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1.
  • Andersson, Mathias H, et al. (författare)
  • A framework for regulating underwater noise during pile driving
  • 2017
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Pile driving is a common technique used during the construction of bridges, offshore wind power, and underwater infrastructure or shoreline structures. It is the process by which a foundation, beam or pole is hammered or vibrated down into the bottom, which can generate extremely loud noise that propagates throughout the surrounding water and sediment. The noise can reach such high levels that marine animals are at risk of disturbance, injury or even death.Sweden currently lacks established thresholds stating the level at which underwater noise potentially disturbs or injures marine animals. Hence, there are no guidance values for allowable underwater noise levels from noiseproducing activities to avoid serious environmental impacts. Several countries in Europe have defined thresholds for when underwater noise can result in severe negative environmental impacts as well as standards for measuring, analysing and reporting underwater noise levels.The purpose of this study is to review the scientific literature on underwater noise from pile driving and its effects on marine life. The study aims to define the noise levels that can cause injury and other negative effects and, on this basis, recommend noise levels that can be used to establish guidance values for regulating underwater noise for Swedish waters and species. The study presents examples of the factors that contribute to sound propagation in Swedish waters and how this influences the noise level from a pile strike as a function of distance at four study areas along the Swedish coast. Additionally, the study contains a thorough technical description of pile driving activities, basic underwater acoustics and noise effects on marine animals. These effects (injury and behavioral, e.g., flight, but not subtle effects) are demonstrated on representative species such as the harbour porpoise (Phocoena phocoena), Atlantic cod (Gadus morhua), Atlantic herring (Clupea harengus) and on fish larvae and eggs. The study’s authors look atthe original sources of information that other countries base their guidelines and thresholds on, so the recommendations follow scientifically determined levels rather than values that have been rounded off or otherwise altered.The study presents sound levels in three different units, each with different biological relevance to the effects caused by a pile driving activity. None of the sound levels have been frequency weighted for a specific species, as this method is not yet fully established. The first unit used is the sound pressure level SPL(peak), which is the maximum overpressure or underpressure of the noise pulse generated by the pile strike. This unit has a high relevance for behavioural effects. The sound exposure level, SEL, is the calculated energy level over a period of time and expresses the energy of the entire sound pulse. SEL is the unit most related to hearing impairing effects. SEL(ss) is the value for a single strike while SEL(cum) is the cumulative value of a determined number of pulses over a period of time. The review revealed that for Atlantic cod and Atlantic herring there are currently no studies that can be used to determine a species’ specific threshold value for injury, but studies show that loud noise can affect both species negatively. Because of this, the recommended noise levels for injury are based mainly on studies on other species exposed to pile driving noise in laboratory environments, supported by studies conducting large-scale experiments in tanks and oceans. The levels at which fish are at risk of death or sustaining serious injury to internal organs is SPL 207 dB re 1 μPa, SEL(ss) 174 dB re 1 μPa2s and SEL(cum) 204 dB re 1 μPa2s. Note that for injury in fish, the cumulative sound exposure level has higher relevance than the single-strike level as the cited studies found injuries after a certain time period of exposure. The thresholds for fish larvae and eggs are based on the fact that no negative effects were observed at exposures of up to SPL(peak) 217 dB re 1 μPa, SEL(ss) 187 dB re 1 μPa2s and SEL(cum) 207 dB re 1 μPa2s. However, there are relatively few studies on early life stages of fish. There are more species-specific studies on harbour porpoises regarding noise than there are for Atlantic cod and Atlantic herring. Nonetheless, only a few can be used to determine thresholds that will lead to injury or negative behavioural effects. The levels at which there is a risk of a temporary impact on hearing, i.e. temporary threshold shift (TTS), for the harbour porpoises is SPL(peak) 194 dB re 1 μPa, SEL(ss) 164 dB re 1 μPa2s and SEL(cum) 175 dB re 1 μPa2s. When it comes to TTS, the cumulative sound exposure level, SEL(cum), is of primary importance. However, this unit is dependent on a specific time and number of pulses. For permanent threshold shift (PTS), the level is set to SPL(peak) 200 dB re 1 μPa, SEL(ss) 179 dB re 1 μPa2s and SEL(cum) 190 dB re 1 μPa2s. The recommended level should be revised as new relevant studies are conducted.
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2.
