| 1. |
- Bergström, Lena, et al.
(författare)
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Distribution of mesopredatory fish determined by habitat variables in a predator-depleted coastal system
- 2016
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Ingår i: Marine Biology. - : Springer Science and Business Media LLC. - 0025-3162 .- 1432-1793. ; 163
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Tidskriftsartikel (refereegranskat)abstract
- Shallow nearshore habitats are highly valued for supporting marine ecosystems, but are subject to intense human-induced pressures. Mesopredatory fish are key components in coastal food webs, and alterations in their abundance may have evident effects also on other parts of the ecosystem. The aim of this study was to clarify the relationship between the abundance of coastal mesopredatory fish, defined as mid-trophic level demersal and benthic species with a diet consisting predominantly of invertebrates, and ambient environmental variables in a fjord system influenced by both eutrophication and overfishing. A field survey was conducted over a coastal gradient comprising 300 data points sampled consistently for fish community and environmental data. Results from multivariate and univariate analyses supported each other, demonstrating that mesopredatory fish abundance at species and functional group level was positively related to the cover of structurally complex vegetation and negatively related to eutrophication, as measured by water transparency. Contrary to other studies showing an inverse relationship to piscivore abundance over time, the spatial distribution of mesopredatory fish was not locally regulated by the abundance of piscivorous fish, probably attributed to piscivores being at historically low levels due to previous overfishing. Mesopredatory fish abundance was highest in areas with high habitat quality and positively related to the abundance of piscivores, suggesting a predominance of bottom-up processes. We conclude that, in parallel with ongoing regulations of fishing pressure, measures to restore habitat function and food web productivity are important for the recovery of coastal fish communities in the area.
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| 2. |
- Bergström, Lena, et al.
(författare)
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Relative impacts of fishing and eutrophication on coastal fish assessed by comparing a no-take area with an environmental gradient
- 2019
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 48:6, s. 565-579
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the relative impacts of pressures on coastal ecosystems is central for implementing relevant measures to reach environmental management objectives. Here, survey data on the species and size composition of coastal fish are evaluated in relation to fishing and eutrophication, by comparing a long-standing no-take area to an environmental gradient in the Baltic Sea. The no-take area represents an intermediate eutrophication level, but the species composition resembles that seen at low eutrophication in areas with fishing. The catch biomass of piscivores is 2-3 times higher in the no-take area than in the other areas, while the biomass of Cyprinids, generally benefitted by eutrophication, corresponds to that of areas with low eutrophication. The results support that fishing may generate eutrophication-like effects, and, conversely, that no-take areas may contribute to improving environmental status in impacted areas by enhancing piscivores, which in turn may contribute to further improvement in the food web.
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| 3. |
- Boyd, Ben J., et al.
(författare)
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Successful oral delivery of poorly water-soluble drugs both depends on the intraluminal behavior of drugs and of appropriate advanced drug delivery systems
- 2019
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Ingår i: European Journal of Pharmaceutical Sciences. - : ELSEVIER. - 0928-0987 .- 1879-0720. ; 137
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Tidskriftsartikel (refereegranskat)abstract
- Poorly water-soluble drugs continue to be a problematic, yet important class of pharmaceutical compounds for treatment of a wide range of diseases. Their prevalence in discovery is still high, and their development is usually limited by our lack of a complete understanding of how the complex chemical, physiological and biochemical processes that occur between administration and absorption individually and together impact on bioavailability. This review defines the challenge presented by these drugs, outlines contemporary strategies to solve this challenge, and consequent in silico and in vitro evaluation of the delivery technologies for poorly water-soluble drugs. The next steps and unmet needs are proposed to present a roadmap for future studies for the field to consider enabling progress in delivery of poorly water-soluble compounds.
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| 4. |
- Domert, Jakob, et al.
