CoPub update: CoPub 5.0 a text mining system to answer biological questions

In this article, we present CoPub 5.0, a publicly available text mining system, which uses Medline abstracts to calculate robust statistics for keyword co-occurrences. CoPub was initially developed for the analysis of microarray data, but we broadened the scope by implementing new technology and new thesauri. In CoPub 5.0, we integrated existing CoPub technology with new features, and provided a new advanced interface, which can be used to answer a variety of biological questions. CoPub 5.0 allows searching for keywords of interest and its relations to curated thesauri and provides highlighting and sorting mechanisms, using its statistics, to retrieve the most important abstracts in which the terms co-occur. It also provides a way to search for indirect relations between genes, drugs, pathways and diseases, following an ABC principle, in which A and C have no direct connection but are connected via shared B intermediates. With CoPub 5.0, it is possible to create, annotate and analyze networks using the layout and highlight options of Cytoscape web, allowing for literature based systems biology. Finally, operations of the CoPub 5.0 Web service enable to implement the CoPub technology in bioinformatics workflows. CoPub 5.0 can be accessed through the CoPub portal http://www.copub.org

Pathway and network-based analysis of genome-wide association studies in multiple sclerosis

Genome-wide association studies (GWAS) testing several hundred thousand SNPs have been performed in multiple sclerosis (MS) and other complex diseases. Typically, the number of markers in which the evidence for association exceeds the genome-wide significance threshold is very small, and markers that do not exceed this threshold are generally neglected. Classical statistical analysis of these datasets in MS revealed genes with known immunological functions. However, many of the markers showing modest association may represent false negatives. We hypothesize that certain combinations of genes flagged by these markers can be identified if they belong to a common biological pathway. Here we conduct a pathway-oriented analysis of two GWAS in MS that takes into account all SNPs with nominal evidence of association (P < 0.05). Gene-wise P-values were superimposed on a human protein interaction network and searches were conducted to identify sub-networks containing a higher proportion of genes associated with MS than expected by chance. These sub-networks, and others generated at random as a control, were categorized for membership of biological pathways. GWAS from eight other diseases were analyzed to assess the specificity of the pathways identified. In the MS datasets, we identified sub-networks of genes from several immunological pathways including cell adhesion, communication and signaling. Remarkably, neural pathways, namely axon-guidance and synaptic potentiation, were also over-represented in MS. In addition to the immunological pathways previously identified, we report here for the first time the potential involvement of neural pathways in MS susceptibilit

Pathway and network-based analysis of genome-wide association studies in multiple sclerosis

Genome-wide association studies (GWAS) testing several hundred thousand SNPs have been performed in multiple sclerosis (MS) and other complex diseases. Typically, the number of markers in which the evidence for association exceeds the genome-wide significance threshold is very small, and markers that do not exceed this threshold are generally neglected. Classical statistical analysis of these datasets in MS revealed genes with known immunological functions. However, many of the markers showing modest association may represent false negatives. We hypothesize that certain combinations of genes flagged by these markers can be identified if they belong to a common biological pathway. Here we conduct a pathway-oriented analysis of two GWAS in MS that takes into account all SNPs with nominal evidence of association (P < 0.05). Gene-wise P-values were superimposed on a human protein interaction network and searches were conducted to identify sub-networks containing a higher proportion of genes associated with MS than expected by chance. These sub-networks, and others generated at random as a control, were categorized for membership of biological pathways. GWAS from eight other diseases were analyzed to assess the specificity of the pathways identified. In the MS datasets, we identified sub-networks of genes from several immunological pathways including cell adhesion, communication and signaling. Remarkably, neural pathways, namely axon-guidance and synaptic potentiation, were also over-represented in MS. In addition to the immunological pathways previously identified, we report here for the first time the potential involvement of neural pathways in MS susceptibility

DNA-based Self-Assembly of Chiral Plasmonic Nanostructures with Tailored Optical Response

Surface plasmon resonances generated in metallic nanostructures can be utilized to tailor electromagnetic fields. The precise spatial arrangement of such structures can result in surprising optical properties that are not found in any naturally occurring material. Here, the designed activity emerges from collective effects of singular components equipped with limited individual functionality. Top-down fabrication of plasmonic materials with a predesigned optical response in the visible range by conventional lithographic methods has remained challenging due to their limited resolution, the complexity of scaling, and the difficulty to extend these techniques to three-dimensional architectures. Molecular self-assembly provides an alternative route to create such materials which is not bound by the above limitations. We demonstrate how the DNA origami method can be used to produce plasmonic materials with a tailored optical response at visible wavelengths. Harnessing the assembly power of 3D DNA origami, we arranged metal nanoparticles with a spatial accuracy of 2 nm into nanoscale helices. The helical structures assemble in solution in a massively parallel fashion and with near quantitative yields. As a designed optical response, we generated giant circular dichroism and optical rotary dispersion in the visible range that originates from the collective plasmon-plasmon interactions within the nanohelices. We also show that the optical response can be tuned through the visible spectrum by changing the composition of the metal nanoparticles. The observed effects are independent of the direction of the incident light and can be switched by design between left- and right-handed orientation. Our work demonstrates the production of complex bulk materials from precisely designed nanoscopic assemblies and highlights the potential of DNA self-assembly for the fabrication of plasmonic nanostructures.Comment: 5 pages, 4 figure

