| 1. |
- Li Zweifel, Ulla, et al.
(author)
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God havsmiljö 2020 : Marin strategi för Nordsjön och Östersjön Del 2: God miljöstatus och miljökvalitetsnormer
- 2012
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Reports (other academic/artistic)abstract
- Havsmiljöförordningens övergripande mål är att upprätthålla eller uppnå en god miljöstatus i de svenska förvaltningsområdena Nordsjön och Östersjön till år 2020. En av uppgifterna i den första förvaltningsperioden är att bestämma vad som kännetecknar god miljöstatus i respektive förvaltningsområde samt att ta fram miljökvalitetsnormer. God miljöstatus baseras på ett ramverk av så kallade deskriptorer som anges i havsmiljödirektivet, det vill säga det EU-direktiv som i Sverige genomförs genom havsmiljöförordningen. Deskriptorerna beskriver god miljöstatus på en övergripande nivå för 11 temaområden. Till varje deskriptor hör en rad kriterier som anger vad som ska ingå i en bedömning av miljöstatus. I Sverige har god miljöstatus formulerats för samtliga 29 kriterier som ska beaktas enligt direktivet. Dessa kvalitativa beskrivningar anger vad som kännetecknar god miljöstatus i Nordsjön och Östersjön. För att praktiskt bedöma om god miljöstatus har uppnåtts föreslås 37 nationella indikatorer. En uppsättning av indikatorer omfattar miljöns tillstånd och avspeglar ekosystemets komponenter i form av nyckelarter, samhällen, och livsmiljöer. En utgångspunkt vid val av indikatorer för miljöns tillstånd har varit koppling till de belastningar som i den inledande bedömningen av miljötillståndet i Nordsjön och Östersjön bedömts ha stor negativ påverkan på ekosystemet. En annan uppsättning indikatorer berör påverkan och belastning på miljön i form av tillförsel av näringsämnen och farliga ämnen, samt biologisk och fysisk störning av miljön. Tillsammans utgör indikatorerna ett verktyg för att följa utvecklingen av miljötillståndet och effekter av åtgärder i havsmiljön. Vid val av indikatorer har arbetet delvis utgått från existerande miljöövervakning och redan utvecklade indikatorer. Med denna utgångspunkt uppfylls en rad av havsmiljödirektivets krav, bland annat en god uppföljning av effekter av tillförsel av näringsämnen. Funktionella indikatorer, det vill säga indikatorer som utvärderats och för vilka god miljöstatus har definierats, saknas dock för tio av havsmiljödirektivets 29 kriterier. För uppföljning av biologisk mångfald saknas bland annat miljöövervakning och metoder för att bedöma livsmiljöers tillstånd. För att kunna bedöma fysiska skador på havsbotten saknas en övergripande sammanställning av information om aktiviteter som påverkar havsbottnar samt metodik för att bedöma effekterna. Det saknas också utvecklade indikatorer för det kriterium som berör uppföljning av storleks- och åldersstruktur hos fiskar. Brist på kunskap gör också att inga förslag på svenska indikatorer kan ges för effekter på levande organismer från marint avfall, undervattensbuller, och främmande arter samt att endast ett begränsat antal indikatorer tagits fram som speglar effekter av farliga ämnen. De indikatorer som fastställs i juli 2012 utgör således inte en slutlig lista för att följa upp havsmiljödirektivet. Bristerna kommer att beaktas i det fortsatta genomförandet av havsmiljöförordningen där nästa steg är att anpassa miljöövervakningsprogrammen till uppföljning av miljötillståndet med valda indikatorer senast år 2014 samt att ta fram åtgärdsprogram till år 2015. God miljöstatus ska uppnås genom tillämpning av miljökvalitetsnormer det vill säga rättsligt bindande regler som avspeglar den lägsta godtagbara miljökvaliteten i Nordsjön och Östersjön. För att nå god miljöstatus har elva svenska miljökvalitetsnormer formulerats. Dessa miljökvalitetsnormer omfattar belastning i form av näringsämnen, farliga ämnen, främmande arter, uttag av arter, fysisk påverkan på havsbottnar och avfall i havsmiljön. Målsättningen har varit att utforma miljökvalitetsnormer som motsvarar alla de belastningar som i den inledande bedömningen har identifierats ha en stor påverkan på miljön.
