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| 2. |
- Mårtensson, Ulrika, et al.
(author)
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Deletion of the G protein-coupled receptor 30 impairs glucose tolerance, reduces bone growth, increases blood pressure, and eliminates estradiol-stimulated insulin release in female mice.
- 2009
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In: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 150:2, s. 687-98
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Journal article (peer-reviewed)abstract
- In vitro studies suggest that the G protein-coupled receptor (GPR) 30 is a functional estrogen receptor. However, the physiological role of GPR30 in vivo is unknown, and it remains to be determined whether GPR30 is an estrogen receptor also in vivo. To this end, we studied the effects of disrupting the GPR30 gene in female and male mice. Female GPR30((-/-)) mice had hyperglycemia and impaired glucose tolerance, reduced body growth, increased blood pressure, and reduced serum IGF-I levels. The reduced growth correlated with a proportional decrease in skeletal development. The elevated blood pressure was associated with an increased vascular resistance manifested as an increased media to lumen ratio of the resistance arteries. The hyperglycemia and impaired glucose tolerance in vivo were associated with decreased insulin expression and release in vivo and in vitro in isolated pancreatic islets. GPR30 is expressed in islets, and GPR30 deletion abolished estradiol-stimulated insulin release both in vivo in ovariectomized adult mice and in vitro in isolated islets. Our findings show that GPR30 is important for several metabolic functions in female mice, including estradiol-stimulated insulin release.
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| 3. |
- Sandberg, Dick, 1967-, et al.
(author)
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Utvändiga träfasader : Inverkan av materialval, konstruktion och ytbehandling på beständigheten hos fasader av gran och tall
- 2011
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Reports (other academic/artistic)abstract
- Den utvändiga fasaden ska ge byggnaden ett uttryck genom utformning och kulör. Fasaden ska också skydda de isolerande skikten i väggen från yttre påverkan. Dessa funktioner kan uppfyllas av i stort sett alla material. Om trä ska trä vara konkurrenskraftigt måste trämaterialet, fasadkonstruktionen och ytbehandlingssystemet väljas och samverka på ett sådant sätt att fasaden får en lång livslängd med litet och lågt underhåll. Därigenom blir träfasaden ekonomiskt och estetiskt attraktiv för brukaren i vid mening.Denna studie belyser kunskapsfronten för utomhusanvändning av träslagen tall (Pinus sylvestris L.) och gran (Picea abies L. Karst.) ovan mark. Specifikt studeras användning i fasader utifrån aspekterna materialval, fasadkonstruktion, ytbehandling samt återvinning.Marknaden efterfrågar träfasadsystem. De behov som marknadens aktörer, dvs. byggherrar, fastighetsförvaltare, arkitekter, konstruktörer, stomleverantörer, entreprenörer och representanter för småhusindustrin, framhäver kan sammanfattas i följande punkter:Behov av specificerad livslängd och givna tidsintervall för underhåll av träfasader. (Ska vara i nivå med konkurrerande material)Det är önskvärt att leverantören av ett fasadsystem ikläder sig ett långsiktigt ansvar för underhåll.Flexibilitet, leverantören ska kunna byta ut eller renovera fasaden vid behov.Byggkrav, träfasadmaterial måste kunna samverka med andra, speciellt brandklassade, material.Fasadsystem skall vara utseendemässigt attraktivt.Den primära marknaden för nya fasadsystem bör vara flerbostadshus, men inte nödvändigtvis flerbostadshus av trä. Fokus ska ligga på fasadsystemets flexibilitet i arkitektoniskt uttryck och i relation till andra material och system. Nybyggnation är viktigt, men miljonprogrammet, renovering och tillbyggnad (ROT) samt energieffektivisering är också viktiga områden.Den svenska marknaden