| 1. |
- Yao, W-M, et al.
(författare)
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Review of Particle Physics
- 2006
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Ingår i: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 33:1, s. 1-1
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Tidskriftsartikel (refereegranskat)
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| 2. |
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| 5. |
- Villa, Luisa L., et al.
(författare)
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Immunologic responses following administration of a vaccine targeting human papillomavirus Types 6, 11, 16, and 18
- 2006
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 24:27-28, s. 5571-5583
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Tidskriftsartikel (refereegranskat)abstract
- Human papillomavirus (HPV) infection causes cervical cancer and genital warts. Young women (1106) were randomized to receive one of three formulations of a quadrivalent HPV (Types 6/11/16/18) L1 virus-like particle (VLP) vaccine or one of two placebo formulations. The goal was to assess vaccine safety and immunogenicity in baseline HPV 6/11/16 or 18-naive and previously infected subjects. All three formulations were highly immunogenic. At Month 2 (postdose 1), among women with vaccine-type antibodies at baseline, vaccine-induced anti-HPV responses were similar to 12- to 26-fold higher than those observed in baseline-naive women, suggesting an anamnestic response. Following an initial, similar sized decline, anti-HPV responses plateaued and remained stable through end-of-study (3.0 years). No vaccine-related serious adverse experiences were reported. (c) 2006 Elsevier Ltd. All rights reserved.
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| 6. |
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| 7. |
- Monoranu, Camelia Maria, et al.
(författare)
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pH measurement as quality control on human post mortem brain tissue : a study of the BrainNet Europe consortium
- 2009
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Ingår i: Neuropathology and Applied Neurobiology. - : Wiley. - 0305-1846 .- 1365-2990. ; 35:3, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Most brain diseases are complex entities. Although animal models or cell culture experiments mimic some disease aspects, human post mortem brain tissue remains essential to advance our understanding of brain diseases using biochemical and molecular techniques. Post mortem artefacts must be properly understood, standardized, and either eliminated or factored into such experiments. Here we examine the influence of several premortem and post mortem factors on pH, and discuss the role of pH as a biochemical marker for brain tissue quality. METHODS: We assessed brain tissue pH in 339 samples from 116 brains provided by 8 different European and 2 Australian brain bank centres. We correlated brain pH with tissue source, post mortem delay, age, gender, freezing method, storage duration, agonal state and brain ischaemia. RESULTS: Our results revealed that only prolonged agonal state and ischaemic brain damage influenced brain tissue pH next to repeated freeze/thaw cycles. CONCLUSIONS: pH measurement in brain tissue is a good indicator of premortem events in brain tissue and it signals limitations for post mortem investigations.
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| 10. |
- Sundqvist, J. O., et al.
(författare)
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MgI emission lines at 12 and 18 mu m in K giants
- 2008
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 486:3, s. 985-993
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Tidskriftsartikel (refereegranskat)abstract
- Context. The solar mid-infrared metallic emission lines have already been observed and analyzed well, and the formation scenario of the Mg I 12 mu m lines has been known for more than a decade. Detections of stellar emission at 12 mu m have, however, been limited to Mg I in very few objects. Previous modeling attempts have been made only for Procyon and two cool evolved stars, with unsatisfactory results for the latter. This prevents the lines' long predicted usage as probes of stellar magnetic fields. Aims. We want to explain our observed Mg I emission lines at 12 mu m in the K giants Pollux, Arcturus, and Aldebaran and at 18 mu m in Pollux and Arcturus. We discuss our modeling of these lines and particularly how various aspects of the model atom affect the emergent line profiles. Methods. High-resolution observational spectra were obtained using TEXES at Gemini North and the IRTF. To produce synthetic line spectra, we employed standard one-dimensional, plane-parallel, non-LTE modeling for trace elements in cool stellar atmospheres. We computed model atmospheres with the MARCS code, applied a comprehensive magnesium model atom, and used the radiative transfer code MULTI to solve for the magnesium occupation numbers in statistical equilibrium. Results. The Mg I emission lines at 12 mu m in the K giants are stronger than in the dwarfs observed so far. We present the first observed stellar emission lines from Mg I at 18 mu m and from Al I, Si I, and presumably Ca I at 12 mu m. We successfully reproduce the observed Mg I emission lines simultaneously in the giants and in the Sun, but show how the computed line profiles depend critically on atomic data input and how the inclusion of energy levels with n > ;= 10 and collisions with neutral hydrogen are necessary to obtain reasonable fits.
