1,721,144 research outputs found
Expression in T-cells of the proapoptotic protein p66SHC is controlled by promoter demethylation.
No full textp66Shc plays a key role in oxidative stress-induced apoptosis. p66Shc gene expression is tissue-specific and controlled by promoter methylation. In T-cells p66Shc expression is induced by a variety of apoptotic stimuli. We have addressed the mechanisms regulating p66Shc expression in T-cells. We show that the increase in p66Shc protein following stimulation with a Ca2+ ionophore results from enhanced gene expression, which is primarily dependent on DNA replication-independent promoter demethylation. Our data underline the role of CpG methylation in the control of p66Shc gene expression and provide evidence that Ca2+ signaling may lead to epigenetic modifications in nondividing cells.
Ó 2006 Elsevier Inc. All rights reserved
The concurrent use of N-and C-terminal antibodies anti-nucleophosmin 1 in immunofluorescence experiments allows for precise assessment of its subcellular localisation in acute myeloid leukaemia patients
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An intrabody specific for the nucleophosmin carboxy-terminal mutant and fused to a nuclear localization sequence binds its antigen but fails to relocate it in the nucleus
No full textThe cytoplasmic accumulation of NPM1 (NPMc+) is found in acute myeloid leukemia (AML) with NPM1 mutation. NPM1 must shuttle between nucleus and cytoplasm to assure physiological protein synthesis and, therefore, the elimination of NPMc+ is not a suitable therapeutic option. We isolated, characterized, and produced a functional scFv intrabody fused to nuclear localization signal(s) (NLS) that does not recognize NPM1 but binds to the mutant-specific C-terminal NES (nuclear export signal) of NPMc+, responsible for its cytoplasmic accumulation. The scFv-NLS fusion accumulated in the nuclei of wild type cells and strongly bound to its antigen in the cytoplasm of NPMc+ expressing cells. However, it failed to relocate the majority of NPMc+ in the nucleus, even when fused to four NLS. Our results show the technical feasibility of producing recombinant intrabodies with defined sub-cellular targeting and nuclear accumulation but the lack of information concerning the features that confer variable strength to the signal peptides impairs the development of biomolecules able to counteract pathological sub-cellular distribution of shuttling proteins. © 2014 The Authors
N-Hydroxycinnamoylamides and related compounds as inhibitors of histone deacetylases, their preparation, pharmaceutical compositions, and use in therapy
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Isolation of cDNAs encoding finger proteins and measurement of the corresponding mRNA levels during myeloid terminal differentiation
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Quantifying geographical accessibility to cancer clinical trials in different income landscapes
Full text linkBackground
Clinical trials are increasingly perceived as a therapeutic opportunity for cancer patients. Favoring their concentration in few high-expertise academic centers maximizes quality of data collection but poses an issue of access equality. Analytical tools to quantify trial accessibility are needed to rationalize resources.
Materials and methods
We constructed a distance-based accessibility index (dAI) using publicly available data on demographics, cancer incidence and trials. Multiple strategies were applied to mitigate or quantify clear sources of bias: reporting biases by text mining multiple registries; reliability of simple geographical distance by comparison with high-quality travel cost data for Italy; index inflation due to highly heterogeneous cancer incidence by log-transformation. We studied inequalities by Gini index and time trend significance by Mann–Kendall test. We simulated different resource allocation models in representative countries and identified locations where new studies would maximally improve the national index.
Results
The dAI approximated well a more realistic but not widely applicable travel cost-based index. Accessibility was unevenly distributed across and within countries (Gini index ∼0.75), with maximal inequalities in high- and upper-middle-income countries (China, United States, Russian Federation). Over time, accessibility increased but less than the total number of trials, most evidently in upper-middle-income countries. Simulations in representative countries (Italy and Serbia) identified ideal locations able to maximally raise the national index.
Conclusions
Access to clinical trials is highly uneven across and within countries and is not mitigated by simple increase in the number of trials; a rational algorithmic approach can be used to mitigate inequalities
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