| 1. |
- Schael, S, et al.
(författare)
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Precision electroweak measurements on the Z resonance
- 2006
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Forskningsöversikt (refereegranskat)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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| 2. |
- Aamodt, K., et al.
(författare)
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The ALICE experiment at the CERN LHC
- 2008
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 3:S08002
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Forskningsöversikt (refereegranskat)abstract
- ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries, Its overall dimensions are 16 x 16 x 26 m(3) with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008.
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| 3. |
- Wortman, J. R., et al.
(författare)
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The 2008 update of the Aspergillus nidulans genome annotation: A community effort
- 2009
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Ingår i: Fungal Genetics and Biology. - : Elsevier BV. - 1096-0937 .- 1087-1845. ; 46, s. S2-S13
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Tidskriftsartikel (refereegranskat)abstract
- The identification and annotation of protein-coding genes is one of the primary goals of whole-genome sequencing projects, and the accuracy of predicting the primary protein products of gene expression is vital to the interpretation of the available data and the design of downstream functional applications. Nevertheless, the comprehensive annotation of eukaryotic genomes remains a considerable challenge. Many genomes submitted to public databases, including those of major model organisms, contain significant numbers of wrong and incomplete gene predictions. We present a community-based reannotation of the Aspergillus nidulans genome with the primary goal of increasing the number and quality of protein functional assignments through the careful review of experts in the field of fungal biology. (C) 2009 Elsevier Inc. All rights reserved.
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| 4. |
- Hagleitner, M M, et al.
(författare)
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Clinical spectrum of immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome).
- 2008
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Ingår i: Journal of medical genetics. - : BMJ. - 1468-6244. ; 45:2, s. 93-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome) is a rare autosomal recessive disease characterised by facial dysmorphism, immunoglobulin deficiency and branching of chromosomes 1, 9 and 16 after PHA stimulation of lymphocytes. Hypomethylation of DNA of a small fraction of the genome is an unusual feature of ICF patients which is explained by mutations in the DNA methyltransferase gene DNMT3B in some, but not all, ICF patients. OBJECTIVE: To obtain a comprehensive description of the clinical features of this syndrome as well as genotype-phenotype correlations in ICF patients. METHODS: Data on ICF patients were obtained by literature search and additional information by means of questionnaires to corresponding authors. Results and CONCLUSIONS: 45 patients all with proven centromeric instability were included in this study. Facial dysmorphism was found to be a common characteristic (n = 41/42), especially epicanthic folds, hypertelorism, flat nasal bridge and low set ears. Hypo- or agammaglobulinaemia was demonstrated in nearly all patients (n = 39/44). Opportunistic infections were seen in several patients, pointing to a T cell dysfunction. Haematological malignancy was documented in two patients. Life expectancy of ICF patients is poor, especially those with severe infections in infancy or chronic gastrointestinal problems and failure to thrive. Early diagnosis of ICF is important since early introduction of immunoglobulin supplementation can improve the course of the disease. Allogeneic stem cell transplantation should be considered as a therapeutic option in patients with severe infections or failure to thrive. Only 19 of 34 patients showed mutations in DNMT3B, suggesting genetic heterogeneity. No genotype-phenotype correlation was found between patients with and without DNMT3B mutations.
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| 5. |
- Mijovilovich, Ana, et al.
(författare)
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The Interpretation of Sulfur K-edge XANES spectra: A case Study on Thiophene and Aliphatic Sulfur Compounds
- 2009
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Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455 .- 1089-5639 .- 1520-5215. ; 113, s. 2750-2756
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Tidskriftsartikel (refereegranskat)abstract
- Sulfur K-edge XANES has been measured for three sulfur model compounds, dibenzothiophene, dibenzothiophene sulfone, and aliphatic sulfur (DL-methionine). The spectra have been simulated with Density Functional Theory (DFT) using a number of methods, including the half core hole approximation. Dipole transition elements were calculated and the transitions were convoluted with linearly increasing Gaussian functions in the first 20 eV of the near edge region. In the case of dibenzothiophene, relaxation of the first excited states in the presence of the core-hole gave a further improvement. The theoretical results reproduce well the features of the spectra and give insight in the relation between geometric structure and molecular orbitals. Though DL-methionine and dibenzothiophene show a similar sharp rise of the white line, their molecular levels are quite different, pointing out the difficulties in finding useful “fingerprints” in the spectra for specific compounds.
