| 1. |
- Bjersing, Jan, 1966, et al.
(författare)
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Anti-proliferative effects of phosphodiester oligodeoxynucleotides
- 2004
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Ingår i: Immunobiology. - : Elsevier BV. - 0171-2985. ; 209:8, s. 637-45
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Tidskriftsartikel (refereegranskat)abstract
- The immunostimulatory effects of cytosine-phosphate-guanosine (CpG)-containing oligodeoxynucleotides (ODNs) have been extensively documented. In this paper, we describe the inhibitory effects of ODNs that contain natural phosphodiester backbones (O-ODNs) on the immunostimulation caused by CpG-containing phosphorothioated ODNs (CpG-S). CpG-S stimulation of mouse splenocyte proliferation was reduced by the addition of O-ODNs that contained or lacked the CpG-motif (CpG-containing phosphodiester oligodeoxynucleotide, CpG-O or GpC-O). The total number of cultured splenocytes was up-regulated by CpG-S, whereas repetitive addition of O-ODNs to the cell cultures inhibited this effect. The frequency of T2-like B cells was found to be increased by CpG-S. The culture supernatants of CpG-S-treated splenocytes contained elevated levels of IL-10 and IL-6. However, IL-10 and IL-6 production was down-regulated significantly by the combination of CpG-S and either CpG-O or GpC-O. The O-ODN mediated inhibition of proliferation was less pronounced in IL-10-/- mice. Thus, the O-ODNs, irrespective of CpG content, exerted inhibitory activities on the proliferation of B cells. These anti-proliferative effects appear to be mediated both by the down-regulation of IL-10 production and increased apoptosis.
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| 2. |
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| 3. |
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| 4. |
- Agarkova, Irina, et al.
(författare)
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The molecular composition of the sarcomeric M-band correlates with muscle fiber type
- 2004
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Ingår i: European Journal of Cell Biology. - 0171-9335. ; 83:5, s. 193-204
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Tidskriftsartikel (refereegranskat)abstract
- The M-band is the transverse structure that cross-links the thick filaments in the center and provides a perfect alignment of the A-band in the activated sarcomere. The molecular composition of the M-bands in adult mouse skeletal muscle is fiber-type dependent. All M-bands in fast fibers contain M-protein while M-bands in slow fibers contain a significant proportion of the EH-myomesin isoform, previously detected only in embryonic heart muscle. This fiber-type specificity develops during the first postnatal weeks. However, the ratio between the amounts of myosin and of myomesin, taken as sum of both isoforms, remains nearly constant in all studied muscles. Ultrastructural analysis demonstrates that some of the soleus fibers show a diffuse appearance of the M-band, resembling the situation in the embryonic heart. A model is proposed to explain the functional consequence of differential M-band composition for the physiological and morphological properties of sarcomeres in different muscle types.
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| 5. |
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| 6. |
- Berntsson, Kent M., 1963, et al.
(författare)
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Rejection of unsuitable substrata as a potential driver of aggregated settlement in the barnacle Balanus improvisus
- 2004
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Ingår i: Marine Ecology-Progress Series. - 0171-8630. ; 275, s. 199-210
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Tidskriftsartikel (refereegranskat)abstract
- Many marine invertebrate larvae have the capacity to reject or accept settlement sites based on a broad range of cues. Species-specific settlement responses to different cues are often inferred from final settlement choice in the field. Little is known about species-specific larval behaviour in response to different cues and, in particular, how the behaviour is linked to final settlement. Rejection of unsuitable substrata may be an important driving force that leads to aggregated settlement patterns. This study examines rejection responses in relation to surface attractiveness for settlement under field and laboratory conditions in the barnacle Balanus improvisus. The attractiveness for settlement was manipulated by varying surface texture in combination with crude extract from conspecific adults. Active rejection behaviour was examined as a function of surface texture and conspecific pheromones in the field and then related to behavioural responses under static and flowing conditions in the laboratory. Recruitment was heavily reduced on substrata with ribbed microtexture compared to smooth substrata and unaffected by crude extract from conspecific adults. On average, 28% of the cyprids that encountered smooth settlement panels recruited. The proportion of cyprids recruiting on 2 microtextured substrata after encounter was 5 and 1% respectively. In behavioural experiments cyprids showed higher motion speed and dispersal rate on textured substrata, which indicated less exploratory behaviour than on smooth substrata, while an addition of conspecific extract increased intensities of surface exploration on all types of substrata. Flume experiments further demonstrated that cyprids are more prone to leave textured substrata and that the rejection rate was independent of conspecific extract. This work emphasises the role of larval behaviour as a potentially powerful mechanism determining final recruitment pattern. It is concluded that the choice of settlement site is an important factor in the settlement process of B. improvisus, and the results suggest that surface topography may be a stronger cue for settlement than chemical attraction by conspecific adults in this species. This study presents an example whereby rejection of unsuitable substrata leads to an increased larval pool on adjacent substrata that are suitable for settlement, and indicates that this process may drive aggregated settlement in the barnacle B. improvisus.
