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21.
Calpain-mediated Bid cleavage and calpain-independent Bak modulation: two separate pathways in cisplatin-induced apoptosis 下载免费PDF全文
Mandic A Viktorsson K Strandberg L Heiden T Hansson J Linder S Shoshan MC 《Molecular and cellular biology》2002,22(9):3003-3013
Calpain is a ubiquitous protease with potential involvement in apoptosis. We report that in human melanoma cells, cisplatin-induced calpain activation occurs early in apoptosis. Calpain activation and subsequent apoptosis were inhibited by calpeptin and PD150606, two calpain inhibitors with different modes of action. Furthermore, cisplatin induced cleavage of the BH3-only protein Bid, yielding a 14-kDa fragment similar to proapoptotic, caspase-cleaved Bid. However, Bid cleavage was inhibited by inhibitors of calpain, but not by inhibitors of caspases or of cathepsin L. Recombinant Bid was cleaved in vitro by both recombinant calpain and by lysates of cisplatin-treated cells. Cleavage was calpeptin sensitive, and the cleavage site was mapped between Gly70 and Arg71. Calpain-cleaved Bid induced cytochrome c release from isolated mitochondria. While calpeptin did not affect cisplatin-induced modulation of Bak to its proapoptotic conformation, a dominant-negative mutant of MEKK1 (dnMEKK) inhibited Bak modulation. dnMEKK did not, however, block Bid cleavage. The combination of dnMEKK and calpeptin had an additive inhibitory effect on apoptosis. In summary, calpain-mediated Bid cleavage is important in drug-induced apoptosis, and cisplatin induces at least two separate apoptotic signaling pathways resulting in Bid cleavage and Bak modulation, respectively. 相似文献
22.
Aho AJ Hautamäki M Mattila R Alander P Strandberg N Rekola J Gunn J Lassila LV Vallittu PK 《Cell and tissue banking》2004,5(4):213-221
The aim of this study was to describe and evaluate the significance of a porous surface with bioactive glass granules (S53P4)
covering an artificial bulk material based on polymethylmetacrylate (PMMA) and fibre-reinforced composite (FRC) technology.
Effort was focused particularly on characters of the porous surface and biomechanical properties of the material in vitro, and test in vivo the implant in reconstruction in an experimental long bone segment defect model. The defect, 10 mm in length, created in
the shaft of rabbit tibia, was reconstructed by the implant and fixed by intramedullary K-wires. The implant was incorporated
within 4 weeks by new bone growth from the host bone covering particularly its posterior surface and cortex/implant junctions
with bridging trabecular bone. Later, at 8 weeks, new bone was found also at the cortex/implant interface and in the medullary
canal of the implant. Histometric measurements revealed direct bone/implant surface contact in 34% at the interface. Bioactive
glass granules in the porous surface evoked the most direct contact with bone. The implants manufactured from PMMA only served
as a control group, and showed significantly lower osteoconductive properties. Biomechanical measurements in vitro of fibre-reinforced PMMA specimens revealed values for bending strength and the flexural modulus to match them to human bone.
This artificial bulk bone material based on PMMA/FRC technology seems to have proposing properties to be used as a bone substitute
on load-bearing conditions.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
23.
Recombining germline-derived CDR sequences for creating diverse single-framework antibody libraries 总被引:10,自引:0,他引:10
Söderlind E Strandberg L Jirholt P Kobayashi N Alexeiva V Aberg AM Nilsson A Jansson B Ohlin M Wingren C Danielsson L Carlsson R Borrebaeck CA 《Nature biotechnology》2000,18(8):852-856
We constructed a single-chain Fv antibody library that permits human complementarity-determining region (CDR) gene fragments of any germline to be incorporated combinatorially into the appropriate positions of the variable-region frameworks VH-DP47 and VL-DPL3. A library of 2 x 109 independent transformants was screened against haptens, peptides, carbohydrates, and proteins, and the selected antibody fragments exhibited dissociation constants in the subnanomolar range. The antibody genes in this library were built on a single master framework into which diverse CDRs were allowed to recombine. These CDRs were sampled from in vivo-processed gene sequences, thus potentially optimizing the levels of correctly folded and functional molecules, and resulting in a molecule exhibiting a lower computed immunogenicity compared to naive immunoglobulins. Using the modularized assembly process to incorporate foreign sequences into an immunoglobulin scaffold, it is possible to vary as many as six CDRs at the same time, creating genetic and functional variation in antibody molecules. 相似文献
24.
