| 1. |
- Hibbett, D. S., et al.
(författare)
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A higher-level phylogenetic classification of the Fungi
- 2007
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Ingår i: Mycological Research. - : Elsevier BV. - 0953-7562 .- 1469-8102. ; 111, s. 509-547
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Tidskriftsartikel (refereegranskat)abstract
- A comprehensive phylogenetic classification of the kingdom Fungi is proposed, with reference to recent molecular phylogenetic analyses, and with input from diverse members of the fungal taxonomic community. The classification includes 195 taxa, down to the level of order, of which 16 are described or validated here: Dikarya subkingdom nov.; Chytridiomycota, Neocallimastigomycota phyla nov.; Monoblepharidomycetes, Neocallimastigomycetes class. nov.; Eurotiomycetidae, Lecarioromycetidae, Mycocaliciomycetidae subclass. nov.; Acarosporales, Corticiales, Baeomycetales, Candelariales, Gloeophyllales, Melanosporales, Trechisporales, Umbilicariales ords. nov. The clade containing Ascomycota and Basidiomycota is classified as subkingdom Dikarya, reflecting the putative synapomorphy of dikaryotic hyphae. The most dramatic shifts in the classification relative to previous works concern the groups that have traditionally been included in the Chytridiomycota and Zygomycota. The Chytridiomycota is retained in a restricted sense, with Blastocladiomycota and Neocallimastigomycota representing segregate phyla of flagellated Fungi. Taxa traditionally placed in Zygomycota are distributed among Glomeromycota and several subphyla incertae sedis, including Mucoromycotina, Entomophthoromycotina, Kickxellomycotina, and Zoopagomycotiria. Microsporidia are included in the Fungi, but no further subdivision of the group is proposed. Several genera of 'basal' Fungi of uncertain position are not placed in any higher taxa, including Basidiobolus, Caulochytrium, Olpidium, and Rozella. (c) 2007 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.
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| 2. |
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| 3. |
- Sodergren, Erica, et al.
(författare)
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The genome of the sea urchin Strongylocentrotus purpuratus.
- 2006
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
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Tidskriftsartikel (refereegranskat)abstract
- We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
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| 4. |
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| 5. |
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| 6. |
- Barkholt, L., et al.
(författare)
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Allogeneic haematopoietic stem cell transplantation for metastatic renal carcinoma in Europe
- 2006
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 17:7, s. 1134-1140
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Tidskriftsartikel (refereegranskat)abstract
- Background: An allogeneic antitumour effect has been reported for various cancers. We evaluated the experience of allogeneic haematopoietic stem cell transplantation (HSCT) for renal cell carcinoma (RCC) in 124 patients from 21 European centres. Patients and methods: Reduced intensity conditioning and peripheral blood stem cells from an HLA-identical sibling (n = 106), a mismatched related (n = 5), or an unrelated (n = 13) donor were used. Immunosuppression was cyclosporine alone, or combined with methotrexate or mycophenolate mofetil. Donor lymphocyte infusions (DLI) were given to 42 patients. The median follow-up was 15 (range 3-41) months. Results: All but three patients engrafted. The cumulative incidence of moderate to severe, grades II-IV acute GVHD was 40% and for chronic GVHD it was 33%. Transplant-related mortality was 16% at one year. Complete (n = 4) or partial (n = 24) responses, median 150 (range 42-600) days post-transplant, were associated with time from diagnosis to HSCT, mismatched donor and acute GVHD II-IV. Factors associated with survival included chronic GVHD (hazards ratio, HR 4.12, P < 0.001), DLI (HR 3.39, P < 0.001), < 3 metastatic sites (HR 2.61, P = 0.002) and a Karnofsky score > 70 (HR 2.33, P = 0.03). Patients (n = 17) with chronic GVHD and given DLI had a 2-year survival of 70%. Conclusion: Patients with metastatic RCC, less than three metastatic locations and a Karnofsky score > 70% can be considered for HSCT. Posttransplant DLI and limited chronic GVHD improved the patient survival.
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| 7. |
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| 8. |
- Bonifacio, P., et al.
