (refereegranskat)abstract Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO.
2.	Andersson, Leif, et al. (författare) ZBED6 : the birth of a new transcription factor in the common ancestor of placental mammals 2010 Ingår i: Transcription. - : Informa UK Limited. - 2154-1272 .- 2154-1264. ; 1:3, s. 144-148 Tidskriftsartikel (refereegranskat)abstract A DNA transposon integrated into -the genome of a primitive mammal some 200 million years ago and, millions of years later, it evolved an essential function in the common ancestor of all placental mammals. This protein, now named ZBED6, was recently discovered because a mutation disrupting one of its binding sites, in an intron of the IGF2 gene, makes pigs grow more muscle. These findings have revealed a new mechanism for regulating muscle growth as well as a novel transcription factor that appears to be of major importance for transcriptional regulation in placental mammals.
3.	Berglund, Lisa, et al. (författare) Glucose-Dependent Insulinotropic Polypeptide (GIP) Stimulates Osteopontin Expression in the Vasculature via Endothelin-1 and CREB. 2016 Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 65:1, s. 239-254 Tidskriftsartikel (refereegranskat)abstract Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with extrapancreatic effects beyond glycemic control. Here we demonstrate unexpected effects of GIP signaling in the vasculature. GIP induces the expression of the pro-atherogenic cytokine osteopontin (OPN) in mouse arteries, via local release of endothelin-1 (ET-1) and activation of cAMP response element binding protein (CREB). Infusion of GIP increases plasma OPN levels in healthy individuals. Plasma ET-1 and OPN levels are positively correlated in patients with critical limb ischemia. Fasting GIP levels are higher in individuals with a history of cardiovascular disease (myocardial infarction, stroke) when compared to controls. GIP receptor (GIPR) and OPN mRNA levels are higher in carotid endarterectomies from patients with symptoms (stroke, transient ischemic attacks, amaurosis fugax) than in asymptomatic patients; and expression associates to parameters characteristic of unstable and inflammatory plaques (increased lipid accumulation, macrophage infiltration and reduced smooth muscle cell content). While GIPR expression is predominantly endothelial in healthy arteries from human, mouse, rat and pig; remarkable up-regulation is observed in endothelial and smooth muscle cells upon culture conditions yielding a "vascular disease-like" phenotype. Moreover, a common variant rs10423928 in the GIPR gene associated with increased risk of stroke in type 2 diabetes patients.
4.	Bericat Vadell, Robert, et al. (författare) Single-electron transfer reactions on surface-modified gold plasmons 2023 Ingår i: Materials Today Chemistry. - : Elsevier. - 2468-5194. ; 34 Tidskriftsartikel (refereegranskat)abstract Photoredox catalysis's relevance in organic synthesis research and innovation will increase in the coming decades. However, the processes rely almost exclusively on expensive noble metal complexes, most notably iridium complexes, to absorb light and transfer a single charge to a substrate or a catalyst to initiate cascade transformations. Light-triggered plasmon resonances generate a non-Fermi-Dirac energy distribution with many hot carriers that decay in similar to 1 ps. Their ultrafast relaxation makes performing single electron transfer (SET) transformations challenging. Herein, a novel photosystem is proposed based on surface-modified gold nanoparticles (aka plasmon "molecularization"), which improved charge separation and, more importantly, enabled SET reactions, expanding the portfolio of photocatalysts available for photoredox catalysis. The photosystem was made into an electrode, permitting its use in photoelectrochemical arrangements that leverage electro- and photo-chemical approaches' benefits and chemical engineering solutions, helping the synthetic chemistry efforts towards greener synthesis and synthesis of more complex structures on a scale.
5.	Eriksson, D, et al. (författare) Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease 2016 Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 595-608 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.
6.	Eriksson K., Susanna, et al. (författare) Geometrical and energetical structural changes in organic dyes for dye-sensitized solar cells probed using photoelectron spectroscopy and DFT 2016 Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 18:1, s. 252-260 Tidskriftsartikel (refereegranskat)abstract The effects of alkoxy chain length in triarylamine based donor acceptor organic dyes are investigated with respect to the electronic and molecular surface structures on the performance of solar cells and the electron lifetime. The dyes were investigated when adsorbed on TiO2 in a configuration that can be used for dye sensitized solar cells (DSCs). Specifically, the two dyes D35 and D45 were compared using photoelectron spectroscopy (PES) and density functional theory (DFT) calculations. The differences in solar cell characteristics when longer alkoxy chains are introduced in the dye donor unit are attributed to geometrical changes in dye packing while only minor differences were observed in the electronic structure. A higher dye load was observed for D45 on TiO2. However, D35 based solar cells result in higher photocurrent although the dye load is lower. This is explained by different geometrical structures of the dyes on the surface.
7.	Hirvikoski, Tatja, et al. (författare) Cognitive functions in children at risk for congenital adrenal hyperplasia treated prenatally with dexamethasone 2007 Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:2, s. 542-548 Tidskriftsartikel (refereegranskat)abstract Context and Objective: In Sweden, from 1985 through 1995, 40 fetuses at risk for congenital adrenal hyperplasia (CAH) were treated with dexamethasone (DEX) to prevent virilization of affected females. We report long-term effects on neuropsychological functions and scholastic performance of this controversial treatment. Design and Patients: Prenatally treated children, 7 to 17 yr old, were assessed with standardized neuropsychological tests (A Developmental Neuropsychological Assessment and Wechsler Intelligence Scales for Children) and child-completed questionnaires measuring self-perceived scholastic competence (Self-Perception Profile for Children). A parent-completed questionnaire (Child Behavior Checklist/4-18 School Scale) was used to evaluate whether the treatment had any impact on the children's school performance. In addition, a child-completed questionnaire measuring social anxiety (The Social Anxiety Scale for Children-Revised) was completed by the prenatally treated children aged 8 to 17 yr (n = 21) and age- and sex-matched controls (n = 26). Results: Of 40 DEX-treated children, 26 (median age, 11 yr) participated in the study. Thirty-five sex- and age- matched healthy children were controls. There were no between-group differences concerning psychometric intelligence, measures of cerebral lateralization, memory encoding, and long-term memory. Short-term treated, CAH-unaffected children performed poorer than the control group on a test assessing verbal working memory (P = 0.003), and they rated lower on a questionnaire assessing self-perception of scholastic competence (P = 0.003). This group also showed increased self-rated social anxiety assessed by The Social Anxiety Scale for Children-Revised (P = 0.026). Prenatally treated, CAH-affected children performed poorer than controls on tests measuring verbal processing speed, although this difference disappeared when controlling for the child's full-scale IQ. Conclusions: This study indicates that prenatal DEX treatment is associated with previously not described long-term effects on verbal working memory and on certain aspects of self-perception that could be related to poorer verbal working memory. These findings may thus question future DEX treatment of congenital adrenal hyperplasia. Therefore, we encourage additional retrospective studies of larger cohorts to either confirm or challenge the present findings.