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| 6. |
- de Groot, I. B., et al.
(författare)
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Validation of the Dutch version of the Hip Disability and Osteoarthritis Outcome Score
- 2007
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 15:1, s. 104-109
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The Hip disability and Osteoarthritis Outcome Score (HOOS) was constructed in Sweden; this questionnaire has proved to be valid for persons with hip disability with or without hip osteoarthritis (OA) and with high demands of physical function. Objective: The objective of this study was to evaluate the internal consistency, reliability, construct validity, and floor and ceiling effects of the Dutch version of the HOOS questionnaire. Patients and methods: After translation with a forward/backward protocol, 74 hip arthroplasty patients and 88 hip OA patients filled in the Dutch HOOS, as well as a Short Form-36 (SF-36), an Oxford Hip Score (OHS) and a VAS-pain questionnaire. Results: The Dutch version of the HOOS questionnaire achieved excellent scores in all of the clinimetric properties. Conclusion: The Dutch HOOS questionnaire has a good internal consistency and reliability. Moreover, the construct validity is good and no floor and ceiling effects were found. The HOOS is a good instrument for patients with different stadia of hip OA. (C) 2006 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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| 7. |
- Dingemans, Milou M L, et al.
(författare)
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Hydroxylation increases the neurotoxic potential of BDE-47 to affect exocytosis and calcium homeostasis in PC12 cells.
- 2008
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 116:5, s. 637-43
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Oxidative metabolism, resulting in the formation of hydroxylated polybrominated diphenyl ether (PBDE) metabolites, may enhance the neurotoxic potential of brominated flame retardants. OBJECTIVE: Our objective was to investigate the effects of a hydroxylated metabolite of 2,2',4,4'-tetra-bromodiphenyl ether (BDE-47; 6-OH-BDE-47) on changes in the intracellular Ca2+ concentration ([Ca2+]i) and vesicular catecholamine release in PC12 cells. METHODS: We measured vesicular catecholamine release and [Ca2+]i using amperometry and imaging of the fluorescent Ca2+-sensitive dye Fura-2, respectively. RESULTS: Acute exposure of PC12 cells to 6-OH-BDE-47 (5 microM) induced vesicular catecholamine release. Catecholamine release coincided with a transient increase in [Ca2+]i, which was observed shortly after the onset of exposure to 6-OH-BDE-47 (120 microM). An additional late increase in [Ca2+]i was often observed at > or =1 microM 6-OH-BDE-47. The initial transient increase was absent in cells exposed to the parent compound BDE-47, whereas the late increase was observed only at 20 microM. Using the mitochondrial uncoupler carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) and thapsigargin to empty intracellular Ca2+ stores, we found that the initial increase originates from emptying of the endoplasmic reticulum and consequent influx of extracellular Ca2+, whereas the late increase originates primarily from mitochondria. CONCLUSION: The hydroxylated metabolite 6-OH-BDE-47 is more potent in disturbing Ca2+ homeostasis and neurotransmitter release than the parent compound BDE-47. The present findings indicate that bioactivation by oxidative metabolism adds considerably to the neurotoxic potential of PBDEs. Additionally, based on the observed mechanism of action, a cumulative neurotoxic effect of PBDEs and ortho-substituted polychlorinated biphenyls on [Ca2+]i cannot be ruled out.
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| 8. |
- Eussen, S J P M, et al.
(författare)
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Changes in markers of cobalamin status after cessation of oral B-vitamin supplements in elderly people with mild cobalamin deficiency
- 2008
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Ingår i: European Journal of Clinical Nutrition. - London : John Libbey. - 0954-3007 .- 1476-5640. ; 62:10, s. 1248-1251
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Tidskriftsartikel (refereegranskat)abstract
- Mildly cobalamin-deficient elderly were supplemented with 1000 microg cobalamin (group C, n=34), 1000 microg cobalamin with 400 microg folic acid (group CF, n=31) or a placebo (n=30) for 6 months. Participants provided one single blood sample 3, 5 or 7 months after cessation of supplementation to monitor early changes in plasma concentrations of cobalamin, holotranscobalamin (holoTC) and methylmalonic acid (MMA). At the end of supplementation (groups C+CF), one participant met our criteria for mild cobalamin deficiency, as did 13, 14 and 43% of the participants assessed at respectively 3, 5 and 7 months post-supplementation. Cobalamin and holoTC declined on average with 47 and 56% relative to concentrations at the end of supplementation for the group assessed at 7 months post-supplementation. Essentially similar declines were observed for those participants assessed at 3 and 5 months post-supplementation. Mean MMA concentrations increased by 15% (P=0.07) in those participants assessed at 3 and 5 months post-supplementation, and increased by 50% (P=0.002) in those participants assessed at 7 months post-supplementation. Considering MMA as a sensitive tissue marker for cobalamin status, oral supplementation may afford adequate cobalamin status for a period of up to 5 months after cessation in the majority of participants.
