470 research outputs found
Recurrent chromosome 22 deletions in osteoblastoma affect inhibitors of the wnt/beta-catenin signaling pathway.
Osteoblastoma is a bone forming tumor with histological features highly similar to osteoid osteoma; the discrimination between the tumor types is based on size and growth pattern. The vast majority of osteoblastomas are benign but there is a group of so-called aggressive osteoblastomas that can be diagnostically challenging at the histopathological level. The genetic aberrations required for osteoblastoma development are not known and no genetic difference between conventional and aggressive osteoblastoma has been reported. In order to identify recurrent genomic aberrations of importance for tumor development we applied cytogenetic and/or SNP array analyses on nine conventional and two aggressive osteoblastomas. The conventional osteoblastomas showed few or no acquired genetic aberrations while the aggressive tumors displayed heavily rearranged genomes. In one of the aggressive osteoblastomas, three neighboring regions in chromosome band 22q12 were homozygously deleted. Hemizygous deletions of these regions were found in two additional cases, one aggressive and one conventional. In total, 10 genes were recurrently and homozygously lost in osteoblastoma. Four of them are functionally involved in regulating osteogenesis and/or tumorigenesis. MN1 and NF2 have previously been implicated in the development of leukemia and solid tumors, and ZNRF3 and KREMEN1 are inhibitors of the Wnt/beta-catenin signaling pathway. In line with deletions of the latter two genes, high beta-catenin protein expression has previously been reported in osteoblastoma and aberrations affecting the Wnt/beta-catenin pathway have been found in other bone lesions, including osteoma and osteosarcoma
On the Location of the Gamma-ray Emission in the 2008 Outburst in the BL Lacertae Object AO 0235+164 through Observations across the Electromagnetic Spectrum
We present observations of a major outburst at centimeter, millimeter,
optical, X-ray, and gamma-ray wavelengths of the BL Lacertae object AO
0235+164. We analyze the timing of multi-waveband variations in the flux and
linear polarization, as well as changes in Very Long Baseline Array (VLBA)
images at 7mm with 0.15 milliarcsecond resolution. The association of the
events at different wavebands is confirmed at high statistical significance by
probability arguments and Monte-Carlo simulations. A series of sharp peaks in
optical linear polarization, as well as a pronounced maximum in the 7 mm
polarization of a superluminal jet knot, indicate rapid fluctuations in the
degree of ordering of the magnetic field. These results lead us to conclude
that the outburst occurred in the jet both in the quasi-stationary "core" and
in the superluminal knot, both parsecs downstream of the supermassive black
hole. We interpret the outburst as a consequence of the propagation of a
disturbance, elongated along the line of sight by light-travel time delays,
that passes through a standing recollimation shock in the core and propagates
down the jet to create the superluminal knot. The multi-wavelength light curves
vary together on long time-scales (months/years), but the correspondence is
poorer on shorter time-scales. This, as well as the variability of the
polarization and the dual location of the outburst, agrees with the
expectations of a multi-zone emission model in which turbulence plays a major
role in modulating the synchrotron and inverse Compton fluxes.Comment: Accepted for Publication in the Astrophysical Journal Letters. 7
pages (including 5 figures). Minor corrections with regard to previous
version, as proposed by the refere
Glucosylsphingosine Is a Highly Sensitive and Specific Biomarker for Primary Diagnostic and Follow-Up Monitoring in Gaucher Disease in a Non-Jewish, Caucasian Cohort of Gaucher Disease Patients
