1,336 research outputs found
Risk attribution of Campylobacter infection by age group using exposure modelling
Knowledge on the relative importance of alternative sources of human campylobacteriosis is important in order to implement effective disease prevention measures. The objective of this study was to assess the relative importance of three key exposure pathways (travelling abroad, poultry meat, pet contact) for different patient age groups in Switzerland. With a stochastic exposure model data on Campylobacter incidence for the years 2002-2007 were linked with data for the three exposure pathways and the results of a case-control study. Mean values for the population attributable fractions (PAF) over all age groups and years were 27% (95% CI 17-39) for poultry consumption, 27% (95% CI 22-32) for travelling abroad, 8% (95% CI 6-9) for pet contact and 39% (95% CI 25-50) for other risk factors. This model provided robust results when using data available for Switzerland, but the uncertainties remained high. The output of the model could be improved if more accurate input data are available to estimate the infection rate per exposure. In particular, the relatively high proportion of cases attributed to ‘other risk factors' requires further attentio
Overexpression of melanoma inhibitory activity (MIA) enhances extravasation and metastasis of A-mel 3 melanoma cells in vivo
The secreted MIA protein is strongly expressed by advanced primary and metastatic melanomas but not in normal melanocytes. Previous studies have shown that MIA serum levels correlate with clinical tumour progression in melanoma patients. To provide direct evidence that MIA plays a role in metastasis of malignant melanomas, A-mel 3 hamster melanoma cells were transfected with sense- and antisense rhMIA cDNA and analysed subsequently for changes in their tumorigenic and metastatic potential. Enforced expression of MIA in A-mel 3 cells significantly increased their metastatic potential without affecting primary tumour growth, cell proliferation or apoptosis rate in hamsters, compared with control or antisense transfected cells. Additionally, MIA overexpressing transfectants showed a higher rate of both tumour cell invasion and extravasation. Cells transfected with MIA antisense generally exerted an opposite response. The above changes in function attributed to the expression of MIA may underlie the contribution of MIA to the malignant phenotype. © 2000 Cancer Research Campaig
Mutations in the 3'-untranslated region of GATA4 as molecular hotspots for congenital heart disease (CHD)
<p>Abstract</p> <p>Background</p> <p>The 3'-untranslated region (3'-UTR) of mRNA contains regulatory elements that are essential for the appropriate expression of many genes. These regulatory elements are involved in the control of nuclear transport, polyadenylation status, subcellular targetting as well as rates of translation and degradation of mRNA. Indeed, 3'-UTR mutations have been associated with disease, but frequently this region is not analyzed. To gain insights into congenital heart disease (CHD), we have been analyzing cardiac-specific transcription factor genes, including <it>GATA4</it>, which encodes a zinc finger transcription factor. Germline mutations in the coding region of <it>GATA4 </it>have been associated with septation defects of the human heart, but mutations are rather rare. Previously, we identified 19 somatically-derived zinc finger mutations in diseased tissues of malformed hearts. We now continued our search in the 609 bp 3'-UTR region of <it>GATA4 </it>to explore further molecular avenues leading to CHD.</p> <p>Methods</p> <p>By direct sequencing, we analyzed the 3'-UTR of <it>GATA4 </it>in DNA isolated from 68 formalin-fixed explanted hearts with complex cardiac malformations encompassing ventricular, atrial, and atrioventricular septal defects. We also analyzed blood samples of 12 patients with CHD and 100 unrelated healthy individuals.</p> <p>Results</p> <p>We identified germline and somatic mutations in the 3'-UTR of <it>GATA4</it>. In the malformed hearts, we found nine frequently occurring sequence alterations and six dbSNPs in the 3'-UTR region of <it>GATA4</it>. Seven of these mutations are predicted to affect RNA folding. We also found further five nonsynonymous mutations in exons 6 and 7 of <it>GATA4</it>. Except for the dbSNPs, analysis of tissue distal to the septation defect failed to detect sequence variations in the same donor, thus suggesting somatic origin and mosaicism of mutations. In a family, we observed c.+119A > T in the 3'-UTR associated with ASD type II.</p> <p>Conclusion</p> <p>Our results suggest that somatic <it>GATA4 </it>mutations in the 3'-UTR may provide an additional molecular rationale for CHD.</p
Arene oxidation with malonoyl peroxides
Malonoyl peroxide 7, prepared in a single step from the commercially available diacid, is an effective reagent for the
oxidation of aromatics. Reaction of an arene with peroxide 7 at room temperature leads to the corresponding protected phenol
which can be unmasked by aminolysis. An ionic mechanism consistent with the experimental findings and supported by isotopic
labeling, Hammett analysis, EPR investigations and reactivity profile studies is proposed
Exponential Distribution of Locomotion Activity in Cell Cultures
In vitro velocities of several cell types have been measured using computer
controlled video microscopy, which allowed to record the cells' trajectories
over several days. On the basis of our large data sets we show that the
locomotion activity displays a universal exponential distribution. Thus, motion
resulting from complex cellular processes can be well described by an
unexpected, but very simple distribution function. A simple phenomenological
model based on the interaction of various cellular processes and finite ATP
production rate is proposed to explain these experimental results.Comment: 4 pages, 3 figure
Measurement of the Luminosity in the ZEUS Experiment at HERA II
The luminosity in the ZEUS detector was measured using photons from electron
bremsstrahlung. In 2001 the HERA collider was upgraded for operation at higher
luminosity. At the same time the luminosity-measuring system of the ZEUS
experiment was modified to tackle the expected higher photon rate and
synchrotron radiation. The existing lead-scintillator calorimeter was equipped
with radiation hard scintillator tiles and shielded against synchrotron
radiation. In addition, a magnetic spectrometer was installed to measure the
luminosity independently using photons converted in the beam-pipe exit window.