(författare)
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First stars XII. Abundances in extremely metal-poor turnoff stars, and comparison with the giants
- 2009
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 501:2, s. 519-530
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Tidskriftsartikel (refereegranskat)abstract
- Context. The detailed chemical abundances of extremely metal-poor (EMP) stars are key guides to understanding the early chemical evolution of the Galaxy. Most existing data, however, treat giant stars that may have experienced internal mixing later. Aims. We aim to compare the results for giants with new, accurate abundances for all observable elements in 18 EMP turno. stars. Methods. VLT/UVES spectra at R similar to 45 000 and S/N similar to 130 per pixel (lambda lambda 330-1000 nm) are analysed with OSMARCS model atmospheres and the TURBOSPECTRUM code to derive abundances for C, Mg, Si, Ca, Sc, Ti, Cr, Mn, Co, Ni, Zn, Sr, and Ba. Results. For Ca, Ni, Sr, and Ba, we find excellent consistency with our earlier sample of EMP giants, at all metallicities. However, our abundances of C, Sc, Ti, Cr, Mn and Co are similar to 0.2 dex larger than in giants of similar metallicity. Mg and Si abundances are similar to 0.2 dex lower (the giant [Mg/Fe] values are slightly revised), while Zn is again similar to 0.4 dex higher than in giants of similar [Fe/H] (6 stars only). Conclusions. For C, the dwarf/giant discrepancy could possibly have an astrophysical cause, but for the other elements it must arise from shortcomings in the analysis. Approximate computations of granulation (3D) effects yield smaller corrections for giants than for dwarfs, but suggest that this is an unlikely explanation, except perhaps for C, Cr, and Mn. NLTE computations for Na and Al provide consistent abundances between dwarfs and giants, unlike the LTE results, and would be highly desirable for the other discrepant elements as well. Meanwhile, we recommend using the giant abundances as reference data for Galactic chemical evolution models.
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| 9. |
- Brose, Ulrich, et al.
(författare)
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Body sizes of consumers and their resources
- 2005
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Ingår i: Ecology. - : Ecological Society of America. - 0012-9658 .- 1939-9170. ; 86:9, s. 2545-2545
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Tidskriftsartikel (refereegranskat)abstract
- Trophic information—who eats whom—and species’ body sizes are two of the most basic descriptions necessary to understand community structure as well as ecological and evolutionary dynamics. Consumer–resource body size ratios between predators and their prey, and parasitoids and their hosts, have recently gained increasing attention due to their important implications for species’ interaction strengths and dynamical population stability. This data set documents body sizes of consumers and their resources. We gathered body size data for the food webs of Skipwith Pond, a parasitoid community of grass-feeding chalcid wasps in British grasslands; the pelagic community of the Benguela system, a source web based on broom in the United Kingdom; Broadstone Stream, UK; the Grand Caric¸aie marsh at Lake Neuchaˆtel, Switzerland; Tuesday Lake, USA; alpine lakes in the Sierra Nevada of California; Mill Stream, UK; and the eastern Weddell Sea Shelf, Antarctica. Further consumer–resource body size data are included for planktonic predators, predatory nematodes, parasitoids, marine fish predators, freshwater invertebrates, Australian terrestrial consumers, and aphid parasitoids. Containing 16 807 records, this is the largest data set ever compiled for body sizes of consumers and their resources. In addition to body sizes, the data set includes information on consumer and resource taxonomy, the geographic location of the study, the habitat studied, the type of the feeding interaction (e.g., predacious, parasitic) and the metabolic categories of the species (e.g., invertebrate, ectotherm vertebrate). The present data set was gathered with the intent to stimulate research on effects of consumer–resource body size patterns on food-web structure, interaction-strength distributions, population dynamics, and community stability. The use of a common data set may facilitate cross-study comparisons and understanding of the relationships between different scientific approaches and models.
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| 10. |
- Bujakowska, Kinga, et al.