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| 7. |
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| 8. |
- Brändström, Helena, et al.
(författare)
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Single nucleotide polymorphisms in the human gene for osteoprotegerin are not related to bone mineral density or fracture in elderly women
- 2004
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 74:1, s. 18-24
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Tidskriftsartikel (refereegranskat)abstract
- Osteoprotegerin (OPG), a secreted member of the tumor necrosis factor receptor family, is a potent inhibitor of osteoclast activation and differentiation. In animal models OPG prevents bone loss, and in humans bone resorption can be reduced by injections of OPG. OPG may also play a role in cardiovascular disease since mice lacking the OPG gene display arterial calcification. In a screening effort of the OPG gene, we recently discovered a single nucleotide polymorphism in the promoter region of OPG (T950C), and reported an association with vascular morphology and function in 59 healthy individuals. Due to the pronounced effect of OPG on bone turnover, the present study was conducted to investigate whether OPG polymorphisms are also associated with bone mineral density or with fracture. The relationship between single nucleotide polymorphisms in the promoter region of OPG (T950C) and the first intron (C1217T), and bone mineral density, measured by DXA in the hip or spine or ultrasound of the heel, was investigated in the Malmö OPRA-study of 1044 women, all 75 years old. The possible relation to fracture incidence was also analyzed. Among the 858 and 864 individuals respectively, genotyped, no significant associations between the investigated single nucleotide polymorphisms and bone mineral density measurements (T950C P = 0.50-0.64, C1217T P = 0.51-1.00), quantitative ultrasound measurements of the calcaneus, or fractures (T950C P = 0.61-0.66, C1217T P = 0.14-0.33) were found. Thus, our results show that polymorphisms in the OPG gene, one of which has previously been found to be associated with cardiovascular morphology and function, are not associated with bone mineral density in elderly Swedish women.
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| 9. |
- Gerdhem, Paul, et al.
(författare)
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Association of the collagen type 1 (COL1A 1) Sp1 binding site polymorphism to femoral neck bone mineral density and wrist fracture in 1044 elderly Swedish women
- 2004
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 74:3, s. 264-269
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Tidskriftsartikel (refereegranskat)abstract
- Identification of risk factors for osteoporosis has been essential for understanding the development of osteoporosis and related fragility fractures. A polymorphism of the binding site for the transcription factor Sp1 of the collagen I alpha 1 gene (COLIA1) has shown an association to bone mass and fracture, but the findings have not been consistent, which may be related to population differences. The Sp1 polymorphism was determined in 1044 women, all 75 years old, participating in the population-based Osteoporosis Prospective Risk Assessment study in Malmö (OPRA). Bone mineral density, heel ultrasound and all previous fractures were registered. BMD was 2.7% lower in the femoral neck in women carrying at least one copy of the "s" allele ( P = 0.027). There was no difference in bone mass at any other site, weight, BMI or age at menopause. Women with a prevalent wrist fracture (n = 181) had an increased presence of the "s" allele. The odds ratio for prevalent wrist fracture was 2.73 (95% CI 1.1-6.8) for the ss homozygotes and 1.4 (95% CI 1.0-2.0) for the Ss heterozygotes when compared with the SS homozygotes. In conclusion, in this large and homogeneous cohort of 75-year-old Swedish women, there was an association among the Sp1 COLIA1 polymorphism, bone mass, and fracture. The presence of at least one copy of the "s" allele was associated with lower femoral neck BMD and previous wrist fracture and in addition, it was related to an increased risk for wrist fracture.
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| 10. |
- Gremare, A., et al.