The redundancy provided a reliable and robust luminosity determination with a
systematic uncertainty of 1.7%. The experimental setup, the techniques used for
luminosity determination and the estimate of the systematic uncertainty are
reported.Comment: 25 pages, 11 figure
A New 76Ge Double Beta Decay Experiment at LNGS
This Letter of Intent has been submitted to the Scientific Committee of the
INFN Laboratori Nazionali del Gran Sasso (LNGS) in March 2004. It describes a
novel facility at the LNGS to study the double beta decay of 76Ge using an
(optionally active) cryogenic fluid shield. The setup will allow to scrutinize
with high significance on a short time scale the current evidence for
neutrinoless double beta decay of 76Ge using the existing 76Ge diodes from the
previous Heidelberg-Moscow and IGEX experiments. An increase in the lifetime
limit can be achieved by adding more enriched detectors, remaining thereby
background-free up to a few 100 kg-years of exposure.Comment: 67 pages, 19 eps figures, 17 tables, gzipped tar fil
Earnings Shocks and Tax-Motivated Income-Shifting: Evidence from European Multinationals
Procedure for short-lived particle detection in the OPERA experiment and its application to charm decays
The OPERA experiment, designed to perform the first observation of oscillations in appearance mode through the detection of
the leptons produced in charged current interactions, has
collected data from 2008 to 2012. In the present paper, the procedure developed
to detect particle decays, occurring over distances of the order of 1 mm
from the neutrino interaction point, is described in detail. The results of its
application to the search for charmed hadrons are then presented as a
validation of the methods for appearance detection
Combined Single-Cell Functional and Gene Expression Analysis Resolves Heterogeneity within Stem Cell Populations.
Heterogeneity within the self-renewal durability of adult hematopoietic stem cells (HSCs) challenges our understanding of the molecular framework underlying HSC function. Gene expression studies have been hampered by the presence of multiple HSC subtypes and contaminating non-HSCs in bulk HSC populations. To gain deeper insight into the gene expression program of murine HSCs, we combined single-cell functional assays with flow cytometric index sorting and single-cell gene expression assays. Through bioinformatic integration of these datasets, we designed an unbiased sorting strategy that separates non-HSCs away from HSCs, and single-cell transplantation experiments using the enriched population were combined with RNA-seq data to identify key molecules that associate with long-term durable self-renewal, producing a single-cell molecular dataset that is linked to functional stem cell activity. Finally, we demonstrated the broader applicability of this approach for linking key molecules with defined cellular functions in another stem cell system.Work in the author’s laboratory is supported by grants from the Leukaemia and Lymphoma Research, the Medical Research Council, Cancer Research UK, Biotechnology and Biological Sciences Research Council, Leukemia Lymphoma Society, and the National Institute for Health Research Cambridge Biomedical Research Centre and core support grants by the Wellcome Trust to the Cambridge Institute for Medical Research and Wellcome Trust-MRC Cambridge Stem Cell Institute. D.G.K. is the recipient of a Canadian Institutes of Health Research Postdoctoral Fellowship. F.B. and F.J.T. are funded by the European Research Council (starting grant “LatentCauses”). For funding for the open access charge, the core support grant was provided by the Wellcome Trust-MRC Cambridge Stem Cell Institute. We acknowledge the support of the University of Cambridge, Cancer Research UK Institute (core grant C14303/A17197), and Hutchison Whampoa Limited.This is the final published version. It first appeared at http://www.cell.com/cell-stem-cell/abstract/S1934-5909%2815%2900162-9
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