är liten (idag ca. 70 000 m3 trä för fasader), men bör inledningsvis ändå prioriteras och därefter de nordiska länderna, samt Schweiz, Österrike och Tyskland.I litteraturen beskrivs mer eller mindre välgrundade rekommendationer för att förlänga träfasaders livslängd och öka dess underhålls-intervall. Vissa av rekommendationerna är dock direkt motstridiga.När aspekterna materialval, fasadkonstruktion och ytbehandling studeras finns det många detaljer som har betydelse för träfasadens beständighet. Det är svårt att sära ut de mest väsentliga faktorerna, men utan att ta hänsyn till aspekter som kostnader, tillgång, eller andra av praktiskt karaktär viktiga faktorer kan följande nyckelfaktorer identifieras för en miljöriktig och beständig fasad av tall eller gran:MaterialvalHög andel kärnved, helst uteslutande kärnvedVirket ska ha stående årsringarHanteringen ska utföras så att virket inte får mekaniska skador, får mikrobiella angrepp, eller blir uppfuktat eller nedsmutsat, dvs. snabb och rätt hantering, samt god emballering.Från marken – fasaden ska börja minst 30 cm ovan marken.Ventilation – utforma fasadbeklädnaden så att fukt snabbt kan torka ut. Ventilera utrymmet bakom fasaden vilket är ett enkelt sätt för att möjliggöra detta.Vattenavrinning – inga horisontella ytor.Flexibilitet – ska gälla både konstruktion och arkitektoniskt utförande. Fasadsystem som kan ”hängas på” befintliga byggnader efterfrågas.Förseglat ändträ – försegling av ändträytor för att förhindra fuktupptagning i träet är helt avgörande för trämaterialets livslängd. Spikning kan öppna nya ändträytor och bör därmed utföras omsorgsfullt och med eftertanke.Rundade virkeskanter – ger bättre täckförmåga hos färgen och minskar risk för mekaniska skador på fasadbrädorna.Val av ytbehandling – spelar en nyckelroll för fasadens prestanda. En träfasad ska levereras som en del av ett komplett underhållspaket.Hantering från skog till fasadKonstruktionYtbehandlingFör ytbehandling finns idag många tillämpningar där nanotekniken utnyttjas för att skapa mervärde hos en yta jämfört med vad dagens mer traditionella produkter kan erbjuda. Nanobaserade ytbehandlingsprodukter marknadsförs redan idag och där uppges de göra ytor smuts- och vattenavvisande, förhindra påväxt av alger, svamp och mossa, förbättra UV- och temperaturresistensen och kulörbeständigheten, förbättra rep- och nötningståligheten, samt ha antigraffiti egenskaper etc. De flesta produkterna är dock nya och för en del finns därför frågetecken vad gäller t.ex. långtidsprestanda och teknisk livslängd, underhållbarhet och därmed sammanhängande ekonomi sett ur ett livscykelperspektiv för den produkt eller system där ytbehandlingen utgör bara en del.En kostnadsanalys som genomförts i studien gör bedömningen att nya nanoteknikbaserade ytbehandlingssystem skulle kunna ge som mest en reduktion av underhållskostnaderna med 15 %. Antagandet är då att fasadrengöring behöver göras vart femte eller sjunde år då traditionella målningssystem används.Återvunnet trä från träfasader definieras enligt Svensk standard som trädbränsle och benämns generellt för returträ eller när materialet är i finfördelad form för returflis.Ett stort problem med att återvinna energin från returträ är att en del av materialet är behandlat på något sätt, t.ex. impregnerat med träskyddsmedel, ytbehandlat eller innehåller andra konstruktionsdelar av t.ex. plast eller metall. Returflis är ett utmärkt bränsle för energiåtervinning förutsatt att anläggningen har tillräcklig rökgasrening och att askan hanteras på ett korrekt sätt. Ett problem idag är vad som ska ske med förorenad askan då den klassas som farligt avfall och därmed inte kan återföras till skogen. Om halterna av tungmetaller inte är för höga kan askan användas som täck- och fyllmaterial annars måste askan gå till deponi.En bättre källsortering och översyn av regelverk skulle dessutom kunna leda till att det renare returträet skulle kunna eldas i konventionella biobränslepannor medan den förorenade andelen då skulle eldas separat.
