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1.  BioJS DAGViewer: A reusable JavaScript component for displaying directed graphs 
F1000Research  2014;3:51.
Summary: The DAGViewer BioJS component is a reusable JavaScript component made available as part of the BioJS project and intended to be used to display graphs of structured data, with a particular emphasis on Directed Acyclic Graphs (DAGs). It enables users to embed representations of graphs of data, such as ontologies or phylogenetic trees, in hyper-text documents (HTML). This component is generic, since it is capable (given the appropriate configuration) of displaying any kind of data that is organised as a graph. The features of this component which are useful for examining and filtering large and complex graphs are described.
Availability: http://github.com/alexkalderimis/dag-viewer-biojs; http://github.com/biojs/biojs; http://dx.doi.org/10.5281/zenodo.8303.
doi:10.12688/f1000research.3-51.v1
PMCID: PMC3945768  PMID: 24627804
3.  Epidermal Growth Factor Regulates Hematopoietic Regeneration Following Radiation Injury 
Nature medicine  2013;19(3):295-304.
The mechanisms which regulate HSC regeneration following myelosuppressive injury are not well understood. We identified epidermal growth factor (EGF) to be highly enriched in the bone marrow (BM) serum of mice bearing deletion of Bak and Bax in Tie2+ cells (Tie2Cre;Bak1−/−;Baxfl/− mice), which displayed radioprotection of the HSC pool and 100% survival following lethal dose total body irradiation (TBI). BM HSCs from wild type mice expressed functional EGFR and systemic administration of EGF promoted the recovery of the HSC pool in vivo and the improved survival of mice following TBI. Conversely, administration of erlotinib, an EGFR antagonist, significantly decreased both HSC regeneration and mice survival following TBI. VavCre;EGFRfl/+ mice also demonstrated delayed recovery of BM stem/progenitor cells following TBI compared to VavCre;EGFR+/+ mice. Mechanistically, EGF reduced radiation-induced apoptosis of HSCs and mediated this effect via repression of the proapoptotic protein, PUMA. EGFR signaling regulates HSC regeneration following myelosuppressive injury.
doi:10.1038/nm.3070
PMCID: PMC3594347  PMID: 23377280
4.  InterMOD: integrated data and tools for the unification of model organism research 
Scientific Reports  2013;3:1802.
Model organisms are widely used for understanding basic biology, and have significantly contributed to the study of human disease. In recent years, genomic analysis has provided extensive evidence of widespread conservation of gene sequence and function amongst eukaryotes, allowing insights from model organisms to help decipher gene function in a wider range of species. The InterMOD consortium is developing an infrastructure based around the InterMine data warehouse system to integrate genomic and functional data from a number of key model organisms, leading the way to improved cross-species research. So far including budding yeast, nematode worm, fruit fly, zebrafish, rat and mouse, the project has set up data warehouses, synchronized data models, and created analysis tools and links between data from different species. The project unites a number of major model organism databases, improving both the consistency and accessibility of comparative research, to the benefit of the wider scientific community.
doi:10.1038/srep01802
PMCID: PMC3647165  PMID: 23652793
5.  p53 Functions in Endothelial Cells to Prevent Radiation-Induced Myocardial Injury in Mice 
Science signaling  2012;5(234):ra52.
p53 functions in the heart to promote myocardial injury after multiple types of stress. However, how p53 regulates radiation-induced myocardial injury, which develops after radiation therapy, is not well understood. Here, we utilize the Cre-loxP system to demonstrate that p53 functioned in endothelial cells to protect mice from myocardial injury after whole-heart irradiation. Mice with an endothelial cell-specific deletion of p53 succumbed to heart failure after whole-heart irradiation due to myocardial necrosis, systolic dysfunction and cardiac hypertrophy. Moreover, the onset of cardiac dysfunction was preceded by alterations in myocardial vascular permeability and density, which resulted in cardiac ischemia and myocardial hypoxia. Mechanistic studies using primary cardiac endothelial cells irradiated in vitro indicated that p53 signaling caused mitotic arrest and protected cardiac endothelial cells against radiation-induced mitotic catastrophe. Furthermore, mice lacking the cyclin-dependent kinase inhibitor p21, which is a transcriptional target of p53, were also sensitized to myocardial injury after wholeheart irradiation. Together, our results demonstrate that the p53/p21 axis functions to prevent radiation-induced myocardial injury in mice.
doi:10.1126/scisignal.2002918
PMCID: PMC3533440  PMID: 22827996
6.  p21 Protects “Super p53” Mice from the Radiation-Induced Gastrointestinal Syndrome 
Radiation research  2011;177(3):307-310.