8.	Hirvikoski, Tatja, et al. (författare) Long-term effects of prenatal treatment with glucocorticoids in CAH 2006 Konferensbidrag (refereegranskat)
9.	Hirvikoski, Tatja, et al. (författare) Prenatal Dexametasone treatment of children at risk for congenital adrenal hyperplasia affects cognitive functions. 2007 Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. ; 92 Tidskriftsartikel (refereegranskat)abstract In Sweden, during 1985-1995, 40 foetuses at risk for congenital adrenal hyperplasia (CAH) were treated with dexamethasone (DEX) in order to prevent virilisation of affected females. We report long-term effects on neuropsychological functions and scholastic performance of this controversial treatment.Prenatally treated children, 7-17 years, were assessed with standardized neuropsychological tests (NEPSY and WISC-III) and child-completed questionnaires measuring self-perceived scholastic competence (SPPC). A parent-completed questionnaire (CBCL/4-18 School Scale) was used to evaluate whether the treatment had any impact on the children’s school performance.Of 40 DEX treated children, 26 (median age 11 years) participated in the study. Thirty-five sex- and age matched healthy children were controls. There were no between-group differences concerning psychometric intelligence, measures of cerebral lateralization, memory encoding, and long term memory. Short term treated, CAH unaffected children performed worse than the control group on a test assessing verbal working memory (p=0.003), and on self-perception of scholastic competence (p=0.003). Prenatally treated, CAH affected children performed poorer than controls on tests measuring verbal processing speed, although this difference disappeared when controlling for the child’s Full-Scale IQ (FSIQ).This study indicates that prenatal DEX treatment is associated with previously not described long-term effects on verbal working memory and certain aspects of self-perception that could be related to poorer verbal working memory. These findings may thus question future DEX treatment of congenital adrenal hyperplasia. Therefore, we encourage additional retrospective studies of larger cohorts to either confirm or challenge the present findings.
10.	Jamehammar, Anna, et al. (författare) Miljöstyrd produktutveckling – Tillämpning inom snickeriindustrin 2004 Rapport (övrigt vetenskapligt/konstnärligt)
11.	Kalha, Curran, et al. (författare) Hard x-ray photoelectron spectroscopy : a snapshot of the state-of-the-art in 2020 2021 Ingår i: Journal of Physics. - : Institute of Physics Publishing (IOPP). - 0953-8984 .- 1361-648X. ; 33:23 Forskningsöversikt (refereegranskat)abstract Hard x-ray photoelectron spectroscopy (HAXPES) is establishing itself as an essential technique for the characterisation of materials. The number of specialised photoelectron spectroscopy techniques making use of hard x-rays is steadily increasing and ever more complex experimental designs enable truly transformative insights into the chemical, electronic, magnetic, and structural nature of materials. This paper begins with a short historic perspective of HAXPES and spans from developments in the early days of photoelectron spectroscopy to provide an understanding of the origin and initial development of the technique to state-of-the-art instrumentation and experimental capabilities. The main motivation for and focus of this paper is to provide a picture of the technique in 2020, including a detailed overview of available experimental systems worldwide and insights into a range of specific measurement modi and approaches. We also aim to provide a glimpse into the future of the technique including possible developments and opportunities.
12.	Keen, Christina, et al. (författare) Supplementation With Fatty Acids Influences the Airway Nitric Oxide and Inflammatory Markers in Patients With Cystic Fibrosis 2010 Ingår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - 0277-2116 .- 1536-4801. ; 50:5, s. 537-544 Tidskriftsartikel (refereegranskat)abstract Objectives: To obtain a balance in the fatty acid (FA) metabolism is important for the inflammatory response and of special importance in cystic fibrosis (CF), which is characterized by impaired FA metabolism, chronic inflammation, and infection in the airways. Nitric oxide (NO) has antimicrobial properties and low nasal (nNO) and exhaled NO (FENO), commonly reported in CF that may affect bacterial status. The present study investigates the effect of different FA blends on nNO and FENO and immunological markers in patients with CF. Patients and Methods: Forty-three patients with CF and "severe" mutations were consecutively enrolled in a randomized double-blind placebo-controlled study with 3 FA blends containing mainly n-3 or n-6 FA or saturated FA acting as placebo. FENO, nNO, serum phospholipid concentrations of FA, and biomarkers of inflammation were measured before and after 3 months of supplementation. Results: Thirty-five patients in clinically stable condition completed the study. The serum phospholipid FA pattern changed significantly in all 3 groups. An increase of the n-6FA, arachidonic acid, was associated with a decrease of FENO and nNO. The inflammatory biomarkers, erythrocyte sedimentation rate, and interleukin-8 decreased after supplementation with n-3 FA and erythrocyte sedimentation rate increased after supplementation with n-6 FA. Conclusions: This small pilot study indicated that the composition of dietary n-3 and n-6 FA influenced the inflammatory markers in CF. FENO and nNO were influenced by changes in the arachidonic acid concentration, supporting previous studies suggesting that both the lipid abnormality and the colonization with Pseudomonas influenced NO in the airways.
13.	Lindehammer, Sabina, et al. (författare) Temporal trends of HLA genotype frequencies of type 1 diabetes patients in Sweden from 1986 to 2005 suggest altered risk 2008 Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 45:4, s. 231-5 Tidskriftsartikel (refereegranskat)abstract The aim of this study was to compare the frequency of human leukocyte antigen (HLA) genotypes in 1-18-year-old patients with type 1 diabetes newly diagnosed in 1986-1987 (n = 430), 1996-2000 (n = 342) and in 2003-2005 (n = 171). We tested the hypothesis that the HLA DQ genotype distribution changes over time. Swedish type 1 diabetes patients and controls were typed for HLA using polymerase chain reaction amplification and allele specific probes for DQ A1* and B1* alleles. The most common type 1 diabetes HLA DQA1-B1genotype 0501-0201/0301-0302 was 36% (153/430) in 1986-1987 and 37% (127/342) in 1996-2000, but decreased to 19% (33/171) in 2003-2005 (P \ 0.0001). The 0501-0201/0501-0201 genotype increased from 1% in 1986-1987 to 7% in 1996-2000 (P = 0.0047) and to 5% in 2003-2005 (P > 0.05). This study in 1-18-year-old Swedish type 1 diabetes patients supports the notion that there is a temporal change in HLA risk.
14.	Montgomery, Anna, 1974- (författare) Counselling in Swedish Community Pharmacies : Understanding the Process of a Pharmaceutical Care Service 2009 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Community pharmacy practice is moving towards patient care and away from the mere dispensing of medicines. In this movement, which is guided by the philosophy of Pharmaceutical care (PC), new counselling services emerge. The purpose of the thesis was to add knowledge about the real-world provision of PC services by studying a defined PC service in Swedish pharmacies. Specific aims of this thesis were to investigate the experiences of professionals working with or close to the service and to describe the content of consultations, counselling behaviour and patterns of follow-up. Further aims were to characterise patients receiving the service and describe their perceived outcomes, in relation to standard service. Data were collected via focus groups, telephone interviews, observations, a patient medication record database and a cross-sectional survey. The practitioners reported greater use of their pharmaceutical knowledge and provision of more thorough patient support. Perceived barriers in delivering the service included difficulties in documenting and getting commitment from colleagues, managers and prescribers. Doctors working close to PC pharmacies held varying opinions about the service. Consultations dealt with issues potentially improving the outcomes of medical treatment, but the level of patient centredness varied and was limited by the practitioners’ focus on the computer screen. The rate of follow-up evaluations was modest, but was higher at pharmacies with a high volume of patients receiving the service. PC patients were mostly elderly and female, using about 10 prescription drugs. In comparison to patients receiving standard service, they were more worried, vulnerable and information-seeking. At the same time, their feelings of safety following the pharmacy visit were more pronounced than those of patients receiving standard service. They also felt better prepared for doctor visits. In order for community pharmacy to better meet patients’ needs and optimise PC services, increased attention should be given to implementation strategies, interprofessional collaboration and educational efforts focusing on patient centredness.