(författare)
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Feeding behaviour and functional response of Abra ovata and A-nitida compared by image analysis
- 2004
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Ingår i: Marine Ecology-Progress Series. - 0171-8630. ; 267, s. 195-208
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Tidskriftsartikel (refereegranskat)abstract
- An automated image analysis system was used to monitor sediment surface feeding activity of 2 bivalves (Abra ovata and A. nitida) inhabiting contrasting environments. A larger variety of feeding behaviours was recorded in A. nitida, whereas A. ovata mostly fed at the sediment surface. There were also clear differences in the behaviour of the 2 species during surface deposit feeding (i.e. a wider extension of the inhalant siphon in A. ovata, and the exhalant siphon being located below the sediment-water interface in A. ovata and above this interface in A. nitida). In A. nitida, increase in feeding activity resulted mostly from an increase in feeding intensity, and not from an increase in the amount of time devoted to feeding. In A. ovata, the most active bivalves tended to increase their activity mostly by increasing the amount of time devoted to feeding. This suggests that feeding intensity was limited in A. ovata but not in A. nitida. Food dilution and food addition experiments were carried out to assess the functional response in the 2 species. The results of the food dilution experiments were statistically insignificant due to high inter-individual variability. Food addition significantly affected feeding activity in A. ovata and A. nitida, although in different ways. In A. ovata, feeding activity was highest at intermediate food concentrations, and inhibited at the highest ones. In A. nitida, increased feeding activity was induced at higher concentrations than in A. ovata, and feeding activity was greatest at the highest food concentration. Such discrepancies in feeding behaviour and functional response in closely related species characterise the difficulty in delineating functional groups in benthic deposit-feeders.
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| 11. |
- Grenklo, Staffan, et al.
(författare)
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Anti-actin antibodies generated against profilin : actin distinguish between non-filamentous and filamentous actin, and label cultured cells in a dotted pattern
- 2004
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Ingår i: European Journal of Cell Biology. - : Elsevier BV. - 0171-9335 .- 1618-1298. ; 83:8, s. 413-423
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Tidskriftsartikel (refereegranskat)abstract
- Actin polymerization is a prominent feature of migrating cells, where it powers the protrusion of the leading edge. Many studies have characterized the well-ordered and dynamic arrangement of filamentous actin in this submembraneous space. However, less is known about the organization of unpolymerized actin. Previously, we reported on the use of covalently coupled profilin:actin to study actin dynamics and presented evidence that profilin-bound actin is a major source of actin for filament growth. To locate profilin:actin in the cell we have now used this non-dissociable complex for antibody generation, and obtained monospecific anti-actin and antiprofilin antibodies from two separate immunizations. Fluorescence microscopy revealed drastic differences in the staining pattern generated by the anti-actin antibody preparations. With one, distinct puncta appeared at the actin-rich leading edge and sometimes aligned with microtubules in the interior of the lamella, while the other displayed typical actin filament staining. Labelling experiments in vitro demonstrated failure of the first antibody to recognize filamentous actin and none of the two bound microtubules. The two anti-profilin antibodies purified in parallel generated a punctated pattern similar to that seen with the first anti-actin antibody. All antibody preparations labelled the nuclei.
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| 12. |
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| 13. |
- Kamenos, Nicholas A., et al.
(författare)
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Nursery-area function of maerl grounds for juvenile queen scallops Aequipecten opercularis and other invertebrates
- 2004
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Ingår i: Marine Ecology Progress Series. - : Inter-Research. - 0171-8630 .- 1616-1599. ; 274, s. 183-189
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Tidskriftsartikel (refereegranskat)abstract
- The services provided by coastal ecosystems such as mangrove forests and sea-grass beds are becoming increasingly recognised, yet the functional role of maerl beds has not been addressed. Maerl forms highly biodiverse habitats composed of loose-lying coralline red algae which build up over thousands of years. These carbonate-rich deposits occur in photic areas with strong water movement; they have a widespread global distribution yet remain one of the most overlooked shallow-water marine habitats, with little known about the ecosystem services maerl may provide. Our diving research in Scotland has shown that pristine live maerl (PLM) grounds fulfil nursery area prerequisites for commercial populations of queen scallops Aequipecten opercularis and other invertebrates, such as the soft clam Mya arenaria, the sea urchins Psammechinus miliaris and Echinus esculentus, and the starfish Asterias rubens, more effectively than impacted dead maerl and other common substrata, The complex architecture of maerl beds attracts high densities of these juvenile invertebrates, which use PLM grounds as nursery areas in preference to adjacent substrata. Considering its global distribution, it is highly likely that ecosystem services provided by maerl are considerable. Maerl is easily damaged and killed by a variety of human activities, yet its protection would maintain vital nursery area function, benefiting commercial fishery yields and, pivotally, regional biodiversity.
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| 14. |
- Kanis, J A, et al.
(författare)
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Epidemiology of osteoporosis and fracture in men.
