| 1. |
- Bodin, Theo, et al.
(författare)
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Road traffic noise, air pollution and myocardial infarction: a prospective cohort study.
- 2016
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 1432-1246 .- 0340-0131. ; 89:5, s. 793-802
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Tidskriftsartikel (refereegranskat)abstract
- Both road traffic noise and air pollution have been linked to cardiovascular disease. However, there are few prospective epidemiological studies available where both road traffic noise and air pollution have been analyzed simultaneously. The aim of this study was to investigate the relation between road traffic noise, air pollution and incident myocardial infarction in both current (1-year average) and medium-term (3-year average) perspective.
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| 2. |
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| 3. |
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| 4. |
- Alhamdow, Ayman, et al.
(författare)
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Chimney sweeps in Sweden : a questionnaire-based assessment of long-term changes in work conditions, and current eye and airway symptoms
- 2017
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 0340-0131 .- 1432-1246. ; 90:2, s. 207-216
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To explore chimney sweeping work tasks, chimney sweeps’ use of protective equipment, and type of fuel used by clients, over time. Further, to assess work-relatedness of current eye and airway symptoms. Methods: In a cross-sectional study in 2011, male Swedish chimney sweeps (n = 483; age 21–69 years) answered a questionnaire about their occupational history and eye and airway symptoms. Results: Between 1960 and 2010, black-soot-sweeping in private homes was the major task, although it decreased during the time period, for chimney sweeps. Between 1975 and 2010, the use of petroleum oil decreased, whereas the use of pellets and wood increased. Also, the use of gloves and masks increased significantly. Black-soot-sweeping in industry was associated with work-related eye symptoms (prevalence odds ratio POR = 3.76, 95% CI: 1.72–8.24, for every 10% increment of working time, adjusted for age and tobacco smoking). Chimney sweeps also had slightly higher prevalence of cough with increasing black-soot-sweeping (POR = 1.06, 95% CI: 0.99–1.13 for every 10% increment, further adjusted for the use of mask), and the association was more pronounced, although nonsignificant, for black-soot-sweeping in industry (adjusted POR = 1.26, 95% CI: 0.98–1.61). Conclusions: Chimney sweeping tasks and use of protective equipment as well as type of fuel used by the clients changed significantly over the last 35 years, which may have changed chimney sweeps’ exposure to soot. Still, chimney sweeps in Sweden have black-soot-sweeping-related eye and airway symptoms.
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| 5. |
- Balakrishnan Kumar, Ramakrishnan, et al.
(författare)
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Structural and Functional Analysis of Calcium Ion Mediated Binding of 5-Lipoxygenase to Nanodiscs
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- An important step in the production of inflammatory mediators of the leukotriene family is the Ca2+ mediated recruitment of 5 Lipoxygenase (5LO) to nuclear membranes. To study this reaction in vitro, the natural membrane mimicking environment of nanodiscs was used. Nanodiscs with 10.5 nm inner diameter were made with the lipid POPC and membrane scaffolding protein MSP1E3D1. Monomeric and dimeric 5LO were investigated. Monomeric 5LO mixed with Ca2+ and nanodiscs are shown to form stable complexes that 1) produce the expected leukotriene products from arachidonic acid and 2) can be, for the first time, visualised by native gel electrophoresis and negative stain transmission electron micros-copy and 3) show a highest ratio of two 5LO per nanodisc. We interpret this as one 5LO on each side of the disc. The dimer of 5LO is visualised by negative stain transmission electron microscopy and is shown to not bind to nanodiscs. This study shows the advantages of nanodiscs to obtain basic structural information as well as functional information of a complex between a monotopic membrane protein and the membrane.
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| 6. |
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| 7. |
- Bergqvist, Filip, et al.
(författare)
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Inhibition of mPGES-1 or COX-2 Results in Different Proteomic and Lipidomic Profiles in A549 Lung Cancer Cells
- 2019
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Pharmacological inhibition of microsomal prostaglandin E synthase (mPGES)-1 for selective reduction in prostaglandin E-2 (PGE(2)) biosynthesis is protective in experimental models of cancer and inflammation. Targeting mPGES-1 is envisioned as a safer alternative to traditional non-steroidal anti-inflammatory drugs (NSAIDs). Herein, we compared the effects of mPGES-1 inhibitor Compound III (CIII) with the cyclooxygenase (COX)-2 inhibitor NS-398 on protein and lipid profiles in interleukin (IL)-1 beta-induced A549 lung cancer cells using mass spectrometry. Inhibition of mPGES-1 decreased PGE(2) production and increased PGF(2 alpha) and thromboxane B-2 (TXB2) formation, while inhibition of COX-2 decreased the production of all three prostanoids. Our proteomics results revealed that CIII downregulated multiple canonical pathways including eIF2, eIF4/P70S6K, and mTOR signaling, compared to NS-398 that activated these pathways. Moreover, pathway analysis predicted that CIII increased cell death of cancer cells (Z = 3.8, p = 5.1E-41) while NS-398 decreased the same function (Z = -5.0, p = 6.5E-35). In our lipidomics analyses, we found alterations in nine phospholipids between the two inhibitors, with a stronger alteration in the lysophospholipid (LPC) profile with NS-398 compared to CIII. Inhibition of mPGES-1 increased the concentration of sphinganine and dihydroceramide (C16:0D hCer), while inhibition of COX-2 caused a general decrease in most ceramides, again suggesting different effects on cell death between the two inhibitors. We showed that CIII decreased proliferation and potentiated the cytotoxic effect of the cytostatic drugs cisplatin, etoposide, and vincristine when investigated in a live cell imaging system. Our results demonstrate differences in protein and lipid profiles after inhibition of mPGES-1 or COX-2 with important implications on the therapeutic potential of mPGES-1 inhibitors as adjuvant treatment in cancer. We encourage further investigations to illuminate the clinical benefit of mPGES-1 inhibitors in cancer.
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| 8. |
- Brattås, Per Ludvik, et al.
(författare)
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TRIM28 Controls a Gene Regulatory Network Based on Endogenous Retroviruses in Human Neural Progenitor Cells
- 2017
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 18:1, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Endogenous retroviruses (ERVs), which make up 8% of the human genome, have been proposed to participate in the control of gene regulatory networks. In this study, we find a region- and developmental stage-specific expression pattern of ERVs in the developing human brain, which is linked to a transcriptional network based on ERVs. We demonstrate that almost 10,000, primarily primate-specific, ERVs act as docking platforms for the co-repressor protein TRIM28 in human neural progenitor cells, which results in the establishment of local heterochromatin. Thereby, TRIM28 represses ERVs and consequently regulates the expression of neighboring genes. These results uncover a gene regulatory network based on ERVs that participates in control of gene expression of protein-coding transcripts important for brain development.
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| 9. |
- Colmorn, Lotte B., et al.
(författare)
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Mode of first delivery and severe maternal complications in the subsequent pregnancy
- 2017
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 96:9, s. 1053-1062
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Severe obstetric complications increase with the number of previous cesarean deliveries. In the Nordic countries most women have two children. We present the risk of severe obstetric complications at the delivery following a first elective or emergency cesarean and the risk by intended mode of second delivery. Material and methods: A two-year population-based data collection of severe maternal complications in women with two deliveries in the Nordic countries (n = 213 518). Denominators were retrieved from the national medical birth registers. Results: Of 35 450 first cesarean deliveries (17%), 75% were emergency and 25% elective. Severe complications at second delivery were more frequent in women with a first cesarean than with a first vaginal delivery, and rates of abnormally invasive placenta, uterine rupture and severe postpartum hemorrhage were higher after a first elective than after a first emergency cesarean delivery [relative risk (RR) 4.1, 95% confidence intervals (CI) 2.0-8.1; RR 1.8, 95% CI 1.3-2.5; RR 2.3, 95% CI 1.5-3.5, respectively]. A first cesarean was associated with up to 97% of severe complications in the second pregnancy. Induction of labor was associated with an increased risk of uterine rupture and severe hemorrhage. Conclusion: Elective repeat cesarean can prevent complete uterine rupture at the second delivery, whereas the risk of severe obstetric hemorrhage, abnormally invasive placenta and peripartum hysterectomy is unchanged by the intended mode of second delivery in women with a first cesarean. Women with a first elective vs. an emergency cesarean have an increased risk of severe complications in the second pregnancy.