(författare)
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Study of Gene-Targeted Mouse Models of Splicing Factor Gene Prpf31 Implicated in Human Autosomal Dominant Retinitis Pigmentosa (RP)
- 2009
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783. ; 50:12, s. 5927-5933
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. Pre-mRNA processing factor 31 (PRPF31) is a ubiquitous protein needed for the assembly of the pre-mRNA splicing machinery. It has been shown that mutations in this gene cause autosomal dominant retinitis pigmentosa 11 (RP11), which is characterized by rod-cell degeneration. Interestingly, mutations in this ubiquitously expressed gene do not lead to phenotypes other than retinal malfunction. Furthermore, the dominant inheritance pattern has shown incomplete penetrance, which poses interesting questions about the disease mechanism of RP11. METHODS. To characterize PRPF31 function in the rod cells, two animal models have been generated. One was a heterozygous knock-in mouse (Prpf31(A216P/+)) carrying a point mutation p.A216P, which has previously been identified in RP11 patients. The second was a heterozygous knockout mouse (Prpf31(+/-)). Retinal degeneration in RP11 mouse models was monitored by electroretinography and histology. RESULTS. Generation of the mouse models is presented, as are results of ERGs and retinal morphology. No degenerative phenotype on fundus examination was found in Prpf31(A216P/+) and Prpf31(+/-) mice. Prpf31(A216P/A216P) and Prpf31(-/-) genotypes were embryonic lethal. CONCLUSIONS. The results imply that Prpf31 is necessary for survival, and there is no compensation mechanism in mouse for the lack of this splicing factor. The authors suggest that p.A216P mutation in Prpf31 does not exert a dominant negative effect and that one Prpf31 wild-type allele is sufficient for maintenance of the healthy retina in mice.
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| 11. |
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| 12. |
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| 13. |
- Gilbert, F., et al.
(författare)
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Sediment reworking by marine benthic species from the Gullmar Fjord (Western Sweden): Importance of faunal biovolume
- 2007
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Ingår i: Journal of Experimental Marine Biology and Ecology. - : Elsevier BV. - 0022-0981. ; 348:1-2, s. 133-144
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Tidskriftsartikel (refereegranskat)abstract
- In order to compare and quantify sediment reworking activities by different species/functional groups of macrofauna, a laboratory experiment was carried out with species from the Gullmarsfjord (Western Sweden). Monospecific communities of Amphiura filiformis, Echinocardium cordatum, Scalibregma inflatum and Abra nitida were introduced in experimental mesocosms, with identical densities (795 ind. m(-2)), for 10 days. Sediment reworking was studied by quantifying downward and upward movements of fluorescent inert tracers (luminophores). Luminophores with different colour were initially deposited both at the sediment surface and within the sediments. Population biomass and biovolume were also determined. Surface tracers reworking coefficients ranged from 0.6 to 2.2 cm(2) y(-1) and 0.9 to 4.1 y(-1), respectively for the biodiffusive-like and non-local transports. Calculated biodiffusive-like coefficient was between 1.0 and 2.3 cm(2) y(-1) for the deep tracers. For both tracers, the E. cordatum population presented the highest reworking coefficients. Among the morphological and/or ethological parameters that could determine overall patterns of reworking and differences between species, results have shown a direct relationship between the apparent biodiffusive mixing and the biovolume of the individuals (D-b=0.35 * Biovolume). This suggests that the biovolume-of macrofauna may allow a rough estimate of the biodiffusive-like reworking intensity of particles deposited on the sediment surface. (c) 2007 Elsevier B.V. All rights reserved.
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| 14. |
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| 15. |
- Moali, C, et al.
