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- Acciari, V. A., et al.
(author)
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Radio Imaging of the Very-High-Energy gamma-Ray Emission Region in the Central Engine of a Radio Galaxy
- 2009
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 325:5939, s. 444-448
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Journal article (peer-reviewed)abstract
- The accretion of matter onto a massive black hole is believed to feed the relativistic plasma jets found in many active galactic nuclei (AGN). Although some AGN accelerate particles to energies exceeding 10(12) electron volts and are bright sources of very-high-energy (VHE) gamma-ray emission, it is not yet known where the VHE emission originates. Here we report on radio and VHE observations of the radio galaxy Messier 87, revealing a period of extremely strong VHE gamma-ray flares accompanied by a strong increase of the radio flux from its nucleus. These results imply that charged particles are accelerated to very high energies in the immediate vicinity of the black hole.
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| 4. |
- Ahmed, Hanna N., et al.
(author)
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Coffee consumption and risk of heart failure in men : An analysis from the Cohort of Swedish Men
- 2009
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In: American Heart Journal. - : MOSBY-ELSEVIER. - 0002-8703 .- 1097-6744. ; 158:4, s. 667-672
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Journal article (peer-reviewed)abstract
- Background A previous study found that consuming 5 or more cups of coffee per day was associated with increased incidence of heart failure (HF). We sought to evaluate this association in a larger population. Methods We measured coffee consumption using food frequency questionnaires among 37,315 men without history of myocardial infarction, diabetes, or HE They were observed for HF hospitalization or mortality from January 1, 1998, until December 3 1, 2006, using record linkage to the Swedish inpatient and cause of death registries. Cox proportional hazards models adjusted for age, dietary, and demographic factors were used to calculate incidence rate ratios (RR) and 95% confidence intervals (CIs). Results For 9 years of follow-up, 784 men experienced an HF event. Compared to men who drank! l cup of coffee per day (unadjusted rate 29.9 HF events/ 10,000 person-years), RR were 0.87 (95% CI 0.69-1.11, unadjusted rate 29.2/10,000 person-years) for 2 cups/d, 0.89 (95% CI 0.70-1.14, unadjusted rate 25.1/10,000 person-years) for 3 cups/d, 0.89 (95% CI 0.69-1.15, unadjusted rate 25.0/10,000 person-years) for 4 cups/d, and 0.89 (95% CI 0.69-1.15, unadjusted rate 18.1/10,000 person-years) for >= 5 cups/d (P for trend in RR = .61). Conclusions This study did not support the hypothesis that high coffee consumption is associated with increased rates of HF hospitalization or mortality. (Am Heart J 2009;158:667-72.)
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| 5. |
- Carlsson, Hanna, 1979, et al.
(author)
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Psoriasin (S100A7) and calgranulin-B (S100A9) induction is dependent on reactive oxygen species and is downregulated by Bcl-2 and antioxidants
- 2005
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In: Cancer Biol Ther. ; 4:9, s. 998-1005
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Journal article (peer-reviewed)abstract
- S-100 proteins are calcium-binding proteins with important growth regulatory functions. Of these proteins, psoriasin and calgranulin-B have been shown to be highly upregulated in ductal carcinoma in situ (DCIS) of the breast and in psoriasis. The purpose of this study was to further elucidate the functional relevance of the overexpression of these two S-100 proteins in psoriasis and DCIS. We report the induction of both proteins by reactive oxygen species, phorbol ester TPA, and the induction of psoriasin in response to the PI3K inhibitor wortmannin. We also demonstrate that Bcl-2 overexpression represses the induction of psoriasin and calgranulin-B under these different conditions. The same effect was obtained with the antioxidant NAC, which indicates that the suppression of psoriasin and calgranulin-B induction is mediated by the antioxidant function of Bcl-2. Furthermore, we demonstrate that overexpression of a dominant negative IKKbeta also inhibits the induction of psoriasin suggesting that the NFkappaB pathway is involved in the induction of this protein. Also, we found NFkappaB responsive DNA elements in the upstream promoter region of psoriasin. MCF10A cells with a stable retroviral overexpression of psoriasin were significantly more resistant to H2O2-induced cell death than control cells further supporting the hypothesis that these S-100 proteins may play a role in oxidative stress response.
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| 6. |
- Ding, Li, et al.
(author)
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Somatic mutations affect key pathways in lung adenocarcinoma
- 2008
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 455:7216, s. 1069-1075
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Journal article (peer-reviewed)abstract
- Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.
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| 7. |
- Hanna-Mitchell, Ann T, et al.
