| 1. |
- Axelsson, Viktoria, et al.
(författare)
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Gliotoxin induces caspase-dependent neurite degeneration and calpain-mediated general cytotoxicity in differentiated human neuroblastoma SH-SY5Y cells.
- 2006
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Ingår i: Biochem Biophys Res Commun. - 0006-291X. ; 345:3, s. 1068-74
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Tidskriftsartikel (refereegranskat)abstract
- In this study, a significant increase by 50% in intracellular free calcium concentration ([Ca(2+)](i)) was observed in differentiated human neuroblastoma (SH-SY5Y) cells after exposure to 0.25microM of the fungal metabolite gliotoxin for 72h. Further, the involvement of caspases and calpains was demonstrated to underlie the gliotoxin-induced cytotoxic and neurite degenerative effects. The caspase inhibitor Z-VAD-fmk almost completely reduced the neurite degeneration from 40% degeneration of neurites to 5% as compared to control. Inhibition of calpains with calpeptin significantly attenuated gliotoxin-induced cytotoxicity, determined as reduction in total cellular protein content, from 43% to 14% as compared to control cells. Western blot analyses of alphaII-spectrin breakdown fragments confirmed activity of the proteases, and that alphaII-spectrin was cleaved by caspases in gliotoxin-exposed cells. These results show that calpains and caspases have a role in the toxicity of gliotoxin in differentiated SH-SY5Y cells and that the process may be Ca(2+)-mediated.
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| 2. |
- Bäckvall, Helena, et al.
(författare)
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Genetic tumor archeology : microdissection and genetic heterogeneity in squamous and basal cell carcinoma
- 2005
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Ingår i: Mutation research. - : Elsevier BV. - 0027-5107 .- 1873-135X. ; 571:02-jan, s. 65-79
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Forskningsöversikt (refereegranskat)abstract
- Carcinogenesis is a multi-step series of somatic genetic events. The complexity of this multi-hit process makes it difficult to determine each single event and the definitive outcome of such events. To investigate the genetic alterations in cancer-related genes, sensitive and reliable detection methods are of major importance for generating relevant results. Another critical issue is the quality of starting material which largely affects the outcome of the analysis. Microdissection of cells defined under the microscope ensures a selection of representative material for subsequent genetic analysis. Skin cancer provides an advantageous model for studying the development of cancer. Detectable lesions occur early during tumor progression, facilitating molecular analysis of the cell populations from both preneoplastic and neoplastic lesions. Alterations of the p53 tumor suppressor gene are very common in non-melanoma skin cancer, and dysregulation of p53 pathways appear to be an early event in the tumor development. A high frequency of epidermal p53 clones has been detected in chronically sun-exposed skin. The abundance of clones containing p53 mutated keratinocytes adjacent to basal cell (BCC) and squamous cell carcinoma (SCC) suggests a role in human skin carcinogenesis. Studies using p53 mutations as a clonality marker have suggested a direct link between actinic keratosis, SCC in situ and invasive SCC. Microdissection-based studies have also shown that different parts of individual BCC tumors can share a common p53 mutation yet differ with respect to additional alterations within the p53 gene, consistent with subclonal development within tumors. Here, we present examples of using well-defined cell populations, including single cells, from complex tissue in combination with molecular tools to reveal features involved in skin carcinogenesis.
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| 3. |
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| 4. |
- Engström, Katarina, 1956, et al.
(författare)
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The myxoid/round cell liposarcoma fusion oncogene FUS-DDIT3 and the normal DDIT3 induce a liposarcoma phenotype in transfected human fibrosarcoma cells.
- 2006
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Ingår i: The American journal of pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 168:5, s. 1642-53
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Tidskriftsartikel (refereegranskat)abstract
- Myxoid/round cell liposarcoma (MLS/RCLS) is the most common subtype of liposarcoma. Most MLS/RCLS carry a t(12;16) translocation, resulting in a FUS-DDIT3 fusion gene. We investigated the role of the FUS-DDIT3 fusion in the development of MLS/RCLS in FUS-DDIT3- and DDIT3-transfected human HT1080 sarcoma cells. Cells expressing FUS-DDIT3 and DDIT3 grew as liposarcomas in severe combined immunodeficient mice and exhibited a capillary network morphology that was similar to networks of MLS/RCLS. Microarray-based comparison of HT1080, the transfected cells, and an MLS/RCLS-derived cell line showed that the FUS-DDIT3- and DDIT3-transfected variants shifted toward an MLS/RCLS-like expression pattern. DDIT3-transfected cells responded in vitro to adipogenic factors by accumulation of fat and transformation to a lipoblast-like morphology. In conclusion, because the fusion oncogene FUS-DDIT3 and the normal DDIT3 induce a liposarcoma phenotype when expressed in a primitive sarcoma cell line, MLS/RCLS may develop from cell types other than preadipocytes. This may explain the preferential occurrence of MLS/RCLS in nonadipose tissues. In addition, development of lipoblasts and the typical MLS/RCLS capillary network could be an effect of the DDIT3 transcription factor partner of the fusion oncogene.