(författare)
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Aggregated Alpha-Synuclein Transfer Efficiently between Cultured Human Neuron-Like Cells and Localize to Lysosomes
- 2016
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson's disease and other alpha-synucleinopathies are progressive neurodegenerative diseases characterized by aggregates of misfolded alpha-synuclein spreading throughout the brain. Recent evidence suggests that the pathological progression is likely due to neuron-to-neuron transfer of these aggregates between neuroanatomically connected areas of the brain. As the impact of this pathological spreading mechanism is currently debated, we aimed to investigate the transfer and subcellular location of alpha-synuclein species in a novel 3D co-culture human cell model based on highly differentiated SH-SY5Y cells. Fluorescently-labeled monomeric, oligomeric and fibrillar species of alpha-synuclein were introduced into a donor cell population and co-cultured with an EGFP-expressing acceptor-cell population of differentiated neuron-like cells. Subsequent transfer and colocalization of the different species were determined with confocal microscopy. We could confirm cell-to-cell transfer of all three alpha-synuclein species investigated. Interestingly the level of transferred oligomers and fibrils and oligomers were significantly higher than monomers, which could affect the probability of seeding and pathology in the recipient cells. Most alpha-synuclein colocalized with the lysosomal/endosomal system, both pre- and postsynaptically, suggesting its importance in the processing and spreading of alpha-synuclein.
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| 5. |
- Enhus, Carolina, et al.
(författare)
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Kontrollprogram för vindkraft i vatten : Sammanställning och granskning, samt förslag till rekommendationer för utformning av kontrollprogram
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Denna rapport har tagits fram med finansiering av kunskapsprogrammet Vindval. Rapporten syftar till att svara på projektmålen gällande granskning och utvärdering av befintliga kontrollprogram, lista de miljöeffekter som upptäckts, samt att ge förslag till rekommendationer för utformning av kontrollprogram.Den havsbaserade vindkraften har utvecklats både tekniskt och geografiskt de senaste 25 åren. Inklusive de parker som var under byggnation fanns det år 2015 totalt 84 havsbaserade vindparker i Europa, fördelat på elva länder. Idag placeras majoriteten av vindkraft i saltvattensområden som Nordsjön, Östersjön och andra havsområden i norra Europa. Etablering av vindkraft till havs medför ett ingrepp och en påverkan på den marina miljön och de organismer som lever där. Kunskapen om hur etablering och drift av havsbaserad vindkraft påverkar det marina livet varierar beroende på organismgrupp, påverkanstyp, område och skala. Olika typer av påverkan uppkommer under de olika faserna av ett vindkraftsverks livstid. Vilken typ av påverkan som sker är beroende av vilket typ av fundament verket etableras med, vilka miljöförhållanden som råder, samt vilka berörda arter som finns i det specifika området. För att dokumentera och synliggöra de potentiella effekter som verksamheten kan ha på den marina miljön upprättas kontrollprogram för uppföljning av arter och miljöeffekter.Kontrollprogrammen i denna sammanställning kommer från vindkraftsparker med en rad likheter och olikheter, i bland annat havsområde, storlek, fundamenttyp och tid sedan driftstart. De absolut mest omfattande kontrollprogrammen i Sverige utgörs av de kontrollprogram som upprättades för Lillgrund, där alla djurgrupper utom marina däggdjur undersöktes. För de europeiska länder som granskades varierar antalet insamlade (befintliga) dokument mellan de olika vindkraftsparkerna. För de båda relativt stora parkerna Egmond aan Zee och Prinses Amalia i Nederländerna har omfattande undersökningar utförts för samtliga organismgrupper, medan dokumenten för danska och brittiska parker varierar i omfattning.Den mest undersökta påverkansfaktorn i granskade kontrollprogram för bottensamhälle och fisk är förlust/tillkomst av habitat, för marina däggdjur undervattensljud och för fågel fysiskt hinder. En jämförelse mellan Vindvals