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| 2. |
- Adler, Andrew F., et al.
(author)
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hESC-Derived Dopaminergic Transplants Integrate into Basal Ganglia Circuitry in a Preclinical Model of Parkinson's Disease
- 2019
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 28:13, s. 5-3473
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Journal article (peer-reviewed)abstract
- Cell replacement is currently being explored as a therapeutic approach for neurodegenerative disease. Using stem cells as a source, transplantable progenitors can now be generated under conditions compliant with clinical application in patients. In this study, we elucidate factors controlling target-appropriate innervation and circuitry integration of human embryonic stem cell (hESC)-derived grafts after transplantation to the adult brain. We show that cell-intrinsic factors determine graft-derived axonal innervation, whereas synaptic inputs from host neurons primarily reflect the graft location. Furthermore, we provide evidence that hESC-derived dopaminergic grafts transplanted in a long-term preclinical rat model of Parkinson's disease (PD) receive synaptic input from subtypes of host cortical, striatal, and pallidal neurons that are known to regulate the function of endogenous nigral dopamine neurons. This refined understanding of how graft neurons integrate with host circuitry will be important for the design of clinical stem-cell-based replacement therapies for PD, as well as for other neurodegenerative diseases. Adler et al. graft hESC-derived dopaminergic progenitors into a rat model of Parkinson's disease. They find grafts correctly innervate host targets and receive appropriate synaptic input after intranigral and intrastriatal placement. Furthermore, the same host neurons projecting toward endogenous dopamine neurons are found to also connect to the grafts.
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| 3. |
- Aldrin-Kirk, Patrick, et al.
(author)
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DREADD Modulation of Transplanted DA Neurons Reveals a Novel Parkinsonian Dyskinesia Mechanism Mediated by the Serotonin 5-HT6 Receptor
- 2016
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In: Neuron. - : Elsevier BV. - 0896-6273. ; 90:5, s. 955-968
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Journal article (peer-reviewed)abstract
- Transplantation of DA neurons is actively pursued as a restorative therapy in Parkinson's disease (PD). Pioneering clinical trials using transplants of fetal DA neuroblasts have given promising results, although a number of patients have developed graft-induced dyskinesias (GIDs), and the mechanism underlying this troublesome side effect is still unknown. Here we have used a new model where the activity of the transplanted DA neurons can be selectively modulated using a bimodal chemogenetic (DREADD) approach, allowing either enhancement or reduction of the therapeutic effect. We show that exclusive activation of a cAMP-linked (Gs-coupled) DREADD or serotonin 5-HT6 receptor, located on the grafted DA neurons, is sufficient to induce GIDs. These findings establish a mechanistic link between the 5-HT6 receptor, intracellular cAMP, and GIDs in transplanted PD patients. This effect is thought to be mediated through counteraction of the D2 autoreceptor feedback inhibition, resulting in a dysplastic DA release from the transplant.
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| 4. |
- Alinezhad, Saeid, et al.
