| 1. |
- Couch, Fergus J., et al.
(author)
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AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A consortium of investigators of modifiers of BRCA1/2 study
- 2007
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In: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 16:7, s. 1416-1421
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Journal article (peer-reviewed)abstract
- The AURKA oncogene is associated with abnormal chromosome segregation and aneuploidy and predisposition to cancer. Amplification of AURKA has been detected at higher frequency in tumors from BRCA1 and BRCA2 mutation carriers than in sporadic breast tumors, suggesting that overexpression of AURKA and inactivation of BRCA1 and BRCA2 cooperate during tumor development and progression. The F31I polymorphism in AURKA has been associated with breast cancer risk in the homozygous state in prior studies. We evaluated whether the AURKA F31I polymorphism modifies breast cancer risk in BRCA1 and BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2. Consortium of Investigators of Modifiers of BRCA1/2 was established to provide sufficient statistical power through increased numbers of mutation carriers to identify polymorphisms that act as modifiers of cancer risk and can refine breast cancer risk estimates in BRCA1 and BRCA2 mutation carriers. A total of 4,935 BRCA1 and 2,241 BRCA2 mutation carriers and 11 individuals carrying both BRCA1 and BRCA2 mutations was genotyped for F31I. Overall, homozygosity for the 311 allele was not significantly associated with breast cancer risk in BRCA1 and BRCA2 carriers combined [hazard ratio (HR), 0.91; 95% confidence interval (95% CI), 0.77-1.061. Similarly, no significant association was seen in BRCA1 (HR, 0.90; 95% Cl, 0.75-1.08) or BRCA2 carriers (HR, 0.93; 95% CI, 0.67-1.29) or when assessing the modifying effects of either bilateral prophylactic oophorectomy or menopausal status of BRCA1 and BRCA2 carriers. In summary, the F31I polymorphism in AURKA is not associated with a modified risk of breast cancer in BRCA1 and BRCA2 carriers.
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| 2. |
- Ammoun, Sylwia, et al.
(author)
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OX1 orexin receptors activate extracellular signal-regulated kinase in Chinese hamster ovary cells via multiple mechanisms : the role of Ca2+ influx in OX1 receptor signaling
- 2006
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In: Molecular Endocrinology. - : The Endocrine Society. - 0888-8809 .- 1944-9917. ; 20:1, s. 80-99
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Journal article (peer-reviewed)abstract
- Activation of OX1 orexin receptors heterologously expressedin Chinese hamster ovary (CHO) cells led to a rapid, strong,and long-lasting increase in ERK phosphorylation (activation).Dissection of the signal pathways to ERK using multiple inhibitorsand dominant-negative constructs indicated involvement of Ras,protein kinase C, phosphoinositide-3-kinase, and Src. Most interestingly,Ca2+ influx appeared central for the ERK response in CHO cells,and the same was indicated in recombinant neuro-2a cells andcultured rat striatal neurons. Detailed investigations in CHOcells showed that inhibition of the receptor- and store-operatedCa2+ influx pathways could fully attenuate the response, whereasinhibition of the store-operated Ca2+ influx pathway alone orthe Ca2+ release was ineffective. If the receptor-operated pathwaywas blocked, an exogenously activated store-operated pathwaycould take its place and restore the coupling of OX1 receptorsto ERK. Further experiments suggested that Ca2+ influx, as such,may not be required for ERK phosphorylation, but that Ca2+,elevated via influx, acts as a switch enabling OX1 receptorsto couple to cascades leading to ERK phosphorylation, cAMP elevation,and phospholipase C activation. In conclusion, the data suggestthat the primary coupling of orexin receptors to Ca2+ influxallows them to couple to other signal pathways; in the absenceof coupling to Ca2+ influx, orexin receptors can act as signalintegrators by taking advantage of other Ca2+ influx pathways.
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| 3. |
- Brose, Ulrich, et al.
(author)
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Body sizes of consumers and their resources
- 2005
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In: Ecology. - : Ecological Society of America. - 0012-9658 .- 1939-9170. ; 86:9, s. 2545-2545
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Journal article (peer-reviewed)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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| 6. |
- Hernandez-Andrade, E., et al.
(author)
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Changes in regional fetal cerebral blood flow perfusion in relation to hemodynamic deterioration in severely growth-restricted fetuses
- 2008
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In: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 32:1, s. 71-76
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Journal article (peer-reviewed)abstract
- Objectives To study regional cerebral blood perfusion with power Doppler ultrasound (PDU) imaging in appropriate-for-gestational age (AGA) fetuses and those with intrauterine growth restriction (IUGR) at different hemodynamic stages of fetal deterioration. Methods Brain blood perfusion was studied with PDU imaging, and the fractional moving blood volume (FMB V) was estimated in 56 growth-restricted and 56 AGA matched fetuses at 26-32 weeks of gestation. Fetuses with IUGR were classified according to progressi. on of hemodynamic deterioration as follows: Group 1, abnormal umbilical artery (UA) pulsatility index (PI) (mean > 2 SD, n = 13); Group 2, abnormal UA-PI and middle cerebral artery (MCA) PI (mean < 2 SD, n = IS); Group 3, abnormal UA-PI, MCA-PI and ductus venosus (D V) PI (mean > 2 SD) but atrial (a-wave) flow present (n = 16); and Group 4, absent or reversed DV atrial flow (n = 12). FMBV was calculated in the complete mid-sagittal, frontal, basal ganglia and cerebellar regions. Results In all growth-restricted fetuses, FMBV was significantly increased in all regions. Fetuses in Group 1 showed considerable increments in FMBV values in the frontal, complete mid-sagittal and cerebellar regions, and a mild increase in the basal ganglia. From Groups 2 to 4, there was a steady reduction (compared with Group 1) in frontal FMBV values (F = 3.25, P = 0.027) together with a significant increment in the basal ganglia values (F = 11.61, P < 0.001). A trend for increasing FMBV values was also observed in the cerebellum, whereas a decreasing trend was noted in the complete mid-sagittal area. Conclusions Brain perfusion in growth-restricted fetuses shows clear regional variations, which change with progression of hemodynamic deterioration. After an initial and early increase in the frontal area, progression of fetal deterioration was rapidly associated with a pronounced decrease in frontal perfusion, together with an increase towards the basal ganglia. Copyright (c) 2008 ISUOG. Published by John Wiley & Sons, Ltd.