(författare)
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Substrate-specific modulation of a multisubstrate proteinase - C-terminal processing of fibrillar procollagens is the only BMP-1-dependent activity to be enhanced by PCPE-1
- 2005
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 280:25, s. 24188-24194
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Tidskriftsartikel (refereegranskat)abstract
- Members of the bone morphogenetic protein-1/tolloid (BMP-1/Tld) family of metalloproteinases, also known as procollagen C-proteinases (PCPs), control multiple biological events ( including matrix assembly, cross-linking, cell adhesion/migration and pattern formation) through enzymatic processing of several extracellular substrates. PCP activities on fibrillar procollagens can be stimulated by another family of extracellular proteins, PCP enhancers (PCPE-1, PCPE-2), which lack intrinsic enzymatic activity. While PCPs have multiple substrates, the extent to which PCPEs is involved in the processing of proteins other than fibrillar procollagens is unknown. In the experiments reported here, PCPE-1 was found to have no effect on the in vitro BMP-1 processing of procollagen VII, the procollagen V N-propeptide, the laminin 5 gamma 2 chain, osteoglycin, prolysyl oxidase, or chordin. In contrast, PCPE-1 enhanced C-terminal processing of human fibrillar procollagen III but only when this substrate was in its native, disulfide-bonded conformation. Surprisingly, processing of procollagen III continued to be enhanced when essentially all the triple-helical region was removed. These and previous results (Ricard-Blum, S., Bernocco, S., Font, B., Moali, C., Eichenberger, D., Farjanel, J., Burchardt, E. R., van der Rest, M., Kessler, E., and Hulmes, D. J. S. ( 2002) J. Biol. Chem. 277, 33864 - 33869; Bernocco, S., Steiglitz, B. M., Svergun, D. I., Petoukhov, M. V., Ruggiero, F., Ricard- Blum, S., Ebel, C., Geourjon, C., Deleage, G., Font, B., Eichenberger, D., Greenspan, D. S., and Hulmes, D. J. S. ( 2003) J. Biol. Chem. 278, 7199 - 7205) indicate that the mechanism of PCPE-1 action involves recognition sites in both the C-propeptide domain and in the C-telopeptide region of the procollagen molecule. PCPEs therefore define a new class of extracellular adaptor proteins that stimulate proteinase activity in a substrate-specific manner, thereby providing a new target for the selective regulation of PCP activity on fibrillar procollagen substrates.
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| 16. |
- Nilsson, Sara C., et al.
(författare)
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A mutation in factor I that is strongly associated with atypical hemolytic uremic syndrome does not affect the function of factor I in complement regulation
- 2007
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Ingår i: Molecular Immunology. - 0161-5890 .- 1872-9142. ; 44:1-3, s. 221-221
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Factor I (FI) is the major complement inhibitor that degrades C3b and C4b in the presence of cofactors C4b binding protein (C4BP), factor H (FH), membrane cofactor protein (MCP) or complement receptor 1 (CR1). Recently, mutations and polymorphisms in complement regulator molecules FH and MCP but also in FI have been associated with atypical hemolytic uremic syndrome (aHUS). HUS is a disorder characterized by hemolytic anemia, thrombocytopenia and acute renal failure. In this study we report three unrelated patients with an identical heterozygous mutation, G261D, in FI heavy chain who developed severe aHUS at different time points in their lives. Two patients also have polymorphisms in FH previously associated with risk of developing aHUS. Testing in particular one patient and control serum samples we did not observe major differences in complement hemolytic activity, FI plasma levels or the capability to degrade C4b or C3b. A recombinant protein was produced in order to analyze the functional consequences of the mutation. Mutant FI had a slightly different migration pattern during electrophoresis under reducing conditions. An alteration due to alternative splicing or glycosylation was ruled out, thus the altered migration may be due to proximity of the mutation to a cysteine residue. The recombinant mutant FI degraded C3b and C4b in a manner comparable to wild type protein. In conclusion, despite the strong association between the heterozygous mutation in FI and aHUS we did not observe any abnormalities in the function of FI regarding complement regulation.
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| 17. |
- Richards, Stephen, et al.
(författare)
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The genome of the model beetle and pest Tribolium castaneum.
- 2008
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Ingår i: Nature. - 1476-4687. ; 452:7190, s. 949-55
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Tidskriftsartikel (refereegranskat)abstract
- Tribolium castaneum is a representative of earth’s most numerous eukaryotic order, a powerful model organism for the study of generalized insect development, and also an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved an ability to interact with a diverse chemical environment as evidenced by large expansions in odorant and gustatory receptors, as well as p450 and other detoxification enzymes. Developmental patterns in Tribolium are more representative of other arthropods than those found in Drosophila, a fact represented in gene content and function. For one, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, and some are expressed in the growth zone crucial for axial elongation in short germ development. Systemic RNAi in T. castaneum appears to use mechanisms distinct from those found in C. elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.
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| 18. |
- Rutherford, Erin C, et al.
(författare)
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Chronic second-by-second measures of L-glutamate in the central nervous system of freely moving rats.