- 2004
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Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 75:2, s. 90-9
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Tidskriftsartikel (refereegranskat)
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| 15. |
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| 16. |
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| 17. |
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| 18. |
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| 19. |
- Moksnes, Per-Olav, 1965
(författare)
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Interference competition for space in nursery habitats: density-dependent effects on growth and dispersal in juvenile shore crabs Carcinus maenas
- 2004
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Ingår i: Marine Ecology-Progress Series. - 0171-8630. ; 281, s. 181-191
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Tidskriftsartikel (refereegranskat)abstract
- In marine organisms with dispersing larval stages, current ecological theory suggests that recruitment of benthic juveniles may be limited by juvenile habitats and regulated by early post-settlement processes. However, few studies have attempted to identify the density-dependent mechanisms responsible for these demographic bottlenecks. I conducted a series of experiments to assess if interference competition for space, within nursery habitats, could result in density-dependent juvenile growth and dispersal from refuge habitats, and regulate local populations of juvenile shore crabs Carcinus maenas in shallow nursery areas in Sweden. In laboratory mesocosms, increased natural densities of similarly sized crabs resulted in decreased growth and increased per capita emigration from mussel habitats, even though food was provided in excess, suggesting that competition for space and mutual interference mediated the density-dependent growth and dispersal. This was supported in a field experiment where a density-dependent relation was found between the abundance of juvenile crabs in nursery areas and their migration rates to experimental mussel patches. The results suggest that interference competition for space and density-dependent emigration from refuge habitats, coupled with habitat-specific mortality, is an important regulating mechanism for juvenile shore crab populations, in particular for older juvenile cohorts that have escaped inter-cohort cannibalism through a size refuge. Density-dependent effects on growth were found only at unusually high natural densities and may, therefore, be less important as a regulating mechanism. However, negative effects on feeding rates and growth at high conspecific densities may represent an important selective force in juvenile migration behavior. Density-dependent dispersal was found at juvenile densities that are regularly found in nursery areas, suggesting that nursery habitats become saturated with juveniles during the recruitment season and represent a limiting resource for local populations, consistent with field observations of shore crab populations in the study area.
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| 20. |
- Sandberg, Johannes, et al.
(författare)
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Pelagic food web structure and carbon budget in the northern Baltic Sea: Potential importance of terrigenous carbon
- 2004
-
Ingår i: Marine Ecology Progress Series. - : Inter-Research. - 0171-8630 .- 1616-1599. ; 268, s. 13-29
-
Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to quantitatively assess the relative importance of terrigenous dissolved organic material (TDOC) as a carbon source for secondary producers (e.g. bacteria) and as a structuring factor for the pelagic food web in the Gulf of Bothnia, northern Baltic Sea. The 3 study sites, situated in Bothnian Bay (BB), the Öre Estuary (ÖE) and the Bothnian Sea (BS), had markedly different freshwater loads and water-residence times. In Bothnian Bay, bacterial biomass and production were higher than expected from the levels of phytoplankton biomass and productivity there, suggesting an uncoupling of bacterial productivity from phytoplankton production. Phytoplankton size structure and size-fractionated production were, however, relatively similar among areas. A simplified carbon budget model suggested that bacterioplankton dominated organic carbon consumption in all of the food webs studied, but was most marked in BB. The model showed that the available autochthonous primary production could not alone support the heterotrophic carbon demand in BB. The most likely explanation of this discrepancy was that the total annual input of terrigenous dissolved organic carbon was bioavailable, resulting in a budget closer to balance with the heterotrophic carbon demand. BB, receiving 38% of the carbon input from land, was consequently a net heterotrophic ecosystem. A sensitivity analysis showed that the bacterial carbon demand, and growth efficiency in particular, had the greatest influence on the resulting budget. TDOC was the dominant carbon source in ÖE, but the losses of carbon through advection to offshore areas and sedimentation was high. The evidence of net heterotrophy in ÖE was therefore weaker than in BB. In BS the input of TDOC was less important, and the carbon used for secondary production originated mainly from autochthonous primary production. Our results suggest that the supply of TDOC is of great importance for the abundance of plankton and as a structuring factor for the aquatic food webs in the Gulf of Bothnia.
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| 21. |
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| 22. |
- Solan, M., et al.