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| 5. |
- Gundale, Michael, et al.
(författare)
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The sensitivity of nitrogen fixation by a feathermoss-cyanobacteria association to litter and moisture variability in young and old boreal forests
- 2009
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Ingår i: Canadian Journal of Forest Research. - 0045-5067 .- 1208-6037. ; 39, s. 2542-2549
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a pair of experiments to assess whether nitrogen (N) fixation by a feathermoss-cyanobacteria association was sensitive to moisture availability and quality of litter inputs, and whether sensitivity to these factors differed between young and old forests. In our first greenhouse experiment, we experimentally varied the frequency of water addition to Pleurozium schreberi (Brid.) Mitt. collected from young and old forest sites. This experiment revealed that the extreme drought treatment reduced N fixation capacity (measured via acetylene reduction), whereas daily watering increased N fixation capacity. The experiment also demonstrated that sensitivity to moisture variability was greater in old forests than in young forests. In a second greenhouse experiment, we repeatedly applied litter extracts from six common boreal species, Pinus sylvestris L., Picea abies (L.) Karst., Betula pubescens Ehrh., Vaccinium myrtillus L., Vaccinium vitis-idaea L., and Empetrum hermaphroditum Lange ex Hagerup. After 43 days, we found no significant effects of litter or litter by stand age interaction on N fixation capacity of P. schreberi, whereas stand age remained a significant factor. These experiments suggest that the N fixation capacity of the P. schreberi - cyanobacteria association is relatively resistant to short-term variation of litter as an environmental driver but that precipitation extremes in old forests may significantly alter the N fixation capacity of the association.
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| 6. |
- Gustafsson, Erik, et al.
(författare)
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Invasive Staphylococcus aureus strains are highly variable in PFGE patterns, agr group and exoprotein production
- 2009
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa Healthcare. - 0036-5548 .- 1651-1980. ; 41:8, s. 577-583
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, we have investigated 37 invasive Staphylococcus aureus strains (collected between 1997 and 2005) from 33 human episodes of septicaemia causing either endocarditis or vertebral osteomyelitis. All S. aureus strains were typed using pulsed field gel electrophoresis (PFGE), and most strains belonged to any of 4 different PFGE clusters. There was no correlation between any of the PFGE clusters with site of infection. All strains showed highly different expression patterns of extracellular proteins, i.e. we found a vast variation in the number of proteins and amount of individual proteins expressed by the different strains. There was no correlation between any cluster of exoprotein patterns with endocarditis or with vertebral osteomyelitis. We did not find any correlation between agr group and endocarditis, as previously reported. On the other hand, a correlation between some of the PFGE clusters with a certain agr group was found. Known risk factors for S. aureus infections were observed in a majority of the patients.
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| 7. |
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| 8. |
- Gustafsson, Helena, et al.
(författare)
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The use of the human neuroblastoma SH-SY5Y cell line for estimation of acute systemic toxicity in vitro.
