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  • Waraky, Ahmed (författare)
  • Insulin-like growth factor 1 receptor, novel functions and future possibilities
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Insulin like growth factor-1 receptor (IGF-1R) has been shown to be important for cancer cell growth and survival, and is often overexpressed in malignant and premalignant tissues. Ligand binding to IGF-1R induces transphosphorylation and activation of the receptor, leading to subsequent activation of the phosphatidyl inositol-3 kinase (PI3K), the mitogen-activated protein kinase (MAPK) and the 14-3-3 pathways. Most of these pathways are shared by other receptor tyrosine kinases. Inhibition of these pathways using specific IGF-1R antibodies has, however, failed in large trials on cancer patients. This opens the possibilities for alternative signaling pathways. Recently, IGF-1R was shown to be SUMOylated and translocated to the cell nucleus. In the nucleus it binds to enhancer-like regions, and regulates expression of genes including CCND1 and AXIN2, and phosphorylates Histone3. The expression of nuclear IGF-1R has also been linked to increased cell growth and aggressive phenotype in cancer. In paper I the effects of picropodophyllin (PPP), an inhibitor of IGF-1R, on cell cycle progression were studied. Previous studies have indicated that PPP treated cells arrest in G2/M. We found that PPP induced G2/M arrest through interfering with microtubule dynamics causing prolonged mitotic arrest and mitotic catastrophe in an IGF-1R independent manner. This mechanism of PPP may contribute to its efficacy in treatment of cancer patients. In paper II the roles of SUMOylated IGF-1R in regulating cell proliferation and cell cycle progression were investigated. We provided evidence that SUMOylation of IGF-1R increases G1/S phase transition through inducing expression of cyclins (D, A and B) and upregulating CDK2. Cells expressing SUMOylated IGF-1R also proliferated faster and formed more colonies in soft agar compared to cells expressing IGF1R with mutated SUMO-binding sites. In paper III we investigated potential binding partners to nuclear IGF-1R in human embryonic stem cells (hESC). We found that nuclear IGF-1R associates with PCNA and phosphorylates it, not only in hESCs but also in other cell types. The nuclear IGF-1R-induced PCNA phosphorylation was followed by ubiquitination of PCNA, probably through DNA damage tolerance (DDT)-dependent E2/E3 ligases (e.g. Rad18 and UBC13). Our data suggest that IGF-1R may contribute to activation of DDT, as externally induced DNA damage in IGF-1R negative cells led to G1 cell cycle arrest and larger S-phase fork stalling compared to cells expressing IGF-1R. In summary, the achieved results may contribute in understanding the complexity of IGF-1R’s roles in cell growth and maintenance of genome stability, as well as the shown mitotic block induced by PPP may be a mechanism that favors anti-IGF-1R treatment in cancer.
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  • Carroll, Daire, et al. (författare)
  • Non-fatal removal of ground pangolin (Smutsia temminckii Smuts, 1832) tracking devices by predators
  • 2024
  • Ingår i: African Journal of Ecology. - 0141-6707. ; 62:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The ground pangolin (Smutsia temminckii Smuts 1832) is vulnerable to extinction due to poaching and trafficking. Recovery of pangolins from the trade and subsequent rehabilitation and release form a core component of pangolin conservation. Post-release monitoring of rehabilitated pangolins through the attachment of very high frequency (VHF) transmitters and satellite devices is carried out to determine the efficacy of release protocols. We report on 14 confirmed and 19 potential incidents of device removal by predators during non-fatal attacks, which occurred over a 6 year period. During this time, 78 devices were deployed 109 times attached to 36 rehabilitated pangolins. These incidents should be considered during the design of future post-release monitoring protocols.