(författare)
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In situ quantification of bioturbation using time-lapse fluorescent sediment profile imaging (f-SPI), luminophore tracers and model simulation
- 2004
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Ingår i: Marine Ecology-Progress Series. - : Inter-Research Science Center. - 0171-8630 .- 1616-1599. ; 271, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- In order to link actual biological data on bioturbation to the abstract parameters in bioturbation models, high-resolution data on the frequency and lengths of particle displacements are required. The temporal variation in bioturbation for a subtidal macrofaunal assemblage was studied non-invasively and in situ using an optically modified fluorescence sensitive time-lapse sediment profile imaging camera (f-SPI), fluorescent-dyed sediment particles (luminophores) and mathematical modelling. This combined approach allowed tracer particles to be non-invasively tracked and their displacements monitored at an unprecedented spatial (78 mum) and temporal (every 10 min) resolution for extended periods of time (16 h). The redistribution of luminophores was digitally acquired from sequential images and compared to model predictions, with particle transport modelled as (1) a diffusive process, allowing the biodiffusion coefficient, D-b, to be estimated, and (2) a non-local process, allowing a reworking activity constant, a, to be calculated. Model predictions of luminophore particle transport for the final image of the f-SPI sequence gave: D-b = 1.26 x 10(2) cm(2) yr(-1); a = 5.23 x 10(-2) cm(-1) yr(-1). Discrete values of a fluctuated widely throughout the sequence and allowed discrete bioturbation events to be identified. Time-lapse movie sequences revealed that most of the bioturbation observed during the deployment could be directly attributed to the behaviour of the brachyuran crab Hyas araneus. Our findings demonstrate that f-SPI provides a rapid and non-invasive means to visualise and quantify, in situ, the extent and influence of discrete infaunal bioturbation events on particle mixing. This technique provides detailed information on the spatial and temporal resolution of such bioturbation events, which could significantly improve existing models of bioturbation.
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| 23. |
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| 24. |
- Stroikin, Yuri, et al.
(författare)
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Inhibition of autophagy with 3-methyladenine results in impaired turnover of lysosomes and accumulation of lipofuscin-like material
- 2004
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Ingår i: European journal of cell biology. - : Elsevier BV. - 0171-9335. ; 83:10, s. 583-590
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Tidskriftsartikel (refereegranskat)abstract
- Autophagy (which includes macro-, micro-, and chaperone-mediated autophagy) is an important biological mechanism for degradation of damaged/obsolete macromolecules and organelles. Ageing non-dividing cells, however, progressively accumulate oxidised proteins, defective organelles and intralysosomal lipofuscin inclusions, suggesting inherent insufficiency of autophagy. To learn more about the role of macroautophagy in the turnover of organelles and lipofuscin formation, we inhibited autophagic sequestration with 3-methyladenine (3 MA) in growth-arrested human fibroblasts, a classical model of cellular ageing. Such treatment resulted in a dramatic accumulation of altered lysosomes, displaying lipofuscin-like autofluorescence, as well as in a moderate increase of mitochondria with lowered membrane potential. The size of the late endosomal compartment appeared not to be significantly altered following 3 MA exposure. The accumulation of lipofuscin-like material was enhanced when 3 MA administration was combined with hyperoxia. The findings suggest that macroautophagy is essential for normal turnover of lysosomes. This notion is supported by reports in the literature of lysosomal membrane proteins inside lysosomes and/or late endosomes, as well as lysosomes with active hydrolases within autophagosomes following vinblastine-induced block of fusion between lysosomes and autophagosomes. The data also suggest that specific components of lysosomes, such as membranes and proteins, may be direct sources of lipofuscin.
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| 25. |
- Titelman, Josefin, 1973, et al.
(författare)
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Ontogenetic vertical distribution patterns in small copepods: field observations and model predictions
- 2004
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Ingår i: Marine Ecology-Progress Series. - 0171-8630. ; 284, s. 49-63
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Tidskriftsartikel (refereegranskat)abstract
- We investigated fine-scale (5m, 4h) species- and stage-specific (N1 to C6) distributions of common copepods at an anchor station in a Swedish fjord during two 24 h periods in October 1997. Generally, both calanoid and cyclopoid nauplii were found near the surface, while copepodids stayed deeper in the water column. No diurnal migration was observed. To analyze the observed distributions, we combined mechanistic models of predation risk from fish and copepods, formulations of temperature-dependent growth and a habitat optimization model, maximizing expected lifetime reproductive output. Motility pattern has implications for encounter rates with copepod predators, and therefore affected optimal vertical positioning in the model. By applying species- and stage-specific motility, and accounting for the ambient copepod predator field, we computed depth profiles of the mortality risk for the observed field situation. Predicted diel and ontogenetic vertical distribution patterns for various levels of fish concentrations were compared with observed distributions, and much of the patterns in the field were explained by the model. While the risk of fish predation governs the deeper habitat selection of the larger copepodids, the risk of copepod predation is probably more important for nauplii and small copepods. In addition, the vertically homogeneous growth profile and dense layers of copepod predators may wipe out potential benefits of diurnal migration.
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| 26. |
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| 27. |
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| 28. |
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| 29. |
- Vasara, Anna I, et al.