- 2007
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Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 102:3, s. 712-22
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Tidskriftsartikel (refereegranskat)abstract
- l-glutamate (Glu) is the main excitatory neurotransmitter in the central nervous system (CNS) and is associated with motor behavior and sensory perception. While microdialysis methods have been used to record tonic levels of Glu, little is known about the more rapid changes in Glu signals that may be observed in awake rats. We have reported acute recording methods using enzyme-based microelectrode arrays (MEA) with fast response time and low detection levels of Glu in anesthetized animals with minimal interference. The current paper concerns modification of the MEA design to allow for reliable measures in the brain of conscious rats. In this study, we characterized the effects of chronic implantation of the MEA into the brains of rats. We were capable of measuring Glu levels for 7 days without loss of sensitivity. We performed studies of tail-pinch induced stress, which caused a robust biphasic increase in Glu. Histological data show chronic implantation of the MEAs caused minimal injury to the CNS. Taken together, our data show that chronic recordings of tonic and phasic Glu can be carried out in awake rats for up to 17 days in vivo allowing longer term studies of Glu regulation in behaving rats.
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| 19. |
- Sivarani, T., et al.
(författare)
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First stars X. The nature of three unevolved carbon-enhanced metal-poor stars
- 2006
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Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 459:1, s. 125-135
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Tidskriftsartikel (refereegranskat)abstract
- Context. On the order of 20% of the very metal-poor stars in the Galaxy exhibit large carbon enhancements. It is important to establish which astrophysical sites and processes are responsible for the elemental abundance patterns of this early Galactic population. Aims. We seek to understand the nature of the progenitors of three main-sequence turnoff Carbon-Enhanced Metal-Poor (CEMP) stars, CS 31080-095, CS 22958-042, and CS 29528-041, based on a detailed abundance analysis. Methods. From high-resolution VLT/UVES spectra (R similar to 43 000), we determine abundances or upper limits for Li, C, N, O, and other important elements, as well as C-12/C-13 isotopic ratios. Results. All three stars have -3.30 <= [Fe/H]<= -2.85 and moderate to high CNO abundances. CS 22958-042 is one of the most carbon-rich CEMP stars known ([C/Fe] = +3.2), while CS 29528-041 (one of the few N-enhanced metal-poor stars known) is one of the most nitrogen rich ([N/Fe] = +3.0). Oxygen is very high in CS 31080-095 ([O/Fe] = +2.35) and in CS 22958-042 ([O/Fe] = +1.35). All three stars exhibit [Sr/Fe] < 0; Ba is not detected in CS 22958-042 ([Ba/Fe] < -0.53),but it is moderately enhanced ([Ba/Fe] similar to 1) in the other two stars. CS 22958-042 displays one of the largest sodium overabundances yet found in CEMP stars ([Na/Fe] = +2.8). CS 22958-042 has C-12/C-13 = 9, similar to most other CEMP stars without enhanced neutron-capture elements, while C-12/C-13 = 40 in CS 31080-095. CS 31080-095 and CS 29528-041 have A(Li) similar to 1.7, below the Spite Plateau, while Li is not detected in CS 22958-042. Conclusions. CS 22958-042 is a CEMP-no star, but the other two stars are in no known class of CEMP star and thus either constitute a new class or are a link between the CEMP-no and CEMP-s classes, adding complexity to the abundance patterns for CEMP stars. We interpret the abundance patterns in our stars to imply that current models for the presumed AGB binary progenitors lack an extra-mixing process, similar to those apparently operating in RGB stars.
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| 20. |
- Spite, M., et al.