15.	Wallander, Karin, et al. (författare) Sensitive Detection of Cell-Free Tumour DNA Using Optimised Targeted Sequencing Can Predict Prognosis in Gastro-Oesophageal Cancer 2023 Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 15:4, s. 1160- Tidskriftsartikel (refereegranskat)abstract Simple Summary Cancer in the stomach and oesophagus is deadly when discovered at a late stage. There are no good biomarkers for its detection or for making a prognostic prediction. In this study, we evaluate the analysis of cell-free DNA as a prognostic cancer biomarker. Cell-free DNA is DNA released from any tissue to a body fluid. When there is a tumour in the body, some of the cell-free DNA will come from that tumour, and it can be detected in a blood sample. We show that the detection of cell-free DNA from the cancer correlates to a worse prognosis than when no tumour DNA is detected. We also show that the method of analysis is important. Either a tissue biopsy must be included as a validation of the genetic variants detected or analysis of the blood cells or another blood sample after tumour resection needs to be analysed to improve detection. In this longitudinal study, cell-free tumour DNA (a liquid biopsy) from plasma was explored as a prognostic biomarker for gastro-oesophageal cancer. Both tumour-informed and tumour-agnostic approaches for plasma variant filtering were evaluated in 47 participants. This was possible through sequencing of DNA from tissue biopsies from all participants and cell-free DNA from plasma sampled before and after surgery (n = 42), as well as DNA from white blood cells (n = 21) using a custom gene panel with and without unique molecular identifiers (UMIs). A subset of the plasma samples (n = 12) was also assayed with targeted droplet digital PCR (ddPCR). In 17/31 (55%) diagnostic plasma samples, tissue-verified cancer-associated variants could be detected by the gene panel. In the tumour-agnostic approach, 26 participants (59%) had cancer-associated variants, and UMIs were necessary to filter the true variants from the technical artefacts. Additionally, clonal haematopoietic variants could be excluded using the matched white blood cells or follow-up plasma samples. ddPCR detected its targets in 10/12 (83%) and provided an ultra-sensitive method for follow-up. Detectable cancer-associated variants in plasma correlated to a shorter overall survival and shorter time to progression, with a significant correlation for the tumour-informed approaches. In summary, liquid biopsy gene panel sequencing using a tumour-agnostic approach can be applied to all patients regardless of the presence of a tissue biopsy, although this requires UMIs and the exclusion of clonal haematopoietic variants. However, if sequencing data from tumour biopsies are available, a tumour-informed approach improves the value of cell-free tumour DNA as a negative prognostic biomarker in gastro-oesophageal cancer patients.
16.	Abrahamsson, Anna, et al. (författare) Real world data on primary treatment for mantle cell lymphoma: a Nordic Lymphoma Group observational study. 2014 Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 124:8, s. 1288-1295 Tidskriftsartikel (refereegranskat)abstract There is consensus that young patients with mantle cell lymphoma (MCL) should receive intensive immunochemotherapy regimens, but optimal treatment of elderly patients as well for as patients with limited or indolent disease is not defined. Our aim was to evaluate and compare outcome in relation to prognostic factors and first-line treatment in patients with MCL in a population-based data set. Data were collected from the Swedish and Danish Lymphoma Registries from the period of 2000-2011. A total of 1389 patients were diagnosed with MCL. During this period, age-standardized incidence MCL increased, most prominently among males. Furthermore, male gender was associated with inferior overall survival (OS) in multivariate analysis (HR 1.36; p=0.002). Forty-three (3.6%) patients with stage I-II disease received radiotherapy with curative intent, showing a 3 year OS of 93%. Twenty-nine (2.4%) patients followed a watch-and-wait approach and showed a 3 year OS of 79.8%. Among patients receiving systemic treatment, rituximab (n=766; HR 0.66; p=0.001) and autologous stem cell transplant (ASCT) (n=273; HR 0.55; p=0.004) were independently associated with improved overall survival in multivariate analysis. Hence, by a population-based approach, we were able to provide novel data on prognostic factors and primary treatment of MCL, applicable to routine clinical practice.
17.	Ahlgren, Kerstin. M, et al. (författare) Diabetes mellitus in dog - : No evidence for a type-1-like phenotype Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Aims/hypothesis Diabetes mellitus (DM) is one of the most common endocrine disorders in dogs, and is commonly proposed to be of autoimmune origin. Although the clinical symptoms of human type 1 diabetes (T1D) and canine DM are similar, the aetiologies may differ. The aim of this study was to investigate if autoimmune aetiology resembling human T1D is as prevalent in dogs as previously reported. Methods Sera from 121 diabetic dogs representing 38 different breeds were tested for islet cell antibodies (ICA) and GAD65 autoantibodies (GADA) and compared with sera from 133 healthy dogs from 40 breeds. ICA was detected by indirect immunofluorescence using both canine and human frozen sections. GADA was detected by in vitro transcription and translation (ITT) of human and canine GAD65, followed by immunoprecipitation. Results None of the canine sera analyzed tested positive for ICA on sections of frozen canine or human ICA pancreas. However, serum from one diabetic dog was weakly positive in the canine GADA assay and serum from one healthy dog was weakly positive in the human GADA assay. Conclusions/interpretations Based on sera from 121 diabetic dogs from 38 different breeds were tested for humoral autoreactivity using four different assays, contrary to previous observations, we find no support for an autoimmune aetiology in canine diabetes.
18.	Ahlgren, Kerstin M. (författare) Immunological Studies using Human and Canine Model Disorders 2011 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The studies presented in this thesis focus on human and canine models for autoimmune disease, with the main aim to gain new knowledge about disease mechanisms and to further evaluate the dog as a model for autoimmune disease. Autoimmune Polyendocrine Syndrome type 1 (APS-1) is a hereditary human multiorgan disease caused by mutations in the autoimmune regulator (AIRE) gene. Hallmarks of APS-1 are chronic mucocutaneous candidiasis caused by Candida albicans, together with the autoimmune endocrine disorders hypoparathyroidism and adrenocortical failure. Many human diseases have an equivalent disease in dogs. Because humans share environment, and in part life style with the dogs they provide an interesting model for further genetic studies. Immune responses to Candida albicans in APS-1 patients displayed an increased secretion of the proinflammatory cytokine IL-17A and similar results were also found in AIRE deficient mice. Anticytokine autoantibodies to IL-17A, IL-17F and IL-22 were detected in APS-1 patients, and a radioligand binding assay for measuring these autoantibodies was developed and evaluated. In the canine studies we investigated whether canine diabetes mellitus could serve as a model for human autoimmune diabetes mellitus. Furthermore, we investigated type I IFN responses in Nova Scotia duck tolling retriever dogs with a systemic autoimmune disease resembling human SLE. Four assays were used in search for signs of humoral autoimmunity in diabetic dogs. However, no evidence for a type 1 diabetes-like phenotype in dogs was found. Sera from Nova Scotia duck tolling retrievers suffering from steroid-responsive meningitis arteritis elicited an increased expression of IFN-inducible genes in the canine MDCK cell line. This suggests that these dogs have an IFN signature, as seen in human SLE.