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| 10. |
- Colmorn, Lotte B., et al.
(författare)
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The Nordic Obstetric Surveillance Study: a study of complete uterine rupture, abnormally invasive placenta, peripartum hysterectomy, and severe blood loss at delivery
- 2015
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 94:7, s. 734-744
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the rates and characteristics of women with complete uterine rupture, abnormally invasive placenta, peripartum hysterectomy, and severe blood loss at delivery in the Nordic countries. Design: Prospective, Nordic collaboration. Setting: The Nordic Obstetric Surveillance Study (NOSS) collected cases of severe obstetric complications in the Nordic countries from April 2009 to August 2012. Sample and methods: Cases were reported by clinicians at the Nordic maternity units and retrieved from medical birth registers, hospital discharge registers, and transfusion databases by using International Classification of Diseases, 10th revision codes on diagnoses and the Nordic Medico-Statistical Committee Classification of Surgical Procedure codes. Main outcome measures: Rates of the studied complications and possible risk factors among parturients in the Nordic countries. Results: The studied complications were reported in 1019 instances among 605362 deliveries during the study period. The reported rate of severe blood loss at delivery was 11.6/10000 deliveries, complete uterine rupture was 5.6/10000 deliveries, abnormally invasive placenta was 4.6/10000 deliveries, and peripartum hysterectomy was 3.5/10000 deliveries. Of the women, 25% had two or more complications. Women with complications were more often >35years old, overweight, with a higher parity, and a history of cesarean delivery compared with the total population. Conclusion: The studied obstetric complications are rare. Uniform definitions and valid reporting are essential for international comparisons. The main risk factors include previous cesarean section. The detailed information collected in the NOSS database provides a basis for epidemiologic studies, audits, and educational activities.
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| 11. |
- Drouin-Ouellet, Janelle, et al.
(författare)
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REST suppression mediates neural conversion of adult human fibroblasts via microRNA-dependent and -independent pathways
- 2017
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Ingår i: EMBO Molecular Medicine. - : EMBO. - 1757-4684 .- 1757-4676. ; 9:8, s. 1117-1131
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Tidskriftsartikel (refereegranskat)abstract
- Direct conversion of human fibroblasts into mature and functional neurons, termed induced neurons (iNs), was achieved for the first time 6 years ago. This technology offers a promising shortcut for obtaining patient- and disease-specific neurons for disease modeling, drug screening, and other biomedical applications. However, fibroblasts from adult donors do not reprogram as easily as fetal donors, and no current reprogramming approach is sufficiently efficient to allow the use of this technology using patient-derived material for large-scale applications. Here, we investigate the difference in reprogramming requirements between fetal and adult human fibroblasts and identify REST as a major reprogramming barrier in adult fibroblasts. Via functional experiments where we overexpress and knockdown the REST-controlled neuron-specific microRNAs miR-9 and miR-124, we show that the effect of REST inhibition is only partially mediated via microRNA up-regulation. Transcriptional analysis confirmed that REST knockdown activates an overlapping subset of neuronal genes as microRNA overexpression and also a distinct set of neuronal genes that are not activated via microRNA overexpression. Based on this, we developed an optimized one-step method to efficiently reprogram dermal fibroblasts from elderly individuals using a single-vector system and demonstrate that it is possible to obtain iNs of high yield and purity from aged individuals with a range of familial and sporadic neurodegenerative disorders including Parkinson's, Huntington's, as well as Alzheimer's disease.
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| 12. |
- Emami Khoonsari, Payam, et al.
(författare)
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The human CSF pain proteome
- 2019
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Ingår i: Journal of Proteomics. - : ELSEVIER SCIENCE BV. - 1874-3919 .- 1876-7737. ; 190, s. 67-76
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Tidskriftsartikel (refereegranskat)abstract
- Chronic pain represents one of the major medical challenges in the 21st century, affecting > 1.5 billion of the world population. Overlapping and heterogenous symptoms of various chronic pain conditions complicate their diagnosis, emphasizing the need for more specific biomarkers to improve the diagnosis and understand the disease mechanisms. We have here investigated proteins found in human CSF with respect to known "pain" genes and in a cohort of patients with dysfunctional pain (fibromyalgia, FM), inflammatory pain (rheumatoid arthritis patients, RA) and non-pain controls utilized semi-quantitative proteomics using mass spectrometry (MS) to explore quantitative differences between these cohorts of patients. We found that "pain proteins" detected in CSF using MS are typically related to synaptic transmission, inflammatory responses, neuropeptide signaling- and hormonal activity. In addition, we found ten proteins potentially associated with chronic pain in FM and RA: neural cell adhesion molecule L1, complement C4-A, lysozyme C, receptor-type tyrosine-protein phosphatase zeta, apolipoprotein D, alpha-1-antichymotrypsin, granulins, calcium/calmodulin-dependent protein kinase type II subunit alpha, mast/stem cell growth factor receptor Kit, prolow-density lipoprotein receptor-related protein 1. These proteins might be of importance for understanding the mechanisms of dysfunctional/inflammatory chronic pain and also for use as potential biomarkers. Significance: Chronic pain is a common disease and it poses a large burden on worldwide health. Fibromyalgia (FM) is a heterogeneous disease of unknown etiology characterized by chronic widespread pain (CWP). The diagnosis and treatment of FM is based on the analysis of clinical assessments and no measurable biomarkers are available. Cerebrospinal fluid (CSF) has been historically considered as a rich source of biomarkers for diseases of nervous system including chronic pain. Here, we explore CSF proteome of FM patients utilizing mass spectrometry based quantitative proteomics method combined with multivariate data analysis in order to monitor the dynamics of the CSF proteome. Our findings in this exploratory study support notable presence of pain related proteins in CSF yet with specific domains including inflammatory responses, neuropeptide signaling- and hormonal activity. We have investigated molecular functions of significantly altered proteins and demonstrate presence of 176 known pain related proteins in CSF. In addition, we found ten proteins potentially associated with pain in FM and RA: neural cell adhesion molecule L1, complement C4-A, lysozyme C, receptor-type tyrosine-protein phosphatase zeta, apolipoprotein D, alpha-1-antichymotrypsin, granulins, calcium/calmodulindependent protein kinase type II subunit alpha, mast/stem cell growth factor receptor Kit, prolow-density lipoprotein receptor-related protein 1. These proteins are novel in the context of FM but are known to be involved in pain mechanisms including inflammatory response and signal transduction. These results should be of clear significance and interest for researchers and clinicians working in the field of pain utilizing human CSF and MS based proteomics.
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| 13. |
- Fernandes-Cerqueira, Catia, et al.
(författare)
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Targeting of anti-citrullinated protein/peptide antibodies in rheumatoid arthritis using peptides mimicking endogenously citrullinated fibrinogen antigens
- 2015
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: We have previously identified endogenously citrullinated peptides derived from fibrinogen in rheumatoid arthritis (RA) synovial tissues. In this study, we have investigated the auto-antigenicity of four of those citrullinated peptides, and explored their feasibility to target anti-citrullinated protein/peptide antibodies (ACPA). Methods: The autoantigenic potential of the fibrinogen peptides was investigated by screening 927 serum samples from the Epidemiological Investigation of RA (EIRA) cohort on a peptide microarray based on the ImmunoCAP ISAC (R) system. In order to assay for ACPA blocking, two independent pools of purified ACPA were incubated with the respective targeting peptide prior to binding to cyclic citrullinated peptide (CCP) 2 using the CCPlus (R) ELISA kit. Results: Two peptides derived from the fibrinogen a chain, Arg573Cit (563-583) and Arg591Cit (580-600), referred to as Cit573 and Cit591, and two peptides from the fibrinogen beta chain, Arg72Cit (62-81) and Arg74Cit (62-81) (Cit72 and Cit74), displayed 65 %, 15 %, 35 %, and 53 % of immune reactivity among CCP2-positive RA sera, respectively. In CCP2-negative RA sera, a positive reactivity was detected in 5 % (Cit573), 6 % (Cit591), 8 % (Cit72), and 4 % (Cit74). In the competition assay, Cit573 and Cit591 peptides reduced ACPA binding to CCP2 by a maximum of 84 % and 63 % respectively. An additive effect was observed when these peptides were combined. In contrast, Cit74 and Cit72 were less effective. Cyclization of the peptide structure containing Cit573 significantly increased the blocking efficiency. Conclusions: Here we demonstrate extensive autoantibody reactivity against in vivo citrullinated fibrinogen epitopes, and further show the potential use of these peptides for antagonizing ACPA.