  • Andersson, Mathias H., et al. (författare)
  • Underlag för reglering av undervattensljud vid pålning
  • 2016
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Vid byggnation av broar, havsbaserad vindkraft och andra havsbaserade eller strandnära konstruktioner används det oftast någon form av pålningsteknik för att få ner konstruktionen i botten. Detta innebär att ett fundament, balk eller spont hamras eller vibreras ner i botten, vilket kan generera mycket höga ljudnivåer som sprids ut i vattnet och ner i botten. Ljudnivåerna är så höga att marina organismer kan störas, skadas eller till och med dödas. Idag saknar Sverige fastställda ljudnivåer för när undervattensbuller blir så högt att de kan skada djur i havet. Det saknas därför också vedertagna begränsningsvärden som anger vilka nivåer av undervattensbuller som kan tillåtas för bullrande aktiviteter utan att riskera allvarliga miljöeffekter. Flera länder i Europa har någon form av gränsvärden för när bullernivån under vattnet kan ge upphov till allvarlig miljöpåverkan liksom standarder för hur undervattensbuller skall mätas och rapporteras. Syftet med denna studie var att ta fram ett vetenskapligt underlag rörande ljudet från pålning i havet och dess påverkan på det marina livet. Slutmålet var att utifrån den vetenskapliga information som finns idag ge förslag på ljudnivåer för skador och negativ påverkan som sedan kan användas för att ta fram begränsningsvärden för reglering av undervattensbuller anpassade för svenska vatten och arter. Studien ger ett antal exempel på vilka faktorer som påverkar ljudutbredningen i svenska vatten och hur detta påverkar ett pålningsslags ljudnivå som funktion av avstånd i fyra typområden kring den svenska kusten. Vidare presenteras ingående både tekniska beskrivningar av pålningsaktiviteter, undervattensakustik samt påverkan på marina djur. Denna påverkan (skada och flyktbeteende men ej subtila effekter) demonstreras med hjälp av ett antal typarter som tandvalen tumlare (Phocoena phocoena) och fiskarterna torsk (Gadus morhua) och sill (Clupea clupea) samt fiskägg och fisklarver. I denna studie har författarna gått tillbaka till de originalkällor av information som andra länders gränsvärden grundas på, så att rekommendationerna bygger på vetenskapliga nivåer och inte värden som har avrundats eller på annat sätt ändrats.Studien presenterar ljudnivåer i tre olika enheter då dessa har olika biologisk relevans för påverkan från en pålningsaktivitet. Inga av dessa värden har frekvensviktats för att anpassas för en specifik art då denna metod ännu inte är helt vedertagen. Den första enheten är ljudtrycksnivå SPL(topp), d.v.s. det maximala över- eller undertryck som den av pålningsslaget genererade ljudpulsen har. Denna enhet har hög relevans för beteendepåverkan. För ljudexponeringsnivå SEL, beräknas ljudnivån över en viss tid och tar då med energin i hela ljudpulsen. SEL är den enhet som visats vara bäst relaterad till hörselskador. SEL(enkel) är värdet för en enkel puls och för det kumulativa SEL(kum) har antalet pulser under en viss tid summerats.Litteraturstudien på torsk och sill visar att det i dagsläget inte finns några studier som kan användas för att fastställa en artspecifik ljudnivå för skada men litteraturen visar tydligt på att höga bullernivåer kan påverka torsk och sill negativt. Istället baseras de föreslagna nivåerna i huvudsak på studier på andra arter som har exponerats för pålningsljud i laboratoriemiljö med stöd av studier från mer storskaliga experiment i tankar och hav. De nivåer då fisk riskerar att dödas eller få allvarliga skador på inre organ är 207 dB re 1 μPa SPL(topp), 174 dB re 1 μPa2s SEL(enkel) och 204 dB re 1 μPa2s SEL(kum). Notera att för skada på fisk har det kumulativa värdet högre relevans än enkelvärdet för SEL eftersom studier visar att skador uppkommer efter en viss tids exponering. Nivåerna för påverkan på fiskägg och larver grundas i att inga negativa effekter har observerats vid exponering för ljudtryck från pålning upp till 217 dB re 1 μPa SPL(topp), 187 dB re 1 μPa2s SEL(enkel) och 207 dB re 1 μPa2s SEL(kum). Det finns emellertid mycket få studier relaterat till pålningsljud för dessa livsstadier. För tumlare finns det fler artspecifika studier gjorda relaterat till buller än för torsk och sill. Det är dock endast ett fåtal som kan användas för att bestämma ljudnivåer som leder till skada eller negativ beteendepåverkan. De ljudnivåer som riskerar ge tillfällig hörselnedsättning (TTS) hos tumlare är 194 dB re 1 μPa SPL(topp), 164 dB re 1 μPa2s SEL(enkel) och 175 dB re 1 μPa2s SEL(kum). Det är framförallt den kumulativa ljudexponeringsnivån SEL(kum) som har stor betydelse för just TTS, dock hänger detta värde ihop med en specifik tid och antalet pulser vilket kan vara svårt att uppskatta i förväg. Vidare avseende permanent hörselskada (PTS) är ljudnivån 200 dB re 1 μPa SPL(topp), 179 dB re 1 μPa2s SEL(enkel) och 190 dB re 1 μPa2s SEL(kum). Föreslagna nivåer bör uppdateras när nya relevanta forskningsstudier tillkommer.