Background
Low molecular weight heparins (LMWH’s) are used to prevent and treat thrombosis. Tests for monitoring LMWH’s include anti-factor Xa (anti-FXa), activated partial thromboplastin time (aPTT) and thrombin generation. Anti-FXa is the current gold standard despite LMWH’s varying affinities for FXa and thrombin.Aim
To examine the effects of two different LMWH’s on the results of 4 different aPTT-tests, anti-FXa activity and thrombin generation and to assess the tests’ concordance.Method
Enoxaparin and tinzaparin were added ex-vivo in concentrations of 0.0, 0.5, 1.0 and 1.5 anti-FXa international units (IU)/mL, to blood from 10 volunteers. aPTT was measured using two whole blood methods (Free oscillation rheometry (FOR) and Hemochron Jr (HCJ)) and an optical plasma method using two different reagents (ActinFSL and PTT-Automat). Anti-FXa activity was quantified using a chromogenic assay. Thrombin generation (Endogenous Thrombin Potential, ETP) was measured on a Ceveron Alpha instrument using the TGA RB and more tissue-factor rich TGA RC reagents.Results
Methods’ mean aPTT at 1.0 IU/mL LMWH varied between 54s (SD 11) and 69s (SD 14) for enoxaparin and between 101s (SD 21) and 140s (SD 28) for tinzaparin. ActinFSL gave significantly shorter aPTT results. aPTT and anti-FXa generally correlated well. ETP as measured with the TGA RC reagent but not the TGA RB reagent showed an inverse exponential relationship to the concentration of LMWH. The HCJ-aPTT results had the weakest correlation to anti-FXa and thrombin generation (Rs0.62–0.87), whereas the other aPTT methods had similar correlation coefficients (Rs0.80–0.92).Conclusions
aPTT displays a linear dose-respone to LMWH. There is variation between aPTT assays. Tinzaparin increases aPTT and decreases thrombin generation more than enoxaparin at any given level of anti-FXa activity, casting doubt on anti-FXa’s present gold standard status. Thrombin generation with tissue factor-rich activator is a promising method for monitoring LMWH’s. 相似文献25.
Miikka Tarkia Antti Saraste Christoffer Stark Tommi V?h?silta Timo Savunen Marjatta Strandberg Virva Saunavaara Tuula Tolvanen Jarmo Teuho Mika Ter?s Olli Mets?l? Petteri Rinne Ilkka Heinonen Nina Savisto Mikko Pietil? Pekka Saukko Anne Roivainen Juhani Knuuti 《PloS one》2015,10(6)
Objective
Inflammation is an important contributor to atherosclerosis progression. A glucose analogue 18F-fluorodeoxyglucose ([18F]FDG) has been used to detect atherosclerotic inflammation. However, it is not known to what extent [18F]FDG is taken up in different stages of atherosclerosis. We aimed to study the uptake of [18F]FDG to various stages of coronary plaques in a pig model.Methods
First, diabetes was caused by streptozotocin injections (50 mg/kg for 3 days) in farm pigs (n = 10). After 6 months on high-fat diet, pigs underwent dual-gated cardiac PET/CT to measure [18F]FDG uptake in coronary arteries. Coronary segments (n = 33) were harvested for ex vivo measurement of radioactivity and autoradiography (ARG).Results
Intimal thickening was observed in 16 segments and atheroma type plaques in 10 segments. Compared with the normal vessel wall, ARG showed 1.7±0.7 times higher [18F]FDG accumulation in the intimal thickening and 4.1±2.3 times higher in the atheromas (P = 0.004 and P = 0.003, respectively). Ex vivo mean vessel-to-blood ratio was higher in segments with atheroma than those without atherosclerosis (2.6±1.2 vs. 1.3±0.7, P = 0.04). In vivo PET imaging showed the highest target-to-background ratio (TBR) of 2.7. However, maximum TBR was not significantly different in segments without atherosclerosis (1.1±0.5) and either intimal thickening (1.2±0.4, P = 1.0) or atheroma (1.6±0.6, P = 0.4).Conclusions
We found increased uptake of [18F]FDG in coronary atherosclerotic lesions in a pig model. However, uptake in these early stage lesions was not detectable with in vivo PET imaging. Further studies are needed to clarify whether visible [18F]FDG uptake in coronary arteries represents more advanced, highly inflamed plaques. 相似文献26.