Exposure of the gastrointestinal (GI) tract to high doses of radiation can lead to lethality from the GI syndrome. Although the molecular mechanism regulating the GI syndrome remains to be fully defined, we have recently demonstrated that p53 within the GI epithelial cells controls the radiation-induced GI syndrome. Mice lacking p53 in the GI epithelium were sensitized to the GI syndrome, while transgenic mice with one additional copy of p53 called “Super p53” mice were protected from the GI syndrome. Here, we cross “Super p53” mice to p21−/− mice that lack the cyclin-dependent kinase inhibitor p21. Super p53; p21−/− mice are sensitized to the GI syndrome compared to Super p53 mice that retain one p21 allele. In addition, mice lacking p21 are not protected from the GI syndrome with one extra copy of p53. These results suggest that p21 protects “Super p53” mice from the GI syndrome.
PMCID: PMC3530410  PMID: 22165824
7.  InterMine: a flexible data warehouse system for the integration and analysis of heterogeneous biological data 
Bioinformatics  2012;28(23):3163-3165.
Summary: InterMine is an open-source data warehouse system that facilitates the building of databases with complex data integration requirements and a need for a fast customizable query facility. Using InterMine, large biological databases can be created from a range of heterogeneous data sources, and the extensible data model allows for easy integration of new data types. The analysis tools include a flexible query builder, genomic region search and a library of ‘widgets’ performing various statistical analyses. The results can be exported in many commonly used formats. InterMine is a fully extensible framework where developers can add new tools and functionality. Additionally, there is a comprehensive set of web services, for which client libraries are provided in five commonly used programming languages.
Availability: Freely available from http://www.intermine.org under the LGPL license.
Contact: g.micklem@gen.cam.ac.uk
Supplementary information: Supplementary data are available at Bioinformatics online.
doi:10.1093/bioinformatics/bts577
PMCID: PMC3516146  PMID: 23023984
8.  YeastMine—an integrated data warehouse for Saccharomyces cerevisiae data as a multipurpose tool-kit 
The Saccharomyces Genome Database (SGD; http://www.yeastgenome.org/) provides high-quality curated genomic, genetic, and molecular information on the genes and their products of the budding yeast Saccharomyces cerevisiae. To accommodate the increasingly complex, diverse needs of researchers for searching and comparing data, SGD has implemented InterMine (http://www.InterMine.org), an open source data warehouse system with a sophisticated querying interface, to create YeastMine (http://yeastmine.yeastgenome.org). YeastMine is a multifaceted search and retrieval environment that provides access to diverse data types. Searches can be initiated with a list of genes, a list of Gene Ontology terms, or lists of many other data types. The results from queries can be combined for further analysis and saved or downloaded in customizable file formats. Queries themselves can be customized by modifying predefined templates or by creating a new template to access a combination of specific data types. YeastMine offers multiple scenarios in which it can be used such as a powerful search interface, a discovery tool, a curation aid and also a complex database presentation format.
Database URL: http://yeastmine.yeastgenome.org
doi:10.1093/database/bar062
PMCID: PMC3308152  PMID: 22434830
9.  modMine: flexible access to modENCODE data 
Nucleic Acids Research  2011;40(D1):D1082-D1088.
In an effort to comprehensively characterize the functional elements within the genomes of the important model organisms Drosophila melanogaster and Caenorhabditis elegans, the NHGRI model organism Encyclopaedia of DNA Elements (modENCODE) consortium has generated an enormous library of genomic data along with detailed, structured information on all aspects of the experiments. The modMine database (http://intermine.modencode.org) described here has been built by the modENCODE Data Coordination Center to allow the broader research community to (i) search for and download data sets of interest among the thousands generated by modENCODE; (ii) access the data in an integrated form together with non-modENCODE data sets; and (iii) facilitate fine-grained analysis of the above data. The sophisticated search features are possible because of the collection of extensive experimental metadata by the consortium. Interfaces are provided to allow both biologists and bioinformaticians to exploit these rich modENCODE data sets now available via modMine.
doi:10.1093/nar/gkr921
PMCID: PMC3245176  PMID: 22080565
10.  p53 Controls Radiation-Induced Gastrointestinal Syndrome in Mice Independent of Apoptosis 
Science (New York, N.Y.)  2009;327(5965):593-596.
Acute exposure to ionizing radiation can cause lethal damage to the gastrointestinal (GI) tract, a condition called the GI syndrome. Whether the target cells mediating the GI syndrome are derived from the epithelium or endothelium, and whether the target cells die by apoptosis or other mechanisms, are controversial issues. Studying mouse models, we found that selective deletion of the pro-apoptotic genes Bak1 and Bax from the GI epithelium or from endothelial cells did not protect mice from developing the GI syndrome after subtotal body gamma irradiation. In contrast, selective deletion of p53 from the GI epithelium, but not endothelial cells, sensitized irradiated mice to the GI syndrome. Transgenic mice overexpressing p53 in all tissues were protected from the GI syndrome after irradiation. These results suggest that the GI syndrome is caused by death of GI epithelial cells by a mechanism that is regulated by p53 but independent of apoptosis.
doi:10.1126/science.1166202
PMCID: PMC2897160  PMID: 20019247
11.  FlyMine: an integrated database for Drosophila and Anopheles genomics 
Genome Biology  2007;8(7):R129.