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  • Andersson, Cecilia K, et al. (författare)
  • Activated MCTC mast cells infiltrate diseased lung areas in cystic fibrosis and idiopathic pulmonary fibrosis
  • 2011
  • Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 12:139
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Although mast cells are regarded as important regulators of inflammation and tissue remodelling, their role in cystic fibrosis (CF) and idiopathic pulmonary fibrosis (IPF) has remained less studied. This study investigates the densities and phenotypes of mast cell populations in multiple lung compartments from patients with CF, IPF and never smoking controls. Methods: Small airways, pulmonary vessels, and lung parenchyma were subjected to detailed immunohistochemical analyses using lungs from patients with CF (20 lung regions; 5 patients), IPF (21 regions; 7 patients) and controls (16 regions; 8 subjects). In each compartment the densities and distribution of MCT and MCTC mast cell populations were studied as well as the mast cell expression of IL-6 and TGF-beta. Results: In the alveolar parenchyma in lungs from patients with CF, MCTC numbers increased in areas showing cellular inflammation or fibrosis compared to controls. Apart from an altered balance between MCTC and MCT cells, mast cell in CF lungs showed elevated expression of IL-6. In CF, a decrease in total mast cell numbers was observed in small airways and pulmonary vessels. In patients with IPF, a significantly elevated MCTC density was present in fibrotic areas of the alveolar parenchyma with increased mast cell expression of TGF-beta. The total mast cell density was unchanged in small airways and decreased in pulmonary vessels in IPF. Both the density, as well as the percentage, of MCTC correlated positively with the degree of fibrosis. The increased density of MCTC, as well as MCTC expression of TGF-beta, correlated negatively with patient lung function. Conclusions: The present study reveals that altered mast cell populations, with increased numbers of MCTC in diseased alveolar parenchyma, represents a significant component of the histopathology in CF and IPF. The mast cell alterations correlated to the degree of tissue remodelling and to lung function parameters. Further investigations of mast cells in these diseases may open for new therapeutic strategies.
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  • Andersson, Anneli, et al. (författare)
  • Continuous and simultaneous determination of venous blood metabolites
  • 2017
  • Ingår i: Talanta. - : Elsevier BV. - 0039-9140. ; 171, s. 270-274
  • Tidskriftsartikel (refereegranskat)abstract
    • Metabolic syndrome is associated with cardiovascular disease, type 2 diabetes mellitus (T2DM) and prediabetes. Metabolic syndrome is a cluster of interrelated clinical disorders. Difficulties in regulating glucose levels in blood are implicated in many of these disorders. Lactate, another energy metabolite, is produced under anaerobic conditions and can be used to monitor the balance between aerobic and anaerobic metabolism. Tested together, these metabolite levels can provide pro-diagnostic information that improves patient outcomes. Glucose and lactate were determined continuously and simultaneously in whole blood using a dual-channel thermal biosensor device in which one channel employed glucose oxidase for glucose analysis in comparison with lactate oxidase for lactate analysis in the others. No detectable clogging or interference was observed using venous blood samples. The linear detection range for both the glucose and lactate assays was 0.5–45 mM. The sampling rate of up to 24 samples per hour with assay cycle time of 2.5 min was achieved. Comparative analysis between our device and the HemoCue method showed an excellent correlation. The device was stable for hundreds of injections over a period of 45 days. The broad linear range, fast response and detection sensitivity are satisfactory for the clinical requirements, e.g. for diabetic or cardiovascular patients in intensive care units or surgical operation, where the tight control of blood glucose can decrease morbidity or mortality.
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  • Andersson, Greger, et al. (författare)
  • Stad och landsbygd
  • 1994
  • Ingår i: Musiken i Sverige.1. - 9170547009 - 9185428825 ; , s. 359-395
  • Bokkapitel (populärvet., debatt m.m.)
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11.
  • Andersson, Leif, et al. (författare)
  • Afghanistans skenande folkökning är ohållbar
  • 2021
  • Ingår i: Expressen. ; :3 oktober
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Sverige har pausat det mycket stora biståndet till Afghanistan, ett land med snabbt ökande befolkning. Landet är nu på väg mot omfattande resursbrist, fattigdom och svält. En viktig del i fortsatt bistånd bör vara familjeplanering som minskar de problem den skenande folkökningen orsakar
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  • Andersson, Lisa, et al. (författare)
  • Mutations in DMRT3 affect locomotion in horses and spinal circuit function in mice
  • 2012
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 488:7413, s. 642-646
  • Tidskriftsartikel (refereegranskat)abstract
    • Locomotion in mammals relies on a central pattern-generating circuitry of spinal interneurons established during development that coordinates limb movement(1). These networks produce left-right alternation of limbs as well as coordinated activation of flexor and extensor muscles(2). Here we show that a premature stop codon in the DMRT3 gene has a major effect on the pattern of locomotion in horses. The mutation is permissive for the ability to perform alternate gaits and has a favourable effect on harness racing performance. Examination of wild-type and Dmrt3-null mice demonstrates that Dmrt3 is expressed in the dI6 subdivision of spinal cord neurons, takes part in neuronal specification within this subdivision, and is critical for the normal development of a coordinated locomotor network controlling limb movements. Our discovery positions Dmrt3 in a pivotal role for configuring the spinal circuits controlling stride in vertebrates. The DMRT3 mutation has had a major effect on the diversification of the domestic horse, as the altered gait characteristics of a number of breeds apparently require this mutation.
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  • 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.
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  • Andersson, M, et al. (författare)
  • A Novel Selection System for Potato Transformation Using a Mutated AHAS Gene.