19.	Ahlgren, Kerstin M, et al. (författare) Lack of evidence for a role of islet autoimmunity in the aetiology of canine diabetes mellitus 2014 Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8, s. e105473- Tidskriftsartikel (refereegranskat)abstract AIMS/HYPOTHESIS:Diabetes mellitus is one of the most common endocrine disorders in dogs and is commonly proposed to be of autoimmune origin. Although the clinical presentation of human type 1 diabetes (T1D) and canine diabetes are similar, the aetiologies may differ. The aim of this study was to investigate if autoimmune aetiology resembling human T1D is as prevalent in dogs as previously reported.METHODS:Sera from 121 diabetic dogs representing 40 different breeds were tested for islet cell antibodies (ICA) and GAD65 autoantibodies (GADA) and compared with sera from 133 healthy dogs. ICA was detected by indirect immunofluorescence using both canine and human frozen sections. GADA was detected by in vitro transcription and translation (ITT) of human and canine GAD65, followed by immune precipitation. Sections of pancreata from five diabetic dogs and two control dogs were examined histopathologically including immunostaining for insulin, glucagon, somatostatin and pancreas polypeptide.RESULTS:None of the canine sera analysed tested positive for ICA on sections of frozen canine or human ICA pancreas. However, serum from one diabetic dog was weakly positive in the canine GADA assay and serum from one healthy dog was weakly positive in the human GADA assay. Histopathology showed marked degenerative changes in endocrine islets, including vacuolisation and variable loss of immune-staining for insulin. No sign of inflammation was noted.CONCLUSIONS/INTERPRETATIONS:Contrary to previous observations, based on results from tests for humoral autoreactivity towards islet proteins using four different assays, and histopathological examinations, we do not find any support for an islet autoimmune aetiology in canine diabetes mellitus.
20.	Ahlgren, Kerstin, M., et al. (författare) Type I Interferon signature in Nova Scotia duck tolling retriever dogs with steroid responsive meningitis-arteritis Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Objective: Dogs of the breed Nova Scotia duck tolling retriever (NSDTR) are prone to develop a disease complex in some aspects resembling human systemic lupus erythematosus (SLE). Peripheral blood mononuclear cells (PBMCs) from human SLE patients have an increased mRNA expression type I interferon (IFN) regulated genes. However, it is unknown whether diseased dogs also display the typical type I IFN signature. Methods: To test canine sera for their capacity to induce type I IFN response Mardin-Darby canine kidney (MDCK) cells were cultured with sera from healthy dogs (n=25), immune-mediated rheumatic disease (IMRD) dogs with anti-nuclear antibodies (ANA+) (n=30) or dogs with steroid responsive meningitis-arteritis (SRMA) (n=25). mRNA expression of the genes MX1, IFIT1 and CXCL10 was measured by quantitative Real Time PCR. Results: A highly significant (p=0.0009) increase in mRNA expression of the type I IFN responsive gene MX1 was detected in cells stimulated by sera from dogs with SRMA, but not from IMRD ANA+ dogs. Expression of IFIT1 was twice as high in cells stimulated by sera from dogs with SRMA compared to both healthy dogs and ANA+ dogs. The mean expression of CXCL10 was nearly ten times higher in cells stimulated by sera from SRMA dogs than by ANA+ dogs and four times higher compared to cells stimulated by control dogs. Conclusion: Presence of type I IFN in sera from diseased NSDTR dogs was found in this study. This implies that this canine model can be used for identification of pathways of importance for autoimmune disorders in humans and for testing of novel therapeutic approaches. Our results can also be a step on the way towards personalized drugs in these dogs.
21.	Albertsson-Lindblad, Alexandra, et al. (författare) Lenalidomide-bendamustine-rituximab in patients older than 65 years with untreated mantle cell lymphoma 2016 Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 128:14, s. 1814-1820 Tidskriftsartikel (refereegranskat)abstract For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter, open-label phase 1/2 trial, we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment for elderly patients with MCL. Patients >65 years with untreated MCL, stages II-IV were eligible for inclusion. Primary end points were maximally tolerable dose (MTD) of LEN and progression-free survival (PFS). Patients received 6 cycles every four weeks of L-B-R (L D1-14, B 90 mg/m(2) IV, days 1-2 and R 375 mg/m(2) IV, day 1) followed by single LEN (days 1-21, every four weeks, cycles 7-13). Fifty-one patients (median age 71 years) were enrolled from 2009 to 2013. In phase 1, the MTD of LEN was defined as 10 mg in cycles 2 through 6, and omitted in cycle 1. After 6 cycles, the complete remission rate (CRR) was 64%, and 36% were MRD negative. At a median follow-up time of 31 months, median PFS was 42 months and 3-year overall survival was 73%. Infection was the most common nonhematologic grade 3 to 5 event and occurred in 21 (42%) patients. Opportunistic infections occurred in 3 patients: 2 Pneumocystis carinii pneumonia and 1 cytomegalovirus retinitis. Second primary malignancies (SPM) were observed in 8 patients (16%). LEN could safely be combined with R-B when added from the second cycle in patients with MCL, and was associated with a high rate of CR and molecular remission. However, we observed a high degree of severe infections and an unexpected high number of SPMs, which may limit its use. This trial is registered at www.Clinicaltrials.gov as #NCT00963534.
22.	Albertsson-Lindblad, Alexandra, et al. (författare) Lenalidomide-bendamustine-rituximab in untreated mantle cell lymphoma > 65 years, the Nordic Lymphoma Group phase I+II trial NLG-MCL4 2016 Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 128:14, s. 1814-1820 Tidskriftsartikel (refereegranskat)abstract For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter open-label phase I/II trial we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment to elderly MCL patients. Patients >65 years with untreated MCL, stage II-IV were eligible for inclusion. Primary endpoints were maximally tolerable dose (MTD) of LEN, and progression-free survival (PFS). Patients received six cycles q4w of L-B-R (L D1-14, B 90 mg/m(2) iv D1-2 and R 375 mg/m(2) iv D1) followed by single LEN (D1-21, q4w, cycles 7-13). 51 patients (median age 71 years) were enrolled 2009-2013. In phase I, the MTD of LEN was defined as 10 mg in cycles 2-6, and omitted in cycle 1. After six cycles, the complete remission rate (CRR) was 64% and 36% were MRD negative. At a median follow-up time of 31 months, median PFS was 42 months and 3 year overall survival was 73%. Infection was the most common non-hematological grade 3-5 event and occurred in 21 (42%) patients. Opportunistic infections occurred in three patients; 2 PCP and 1 CMV retinitis. Second primary malignancies (SPM) were observed in eight patients (16%). LEN could safely be combined with R-B, when added from the second cycle in patients with MCL, and was associated with a high rate of CR and molecular remission. However, we observed a high degree of severe infections and an unexpected high number of SPMs which may limit its use. http://clinicaltrials.gov: NCT00963534.
23.	Amemiya, Chris T., et al. (författare) The African coelacanth genome provides insights into tetrapod evolution 2013 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 496:7445, s. 311-316 Tidskriftsartikel (refereegranskat)abstract The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution.