- 2007
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Konferensbidrag (refereegranskat)abstract
- Acute systemic toxicity, expressed as human lethal blood peak concentration or the dose inducing 50 % lethality in an animal population (LD50), can be estimated by general cytotoxicity tests using proliferating mammalian cell lines for 70-80 % of all chemicals. The cytotoxicity for the remaining chemicals over or under estimate the LD50 values/human lethal blood peak concentrations because of their very specific molecular targets or toxicokinetic features in vivo. The objective of the EU funded integrated project “ACuteTox” is to develop a strategy in which organ-specific endpoints and toxicokinetic features are taken into consideration in the in vitro prediction of acute systemic toxicity. The human neurotblastoma SH-SY5Y cell line was used as a model for studies on neurospecific targets, which are know to be crucial for survival. All endpoints were investigated after short exposure times (minutes to an hour) at concentrations of the test chemicals that did not affect the cell viability, measured as cell membrane leakage of lactate dehydrogenase. The effects of 23-26 compounds (drugs, pesticides and industrial chemicals) were studied on the cell membrane potential (CMP), voltage dependent Ca2+ channels (VDCC), muscarinic acetylcholine receptor (mAChR) function, acetylcholinesterase (AChE) activity and noradrenalin uptake. The results showed that the CMP was altered by atropine, amphetamine, mercury chloride, methadone, nicotine, pentachlorphenol, sodium lauryl sulphate (SLS) and verapamil, where as an effect on VDCC could be detected for amphetamine, atropine, colchicine, pentachlorphenol, SLS and verapamil. The mAChR function was measured as carbachol-induced Ca2+, i.e. activation of phospholipase C. Amphetamine, pentachlorphenol, SDS and verapamil attenuated the carbachol response by 50% at concentrations about 1 mM, but the specific mAChR antagonist atropine had the same effect at 3 nM. Nicotine, caffeine, pentachlorphenol, methadone, mercury chloride, SLS and the specific inhibitors physostigmine, dichlorvos and malathion attenuated the AChE activity at significantly non-cytotoxic concentrations in SH-SY5Y cells after 60 minutes of exposure. Parathion did not inhibit the AChE activity after 60 minutes exposure, but after 48 hr, indicating that oxidation of parathion to the active inhibitor paraoxon took place in the cell culture. This phenomenon was also observed for malathion, which displayed a lower EC50 value after the prolonged exposure time. The noradrenalin uptake was affected by atropine, caffeine, carbamazepine, amphetamine, diazepam, isopropanol, methadone, SLS and verapamil. A comparison of the active concentrations with the basal cytotoxicity measured as neutral red uptake in mouse fibroblast 3T3 cells indicated that the AChE assay is useful for detection of AChE inhibitors and possibly also AChR ligands. The VDCC endpoint was useful as an alert only for verapamil and the mAChR function was only specifically affected by atropine. The noradrenalin uptake indicated a clear alert for amphetamine and methadone, which was expected, but not for the other test compounds. These results indicate that the usefulness of these endpoints in a general test battery for estimation of acute systemic toxicity is limited, except for AChE activity measurements. However, the results clearly showed that the compounds with known mechanisms (e.g. atropine, verapamil, amphetamine and methodone ) displayed expected effects on their specific endpoints.
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| 9. |
- Gustafsson, Lotta, et al.
(författare)
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Utan sömn ingen fart
- 2008
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Ingår i: TEMPO - Om fart och det föränderliga. - 9789170610608
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Bokkapitel (populärvet., debatt m.m.)
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| 10. |
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| 11. |
- Johard, Helena, et al.
(författare)
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Intrinsic neurons of Drosophila mushroom bodies express short neuropeptide F: : relations to extrinsic neurons expressing different neurotransmitters
- 2008
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Ingår i: The Journal of comparative neurology. - 0021-9967. ; 507:4, s. 1479-96
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Tidskriftsartikel (refereegranskat)abstract
- Mushroom bodies constitute prominent paired neuropils in the brain of insects, known to be involved in higher olfactory processing and learning and memory. In Drosophila there are about 2,500 intrinsic mushroom body neurons, Kenyon cells, and a large number of different extrinsic neurons connecting the calyx, peduncle, and lobes to other portions of the brain. The neurotransmitter of the Kenyon cells has not been identified in any insect. Here we show expression of the gene snpf and its neuropeptide products (short neuropeptide F; sNPFs) in larval and adult Drosophila Kenyon cells by means of in situ hybridization and antisera against sequences of the precursor and two of the encoded peptides. Immunocytochemistry displays peptide in intrinsic neuronal processes in most parts of the mushroom body structures, except for a small core in the center of the peduncle and lobes and in the alpha'- and beta'-lobes. Weaker immunolabeling is seen in Kenyon cell bodies and processes in the calyx and initial peduncle and is strongest in the more distal portions of the lobes. We used different antisera and Gal4-driven green fluorescent protein to identify Kenyon cells and different populations of extrinsic neurons defined by their signal substances. Thus, we display neurotransmitter systems converging on Kenyon cells: neurons likely to utilize dopamine, tyramine/octopami
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| 12. |
- Klingberg, Torkel, et al.
(författare)
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Computerized training of working memory in children with ADHD--a randomized, controlled trial.
- 2005
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Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567 .- 1527-5418. ; 44:2, s. 177-186
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Deficits in executive functioning, including working memory (WM) deficits, have been suggested to be important in attention-deficit/hyperactivity disorder (ADHD). During 2002 to 2003, the authors conducted a multicenter, randomized, controlled, double-blind trial to investigate the effect of improving WM by computerized, systematic practice of WM tasks. METHOD: Included in the trial were 53 children with ADHD (9 girls; 15 of 53 inattentive subtype), aged 7 to 12 years, without stimulant medication. The compliance criterion (>20 days of training) was met by 44 subjects, 42 of whom were also evaluated at follow-up 3 months later. Participants were randomly assigned to use either the treatment computer program for training WM or a comparison program. The main outcome measure was the span-board task, a visuospatial WM task that was not part of the training program. RESULTS: For the span-board task, there was a significant treatment effect both post-intervention and at follow-up. In addition, there were significant effects for secondary outcome tasks measuring verbal WM, response inhibition, and complex reasoning. Parent ratings showed significant reduction in symptoms of inattention and hyperactivity/impulsivity, both post-intervention and at follow-up. CONCLUSIONS: This study shows that WM can be improved by training in children with ADHD. This training also improved response inhibition and reasoning and resulted in a reduction of the parent-rated inattentive symptoms of ADHD.
