1,579 research outputs found
ALIGNMENT OF BUSINESS AND IS/IT STRATEGY AT TELENOR SWEDEN
No full textNeculau, Andrei. Habib, Stephanie. Henriksson, Aron. Magarian Kenaraki, Miganoush Katrin. Liu, Yuanchang. 2009. Alignment of Business and IS/IT Strategy at Telenor Sweden.strategic alignment, IS/IT strategy, business strategy, organizational strategy, case study, Telenor
K-T boundary in DSDP Holes 62-465 and 74-527 (Table 2)
No full textThe global extinctions linked to the Cretaceous-Tertiary (K-T) boundary severely affected marine pelagic organisms. The K-T boundary intervals at Deep Sea Drilling Project (DSDP) Site 527 (Leg 74) in the South Atlantic Ocean and Site 465 (Leg 62) in the Pacific Ocean were studied for changes in calcareous nannofossil assemblages from the late Maastrichtian to the early Paleocene. The sections analysed cover 180 kyr of the terminal Cretaceous and 200 kyr of the earliest Tertiary.
Absolute and relative abundances of calcareous nannoplankton were calculated for both the entire flora and for individual species. No decrease in the number of species occurs towards the K-T boundary; relative and absolute abundances of different species are fairly stable throughout the terminal 180 kyr of the Cretaceous. At the K-T boundary the calcareous nannoflora shows a drastic and instantaneous decrease in absolute abundance. Typical Cretaceous species became extinct at the K-T boundary, but are present in the lowermost Tertiary as a result of bioturbation and reworking of the sediments.
Very few species survived the K-T boundary. The species that occur sporadically in extremely low numbers in the Cretaceous, exhibit stable relative and absolute abundances through the lower Tertiary. Evolving Tertiary species appeared at the boundary and vary only moderately in absolute abundance through the lowermost Paleocene.
The productivity of calcareous nannoplankton is determined here as the nannofossil accumulation rate (NFAR), which is suggested as an estimate of surface-water primary productivity. The terminal Cretaceous NFAR values were high and stable. At the K-T boundary the calcareous nannoflora suffered a 70-150-fold decrease in NFAR, indicating a catastrophic event. The Tertiary NFAR values remained low and fairly constant through the first 200 kyr. The productivity of calcareous nanno- plankton in the earliest Tertiary was dominated by the calcareous dinoflagellate Thoracosphaera sp
Stroke is predicted by low visuospatial in relation to other intellectual abilities and coronary heart disease by low general intelligence
No full textBACKGROUND: Low intellectual ability is associated with an increased risk of coronary heart disease and stroke. Most studies have used a general intelligence score. We studied whether three different subscores of intellectual ability predict these disorders.METHODS: We studied 2,786 men, born between 1934 and 1944 in Helsinki, Finland, who as conscripts at age 20 underwent an intellectual ability test comprising verbal, visuospatial (analogous to Raven's progressive matrices) and arithmetic reasoning subtests. We ascertained the later occurrence of coronary heart disease and stroke from validated national hospital discharge and death registers.RESULTS: 281 men (10.1%) had experienced a coronary heart disease event and 131 (4.7%) a stroke event. Coronary heart disease was predicted by low scores in all subtests, hazard ratios for each standard deviation (SD) lower score ranging from 1.21 to 1.30 (confidence intervals 1.08 to 1.46). Stroke was predicted by a low visuospatial reasoning score, the corresponding hazard ratio being 1.23 (95% confidence interval 1.04 to 1.46), adjusted for year and age at testing. Adjusted in addition for the two other scores, the hazard ratio was 1.40 (1.10 to 1.79). This hazard ratio was little affected by adjustment for socioeconomic status in childhood and adult life, whereas