(author)
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The impact of neurotrophin-3 on the dorsal root transitional zone following injury
- 2008
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In: Spinal Cord. - 1362-4393 .- 1476-5624. ; 46:12, s. 804-810
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Journal article (peer-reviewed)abstract
- Study design: Morphological and Stereological assessment of the dorsal root transitional zone (DRTZ) following complete crush injury, using light microscopy (LM) and transmission electron microscopy (TEM).Objectives: To assess the effect of exogenous neurotrophin-3 (NT-3) on the response of glial cells and axons to dorsal root damage.Setting: Department of Anatomy, University College Cork, Ireland and Department of Physiology, UMDS, University of London, UK.Methods: Cervical roots (C6-8) from rats which had undergone dorsal root crush axotomy 1 week earlier, in the presence (n = 3) and absence (n = 3) of NT-3, were processed for LM and TEM.Results: Unmyelinated axon number and size was greater in the DRTZ proximal ( Central Nervous System; CNS) and distal ( Peripheral Nervous System; PNS) compartments of NT-3-treated tissue. NT-3 was associated with a reduced astrocytic response, an increase in the proportion of oligodendrocytic tissue and a possible inhibition or delay of microglial activation. Disrupted-myelin volume in the DRTZ PNS and CNS compartments of treated tissue was lower, than in control tissue. In the PNS compartment, NT-3 treatment increased phagocyte and blood vessel numbers. It decreased myelinating activity, as sheath thickness was significantly lower and may also account for the noted lower Schwann cell and organelle volume in the test group.Conclusions: Our observations suggest that NT-3 interacts with non-neuronal tissue to facilitate the regenerative effort of damaged axons. This may be as a consequence of a direct action or indirectly mediated by modulation of non-neuronal responses to injury.
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| 8. |
- Krop, I., et al.
(author)
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A putative role for psoriasin in breast tumor progression
- 2005
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In: Cancer Research. ; 65:24, s. 11326-34
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Journal article (peer-reviewed)abstract
- Psoriasin (S100A7) was identifi;ed as a gene highly expressed in psoriatic keratinocytes and highly and more frequently expressed in ductal carcinoma in situ (DCIS) than in invasive breast carcinomas (IBC), suggesting a potential role in tumor progression. Psoriasin expression is associated with poor prognostic factors in both DCIS and IBC. Several putative functions have been proposed for psoriasin in various disease types, but none of these can fully explain its involvement in breast tumor progression. Here, we show that down-regulation of endogenous psoriasin expression via stable short hairpin RNAs in a human IBC cell line (MDA-MB-468) increases cell migration and invasion without influencing cell proliferation and survival in vitro but inhibits tumor growth in vivo. These seemingly paradoxical results are potentially explained by the dramatic up-regulation and down-regulation of matrix metalloproteinase-13 and vascular endothelial growth factor (VEGF), respectively, observed in cells with decreased psoriasin levels compared with controls. Correlating with this, high psoriasin expression in human IBC is associated with increased angiogenesis and worse clinical outcome, and psoriasin mRNA levels are coordinately regulated with VEGF and other genes related to hypoxia and mitochondrial reactive oxygen species (ROS). Based on these results, we propose that psoriasin may play a role in breast tumor progression by promoting angiogenesis and enhancing the selection for cells that overcome its anti-invasive function. This hypothesis may explain why psoriasin expression is highest in high-grade and/or estrogen receptor-negative tumors, as these are associated with increased hypoxia and ROS, a setting in which the angiogenic effects of psoriasin are most important.
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| 9. |
- Murphy, Shaun P, et al.
(author)
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Evidence for participation of uterine natural killer cells in the mechanisms responsible for spontaneous preterm labor and delivery
- 2009
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In: AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY. - : Elsevier BV. - 0002-9378. ; 200:3, s. 308.e1-308.e9
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The purpose of this study was to determine in a mouse model whether uterine natural killer (uNK) cell cytotoxic activation induces infection/inflammation-associated preterm labor and delivery. STUDY DESIGN: Wild type or interleukin (IL)-10(-/-) mice were injected intraperitoneally with lipopolysaccharide on gestational day 14. Mice were either killed for collection of uteroplacental tissue, spleen, and serum or allowed to deliver. Uteroplacental tissue was used for histology and characterization of uNK cells. RESULTS: Low-dose lipopolysaccharide treatment triggered preterm labor and delivery in IL-10(-/-), but not wild type mice, in a manner independent of progesterone levels. Preterm labor and delivery in IL-10(-/-) mice was associated with an increased number and placental infiltration of cytotoxic uNK cells and placental cell death. Depletion of NK cells or tumor necrosis factor (TNF)-alpha neutralization in these mice restored term delivery. Furthermore, TNF-alpha neutralization prevented uNK cell infiltration and placental cell apoptosis. CONCLUSION: The uNK cell-TNF-alpha-IL-10 axis plays an important role in the genesis of infection/inflammation-induced pretermlabor/delivery.
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