Cellular and humoral immune responses and protection against schistosomes induced by a radiation-attenuated vaccine in chimpanzees

The radiation-attenuated Schistosoma mansoni vaccine is highly effective in rodents and primates but has never been tested in humans, primarily for safety reasons. To strengthen its status as a paradigm for a human recombinant antigen vaccine, we have undertaken a small-scale vaccination and challenge experiment in chimpanzees (Pan troglodytes). Immunological, clinical, and parasitological parameters were measured in three animals after multiple vaccinations, together with three controls, during the acute and chronic stages of challenge infection up to chemotherapeutic cure. Vaccination induced a strong in vitro proliferative response and early gamma interferon production, but type 2 cytokines were dominant by the time of challenge. The controls showed little response to challenge infection before the acute stage of the disease, initiated by egg deposition. In contrast, the responses of vaccinated animals were muted throughout the challenge period. Vaccination also induced parasite-specific immunoglobulin M (IgM) and IgG, which reached high levels at the time of challenge, while in control animals levels did not rise markedly before egg deposition. The protective effects of vaccination were manifested as an amelioration of acute disease and overall morbidity, revealed by differences in gamma-glutamyl transferase level, leukocytosis, eosinophilia, and hematocrit. Moreover, vaccinated chimpanzees had a 46% lower level of circulating cathodic antigen and a 38% reduction in fecal egg output, compared to controls, during the chronic phase of infection

A holistic measurement model of movement competency in children

Different countries have different methods for assessing movement competence in children; however, it is unclear whether the test batteries that are used measure the same aspects of movement competence. The aim of this paper was to (1) investigate whether the Test of Gross Motor Development (TGMD-2) and Körperkoordinations Test für Kinder (KTK) measure the same aspects of children’s movement competence and (2) examine the factorial structure of the TGMD-2 and KTK in a sample of Australian children. A total of 158 children participated (M age = 9.5; SD = 2.2). First, confirmatory factor analysis examined the independent factorial structure of the KTK and TGMD-2. Second, it was investigated whether locomotor, object control and body coordination loaded on the latent variable Movement Competency. Confirmatory factor analysis indicated an adequate fit for both the KTK and TGMD-2. An adequate fit was also achieved for the final model. In this model, locomotor (r = .86), object control (r = .71) and body coordination (r = .52) loaded on movement competence. Findings support our hypothesis that the TGMD-2 and KTK measure discrete aspects of movement competence. Future researchers and practitioners should consider using a wider range of test batteries to assess movement competence

Advances in small lasers

M.T.H was supported by an Australian Research council Future Fellowship research grant for this work. M.C.G. is grateful to the Scottish Funding Council (via SUPA) for financial support.Small lasers have dimensions or modes sizes close to or smaller than the wavelength of emitted light. In recent years there has been significant progress towards reducing the size and improving the characteristics of these devices. This work has been led primarily by the innovative use of new materials and cavity designs. This Review summarizes some of the latest developments, particularly in metallic and plasmonic lasers, improvements in small dielectric lasers, and the emerging area of small bio-compatible or bio-derived lasers. We examine the different approaches employed to reduce size and how they result in significant differences in the final device, particularly between metal- and dielectric-cavity lasers. We also present potential applications for the various forms of small lasers, and indicate where further developments are required.PostprintPeer reviewe

Participatory Workshops are Not Enough to Prevent Policy Implementation Failures: An Example of a Policy Development Process Concerning the Drug Interferon-beta for Multiple Sclerosis

A possible explanation for policy implementation failure is that the views of the policy’s target groups are insufficiently taken into account during policy development. It has been argued that involving these groups in an interactive process of policy development could improve this. We analysed a project in which several target populations participated in workshops aimed to optimise the utilisation of an expensive novel drug (interferon beta) for patients with Multiple Sclerosis. All participants seemed to agree on the appropriateness of establishing a central registry of Multiple Sclerosis patients and developing guidelines. Nevertheless, these policy measures were not implemented. Possible explanations include (1) the subject no longer had high priority when the costs appeared lower than expected, (2) the organisers had paid insufficient attention to the perceived problems of parties involved, and (3) changes within the socio-political context. The workshops in which representatives of the policy’s target populations participated did not provide enough interactivity to prevent policy implementation failure