(författare)
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First stars IX - Mixing in extremely metal-poor giants. Variation of the C-12/C-13, [Na/Mg] and [Al/Mg] ratios
- 2006
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Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 455:1, s. 291-301
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Tidskriftsartikel (refereegranskat)abstract
- Context. Extremely metal-poor (EMP) stars preserve a fossil record of the composition of the ISM when the Galaxy formed. It is crucial, however, to verify whether internal mixing has modified their surface composition, especially in the giants where most elements can be studied. Aims. We aim to understand the CNO abundance variations found in some, but not all EMP field giants analysed earlier. Mixing beyond the first dredge-up of standard models is required, and its origin needs clarification. Methods. The C-12/C-13 ratio is the most robust diagnostic of deep mixing, because it is insensitive to the adopted stellar parameters and should be uniformly high in near-primordial gas. We have measured C-12 and C-13 abundances in 35 EMP giants (including 22 with [Fe/H] < -3.0) from high-quality VLT/UVES spectra analysed with LTE model atmospheres. Correlations with other abundance data are used to study the depth of mixing. Results. The C-12/C-13 ratio is found to correlate with [C/Fe] (and Li/H), and clearly anti-correlate with [N/Fe], as expected if the surface abundances are modified by CNO processed material from the interior. Evidence for such deep mixing is observed in giants above log L/L-circle dot = 2.6, brighter than in less metal-poor stars, but matching the bump in the luminosity function in both cases. Three of the mixed stars are also Na- and Al-rich, another signature of deep mixing, but signatures of the ON cycle are not clearly seen in these stars. Conclusions. Extra mixing processes clearly occur in luminous RGB stars. They cannot be explained by standard convection, nor in a simple way by rotating models. The Na- and Al-rich giants could be AGB stars themselves, but an inhomogeneous early ISM or pollution from a binary companion remain possible alternatives.
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| 21. |
- von Lukowicz, Tobias, et al.
(författare)
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PARP1 is required for adhesion molecule expression in atherogenesis.
- 2008
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Ingår i: Cardiovascular research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 78:1, s. 158-66
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Atherosclerosis is the leading cause of death in Western societies and a chronic inflammatory disease. However, the key mediators linking recruitment of inflammatory cells to atherogenesis remain poorly defined. Poly(ADP-ribose) polymerase 1 (PARP1) is a nuclear enzyme, which plays a role in acute inflammatory diseases. METHODS AND RESULTS: In order to test the role of PARP in atherogenesis, we applied chronic pharmacological PARP inhibition or genetic PARP1 deletion in atherosclerosis-prone apolipoprotein E-deficient mice and measured plaque formation, adhesion molecules, and features of plaque vulnerability. After 12 weeks of high-cholesterol diet, plaque formation in male apolipoprotein E-deficient mice was decreased by chronic inhibition of enzymatic PARP activity or genetic deletion of PARP1 by 46 or 51%, respectively (P < 0.05, n >or= 9). PARP inhibition or PARP1 deletion reduced PARP activity and diminished expression of inducible nitric oxide synthase, vascular cell adhesion molecule-1, and P- and E-selectin. Furthermore, chronic PARP inhibition reduced plaque macrophage (CD68) and T-cell infiltration (CD3), increased fibrous cap thickness, and decreased necrotic core size and cell death (P < 0.05, n >or= 6). CONCLUSION: Our data provide pharmacological and genetic evidence that endogenous PARP1 is required for atherogenesis in vivo by increasing adhesion molecules with endothelial activation, enhancing inflammation, and inducing features of plaque vulnerability. Thus, inhibition of PARP1 may represent a promising therapeutic target in atherosclerosis.
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| 22. |
- Windahl, Sara H, 1971, et al.
(författare)
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Bone protection by estrens occurs through non-tissue-selective activation of the androgen receptor.
- 2006
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Ingår i: The Journal of clinical investigation. - 0021-9738. ; 116:9, s. 2500-9
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Tidskriftsartikel (refereegranskat)abstract
- The use of estrogens and androgens to prevent bone loss is limited by their unwanted side effects, especially in reproductive organs and breast. Selective estrogen receptor modulators (SERMs) partially avoid such unwanted effects, but their efficacy on bone is only moderate compared with that of estradiol or androgens. Estrens have been suggested to not only prevent bone loss but also exert anabolic effects on bone while avoiding unwanted effects on reproductive organs. In this study, we compared the effects of a SERM (PSK3471) and 2 estrens (estren-alpha and estren-beta) on bone and reproductive organs to determine whether estrens are safe and act via the estrogen receptors and/or the androgen receptor (AR). Estrens and PSK3471 prevented gonadectomy-induced bone loss in male and female mice, but none showed true anabolic effects. Unlike SERMs, the estrens induced reproductive organ hypertrophy in both male and female mice and enhanced MCF-7 cell proliferation in vitro. Estrens directly activated transcription in several cell lines, albeit at much higher concentrations than estradiol or the SERM, and acted for the most part through the AR. We conclude that the estrens act mostly through the AR and, in mice, do not fulfill the preclinical efficacy or safety criteria required for the treatment or prevention of osteoporosis.
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