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| 14. |
- Fraser, Magdalena
(författare)
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People of the Dolmens and Stone Cists : An archaeogenetic Investigation of Megalithic Graves from the Neolithic Period on Gotland
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The study of ancient genomics of pre-historic human remains has in recent years offered unprecedented knowledge regarding pre-historic migration and population structure on the European continent which has fundamentally altered the current views in the archaeological community. However, the merging of the two fields, archaeology and genetics, is still in its infancy and much work is still needed in order for these fields to integrate. In this thesis I explore how genetic analyses, in combination with contextual radiocarbon dating and isotopic analyses for diet and mobility can be used to investigate demographic events on a local and regional level. This is done through the investigation of people buried in five previously excavated megalithic tombs on the Island of Gotland dated to the Neolithic period. I present the genomic population structure and archaeological background for the pre-historic European reference data and show how this is used to investigate population continuity, demographic shifts, cultural duality, and admixture for local and regional contexts. I present new data and explore the Strontium-baseline for the Gotland biosphere which is used for the mobility analyses. I show that mitochondrial haplogroup data is especially useful in combination with isotopic data, and radiocarbon dating for investigation of demographic shifts on a larger scale. I also show that genomic data gives unique insights into the individuals’ life history which, together with the established demographic background allows for fine scale investigation of population demographic events within and between different archaeological contexts. Finally I show that the different Neolithic contexts on Gotland to a large extent involves immigration of new groups to the island, and that the contextual breaks seen in the archaeological record during the Neolithic period are connected with cultural and population demographic shifts. This dissertation demonstrates that genomic analyses, in combination with archaeology and isotopic analyses, as well as contextual osteological analyses and radiocarbon dating, present unique insights into the life history of the actual people who lived the lives we try to understand.
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| 15. |
- Fraser, Magdalena, et al.
(författare)
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The stone cist conundrum : A multidisciplinary approach to investigate Late Neolithic/Early Bronze Age population demography on the island of Gotland
- 2018
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Ingår i: Journal of Archaeological Science. - : Elsevier BV. - 2352-409X .- 2352-4103. ; 20, s. 324-337
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Tidskriftsartikel (refereegranskat)abstract
- The Late Neolithic period in Scandinavia [LN, c. 2350-1700 cal BCE] marks a time of considerable changes in settlement patterns, economy, and material culture. This shift also lays the foundation for the demographic developments in the Early Bronze Age [EBA, c. 1700-1100 cal BCE]. However, little is presently known regarding the developments from these time-periods on the island of Gotland in the Baltic Sea. During the Middle Neolithic period [MN, c. 3300-2350 cal BCE], Gotland was inhabited by groups associated with the Funnel Beaker culture [TRB, c. 4000-2700 cal BCE], and the sub-Neolithic Pitted Ware culture [PWC, c. 3300-2300 cal BCE]. Some indications of connections with the Bathe Axe/Corded Ware cultures [BAC/CWC, c. 2800-2300 cal BCE] have also been found, but no typical BAC/CWC burials have been located on the island to date. Here, we investigate the chronological and internal relationship of twenty-three individuals buried in four LN/EBA stone cist burials; Haffinds, Hagur, Suderkvie, and Utalskog on Gotland. We present eleven mitochondrial genomes [from 23 X to 1271 X coverage], and twenty-three new radiocarbon dates, as well as stable isotope data for diet. We examine the local Sr-baseline range for Gotland, and present new Sr-data to discuss mobility patterns of the individuals. The genetic results are compared and discussed in light of earlier cultural periods from Gotland [TRB and PWC], and CWC from the European continent, as well as contemporaneous LN secondary burials in the MN Ansarve dolmen. We find that all burials were used into the EBA, but only two of the cists showed activity already during the LN. We also see some mobility to Gotland during the LN/EBA period based on Strontium and mitochondrial data. We see a shift in the dietary pattern compared to the preceding period on the island [TRB and PWC], and the two LN individuals from the Ansarve dolmen exhibited different dietary and mobility patterns compared to the individuals from the LN/EBA stone cist burials. We find that most of the cist burials were used by individuals local to the area of the burials, with the exception of the large LN/EBA Haffinds cist burial which showed higher levels of mobility. Our modeling of ancestral mitochondrial contribution from chronologically older individuals recovered in the cultural contexts of TRB, PWC and CWC show that the best model is a 55/45 mix of CWC and TRB individuals. A 3-way model with a slight influx from PWC [5%] also had a good fit. This is difficult to reconcile with the current archaeological evidence on the island. We suggest that the maternal CWC/TRB contribution we see in the local LN/EBA individuals derives from migrants after the Scandinavian MN period, which possible also admixed with smaller local groups connected with the PWC. Further genomic analyses of these groups on Gotland will help to clarify the demographic history during the MN to EBA time periods.
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| 16. |
- Friedrichsen, Maria, et al.
(författare)
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Palliative care consultation team on acute wards-an intervention study with pre-post comparisons
- 2017
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Ingår i: Supportive Care in Cancer. - : SPRINGER. - 0941-4355 .- 1433-7339. ; 25:2, s. 371-380
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Tidskriftsartikel (refereegranskat)abstract
- There is little evidence regarding primary healthcare team members perceptions concerning palliative care consultation team (PCCT) and palliative care (PC) issues on their own wards. This study aimed to study whether a PCCT can influence and change primary healthcare team members perceptions regarding the palliative care at the end of life they are providing to patients in their own acute wards. The intervention was a PCCT visiting surgical and internal medicine wards in 1 year. We used a quasi-experimental design with pre-post-testing, measuring at baseline, and after 1 years intervention. A questionnaire was answered by all primary healthcare team members in three acute wards. A total of 252 team members (pre-post-intervention n = 132/n = 120) participated in the study. Overall, 11 of the 12 statements scored significantly higher after the intervention than before. Responses varied significantly between different professions and depending on the number of dying patients cared for during the last month. The five with the highest Wald values were as follows: the presence of a break point dialogue with a patient, where the changed aim and focus of care was discussed; early detection of impending death; adequate symptom relief and psychological and existential issues. It is possible to change perceptions about end-of-life care in primary healthcare team members on acute wards. Palliative care consultation teams should be a natural part wherever dying patients are cared for.
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| 17. |
- Garmy, Pernilla, et al.
(författare)
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Insufficient Sleep Is Associated with Obesity and Excessive Screen Time Amongst Ten-Year-Old Children in Sweden
- 2018
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Ingår i: Journal of Pediatric Nursing. - : Elsevier BV. - 0882-5963. ; 39, s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study investigated sleep, television, computer habits, and obesity in school-age children. Design and methods: This was a cross-sectional self-report survey of 1260 children in grade 4 (mean age, 10.1) living in southern Sweden (49.1% boys). The heights and weights of 1097 (87.1%) of the children were recorded. Descriptive statistics, bivariate analyses, and multiple logistic regression were employed. Results: The median length of self-reported sleep on weeknights was 9.5. h. Approximately 40% of the children reported receiving <. 9. h of sleep. The median bedtime was 9. PM (21:00). On weekends, the median bedtime was 1 h later, and they delayed getting up by 1.5. h. The median time spent watching TV and using a computer was 1 h each. The prevalence of being overweight (including obesity) was 18%. Insufficient sleep (<. 9. h) was associated with being overweight, watching TV, or using a computer for two or more hours each day, difficulty falling asleep, and being tired at school. Conclusions: School-age children who receive less sleep are more likely to be overweight and report excessive television and computer use. A strong and urgent need exists to highlight the importance of healthy sleep and media habits. It is challenging for pediatric nurses and school nurses to teach children and their families about healthy sleep and media habits.