24.	Andersson, Johanna, et al. (författare) go: NEUTRAL 2014 Rapport (övrigt vetenskapligt/konstnärligt)abstract go: NEUTRAL är ett samarbete mellan Skanska, ÅF, Siemens, IVL Svenska Miljöinstitutet och Business Region Göteborg som syftar till att öka möjligheterna att utveckla energieffektiva och hållbara lösningar genom att få till en samverkan mellan olika aktörer i byggbranschen i ett tidigt skede. Det övergripande målet med förstudien är att börja utveckla, testa och tillämpa en modell för tidig samverkan i profilprojekt för innovativt hållbart byggande. Ett delmål är att definiera och utveckla vilka hållbarhetskriterier som ska gälla för samarbetet. Detta har utförts genom att utveckla ett koncept kring namnet go: NEUTRAL. I förstudien presenteras en preliminär utformning av mål för konceptet go: NEUTRAL bestående av ett övergripande mål och tre delmål. För att lyckas med samverkan kring hållbarhetsfrågor i byggprocessen krävs kunskap om hur man kan skapa förutsättningar för tidig samverkan. För att skaffa denna kunskap har följande sammanställningar utförts under förstudien: Kartläggning av olika aktörers motiv till tidig samverkan, Identifiering av hinder för tidig samverkan, samt Identifiering av områden som är viktiga att beakta för att skapa goda förutsättningar för tidig samverkan. Konceptet go: NEUTRAL är skapat och förutsättningar för samverkan är undersökta, men inte färdigutvecklat. Förstudiens plan för vidare arbete är uppdelad i tre områden: a) Fastställ ramar för samverkan mellan parter, b) vidareutveckla konceptet go: NEUTRAL, samt c) utveckla processen.
25.	Andersson, Johanna, et al. (författare) go: NEUTRAL - Förstudie 2014 Rapport (övrigt vetenskapligt/konstnärligt)abstract Inom byggbranschen har utvecklingen av energibesparande åtgärder och byggnation med material och komponenter som leder till lägre energianvändning, klimatpåverkan och resursbesparing påskyndats genom att medvetenheten om klimatfrågans betydelse och den byggda miljöns bidrag till de totala utsläppen har ökat. Exploateringsprojekt är begränsad i budget, bygger på samverkan mellan många aktörer och genomförs under stor tidspress. I dessa projekt används ofta beprövad och etablerade tekniska lösningar, vilket medför att utrymmet för innovationer begränsas och därmed att projektets potentiella bidrag till en hållbar stadsutveckling inte utnyttjas fullt ut. För att få till en samverkan mellan olika aktörer i ett tidigit skede, och därmed öka möjlighetena att utveckla energi- och klimateffektiva samt hållbara lösningar, initierade Skanska detta projekt som gavs nament go: NETURAL. Övriga medverkande aktörer i projektet är ÅF, Siemens, Business Region Göteborg och IVL Svenska Miljöinstitutet.
26.	Banbrytande ledare och forskare : vänbok till Lars Thomasson 2018 Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)
27.	Barone, Giovanni D., et al. (författare) Recent developments in the production and utilization of photosynthetic microorganisms for food applications 2023 Ingår i: Heliyon. - : Elsevier. - 2405-8440. ; 9:4 Forskningsöversikt (refereegranskat)abstract The growing use of photosynthetic microorganisms for food and food-related applications is driving related biotechnology research forward. Increasing consumer acceptance, high sustain-ability, demand of eco-friendly sources for food, and considerable global economic concern are among the main factors to enhance the focus on the novel foods. In the cases of not toxic strains, photosynthetic microorganisms not only provide a source of sustainable nutrients but are also potentially healthy. Several published studies showed that microalgae are sources of accessible protein and fatty acids. More than 400 manuscripts were published per year in the last 4 years. Furthermore, industrial approaches utilizing these microorganisms are resulting in new jobs and services. This is in line with the global strategy for bioeconomy that aims to support sustainable development of bio-based sectors. Despite the recognized potential of the microalgal biomass value chain, significant knowledge gaps still exist especially regarding their optimized production and utilization. This review highlights the potential of microalgae and cyanobacteria for food and food-related applications as well as their market size. The chosen topics also include advanced production as mixed microbial communities, production of high-value biomolecules, photopro-duction of terpenoid flavoring compounds, their utilization for sustainable agriculture, applica-tion as source of nutrients in space, and a comparison with heterotrophic microorganisms like yeast to better evaluate their advantages over existing nutrient sources. This comprehensive assessment should stimulate further interest in this highly relevant research topic.
28.	Berglund, Jonas, et al. (författare) Novel origins of copy number variation in the dog genome 2012 Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X .- 1474-7596. ; 13:8, s. R73- Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Copy number variants (CNVs) account for substantial variation between genomes and are a major source of normal and pathogenic phenotypic differences. The dog is an ideal model to investigate mutational mechanisms that generate CNVs as its genome lacks a functional ortholog of the PRDM9 gene implicated in recombination and CNV formation in humans. Here we comprehensively assay CNVs using high-density array comparative genomic hybridization in 50 dogs from 17 dog breeds and 3 gray wolves. RESULTS: We use a stringent new method to identify a total of 430 high-confidence CNV loci, which range in size from 9 kb to 1.6 Mb and span 26.4 Mb, or 1.08%, of the assayed dog genome, overlapping 413 annotated genes. Of CNVs observed in each breed, 98% are also observed in multiple breeds. CNVs predicted to disrupt gene function are significantly less common than expected by chance. We identify a significant overrepresentation of peaks of GC content, previously shown to be enriched in dog recombination hotspots, in the vicinity of CNV breakpoints. CONCLUSIONS: A number of the CNVs identified by this study are candidates for generating breed-specific phenotypes. Purifying selection seems to be a major factor shaping structural variation in the dog genome, suggesting that many CNVs are deleterious. Localized peaks of GC content appear to be novel sites of CNV formation in the dog genome by non-allelic homologous recombination, potentially activated by the loss of PRDM9. These sequence features may have driven genome instability and chromosomal rearrangements throughout canid evolution.
29.	Bergström, Staffan, et al. (författare) Utred självvalt livsslut 2016 Ingår i: Läkartidningen. - 0023-7205. ; 113:34-35 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
30.	Bianchi, Matteo, et al. (författare) Contribution of rare genetic variation to disease susceptibility in a large Scandinavian myositis cohort 2022 Ingår i: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 74:2, s. 342-352 Tidskriftsartikel (refereegranskat)abstract Objective Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of complex autoimmune conditions characterized by inflammation in skeletal muscle and extramuscular compartments, and interferon (IFN) system activation. We undertook this study to examine the contribution of genetic variation to disease susceptibility and to identify novel avenues for research in IIMs.Methods Targeted DNA sequencing was used to mine coding and potentially regulatory single nucleotide variants from ~1,900 immune-related genes in a Scandinavian case–control cohort of 454 IIM patients and 1,024 healthy controls. Gene-based aggregate testing, together with rare variant– and gene-level enrichment analyses, was implemented to explore genotype–phenotype relations.Results Gene-based aggregate tests of all variants, including rare variants, identified IFI35 as a potential genetic risk locus for IIMs, suggesting a genetic signature of type I IFN pathway activation. Functional annotation of the IFI35 locus highlighted a regulatory network linked to the skeletal muscle–specific gene PTGES3L, as a potential candidate for IIM pathogenesis. Aggregate genetic associations with AGER and PSMB8 in the major histocompatibility complex locus were detected in the antisynthetase syndrome subgroup, which also showed a less marked genetic signature of the type I IFN pathway. Enrichment analyses indicated a burden of synonymous and noncoding rare variants in IIM patients, suggesting increased disease predisposition associated with these classes of rare variants.Conclusion Our study suggests the contribution of rare genetic variation to disease susceptibility in IIM and specific patient subgroups, and pinpoints genetic associations consistent with previous findings by gene expression profiling. These features highlight genetic profiles that are potentially relevant to disease pathogenesis.
