| 1. |
- Aguda, Adeleke H., 1969-
(författare)
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Structural Study of the WH2 Family and Filamin: Implications for Actin Cytoskeleton Regulation
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cellular processes like motility, chemotaxis, phagocytosis and morphogenesis are dependent on the dynamic regulation of the actin cytoskeleton. This cytoskeleton system is tightly controlled by a number of diverse actin-binding proteins (ABPs) by various mechanisms described as nucleation, polymerization, capping, severing, depolymerization and sequestration. The ABPs are grouped based on sequence identity as in the Wiskott-Aldrich Syndrome protein homology domain 2 (WH2), and the calponin homology domain (CH) containing proteins.In this work, we elucidate the crystal structures of hybrids of gelsolin domain 1 with thymosin β4, ciboulot domain 2, and the second WH2 domain of N-WASP each bound to actin. We show that the single WH2 motif containing protein thymosin β4 in part sequesters actin by binding its pointed end via a C-terminal helix. This interaction prevents the addition of bound actin protomers to the barbed end of the filament. We propose that sequence variations in some WH2 motifs conferred F-actin binding ability to multiple repeat-containing proteins. These F-actin binding domains interact with the barbed end of a filament and the adjacent WH2 motifs are then freed to add their bound actin to the growing filament end. We demonstrate the binding of ciboulot domains 2 and 3 to both G- and F-actin and that full length ciboulot is capable of binding two actin monomers simultaneously. We have also cloned, expressed, purified and crystallized rod domains 14-16 from the actin crosslinking protein a-filamin. Preliminary X-ray crystallography data gives us hope that we shall be able to solve the structure of this triple domain repeat.
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| 2. |
- Rosén, Stefan, et al.
(författare)
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Molecular characterization of a saline-soluble lectin from a parasitic fungus : Extensive sequence similarities between fungal lectins
- 1996
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Ingår i: European Journal of Biochemistry. - : Wiley. - 0014-2956 .- 1432-1033. ; 238:3, s. 822-829
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Tidskriftsartikel (refereegranskat)abstract
- It has been proposed that the interactions between several parasite and pathogenic fungi and their hosts are mediated by soluble lectins present in the fungus. We have cloned and analyzed a gene encoding such a lectin (AOL) from the nematophagous fungus Arthrobotrys oligospora (deuteromycete). The deduced primary structure of the AOL gene displayed an extensive similarity (identity 46.3%) to that of a gene encoding a lectin (ABL) recently isolated from the mushroom Agaricus bisporus (basidiomycete), but not to any other fungal, microbial, plant, or animal lectins. The similarities between AOL and ABL were further demonstrated by the observation that an antibody specific for AOL cross-reacted with ABL. Together with data showing that AOL has a binding specificity that is similar to that of ABL [Rosen, S., Bergstrom, J., Karlsson, K.-A., and Tunlid, A. (1996) Eur. J. Biochem. 238, 830-837], these results indicate that AOL and ABL are members of a novel family of saline- soluble lectins present in fungi. Southern blots indicated that there is only one AOL gene in the genome encoding a subunit (monomer) of the lectin. The primary structure of AOL did not show the presence of a typical N-terminal signal sequence. Comparison of the deduced primary structure with the molecular mass of AOL as determined by electrospray mass spectrometry (16153 Da), indicated that AOL has an acetylated N-terminal but no other post- translational modifications, and that a minor isoform is formed by deamidation. Circular dichroism (CD) spectroscopy suggested that the secondary structure of AOl contains 34% β-sheets, 21% α-helix, and 45% turns and coils.
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| 3. |
- Aguda, Adeleke Halilu, et al.
(författare)
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Expression, crystallization and preliminary crystallographic data analysis of filamin A repeats 14-16
- 2007
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Ingår i: Acta Crystallographica. Section F. - 1744-3091 .- 1744-3091. ; 63:4, s. 291-293
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Tidskriftsartikel (refereegranskat)abstract
- Human filamin A is a 280 kDa protein involved in actin-filament cross-linking. It is structurally divided into an actin-binding headpiece (ABD) and a rod domain containing 24 immunoglobulin-like (Ig) repeats. A fragment of human filamin A (Ig repeats 14-16) was cloned and expressed in Escherichia coli and the purified protein was crystallized in 1.6 M ammonium sulfate, 2% PEG 1000 and 100 mM HEPES pH 7.5. The crystals diffracted to 1.95 A and belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 50.63, b = 52.10, c = 98.46 A, alpha = beta = gamma = 90 degrees.