syntesrapport (Bergström m.fl. 2012) och resultaten från sammanställda kontrollprogram visar att omfattningen av de påverkansfaktorer som redovisades i syntesrapporten i stort sett gäller även för de granskade kontrollprogrammen. Graden av påverkan har dock justerats något åt det mindre hållet för några påverkansfaktorer utifrån resultaten i befintliga kontrollprogram.Kontrollprogrammen visar att hårdbottenlevande arter etablerar sig på fundamenten, men efter olika lång tid. Vilka arter som dominerar beror på en rad faktorer, såsom djup, salthalt, exponeringsgrad och strömmar, och skillnader förekommer mellan parker i olika områden. Generellt verkar inverkan på mjukbottenlevande djur på större skala vara liten, trots etableringen av nya hårda substrat. Dock ses lokala förändringar kring fundamenten, kopplade till etableringen av arter nya för området, strömförhållanden m.m. Gällande fisk är det inte helt tydligt om tillkomsten av habitat (reveffekten) ökar biomassan i området eller om det snarare handlar om en omfördelning av befintlig biomassa. Resultaten från insamlade kontrollprogram visar att flertalet fiskarter vid flera vindparker har tydliga rumsliga och säsongs- och/eller dygnsberoende variationer i utbredningsmönster. I många områden är eventuella effekter på fisksamhället svåra att skilja från den naturliga variationen i området. I några fall påvisades möjliga effekter av trålningsskydd, men för andra parker sågs ingen effekt jämfört med referensområdena. Kontrollprogrammen för marina däggdjur tyder på att effekterna generellt är park- eller områdesspecifika. Majoriteten av undersökningarna visar att djuren undviker området i anläggningsfasen, men sedan återkommer när parken är i drift. Detta kan dock ta olika lång tid, och i några fall återhämtar populationen i området sig inte alls. I ett fall var tumlaraktiviteten högre inne i parkområdet, vilket är i motsats till tidigare resultat för andra parker. Effekten på fågel av parkens fysiska närvaro verkar vara väldigt artspecifik. Fåglarna undviker generellt parken i anläggningsfasen, men under driftsfasen undviker vissa arter parken och vissa attraheras av den. I några fall verkar fåglarna ha ändrat sin rumsliga utbredning i förhållande till parken. Flyttande fåglar väjer generellt för området, vilket bidrar till en ökad flygsträcka men också en minskad kollisionsrisk. Hur nära fåglarna flyger parken verkar variera mellan dag och natt för vissa arter, samt är beroende av vilka väderförhållanden som råder (dimma till exempel). Kollisionsrisken anses liten för majoriteten av arter, och de få fåglar som förolyckas påverkar sannolikt inte populationen i de specifika områdena.Vindkraftparker i olika områden skiljer sig med avseende på fysiska och geografiska förutsättningar, och den påverkan som behöver följas upp beror av vilka arter eller organismgrupper som finns i det specifika området. Därför varierar behovet av kontrollprogrammens omfattning för olika vindkraftparker och områden. Det är viktigt att redan i ett tidigt skede undersöka och skaffa information kring vilka ekosystemkomponenter (arter, artkomplex eller biotoper) som förekommer i området där vindkraften planeras, vilka aktiviteter som troligen kommer att utföras, samt vilken påverkan som aktiviteterna kan tänkas leda till för respektive ekosystemkomponent, det vill säga att ha en tydlig frågeställning. Valet av provtagningsdesign bör baseras på den naturliga variationen hos berörd ekosystemkomponent, typ av förväntad påverkan, samt krav på statistisk styrka. Det är av stor vikt att anpassa kontrollprogrammens rumsliga och tidsmässiga skala efter vilka arter/organismgrupper som möjligen kan påverkas, samt av vilken påverkan. Det är även viktigt att redogöra för och följa upp de kunskapsluckor och osäkerheter som förekommer.Resultatet av denna rapport bidrar med ny information kring miljöeffekter av vindkraft i vatten, samt belyser de utmaningar som finns kopplade till uppföljning av vindkraftens effekter på akvatiskt liv. De förslag till rekommendationer som ges i rapporten syftar till att underlätta tillämpningen av tillsyn och kontrollprogram och utgöra ett underlag för väl avvägda och transparenta beslut vid etablering av vindkraft i vatten.
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| 6. |
- Gustafsson, Gabriel, et al.