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| 13. |
- 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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| 17. |
- Johansson, Sofia, et al.
(författare)
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Dysregulation of cell death machinery in the prefrontal cortex of human alcoholics
- 2009
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Ingår i: International Journal of Neuropsychopharmacology. - 1461-1457 .- 1469-5111. ; 12:1, s. 109-115
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Tidskriftsartikel (refereegranskat)abstract
- In human alcoholics, the cell density is decreased in the prefrontal cortex (PFC) and other brain areas. This may be due to persistent activation of cell death pathways. To address this hypothesis, we examined the status of cell death machinery in the dorsolateral PFC in alcoholics. Protein and mRNA expression levels of several key pro- and anti-apoptotic genes were compared in post-mortem samples of 14 male human alcoholics and 14 male controls. The findings do not support the hypothesis. On the contrary, they show that several components of intrinsic apoptotic pathway are decreased in alcoholics. No differences were evident in the motor cortex, which is less damaged in alcoholics and was analysed for comparison. Thus, cell death mechanisms may be dysregulated by inhibition of intrinsic apoptotic pathway in the PFC in human alcoholics. This inhibition may reflect molecular adaptations that counteract alcohol neurotoxicity in cells that survive after many years of alcohol exposure and withdrawal.
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| 18. |
- Johansson, Sofia, et al.
(författare)
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Validation of endogenous controls for quantitative gene expression analysis : Application on brain cortices of human chronic alcoholics
- 2007
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993 .- 1872-6240. ; 1132:1, s. 20-8
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Tidskriftsartikel (refereegranskat)abstract
- Real-time PCR is frequently used for gene expression quantification due to its methodological sensitivity and reproducibility. The gene expression is quantified by normalization to one or more reference genes, usually beta-actin (ACTB), glyceraldehyde-3-phosphate dehydrogenase (GAPD) or to ribosomal RNA (18S). However, different environmental or pathological conditions might also influence the expression of normalizing genes, which could severely skew the interpretation of quantitative results. This study evaluates whether 16 genes frequently used as endogenous controls in expression studies, can serve as such for comparison of human brain tissues of chronic alcoholics and control subjects. The prefrontal and motor cortices that are affected differently by chronic alcohol consumption were analyzed. The reference genes that have no or small differences in expression in alcoholics and control subjects, were found to be specific for each region: beta-actin (ACTB) and ribosomal large P0 (RPLP0) for the prefrontal cortex while importin 8 (IPO8) and RNA polymerase II (POLR2A) for the motor cortex. Four out of sixteen analyzed genes demonstrated significant differences in expression between alcoholics and controls: phosphoglycerate kinase (PGK1), hypoxanthine phosphoribosyl transferase (HPRT1) and peptidylprolyl isomerase A (PPIA) in the motor cortex and beta-2-microglobulin (B2M) in the prefrontal cortex. Our study demonstrates the importance of validation of endogenous control genes prior to real-time PCR analysis of human brain tissues. Prescribed and non-prescribed drugs, pathological or environmental conditions along with alcohol abuse may differentially influence expression of reference genes.
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| 19. |
- Kawamura, Harukiyo, et al.
(författare)
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Vascular endothelial growth factor (VEGF)-A165b is a weak in vitro agonist for VEGF receptor-2 due to lack of coreceptor binding and deficient regulation of kinase activity
- 2008
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 68:12, s. 4683-4692
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Tidskriftsartikel (refereegranskat)abstract
- Vascular endothelial growth factor (VEGF)-A165b is a COOH-terminal splice variant of VEGF-A that has been implicated in negative regulation of angiogenesis. We compared the properties of VEGF-A165b with those of VEGF-A121, VEGF-A145, and VEGF-A165. Induction of tyrosine phosphorylation sites in VEGFR-2 differed between the VEGF ligands as determined by tryptic phosphopeptide mapping and by use of phosphosite-specific antibodies. VEGF-A165b was considerably poorer in inducing phosphorylation of the positive regulatory site Y1052 in VEGFR-2. Whereas this did not affect activation of VEGFR-2 in vitro, we show that VEGF-A165b failed to induce vasculogenesis and sprouting angiogenesis in differentiating embryonic stem cells and vascularization of s.c. Matrigel plugs. In addition, the ability of the different VEGF ligands to induce angiogenesis correlated with their abilities to bind the VEGF coreceptor neuropilin 1 (NRP1). Our data indicate that loss of VEGFR-2/NRP1 complex formation and Y1052 phosphorylation contribute to the lack of angingenic properties of VEGF-A165b.