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| 7. |
- Hernandez-Andrade, E., et al.
(author)
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Evaluation of fetal regional cerebral blood perfusion using power Doppler ultrasound and the estimation of fractional moving blood volume
- 2007
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In: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 29:5, s. 556-561
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Journal article (peer-reviewed)abstract
- Objective To standardize the evaluation of regional fetal brain blood perfusion, using power Doppler ultrasound (PDU) to estimate the fractional moving blood volume (FMBV) and to evaluate the reproducibility of this estimation. Methods Brain blood perfusion was evaluated in 35 normally grown fetuses at 28-30 weeks of gestation, using PDU. The following cerebral regions were included in the PDU color box: anterior sagittal, complete sagittal, basal ganglia, and cerebellar. Ten consecutive good-quality images of each anatomical plane were recorded and the delimitation of the region of interest (ROI) was performed off-line. FMBV was quantified in the ROI of all images and the mean considered as the final value. Differences between regions, variability, reproducibility and agreement between observers were assessed. Results Power Doppler images of the described anatomical planes were obtained in all cases, regardless of fetal position. The median time for the acquisition of the images was 7 (range 4-12) min. Mean (range) FMBV values were: anterior sagittal, 16.5 (10.7-22.8)%, inter-patient coefficient of variation (CV) 0.22; complete sagittal, 13.5 (8.8-.16.1)%, CV 0.27; basal ganglia, 18.3 (10.7-27.6) %, CV 0.27; and cerebellar, 6.6 (3.0-11.0) %, CV 0.38. There were statistically significant differences in FMBV between cerebellar and complete sagittal ROIs with the frontal and basal ganglia regions. Reproducibility analyses showed an intraclass correlation coefficient of 0.91 (95% CI 0.67-0.97) and an interclass correlation coefficient of 0.87 (95% CI 0.70-0.94). Interobserver agreement showed a mean difference between observers of -0.2 (SD 2.7) with 95% limits of agreement -5.6 to 5.2. Conclusions When the regions of interest are well defined, the FMBV estimate offers a method to quantify blood flow perfusion in different fetal cerebral areas. There appear to be regional differences in FMBV within the fetal brain. Copyright (c) 2007 ISUOG. Published by John Wiley & Sons, Ltd.
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| 8. |
- Huttunen, Roope J., et al.
(author)
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Quantitative detection of cell surface protein expression by time-resolved fluorimetry
- 2007
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In: Luminescence. - : Wiley. - 1522-7243 .- 1522-7235. ; 22:3, s. 163-170
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Journal article (peer-reviewed)abstract
- A method is introduced for quantitative detection of cell surface protein expression. The method is based on immunocytochemistry, the use of long decay time europium(III) chelate and platinum(II) porphyrin labels, and detection of photoluminescence emission from adhered cells by time-resolved fluorimetry. After immunocytochemistry, the assay wells are evaporated to dryness and measured in the dry state. This protocol allows repeated and postponed analysis and microscopy imaging. In order to investigate the performance of the method, we chose expression of intercellular adhesion molecule-1 (ICAM-1) of endothelial cell line EAhy926 as a research target. The expression of ICAM-1 on the cells was enhanced by introduction of a cytokine, tumour necrosis factor-alpha (TNF alpha). The method gave signal: background ratios (S:B) of 20 and 9 for europium and platinum labels, respectively, whereas prompt fluorescent FITC label gave a S:13 of 3. Screening window coefficients (=Z'-factor) were >0.5 for all the three labels, thus indicating a score for an excellent screening assay. In conclusion, the method appears to be an appropriate choice for protein expression analysis, both in high-throughput screening applications, and for detailed sample investigation by fluorescent microscopy imaging. Copyright (C) 2007 John Wiley & Sons, Ltd.
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| 10. |
- Saetre, Peter, et al.
(author)
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The genetic contribution to canine personality.
- 2006
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In: Genes, Brain and Behavior. - 1601-1848 .- 1601-183X. ; 5:3, s. 240-8
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Journal article (peer-reviewed)abstract
- The domestic dog may be exceptionally well suited for behavioral genetic studies owing to its population history and the striking behavior differences among breeds. To explore to what extent and how behavioral traits are transmitted between generations, heritabilities and genetic correlations for behavioral traits were estimated in a cohort containing over 10,000 behaviorally tested German shepherd and Rottweiler dogs. In both breeds, the pattern of co-inheritance was found to be similar for the 16 examined behavioral traits. Furthermore, over 50% of the additive genetic variation of the behavioral traits could be explained by one underlying principal component, indicating a shared genetic component behind most of the examined behavioral traits. Only aggression appears to be inherited independently of the other traits. The results support a genetic basis for a broad personality trait previously named shyness-boldness dimension, and heritability was estimated to be 0.25 in the two breeds. Therefore, breeds of dogs appear to constitute a valuable resource for behavioral genetic research on the normal behavioral differences in broad personality traits.
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