Gaucher disease (GD) is the most common lysosomal storage disorder (LSD). Based on a deficient ÎČ-glucocerebrosidase it leads to an accumulation of glucosylceramide. Standard diagnostic procedures include measurement of enzyme activity, genetic testing as well as analysis of chitotriosidase and CCL18/PARC as biomarkers. Even though chitotriosidase is the most well-established biomarker in GD, it is not specific for GD. Furthermore, it may be false negative in a significant percentage of GD patients due to mutation. Additionally, chitotriosidase reflects the changes in the course of the disease belatedly. This further enhances the need for a reliable biomarker, especially for the monitoring of the disease and the impact of potential treatments.Here, we evaluated the sensitivity and specificity of the previously reported biomarker Glucosylsphingosine with regard to different control groups (healthy control vs. GD carriers vs. other LSDs).Only GD patients displayed elevated levels of Glucosylsphingosine higher than 12 ng/ml whereas the comparison controls groups revealed concentrations below the pathological cut-off, verifying the specificity of Glucosylsphingosine as a biomarker for GD. In addition, we evaluated the biomarker before and during enzyme replacement therapy (ERT) in 19 patients, demonstrating a decrease in Glucosylsphingosine over time with the most pronounced reduction within the first 6 months of ERT. Furthermore, our data reveals a correlation between the medical consequence of specific mutations and Glucosylsphingosine.In summary, Glucosylsphingosine is a very promising, reliable and specific biomarker for GD
Mutations in components of complement influence the outcome of Factor I-associated atypical hemolytic uremic syndrome
Genetic studies have shown that mutations of complement inhibitors such as membrane cofactor protein, Factors H, I, or B and C3 predispose patients to atypical hemolytic uremic syndrome (aHUS). Factor I is a circulating serine protease that inhibits complement by degrading C3b and up to now only a few mutations in the CFI gene have been characterized. In a large cohort of 202 patients with aHUS, we identified 23 patients carrying exonic mutations in CFI. Their overall clinical outcome was unfavorable, as half died or developed end-stage renal disease after their first syndrome episode. Eight patients with CFI mutations carried at least one additional known genetic risk factor for aHUS, such as a mutation in MCP, CFH, C3 or CFB; a compound heterozygous second mutation in CFI; or mutations in both the MCP and CFH genes. Five patients exhibited homozygous deletion of the Factor H-related protein 1 (CFHR-1) gene. Ten patients with aHUS had one mutation in their CFI gene (Factor I-aHUS), resulting in a quantitative or functional Factor I deficiency. Patients with a complete deletion of the CFHR-1 gene had a significantly higher risk of a bad prognosis compared with those with one Factor I mutation as their unique vulnerability feature. Our results emphasize the necessity of genetic screening for all susceptibility factors in patients with aHUS
Location of the Gamma-Ray Flaring Emission in the Parse-Scale Jet of the BL Lac Object AO 0235+164
We locate the gamma-ray and lower frequency emission in flares of the BL Lac
object AO 0235+164 at >12pc in the jet of the source from the central engine.
We employ time-dependent multi-spectral-range flux and linear polarization
monitoring observations, as well as ultra-high resolution (~0.15
milliarcsecond) imaging of the jet structure at lambda=7mm. The time
coincidence in the end of 2008 of the propagation of the brightest superluminal
feature detected in AO 0235+164 (Qs) with an extreme multi-spectral-range
(gamma-ray to radio) outburst, and an extremely high optical and 7mm (for Qs)
polarization degree provides strong evidence supporting that all these events
are related. This is confirmed at high significance by probability arguments
and Monte-Carlo simulations. These simulations show the unambiguous correlation
of the gamma-ray flaring state in the end of 2008 with those in the optical,
millimeter, and radio regime, as well as the connection of a prominent X-ray
flare in October 2008, and of a series of optical linear polarization peaks,
with the set of events in the end of 2008. The observations are interpreted as
the propagation of an extended moving perturbation through a re-collimation
structure at the end of the jet's acceleration and collimation zone.Comment: To be published in the proceedings of High Energy Phenomena in
Relativistic Outflows III (HEPRO III, IJMPCS). 6 page
Crossing the Dripline to 11N Using Elastic Resonance Scattering
The level structure of the unbound nucleus 11N has been studied by 10C+p
elastic resonance scattering in inverse geometry with the LISE3 spectrometer at
GANIL, using a 10C beam with an energy of 9.0 MeV/u. An additional measurement
was done at the A1200 spectrometer at MSU. The excitation function above the
10C+p threshold has been determined up to 5 MeV. A potential-model analysis
revealed three resonance states at energies 1.27 (+0.18-0.05) MeV (Gamma=1.44