Raymond H. G. Klaassen Roine Strandberg Mikael Hake Patrik Olofsson Anders P. Tøttrup Thomas Alerstam 《Journal of avian biology》2010,41(2):200-207
Loop migration among birds is characterized by the spring route lying consistently west or east of the autumn route. The existence of loops has been explained by general wind conditions or seasonal differences in habitat distribution. Loop migration has predominantly been studied at the population level, for example by analysing ring recoveries. Here we study loop migration of individual marsh harriers Circus aeruginosus tracked by satellite telemetry. We show that despite a generally narrow migration corridor the harriers travelled in a distinct clockwise loop through Africa and southern Europe, following more westerly routes in spring than in autumn. We used the Normalized Difference Vegetation Index (NDVI) to identify potential feeding habitat in Africa. Suitable habitat seemed always more abundant along the western route, both in spring and autumn, and no important stopover site was found along the eastern route. Observed routes did thus not coincide with seasonal variation in habitat availability. However, favourable habitat might be more important during spring migration, when the crossing of the Sahara seems more challenging, and thus habitat availability might play an indirect role in the harriers’ route choice. Grid‐based wind data were used to reconstruct general wind patterns, and in qualitative agreement with the observed loop marsh harriers predominantly encountered westerly winds in Europe and easterly winds in Africa, both in autumn and in spring. By correlating tail‐ and crosswinds with forward and perpendicular movement rates, respectively, we show that marsh harriers are partially drifted by wind. Thus, we tentatively conclude that wind rather than habitat seems to have an overriding effect on the shape of the migration routes of marsh harriers. General wind conditions seem to play an important role also in the evolution of narrow migratory loops as demonstrated for individual marsh harriers. 相似文献
27.
Viklund A Braam A Näsholm A Strandberg E Philipsson J 《Animal : an international journal of animal bioscience》2010,4(5):682-691
For many years, the breeding value estimation for Swedish riding horses has been based on results from Riding Horse Quality Tests (RHQTs) of 4-year-olds only. Traits tested are conformation, gaits and jumping ability. An integrated index including competition results is under development to both get as reliable proofs as possible and increases the credibility of the indexes among breeders, trainers and riders. The objectives of this study were to investigate the suitability of competition data for use in genetic evaluations of horses and to examine how well young horse performance agrees with performance later in life. Competition results in dressage and show jumping for almost 40 000 horses from the beginning of the 1960s until 2006 were available. For RHQT data of 14 000 horses judged between 1988 and 2007 were used. Genetic parameters were estimated for accumulated competition results defined for different age groups (4 to 6 years of age, 4 to 9 years of age and lifetime), and for different birth year groups. Genetic correlations were estimated between results at RHQT and competitions with a multi-trait animal model. Heritabilities were higher for show jumping than dressage and increased with increasing age of the horse and amount of information. For dressage, heritabilities increased from 0.11 for the youngest group to 0.16 for lifetime results. For show jumping corresponding values increased from 0.24 to 0.28. Genetic correlations between competition results for the different age groups were highly positive (0.84 to 1.00), as were those between jumping traits at RHQT and competition results in show jumping (0.87 to 0.89). For dressage-related traits as 4-year-old and dressage competition results the estimated genetic correlations were between 0.47 and 0.77. We suggest that lifetime results from competitions should be integrated into the genetic evaluation system. However, genetic parameters showed that traits had changed during the over 35-year period covered due to the development of the sport, which needs to be considered in future genetic evaluations. 相似文献
28.