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| 13. |
- Matchkov, Vladimir V, et al.
(författare)
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Interaction between Na+/K+-pump and Na+/Ca2+-exchanger modulates intercellular communication.
- 2007
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Ingår i: Circulation research. - 1524-4571. ; 100:7, s. 1026-35
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Tidskriftsartikel (refereegranskat)abstract
- Ouabain, a specific inhibitor of the Na(+)/K(+)-pump, has previously been shown to interfere with intercellular communication. Here we test the hypothesis that the communication between vascular smooth muscle cells is regulated through an interaction between the Na(+)/K(+)-pump and the Na(+)/Ca(2+)-exchanger leading to an increase in the intracellular calcium concentration ([Ca(2+)](i)) in discrete areas near the plasma membrane. [Ca(2+)](i) in smooth muscle cells was imaged in cultured rat aortic smooth muscle cell pairs (A7r5) and in rat mesenteric small artery segments simultaneously with force. In A7r5 coupling between cells was estimated by measuring membrane capacitance. Smooth muscle cells were uncoupled when the Na(+)/K(+)-pump was inhibited either by a low concentration of ouabain, which also caused a localized increase of [Ca(2+)](i) near the membrane, or by ATP depletion. Reduction of Na(+)/K(+)-pump activity by removal of extracellular potassium ([K(+)](o)) also uncoupled cells, but only after inhibition of K(ATP) channels. Inhibition of the Na(+)/Ca(2+)-exchange activity by SEA0400 or by a reduction of the equilibrium potential (making it more negative) also uncoupled the cells. Depletion of intracellular Na(+) and clamping of [Ca(2+)](i) at low concentrations prevented the uncoupling. The experiments suggest that the Na(+)/K(+)-pump may affect gap junction conductivity via localized changes in [Ca(2+)](i) through modulation of Na(+)/Ca(2+)-exchanger activity.
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| 14. |
- Nordberg, Kjell, et al.
(författare)
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Stable carbon isotope evidence of the establishment of a new, opportunistic foraminiferal fauna in a Swedish Skagerrak fjord basin, in 1979/1980
- 2009
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Ingår i: Marine Micropaleontology. - : Elsevier BV. - 1872-6186 .- 0377-8398. ; 73:1-2, s. 117-128
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Tidskriftsartikel (refereegranskat)abstract
- Significant faunal changes reported fromrecent, coastal environments,which are not directly influenced by urban and industrial impact, are rarely seen. In Gullmar Fjord on the Swedish west coast, a significant foraminiferal fauna change occurred in connectionwith severe low-oxygen conditions that evolved in thewinter of 1979/1980. A foraminiferal fauna marked by common Skagerrak–Kattegat species, which had previously characterised the deep fjord basin, was replaced by the opportunistic, low-oxygen tolerant species Stainforthia fusiformis (Williamsson). To study this phenomenon further we performed stable oxygen and carbon isotope analyses on the indicator species itself, S. fusiformis, both on specimens from sediment cores representing approximately the last 85 years and on living (stained) individuals taken from a transect across the deep fjord basin. Our purpose was to detail how and why S. fusiformis, came to dominate the fauna. The oxygen isotope results suggest that salinities and temperatures in the deep basin have been relatively constant over the last c. 85 years, while the carbon isotopes show a significant change towards more negative values in association with the faunal shift of 1979/1980. The combined results from both the cores and the surface sediments suggest that S. fusiformis did not inhabit the deep basin until 1980. Before then, almost all specimens of S. fusiformis were small sized and their carbon isotope values suggest they were re-deposited shallow-water specimens that had been transported down to the central, deep basin as part of a suspension load. After a major faunal extinction in 1979–1980, S.fusiformis of all sizes suddenly appeared in large numbers and their carbon isotopic values were similar to the signal from registered in the recent, living fauna within the deep basin. This suggests that the opportunistic S. fusiformis established itself in the deep basin as a consequence of the severe low-oxygen event and the faunal crash of the previously dominating Skagerrak–Kattegat fauna.
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