1,223 research outputs found
Epstein-Barr virus nuclear antigen 3A protein regulates CDKN2B transcription via interaction with MIZ-1
Get PDFThe Epstein-Barr virus (EBV) nuclear antigen 3 family of protein is critical for the EBV-induced primary B-cell growth transformation process. Using a yeast two-hybrid screen we identified 22 novel cellular partners of the EBNA3s. Most importantly, among the newly identified partners, five are known to play direct and important roles in transcriptional regulation. Of these, the Myc-interacting zinc finger protein-1 (MIZ-1) is a transcription factor initially characterized as a binding partner of MYC. MIZ-1 activates the transcription of a number of target genes including the cell cycle inhibitor CDKN2B. Focusing on the EBNA3A/MIZ-1 interaction we demonstrate that binding occurs in EBV-infected cells expressing both proteins at endogenous physiological levels and that in the presence of EBNA3A, a significant fraction of MIZ-1 translocates from the cytoplasm to the nucleus. Moreover, we show that a trimeric complex composed of a MIZ-1 recognition DNA element, MIZ-1 and EBNA3A can be formed, and that interaction of MIZ-1 with nucleophosmin (NPM), one of its coactivator, is prevented by EBNA3A. Finally, we show that, in the presence of EBNA3A, expression of the MIZ-1 target gene, CDKN2B, is downregulated and repressive H3K27 marks are established on its promoter region suggesting that EBNA3A directly counteracts the growth inhibitory action of MIZ-1
Guidelines for initiation of anti-tumour necrosis factor therapy in rheumatoid arthritis: similarities and differences across Europe.
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The contamination of the surface of Vesta by impacts and the delivery of the dark material
Full text linkThe Dawn spacecraft observed the presence of dark material, which in turn
proved to be associated with OH and H-rich material, on the surface of Vesta.
The source of this dark material has been identified with the low albedo
asteroids, but it is still a matter of debate whether the delivery of the dark
material is associated with a few large impact events, to micrometeorites or to
the continuous, secular flux of impactors on Vesta. The continuous flux
scenario predicts that a significant fraction of the exogenous material
accreted by Vesta should be due to non-dark impactors likely analogous to
ordinary chondrites, which instead represent only a minor contaminant in the
HED meteorites. We explored the continuous flux scenario and its implications
for the composition of the vestan regolith, taking advantage of the data from
the Dawn mission and the HED meteorites. We used our model to show that the
stochastic events scenario and the micrometeoritic flux scenario are natural
consequences of the continuous flux scenario. We then used the model to
estimate the amounts of dark and hydroxylate materials delivered on Vesta since
the LHB and we showed how our results match well with the values estimated by
the Dawn mission. We used our model to assess the amount of Fe and siderophile
elements that the continuous flux of impactors would mix in the vestan
regolith: concerning the siderophile elements, we focused our attention on the
role of Ni. The results are in agreement with the data available on the Fe and
Ni content of the HED meteorites and can be used as a reference frame in future
studies of the data from the Dawn mission and of the HED meteorites. Our model
cannot yet provide an answer to the fate of the missing non-carbonaceous
contaminants, but we discuss possible reasons for this discrepancy.Comment: 31 pages, 7 figures, 4 tables. Accepted for publication on the
journal ICARUS, "Dark and Bright Materials on Vesta" special issu
JAMI: a Java library for molecular interactions and data interoperability.
Get PDFBACKGROUND: A number of different molecular interactions data download formats now exist, designed to allow access to these valuable data by diverse user groups. These formats include the PSI-XML and MITAB standard interchange formats developed by Molecular Interaction workgroup of the HUPO-PSI in addition to other, use-specific downloads produced by other resources. The onus is currently on the user to ensure that a piece of software is capable of read/writing all necessary versions of each format. This problem may increase, as data providers strive to meet ever more sophisticated user demands and data types. RESULTS: A collaboration between EMBL-EBI and the University of Cambridge has produced JAMI, a single library to unify standard molecular interaction data formats such as PSI-MI XML and PSI-MITAB. The JAMI free, open-source library enables the development of molecular interaction computational tools and pipelines without the need to produce different versions of software to read different versions of the data formats. CONCLUSION: Software and tools developed on top of the JAMI framework are able to integrate and support both PSI-MI XML and PSI-MITAB. The use of JAMI avoids the requirement to chain conversions between formats in order to reach a desired output format and prevents code and unit test duplication as the code becomes more modular. JAMI's model interfaces are abstracted from the underlying format, hiding the complexity and requirements of each data format from developers using JAMI as a library
Interest of a systematic screening of comorbidities in chronic inflammatory rheumatisms
Get PDFBackgroundPatients with chronic inflammatory rheumatisms (CIR) have a greater risk of cardiovascular events, infections, lung diseases and osteoporosis. European League against Rheumatisms (EULAR) recommends annual evaluation of the cardiovascular risks.MethodsA program of comorbidity screening was set up in a daily clinic of our Rheumatology department and includes:– rheumatism evaluation;– cardiovascular evaluation; clinical examination, blood tests, modified systematic coronary risk evaluation (mSCORE) calculation, vessel ultrasound and echocardiography;– lung evaluation; self-questionnaires and spirometry;– osteoporosis; bone mineral density and FRAX calculation;– check-up of vaccinal status and the recommended neoplasic screenings.ResultsNinety-two patients already benefited from this systematic screening with 83% (n=76) of rheumatoid arthritis, 11% (n=10) of spondyloarthritis, 3% (n=2) of psoriatic arthritis and 4% (n=4) of other diseases. The mean rheumatism duration was 14±9 years, the mean age was 59±11 years and 64% were women. Hypertension was diagnosed in 8.7% (n=8) of the patients; dyslipidemia in 9.8% (n=9); diabetes in 6.5% (n=6) of the patients. The echocardiography showed significant abnormalities (valvular and hypokinesia) in 9% (n=8) of the patients, a significant supra-aortic vessel stenosis was found in 4.5% (n=4) of the population and an abdominal aortic aneuvrysm was diagnosed in 5.7% (n=5). Among 92 patients, 18.4% (n=14) were estimated at high risk of lethal cardiovascular event with a mSCORE≥5 and 27.5% (n=25) patients were sent to a cardiologist to pursue further cardiovascular investigations. Among these, 8 had a myocardial scintigraphy and all were normal. Moreover, 32.6% (n=30) of the patients were estimated at risk of chronic obstructive pulmonary disease or sleep apnea syndrome and were recommended to consult pneumologist. An anti-osteoporosis drug was introduced in 12% (n=11) of the patients. The update of the vaccinations and the neoplasic screenings were prescribed for respectively 52.7% (n=48) and 35.2% (n=32) of the patients.DiscussionA daily hospitalization for comorbidity screening seems worthy with significant abnormalities discovered in 36.2% of the patients. Further investigations were recommended in 50% of the patients. Patient’ satisfaction and the effective impact of the proposed or prescribed measures are under evaluation
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