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| 18. |
- Grassi, Daniela A., et al.
(författare)
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TRIM28 and the control of transposable elements in the brain
- 2019
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 1705, s. 43-47
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Forskningsöversikt (refereegranskat)abstract
- TRIM28 is an epigenetic co-repressor protein that mediates transcriptional silencing. TRIM28 participates, together with the large family of Kruppel-associated box domain zinc finger proteins (KRAB-ZFP) transcription factors, in the repression of transposable elements (TE). Recent advances indicate that TRIM28-based repression of TEs occurs in the mammalian brain and may provide beneficial effects through the regulation of transcriptional networks. Here, we provide an overview of TRIM28-related functions, highlighting the role of controlling TEs in neural progenitor cells and discuss how this mechanism may have contributed to the evolution of the complex human brain. Finally, we outline future considerations for the field.
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| 19. |
- Greenwood, Sarah L., et al.
(författare)
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The Bothnian Sea ice stream : early Holocene retreat dynamics of the south-central Fennoscandian Ice Sheet
- 2017
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Ingår i: Boreas. - : Wiley. - 0300-9483 .- 1502-3885. ; 46:2, s. 346-362
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Tidskriftsartikel (refereegranskat)abstract
- The Gulf of Bothnia hosted a variety of palaeo-glaciodynamic environments throughout the growth and decay of the last Fennoscandian Ice Sheet, from the main ice-sheet divide to a major corridor of marine-and lacus-trine-based deglaciation. Ice streaming through the Bothnian and Baltic basins has been widely assumed, and the damming and drainage of the huge proglacial Baltic Ice Lake has been implicated in major regional and hemispheric climate changes. However, the dynamics of palaeo-ice flow and retreat in this large marine sector have until now been inferred only indirectly, from terrestrial, peripheral evidence. Recent acquisition of high-resolution multibeam bathymetry opens these basins up, for the first time, to direct investigation of their glacial footprint and palaeo-ice sheet behaviour. Here we report on a rich glacial landform record: in particular, a palaeo-ice stream pathway, abundant traces of high subglacial meltwater volumes, and widespread basal crevasse squeeze ridges. The Bothnian Sea ice stream is a narrow flow corridor that was directed southward through the basin to a terminal zone in the south-central Bothnian Sea. It was activated after initial margin retreat across the Aland sill and into the Bothnian basin, and the exclusive association of the ice-stream pathway with crevasse squeeze ridges leads us to interpret a short-lived stream event, under high extension, followed by rapid crevasse-triggered break-up. We link this event with a c. 150-year ice-rafted debris signal in peripheral varved records, at c. 10.67 cal. ka BP. Furthermore, the extensive glacifluvial system throughout the Bothnian Sea calls for considerable input of surface meltwater. We interpret strongly atmospherically driven retreat of this marine-based ice-sheet sector.
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| 20. |
- Idborg, Helena, et al.
(författare)
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Circulating Levels of Interferon Regulatory Factor-5 Associates With Subgroups of Systemic Lupus Erythematosus Patients
- 2019
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Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Systemic Lupus Erythematosus (SLE) is a heterogeneous autoimmune disease, which currently lacks specific diagnostic biomarkers. The diversity within the patients obstructs clinical trials but may also reflect differences in underlying pathogenesis. Our objective was to obtain protein profiles to identify potential general biomarkers of SLE and to determine molecular subgroups within SLE for patient stratification. Plasma samples from a cross-sectional study of well-characterized SLE patients (n = 379) and matched population controls (n = 316) were analyzed by antibody suspension bead array targeting 281 proteins. To investigate the differences between SLE and controls, Mann-Whitney U-test with Bonferroni correction, generalized linear modeling and receiver operating characteristics (ROC) analysis were performed. K-means clustering was used to identify molecular SLE subgroups. We identified Interferon regulating factor 5 (IRF5), solute carrier family 22 member 2 (SLC22A2) and S100 calcium binding protein A12 (S100A12) as the three proteins with the largest fold change between SLE patients and controls (SLE/Control = 1.4, 1.4, and 1.2 respectively). The lowest p-values comparing SLE patients and controls were obtained for S100A12, Matrix metalloproteinase-1 (MMP1) and SLC22A2 (p(adjusted) = 3 x 10(-9), 3 x 10(-6), and 5 x 10(-6) respectively). In a set of 15 potential biomarkers differentiating SLE patients and controls, two of the proteins were transcription factors, i.e., IRF5 and SAM pointed domain containing ETS transcription factor (SPDEF). IRF5 was up-regulated while SPDEF was found to be down-regulated in SLE patients. Unsupervised clustering of all investigated proteins identified three molecular subgroups among SLE patients, characterized by (1) high levels of rheumatoid factor-IgM, (2) low IRF5, and (3) high IRF5. IRF5 expressing microparticles were analyzed by flow cytometry in a subset of patients to confirm the presence of IRF5 in plasma and detection of extracellular IRF5 was further confirmed by immunoprecipitation-mass spectrometry (IP-MS). Interestingly IRF5, a known genetic risk factor for SLE, was detected extracellularly and suggested by unsupervised clustering analysis to differentiate between SLE subgroups. Our results imply a set of circulating molecules as markers of possible pathogenic importance in SLE. We believe that these findings could be of relevance for understanding the pathogenesis and diversity of SLE, as well as for selection of patients in clinical trials.
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| 21. |
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| 22. |
- Idborg, Helena, et al.
(författare)
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Two subgroups in systemic lupus erythematosus with features of antiphospholipid or Sjogren's syndrome differ in molecular signatures and treatment perspectives
- 2019
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Ingår i: Arthritis Research & Therapy. - : BioMed Central. - 1478-6362 .- 1478-6354. ; 21
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPrevious studies and own clinical observations of patients with systemic lupus erythematosus (SLE) suggest that SLE harbors distinct immunophenotypes. This heterogeneity might result in differences in response to treatment in different subgroups and obstruct clinical trials. Our aim was to understand how SLE subgroups may differ regarding underlying pathophysiology and characteristic biomarkers.MethodsIn a cross-sectional study, including 378 well-characterized SLE patients and 316 individually matched population controls, we defined subgroups based on the patients' autoantibody profile at inclusion. We selected a core of an antiphospholipid syndrome-like SLE (aPL+ group; positive in the lupus anticoagulant (LA) test and negative for all three of SSA (Ro52 and Ro60) and SSB antibodies) and a Sjogren's syndrome-like SLE (SSA/SSB+ group; positive for all three of SSA (Ro52 and Ro60) and SSB antibodies but negative in the LA test). We applied affinity-based proteomics, targeting 281 proteins, together with well-established clinical biomarkers and complementary immunoassays to explore the difference between the two predefined SLE subgroups.ResultsThe aPL+ group comprised 66 and the SSA/SSB+ group 63 patients. The protein with the highest prediction power (receiver operating characteristic (ROC) area under the curve=0.89) for separating the aPL+ and SSA/SSB+ SLE subgroups was integrin beta-1 (ITGB1), with higher levels present in the SSA/SSB+ subgroup. Proteins with the lowest p values comparing the two SLE subgroups were ITGB1, SLC13A3, and CERS5. These three proteins, rheumatoid factor, and immunoglobulin G (IgG) were all increased in the SSA/SSB+ subgroup. This subgroup was also characterized by a possible activation of the interferon system as measured by high KRT7, TYK2, and ETV7 in plasma. In the aPL+ subgroup, complement activation was more pronounced together with several biomarkers associated with systemic inflammation (fibrinogen, -1 antitrypsin, neutrophils, and triglycerides).ConclusionsOur observations indicate underlying pathogenic differences between the SSA/SSB+ and the aPL+ SLE subgroups, suggesting that the SSA/SSB+ subgroup may benefit from IFN-blocking therapies while the aPL+ subgroup is more likely to have an effect from drugs targeting the complement system. Stratifying SLE patients based on an autoantibody profile could be a way forward to understand underlying pathophysiology and to improve selection of patients for clinical trials of targeted treatments.