  • 2003
  • Ingår i: Plant Cell Reports. - : Springer Science and Business Media LLC. - 1432-203X .- 0721-7714. ; 22:4, s. 261-267
  • Tidskriftsartikel (refereegranskat)abstract
    • Acetohydroxyacid synthase (AHAS) is the target enzyme for a number of herbicides. A S653N mutation in the AHAS gene results in an increased tolerance to imidazolinone herbicides. We have investigated the use of the mutated gene as selection gene for potato transformation. This resulted in a transformation system with a very high transformation frequency and low rate of escapes. The mutated AHAS gene was introduced into transformed potato together with a -glucuronidase (GUS) gene. Selection on 0.5 M Imazamox yielded GUS expression in 93–100% of regenerated shoots. Furthermore the mutated AHAS gene was used as selection gene for production of high-amylopectin potato lines. The high transformation frequency was verified and potato lines with the desirable starch quality were obtained.
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  • Andersson, Magnus V., et al. (författare)
  • Kirurgi – omistligt komplement till medicinsk behandling
  • 2009
  • Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 106:45, s. 3003-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Kirurgi på rätt indikation och vid rätt tidpunkt är ett omistligt komplement till medicinsk behandling vid inflammatorisk tarmsjukdom, som förebygger sjukdomskomplikationer, förbättrar patienternas livskvalitet och ibland är livräddande. Kirurgi för ulcerös kolit görs oftast som ett tvåstegsförfarande: först kolektomi plus ileostomi med rektum lämnad intakt och i senare skede, med optimerad patient, tarmrekonstruktion anpassad efter patientens individuella livssituation. Kirurgi vid Crohns sjukdom korrigerar komplikationer (stenoser och fistlar) och sparar tarm genom begränsade resektioner och strikturplastiker. Laparoskopisk kir­urgi verkar ha viktiga fördelar vid primära tarmresektioner. Modern medicinsk behandling har förändrat indikationerna men ännu inte minskat behovet av kirurgi. Pågående antiinflammatorisk och immunmodulerande behandling är viktig att beakta i samband med kirurgi. Ett nära samspel mellan gastroenterolog och kolorektalkirurg är nödvändigt för att uppnå bästa möjliga långtidsprognos för de individer som lever med IBD.
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  • Andersson Sjöland, Annika, et al. (författare)
  • Fibroblast phenotypes and their activity are changed in the wound healing process after lung transplantation.
  • 2011
  • Ingår i: The Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1557-3117 .- 1053-2498. ; 30, s. 945-954
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Lung transplantation (LTx) is established as a life-saving treatment in end-stage lung disease. However, long-term survival is hampered by the development of chronic rejection, almost synonymous with bronchiolitis obliterans syndrome (BOS). The rejection is characterized by deposition of extracellular matrix in small airways. Fibroblasts/myofibroblasts are the main producers of extracellular matrix molecules such as proteoglycans. This study compared fibroblast phenotype and activity in the wound healing process at different points after LTx in patients who later did, or did not, develop BOS. METHODS: Distally derived fibroblasts from patients 6 and 12 months after LTx and from healthy controls were analyzed for production of the proteoglycans versican, perlecan, biglycan, and decorin, with and without transforming growth factor (TGF)-β(1). Fibroblast migration and proliferation were also studied. RESULTS: At 6 and 12 months after LTx, versican production was higher in fibroblasts from LTx patients (p < 0.01 p < 0.01) than from controls. Fibroblasts from patients who later developed BOS were more responsive to TGF-β(1)-induced synthesis of versican and biglycan than patients without signs of rejection (p < 0.05). Production of perlecan and decorin was negatively correlated with fibroblast proliferation in fibroblasts at 6 months after LTx. In a more detailed case study of 2 patients, one with and one without BOS, the altered proteoglycan profile was associated with impaired lung function. CONCLUSIONS: LTx changes the phenotype of fibroblasts to a non-proliferative but extracellular matrix-producing cell due to wound healing involving TGF-β(1). If not controlled, this may lead to development of BOS.
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  • Andersson Sjöland, Annika, et al. (författare)
  • Fibrocytes and the tissue niche in lung repair
  • 2011
  • Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 12
  • Forskningsöversikt (refereegranskat)abstract
    • Human fibrocytes are bone marrow-derived mesenchymal progenitor cells that express a variety of markers related to leukocytes, hematopoietic stem cells and a diverse set of fibroblast phenotypes. Fibrocytes can be recruited from the circulation to the tissue where they further can differentiate and proliferate into various mesenchymal cell types depending on the tissue niche. This local tissue niche is important because it modulates the fibrocytes and coordinates their role in tissue behaviour and repair. However, plasticity of a niche may be co-opted in chronic airway diseases such as asthma, idiopathic pulmonary fibrosis and obliterative bronchiolitis. This review will therefore focus on a possible role of fibrocytes in pathological tissue repair processes in those diseases.
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  • Andersson Sjöland, Annika, et al. (författare)
  • Fibrocytes are associated with vascular and parenchymal remodelling in patients with obliterative bronchiolitis.