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| 4. |
- Andersson, Derek, et al.
(författare)
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Myrosinases from root and leaves of Arabidopsis thaliana have different catalytic properties
- 2009
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Ingår i: Phytochemistry. - : Elsevier BV. - 0031-9422 .- 1873-3700. ; 70:11-12, s. 1345-1354
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Tidskriftsartikel (refereegranskat)abstract
- Myrosinases (EC 3.2.1.147) are beta-thioglucoside glucosidases present in Brassicaceae plants. These enzymes serve to protect plants against pathogens and insect pests by initiating breakdown of the secondary metabolites glucosinolates into toxic products. Several forms of myrosinases are present in plants but the properties and role of different isoenzymes are not well understood. The dicot plant model organism Arabidopsis thaliana seems to contain six myrosinase genes (TGG1-TGG6). In order to compare the different myrosinases, cDNAs corresponding to TGG1 from leaves and TGG4 and TGG5 from roots were cloned and overexpressed in Pichia pastoris. The His-tagged recombinant proteins were purified using affinity chromatography and the preparations were homogenous according to SDS-PAGE analysis. Myrosinase activity was confirmed for all forms and compared with respect to catalytic activity towards the allyl-glucosinolate sinigrin. There was a 22-fold difference in basal activity among the myrosinases. The enzymes were active in a broad pH range, are rather thermostable and active in a wide range of salt concentrations but sensitive to high salt concentrations. The myrosinases showed different activation-inhibition responses towards ascorbic acid with maximal activity around 0.7-1 mM. No activity was registered towards desulphosinigrin and this compound did not inhibit myrosinase activity towards sinigrin. All myrosinases also displayed O-beta-glucosidase activity, although with lower efficiency compared to the myrosinase activity. The differences in catalytic properties among myrosinase isozymes for function in planta are discussed.
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| 5. |
- Andersson, Gerhard, et al.
(författare)
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Evaluation of quality of life and symptoms after translabyrinthine acoustic neuroma surgery
- 1997
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Ingår i: The American journal of otology. - 0192-9763. ; 18:4, s. 421-426
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:This study aimed to describe the consequences of acoustic neuroma surgery in terms of symptoms and quality of life.STUDY DESIGN:This study was a retrospective case review.SETTING:The surgery was conducted in Uppsala, Sweden.PATIENTS:A consecutive sample of acoustic neuroma patients operated on between 1988 and 1994.INTERVENTION:All patients had been operated on with the translabyrinthine technique.MAIN OUTCOME MEASURES:A questionnaire was constructed including questions about the surgery and symptoms. The House and Brackmann scale was used for grading facial function and the Brackmann and Bars scale was used for self-assessment of facial function.RESULTS:Follow-up data were collected by a postal questionnaire sent out and returned by 141 patients, which yielded a 90% response rate. Normal to moderately impaired facial function (House I-III) was evident in 85.2% of patients, although residual facial problems were reported. Most considered hearing to be worse after surgery (80%), and tinnitus was found in 60% of the sample. Balance problems (45%), dizziness (19%), and headache/pain (22%) were also reported. Work ability was affected in 23%, and 37% reported a continued need for medical consultations, mainly because of facial problems and pain. Most (89%) were pleased with the preoperative information.CONCLUSIONS:This study showed that few patients with acoustic neuroma had experienced negative social consequences after surgery. Although not linked to the operation, residual symptoms were reported that may necessitate further rehabilitation.
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| 6. |
- Andersson, Gerhard, et al.
(författare)
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Tinnitus and translabyrinthine acoustic neuroma surgery
- 1997
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Ingår i: Audiology & neuro-otology. - : S. Karger AG. - 1420-3030 .- 1421-9700. ; 2:6, s. 403-409
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this investigation was to study the effects of translabyrinthine acoustic neuroma surgery on tinnitus in a consecutive sample of patients operated on between 1988 and 1994 in Uppsala (Sweden). A postal questionnaire was returned by 141 patients, yielding a 90% response rate without reminder. The results showed that tinnitus was experienced by 70% of the patients before surgery and 60% after surgery. In general, low degrees of tinnitus distress were found, which was confirmed by the questionnaire results. Ratings of tinnitus distress after surgery, using the Klockhoff and Lindblom grading system, showed that 48% had tinnitus of grade I, 46% of grade II, and 6% of grade III. Pre- and postsurgery grading of distress did not change significantly. There was a 35% risk for developing tinnitus when no preoperative tinnitus was present and a 15% chance that tinnitus disappears when present preoperatively.