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| 23. |
- Jakobsson, Albin, et al.
(författare)
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Three-dimensional functional human neuronal networks in uncompressed low-density electrospun fiber scaffolds
- 2017
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Ingår i: Nanomedicine. - : Elsevier. - 1549-9634 .- 1549-9642. ; 13:4, s. 1563-1573
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate an artificial three-dimensional (3D) electrical active human neuronal network system, by the growth of brain neural progenitors in highly porous low density electrospun poly-ε-caprolactone (PCL) fiber scaffolds. In neuroscience research cell-based assays are important experimental instruments for studying neuronal function in health and disease. Traditional cell culture at 2D-surfaces induces abnormal cell–cell contacts and network formation. Hence, there is a tremendous need to explore in vivo-resembling 3D neural cell culture approaches. We present an improved electrospinning method for fabrication of scaffolds that promote neuronal differentiation into highly 3D integrated networks, formation of inhibitory and excitatory synapses and extensive neurite growth. Notably, in 3D scaffolds in vivo-resembling intermixed neuronal and glial cell network were formed, whereas in parallel 2D cultures a neuronal cell layer grew separated from an underlying glial cell layer. Hence, the use of the 3D cell assay presented will most likely provide more physiological relevant results.
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| 24. |
- Jakobsson, Hedvig E, et al.
(författare)
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Draft Genome Sequence of Moraxella catarrhalis Type Strain CCUG 353T.
- 2016
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Ingår i: Genome Announcements. - 2169-8287. ; 4:3
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Tidskriftsartikel (refereegranskat)abstract
- Moraxella catarrhalis is a Gram-negative commensal and pathogenic bacterium found in the human respiratory tract. It is associated with otitis media and respiratory tract infections. Here, we report the draft genome sequence of M. catarrhalis type strain CCUG 353(T), composed of 18 contigs and a total size of 1.89 Mb.
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| 25. |
- Jakobsson, Jonas, et al.
(författare)
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Charting the human respiratory tract with airborne nanoparticles : Evaluation of the Airspace Dimension Assessment technique
- 2018
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Ingår i: Journal of Applied Physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 125:6, s. 1832-1840
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Tidskriftsartikel (refereegranskat)abstract
- Airspace Dimension Assessment (AiDA) is a technique to assess lung morphology by measuring lung deposition of inhaled nanoparticles. Nanoparticles deposit in the lungs predominately by diffusion, and average diffusion distances, corresponding to effective airspace radii (rAiDA), can be inferred from measurements of particle recovery after varied breath holds. Also, particle recovery after a 0-s breath hold (R0) may hold information about the small conducting airways. This study investigates rAiDA at different volumetric sample depths in the lungs of healthy subjects. Measurements were performed with 50-nm polystyrene nanospheres on 19 healthy subjects aged 17– 67 yr. Volumetric sample depths ranged from 200 to 5,000 ml and breath-hold times from 5 to 20 s. At the examined volumetric sample depths, rAiDA values ranged from ~200 – 600 m, which correspond to dimensions of the bronchiolar and the gas-exchanging regions of the lungs. R 0 decreased with volumetric sample depth and showed more intersubject variation than rAiDA. Correlations were found between the AiDA parameters, anthropometry, and lung function tests, but not between rAiDA and R0. For repeated measurements on 3 subjects over an 18-mo period, rAiDA varied on average within 7 m ( 2.4%). The results indicate that AiDA has potential as an efficient new in vivo technique to assess individual lung properties. The information obtained by such measurements may be of value for lung diagnostics, especially for the distal lungs, which are challenging to examine directly by other means. NEW & NOTEWORTHY This is the first study to measure effective airspace radii (rAiDA) at volumetric sample depths 200 –5,000 ml in healthy subjects by Airspace Dimension Assessment (AiDA). Observed rAiDA were 200 – 600 m, which corresponds to airspaces for the bronchiolar and the gas-exchanging regions around airway generation 14 –17. rAiDA correlated with lung function tests and anthropometry. Measurements of rAiDA on 3 subjects over 11–18 mo were within 7 m.
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| 26. |
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| 27. |
- Jakobsson, Jonas K F, et al.
(författare)
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A new method for measuring lung deposition efficiency of airborne nanoparticles in a single breath
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Assessment of respiratory tract deposition of nanoparticles is a key link to understanding their health impacts. An instrument was developed to measure respiratory tract deposition of nanoparticles in a single breath. Monodisperse nanoparticles are generated, inhaled and sampled from a determined volumetric lung depth after a controlled residence time in the lung. The instrument was characterized for sensitivity to inter-subject variability, particle size (22, 50, 75 and 100 nm) and breath-holding time (3-20 s) in a group of seven healthy subjects. The measured particle recovery had an inter-subject variability 26-50 times larger than the measurement uncertainty and the results for various particle sizes and breath-holding times were in accordance with the theory for Brownian diffusion and values calculated from the Multiple-Path Particle Dosimetry model. The recovery was found to be determined by residence time and particle size, while respiratory flow-rate had minor importance in the studied range 1-10 L/s. The instrument will be used to investigate deposition of nanoparticles in patients with respiratory disease. The fast and precise measurement allows for both diagnostic applications, where the disease may be identified based on particle recovery, and for studies with controlled delivery of aerosol-based nanomedicine to specific regions of the lungs.
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| 28. |
- Jakobsson, Jonas K F, et al.
(författare)
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Altered deposition of inhaled nanoparticles in subjects with chronic obstructive pulmonary disease
- 2018
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Ingår i: BMC Pulmonary Medicine. - : BioMed Central Ltd.. - 1471-2466. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Respiratory tract deposition of airborne particles is a key link to understand their health impact. Experimental data are limited for vulnerable groups such as individuals with respiratory diseases. The aim of this study is to investigate the differences in lung deposition of nanoparticles in the distal lung for healthy subjects and subjects with respiratory disease. Methods: Lung deposition of nanoparticles (50 and 100 nm) was measured after a 10 s breath-hold for three groups: healthy never-smoking subjects (n = 17), asymptomatic (active and former) smokers (n = 15) and subjects with chronic obstructive pulmonary disease (n = 16). Measurements were made at 1300 mL and 1800 mL volumetric lung depth. Each subject also underwent conventional lung function tests, including post bronchodilator FEV1, VC, and diffusing capacity for carbon monoxide, DL,CO. Patients with previously diagnosed respiratory disease underwent a CT-scan of the lungs. Particle lung deposition fraction, was compared between the groups and with conventional lung function tests. Results: We found that the deposition fraction was significantly lower for subjects with emphysema compared to the other subjects (p = 0.001-0.01), but no significant differences were found between healthy never-smokers and smokers. Furthermore, the particle deposition correlated with pulmonary function tests, FEV1%Pred (p < 0.05), FEV1/VC%Pred (p < 0.01) and DL,CO (p < 0.0005) when all subjects were included. Furthermore, for subjects with emphysema, deposition fraction correlated strongly with DL,CO (Pearson's r = 0.80-0.85, p < 0.002) while this correlation was not found within the other groups. Conclusions: Lower deposition fraction was observed for emphysematous subjects and this can be explained by enlarged distal airspaces in the lungs. As expected, deposition increases for smaller particles and deeper inhalation. The observed results have implications for exposure assessment of air pollution and dosimetry of aerosol-based drug delivery of nanoparticles.
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| 29. |
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| 30. |
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| 31. |
- Jakobsson, Liselotte, 1953-, et al.