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| 4. |
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| 5. |
- Bankell, Elisabeth, et al.
(author)
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LL-37-induced caspase-independent apoptosis is associated with plasma membrane permeabilization in human osteoblast-like cells
- 2021
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In: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 135
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Journal article (peer-reviewed)abstract
- The host defense peptide LL-37 is active against both gram-positive and gram-negative bacteria, but it has also been shown to reduce human host cell viability. However, the mechanisms behind LL-37-induced human host cell cytotoxicity are not yet fully understood. Here, we assess if LL-37-evoked attenuation of human osteoblast-like MG63 cell viability is associated with apoptosis, and if the underlying mechanism may involve LL-37-induced plasma membrane permeabilization. MG63 cell viability and plasma membrane permeabilization were investigated by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and by measuring lactate dehydrogenase (LDH) release, respectively. Apoptosis was assessed by the terminal deoxynucleotidyl dUTP nick end labeling (TUNEL) assay and Annexin V flow cytometry, and caspase-3 and poly (ADP-ribose) polymerase (PARP) cleavage were determined by Western blot. LL-37 (4 and 10 μM) reduced both cell number and cell viability, and these effects were associated with a pro-apoptotic effect demonstrated by positive TUNEL staining and Annexin V flow cytometry. LL-37-induced apoptosis was not coupled to either caspase-3 or PARP cleavage, suggesting that LL-37 causes caspase-independent apoptosis in MG63 cells. Both LL-37 and the well-known plasma membrane permeabilizer Triton X-100 reduced cell viability and stimulated LDH release. Triton X-100-treated cells showed positive TUNEL staining, and the detergent accumulated cells in late apoptosis/necrosis. Similar to LL-37, Triton X-100 caused no PARP cleavage. We conclude that LL-37 promotes caspase-independent apoptosis, and that this effect seems coupled to plasma membrane permeabilization in human MG63 cells.
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| 6. |
- Dahl, Sara, et al.
(author)
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The host defense peptide LL-37 triggers release of nucleic acids from human mast cells
- 2018
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In: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 109, s. 39-45
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Journal article (peer-reviewed)abstract
- The human host defense peptide LL-37 possesses antimicrobial activity but also affects host cell function and viability. Mast cells are involved in innate immunity but no data have been presented on effects of LL-37 on human mast cell viability and export of nucleic acids. Here, we demonstrated by immunofluorescence microscopy that synthesized LL-37 was internalized by human LAD2 mast cells and detected both in cytoplasm and nucleus. Treatment with high (4 and 10 μM) but not low (1 μM) concentrations of LL-37 for 4 h reduced cell viability assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Stimulation with 10 μM LL-37 for 4 h enhanced export of nucleic acids, total protein and lactate dehydrogenase (LDH), suggesting that both nuclear and plasma membranes are permeabilized by LL-37. Although LL-37 triggered release of nucleic acids, no extracellular trap-like structures were observed by laser scanning confocal microscopy of cells incubated with the plasma membrane impermeable nucleic acid fluorophore SYTOX-Green, indicating that LL-37 promotes export of nucleic acids but not formation of extracellular traps. On the other hand, phorbol-12-myristate-13-acetate (PMA), which is a well-known inducer of extracellular traps, stimulated export of nucleic acids and also formation of extracellular trap-like structures. However, PMA had no effect on export of either total protein or LDH. Hence, LL-37 and PMA seem to stimulate export of nucleic acids from LAD2 mast cells through different pathways. In conclusion, we demonstrate that LL-37 triggers release of nucleic acids from human mast cells but not the formation of extracellular trap-like structures.
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| 7. |
- Holm, Anders, et al.
(author)
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The G protein-coupled oestrogen receptor 1 agonist G-1 disrupts endothelial cell microtubule structure in a receptor-independent manner.
