Taverna, reloaded

The Taverna workflow management system is an open source project with a history of widespread adoption within multiple experimental science communities, and a long-term ambition of effectively supporting the evolving need of those communities for complex, data-intensive, service-based experimental pipelines. This short paper describes how the recently overhauled technical architecture of Taverna addresses issues of efficiency, scalability, and extensibility, and presents performance results based on a collection of synthetic workflows, as well as a concrete case study involving a production workflow in the area of cancer research.</p

Genome-Wide Identification, Functional Analysis and Expression Profiling of the Aux/IAA Gene Family in Tomato

Auxin is a central hormone that exerts pleiotropic effects on plant growth including the development of roots, shoots, flowers and fruit. The perception and signaling of the plant hormone auxin rely on the cooperative action of several components,among which auxin/indole-3-acetic acid (Aux/IAA) proteins play a pivotal role. In this study, we identified and comprehensively analyzed the entire Aux/IAA gene family in tomato (Solanum lycopersicum), a reference species for Solanaceae plants, and the model plant for fleshy fruit development. Functional characterization using a dedicated single cell system revealed that tomato Aux/IAA proteins function as active repressors of auxin-dependent gene transcription, with, however, different Aux/IAA members displaying varying levels of repression. Phylogenetic analysis indicated that the Aux/IAA gene family is slightly contracted in tomato compared with Arabidopsis, with a lower representation of non-canonical proteins. Sl-IAA genes display distinctive expression pattern in different tomato organs and tissues, and some of them display differential responses to auxin and ethylene, suggesting that Aux/IAAs may play a role in linking both hormone signaling pathways. The data presented here shed more light on Sl-IAA genes and provides new leads towards the elucidation of their function during plant development and in mediating hormone cross-talk

Feasibility of Clinical Evaluation of Individuals With Increased Risk for HPV-associated Oropharynx Cancer

BACKGROUND: Human papillomavirus-associated oropharynx squamous cell carcinoma (HPV-OPSCC) has no known pre-malignant lesion. While vaccination offers future primary prevention, there is current interest in secondary prevention. The feasibility of clinical evaluation of individuals at increased risk for HPV-OPSCC is unclear. METHODS: Individuals with risk factors for HPV-OPSCC were enrolled in a prospective study (MOUTH). Participants positive for biomarkers associated with HPV-OPSCC were eligible for a clinical evaluation which comprised a head and neck examination and imaging with ultrasound and/or magnetic resonance imaging (MRI). This study was designed to evaluate feasibility of clinical evaluation in a screening study. RESULTS: Three hundred and eighty-four participants were eligible for clinical evaluation. Of the 384, 204 (53%) completed a head and neck examination or imaging. Of these, 66 (32%) completed MRI (n = 51) and/or ultrasound (n = 64) studies. CONCLUSIONS: Clinical evaluations, including head and neck examination and imaging, are feasible in the context of a screening study for HPV-OPSCC

CaGrid Workflow Toolkit: A taverna based workflow tool for cancer grid

SOFTWAR

Phenotypes Associated with Down-Regulation of Sl-IAA27 Support Functional Diversity Among Aux/IAA Family Members in Tomato

The phytohormone auxin is known to regulate several aspects of plant development, and Aux/IAA transcription factors play a pivotal role in auxin signaling. To extend our understanding of the multiple functions of Aux/IAAs further, the present study describes the functional characterization of Sl-IAA27, a member of the tomato Aux/IAA gene family. Sl-IAA27 displays a distinct behavior compared with most Aux/IAA genes regarding the regulation of its expression by auxin, and the Sl-IAA27-encoded protein harbors a unique motif of unknown function also present in Sl-IAA9 and remarkably conserved in monocot and dicot species. Tomato transgenic plants underexpressing the Sl-IAA27 gene revealed multiple phenotypes related to vegetative and reproductive growth. Silencing of Sl-IAA27 results in higher auxin sensitivity, altered root development and reduced Chl content in leaves. Both ovule and pollen display a dramatic loss of fertility in Sl-IAA27 down-regulated lines,and the internal anatomy of the flower and the fruit are modified, with an enlarged placenta in smaller fruits. In line with the reduced Chl content in Sl-IAA27 RNA interference(RNAi) leaves, genes involved in Chl synthesis display lower expression at the level of transcript accumulation. Even though Sl-IAA27 is closely related to Sl-IAA9 in terms of sequence homology and the encoded proteins share common structural features, the data indicate that the two genes regulate tomato fruit initiation and development in a distinct manner

(Not) being at home: Hsu Ming Teo's Behind the Moon (2005) and Michelle de Kretser's Questions of Travel (2012)