  • 2009
  • Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 10:Oct 30
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The aim of the present study was to explore the occurrence of fibrocytes in tissue and to investigate whether the appearance of fibrocytes may be linked to structural changes of the parenchyme and vasculature in the lungs of patients with obliterative bronchiolitis (OB) following lung or bone marrow transplantation. METHODS: Identification of parenchyme, vasculature, and fibrocytes was done by histological methods in lung tissue from bone marrow or lung-transplanted patients with obliterative bronchiolitis, and from controls. RESULTS: The transplanted patients had significantly higher amounts of tissue in the alveolar parenchyme (46.5 +/- 17.6%) than the controls (21.7 +/- 7.6%) (p < 0.05). The patients also had significantly increased numbers of fibrocytes identified by CXCR4/prolyl4-hydroxylase, CD45R0/prolyl4-hydroxylase, and CD34/prolyl4-hydroxylase compared to the controls (p < 0.01). There was a correlation between the number of fibrocytes and the area of alveolar parenchyma; CXCR4/prolyl 4-hydroxylase (p < 0.01), CD45R0/prolyl 4-hydroxylase (p < 0.05) and CD34/prolyl 4-hydroxylase (p < 0.05). In the pulmonary vessels, there was an increase in the endothelial layer in patients (0.31 +/- 0.13%) relative to the controls (0.037 +/- 0.02%) (p < 0.01). There was a significant correlation between the number of fibrocytes and the total area of the endothelial layer CXCR4/prolyl 4-hydroxylase (p < 0.001), CD45R0/prolyl 4-hydroxylase (p < 0.001) and CD34/prolyl 4-hydroxylase (p < 0.01). The percent areas of the lumen of the vessels were significant (p < 0.001) enlarged in the patient with OB compared to the controls. There was also a correlation between total area of the lumen and number of fibrocytes, CXCR4/prolyl 4-hydroxylase (p < 0.01), CD45R0/prolyl 4-hydroxylase (p < 0.001) and CD34/prolyl 4-hydroxylase (p < 0.01). CONCLUSION: Our results indicate that fibrocytes are associated with pathological remodelling processes in patients with OB and that tissue fibrocytes might be a useful biomarker in these processes.
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  • Baranowska, Izabella, et al. (författare)
  • Sensory ataxic neuropathy in golden retriever dogs is caused by a deletion in the mitochondrial tRNATyr gene
  • 2009
  • Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 5:5, s. e1000499-
  • Tidskriftsartikel (refereegranskat)abstract
    • Sensory ataxic neuropathy (SAN) is a recently identified neurological disorder in golden retrievers. Pedigree analysis revealed that all affected dogs belong to one maternal lineage, and a statistical analysis showed that the disorder has a mitochondrial origin. A one base pair deletion in the mitochondrial tRNA(Tyr) gene was identified at position 5304 in affected dogs after re-sequencing the complete mitochondrial genome of seven individuals. The deletion was not found among dogs representing 18 different breeds or in six wolves, ruling out this as a common polymorphism. The mutation could be traced back to a common ancestor of all affected dogs that lived in the 1970s. We used a quantitative oligonucleotide ligation assay to establish the degree of heteroplasmy in blood and tissue samples from affected dogs and controls. Affected dogs and their first to fourth degree relatives had 0-11% wild-type (wt) sequence, while more distant relatives ranged between 5% and 60% wt sequence and all unrelated golden retrievers had 100% wt sequence. Northern blot analysis showed that tRNA(Tyr) had a 10-fold lower steady-state level in affected dogs compared with controls. Four out of five affected dogs showed decreases in mitochondrial ATP production rates and respiratory chain enzyme activities together with morphological alterations in muscle tissue, resembling the changes reported in human mitochondrial pathology. Altogether, these results provide conclusive evidence that the deletion in the mitochondrial tRNA(Tyr) gene is the causative mutation for SAN.
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  • Baranowska Körberg, Izabella, et al. (författare)
  • A Simple Repeat Polymorphism in the MITF-M Promoter Is a Key Regulator of White Spotting in Dogs
  • 2014
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8, s. e104363-
  • Tidskriftsartikel (refereegranskat)abstract
    • The white spotting locus (S) in dogs is colocalized with the MITF (microphtalmia-associated transcription factor) gene. The phenotypic effects of the four S alleles range from solid colour (S) to extreme white spotting (s(w)). We have investigated four candidate mutations associated with the s(w) allele, a SINE insertion, a SNP at a conserved site and a simple repeat polymorphism all associated with the MITF-M promoter as well as a 12 base pair deletion in exon 1B. The variants associated with white spotting at all four loci were also found among wolves and we conclude that none of these could be a sole causal mutation, at least not for extreme white spotting. We propose that the three canine white spotting alleles are not caused by three independent mutations but represent haplotype effects due to different combinations of causal polymorphisms. The simple repeat polymorphism showed extensive diversity both in dogs and wolves, and allele-sharing was common between wolves and white spotted dogs but was non-existent between solid and spotted dogs as well as between wolves and solid dogs. This finding was unexpected as Solid is assumed to be the wild-type allele. The data indicate that the simple repeat polymorphism has been a target for selection during dog domestication and breed formation. We also evaluated the significance of the three MITF-M associated polymorphisms with a Luciferase assay, and found conclusive evidence that the simple repeat polymorphism affects promoter activity. Three alleles associated with white spotting gave consistently lower promoter activity compared with the allele associated with solid colour. We propose that the simple repeat polymorphism affects cooperativity between transcription factors binding on either flanking sides of the repeat. Thus, both genetic and functional evidence show that the simple repeat polymorphism is a key regulator of white spotting in dogs.