(author)
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Validation of novel biomarkers for prostate cancer progression by the combination of bioinformatics, clinical and functional studies
- 2016
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
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Journal article (peer-reviewed)abstract
- The identification and validation of biomarkers for clinical applications remains an important issue for improving diagnostics and therapy in many diseases, including prostate cancer. Gene expression profiles are routinely applied to identify diagnostic and predictive biomarkers or novel targets for cancer. However, only few predictive markers identified in silico have also been validated for clinical, functional or mechanistic relevance in disease progression. In this study, we have used a broad, bioinformatics-based approach to identify such biomarkers across a spectrum of progression stages, including normal and tumor-adjacent, premalignant, primary and late stage lesions. Bioinformatics data mining combined with clinical validation of biomarkers by sensitive, quantitative reverse-transcription PCR (qRT-PCR), followed by functional evaluation of candidate genes in disease-relevant processes, such as cancer cell proliferation, motility and invasion. From 300 initial candidates, eight genes were selected for validation by several layers of data mining and filtering. For clinical validation, differential mRNA expression of selected genes was measured by qRT-PCR in 197 clinical prostate tissue samples including normal prostate, compared against histologically benign and cancerous tissues. Based on the qRT-PCR results, significantly different mRNA expression was confirmed in normal prostate versus malignant PCa samples (for all eight genes), but also in cancer-adjacent tissues, even in the absence of detectable cancer cells, thus pointing to the possibility of pronounced field effects in prostate lesions. For the validation of the functional properties of these genes, and to demonstrate their putative relevance for disease-relevant processes, siRNA knock-down studies were performed in both 2D and 3D organotypic cell culture models. Silencing of three genes (DLX1, PLA2G7 and RHOU) in the prostate cancer cell lines PC3 and VCaP by siRNA resulted in marked growth arrest and cytotoxicity, particularly in 3D organotypic cell culture conditions. In addition, silencing of PLA2G7, RHOU, ACSM1, LAMB1 and CACNA1D also resulted in reduced tumor cell invasion in PC3 organoid cultures. For PLA2G7 and RHOU, the effects of siRNA silencing on proliferation and cell-motility could also be confirmed in 2D monolayer cultures. In conclusion, DLX1 and RHOU showed the strongest potential as useful clinical biomarkers for PCa diagnosis, further validated by their functional roles in PCa progression. These candidates may be useful for more reliable identification of relapses or therapy failures prior to the recurrence local or distant metastases.
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| 5. |
- Alvehus, Malin, et al.
(author)
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Adipose tissue IL-8 is increased in normal weight women after menopause and reduced after gastric bypass surgery in obese women
- 2012
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In: Clinical Endocrinology. - : Wiley-Blackwell. - 0300-0664 .- 1365-2265. ; 77:5, s. 684-690
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Journal article (peer-reviewed)abstract
- Objective: The menopausal transition is characterized by increased body fat accumulation, including redistribution from peripheral to central fat depots. This distribution is associated with an increased risk of type 2 diabetes and cardiovascular disease which are linked to low-grade inflammation. We determined whether postmenopausal women have higher levels of inflammatory markers, compared to premenopausal women. We also wanted to determine if these markers are reduced by stable weight loss in obese women. Design and methods: Anthropometric data, blood samples, and subcutaneous adipose tissue biopsies were collected from normal weight premenopausal and postmenopausal women and obese women before and 2 years after gastric bypass surgery. Serum protein levels and adipose tissue gene expression of inflammatory markers were investigated. Results: IL-8 expression in adipose tissue and circulating levels were higher in postmenopausal versus premenopausal women. IL-8 expression was associated with waist circumference, independent of menopausal status. IL-6 expression and serum levels of monocyte chemoattractant protein (MCP)-1 were higher in postmenopausal versus premenopausal women. Two years after gastric bypass surgery, adipose expression of IL-8, tumor necrosis factor-α, and MCP-1 decreased significantly. Serum insulin levels were associated with inflammation-related gene expression before gastric bypass surgery, but these associations disappeared after surgery. Conclusion: Postmenopausal women have an increased inflammatory response in the subcutaneous fat and circulation. Inflammatory markers in adipose tissue decreased significantly after surgery-induced weight loss. This effect may be beneficial for metabolic control and reduced cardiovascular risk after weight loss. © 2011 Blackwell Publishing Ltd.
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| 6. |
- Ander, Malin, et al.