31.	Birzniece, Vita, et al. (författare) Neuroactive steroid effects on cognitive functions with a focus on the serotonin and GABA systems. 2006 Ingår i: Brain Research Reviews. - : Elsevier BV. - 0165-0173 .- 1872-6321. ; 51:2, s. 212-239 Tidskriftsartikel (refereegranskat)
32.	Blaxter, Mark, et al. (författare) Why sequence all eukaryotes? 2022 Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 119:4 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Life on Earth has evolved from initial simplicity to the astounding complexity we experience today. Bacteria and archaea have largely excelled in metabolic diversification, but eukaryotes additionally display abundant morphological innovation. How have these innovations come about and what constraints are there on the origins of novelty and the continuing maintenance of biodiversity on Earth? The history of life and the code for the working parts of cells and systems are written in the genome. The Earth BioGenome Project has proposed that the genomes of all extant, named eukaryotes-about 2 million species-should be sequenced to high quality to produce a digital library of life on Earth, beginning with strategic phylogenetic, ecological, and high-impact priorities. Here we discuss why we should sequence all eukaryotic species, not just a representative few scattered across the many branches of the tree of life. We suggest that many questions of evolutionary and ecological significance will only be addressable when whole-genome data representing divergences at all of the branchings in the tree of life or all species in natural ecosystems are available. We envisage that a genomic tree of life will foster understanding of the ongoing processes of speciation, adaptation, and organismal dependencies within entire ecosystems. These explorations will resolve long-standing problems in phylogenetics, evolution, ecology, conservation, agriculture, bioindustry, and medicine.
33.	Bogatikov, Evgenii, et al. (författare) miR-1933-3p is upregulated in skeletal muscles of MuSK+ EAMG mice and affects Impa1 and Mrpl27 2020 Ingår i: Neuroscience research. - : Elsevier BV. - 0168-0102 .- 1872-8111. ; 151, s. 46-52 Tidskriftsartikel (refereegranskat)abstract MuSK antibody seropositive (MuSK+) Myasthenia Gravis (MG) typically affects skeletal muscles of the bulbar area, including the omohyoid muscle, causing focal fatigue, weakness and atrophy. The profile of circulating extracellular microRNA (miRNA) is changed in MuSK + MG, but the intracellular miRNA profile in skeletal muscles of MuSK + MG and MuSK + experimental autoimmune MG (EAMG) remains unknown. This study elucidated the intracellular miRNA profile in the omohyoid muscle of mice with MuSK + EAMG. The levels of eleven mouse miRNAs were elevated and two mouse miRNAs were reduced in muscles of MuSK + EAMG mice. Transient expression of miR-1933-3p and miR-1930-5p in mouse muscle (C2C12) cells revealed several downregulated genes, out of which five had predicted binding sites for miR-1933-3p. The mRNA expression of mitochondrial ribosomal protein L27 (Mrpl27) and Inositol monophosphatase I (Impa1) was reduced in miR-1933-3p transfected C2C12 cells compared to control cells (p = 0.032 versus p = 0.020). Further, transient expression of miR-1933-3p reduced Impa1 protein accumulation in C2C12 cells. These findings provide novel insights of dysregulated miRNAs and their intracellular pathways in muscle tissue afflicted with MuSK + EAMG, providing a possible link to mitochondrial dysfunction and muscle atrophy observed in MuSK + MG.
34.	Brown, Anna-Leigh, et al. (författare) TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A 2022 Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 603, s. 131-137 Tidskriftsartikel (refereegranskat)abstract Variants of UNC13A, a critical gene for synapse function, increase the risk of amyotrophic lateral sclerosis and frontotemporal dementia1,2,3, two related neurodegenerative diseases defined by mislocalization of the RNA-binding protein TDP-434,5. Here we show that TDP-43 depletion induces robust inclusion of a cryptic exon in UNC13A, resulting in nonsense-mediated decay and loss of UNC13A protein. Two common intronic UNC13A polymorphisms strongly associated with amyotrophic lateral sclerosis and frontotemporal dementia risk overlap with TDP-43 binding sites. These polymorphisms potentiate cryptic exon inclusion, both in cultured cells and in brains and spinal cords from patients with these conditions. Our findings, which demonstrate a genetic link between loss of nuclear TDP-43 function and disease, reveal the mechanism by which UNC13A variants exacerbate the effects of decreased TDP-43 function. They further provide a promising therapeutic target for TDP-43 proteinopathies.
35.	Bäckström, Torbjörn, 1948-, et al. (författare) Pathogenesis in menstrual cycle-linked CNS disorders. 2003 Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1007, s. 42-53 Forskningsöversikt (övrigt vetenskapligt/konstnärligt)
36.	Ching, Yung-Hao, et al. (författare) High resolution mapping and positional cloning of ENU-induced mutations in the Rw region of mouse chromosome 5 2010 Ingår i: BMC Genetics. - : Springer Science and Business Media LLC. - 1471-2156. ; 11, s. 106- Tidskriftsartikel (refereegranskat)abstract Background: Forward genetic screens in mice provide an unbiased means to identify genes and other functional genetic elements in the genome. Previously, a large scale ENU mutagenesis screen was conducted to query the functional content of a similar to 50 Mb region of the mouse genome on proximal Chr 5. The majority of phenotypic mutants recovered were embryonic lethals. Results: We report the high resolution genetic mapping, complementation analyses, and positional cloning of mutations in the target region. The collection of identified alleles include several with known or presumed functions for which no mutant models have been reported (Tbc1d14, Nol14, Tyms, Cad, Fbxl5, Haus3), and mutations in genes we or others previously reported (Tapt1, Rest, Ugdh, Paxip1, Hmx1, Otoe, Nsun7). We also confirmed the causative nature of a homeotic mutation with a targeted allele, mapped a lethal mutation to a large gene desert, and localized a spermiogenesis mutation to a region in which no annotated genes have coding mutations. The mutation in Tbc1d14 provides the first implication of a critical developmental role for RAB-GAP-mediated protein transport in early embryogenesis. Conclusion: This collection of alleles contributes to the goal of assigning biological functions to all known genes, as well as identifying novel functional elements that would be missed by reverse genetic approaches.
37.	Clark, Andrew G., et al. (författare) Evolution of genes and genomes on the Drosophila phylogeny 2007 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218 Tidskriftsartikel (refereegranskat)abstract Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
38.	Cornelissen, Johannes H C, et al. (författare) Global negative vegetation feedback to climate warming responses of leaf litter decomposition rates in cold biomes 2007 Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 10:7, s. 619-627 Tidskriftsartikel (refereegranskat)abstract Whether climate change will turn cold biomes from large long-term carbon sinks into sources is hotly debated because of the great potential for ecosystem-mediated feedbacks to global climate. Critical are the direction, magnitude and generality of climate responses of plant litter decomposition. Here, we present the first quantitative analysis of the major climate-change-related drivers of litter decomposition rates in cold northern biomes worldwide.Leaf litters collected from the predominant species in 33 global change manipulation experiments in circum-arctic-alpine ecosystems were incubated simultaneously in two contrasting arctic life zones. We demonstrate that longer-term, large-scale changes to leaf litter decomposition will be driven primarily by both direct warming effects and concomitant shifts in plant growth form composition, with a much smaller role for changes in litter quality within species. Specifically, the ongoing warming-induced expansion of shrubs with recalcitrant leaf litter across cold biomes would constitute a negative feedback to global warming. Depending on the strength of other (previously reported) positive feedbacks of shrub expansion on soil carbon turnover, this may partly counteract direct warming enhancement of litter decomposition.