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| 9. |
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| 10. |
- Roest, Pauline A. M., et al.
(författare)
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Exposure of neural crest cells to elevated glucose leads to congenital heart defects, an effect that can be prevented by N-acetylcysteine
- 2007
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Ingår i: Birth defects research. Clinical and molecular teratology. - : Wiley. - 1542-0752 .- 1542-0760. ; 79:3, s. 231-235
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Diabetes mellitus during pregnancy increases the risk for congenital heart disease in the offspring. The majority of the cardiovascular malformations occur in the outflow tract and pharyngeal arch arteries, where neural crest cells are essential for normal development. We studied the effects of specific exposure of neural crest cells to elevated glucose on heart development. Antioxidants reduce the damaging effect of glucose on neural crest cells in vitro; therefore, we investigated the effect of supplementing N-acetylcysteine in vivo. METHODS: Cardiac neural crest of HH 8-12 chicken embryos was directly exposed by a single injection in the neural tube with 30 mM D-glucose (or 30 mM L-glucose as a control). To examine the effect of a reduction in oxidative stress, we added 2 mM N-acetylcysteine to the injected D-glucose. RESULTS: Exposure of neural crest cells to elevated D-glucose-induced congenital heart malformations in 82% of the embryos. In the embryos injected with L-glucose, only 9% developed a heart malformation. As expected, all malformations were located in the outflow tract and pharyngeal arch arteries. The frequency of heart malformations decreased from 82% to 27% when 2 mM N-acetylcysteine was added to the injected D-glucose. CONCLUSIONS: These data are the first to confirm that the vulnerability of neural crest cells to elevated glucose induces congenital heart malformations. The fact that N-acetylcysteine limits the teratogenicity of glucose implies that its damaging effect is mediated by an increase of oxidative stress in the neural crest cells.
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| 11. |
- Butler, Geraldine, et al.
(författare)
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Evolution of pathogenicity and sexual reproduction in eight Candida genomes.
- 2009
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 459:7247, s. 657-62
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Tidskriftsartikel (refereegranskat)abstract
- Candida species are the most common cause of opportunistic fungal infection worldwide. Here we report the genome sequences of six Candida species and compare these and related pathogens and non-pathogens. There are significant expansions of cell wall, secreted and transporter gene families in pathogenic species, suggesting adaptations associated with virulence. Large genomic tracts are homozygous in three diploid species, possibly resulting from recent recombination events. Surprisingly, key components of the mating and meiosis pathways are missing from several species. These include major differences at the mating-type loci (MTL); Lodderomyces elongisporus lacks MTL, and components of the a1/2 cell identity determinant were lost in other species, raising questions about how mating and cell types are controlled. Analysis of the CUG leucine-to-serine genetic-code change reveals that 99% of ancestral CUG codons were erased and new ones arose elsewhere. Lastly, we revise the Candida albicans gene catalogue, identifying many new genes.
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| 12. |
- Dhonukshe-Rutten, Rosalie A M, et al.
(författare)
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Low bone mineral density and bone mineral content are associated with low cobalamin status in adolescents.