(author)
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Development of health-related quality of life and symptoms of anxiety and depression among persons diagnosed with cancer during adolescence : a 10-year follow-up study
- 2016
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In: Psycho-Oncology. - : Wiley. - 1057-9249 .- 1099-1611. ; 25:5, s. 582-589
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Journal article (peer-reviewed)abstract
- Objective: The main aim was to investigate the development of health-related quality of life (HRQOL) and symptoms of anxiety and depression in a cohort diagnosed with cancer during adolescence from shortly after up to 10 years after diagnosis.Methods: Participants (n = 61) completed the SF-36 and the HADS shortly; six, 12, and 18 months; and two, three, four, and 10 years (n = 28) after diagnosis. Polynomial change trajectories were used to model development.Results: Polynomial change trajectories showed an initial increase which abated over time into a decrease which abated over time for the SF-36 subscales Mental Health and Vitality; an initial decline which abated over time into an increase for HADS anxiety; and an initial decline which abated over time into an increase which abated over time for HADS depression. The SF-36 mental component summary showed no change from two to 10 years after diagnosis whereas the SF-36 physical component summary showed an increase from two years after diagnosis which declined over time. Ten years after diagnosis 29% reported possible anxiety.Conclusions: Development of HRQOL and symptoms of anxiety and depression appears to be nonlinear among persons diagnosed with cancer during adolescence. Well into permanent survivorship an increase in symptoms of anxiety is shown and approximately a third of the participants report possible anxiety. The findings indicate the need for: studies designed to pinpoint the times of highest psychological risk, clinical follow-up focusing on psychological problems, and development of effective psychological interventions for survivors of adolescent cancer
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| 7. |
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| 8. |
- Andersson, Linda, 1973, et al.
(author)
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Deficiency in perilipin 5 reduces mitochondrial function and membrane depolarization in mouse hearts.
- 2017
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In: The international journal of biochemistry & cell biology. - : Elsevier BV. - 1878-5875 .- 1357-2725. ; 91:Pt A, s. 9-13
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Journal article (peer-reviewed)abstract
- Myocardial triglycerides stored in lipid droplets are important in regulating the intracellular delivery of fatty acids for energy generation in mitochondria, for membrane biosynthesis, and as agonists for intracellular signaling. Previously, we showed that deficiency in the lipid droplet protein perilipin 5 (Plin5) markedly reduces triglyceride storage in cardiomyocytes and increases the flux of fatty acids into phospholipids. Here, we investigated whether Plin5 deficiency in cardiomyocytes alters mitochondrial function. We found that Plin5 deficiency reduced mitochondrial oxidative capacity. Furthermore, in mitochondria from Plin5((-/)(-)) hearts, the fatty acyl composition of phospholipids in mitochondrial membranes was altered and mitochondrial membrane depolarization was markedly compromised. These findings suggest that mitochondria isolated from hearts deficient in Plin5, have specific functional defects.
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| 9. |
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| 10. |
- Ben-Shabat, Ilan, et al.
(author)
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Isolated hepatic perfusion as a treatment for liver metastases of uveal melanoma.
- 2015
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In: Journal of visualized experiments : JoVE. - : MyJove Corporation. - 1940-087X. ; :95
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Journal article (peer-reviewed)abstract
- Isolated hepatic perfusion (IHP) is a procedure where the liver is surgically isolated and perfused with a high concentration of the chemotherapeutic agent melphalan. Briefly, the procedure starts with the setup of a percutaneous veno-venous bypass from the femoral vein to the external jugular vein. Via a laparotomy, catheters are then inserted into the proper hepatic artery and the caval vein. The portal vein and the caval vein, both supra- and infrahepatically, are then clamped. The arterial and venous catheters are connected to a heart lung machine and the liver is perfused with melphalan (1 mg/kg body weight) for 60 min. This way it is possible to locally perfuse the liver with a high dose of a chemotherapeutic agent, without leakage to the systemic circulation. In previous studies including patients with isolated liver metastases of uveal melanoma, an overall response rate of 33-100% and a median survival between 9 and 13 months, have been reported. The aim of this protocol is to give a clear description of how to perform the procedure and to discuss IHP as a treatment option for liver metastases of uveal melanoma.
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