39.	Dahlqvist, Johanna, 1979-, et al. (författare) Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA 2022 Ingår i: Rheumatology. - Oxford, United Kingdom : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:8, s. 3461-3470 Tidskriftsartikel (refereegranskat)abstract Objective To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV). Methods Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay. Results PR3-ANCA(+) AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 x 10(-61), odds ratio (OR) 0.10; rs9277341, P = 1.5 x 10(-44), OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 x 10(-10), OR 2.9). MPO-ANCA(+) AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 x 10(-25), OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 x 10(-7), OR 3.0), the latter a novel susceptibility locus for MPO-ANCA(+) granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele. Conclusion We identified a novel susceptibility locus for MPO-ANCA(+) AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types.
40.	Dalen, Monica, et al. (författare) Educational attainment and cognitive competence in adopted men : A study of international and national adoptees, siblings and a general Swedish population 2008 Ingår i: Children and youth services review. - : Elsevier BV. - 0190-7409 .- 1873-7765. ; 30:10, s. 1211-1219 Tidskriftsartikel (refereegranskat)abstract Internationally and nationally adopted young men were recently reported to have lower than average scores on intelligence tests at military conscription, compared with non-adopted conscripts in Sweden. In this study we used the Swedish national registers to analyse how this lower cognitive competence influences the educational attainment of adoptees. Intelligence test scores at conscription were analysed in relation to educational attainment at follow-up at 25-34 years in male international (n = 2.314) and national (n = 1.153) adoptees, compared with the general population in the same birth cohorts.Korean adoptees more often had obtained a post-secondary education compared with the general population while Non-Korean and national adoptees less often had such an education at follow-up. The international adoptees had a better chance than the general population to complete a post-secondary level and a lower risk to remain at a basic level when their cognitive competence, as measured by intelligence test scores, had been accounted for. This effect was quite similar in biological children in families of international adoptees who had the best test scores, in the Korean adoptees who had slightly better test scores than the general population, and in the Non-Korean adoptees who had considerably lower test scores. National adoptees had similar outcomes in these respects as the general population when test scores had been accounted for. Higher age at adoption was associated with a lower educational attainment in the Non-Korean but not in the Korean adoptees, an effect that was attenuated when test scores were accounted for.We conclude that a lower than average cognitive competence did influence the educational attainment of the Non-Korean international and the Swedish-born adoptees in this study. international but not national adoptees had attained a higher educational level than predicted from their scores on intelligence tests. This education promoting effect was similar in the Korean adoptees, who had high test scores in comparison with the general population, and the Non-Korean adoptees who had comparatively low test scores.
41.	Ekman, Diana, et al. (författare) Stratified genetic analysis reveals sex differences in MPO-ANCA-associated vasculitis 2023 Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:9, s. 3213-3218 Tidskriftsartikel (refereegranskat)abstract Objective: To identify and genetically characterize subgroups of patients with ANCA-associated vasculitides (AAV) based on sex and ANCA subtype. Methods: A previously established SNP dataset derived from DNA sequencing of 1853 genes and genotyping of 1088 Scandinavian cases with AAV and 1589 controls was stratified for sex and ANCA subtype and analysed for association with five top AAV SNPs. rs9274619, a lead variant at the HLA-DQB1/HLA-DQA2 locus previously associated with AAV positive for myeloperoxidase (MPO)-ANCA, was analysed for association with the cumulative disease involvement of ten different organ systems. Results: rs9274619 showed a significantly stronger association to MPO-ANCA-positive females than males [P = 2.0 × 10-4, OR = 2.3 (95% CI 1.5, 3.5)], whereas proteinase 3 (PR3)-ANCA-associated variants rs1042335, rs9277341 (HLA-DPB1/A1) and rs28929474 (SERPINA1) were equally associated with females and males with PR3-ANCA. In MPO-ANCA-positive cases, carriers of the rs9274619 risk allele were more prone to disease engagement of eyes [P = 0.021, OR = 11 (95% CI 2.2, 205)] but less prone to pulmonary involvement [P = 0.026, OR = 0.52 (95% CI 0.30, 0.92)]. Moreover, AAV with both MPO-ANCA and PR3-ANCA was associated with the PR3-ANCA lead SNP rs1042335 [P = 0.0015, OR = 0.091 (95% CI 0.0022, 0.55)] but not with rs9274619. Conclusions: Females and males with MPO-ANCA-positive AAV differ in genetic predisposition to disease, suggesting at least partially distinct disease mechanisms between the sexes. Double ANCA-positive AAV cases are genetically similar to PR3-ANCA-positive cases, providing clues to the clinical follow-up and treatment of these patients.
42.	Ekstedt, Mirjam, Professor, et al. (författare) Nursing students' perception of the clinical learning environment and supervision in relation to two different supervision models : a comparative cross-sectional study 2019 Ingår i: BMC Nursing. - : BioMed Central. - 1472-6955. ; 18:1, s. 1-12 Tidskriftsartikel (refereegranskat)abstract Background: Knowledge concerning nursing students' experiences of the clinical learning environment and how supervision is carried out is largely lacking. This study compares nursing students' perceptions of the clinical learning environment and supervision in two different supervision models: peer learning in student-dedicated units, with students working together in pairs and supervised by a "preceptor of the day" (model A), and traditional supervision, in which each student is assigned to a personal preceptor (model B). Methods: The study was performed within the nursing programme at a university college in Sweden during students' clinical placements (semesters 3 and 4) in medical and surgical departments at three different hospitals. Data was collected using the Clinical Learning Environment, Supervision and Nurse Teacher evaluation scale, CLES+T, an instrument tested for reliability and validity, and a second instrument developed for this study to obtain deeper information regarding how students experienced the organisation and content of the supervision. Independent t-tests were used for continuous variables, Mann-Whitney U-tests for ordinal variables, and the chi-square or Fischer's exact tests for categorical variables. Results: Overall, the students had positive experiences of the clinical learning environment and supervision in both supervision models. Students supervised in model A had more positive experiences of the cooperation and relationship between student, preceptor, and nurse teacher, and more often than students in model B felt that the ward had an explicit model for supervising students. Students in model A were more positive to having more than one preceptor and felt that this contributed to the assessment of their learning outcomes. Conclusions: A good learning environment for students in clinical placements is dependent on an explicit structure for receiving students, a pedagogical atmosphere where staff take an interest in supervision of students and are easy to approach, and engagement among and collaboration between preceptors and nurse teachers. This study also indicates that supervision based on peer learning in student-dedicated rooms with many preceptors can be more satisfying for students than a model where each student is assigned to a single preceptor.
43.	Elmund, Anna, et al. (författare) Intercountry adoptees in out-of-home care : A national cohort study 2007 Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 96, s. 437-442 Tidskriftsartikel (refereegranskat)abstract Aim: To investigate risks of placements in out-of-home care for non-European adoptees. Methods: Intercountry adoptees born outside Europe 1973-1984 (n = 16 522) were compared with same age peers from the majority population (n = 1 026 523) using national demographic and child welfare registers. Multivariate analyses were performed using logistic regression models, and odds ratios (OR) for different forms of out-of-home care placements were calculated. Results: After adjustments for socio-demographic background variables, the OR:s for placements of intercountry adoptees in residential care from age 10 were 5.1 (95% Cl 4.6-5.8) and 3.0 (95% Cl 2.6-3.6) for placements in foster care from age 10. For placements in all forms of out-of home care up to age 10, the odds were on par with the majority population. Higher child age at adoption, origin from Latin America, single parent adoption and maternal age above 35 at birth of the child were identified as significant predictors of out-of-home care from age 10. Conclusion: Intercountry adoptees emerge as a risk group for placements in out-of home care during adolescence, especially for entries into residential care (in Sweden usually triggered by persistent behaviour problems).