- 2005
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Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 44:6, s. 341-347
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cobalamin deficiency is prevalent in vegetarians and has been associated with increased risk of osteoporosis. AIM OF THE STUDY: To examine the association between cobalamin status and bone mineral density in adolescents formerly fed a macrobiotic diet and in their counterparts. METHODS: In this cross-sectional study bone mineral density (BMD) and bone mineral content (BMC) were determined by DEXA in 73 adolescents (9-15 y) who were fed a macrobiotic diet up to the age of 6 years followed by a lacto-(-ovo-) vegetarian or omnivorous diet. Data from 94 adolescents having consumed an omnivorous diet throughout their lives were used as controls. Serum concentrations of cobalamin, methylmalonic acid (MMA) and homocysteine were measured and calcium intake was assessed by questionnaire. Analysis of covariance (MANCOVA) was performed to calculate adjusted means for vitamin B12 and MMA for low and normal BMC and BMD groups. RESULTS: Serum cobalamin concentrations were significantly lower (geometric mean (GM) 246 pmol/L vs. 469 pmol/L) and MMA concentrations were significantly higher (GM 0.27 micromol/L vs. 0.16 micromol/L) in the formerly macrobiotic-fed adolescents compared to their counterparts. In the total study population, after adjusting for height, weight, bone area, percent lean body mass, age, puberty and calcium intake, serum MMA was significantly higher in subjects with a low BMD (p = 0.0003) than in subjects with a normal BMD. Vitamin B12 was significantly lower in the group with low BMD (p = 0.0035) or BMC (p = 0.0038) than in the group with normal BMD or BMC. When analyses were restricted to the group of formerly macrobiotic-fed adolescents, MMA concentration remained higher in the low BMD group compared to the normal BMD group. CONCLUSIONS: In adolescents, signs of an impaired cobalamin status, as judged by elevated concentrations of methylmalonic acid, were associated with low BMD. This was especially true in adolescents fed a macrobiotic diet during the first years of life, where cobalamin deficiency was more prominent.
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| 13. |
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| 14. |
- Mukhtyar, C., et al.
(författare)
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EULAR recommendations for the management of large vessel vasculitis
- 2009
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 68:3, s. 318-323
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To develop European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis. Methods: An expert group (10 rheumatologists, 3 nephrologists, 2 immunolgists, 2 internists representing 8 European countries and the USA, a clinical epidemiologist and a representative from a drug regulatory agency) identified 10 topics for a systematic literature search through a modified Delphi technique. In accordance with standardised EULAR operating procedures, recommendations were derived for the management of large vessel vasculitis. In the absence of evidence, recommendations were formulated on the basis of a consensus opinion. Results: Seven recommendations were made relating to the assessment, investigation and treatment of patients with large vessel vasculitis. The strength of recommendations was restricted by the low level of evidence and EULAR standardised operating procedures. Conclusions: On the basis of evidence and expert consensus, management recommendations for large vessel vasculitis have been formulated and are commended for use in everyday clinical practice.
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| 15. |
- Mukhtyar, C., et al.
(författare)
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EULAR recommendations for the management of primary small and medium vessel vasculitis
- 2009
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 68:3, s. 310-317
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To develop European League Against Rheumatism (EULAR) recommendations for the management of small and medium vessel vasculitis. Methods: An expert group ( consisting of 10 rheumatologists, 3 nephrologists, 2 immunologists, 2 internists representing 8 European countries and the USA, a clinical epidemiologist and a representative from a drug regulatory agency) identified 10 topics for a systematic literature search using a modified Delphi technique. In accordance with standardised EULAR operating procedures, recommendations were derived for the management of small and medium vessel vasculitis. In the absence of evidence, recommendations were formulated on the basis of a consensus opinion. Results: In all, 15 recommendations were made for the management of small and medium vessel vasculitis. The strength of recommendations was restricted by low quality of evidence and by EULAR standardised operating procedures. Conclusions: On the basis of evidence and expert consensus, recommendations have been made for the evaluation, investigation, treatment and monitoring of patients with small and medium vessel vasculitis for use in everyday clinical practice.
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| 16. |
- Nilsson, Maria, et al.
(författare)
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The antibacterial activity of peptides derived from human beta-2 glycoprotein I is inhibited by protein H and M1 protein from Streptococcus pyogenes.
- 2008
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Ingår i: Molecular Microbiology. - : Wiley. - 1365-2958 .- 0950-382X. ; 67:3, s. 482-492
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Tidskriftsartikel (refereegranskat)abstract
- During the last years, the importance of antibacterial peptides has attracted considerable attention. We report here that peptides derived from the fifth domain of beta-2 glycoprotein I (beta(2)GPI), a human heparin binding plasma protein, have antibacterial activities against Gram-positive and Gram-negative bacteria. Streptococcus pyogenes, an important human pathogen that can survive and grow in human blood, has developed mechanisms to escape the attack by these peptides. Thus, protein H and M1 protein, two surface proteins of the highly pathogenic S. pyogenes AP1 strain, bind full-length beta(2)GPI and thereby prevent the processing of beta(2)GPI by proteases from polymorphonuclear neutrophils (PMNs) into antibacterial peptides. In addition, protein H and M1 protein, released from the bacterial cell wall by PMN-derived proteases, bind to, and inhibit the activity of, beta(2)GPI-derived antibacterial peptides. Taken together, the data suggest that the interaction between the streptococcal proteins and beta(2)GPI or beta(2)GPI-derived peptides presents a novel mechanism to resist an antibacterial attack by beta(2)GPI-cleavage products.