This novel web-based database provides unique accessibility and querying of integrated genomic and proteomic data for Drosophila and Anopheles.
FlyMine is a data warehouse that addresses one of the important challenges of modern biology: how to integrate and make use of the diversity and volume of current biological data. Its main focus is genomic and proteomics data for Drosophila and other insects. It provides web access to integrated data at a number of different levels, from simple browsing to construction of complex queries, which can be executed on either single items or lists.
doi:10.1186/gb-2007-8-7-r129
PMCID: PMC2323218  PMID: 17615057
12.  IL-7 is a potent and proviral strain–specific inducer of latent HIV-1 cellular reservoirs of infected individuals on virally suppressive HAART 
Journal of Clinical Investigation  2005;115(1):128-137.
The persistence of HIV-1 in virally suppressed infected individuals on highly active antiretroviral therapy (HAART) remains a major therapeutic problem. The use of cytokines has been envisioned as an additional therapeutic strategy to stimulate latent proviruses in these individuals. Immune activation therapy using IL-2 has shown some promise. In the present study, we found that IL-7 was significantly more effective at enhancing HIV-1 proviral reactivation than either IL-2 alone or IL-2 combined with phytohemagglutinin (PHA) in CD8-depleted PBMCs. IL-7 also showed a positive trend for inducing proviral reactivation from resting CD4+ T lymphocytes from HIV-1–infected patients on suppressive HAART. Moreover, the phylogenetic analyses of viral envelope gp120 genes from induced viruses indicated that distinct proviral quasispecies had been activated by IL-7, as compared with those activated by the PHA/IL-2 treatment. These studies thus demonstrate that different activators of proviral latency may perturb and potentially deplete only selected, specific portions of the proviral archive in virally suppressed individuals. The known immunomodulatory effects of IL-7 could be combined with its ability to stimulate HIV-1 replication from resting CD4+ T lymphocytes, in addition to other moieties, to potentially deplete HIV-1 reservoirs and lead to the rational design of immune-antiretroviral approaches.
doi:10.1172/JCI200522574
PMCID: PMC539197  PMID: 15630452
13.  In a Subset of Subjects on Highly Active Antiretroviral Therapy, Human Immunodeficiency Virus Type 1 RNA in Plasma Decays from 50 to <5 Copies per Milliliter, with a Half-Life of 6 Months 
Journal of Virology  2003;77(3):2271-2275.
Three of five virally suppressed human immunodeficiency virus type I (HIV-1)-infected patients treated with highly active antiretroviral therapy and followed intensively with a supersensitive reverse transcriptase PCR assay with a lower limit of quantitation of 5 copies/ml showed statistically significant viral load decays below 50 copies/ml, with half-lives of 5 to 8 months and a mean of 6 months. This range of half-lives is consistent with the estimated half-life of the latent HIV-1 reservoir in the peripheral blood. Those patients without decay of viral load in plasma may have significant cryptic HIV-1 residual replication.
doi:10.1128/JVI.77.3.2271-2275.2003
PMCID: PMC140859  PMID: 12525664
14.  Footprinting, circular dichroism and UV melting studies on neomycin B binding to the packaging region of human immunodeficiency virus type-1 RNA 
Nucleic Acids Research  2002;30(13):2825-2831.
We have studied the binding of neomycin to a 171mer RNA (ψ-RNA) from the packaging region of the LAI strain of human immunodeficiency virus type-1, HIV-1 (LAI). The RNase I footprinting studies reveal that the primary binding site for the drug is in stem–loop 1, which contains the dimer initiation site of HIV-1. Loading this site with neomycin causes a structural change in the RNA, allowing nucleotides in the neighboring stem–loop 2 to participate in the drug site. Drug binding to secondary sites induces structural changes in other stem–loops of the RNA. Footprinting plots, showing cutting at a site as a function of drug concentration, were analyzed using a two-state model to obtain relative site-specific binding constants. Circular dichroism measurements show that neomycin binding to ψ-RNA changes the intensity of the strong negative CD band at 208 nm, confirming that neomycin induces structural changes. Melting studies of the RNA showed melting transitions in the absence of drug at 28.2, 37.2, 47.4, 55.5 and 60.8°C. Only the first two were affected by drug binding, the reason for this being explained by our analysis.
PMCID: PMC117057  PMID: 12087166

Results 1-14 (14)