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  • Bengtsson, Stefan, et al. (författare)
  • Mind the gap! Moving from awareness to action : Showcasing emergent research from the Swedish Graduate School in Education for Sustainable Development (GRESD)
  • 2015
  • Ingår i: Abstract list of WEEC 2015. - : WEEC.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction: The main purpose of the symposium is to showcase some recent research findings produced by PhD students accepted by or affiliated with the Swedish Graduate School in Education for Sustainable development (GRESD). Objectives: GRESD started as a state sponsored one-time research capacity development project that accepted 9 post-graduate student and included additional 9 post-graduate students all focusing on ESD in their PhD projects. With the project coming to an end and having produced a number of dissertations targeting an international research audience, it is the intention to showcase some of the central contributions made and to receive feedback on from practitioners and researchers on how existent research projects can tie into and contribute to existent demands in environmental education (EE) practice and practice. The presentations of research results are aimed to cover a wide range of issues, including topics such as evaluation of classroom practices, students qualifications, globalization and teachers’ ethical reflections the role of place-specific artifacts in learning. As GRESD is a collaboration between eight universities with their specific traditions and approaches to educational research, approaches show a creative variety of theoretical backgrounds. This variation is also reflected in the presentations that are putting into play Lacanian psychoanalysis, discourse theory, pragmatist theory and phenomenography in order to shed new light on critical areas of environmental education. Methods: The symposium will consist of an introduction (10 minutes) brief presentations (10-15 minutes each) of central research findings in the context of their overarching research projects, followed by a synthesis and suggestions by a selected commentator (20 minutes) and general discussions with the audience (20 minutes). The dialogue following the presentations is intended to outline possible future research projects as well as emerging areas topics in the portrayed GRESD research that could feed into existing demands in EE practice and research.
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40.
  • Enes, Sara Rolandsson, et al. (författare)
  • MSC from fetal and adult lungs possess lung-specific properties compared to bone marrow-derived MSC
  • 2016
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 29160-
  • Tidskriftsartikel (refereegranskat)abstract
    • Mesenchymal stromal cells (MSC) are multipotent cells with regenerative and immune-modulatory properties. Therefore, MSC have been proposed as a potential cell-therapy for bronchiolitis obliterans syndrome (BOS). On the other hand, there are publications demonstrating that MSC might be involved in the development of BOS. Despite limited knowledge regarding the functional role of tissue-resident lung-MSC, several clinical trials have been performed using MSC, particularly bone marrow (BM)-derived MSC, for various lung diseases. We aimed to compare lung-MSC with the well-characterized BM-MSC. Furthermore, MSC isolated from lung-transplanted patients with BOS were compared to patients without BOS. Our study show that lung-MSCs are smaller, possess a higher colony-forming capacity and have a different cytokine profile compared to BM-MSC. Utilizing gene expression profiling, 89 genes including lung-specific FOXF1 and HOXB5 were found to be significantly different between BM-MSC and lung-MSC. No significant differences in cytokine secretion or gene expression were found between MSC isolated from BOS patients compared recipients without BOS. These data demonstrate that lung-resident MSC possess lung-specific properties. Furthermore, these results show that MSC isolated from lung-transplanted patients with BOS do not have an altered phenotype compared to MSC isolated from good outcome recipients.
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41.
  • Fegraeus, K. Jaderkvist, et al. (författare)
  • Different DMRT3 Genotypes Are Best Adapted for Harness Racing and Riding in Finnhorses
  • 2015
  • Ingår i: Journal of Heredity. - : Oxford University Press (OUP). - 0022-1503 .- 1465-7333. ; 106:6, s. 734-740
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies showed a positive effect of the DMRT3 "gait keeper" mutation on harness racing performance in Standardbreds, French-, and Nordic trotters. The mutation has also been shown to influence riding traits in multiple breeds. This study investigated the effect of the DMRT3 mutation on harness racing performance and riding traits in Finnhorses. Finnhorses used for harness racing (n = 180) and for riding (n = 59) were genotyped for the DMRT3 mutation. For the trotters the genotypes were evaluated for association with racing performance (number of starts, victories, placings, earnings, and race times). At 3-6 years of age the AA genotype was superior compared with the CA and CC genotypes. The AA horses had a significantly higher proportion of victories (P = 1.4 x 10(-6)) and placings (P = 4.1 x 10(-7)), better race times (P = 0.01), and earned more money (P = 0.009) compared with C-horses. For the Finnhorses used for riding the owners answered a questionnaire to score how well the horse performed the gaits walk, trot, and canter on a scale from 1 to 6. These scores were tested for association with the DMRT3 genotypes. Although AA horses were more successful as racehorses, the CC and CA horses appear more adapted for classical riding disciplines. The AA horses received significantly lower gait scores compared with C-horses for the majority of gaits. Except for rhythm in extended canter (P = 0.05), there were no significant differences between CA and CC horses. This study shows that there are different optimal genotypes for different disciplines and the DMRT3 mutation clearly influences gaits and performance in Finnhorses.