- 2012
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In: Molecular and Cellular Biochemistry. - : Springer Science and Business Media LLC. - 0300-8177 .- 1573-4919. ; 366:1-2, s. 239-249
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Journal article (peer-reviewed)abstract
- The G protein-coupled oestrogen receptor GPER1, also known as GPR30, has been implicated in oestrogen signalling, but the physiological importance of GPER1 is not fully understood. The GPER1 agonist G-1 has become an important tool to assess GPER1-mediated cellular effects. Here, we report that this substance, besides acting via GPER1, affects the microtubule network in endothelial cells. Treatment with G-1 (3 μM) for 24 h reduced DNA synthesis by about 60 % in mouse microvascular endothelial bEnd.3 cells. Treatment with 3 μM G-1 prevented outgrowth of primary endothelial cells from mouse aortic explants embedded in Matrigel. Treatment with G-1 (0.3-3 μM) for 24 h disrupted bEnd.3 cell and HUVEC microtubule structure in a concentration-dependent manner as assessed by laser-scanning confocal immunofluorescence microscopy. G-1-induced (3 μM) disruption of microtubule was observed also after acute (3 and 6 h) treatment and in the presence of the protein synthesis inhibitor cycloheximide. Disruption of microtubules by 3 μM G-1 was observed in aortic smooth muscle cells obtained from both GPER1 knockout and wild-type mice, suggesting that G-1 influences microtubules through a mechanism independent of GPER1. G-1 dose dependently (10-50 μM) stimulated microtubule assembly in vitro. On the other hand, microtubules appeared normal in the presence of 10-50 μM G-1 as determined by electron microscopy. We suggest that G-1-promoted endothelial cell anti-proliferation is due in part to alteration of microtubule organization through a mechanism independent of GPER1. This G-1-promoted mechanism may be used to block unwanted endothelial cell proliferation and angiogenesis such as that observed in, e.g. cancer.
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| 8. |
- Janson, Per-Olof, 1940, et al.
(author)
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Acromegaly and Cushing's syndrome due to ectopic production of GHRH and ACTH by a thymic carcinoid tumour: in vitro responses to GHRH and GHRP-6.
- 1998
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In: Clinical endocrinology. - 0300-0664. ; 48:2, s. 243-50
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Journal article (peer-reviewed)abstract
- A 50-year-old male presented with diabetes mellitus and Cushing's syndrome associated with a large mediastinal mass. The levels of serum cortisol were high (1500-1800 nmol/l) without diurnal variation. Plasma ACTH levels (200-250 ng/l) and urinary excretion of cortisol were also increased. The levels of these hormones did not change in response to stimulation with corticotrophin releasing hormone (CRH) or suppression with high doses of dexamethasone. The patient had an elevated baseline GH level (7.3 mU/l), and the levels of immunoreactive GH-releasing hormone (GHRH) in eight plasma samples were markedly increased (600-1500 ng/l). Circulating levels of IGF-1, chromogranin A and neuropeptide Y (NPY) were also increased. Computer-assisted tomography and octreotide scintigraphy revealed a large mediastinal tumour and metastases in the left supraclavicular fossa. During treatment with octreotide, the baseline GH level was decreased (to 4.4 mU/l), while the GH pulse height was unchanged. Surgical removal of most of the tumour tissue resulted in a further decrease in the baseline serum GH level to a value (1.6 mU/l) about 20% of that before treatment, while the pulse height and mean GH were affected to a lesser extent. Postoperatively, circulating levels of cortisol and IGF-1 decreased, and the patient exhibited clinical improvement. Histological examination showed a neuroendocrine tumour with characteristics consistent with a foregut carcinoid of thymic origin. Immunoreactive GHRH, ACTH and NPY, but not immunoreactive GH, were detected in 80-90% of the tumour cells and the three peptides appeared to be co-localized. In primary culture, cells from this tumour displayed calcium influx in response to GHRH or GH releasing peptide-6 (GHRP-6), while there were not such responses by cells from another carcinoid not producing GHRH, ACTH or NPY. These results demonstrate a rare case of ectopic production of GHRH, ACTH and NPY, and indicate that the tumour cells were responsive to GHRH and GHRP-6 as well as octreotide.