(författare)
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The influence from sense of coherence on perceived health after prostatectomy : a 5 year follow up
- 2017
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Ingår i: Medical and Clinical Research. - 0976-5530. ; 2:2
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the study was to to describe which factors of health related quality of life were associated with a high sense of coherence in a 5 year perspective. The sense of coherence, SOC-scale, EORTC QLQ C-30 and PR 25 questionnaires were applied to a sample of 222 men at baseline and over 5 years following radical prostatectomy. Result showed significant association to SOC in psychological aspects (emotional and cognitive functioning, p=<0.00-0.04 respectively 0.04) and for hormone treatment related symptoms (i.e. manhood p=<0.05). High SOC was associated with quality of life (index) in the early post treatment period and to aspects of general functioning (role-, emotional- respectively cognitive) in year 3 and 5. High sense of coherence was interpreted to be a health resource for experiencing life quality connected to different aspects at different time points of the data collection. The result showed stability in SOC and QoL scoring over 5 years.
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| 32. |
- Jakobsson, Liselotte, et al.
(författare)
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The influence from sense of coherence on perceived health after prostatectomy : a 5 year follow up
- 2017
-
Ingår i: Medical and Clinical Research. - 0976-5530. ; 2:2
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of the study was to to describe which factors of health related quality of life were associated with a high sense of coherence in a 5 year perspective. The sense of coherence, SOC-scale, EORTC QLQ C-30 and PR 25 questionnaires were applied to a sample of 222 men at baseline and over 5 years following radical prostatectomy. Result showed significant association to SOC in psychological aspects (emotional and cognitive functioning, p=<0.00-0.04 respectively 0.04) and for hormone treatment related symptoms (i.e. manhood p=<0.05). High SOC was associated with quality of life (index) in the early post treatment period and to aspects of general functioning (role-, emotional- respectively cognitive) in year 3 and 5. High sense of coherence was interpreted to be a health resource for experiencing life quality connected to different aspects at different time points of the data collection. The result showed stability in SOC and QoL scoring over 5 years.
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| 33. |
- Jakobsson, Maija, et al.
(författare)
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Emergency peripartum hysterectomy: results from the prospective Nordic Obstetric Surveillance Study (NOSS)
- 2015
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 94:7, s. 745-754
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the prevalence and risk factors of emergency peripartum hysterectomy. Design:Nordic collaborative study. Population605362 deliveries across the five Nordic countries. Methods: We collected data prospectively from patients undergoing emergency peripartum hysterectomy within 7days of delivery from medical birth registers and hospital discharge registers. Control populations consisted of all other women delivering on the same units during the same time period. Main outcome measures: Emergency peripartum hysterectomy rate. Results: The total number of emergency peripartum hysterectomies reached 211, yielding an incidence rate of 3.5/10000 (95% confidence interval 3.0-4.0) births. Finland had the highest prevalence (5.1) and Norway the lowest (2.9). Primary indications included an abnormally invasive placenta (n=91, 43.1%), atonic bleeding (n=69, 32.7%), uterine rupture (n=31, 14.7%), other bleeding disorders (n=12, 5.7%), and other indications (n=8, 3.8%). The delivery mode was cesarean section in nearly 80% of cases. Previous cesarean section was reported in 45% of women. Both preterm and post-term birth increased the risk for emergency peripartum hysterectomy. The number of stillbirths was substantially high (70/1000), but the case fatality rate stood at 0.47% (one death, maternal mortality rate 0.17/100000 deliveries). Conclusions: A combination of prospective data collected from clinicians and information gathered from register-based databases can yield valuable data, improving the registration accuracy for rare, near-miss cases. However, proper and uniform clinical guidelines for the use of well-defined international diagnostic codes are still needed.
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| 34. |
- Jönsson, Marie, et al.
(författare)
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Comprehensive analysis of microRNA expression in regionalized human neural progenitor cells reveals microRNA-10 as a caudalizing factor.
- 2015
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Ingår i: Development: For advances in developmental biology and stem cells. - : The Company of Biologists. - 1477-9129. ; 142:18, s. 3166-3177
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Tidskriftsartikel (refereegranskat)abstract
- MicroRNAs (miRNAs) have been implicated in regulating multiple processes during brain development in various species. However, the function of miRNAs in human brain development remains largely unexplored. Here, we provide a comprehensive analysis of miRNA expression of regionalized neural progenitor cells derived from human embryonic stem cells and human foetal brain. We found miR-92b-3p and miR-130b-5p to be specifically associated with neural progenitors and several miRNAs that display both age-specific and region-specific expression patterns. Among these miRNAs, we identified miR-10 to be specifically expressed in the human hindbrain and spinal cord, while being absent from rostral regions. We found that miR-10 regulates a large number of genes enriched for functions including transcription, actin cytoskeleton and ephrin receptor signalling. When overexpressed, miR-10 influences caudalization of human neural progenitor cells. Together, these data confirm a role for miRNAs in establishing different human neural progenitor populations. This dataset also provides a comprehensive resource for future studies investigating the functional role of different miRNAs in human brain development.
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| 35. |
- Jönsson, Marie E., et al.
(författare)
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Activation of neuronal genes via LINE-1 elements upon global DNA demethylation in human neural progenitors
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation contributes to the maintenance of genomic integrity in somatic cells, in part through the silencing of transposable elements. In this study, we use CRISPR-Cas9 technology to delete DNMT1, the DNA methyltransferase key for DNA methylation maintenance, in human neural progenitor cells (hNPCs). We observe that inactivation of DNMT1 in hNPCs results in viable, proliferating cells despite a global loss of DNA CpG-methylation. DNA demethylation leads to specific transcriptional activation and chromatin remodeling of evolutionarily young, hominoid-specific LINE-1 elements (L1s), while older L1s and other classes of transposable elements remain silent. The activated L1s act as alternative promoters for many protein-coding genes involved in neuronal functions, revealing a hominoid-specific L1-based transcriptional network controlled by DNA methylation that influences neuronal protein-coding genes. Our results provide mechanistic insight into the role of DNA methylation in silencing transposable elements in somatic human cells, as well as further implicating L1s in human brain development and disease.
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| 36. |
- Kentson, Magnus, et al.
(författare)
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Factors associated with experience of fatigue, and functional limitations due to fatigue in patients with stable COPD
- 2016
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Ingår i: Therapeutic Advances in Respiratory Disease. - : Sage Publications. - 1753-4658 .- 1753-4666. ; 10:5, s. 410-424
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this study was to determine the influence of selected physiological, psychological and situational factors on experience of fatigue, and functional limitations due to fatigue in patients with stable chronic obstructive pulmonary disease (COPD). Methods: In total 101 patients with COPD and 34 control patients were assessed for experience of fatigue, functional limitation due to fatigue (Fatigue Impact Scale), physiological [lung function, 6-minute walk distance (6MWD), body mass index (BMI), dyspnoea, interleukin (IL)-6, IL-8, high sensitivity C-reactive protein (hs-CRP), surfactant protein D], psychological (anxiety, depression, insomnia), situational variables (age, sex, smoking, living alone, education), and quality of life. Results: Fatigue was more common in patients with COPD than in control patients (72% versus 56%, p < 0.001). Patients with COPD and fatigue had lower lung function, shorter 6MWD, more dyspnoea, anxiety and depressive symptoms, and worse health status compared with patients without fatigue (all p < 0.01). No differences were found for markers of systemic inflammation. In logistic regression, experience of fatigue was associated with depression [odds ratio (OR) 1.69, 95% confidence interval (CI) 1.28-2.25) and insomnia (OR 1.75, 95% CI 1.19-2.54). In linear regression models, depression, surfactant protein D and dyspnoea explained 35% (R-2) of the variation in physical impact of fatigue. Current smoking and depression explained 33% (R-2) of the cognitive impact of fatigue. Depression and surfactant protein D explained 48% (R-2) of the psychosocial impact of fatigue. Conclusions: Experiences of fatigue and functional limitation due to fatigue seem to be related mainly to psychological but also to physiological influencing factors, with depressive symptoms, insomnia problems and dyspnoea as the most prominent factors. Systemic inflammation was not associated with perception of fatigue but surfactant protein D was connected to some dimensions of the impact of fatigue
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| 37. |
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| 38. |
- Larsson, Karin, et al.