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42.
  • Gunnarsson, Ulrika (författare)
  • Genetic Studies of Pigmentation in Chicken
  • 2009
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Domestic animals have been selected by humans for thousands of years, which have drastically altered their genetic constitution and phenotypes. In this thesis, several of the most important genes causing pigmentation differences between the wild red junglefowl (Gallus gallus) and domestic chickens have been identified. Pigmentation phenotypes are easily scored, and the genes underlying these phenotypes are valuable models to study gene function and gene interaction. Dominant white colour is widespread among domestic chickens. The Dominant white allele specifically inhibits the expression of black (eumelanin) pigment and we identified several insertion/deletion mutations in the PMEL17 gene causing the different phenotypes controlled by this locus. The Silver allele on the other hand inhibits the expression of red (pheomelanin) colour and is a genetic variant of the SLC45A2 gene. Silver is the first pheomelanin-specific mutation(s) reported for this gene. An 8 kb deletion, including a conserved enhancer element, 14 kb upstream of the transcription factor SOX10 is causing the Dark brown phenotype. This phenotype restricts the expression of eumelanin and enhances red pheomelanin in specific parts of the plumage. These three gene identifications have extended the knowledge about genes affecting melanocyte function. Carotenoid-based pigmentation is of utmost importance in birds and other animals. The yellow skin allele in chicken allows deposition of carotenoids in skin and explains why most domestic chickens have yellow legs. We demonstrated that the yellow skin phenotype is caused by a tissue specific regulatory mutation in the gene for the enzyme beta-caroten dioxygenase 2 (BCDO2). This was the first identification of a specific gene underlying carotenoid-based pigmentation. Interestingly, the yellow skin haplotype was shown to originate from the grey junglefowl (Gallus sonneratii) and not the red junglefowl as expected, thus presenting the first conclusive evidence for a hybrid origin of the domestic chicken.  
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43.
  • Hallgren, Oskar, et al. (författare)
  • Enhanced ROCK1 dependent contractility in fibroblast from chronic obstructive pulmonary disease patients
  • 2012
  • Ingår i: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: During wound healing processes fibroblasts account for wound closure by adopting a contractile phenotype. One disease manifestation of COPD is emphysema which is characterized by destruction of alveolar walls and our hypothesis is that fibroblasts in the COPD lungs differentiate into a more contractile phenotype as a response to the deteriorating environment. Methods: Bronchial (central) and parenchymal (distal) fibroblasts were isolated from lung explants from COPD patients (n = 9) (GOLD stage IV) and from biopsies from control subjects and from donor lungs (n = 12). Tissue-derived fibroblasts were assessed for expression of proteins involved in fibroblast contraction by western blotting whereas contraction capacity was measured in three-dimensional collagen gels. Results: The basal expression of rho-associated coiled-coil protein kinase 1 (ROCK1) was increased in both centrally and distally derived fibroblasts from COPD patients compared to fibroblasts from control subjects (p < 0.001) and (p < 0.01), respectively. Distally derived fibroblasts from COPD patients had increased contractile capacity compared to control fibroblasts (p < 0.01). The contraction was dependent on ROCK1 activity as the ROCK inhibitor Y27632 dose-dependently blocked contraction in fibroblasts from COPD patients. ROCK1-positive fibroblasts were also identified by immunohistochemistry in the alveolar parenchyma in lung tissue sections from COPD patients. Conclusions: Distally derived fibroblasts from COPD patients have an enhanced contractile phenotype that is dependent on ROCK1 activity. This feature may be of importance for the elastic dynamics of small airways and the parenchyma in late stages of COPD.
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44.
  • Hayward, Alexander, et al. (författare)
  • ZBED Evolution : Repeated Utilization of DNA Transposons as Regulators of Diverse Host Functions
  • 2013
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:3, s. e59940-
  • Tidskriftsartikel (refereegranskat)abstract
    • ZBED genes originate from domesticated hAT DNA transposons and encode regulatory proteins of diverse function in vertebrates. Here we reveal the evolutionary relationship between ZBED genes and demonstrate that they are derived from at least two independent domestication events in jawed vertebrate ancestors. We show that ZBEDs form two monophyletic clades, one of which has expanded through several independent duplications in host lineages. Subsequent diversification of ZBED genes has facilitated regulation of multiple diverse fundamental functions. In contrast to known examples of transposable element exaptation, our results demonstrate a novel unprecedented capacity for the repeated utilization of a family of transposable element-derived protein domains sequestered as regulators during the evolution of diverse host gene functions in vertebrates. Specifically, ZBEDs have contributed to vertebrate regulatory innovation through the donation of modular DNA and protein interacting domains. We identify that C7ORF29, ZBED2, 3, 4, and ZBEDX form a monophyletic group together with ZBED6, that is distinct from ZBED1 genes. Furthermore, we show that ZBED5 is related to Buster DNA transposons and is phylogenetically separate from other ZBEDs. Our results offer new insights into the evolution of regulatory pathways, and suggest that DNA transposons have contributed to regulatory complexity during genome evolution in vertebrates.