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| 17. |
- Onur, E, et al.
(författare)
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Intelligent End-To-End Resource Virtualization Using Service Oriented Architecture
- 2009
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Ingår i: 2009 IEEE GLOBECOM Workshops. - 9781424456260 - 9781424456246 ; , s. 345-350
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Konferensbidrag (refereegranskat)abstract
- Service-oriented architecture can be considered as a philosophy or paradigm in organizing and utilizing services and capabilities that may be under the control of different ownership domains. Virtualization provides abstraction and isolation of lower level functionalities, enabling portability of higher level functions and sharing of physical resources. However, dynamics, environmental conditions and increasing complexity / heterogeneity of underlying resources call for adaptive resource handling. In this view an intelligent distributed architecture that enables dynamic user management and control on network-wide resource sharing by using the service oriented architecture concept is presented. Additionally, the proposed architecture supports trading of resources that will enable the transformation of traditional business models.
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| 18. |
- Roest, Pauline A.M., et al.
(författare)
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Specific Local Cardiovascular Changes of N-epsilon-(Carboxymethyl)lysine, Vascular Endothelial Growth Factor, and Smad2 in the Developing Embryos Coincide With Maternal Diabetes-Induced Congenital Heart Defects
- 2009
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 58:5, s. 1222-1228
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Embryos exposed to a diabetic environment in utero have an increased risk to develop congenital heart malformations. The mechanism behind the teratogenicity of diabetes still remains enigmatic. Detrimental effects of glycation products in diabetic patients have been well documented. We therefore studied a possible link between glycation products and the development of congenital cardiovascular malformations. Furthermore, we investigated other possible mechanisms involved in this pathogenesis: alterations in the levels of vascular endothelial growth factor (VEGF) or phosphorylated Smad2 (the latter can be induced by both glycation products and VEGF). RESEARCH DESIGN AND METHODS: We examined the temporal spatial patterning of the glycation products Nepsilon(carboxymethyl)lysine (CML) and methylglyoxal (MG) adducts, VEGF expression, and phosphorylated Smad2 during cardiovascular development in embryos from normal and diabetic rats. RESULTS: Maternal diabetes increased the CML accumulation in the areas susceptible to diabetes-induced congenital heart disease, including the outflow tract of the heart and the aortic arch. No MG adducts could be detected, suggesting that CML is more likely to be indicative for increased oxidative stress than for glycation. An increase of CML in the outflow tract of the heart was accompanied by an increase in phosphorylated Smad2, unrelated to VEGF. VEGF showed a time-specific decrease in the outflow tract of embryos from diabetic dams. CONCLUSIONS: From our results, we can conclude that maternal diabetes results in transient and localized alterations in CML, VEGF expression, and Smad2 phosphorylation overlapping with those regions of the developing heart that are most sensitive to diabetes-induced congenital heart disease.
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| 19. |
- van Baarlen, Peter, et al.
(författare)
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Differential NF-κB pathways induction by Lactobacillus plantarum in the duodenum of healthy humans correlating with immune tolerance
- 2009
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - Washington, DC : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 106:7, s. 2371-2376
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Tidskriftsartikel (refereegranskat)abstract
- How do we acquire immune tolerance against food microorganisms and commensal bacteria that constitute the intestinal microbiota? We investigated this by stimulating the immune system of adults with commensal Lactobacillus plantarum bacteria. We studied the in vivo human responses to L. plantarum in a randomized double-blind placebo-controlled cross-over study. Healthy adults ingested preparations of living and heat-killed L. plantarum bacteria. Biopsies were taken from the intestinal duodenal mucosa and altered expression profiles were analyzed using whole-genome microarrays and by biological pathway reconstructions. Expression profiles of human mucosa displayed striking differences in modulation of NF-kappaB-dependent pathways, notably after consumption of living L. plantarum bacteria in different growth phases. Our in vivo study identified mucosal gene expression patterns and cellular pathways that correlated with the establishment of immune tolerance in healthy adults.
