64 research outputs found
MĂ©todos de manejo de aveia preta para evitar sua ressurgĂȘncia como planta daninha em trigo
Bragatston study protocol: a multicentre cohort study on automated quantification of cardiovascular calcifications on radiotherapy planning CT scans for cardiovascular risk prediction in patients with breast cancer
Introduction Cardiovascular disease (CVD) is an
important cause of death in breast cancer survivors.
Some breast cancer treatments including anthracyclines,
trastuzumab and radiotherapy can increase the risk of
CVD, especially for patients with pre-existing CVD risk
factors. Early identification of patients at increased CVD
risk may allow switching to less cardiotoxic treatments,
active surveillance or treatment of CVD risk factors. One of
the strongest independent CVD risk factors is the presence
and extent of coronary artery calcifications (CAC). In
clinical practice, CAC are generally quantified on ECGtriggered cardiac CT scans. Patients with breast cancer
treated with radiotherapy routinely undergo radiotherapy
planning CT scans of the chest, and those scans could
provide the opportunity to routinely assess CAC before a
potentially cardiotoxic treatment. The Bragatston study
aims to investigate the association between calcifications
in the coronary arteries, aorta and heart valves (hereinafter
called âcardiovascular calcificationsâ) measured
automatically on planning CT scans of patients with breast
cancer and CVD risk.
Methods and analysis In a first step, we will optimise
and validate a deep learning algorithm for automated
quantification of cardiovascular calcifications on
planning CT scans of patients with breast cancer.
Then, in a multicentre cohort study (University Medical
Center Utrecht, Utrecht, Erasmus MC Cancer Institute,
Rotterdam and Radboudumc, Nijmegen, The Netherlands),
the association between cardiovascular calcifications
measured on planning CT scans of patients with breast
cancer (nâ16 000) and incident (non-)fatal CVD events
will be evaluated. To assess the added predictive value of
these calcifications over traditional CVD risk factors and
treatment characteristics, a case-cohort analysis will be
performed among all cohort members diagnosed with a
CVD event during follow-up (nâ200) and a random sample
of the baseline cohort (nâ600).
Ethics and dissemination The Institutional Review
Boards of the participating hospitals decided that the
Medical R
hnRNP A1 proofreads 3' splice site recognition by U2AF.
One of the earliest steps in metazoan pre-mRNA splicing involves binding of U2 snRNP auxiliary factor (U2AF) 65 KDa subunit to the polypyrimidine (Py) tract and of the 35 KDa subunit to the invariant AG dinucleotide at the intron 3' end. Here we use in vitro and in vivo depletion, as well as reconstitution assays using purified components, to identify hnRNP A1 as an RNA binding protein that allows U2AF to discriminate between pyrimidine-rich RNA sequences followed or not by a 3' splice site AG. Biochemical and NMR data indicate that hnRNP A1 forms a ternary complex with the U2AF heterodimer on AG-containing/uridine-rich RNAs, while it displaces U2AF from non-AG-containing/uridine-rich RNAs, an activity that requires the glycine-rich domain of hnRNP A1. Consistent with the functional relevance of this activity for splicing, proofreading assays reveal a role for hnRNP A1 in U2AF-mediated recruitment of U2 snRNP to the pre-mRNA
The three-dimensional structure of the HRDC domain and implications for the Werner and Bloom syndrome proteins
BACKGROUND: The HRDC (helicase and RNaseD Câterminal) domain is found at the C terminus of many RecQ helicases, including the human Werner and Bloom syndrome proteins. RecQ helicases have been shown to unwind DNA in an ATPâdependent manner. However, the specific functional roles of these proteins in DNA recombination and replication are not known. An HRDC domain exists in both of the human RecQ homologues that are implicated in human disease and may have an important role in their function. RESULTS: We have determined the threeâdimensional structure of the HRDC domain in the Saccharomyces cerevisiae RecQ helicase Sgs1p by nuclear magnetic resonance (NMR) spectroscopy. The structure resembles auxiliary domains in bacterial DNA helicases and other proteins that interact with nucleic acids. We show that a positively charged region on the surface of the Sgs1p HRDC domain can interact with DNA. Structural similarities to bacterial DNA helicases suggest that the HRDC domain functions as an auxiliary domain in RecQ helicases. Homology models of the Werner and Bloom HRDC domains show different surface properties when compared with Sgs1p. CONCLUSIONS: The HRDC domain represents a structural scaffold that resembles auxiliary domains in proteins that are involved in nucleic acid metabolism. In Sgs1p, the HRDC domain could modulate the helicase function via auxiliary contacts to DNA. However, in the Werner and Bloom syndrome helicases the HRDC domain may have a role in their functional differences by mediating diverse molecular interaction
Observation and assignment of submillimetre laser lines from CH3OH pumped by isotopic CO2 lasers
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