(författare)
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Subchondral bone reaction associated with chondral defect and attempted cartilage repair in goats.
- 2004
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Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 74:1, s. 107-14
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Tidskriftsartikel (refereegranskat)abstract
- Repair of cartilage damage with autologous chondrocyte transplantation (ACT) has become popular in clinical use during the past few years. Although clinical results have mostly been successful, several unanswered questions remain regarding the biological mechanism of the repair process. The aim of this study was to develop a goat model for ACT. The repair was not successful due to the graft delamination, but we characterize the subchondral changes seen after the procedure. A chondral lesion was created in 14 goat knees, operated on 1 month later with ACT, and covered with periosteum or a bioabsorbable poly-L/D-lactide scaffold. After 3 months, only two of the five lesions repaired with ACT showed partly hyaline-like repair tissue, and all lesions (n = 4) with the scaffold failed. Even though the lesions did not extend through the calcified cartilage, the bone volume and collagen organization of bone structure were decreased when assessed by quantitative polarized light microscopy. There was a significant loss of bone matrix and distortion of the trabecular structure of subchondral bone, which extended several millimeters into the bone. The subchondral bone demonstrated strong hyaluronan staining in the bone marrow and cartilaginous areas with signs of endochondral ossification, suggesting structural remodeling of the bone. The goat model used here proved not to be an optimal model for ACT. The changes in subchondral bone may alter the biomechanical properties of the subchondral plate and thus the long-term survival of the repair tissue after ACT.
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| 30. |
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| 31. |
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| 32. |
- Carlsson, Pernilla, et al.
(författare)
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Heparin biosynthesis
- 2012
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Ingår i: Handbook of experimental pharmacology. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 0171-2004. ; 207, s. 23-41
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Tidskriftsartikel (refereegranskat)abstract
- Heparin and heparan sulfate share the same polysaccharide backbone structure but differ in sulfation degree and expression pattern. Whereas heparan sulfate is found in virtually all cells of the human body, heparin expression is restricted to mast cells, where it has a function in storage of granular components such as histamine and mast cell specific proteases. Although differing in charge and sulfation pattern, current knowledge indicates that the same pathway is used for synthesis of heparin and heparan sulfate, with a large number of different enzymes taking part in the process. At present, little is known about how the individual enzymes are coordinated and how biosynthesis is regulated. These questions are addressed in this chapter together with a review of the basic enzymatic steps involved in initiation, elongation, and modification of the polysaccharides.
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| 33. |
- Dong, Min, et al.
(författare)
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The Structure and Classification of Botulinum Toxins
- 2021
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Ingår i: Botulinum Toxin Therapy. - Cham : Springer International Publishing. - 0171-2004. - 9783030663056 ; 263, s. 11-33
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Bokkapitel (refereegranskat)abstract
- Botulinum neurotoxins (BoNTs) are a family of bacterial protein toxins produced by various Clostridium species. They are traditionally classified into seven major serotypes (BoNT/A-G). Recent progress in sequencing microbial genomes has led to an ever-growing number of subtypes, chimeric toxins, BoNT-like toxins, and remotely related BoNT homologs, constituting an expanding BoNT superfamily. Recent structural studies of BoNTs, BoNT progenitor toxin complexes, tetanus neurotoxin (TeNT), toxin-receptor complexes, and toxin-substrate complexes have provided mechanistic understandings of toxin functions and the molecular basis for their variations. The growing BoNT superfamily of toxins present a natural repertoire that can be explored to develop novel therapeutic toxins, and the structural understanding of their variations provides a knowledge basis for engineering toxins to improve therapeutic efficacy and expand their clinical applications.
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| 34. |
- Edvinsson, Lars
(författare)
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Role of cgrp in migraine
- 2019
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Ingår i: Handbook of Experimental Pharmacology. - Cham : Springer International Publishing. - 1865-0325 .- 0171-2004. ; 255, s. 121-130
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Bokkapitel (refereegranskat)abstract
- Migraine is a common neurological disorder that afflicts up to 15% of the adult population in most countries, with predominance in females. It is characterized by episodic, often disabling headache, photophobia and phonophobia, autonomic symptoms (nausea and vomiting), and in a subgroup an aura in the beginning of the attack. Although still debated, many researchers consider migraine to be a disorder in which CNS dysfunction plays a pivotal role while various parts of the trigeminal system are necessary for the expression of associated symptoms. Treatment of migraine has in recent years seen the development of drugs that target the trigeminal sensory neuropeptide calcitonin gene-related peptide (CGRP) or its receptor. Several of these drugs are now approved for use in frequent episodic and in chronic migraine. CGRP-related therapies offer considerable improvements over existing drugs, as they are the first to be designed specifically to act on the trigeminal pain system: they are more specific and have little or no adverse effects. Small molecule CGRP receptor antagonists, gepants, are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (Eptinezumab, Fremanezumab, and Galcanezumab) or the CGRP receptor (Erenumab) effectively prevent migraine attacks. The neurobiology of CGRP signaling is briefly summarized together with key clinical evidence for the role of CGRP in migraine headache, including the efficacy of CGRP-targeted treatments.