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| 20. |
- Dingemans, Milou M. L., et al.
(författare)
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Hexabromocyclododecane Inhibits Depolarization-Induced Increase in Intracellular Calcium Levels and Neurotransmitter Release in PC12 Cells
- 2009
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Ingår i: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-6080 .- 1096-0929. ; 107:2, s. 490-497
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Tidskriftsartikel (refereegranskat)abstract
- Environmental levels of the brominated flame retardant (BFR) hexabromocyclododecane (HBCD) have been increasing. HBCD has been shown to cause adverse effects on learning and behavior in mice, as well as on dopamine uptake in rat synaptosomes and synaptic vesicles. For other BFRs, alterations in the intracellular Ca2+ homeostasis have been observed. Therefore, the aim of this study was to investigate whether the technical HBCD mixture and individual stereoisomers affect the intracellular Ca2+ concentration ([Ca2+](i)) in a neuroendocrine in vitro model (PC12 cells). [Ca2+](i) and vesicular catecholamine release were measured using respectively single-cell Fura-2 imaging and amperometry. Exposure of PC12 cells to the technical HBCD mixture or individual stereoisomers did neither affect basal [Ca2+](i), nor the frequency of basal neurotransmitter release. However, exposure to HBCD (0-20 mu M) did cause a dose-dependent reduction of a subsequent depolarization-evoked increase in [Ca2+](i). This effect was apparent only when HBCD was applied at least 5 min before depolarization (maximum effect after 20 min exposure). The effects of alpha- and beta-HBCD were comparable to that of the technical mixture, whereas the inhibitory effect of gamma-HBCD was larger. Using specific blockers of L-, N- or P/Q-type voltage-gated Ca2+ channels (VGCCs) it was shown that the inhibitory effect of HBCD is not VGCC-specific. Additionally, the number of cells showing depolarization-evoked neurotransmitter release was markedly reduced following HBCD exposure. Summarizing, HBCD inhibits depolarization-evoked [Ca2+](i) and neurotransmitter release. As increasing HBCD levels should be anticipated, these findings justify additional efforts to establish an adequate exposure, hazard and risk assessment.
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| 21. |
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| 22. |
- Liu, H J, et al.
(författare)
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Electronic structure of cobalt nanocrystals suspended in liquid
- 2007
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Ingår i: Nano letters (Print). - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 7:7, s. 1919-1922
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Tidskriftsartikel (refereegranskat)abstract
- The electronic structure of cobalt nanocrystals suspended in liquid as a function of size has been investigated using in situ X-ray absorptionand emission spectroscopy. A sharp absorption peak associated with the ligand molecules is found that increases in intensity upon reducingthe nanocrystal size. X-ray Raman features due to d−d and to charge-transfer excitations of ligand molecules are identified. The study revealsthe local symmetry of the surface of E-Co phase nanocrystals, which originates from a dynamic interaction between Co nanocrystals andsurfactant + solvent molecules.
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| 23. |
- Maas, Coen, et al.
(författare)
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Misfolded proteins activate Factor XII in humans, leading to kallikrein formation without initiating coagulation
- 2008
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 118:9, s. 3208-3218
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Tidskriftsartikel (refereegranskat)abstract
- When blood is exposed to negatively charged surface materials such as glass, an enzymatic cascade known as the contact system becomes activated. This cascade is initiated by autoactivation of Factor XII and leads to both coagulation (via Factor XI) and an inflammatory response (via the kallikrein-kinin system). However, while Factor XII is important for coagulation in vitro, it is not important for physiological hemostasis, so the physiological role of the contact system remains elusive. Using patient blood samples and isolated proteins, we identified a novel class of Factor XII activators. Factor XII was activated by misfolded protein aggregates that formed by denaturation or by surface adsorption, which specifically led to the activation of the kallikreinkinin system without inducing coagulation. Consistent with this, we found that Factor XII, but not Factor XI, was activated and kallikrein was formed in blood from patients with systemic amyloidosis, a disease marked by the accumulation and deposition of misfolded plasma proteins. These results show that the kallikrein-kinin system can be activated by Factor XII, in a process separate from the coagulation cascade, and point to a protective role for Factor XII following activation by misfolded protein aggregates.
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