the same adjustments attenuated the associations between intellectual ability and coronary heart disease. The associations with stroke were also unchanged when adjusted for systolic blood pressure at 20 years and reimbursement for adult antihypertensive medication.CONCLUSIONS: Stroke is predicted by low visuospatial reasoning scores in relation to scores in the two other subtests. This association may be mediated by common underlying causes such as impaired brain development, rather than by mechanisms associated with risk factors shared by stroke and coronary heart disease, such as socio-economic status, hypertension and atherosclerosis
Molecular mechanisms underlying increased PDYN and dynorphin expression in the prefrontal cortex of alcoholic men
No full textAlcohol dependence is a chronic relapsing disorder caused by drug x gene x environment interactions for which pharmacotherapy is but moderately effective. The prefrontal cortex is a brain region important for cognitive control / behavioral flexibility which function is impaired in alcoholics. Although the exact role of the dynorphin / κ-opioid receptor system in alcohol dependence is unknown, it has been suggested to contribute to the psychopathology of this disorder. Consistently, prodynorphin gene and dynorphin peptide expression is increased in the prefrontal cortex of alcoholic men.The aim of this thesis was to identify molecular mechanisms underlying these alterations. In line with this aim, we have shown that prodynorphin is regulated by the transcriptional control protein repressor element 1 silencing transcription factor in vitro and that repressor element 1 silencing transcription factor target gene and protein expression is altered in the prefrontal cortex of alcoholic men.List of scientific papersI. Richard Henriksson, Alexander Kuzmin, Anna Ökvist, Clive Harper, Donna Sheedy, Therese Garrick, Tatjana Yakovleva, Georgy Bakalkin. Elevated synaptophysin I in the prefrontal cortex of human chronic alcoholics. Synapse. 2008; 62(11):829-33. https://doi.org/10.1002/syn.20559 II. Hiroyuki Watanabe, Richard Henriksson, Yoshinori N. Ohnishi, Yoko H. Ohnishi, Clive Harper, Donna Sheedy, Therese Garrick, Fred Nyberg, Eric J. Nestler, Georgy Bakalkin, Tatjana Yakovleva. FOSB proteins in the orbitofrontal and dorsolateral prefrontal cortices of human alcoholics. Addict Biol. 2009; 14(3):294-7. https://doi.org/10.1111/j.1369-1600.2009.00155.x III. Richard Henriksson, Cristina M. Bäckman, Brandon K. Harvey, Ranjan Sen, Toni S. Shippenberg. REST regulates PDYN and REST target gene and protein expression is altered in the prefrontal cortex of alcoholic men. [Manuscript]</p
The mRNA expression of hTERT in human breast carcinomas correlates with VEGF expression
No full textBackground
Telomerase is a ribonucleoprotein enzyme that synthesises telomeres after cell division and maintains chromosomal stability leading to cellular immortalisation. hTERT (human telomerase reverse transcriptase) is the rate-limiting determinant of telomerase reactivation. Telomerase has been associated with negative prognostic indicators in some studies. The present study aims to detect any correlation between hTERT and the negative prognostic indicators VEGF and PCNA by quantitatively measuring the mRNA expression of these genes in human breast cancer and in adjacent non-cancerous tissue (ANCT).
Materials and methods
RNA was extracted from 38 breast carcinomas and 40 ANCT. hTERT and VEGF165, VEGF189 and PCNA mRNA expressions were estimated by reverse transcriptase-PCR (RT-PCR) and Taqman methodology.
Results
The level of expression of VEGF-165 and PCNA was significantly higher in carcinoma tissue than ANCT (p = 0.02). The ratio of VEGF165/189 expression was significantly higher in breast carcinoma than ANCT (p = 0.025). hTERT mRNA expression correlated with VEGF-189 mRNA (p = 0.008) and VEGF165 (p = 0.07).