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45.
  • Hedrick, P. W., et al. (författare)
  • Are dogs genetically special?
  • 2011
  • Ingår i: Heredity. - : Springer Science and Business Media LLC. - 0018-067X .- 1365-2540. ; 106:5, s. 712-713
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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46.
  • Jiang, Lin, et al. (författare)
  • The role of ZBED6 in transcriptional regulation studied by transcriptome  analysis after RNAi in mouse myoblasts
  • Forskningsöversikt (övrigt vetenskapligt/konstnärligt)abstract
    • ZBED6 is a recently discovered transcription factor that has evolved from a domesticated DNA transposon and is unique to placental mammals. Here we further characterize the functional significance of ZBED6 based on transcriptome analysis of mouse myoblasts after Zbed6-silencing. ZBED6 appears as an important transcriptional regulator since differential expression of more than 700 genes was observed after Zbed6-silencing. The most significantly enriched GO term was muscle protein and contractile fiber, which is consistent with increased myotube formation. Twenty small nucleolar RNAs showed differential expression and all increased in expression after Zbed6-silencing. This is particularly interesting because ZBED6 localization is strongly enriched in the nucleolus. There was an overrepresentation of genes with ZBED6 binding sites among the differentially expressed genes after silencing, suggesting that ZBED6 acts as a transcriptional regulator at many loci. Many genes showed significant down-regulation after Zbed6-silencing, which begs the question of whether ZBED6 acts as an activator at some of these loci or if the decreased mRNA levels of these genes all represent secondary effects. The co-localization of histone marks and ZBED6 binding sites and the effect of ZBED6-silencing on distribution of histone marks was evaluated by ChIP-seq. There was a strong association between ZBED6 binding sites and the H3K4me3, H3K4me2 and H3K27ac modifications, which are usually found at active promoters, but no association with the repressive marks H3K27me3. We propose that ZBED6 preferentially binds to active promoters and modulates transcriptional activity by a novel mechanism rather than by recruiting repressive histone modifications.  
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47.
  • Jiang, Lin, et al. (författare)
  • ZBED6 Modulates the Transcription of Myogenic Genes in Mouse Myoblast Cells
  • 2014
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:4, s. e94187-
  • Tidskriftsartikel (refereegranskat)abstract
    • ZBED6 is a recently discovered transcription factor, unique to placental mammals, that has evolved from a domesticated DNA transposon. It acts as a repressor at the IGF2 locus. Here we show that ZBED6 acts as a transcriptional modulator in mouse myoblast cells, where more than 700 genes were differentially expressed after Zbed6-silencing. The most significantly enriched GO term was muscle protein and contractile fiber, which was consistent with increased myotube formation. Twenty small nucleolar RNAs all showed increased expression after Zbed6-silencing. The co-localization of histone marks and ZBED6 binding sites and the effect of Zbed6-silencing on distribution of histone marks was evaluated by ChIP-seq analysis. There was a strong association between ZBED6 binding sites and the H3K4me3, H3K4me2 and H3K27ac modifications, which are usually found at active promoters, but no association with the repressive mark H3K27me3. Zbed6-silencing led to increased enrichment of active marks at myogenic genes, in agreement with the RNA-seq findings. We propose that ZBED6 preferentially binds to active promoters and modulates transcriptional activity without recruiting repressive histone modifications.
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50.
  • Jäderkvist Fegraeus, Kim, et al. (författare)
  • Lack of significant associations with early career performance suggest no link between the DMRT3 "Gait Keeper" mutation and precocity in Coldblooded trotters
  • 2017
  • Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 12:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The Swedish-Norwegian Coldblooded trotter (CBT) is a local breed in Sweden and Norway mainly used for harness racing. Previous studies have shown that a mutation from cytosine (C) to adenine (A) in the doublesex and mab-3 related transcription factor 3 (DMRT3) gene has a major impact on harness racing performance of different breeds. An association of the DMRT3 mutation with early career performance has also been suggested. The aim of the current study was to investigate this proposed association in a randomly selected group of CBTs. 769 CBTs (485 raced, 284 unraced) were genotyped for the DMRT3 mutation. The association with racing performance was investigated for 13 performance traits and three different age intervals: 3 years, 3 to 6 years, and 7 to 10 years of age, using the statistical software R. Each performance trait was analyzed for association with DMRT3 using linear models. The results suggest no association of the DMRT3 mutation with precocity (i.e. performance at 3 years of age). Only two traits (race time and number of disqualifications) were significantly different between the genotypes, with AA horses having the fastest times and CC horses having the highest number of disqualifications at 3 years of age. The frequency of the AA genotype was significantly lower in the raced CBT sample compared with the unraced sample and less than 50% of the AA horses participated in a race. For the age intervals 3 to 6 and 7 to 10 years the AA horses also failed to demonstrate significantly better performance than the other genotypes. Although suggested as the most favorable genotype for racing performance in Standardbreds and Finnhorses across all ages, the AA genotype does not appear to be associated with superior performance, early or late, in the racing career of CBTs.
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