(författare)
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Biological characterization of new inhibitors of microsomal PGE synthase-1 in preclinical models of inflammation and vascular tone
- 2019
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Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 176:24, s. 4625-4638
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose Microsomal PGE synthase-1 (mPGES-1), the inducible synthase that catalyses the terminal step in PGE(2) biosynthesis, is of high interest as therapeutic target to treat inflammation. Inhibition of mPGES-1 is suggested to be safer than traditional NSAIDs, and recent data demonstrate anti-constrictive effects on vascular tone, indicating new therapeutic opportunities. However, there is a lack of potent mPGES-1 inhibitors lacking interspecies differences for conducting in vivo studies in relevant preclinical disease models. Experimental Approach Potency was determined based on the reduction of PGE(2) formation in recombinant enzyme assays, cellular assay, human whole blood assay, and air pouch mouse model. Anti-inflammatory properties were assessed by acute paw swelling in a paw oedema rat model. Effect on vascular tone was determined with human ex vivo wire myography. Key Results We report five new mPGES-1 inhibitors (named 934, 117, 118, 322, and 323) that selectively inhibit recombinant human and rat mPGES-1 with IC50 values of 10-29 and 67-250 nM respectively. The compounds inhibited PGE(2) production in a cellular assay (IC50 values 0.15-0.82 mu M) and in a human whole blood assay (IC50 values 3.3-8.7 mu M). Moreover, the compounds blocked PGE(2) formation in an air pouch mouse model and reduced acute paw swelling in a paw oedema rat model. Human ex vivo wire myography analysis showed reduced adrenergic vasoconstriction after incubation with the compounds. Conclusion and Implications These mPGES-1 inhibitors can be used as refined tools in further investigations of the role of mPGES-1 in inflammation and microvascular disease.
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| 39. |
- Laura Aaltonen, H., et al.
(författare)
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Airspace Dimension Assessment with nanoparticles reflects lung density as quantified by MRI
- 2018
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Ingår i: International Journal of Nanomedicine. - 1176-9114 .- 1178-2013. ; 13, s. 2989-2995
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Tidskriftsartikel (refereegranskat)abstract
- Background: Airspace Dimension Assessment with inhaled nanoparticles is a novel method to determine distal airway morphology. This is the first empirical study using Airspace Dimension Assessment with nanoparticles (AiDA) to estimate distal airspace radius. The technology is relatively simple and potentially accessible in clinical outpatient settings. Method: Nineteen never-smoking volunteers performed nanoparticle inhalation tests at multiple breath-hold times, and the difference in nanoparticle concentration of inhaled and exhaled gas was measured. An exponential decay curve was fitted to the concentration of recovered nanoparticles, and airspace dimensions were assessed from the half-life of the decay. Pulmonary tissue density was measured using magnetic resonance imaging (MRI). Results: The distal airspace radius measured by AiDA correlated with lung tissue density as measured by MRI (ρ = -0.584; p = 0.0086). The linear intercept of the logarithm of the exponential decay curve correlated with forced expiratory volume in one second (FEV1) (ρ = 0.549; p = 0.0149). Conclusion: The AiDA method shows potential to be developed into a tool to assess conditions involving changes in distal airways, eg, emphysema. The intercept may reflect airway properties; this finding should be further investigated.
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| 40. |
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| 41. |
- Löndahl, Jakob, et al.
(författare)
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Do nanoparticles provide a new opportunity for diagnosis of distal airspace disease?
- 2017
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Ingår i: International Journal of Nanomedicine. - 1176-9114. ; 12, s. 41-51
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Tidskriftsartikel (refereegranskat)abstract
- There is a need for efficient techniques to assess abnormalities in the peripheral regions of the lungs, for example, for diagnosis of pulmonary emphysema. Considerable scientific efforts have been directed toward measuring lung morphology by studying recovery of inhaled micron-sized aerosol particles (0.4-1.5 μm). In contrast, it is suggested that the recovery of inhaled airborne nanoparticles may be more useful for diagnosis. The objective of this work is to provide a theoretical background for the use of nanoparticles in measuring lung morphology and to assess their applicability based on a review of the literature. Using nanoparticles for studying distal airspace dimensions is shown to have several advantages over other aerosol-based methods. 1) Nanoparticles deposit almost exclusively by diffusion, which allows a simpler breathing maneuver with minor artifacts from particle losses in the oropharyngeal and upper airways. 2) A higher breathing flow rate can be utilized, making it possible to rapidly inhale from residual volume to total lung capacity (TLC), thereby eliminating the need to determine the TLC before measurement. 3) Recent studies indicate better penetration of nanoparticles than micron-sized particles into poorly ventilated and diseased regions of the lungs; thus, a stronger signal from the abnormal parts is expected. 4) Changes in airspace dimensions have a larger impact on the recovery of nanoparticles. Compared to current diagnostic techniques with high specificity for morphometric changes of the lungs, computed tomography and magnetic resonance imaging with hyperpolarized gases, an aerosol-based method is likely to be less time consuming, considerably cheaper, simpler to use, and easier to interpret (providing a single value rather than an image that has to be analyzed). Compared to diagnosis by carbon monoxide (DL,CO), the uptake of nanoparticles in the lung is not affected by blood flow, hemoglobin concentration or alterations of the alveolar membranes, but relies only on lung morphology.
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| 42. |
- Malmevik, Josephine, et al.
(författare)
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Distinct cognitive effects and underlying transcriptome changes upon inhibition of individual miRNAs in hippocampal neurons.
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- MicroRNAs (miRNA) are small, non-coding RNAs mediating post-transcriptional regulation of gene expression. miRNAs have recently been implicated in hippocampus-dependent functions such as learning and memory, although the roles of individual miRNAs in these processes remain largely unknown. Here, we achieved stable inhibition using AAV-delivered miRNA sponges of individual, highly expressed and brain-enriched miRNAs; miR-124, miR-9 and miR-34, in hippocampal neurons. Molecular and cognitive studies revealed a role for miR-124 in learning and memory. Inhibition of miR-124 resulted in an enhanced spatial learning and working memory capacity, potentially through altered levels of genes linked to synaptic plasticity and neuronal transmission. In contrast, inhibition of miR-9 or miR-34 led to a decreased capacity of spatial learning and of reference memory, respectively. On a molecular level, miR-9 inhibition resulted in altered expression of genes related to cell adhesion, endocytosis and cell death, while miR-34 inhibition caused transcriptome changes linked to neuroactive ligand-receptor transduction and cell communication. In summary, this study establishes distinct roles for individual miRNAs in hippocampal function.
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| 43. |
- Malmström, Helena Jankovic, et al.
(författare)
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Ancient mitochondrial DNA from the northern fringe of the Neolithic farming expansion in Europe sheds light on the dispersion process
- 2015
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Ingår i: Philosophical Transactions of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 370:1660
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Tidskriftsartikel (refereegranskat)abstract
- The European Neolithization process started around 12 000 years ago in the Near East. The introduction of agriculture spread north and west throughout Europe and a key question has been if this was brought about by migrating individuals, by an exchange of ideas or a by a mixture of these. The earliest farming evidence in Scandinavia is found within the Funnel Beaker Culture complex (Trichterbecherkultur, TRB) which represents the northernmost extension of Neolithic farmers in Europe. The TRB coexisted for almost a millennium with hunter-gatherers of the Pitted Ware Cultural complex (PWC). If migration was a substantial part of the Neolithization, even the northerly TRB community would display a closer genetic affinity to other farmer populations than to hunter-gatherer populations. We deep-sequenced the mitochondrial hypervariable region 1 from seven farmers (six TRB and one Battle Axe complex, BAC) and 13 hunter-gatherers (PWC) and authenticated the sequences using postmortem DNA damage patterns. A comparison with 124 previously published sequences from prehistoric Europe shows that the TRB individuals share a close affinity to Central European farmer populations, and that they are distinct from hunter-gatherer groups, including the geographically close and partially contemporary PWC that show a close affinity to the European Mesolithic hunter-gatherers.