Conclusions
hTERT mRNA expression is associated with the expression of the VEGF189 and 165 isoforms. This could explain the poorer prognosis reported in breast tumours expressing high levels of hTERT. The relative expression of the VEGF isoforms is significantly different in breast tumour to ANCT, and this may be important in breast carcinogenesis
Molecular aspects of proinsulin C-peptide interactions
No full textInsulin biosynthesis in the beta-cells of the pancreas begins with the generation of preproinsulin, which is converted to proinsulin. Proinsulin is cleaved into equimolar amounts of insulin and connecting peptide (C-peptide), which are released into the circulation. The 31-aminoacid-residue C-peptide has been held solely to contribute to proper folding, disulphide bridge formation and processing of insulin, but many reports now suggest that it may be a hormone itself. It has a beneficial effect on glycaemic control and may protect against diabetic complications.Comparison of the primary structures of proinsulin from 37 species showed that insulin A- and B-chains are considerably more conserved than C-peptide. Residues of Cpeptide conserved among mammalians reflect functional importance. It had been proposed that C-peptide biological activity involves association with lipid bilayers independently of chiral interactions, possibly involving its non-polar mid-section. The structure and capacity of human C-peptide to insert into lipid bilayers were assessed using circular dichroism and NMR spectroscopy. Lack of stable C-peptide secondary structure in aqueous solution was retained in the presence of lipid vesicles or micelles. C-peptide and lipid vesicles did not co-migrate upon size exclusion chromatography, which suggested that C-peptide is not likely to act via stable interactions with lipid membranes.Specific binding of C-peptide to primary cells had also been presented, but a receptor specific for C-peptide had not been purified. Binding of rhodaminelabelled human C-peptide (Rh-C-peptide) to intact or detergent-solubilized human skin fibroblasts was studied with fluorescence correlation spectroscopy. The zwitterionic detergent CHAPS released macromolecules with maintained C-peptide binding capacity from skin fibroblasts and may be useful in future purification protocols. A biologically active pentapeptide consisting of the C-terminal five amino acid residues of C-peptide had been found to displace cell membrane-associated Rh-C-peptide.The relative importance of each pentapeptide residue was assessed by determination of the displacing capacity of C-peptide analogues, and it was concluded that Glu-27 is critically involved in binding to cellular targets. The importance of conserved residues for biological activity of C-peptide was evaluated by incubation of mouse fibroblasts with physiological concentrations of C-peptide analogues. The capacity to induce phosphorylation of extracellular-signal regulated kinase (ERK) 1/2 correlates with the presence of residues Glu-3, -11 and -27 as well as non-helix-breaking residues in the N-terminal third of C-peptide, which forms a helical structure in trifluoroethanol. A tripartite model of C-peptide activity is suggested, since the acidic N-terminal part, the non-polar mid-section, and the partially conserved C-terminal part are all implied in biological activities.Reported insulinomimetic effects of C-peptide may be related to similarities with insulin. However, C-peptide binding to or interference with insulin binding to soluble, truncated insulin receptor (IR) or IGF-1 receptor was not detected with surface plasmon resonance (SPR) technology, and did not affect signalling pathways mediated by IR subtypes A or B in hamster beta-cells. Insulin oligomerization was detected and characterized with SPR and mass spectrometry. C-peptide augmented insulinlinsulin interactions in solution and reduced the amount of insulin hexamers in gas phase, which may explain clinical findings that C-peptide reinforces the effects of insulin on glucose metabolism. The molecular and clinical data are compatible with a role of C-peptide to promote insulin disaggregation, which appears