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| 7. |
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| 8. |
- Brunt, David, 1949-, et al.
(författare)
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Residents' Perceptions of Quality in Supported Housing for People with Psychiatric Disabilities
- 2019
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Ingår i: Issues in Mental Health Nursing. - : Taylor & Francis. - 0161-2840 .- 1096-4673. ; 40:8, s. 697-705
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Tidskriftsartikel (refereegranskat)abstract
- The residents' perspective of the quality of housing support for people with psychiatric disabilities living in congregate supported housing has been studied and a comparison has been made with the findings from those from a previous study in ordinary housing with outreach support. One-hundred and seventy-eight residents from 27 supported housing facilities in eight Swedish municipalities completed the Quality of Psychiatric Care-Housing (QPC-H) instrument. The highest quality ratings were found for: Secluded Environment, Encounter and Support, while Participation, Housing Specific and Secure Environment were rated at lower levels. Despite relatively high ratings, a majority of items did not attain the 80% cutoff point deemed as defining satisfactory quality of service. The residents in ordinary housing with outreach support rated higher levels for the majority of the QPC-H dimensions in comparison with those in supported housing. A conclusion is that the quality of care in supported housing facilities has a number of deficiencies that need to be addressed. Supported housing is generally rated as having a lower quality of care than in ordinary housing with outreach support. Suggestions for the content of staff training are made based on the results.
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| 9. |
- Carling, Tobias, et al.
(författare)
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Hyperparathyroidism of multiple endocrine neoplasia type 1 : candidate gene and parathyroid calcium sensing protein expression
- 1995
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Ingår i: Surgery. - 0039-6060 .- 1532-7361. ; 118:6, s. 924-931
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Hyperparathyroidism affects most patients with multiple endocrine neoplasia type 1 (MEN 1). This study investigates expression of the candidate MEN1 gene phospholipase C beta 3 (PLC beta 3) and expression and function of a putative calcium sensing protein (CAS) in hyperparathyroidism of MEN 1.METHODS:In 31 parathyroid glands from 17 patients with MEN 1, CAS distribution was studied immunohistochemically and parallel sections were explored for PLC beta 3 mRNA expression by in situ hybridization. Enzymatically dispersed parathyroid cells were analyzed for cytoplasmic calcium concentrations [Ca2+]i and parathyroid hormone (PTH) release.RESULTS:All glands exhibited a heterogeneously reduced CAS immunoreactivity, especially meager in nodularly assembled parathyroid cells. Calcium regulated [Ca2+]i and PTH release tended to be more deranged in the glands possessing the lowest immunostaining. Parathyroid PLC beta 3 invariably was homogeneously expressed, and this included even MEN 1 patients with reduced PLC beta 3 expression in endocrine pancreatic tumors.CONCLUSIONS:The findings support variable calcium insensitivity of [Ca2+]i and PTH release in hyperparathyroidism of MEN 1, apparently coupled to heterogeneously reduced CAS expression. For clarification of the role of PLC beta 3 in MEN 1 parathyroid tumorigenesis further study of this protein is required.
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| 10. |
- Ek, Weronica E., et al.
(författare)
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Tea and coffee consumption in relation to DNA methylation in four European cohorts
- 2017
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 26:16, s. 3221-3231
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Tidskriftsartikel (refereegranskat)abstract
- Lifestyle factors, such as food choices and exposure to chemicals, can alter DNA methylation and lead to changes in gene activity. Two such exposures with pharmacologically active components are coffee and tea consumption. Both coffee and tea has been suggested to play an important role in modulating disease-risk in humans by suppressing tumour progression, decreasing inflammation and influencing estrogen metabolism. These mechanisms may be mediated by changes in DNA methylation.To investigate if DNA methylation in blood is associated with coffee and tea consumption we performed a genome-wide DNA methylation study for coffee and tea consumption in four European cohorts (N = 3,096). DNA methylation was measured from whole blood at 421,695 CpG sites distributed throughout the genome and analysed in men and women both separately and together in each cohort. Meta-analyses of the results and additional regional-level analyses were performed.After adjusting for multiple testing, the meta-analysis revealed that two individual CpG-sites, mapping to DNAJC16 and TTC17, were differentially methylated in relation to tea consumption in women. No individual sites were associated in men or in the sex-combined analysis for tea or coffee. The regional analysis revealed that 28 regions were differentially methylated in relation to tea consumption in women. These regions contained genes known to interact with estradiol metabolism and cancer. No significant regions were found in the sex-combined and male-only analysis for either tea or coffee consumption.
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