Viklund A Näsholm A Strandberg E Philipsson J 《Animal : an international journal of animal bioscience》2010,4(11):1823-1831
For Swedish Warmblood sport horses, breeding values (BVs) are predicted using a multiple-trait animal model with results from competitions and young horse performance tests. Data go back to the beginning of the 1970s, and earlier studies have indicated that some of the recorded traits have changed through the years. The objective of this study was to investigate the effects of including all performance data or excluding the older ones compared to a bivariate model (BM) considering performance traits in early and late periods as separate traits. The bivariate approach was assumed to give the most correct BVs for the actual breeding population. Competition results in dressage and show jumping for almost 40 000 horses until 2006 were available. For riding horse quality test (RHQT), data of 14 000 horses judged between 1973 and 2007 were used. Genetic correlations of 0.69 to 1.00 were estimated between traits recorded at different time periods (RHQT data) or different birth year groups (competition data). A cross-validation study and comparison of BVs using different sets of data showed that most accurate and similar results were obtained when BVs were predicted from either the BM or the univariate model including all data from the beginning of the recording. We recommend using all data and applying the univariate model to minimise the computational efforts for genetic evaluations and for provision of reliable BVs for as many horses as possible. 相似文献
29.
Anneli Ritala Kristian Aspegren Ulrika Kurtén Marjatta Salmenkallio-Marttila Leena Mannonen Riitta Hannus Veli Kauppinen Teemu H. Teeri Tor-Magnus Enari 《Plant molecular biology》1994,24(2):317-325
Transgenic, fertile barley (Hordeum vulgare L.) from the Finnish elite cultivar Kymppi was obtained by particle bombardment of immature embryos. Immature embryos were bombarded to the embryonic axis side and grown to plants without selection. Neomycin phosphotransferase II (NPTII) activity was screened in small plantlets. One out of a total of 227 plants expressed the transferred nptII gene. This plant has until now produced 98 fertile spikes (T0), and four of the 90 T0 spikes analyzed to date contained the nptII gene. These shoots were further analyzed and they expressed the transferred gene. From green grains, embryos were isolated and grown to plantlets (T1). The four transgenic shoots of Toivo (the T0 plant) produced 25 plantlets as T1 progeny. Altogether fifteen of these T1 plants carried the transferred nptII gene as detected with the PCR technique, fourteen of which expressed the nptII gene. The integration and inheritance of the transferred nptII gene was confirmed by Southern blot hybridization. Although present as several copies, the transferred gene was inherited as a single Mendelian locus into the T2 progeny. 相似文献
30.
Jonas Strandberg Kjell Arne Johanson 《Journal of Zoological Systematics and Evolutionary Research》2011,49(2):110-118
The genus Apsilochorema Ulmer, 1907 is unique in the family Hydrobiosidae Ulmer, being widely distributed in the Palaearctic, Oriental and Australian Regions. All other 49 genera in the family, except the New World Atopsyche Banks, 1905, are confined to a single biogeographical Region. This unique distribution has independently stimulated researchers to formulate competing hypotheses about the biogeographical history of the genus. Molecular sequence data from mitochondrial cytochrome oxidase I (COI) and nuclear cadherin (CAD) genes of Apsilochorema species from the Oriental and Australian areas were analysed phylogenetically. The results retain a monophyletic Apsilochorema, which forms the sistergroup to the other genera in the subfamily Apsilochorematinae. The results from the biogeographical analyses dispute the earlier assumptions of an Oriental or northern Gondwana origin for the genus, revealing unambiguously an initial Australian radiation of the ancestral Apsilochorema with a subsequent dispersal into the Oriental Region. All but one of the Apsilochorema species occurring on the Pacific islands had an Oriental ancestor. The exception is the sistergroup to the New Caledonian species, which is found in both Australia and Oriental Regions. The molecular dating analysis, using a relaxed clock model, indicates that the genus Apsilochorema is about 36.4 MY old and that it dispersed from Australia into the Oriental Region about 28.3 Ma. It also gives an estimate of the approximate ages of the dispersals into New Caledonia to about 15.3 Ma; to the Solomon Islands at about 16.2 Ma; to the Fiji Islands at about 16.1 Ma; and to the Vanuatu Islands at about 5.4 Ma. 相似文献