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| 9. |
- Jönsson, Daniel, et al.
(author)
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Demonstration of mitochondrial oestrogen receptor beta and oestrogen-induced attenuation of cytochrome c oxidase subunit I expression in human periodontal ligament cells.
- 2007
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In: Archives of Oral Biology. - : Elsevier BV. - 1879-1506 .- 0003-9969. ; 52:7, s. 669-676
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Periodontal ligament (PDL) cells express oestrogen receptor beta (ERbeta) protein, but cellular functions regulated by ERbeta in these cells have not been identified. In this study we determine if ERbeta is localised to mitochondria and if oestrogen regulates mitochondrial function in human PDL cells obtained from teeth extracted for orthodontic reasons. DESIGN: Subcellular distribution of ERbeta was determined by confocal microscopy of cells co-stained with ERbeta antibody and the mitochondrion-selective probe MitoTracker and by immunogold electron microscopy. Expression of the mitochondrial enzyme cytochrome c oxidase subunit I, involved in oxidative phosphorylation, was determined by Western blotting in cells treated with or without physiological concentrations of the endogenous oestrogen 17beta-oestradiol. RESULTS: ERbeta immunoreactivity was observed both in the nuclei and the cytoplasm. MitoTracker-labelling was observed in the cytoplasm, especially in the perinuclear region, but not in the nuclei. Co-localisation of ERbeta and MitoTracker was observed in cells derived from both male and female subjects. Mitochondrial localisation of ERbeta was confirmed by immunogold electron microscopy. Cells treated with or without 17beta-oestradiol (100 nM) displayed an identical pattern of staining for mitochondria. Treatment with 100 nM 17beta-oestradiol attenuated cytochrome c oxidase subunit I expression by about 30%, while combined treatment with 17beta-oestradiol and the ER blocker ICI 182780 (10 microM) had no effect. CONCLUSION: This study demonstrates mitochondrial localisation of ERbeta and oestrogen-induced decrease in the expression of cytochrome c oxidase subunit I in human PDL cells, suggesting that oestrogen probably via ERbeta influences mitochondrial function and PDL cell energy
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| 10. |
- Karbalaei, Mardjaneh, et al.
(author)
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Detrusor Induction of miR-132/212 following Bladder Outlet Obstruction: Association with MeCP2 Repression and Cell Viability.
- 2015
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:1
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Journal article (peer-reviewed)abstract
- The microRNAs (miRNAs) miR-132 and miR-212 have been found to regulate synaptic plasticity and cholinergic signaling and recent work has demonstrated roles outside of the CNS, including in smooth muscle. Here, we examined if miR-132 and miR-212 are induced in the urinary bladder following outlet obstruction and whether this correlates with effects on gene expression and cell growth. Three to seven-fold induction of miR-132/212 was found at 10 days of obstruction and this was selective for the detrusor layer. We cross-referenced putative binding sites in the miR-132/212 promoter with transcription factors that were predicted to be active in the obstruction model. This suggested involvement of Creb and Ahr in miR-132/212 induction. Creb phosphorylation (S-133) was not increased, but the number of Ahr positive nuclei increased. Moreover, we found that serum stimulation and protein kinase C activation induced miR-132/212 in human detrusor cells. To identify miR-132/212 targets, we correlated the mRNA levels of validated targets with the miRNA levels. Significant correlations between miR-132/212 and MeCP2, Ep300, Pnkd and Jarid1a were observed, and the protein levels of MeCP2, Pnkd and Ache were reduced after obstruction. Reduction of Ache however closely matched a 90% reduction of synapse density arguing that its repression was unrelated to miR-132/212 induction. Importantly, transfection of antimirs and mimics in cultured detrusor cells increased and decreased, respectively, the number of cells and led to changes in MeCP2 expression. In all, these findings show that obstruction of the urethra increases miR-132 and miR-212 in the detrusor and suggests that this influences gene expression and limits cell growth.
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