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| 20. |
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| 21. |
- Ryde, Nils, et al.
(författare)
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Water Vapor on Supergiants : The 12 μm TEXES Spectra of μ Cephei
- 2006
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 645:1, s. 652-658
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Tidskriftsartikel (refereegranskat)abstract
- Several recent papers have argued for warm, semidetached, molecular layers surrounding red giant and supergiant stars, a concept known as a MOLsphere. Spectroscopic and interferometric analyses have often corroborated this general picture. Here we present high-resolution spectroscopic data of pure rotational lines of water vapor at 12 mu m for the supergiant mu Cep. This star has often been used to test the concept of molecular layers around supergiants. Given the prediction of an isothermal, optically thick water vapor layer in local thermodynamic equilibrium around the star ( MOLsphere), we expected the 12 mu m lines to be in emission or at least in absorption but filled in by emission from the molecular layer around the star. Our data, however, show the contrary; we find definite absorption. Thus, our data do not easily fit into the suggested isothermal MOLsphere scenario. The 12 mu m lines, therefore, put new, strong constraints on the MOLsphere concept and on the nature of water seen in signatures across the spectra of early M supergiants. We also find that the absorption is even stronger than that calculated from a standard, spherically symmetric model photosphere without any surrounding layers. A cool model photosphere, representing cool outer layers, is, however, able to reproduce the lines, but this model does not account for water vapor emission at 6 mu m. Thus, a unified model for water vapor on mu Cep appears to be lacking. It does seem necessary to model the underlying photospheres of these supergiants in their whole complexity. The strong water vapor lines clearly reveal inadequacies of classical model atmospheres.
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| 22. |
- Sundqvist, Anders, et al.
(författare)
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Control of lipid metabolism by phosphorylation-dependent degradation of the SREBP family of transcription factors by SCF(Fbw7)
- 2005
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 1:6, s. 379-391
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Tidskriftsartikel (refereegranskat)abstract
- The sterol regulatory element binding protein (SREBP) family of transcription factors controls cholesterol and lipid metabolism. The nuclear forms of these proteins are rapidly degraded by the ubiquitin-proteasome pathway, but the signals and factors required for this are unknown. Here, we identify a phosphodegron in SREBP1a that serves as a recognition motif for the SCF(Fbw7) ubiquitin ligase. Fbw7 interacts with nuclear SREBP1a and enhances its ubiquitination and degradation in a manner dependent on the phosphorylation of T426 and S430 by GSK-3. Fbw7 also degrades nuclear SREBP1c and SREBP2, and inactivation of endogenous Fbw7 results in stabilization of nuclear SREBP1 and -2, enhanced expression of SREBP target genes, enhanced synthesis of cholesterol and fatty acids, and enhanced receptor-mediated uptake of LDL. Thus, our results suggest that Fbw7 may be a major regulator of lipid metabolism through control of the phosphorylation-dependent degradation of the SREBP family of transcription factors.
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| 23. |
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| 24. |
- Villa, LL, et al.