relevant where insulin concentrations are high, i.e. at the secretion and injection sites.List of scientific papersI. Henriksson M, Shafqat J, Liepinsh E, Tally M, Wahren J, Jornvall H, Johansson J (2000). Unordered structured of proinsulin C-peptide in aqueous solution and in the presence of lipid vesicles. Cell Mol Life Sci. 57(2): 337-42. https://doi.org/10.1007/PL00000695 II. Henriksson M, Pramanik A, Shafqat J, Zhong Z, Tally M, Ekberg K, Wahren J, Rigler R, Johansson J, Jornvall H (2001). Specific binding of proinsulin C-peptide to intact and to detergent-solubilized human skin fibroblasts. Biochem Biophys Res Commun. 280(2): 423-7. https://doi.org/10.1006/bbrc.2000.4135 III. Pramanik A, Ekberg K, Zhong Z, Shafqat J, Henriksson M, Jansson O, Tibell A, Tally M, Wahren J, Jornvall H, Rigler R, Johansson J (2001). C-peptide binding to human cell membranes: importance of Glu27. Biochem Biophys Res Commun. 284(1): 94-8. https://doi.org/10.1006/bbrc.2001.4917 IV. Henriksson M, Nordling E, Melles E, Shafqat J, Stahlberg M, Ekberg K, Persson B, Bergman T, Wahren J, Johansson J, Jornvall H (2005). Separate functional features of proinsulin C-peptide. Cell Mol Life Sci. 62(15): 1772-8. https://doi.org/10.1007/s00018-005-5180-6 V. Shafqat J, Melles E, Sigmundsson K, Johansson BL, Ekberg K, Alvelius G, Henriksson M, Johansson J, Wahren J, Jornvall H (2006). Proinsulin C-peptide elicits disaggregation of insulin resulting in enhanced physiological insulin effects. [Submitted]VI. Henriksson M, Johansson J, Moede T, Leibiger I, Shafqat J, Berggren PO, Jornvall H (2006). Structural and functional features of proinsulin C-peptide in relation to insulin and IGF-1 receptor signalling.. [Submitted]</p
Intervertebral disc regeneration. Studies on stem cell niches and cell transplantation
No full textAbstract
Intervertebral disc regeneration
Studies on stem cell niches and cell transplantation
Helena Barreto Henriksson
Gothenburg 2010
Low back pain is a common condition in the Western world and disc degeneration (DD) is considered a major cause. DD is characterized by dysfunctional cells and decreased matrix production. The aim of this thesis was to explore normal growth and regeneration in the intervertebral disc (IVD). Further, to test possibilities of cell therapy treatment for DDs.
The methods used include in vitro- and in vivo experiments. In vitro methods were: monolayer, 3D cell cultures and explants models with human mesenchymal stem cells (hMSCs), articular chondrocytes and IVD cells. Cells/ tissues were analyzed for cell proliferation markers; BrdU, KI67, migration markers: β1-INTEGRIN, SNAIL-homolog-1 (SNAI1), SNAIL-homolog-2 (SLUG), progenitor/stem cell markers: STRO1, C-KIT, Notch1, CD105 and chondrogenic lineage markers: GDF5 and SOX9, matrix markers: COLLAGEN I and II, glycosaminoglycans, AGGRECAN by biochemical methods, flowcytometry, Real-time PCR and microscopy. Disc appearance was evaluated with MRI.
Results from normal regeneration studies: a potential stem cell niche was identified in the IVD region lateral to the epihyseal plate and in the annulus fibrosus outer region, based on findings of label-retaining cells and presence of cells expressing stem cell/progenitor markers, in young and mature animals. Migrating cells expressing SNAI1, SLUG, β1-integrin and GDF5 and SOX9 around niches were observed. Results from the cell therapy experiments; In vitro analyses; 3D co-culture system of hMSC and IVD cells showed an increased COLLAGEN II production. In vivo: Xenotransplanted cells survived in vivo 6 months (porcine IVDs) and produced matrix in hydrogel/MSCs injected IVDs. Taken together, these findings illustrate a normal slow regeneration of the IVD, and that growth and regeneration is presumably supported by progenitor cells deriving from niches adjacent to the IVD. Further, that human IVD cells and MSCs interact positively on matrix production when co-cultured and the survival of transplanted cells in vivo support the possibility for cell therapy treatment of DD. These results encourage further studies to arrest IVD degeneration, by stimulation of regenerative mechanisms in situ or by cell therapy.