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| 35. |
- Fredholm, BB
(författare)
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Notes on the history of caffeine use
- 2011
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Ingår i: Handbook of experimental pharmacology. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 0171-2004. ; :200, s. 1-9
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Tidskriftsartikel (refereegranskat)
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| 36. |
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| 37. |
- Groome, J. R., et al.
(författare)
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Gating pore currents in sodium channels
- 2018
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Ingår i: Handbook of Experimental Pharmacology. - Cham : Springer. - 0171-2004 .- 1865-0325. ; , s. 371-399
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Tidskriftsartikel (refereegranskat)abstract
- Voltage-gated sodium channels belong to the superfamily of voltage-gated cation channels. Their structure is based on domains comprising a voltage sensor domain (S1–S4 segments) and a pore domain (S5–S6 segments). Mutations in positively charged residues of the S4 segments may allow protons or cations to pass directly through the gating pore constriction of the voltage sensor domain; these anomalous currents are referred to as gating pore or omega (ω) currents. In the skeletal muscle disorder hypokalemic periodic paralysis, and in arrhythmic dilated cardiomyopathy, inherited mutations of S4 arginine residues promote omega currents that have been shown to be a contributing factor in the pathogenesis of these sodium channel disorders. Characterization of gating pore currents in these channelopathies and with artificial mutations has been possible by measuring the voltage-dependence and selectivity of these leak currents. The basis of gating pore currents and the structural basis of S4 movement through the gating pore has also been studied extensively with molecular dynamics. These simulations have provided valuable insight into the nature of S4 translocation and the physical basis for the effects of mutations that promote permeation of protons or cations through the gating pore.
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- Lazarus, M, et al.
(författare)
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Adenosine and Sleep
- 2019
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Ingår i: Handbook of experimental pharmacology. - Cham : Springer International Publishing. - 0171-2004. ; 253, s. 359-381
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Tidskriftsartikel (refereegranskat)
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| 45. |
- Törnblom, Hans, 1966, et al.
(författare)
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Centrally targeted pharmacotherapy for chronic abdominal pain: Understanding and management
- 2016
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Ingår i: Gastrointestinal Pharmacology. Handbook of Experimental Pharmacology, vol 239. Greenwood, Van Meerveld B. (eds). - Cham : Springer. - 0171-2004. - 9783319563602 ; , s. 417-440
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Chronic abdominal pain has a widespread impact on the individual and the society. Identifying and explainingmechanisms of importance for the pain experiencewithin a biopsychosocial context are central in order to select treatment that has a chance for symptom reduction. With current knowledge of brain-gut interactions, chronic abdominal pain, which mostly appears in functional gastrointestinal disorders, to a large extent involves pain mechanisms residing within the brain. As such, the use of centrally targeted pharmacotherapy as an effective treatment option is obvious in a selected number of patients. The antidepressants are most common, but also other classes of medications can be used, either alone or in combination. The latter option refers to when there is insufficient effect of one drug alone or side effects limiting dosage, and when combined in lower doses, certain drugs give rise to augmentation effects. This chapter outlines basic mechanisms of importance for the understanding of chronic abdominal pain and the pharmacologic treatment options. © Springer International Publishing AG 2016.
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| 46. |
- Westgren, M
(författare)
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Fetal medicine and treatment
- 2011
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Ingår i: Handbook of experimental pharmacology. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 0171-2004. ; 205, s. 271-83
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Tidskriftsartikel (refereegranskat)
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| 47. |
- Yadav, Vikas, et al.