This article examines some interventions of Asian Australian writing into the debate over multiculturalism, and the shift from negative stereotyping of Asian migrants, to reification of racial divisions and propagation of a masked racism, to the creation of new alignments and the revival of pre-existing affiliations by migrant and second generation subjects. It compares the practices of not-at-homeness by Asian migrants and their descendants and white Australians in Hsu Ming Teo’s Behind the Moon with those of a Sri Lankan refugee and a white Australian traveller in Michelle de Kretser’s Questions of Travel. The changing concepts of belonging in the novels show a realignment of core and periphery relations within the nation state under the pressures of multiculturalism and globalization: where home is and how it is configured are questions as important for white Australians whose sense of territory is challenged as they are for Asian migrants who seek to establish a new belonging

Patrocles: a database of polymorphic miRNA-mediated gene regulation in vertebrates

The Patrocles database (http://www.patrocles.org/) compiles DNA sequence polymorphisms (DSPs) that are predicted to perturb miRNA-mediated gene regulation. Distinctive features include: (i) the coverage of seven vertebrate species in its present release, aiming for more when information becomes available, (ii) the coverage of the three compartments involved in the silencing process (i.e. targets, miRNA precursors and silencing machinery), (iii) contextual information that enables users to prioritize candidate ‘Patrocles DSPs’, including graphical information on miRNA-target coexpression and eQTL effect of genotype on target expression levels, (iv) the inclusion of Copy Number Variants and eQTL information that affect miRNA precursors as well as genes encoding components of the silencing machinery and (v) a tool (Patrocles finder) that allows the user to determine whether her favorite DSP may perturb miRNA-mediated gene regulation of custom target sequences. To support the biological relevance of Patrocles' content, we searched for signatures of selection acting on ‘Patrocles single nucleotide polymorphisms (pSNPs)’ in human and mice. As expected, we found a strong signature of purifying selection against not only SNPs that destroy conserved target sites but also against SNPs that create novel, illegitimate target sites, which is reminiscent of the Texel mutation in sheep

Towards BioDBcore: a community-defined information specification for biological databases

The present article proposes the adoption of a community-defined, uniform, generic description of the core attributes of biological databases, BioDBCore. The goals of these attributes are to provide a general overview of the database landscape, to encourage consistency and interoperability between resources and to promote the use of semantic and syntactic standards. BioDBCore will make it easier for users to evaluate the scope and relevance of available resources. This new resource will increase the collective impact of the information present in biological database

A torque-based method demonstrates increased rigidity in Parkinson’s disease during low-frequency stimulation

Low-frequency oscillations in the basal ganglia are prominent in patients with Parkinson’s disease off medication. Correlative and more recent interventional studies potentially implicate these rhythms in the pathophysiology of Parkinson’s disease. However, effect sizes have generally been small and limited to bradykinesia. In this study, we investigate whether these effects extend to rigidity and are maintained in the on-medication state. We studied 24 sides in 12 patients on levodopa during bilateral stimulation of the STN at 5, 10, 20, 50, 130 Hz and in the off-stimulation state. Passive rigidity at the wrist was assessed clinically and with a torque-based mechanical device. Low-frequency stimulation at ≤20 Hz increased rigidity by 24 % overall (p = 0.035), whereas high-frequency stimulation (130 Hz) reduced rigidity by 18 % (p = 0.033). The effects of low-frequency stimulation (5, 10 and 20 Hz) were well correlated with each other for both flexion and extension (r = 0.725 ± SEM 0.016 and 0.568 ± 0.009, respectively). Clinical assessments were unable to show an effect of low-frequency stimulation but did show a significant effect at 130 Hz (p = 0.002). This study provides evidence consistent with a mechanistic link between oscillatory activity at low frequency and Parkinsonian rigidity and, in addition, validates a new method for rigidity quantification at the wrist

Analysis of the diverse antigenic landscape of the malaria protein RH5 identifies a potent vaccine-induced human public antibody clonotype

The highly conserved and essential Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) has emerged as the leading target for vaccines against the disease-causing blood stage of malaria. However, the features of the human vaccine-induced antibody response that confer highly potent inhibition of malaria parasite invasion into red blood cells are not well defined. Here, we characterize 236 human IgG monoclonal antibodies, derived from 15 donors, induced by the most advanced PfRH5 vaccine. We define the antigenic landscape of this molecule and establish that epitope specificity, antibody association rate, and intra-PfRH5 antibody interactions are key determinants of functional anti-parasitic potency. In addition, we identify a germline IgG gene combination that results in an exceptionally potent class of antibody and demonstrate its prophylactic potential to protect against P. falciparum parasite challenge in vivo. This comprehensive dataset provides a framework to guide rational design of next-generation vaccines and prophylactic antibodies to protect against blood-stage malaria