+-0.2 MeV), 2.01(+0.15-0.05) MeV, (Gamma=0.84 +-$0.2 MeV) and 3.75(+-0.05) MeV,
(Gamma=0.60 +-0.05 MeV) with the spin-parity assignments I(pi) =1/2+, 1/2- and
5/2+, respectively. Hence, 11N is shown to have a ground state parity inversion
completely analogous to its mirror partner, 11Be. A narrow resonance in the
excitation function at 4.33 (+-0.05) MeV was also observed and assigned
spin-parity 3/2-.Comment: 14 pages, 9 figures, twocolumn Accepted for publication in PR
Deep phenotyping of the unselected COPSAC2010 birth cohort study
BACKGROUND: We hypothesize that perinatal exposures, in particular the human microbiome and maternal nutrition during pregnancy, interact with the genetic predisposition to cause an abnormal immune modulation in early life towards a trajectory to chronic inflammatory diseases such as asthma and others. OBJECTIVE: The aim of this study is to explore these interactions by conducting a longitudinal study in an unselected cohort of pregnant women and their offspring with emphasis on deep clinical phenotyping, exposure assessment, and biobanking. Exposure assessments focus on the human microbiome. Nutritional intervention during pregnancy in randomized controlled trials are included in the study to prevent disease and to be able to establish causal relationships. METHODS: Pregnant women from eastern Denmark were invited during 2008â2010 to a novel unselected âCOPSAC(2010)â cohort. The women visited the clinic during pregnancy weeks 24 and 36. Their children were followed at the clinic with deep phenotyping and collection of biological samples at nine regular visits until the age of 3 and at acute symptoms. Randomized controlled trials of highâdose vitamin D and fish oil supplements were conducted during pregnancy, and a trial of azithromycin for acute lung symptoms was conducted in the children with recurrent wheeze. RESULTS: Seven hundred and thirtyâeight mothers were recruited from week 24 of gestation, and 700 of their children were included in the birth cohort. The cohort has an overârepresentation of atopic parents. The participant satisfaction was high and the adherence equally high with 685 children (98%) attending the 1 year clinic visit and 667 children (95%) attending the 2 year clinic visit. CONCLUSIONS: The COPSAC(2010) birth cohort study provides longitudinal clinical followâup with highly specific endâpoints, exposure assessments, and biobanking. The cohort has a high adherence rate promising strong data to elucidate the interaction between genomics and the exposome in perinatal life leading to lifestyleârelated chronic inflammatory disorders such as asthma
Projectile Coulomb excitation with fast radioactive beams
5 pages, 5 figures, 1 table.-- PACS nrs.: 23.20.Ck; 27.20.+n.We report a search for γ rays emanating from Coulomb excitation of fast (30-46 MeV/u) radioactive projectiles He-8, Be-11, Be-12, Be-14 interacting with a lead target. These are clearly identified by their Doppler shift. The 320 keV 1/2(-) --> 1/2(+)γ transition from Be-11 was observed with a cross-section of 191 ± 26 mb which is noticeably less than expected from the known lifetime and in the perturbation limit of pure Coulomb excitation. In the other nuclei rather stringent upper limits of 0.01 to 0.2 Weisskopf units, are placed on the hypothetical transition to 1(-) states.We would like to thank F. Geoffroy, R. Hue and L. Petizon for their technical assistance during the experiment, N. Alamanos, G. Baur aud C. Bertulani for discussions and R. Lombard for drawing our attention to the Bertlmann-Martin bound. This work was partly supported by la Région Basse Normandie. One of us, G. Schrieder,
would like to thank for the support by the German Federal Minister for Research and Technology (BMFT) under contract 06DA641.Peer reviewe
Consumption of predefined 'Nordic' dietary items in ten European countries - an investigation in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
Health-beneficial effects of adhering to a healthy Nordic diet index have been suggested. However, it has not been examined to what extent the included dietary components are exclusively related to the Nordic countries or if they are part of other European diets as well, suggesting a broader preventive potential. The present study describes the intake of seven a priori defined healthy food items (apples/pears, berries, cabbages, dark bread, shellfish, fish and root vegetables) across ten countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) and examines their consumption across Europe
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