(författare)
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Targeting Oncogenic WNT Signalling with WNT Signalling-Derived Peptides
- 2021
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Ingår i: Handbook of experimental pharmacology. - Cham : Springer International Publishing. - 0171-2004. - 9783030854980 - 9783030854997 ; , s. 279-303
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Bokkapitel (refereegranskat)abstract
- WNT signalling is known to be a crucial regulator of embryonic development and tissue homeostasis. Aberrant expression of WNT signalling elements or their mutations has been implicated in carcinogenesis and/or the progression of several different cancer types. Investigations of how WNT signalling affects carcinogenesis and cancer progression have revealed that it has essential roles in the regulation of proliferation, apoptosis, and cancer stemness and in angiogenesis and metastasis. Consequently, WNT-targeted therapy has gained much attention and has resulted in the development of several small molecules, the majority of which act as inhibitors of different WNT signalling events. However, although numerous inhibitory WNT signalling drug candidates have been included in clinical trials, no significant breakthroughs have been made. This could possibly be due to problems with inefficient binding to the target, compensatory signalling mechanisms and toxicity towards normal cells. Therapeutic peptides targeting WNT signalling in cancer cells have been developed as an alternative approach, with the hope that they might overcome the limitations reported for small WNT inhibitory molecules. In this chapter, we describe recent developments made in the design and characterization of WNT signalling-derived peptides aiming at their use as alternative cancer therapeutics and/or combined adjuvant therapy to conventional therapies.
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| 48. |
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| 49. |
- Roloff, Tim C, et al.
(författare)
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Chromatin, epigenetics and stem cells
- 2005
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Ingår i: European Journal of Cell Biology. - : Elsevier BV. - 0171-9335. ; 84:2-3, s. 123-135
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetics is a term that has changed its meaning with the increasing biological knowledge on developmental processes. However, its current application to stem cell biology is often imprecise and is conceptually problematic. This article addresses two different subjects, the definition of epigenetics and chromatin states of stem and differentiated cells. We describe mechanisms that regulate chromatin changes and provide an overview of chromatin states of stem and differentiated cells. Moreover, a modification of the current epigenetics definition is proposed that is not restricted by the heritability of gene expression throughout cell divisions and excludes translational gene expression control.
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| 50. |
- Mogemark, Lena, et al.
(författare)
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Disruption of target cell adhesion structures by the Yersinia effector YopH requires interaction with the substrate domain of p130Cas.
- 2005
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Ingår i: European Journal of Cell Biology. - : Elsevier BV. - 0171-9335 .- 1618-1298. ; 84:4, s. 477-489
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Tidskriftsartikel (refereegranskat)abstract
- The docking protein p130Cas has, together with FAK, been found as a target of the Yersinia virulence effector YopH. YopH is a protein tyrosine phosphatase that is delivered into host cells via the bacterial type III secretion machinery, and the outcome of its activity is inhibition of host cell phagocytosis. In the present study using p130Cas-/- cells, and p130Cas-/- cells expressing variants of GFPp130Cas, we show that this docking protein, via its substrate domain, is responsible for subcellular targeting of YopH in eukaryotic cells. Since YopH inhibits phagocytosis, p130Cas was expected to be critical for signalling mediating bacterial internalization. However, p130Cas-/- cells did not exhibit reduced capacity to internalize Yersinia. On the other hand, when a dominant negative variant of p130Cas was expressed in these cells, the phagocytic capacity was severely impaired. Moreover, the p130Cas-/- cells displayed a marked reduced sensitivity towards YopH-mediated detachment compared to wild-type cells. Transfecting these cells with full-length p130Cas rendered cells hypersensitive to both mechanical and Yersinia-mediated detachment. This hypersensitivity was not seen upon transfection with the dominant negative substrate domain-deleted variant of p130Cas. This implicates p130Cas as a prominent regulator of cell adhesion, where its substrate-binding domain has a significant function.The docking protein p130Cas has, together with FAK, been found as a target of the Yersinia virulence effector YopH. YopH is a protein tyrosine phosphatase that is delivered into host cells via the bacterial type III secretion machinery, and the outcome of its activity is inhibition of host cell phagocytosis. In the present study using p130Cas-/- cells, and p130Cas-/- cells expressing variants of GFPp130Cas, we show that this docking protein, via its substrate domain, is responsible for subcellular targeting of YopH in eukaryotic cells. Since YopH inhibits phagocytosis, p130Cas was expected to be critical for signalling mediating bacterial internalization. However, p130Cas-/- cells did not exhibit reduced capacity to internalize Yersinia. On the other hand, when a dominant negative variant of p130Cas was expressed in these cells, the phagocytic capacity was severely impaired. Moreover, the p130Cas-/- cells displayed a marked reduced sensitivity towards YopH-mediated detachment compared to wild-type cells. Transfecting these cells with full-length p130Cas rendered cells hypersensitive to both mechanical and Yersinia-mediated detachment. This hypersensitivity was not seen upon transfection with the dominant negative substrate domain-deleted variant of p130Cas. This implicates p130Cas as a prominent regulator of cell adhesion, where its substrate-binding domain has a significant function.
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