ISBN 978-91-628-8147-
The impact of blood component transfusion practices on patient survival after abdominal aortic aneurysm surgery
No full textBackground: The aim of the present study was to investigate the blood transfusion practice in patients operated for abdominal aortic aneurysm (AAA) with special emphasis on massive transfusion in cases with rupture. Material and methods: From a database, 504 patients operated for AAA were stratified into 2 groups; an early transfusion period (1992-1999) and a late transfusion period (2000-2008) to evaluate the changes in transfusion practices over the course of time. Results: Patients operated for nonruptured AAA (n = 330) showed a decreased mortality rate from 4% (early transfusion period) to 1% (late transfusion period) without significant changes in the transfusion practices. In patients operated for ruptured AAA (n = 174) an unexpected low mortality rate was found compared to the 30-day mortality reported in earlier studies. The transfusion practices in ruptured AAA surgery showed a significant increase in platelet use and change of fresh frozen plasma: red blood cell ratio from 0.8 to 0.9 between the early and the late transfusion period. Conclusion: The present database study shows that the operating mortality for AAA surgery has declined during the past decades. The cause of the decline in mortality in patients with ruptured AAA was interpreted as partly due to a modern blood component therapy. © The Author(s) 2012.Correspondence Address: Henriksson, A.E.; Laboratory Medicine, Sundsvall County Hospital, SE-851 86 Sundsvall, Sweden; email: [email protected]</p
Molecular characterization of the cancer susceptibility protein wrap53β in Cajal body formation and DNA repair
No full textWRAP53β is a multifaceted protein involved in several biological processes including Cajal body maintenance, cancer cell survival and DNA damage repair. By directing factors to Cajal bodies and DNA double-strand breaks (DSBs), WRAP53β facilitates site-specific interactions necessary for proper biological responses. The Cajal body is a subnuclear organelle implicated in cellular processes such as splicing machinery maturation and telomere maintenance.In Paper I, we reveal that WRAP53β is an essential structural component of Cajal bodies. Furthermore, WRAP53β is required for the intracellular targeting of factors to this site. WRAP53β associates with the survival of motor neuron (SMN) complex in the cytoplasm, mediates its nuclear import and subsequent Cajal body accumulation. In addition, we find that the interaction between WRAP53β and SMN is disrupted in the severe neurodegenerative disorder spinal muscular atrophy, suggesting clinical relevance of WRAP53β-mediated SMN transport.In Paper II, we study the relationship between WRAP53β expression and cancer cell survival. We demonstrate that WRAP53β is overexpressed in a panel of different cancer cell lines in comparison to primary cells. WRAP53β depletion results in massive induction of cancer cell death, whereas normal human fibroblasts are largely insensitive to WRAP53β knockdown. The cell death associated with WRAP53β silencing occurs via the intrinsic mitochondrial pathway as demonstrated by Bax/Bak activation, loss of mitochondrial membrane potential and release of cytochrome c. Finally, we show that high WRAP53β expression levels correlate with poor prognosis and radioresistance of head and neck cancer patients.In Paper III, we establish WRAP53β as a novel player in the DNA damage response. We show that WRAP53β rapidly and transiently localizes to DNA DSBs in an ATM- and PARP-dependent manner. WRAP53β binds the E3 ligase RNF8 and facilitates its interaction with MDC1, which is essential for the downstream recruitment of repair proteins 53BP1, BRCA1 and RAD51 to damaged sites. Knockdown of WRAP53β results in deficient DNA DSB repair, whereas WRAP53β overexpression enhances repair efficiency and provides resistance to DNA damaging agents. Furthermore, reduced expression of WRAP53β is related to decreased ovarian cancer patient survival.In summary, our data identify WRAP53β as a novel structural and regulatory component of Cajal bodies as well as an important factor in carcinogenesis and DNA repair.List of scientific papersI. Mahmoudi S, Henriksson S, Weibrecht I, Smith S, Söderberg O, Strömblad S, Wiman KG and Farnebo M. WRAP53 is Essential for Cajal Body Formation and for Targeting the SMN Complex to Cajal Bodies. PLoS Biology. 2010 Nov 2;8(11):e1000521. https://doi.org/10.1371/journal.pbio.1000521 II. Mahmoudi S*, Henriksson S*, Farnebo L, Roberg K and Farnebo M. WRAP53 promotes cancer cell survival and is a potential target for cancer therapy. Cell Death and Disease. 2011 Jan 13;2:e114. https://pubmed.ncbi.nlm.nih.gov/21368886 III. Henriksson S, Hedström E, Rassoolzadeh H, Julner A, Imreh G, Zhivotovsky B, Jirström K, Brennan DJ, Helleday T and Farnebo M. The Cajal body protein WRAP53β regulates RNF8-mediated repair of DNA double-strand breaks. [Manuscript]</p
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