44.	Eriksson, Daniel, et al. (författare) Common genetic variation in the autoimmune regulator (AIRE) locus is associated with autoimmune Addison’s disease in Sweden 2018 Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8:1 Tidskriftsartikel (refereegranskat)abstract Autoimmune Addison's disease (AAD) is the predominating cause of primary adrenal failure. Despite its high heritability, the rarity of disease has long made candidate-gene studies the only feasible methodology for genetic studies. Here we conducted a comprehensive reinvestigation of suggested AAD risk loci and more than 1800 candidate genes with associated regulatory elements in 479 patients with AAD and 2394 controls. Our analysis enabled us to replicate many risk variants, but several other previously suggested risk variants failed confirmation. By exploring the full set of 1800 candidate genes, we further identified common variation in the autoimmune regulator (AIRE) as a novel risk locus associated to sporadic AAD in our study. Our findings not only confirm that multiple loci are associated with disease risk, but also show to what extent the multiple risk loci jointly associate to AAD. In total, risk loci discovered to date only explain about 7% of variance in liability to AAD in our study population.
45.	Eriksson, Daniel, et al. (författare) Cytokine Autoantibody Screening in the Swedish Addison Registry Identifies Patients With Undiagnosed APS1 2018 Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 103:1, s. 179-186 Tidskriftsartikel (refereegranskat)abstract Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features autoimmune Addison disease as a major component. Although APS1 accounts for only a small fraction of all patients with Addison disease, early identification of these individuals is vital to prevent the potentially lethal complications of APS1.Objective: To determine whether available serological and genetic markers are valuable screening tools for the identification of APS1 among patients diagnosed with Addison disease.Design: We systematically screened 677 patients with Addison disease enrolled in the Swedish Addison Registry for autoantibodies against interleukin-22 and interferon-α4. Autoantibody-positive patients were investigated for clinical manifestations of APS1, additional APS1-specific autoantibodies, and DNA sequence and copy number variations of AIRE.Results: In total, 17 patients (2.5%) displayed autoantibodies against interleukin-22 and/or interferon-α4, of which nine were known APS1 cases. Four patients previously undiagnosed with APS1 fulfilled clinical, genetic, and serological criteria. Hence, we identified four patients with undiagnosed APS1 with this screening procedure.Conclusion: We propose that patients with Addison disease should be routinely screened for cytokine autoantibodies. Clinical or serological support for APS1 should warrant DNA sequencing and copy number analysis of AIRE to enable early diagnosis and prevention of lethal complications.
46.	Eskelund, Christian Winther, et al. (författare) Lenalidomide plus bendamustine-rituximab does not overcome the adverse impact of TP53 mutations in mantle cell lymphoma 2018 Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 103:11, s. E541-E543 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
47.	Essén, Anna, et al. (författare) Innovation as emergence in healthcare : Unpacking change from within 2013 Ingår i: Social Science and Medicine. - : Elsevier BV. - 0277-9536 .- 1873-5347. ; 93, s. 203-211 Tidskriftsartikel (refereegranskat)abstract The contemporary healthcare literature suffers from a disproportionate focus on 'given' externally created innovations, and belief in ordered, planned and well-funded implementation processes. As an alternative, the present paper highlights the potential of emergent change processes, using the continuous invention and re-invention of the Rheumatology Quality Registry in Sweden as an example. This 19 year long process, which is still ongoing, does not exhibit the sequential steps that are allegedly determinants of success in the innovation and implementation literature. Yet, it has produced system-wide improvements. We draw on more than 100 informal and formal meetings with practitioners involved in the process studied, observations, documentation analysis and quantitative registry-data. A total of 67 interviews with registry-users and external stakeholders were also performed. The dissipative structures model (complexity theory) was used to analyze the data. The studied process illustrates an ongoing, practice-driven improvement process, which was sparked by abstract and indirect energies that interacted with more concrete innovations such as new drugs. For example, participants tapped new information technologies, changing perspectives and governmental priorities to challenge current ways of working and introduce new ideas. Ideas were realized and spread through various self-organized processes that involved the re-arrangement of existing resources rather than acquisition of new resources. Taken together, these processes brought Swedish rheumatology to new levels of functioning 1992-2011. An important implication of our work is that incremental and practice-driven change processes can significantly transform care systems in the long run. Policy makers need to acknowledge and foster such ongoing innovation processes at micro-level, rather than focusing exclusively on innovations as externally created 'things' that await 'implementation'.
48.	Foss Lindblad, Rita, et al. (författare) Pre-service teacher student's preference of publil's developmental competences : A critical examination of educational restructuring and OECEs impact on "the learner". 2016 Konferensbidrag (refereegranskat)
49.	Gillespie, Ulrika, et al. (författare) A comprehensive pharmacist intervention to reduce morbidity in patients 80 years or older : a randomized controlled trial 2009 Ingår i: Archives of Internal Medicine. - : American Medical Association (AMA). - 0003-9926 .- 1538-3679. ; 169:9, s. 894-900 Tidskriftsartikel (refereegranskat)abstract BACKGROUNDPatients 80 years or older are underrepresented in scientific studies. The objective of this study was to investigate the effectiveness of interventions performed by ward-based pharmacists in reducing morbidity and use of hospital care among older patients.METHODSA randomized controlled study of patients 80 years or older was conducted at the University Hospital of Uppsala, Uppsala, Sweden. Four hundred patients were recruited consecutively between October 1, 2005, and June 30, 2006, and were randomized to control (n = 201) and intervention (n = 199) groups. The interventions were performed by ward-based pharmacists. The control group received standard care without direct involvement of pharmacists at the ward level. The primary outcome measure was the frequency of hospital visits (emergency department and readmissions [total and drug-related]) during the 12-month follow-up period.RESULTSThree hundred sixty-eight patients (182 in the intervention group and 186 in the control group) were analyzed. For the intervention group, there was a 16% reduction in all visits to the hospital (quotient, 1.88 vs 2.24; estimate, 0.84; 95% confidence interval [CI], 0.72-0.99) and a 47% reduction in visits to the emergency department (quotient, 0.35 vs 0.66; estimate, 0.53; 95% CI, 0.37-0.75). Drug-related readmissions were reduced by 80% (quotient, 0.06 vs 0.32; estimate, 0.20; 95% CI, 0.10-0.41). After inclusion of the intervention costs, the total cost per patient in the intervention group was $230 lower than that in the control group.CONCLUSIONIf implemented on a population basis, the addition of pharmacists to health care teams would lead to major reductions in morbidity and health care costs.
50.	Guenna Holmgren, Amina, et al. (författare) Restraint in somatic healthcare : how should it be regulated? 2023 Ingår i: Journal of Medical Ethics. - : BMJ Publishing Group Ltd. - 0306-6800 .- 1473-4257. Tidskriftsartikel (refereegranskat)abstract Restraint is regularly used in somatic healthcare settings, and countries have chosen different paths to regulate restraint in somatic healthcare. One overarching problem when regulating restraint is to ensure that patients with reduced decision-making capacity receive the care they need and at the same time ensure that patients with a sufficient degree of decision-making capacity are not forced into care that they do not want. Here, arguments of justice, trust in the healthcare system, minimising harm and respecting autonomy are contrasted with different national regulations. We conclude that a regulation that incorporates an assessment of patients’ decision-making capacity and considers the patient’s best interests is preferable, in contrast to regulations based on psychiatric diagnoses or regulations where there are no legal possibilities to exercise restraint at all in somatic care.

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