(författare)
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Secretion and uptake of α-synuclein via extracellular vesicles in cultured cells
- 2018
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Ingår i: Cellular and molecular neurobiology. - : Springer Science and Business Media LLC. - 0272-4340 .- 1573-6830. ; 38:8, s. 1539-1550
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Tidskriftsartikel (refereegranskat)abstract
- In Parkinson’s disease and other Lewy body disorders, the propagation of pathology has been accredited to the spreading of extracellular α-synuclein (α-syn). Although the pathogenic mechanisms are not fully understood, cell-to-cell transfer of α-syn via exosomes and other extracellular vesicles (EVs) has been reported. Here, we investigated whether altered molecular properties of α-syn can influence the distribution and secretion of α-syn in human neuroblastoma cells. Different α-syn variants, including α-syn:hemi-Venus and disease-causing mutants, were overexpressed and EVs were isolated from the conditioned medium. Of the secreted α-syn, 0.1–2% was associated with vesicles. The major part of EV α-syn was attached to the outer membrane of vesicles, whereas a smaller fraction was found in their lumen. For α-syn expressed with N-terminal hemi-Venus, the relative levels associated with EVs were higher than for WT α-syn. Moreover, such EV-associated α-syn:hemi-Venus species were internalized in recipient cells to a higher degree than the corresponding free-floating forms. Among the disease-causing mutants, A53T α-syn displayed an increased association with EVs. Taken together, our data suggest that α-syn species with presumably lost physiological functions or altered aggregation properties may shift the cellular processing towards vesicular secretion. Our findings thus lend further support to the tenet that EVs can mediate spreading of harmful α-syn species and thereby contribute to the pathology in α-synucleinopathies.
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| 7. |
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| 8. |
- Almandoz Gil, Leire, 1988-
(författare)
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Characterization of Physiological and Pathological Alpha-Synuclein : Implications for Parkinson’s Disease and Related Disorders
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aggregated alpha-synuclein is the main component of Lewy bodies and Lewy neurites, intraneuronal inclusions found in the brains of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) patients (synucleinopathies). Alpha-synuclein is a presynaptic protein, which is most commonly an unfolded monomer in its physiological state. However, under pathological conditions it can start to misfold and enter an aggregation pathway that will lead to the formation of oligomers of increasing size and finally insoluble fibrils. The oligomers have been hypothesized to be the most neurotoxic species, but studies of their properties have been hindered by their heterogeneity and kinetic instability. The overall aim of this thesis was to characterize and compare physiological and pathological forms of alpha-synuclein from different sources: recombinant monomers, oligomers formed in vitro through exposure to oxidative stress related reactive aldehydes, aggregates from a synucleinopathy mouse model and from synucleinopathy patients.In paper I we studied the effect of low molar excess of two lipid peroxidation products, 4-oxo-2-nonenal (ONE) and 4-hydroxy-2-nonenal (HNE), on the oligomerization of alpha-synuclein. Through biophysical methods we observed that, although both aldehydes bound to alpha-synuclein directly, ONE produced SDS-stable oligomers more rapidly than HNE. Moreover, ONE induced oligomerization at both acidic and neutral pH, while HNE only formed oligomers at neutral pH.In paper II we mapped the surface exposed epitopes of in vitro and in vivo generated alpha-synuclein species by using immunoglobulin Y antibodies raised against short linear peptides covering most of the alpha-synuclein sequence. Monomers were found to react with most antibodies, while the latter part of the N-terminus and mid-region of HNE oligomers and fibrils was found to be occluded in oligomers and fibrils. Through immunohistochemistry we compared alpha-synuclein aggregates in brain tissue from patients with synucleinopathies as well as from a mouse model expressing A30P human alpha-synuclein. Although the exposed epitopes were found to be similar overall, subtle differences were detected in the C-terminus.An additional aim of this thesis was to characterize synaptic aggregates of alpha-synuclein. In paper III we obtained synaptosomal preparations of the A30P mouse model and found that a subset of the alpha-synuclein present in the synaptosomes was proteinase K resistant and therefore aggregated. Further biochemical analyses showed that the aggregated alpha-synuclein mainly was of human, i.e. transgenic, origin and that Ser 129 was not phosphorylated, which otherwise is a common post translational modification of alpha-synuclein in Lewy bodies.It has been suggested that alpha-synuclein plays a role in neurotransmitter release by binding to the SNARE protein VAMP-2 and thereby chaperoning the SNARE complex assembly. In paper IV we used proximity ligation assay to visualize the co-localization of alpha-synuclein and the SNARE proteins in primary neurons from non-transgenic and A30P transgenic mice.In conclusion, in this thesis we have characterized a variety of alpha-synuclein species and shed light on the diversity of alpha-synuclein aggregates. Additionally, we have characterized synaptic species of alpha-synuclein and analyzed the co-localization between alpha-synuclein and SNARE proteins in neurons.