(författare)
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Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial
- 2005
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Ingår i: The Lancet Oncology. - 1474-5488 .- 1470-2045. ; 6:5, s. 271-278
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Tidskriftsartikel (refereegranskat)abstract
- Background A randomised double-blind placebo-controlled phase II study was done to assess the efficacy of a prophylactic quadrivalent vaccine targeting the human papillomavirus (HPV) types associated with 70% of cervical cancers (types 16 and 18) and with 90% of genital warts (types 6 and 11). Methods 277 young women (mean age 20.2 years [SD 1.7]) were randomly assigned to quadrivalent HPV (20 μ g type 6, 40 μ g type 11, 40 μ g type 16, and 20 μ g type 18) L1 virus-like-particle (VLP) vaccine and 275 (mean age 20.0 years [1.7]) to one of two placebo preparations at day 1, month 2, and month 6. For 36 months, participants underwent regular gynaecological examinations, cervicovaginal sampling for HPV DNA, testing for serum antibodies to HPV, and Pap testing. The primary endpoint was the combined incidence of infection with HPV 6, 11, 16, or 18, or cervical or external genital disease (ie, persistent HPV infection, HPV detection at the last recorded visit, cervical intraepithelial neoplasia, cervical cancer, or external genital lesions caused by the HPV types in the vaccine). Main analyses were done per protocol. Findings Combined incidence of persistent infection or disease with HPV 6, 11, 16, or 18 fell by 90% (95% CI 71-97, p< 0.0001) in those assigned vaccine compared with those assigned placebo. Interpretation A vaccine targeting HPV types 6, 11, 16, 18 could substantially reduce the acquisition of infection and clinical disease caused by common HPV types.
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| 27. |
- Watanabe, Hiroyuki, et al.
(författare)
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FOSB proteins in the orbitofrontal and dorsolateral prefrontal cortices of human alcoholics
- 2009
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Ingår i: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 14:3, s. 294-297
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Tidskriftsartikel (refereegranskat)abstract
- The transcription factor DeltaFosB is accumulated in the addiction circuitry, including the orbitofrontal and medial prefrontal cortices of rodents chronically exposed to ethanol or other drugs of abuse, and has been suggested to play a direct role in addiction maintenance. To address this hypothesis in the context of substance dependence in humans, we compared the immunoreactivities of FOSB proteins in the orbitofrontal and dorsolateral prefrontal cortices (OFC and DLPFC respectively) between controls and alcoholics using semiquantitative immunoblotting. In both structures, we detected three forms of FOSB, one of which was DeltaFOSB, but in neither case did their immunoreactivities differ between the groups. Our results indicate that the DeltaFOSB immunoreactivity in the human brain is very low, and that it is not accumulated in the OFC and DLPFC of human alcoholics, suggesting that it may not be directly involved in addiction maintenance, at least not in ethanol dependence.
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| 28. |
- Ökvist, Anna, et al.
(författare)
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Neuroadaptations in human chronic alcoholics : dysregulation of the NF-κB system
- 2007
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 2:9, s. e930-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Alcohol dependence and associated cognitive impairments apparently result from neuroadaptations to chronic alcohol consumption involving changes in expression of multiple genes. Here we investigated whether transcription factors of Nuclear Factor-kappaB (NF-kappaB) family, controlling neuronal plasticity and neurodegeneration, are involved in these adaptations in human chronic alcoholics. METHODS AND FINDINGS: Analysis of DNA-binding of NF-kappaB (p65/p50 heterodimer) and the p50 homodimer as well as NF-kappaB proteins and mRNAs was performed in postmortem human brain samples from 15 chronic alcoholics and 15 control subjects. The prefrontal cortex involved in alcohol dependence and cognition was analyzed and the motor cortex was studied for comparison. The p50 homodimer was identified as dominant kappaB binding factor in analyzed tissues. NF-kappaB and p50 homodimer DNA-binding was downregulated, levels of p65 (RELA) mRNA were attenuated, and the stoichiometry of p65/p50 proteins and respective mRNAs was altered in the prefrontal cortex of alcoholics. Comparison of a number of p50 homodimer/NF-kappaB target DNA sites, kappaB elements in 479 genes, down- or upregulated in alcoholics demonstrated that genes with kappaB elements were generally upregulated in alcoholics. No significant differences between alcoholics and controls were observed in the motor cortex. CONCLUSIONS: We suggest that cycles of alcohol intoxication/withdrawal, which may initially activate NF-kappaB, when repeated over years downregulate RELA expression and NF-kappaB and p50 homodimer DNA-binding. Downregulation of the dominant p50 homodimer, a potent inhibitor of gene transcription apparently resulted in derepression of kappaB regulated genes. Alterations in expression of p50 homodimer/NF-kappaB regulated genes may contribute to neuroplastic adaptation underlying alcoholism.
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