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| 44. |
- Mattisson, Kristoffer, et al.
(författare)
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Modelling the association between health indicators and commute mode choice: a cross-sectional study in southern Sweden
- 2018
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Ingår i: Journal of Transport and Health. - : Elsevier BV. - 2214-1405. ; 11, s. 110-121
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Tidskriftsartikel (refereegranskat)abstract
- The impact of commuting on health depends, in part, on the mode of travel. A sizeable body of literature addresses associations between mode choice and health status, but little is known about how a person's health affects commuting mode choice. Stress, exhaustion and obesity are threats to public health that increase in modern societies. Understanding how these concerns impact mode choice is important in order to plan effective interventions. Differences in health status among different groups and geographical areas could influence the effectiveness of policy interventions to promote greater use of particular modes, such as public transit and cycling. We investigated associations between health and commuting mode choice using a cross-sectional population-based public health questionnaire data collected from 7574 commuters in southern Sweden in 2012, integrated with register data on residential and location, information on transportation networks, and other spatial data. Discrete Multinomial Logit (MNL) models were used to study the relationships between health indicators (everyday stress, vitality, long term illness, walking difficulties, and body mass index) and commuting mode (active, car and public transportation). Along with the health indicators, the models included conventional mode choice indicators such as socio-demographic attributes, commuting characteristics, and spatial variables. Everyday stress, obesity, and difficulty walking were negatively associated with the use of active and public modes. Understanding the relationship between health and mode choice in commuting, in relation to conventional indicators, can help support decision-makers and transportation planners develop more efficient interventions aimed at encourage car commuter's switch to more environmentally friendly and healthy modes such as active and public transportation. © 2018 Elsevier Ltd
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| 45. |
- Melandri, A., et al.
(författare)
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GRB171010A/SN 2017htp : a GRB-SN at z=0.33
- 2019
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 490:4, s. 5366-5374
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Tidskriftsartikel (refereegranskat)abstract
- The number of supernovae known to be connected with long-duration gamma-ray bursts (GRBs) is increasing and the link between these events is no longer exclusively found at low redshift (z less than or similar to 0.3) but is well established also at larger distances. We present a new case of such a liaison at z = 0.33 between GRB171010A and SN 2017htp. It is the second closest GRB with an associated supernova of only three events detected by Fermi-LAT. The supernova is one of the few higher redshift cases where spectroscopic observations were possible and shows spectral similarities with the well-studied SN 1998bw, having produced a similar Ni mass (M-Ni = 0.33 +/- 0.02 M-circle dot) with slightly lower ejected mass (M-ej = 4.1 +/- 0.7 M-circle dot) and kinetic energy (E-K = 8.1 +/- 2.5 x 10(51) erg). The host-galaxy is bigger in size than typical GRB host galaxies, but the analysis of the region hosting the GRB revealed spectral properties typically observed in GRB hosts and showed that the progenitor of this event was located in a very bright H II region of its face-on host galaxy, at a projected distance of similar to 10 kpc from its galactic centre. The star-formation rate (SFRGRB similar to 0.2 M-circle dot yr(-1)) and metallicity (12 + log(O/H) similar to 8.15 +/- 0.10) of the GRB star-forming region are consistent with those of the host galaxies of previously studied GRB-SN systems.
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| 46. |
- Naidoo, Thijessen, et al.
(författare)
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Patterns of variation in cis-regulatory regions : examining evidence of purifying selection
- 2018
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Ingår i: BMC Genomics. - : BIOMED CENTRAL LTD. - 1471-2164. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Background: With only 2 % of the human genome consisting of protein coding genes, functionality across the rest of the genome has been the subject of much debate. This has gained further impetus in recent years due to a rapidly growing catalogue of genomic elements, based primarily on biochemical signatures (e.g. the ENCODE project). While the assessment of functionality is a complex task, the presence of selection acting on a genomic region is a strong indicator of importance. In this study, we apply population genetic methods to investigate signals overlaying several classes of regulatory elements.Results: We disentangle signals of purifying selection acting directly on regulatory elements from the confounding factors of demography and purifying selection linked to e.g. nearby protein coding regions. We confirm the importance of regulatory regions proximal to coding sequence, while also finding differential levels of selection at distal regions. We note differences in purifying selection among transcription factor families. Signals of constraint at some genomic classes were also strongly dependent on their physical location relative to coding sequence. In addition, levels of selection efficacy across genomic classes differed between African and non-African populations.Conclusions: In order to assign a valid signal of selection to a particular class of genomic sequence, we show that it is crucial to isolate the signal by accounting for the effects of demography and linked-purifying selection. Our study highlights the intricate interplay of factors affecting signals of selection on functional elements.
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| 47. |
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| 48. |
- Owers, Katharine A., et al.
(författare)
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Adaptation to infectious disease exposure in indigenous Southern African populations
- 2017
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Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : ROYAL SOC. - 0962-8452 .- 1471-2954. ; 284:1852
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Tidskriftsartikel (refereegranskat)abstract
- Genetic analyses can provide information about human evolutionary history that cannot always be gleaned from other sources. We evaluated evidence of selective pressure due to introduced infectious diseases in the genomes of two indigenous southern African San groups-the double dagger Khomani who had abundant contact with other people migrating into the region and the more isolated Ju vertical bar'hoansi. We used a dual approach to test for increased selection on immune genes compared with the rest of the genome in these groups. First, we calculated summary values of statistics that measure genomic signatures of adaptation to contrast selection signatures in immune genes and all genes. Second, we located regions of the genome with extreme values of three selection statistics and examined these regions for enrichment of immune genes. We found stronger and more abundant signals of selection in immune genes in the double dagger Khomani than in the Ju vertical bar'hoansi. We confirm this finding within each population to avoid effects of different demographic histories of the two populations. We identified eight immune genes that have potentially been targets of strong selection in the double dagger Khomani, whereas in the Juj'hoansi, no immune genes were found in the genomic regions with the strongest signals of selection. We suggest that the more abundant signatures of selection at immune genes in the double dagger Khomani could be explained by their more frequent contact with immigrant groups, which likely led to increased exposure and adaptation to introduced infectious diseases.
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| 49. |
- Petersson, Klara, et al.
(författare)
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Acoustofluidic hematocrit determination
- 2018
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Ingår i: Analytica Chimica Acta. - : Elsevier BV. - 0003-2670. ; 1000, s. 199-204
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Tidskriftsartikel (refereegranskat)abstract
- Hematocrit (HCT) measurements of blood from patients, blood donors and athletes are routinely performed on a daily basis. These measurements are often performed in centralized hospital labs by whole blood analyzers, which leads to long time-to-result. On site measurements, based on centrifugation can be done, but these assays require manual handling, are slow and can just measure HCT in contrast to the central lab whole blood analyzers. In this work, we present a microfluidic based method to measure HCT in blood samples by acoustic separation of whole blood into discrete regions of plasma and red blood cells. Comparison of the areas of the red blood cell and plasma regions gives an accurate HCT value, with a linear correlation to the centrifugation-based reference method. A readout can be performed within 2 s of acoustic actuation providing a readout accuracy of approximately 3% points (pp) HCT. Additional accuracy can be achieved by extending the acoustic actuation to 20 s, yielding an error of less than 1 pp HCT. This acoustic tool is optimal for integration into a lab-on-a-chip device with in-line measurements of different clinical parameters.
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| 50. |
- Petersson, Klara, et al.
(författare)
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Twenty second acoustofluidic whole blood hematocrit assay
- 2016
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Ingår i: 20th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2016. - 9780979806490 ; , s. 635-636
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Konferensbidrag (refereegranskat)abstract
- This abstract reports a novel acoustofluidic method to measure the hematocrit level of a whole blood sample within 20 seconds. The method is substantially faster than conventional centrifugation methods, has no moving parts and can be fully automated and integrated with further unit operations for analysis of blood samples at the point of care [1].
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