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| 9. |
- Almandoz-Gil, Leire, et al.
(författare)
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In situ proximity ligation assay reveals co-localization of alpha-synuclein and SNARE proteins in murine primary neurons
- 2018
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Ingår i: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The aggregation of alpha-synuclein (alpha Syn) is the pathological hallmark of Parkinson's disease, dementia with Lewy bodies and related neurological disorders. However, the physiological function of the protein and how this function relates to its pathological effects remain poorly understood. One of the proposed roles of aSyn is to promote the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly by binding to VAMP-2. The objective of this study was to visualize the co-localization between aSyn and the SNARE proteins (VAMP-2, SNAP-25, and syntaxin-1) for the first time using in situ proximity ligation assay (PLA). Cortical primary neurons were cultured from either non-transgenic or transgenic mice expressing human aSyn with the A30P mutation under the Thy-1 promoter. With an antibody recognizing both mouse and human aSyn, a PLA signal indicating close proximity between aSyn and the three SNARE proteins was observed both in the soma and throughout the processes. No differences in the extent of PLA signals were seen between non-transgenic and transgenic neurons. With an antibody specific against human aSyn, the PLA signal was mostly located to the soma and was only present in a few cells. Taken together, in situ PLA is a method that can be used to investigate the co-localization of aSyn and the SNARE proteins in primary neuronal cultures
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| 10. |
- Almandoz-Gil, Leire, et al.
(författare)
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Low molar excess of 4-oxo-2-nonenal and 4-hydroxy-2-nonenal promote oligomerization of alpha-synuclein through different pathways
- 2017
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Ingår i: Free Radical Biology & Medicine. - : Elsevier BV. - 0891-5849 .- 1873-4596. ; 110, s. 421-431
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Tidskriftsartikel (refereegranskat)abstract
- Aggregated alpha-synuclein is the main component of Lewy bodies, intraneuronal inclusions found in brains with Parkinson's disease and dementia with Lewy bodies. A body of evidence implicates oxidative stress in the pathogenesis of these diseases. For example, a large excess (30:1, aldehyde:protein) of the lipid peroxidation end products 4-oxo-2-nonenal (ONE) or 4-hydroxy-2-nonenal (HNE) can induce alpha-synuclein oligomer formation. The objective of the study was to investigate the effect of these reactive aldehydes on alpha-synuclein at a lower molar excess (3:1) at both physiological (7.4) and acidic (5.4) pH. As observed by size-exclusion chromatography, ONE rapidly induced the formation of alpha-synuclein oligomers at both pH values, but the effect was less pronounced under the acidic condition. In contrast, only a small proportion of alpha-synuclein oligomers were formed with low excess HNE-treatment at physiological pH and no oligomers at all under the acidic condition. With prolonged incubation times (up to 96 h), more alpha-synuclein was oligomerized at physiological pH for both ONE and HNE. As determined by Western blot, ONE-oligomers were more SDS-stable and to a higher-degree cross-linked as compared to the HNE-induced oligomers. However, as shown by their greater sensitivity to proteinase K treatment, ONE-oligomers, exhibited a less compact structure than HNE-oligomers. As indicated by mass spectrometry, ONE modified most Lys residues, whereas HNE primarily modified the His50 residue and fewer Lys residues, albeit to a higher degree than ONE. Taken together, our data show that the aldehydes ONE and HNE can modify alpha-synuclein and induce oligomerization, even at low molar excess, but to a higher degree at physiological pH and seemingly through different pathways.
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