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  • Odhagen, Erik, et al. (författare)
  • Readmission Rates Due to Post-Tonsillectomy Haemorrhage in Sweden: SIGNIFICANT DIFFERENCES BETWEEN SURGICAL CENTRES : Significant Differences Between Surgical Centres
  • 2016
  • Konferensbidrag (refereegranskat)abstract
    • Objectives: Post-surgical haemorrhage is the major complication of tonsil surgery. Post-tonsillectomy haemorrhage often results in readmission to hospital, sometimes demands return to theatre and can be a life-threatening occurrence. There are large differences in previously reported rates of post-tonsillectomy haemorrhage. The aim of this study is to determine readmission rates due to post-tonsillectomy haemorrhage in Sweden 2012-2014.Method: This is a population-based cohort study based on matched data from two healthcare registries in Sweden; the Swedish National Patient Register (NPR) and the National Tonsil Surgery Register in Sweden (NTSRS). All patients who underwent tonsillectomy, with or without simultaneous adenoidectomy, on benign indications from 2012 to 2014 were included in the study. The unique Personal Identity numbers were used to follow patients over time in NPR and identify readmission due to haemorrhage within 30 days from surgery. In NTSRS, readmission was reported by the patient in a questionnaire 30 days after surgery.Results: By matching the two registries a total of 22 800 unique patients were identified and included in the study. A total of 1726 patients (7.6%) were readmitted to hospital due to post-surgical haemorrhage. Tonsil surgery was conducted at 56 different surgical centres. Readmission rates due to post-tonsillectomy haemorrhage ranged from 0% to 22.4% at different surgical centres. 11 of 56 surgical centres had significant lower readmission rates compared to the average in Sweden. 12 of 56 surgical centres had significant higher readmission rates than the average.Conclusions: The rate of hospital readmissions due to post-surgical haemorrhage following tonsillectomy in Sweden 2012-2014 was 7.6%. There were significant differences in readmission rates between different surgical centres. This suggests that quality improvement interventions should be explored in units with high readmission rates to decrease post-tonsillectomy morbidity.
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  • Taslim, Shaiyek, et al. (författare)
  • Investigation of suitability of operating frequency and electro technical modeling of microwave oven
  • 2011
  • Ingår i: 2011 10th International Conference on Environment and Electrical Engineering, EEEIC.EU 2011. - 9781424487820
  • Konferensbidrag (refereegranskat)abstract
    • This paper is about electro-technical modeling of microwave oven. The aim of the work is to investigate the suitability of the operating frequency and to investigate why food which has been warmed in a microwave oven often requires a non-uniform temperature distribution. This would be done by making an electromagnetic model that determines the field distribution and the heat transfer to the food, as well as a thermal model that describes the heat transfer between different parts of the food.
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  • Larsson, Christer, et al. (författare)
  • Carbachol-stimulated Ca2+ increase in single neuroblastoma SH-SY5Y cells: effects of ethanol
  • 1998
  • Ingår i: Alcoholism: Clinical and Experimental Research. - : Wiley. - 0145-6008 .- 1530-0277. ; 22:3, s. 637-645
  • Tidskriftsartikel (refereegranskat)abstract
    • The effect of ethanol on the characteristics of carbachol-stimulated release of Ca2+ from intracellular Ca2+ stores was studied in single SH-SY5Y cells. Stimulation with carbachol, in the absence of extracellular Ca2+, elicited a rapid Ca2+ increase in SH-SY5Y cells peaking within seconds after addition of maximal agonist concentration. The Ca2+ response pattern in single cells resembled the population response, and there was no evidence of oscillatory changes in cytosolic [Ca2+] ([Ca2+]i). However, cell-to-cell variability could be detected in the magnitude and the latency time of the response, and in the rate of [Ca2+]i increase. In a carbachol dose-response analysis, the EC50 for the number of responsive cells and for the peak [Ca2+]i response was lower than that for carbachol-induced inositol 1,4,5-trisphosphate formation by a factor of 5 to 50. Ethanol (100 mM) caused a significant suppression of the number of responsive cells, but only when cells were stimulated with nonsaturating carbachol concentrations (1 and 10 microM). The suppression by ethanol was evident primarily in those cells that gave a Ca2+ response after several seconds of stimulation, whereas cells that responded within the initial seconds of receptor stimulation remained relatively unaffected. In responding cells stimulated with 10 microM carbachol, ethanol exposure also suppressed the maximal Ca2+ increase primarily in those cells that responded late. We suggest that ethanol suppression of muscarinic receptor-mediated signal transduction through the phospholipase C pathway may depend on the potentiation of feedback inhibition that requires receptor stimulation.
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