ENA as an Information Hub

The European Nucleotide Archive (ENA; "http://www.ebi.ac.uk/ena/":http://www.ebi.ac.uk/ena/) is a comprehensive repository for public nucleotide sequence data from nearly four hundred thousand taxonomic nodes. Together with partners in the International Nucleotide Sequence Database Collaboration (INSDC; EBI, NCBI and DDBJ) we provide a broad spectrum of sequences, from raw reads (Sequence Read Archive data class), assembled contigs (Whole Genome Shotgun data class), assemblies of EST transcripts (Transcriptome Shotgun Assembly data set), to partial or complete assembled nucleic acid molecules with functional annotation derived from direct and third party experimental evidence (Standard and TPA data classes, respectively). Resources beyond ENA, such as RNA and protein databases, genome collections and model organism services, use data stored and presented at ENA as both source and underlying supporting evidence for their records. Integration of the growing wealth of molecular information is a great challenge that brings opportunities for ENA to serve as a bioinformatics data information hub, allowing, through its provision of permanent identifiers for sequence and project records, community-recognized identifiers for navigation across databases.

As a comprehensive repository of directly sequenced nucleic acid molecules we have the unique opportunity to obtain exact provenance information directly from the submitting researchers. Our pre-publication biocuration efforts are focused on obtaining rich and accurate information on the sample that has been sequenced and on the methodology surrounding its preparation for sequencing. We present here an insight into data flow in the archive and a straightforward biologist-orientated submission system with a rule-based validator for smaller sets of sequences

Dimeric benzoboroxoles for targeted activity against Mycobacterium tuberculosis

Dimeric benzoboroxoles that are covalently linked by a short scaffold enhance selective anti-tubercular activity. These multimeric benzoboroxole compounds are capable of engaging the specific extracellular Mycobacterium tuberculosis glycans, do not lead to the evolution of resistance and bypass the need to cross the impermeable mycobacterial cell envelope barrier

Analysing and modelling train driver performance

Arguments for the importance of contextual factors in understanding human performance have been made extremely persuasive in the context of the process control industries. This paper puts these arguments into the context of the train driving task, drawing on an extensive analysis of driver performance with the Automatic Warning System (AWS). The paper summarises a number of constructs from applied psychological research which are thought to be important in understanding train driver performance. A “Situational Model” is offered as a framework for investigating driver performance. The model emphasises the importance of understanding the state of driver cognition at a specific time (“Now”) in a specific situation and a specific context

Thermal Stress Flow Analysis in Fabrication of Acetabular Shells Using SLM

Additive Manufacturing (AM), more popularly known as 3D Printing, is a process for producing functional artifacts by adding layers of materials from data generated directly from 3D solid CAD models. Additive Manufacturing (AM) is the formalized term for what used to be called Rapid Prototyping and what is commonly referred to as 3D Printing. The key to how AM works is that parts are made by adding layers of material; each layer corresponding to a thin cross-section of the part derived from the original CAD data. Although most AM machines produce parts using polymers, there are an increasing number of machines that can directly fabricate in metals. The majority of these machines fabricate from raw material in powder form using a directed energy beam to create a local melt zone. Total hip replacement is recommended for people who have medical issues related to excessive wear of the acetabular, osteoarthritis, accident or age. Researches have shown that large numbers of hip arthroplasties (where the articular surface of a musculoskeletal joint is replaced), hip remodelling, or realignment are carried out annually and will increase in the next few decades. Manufacturing of acetabular shells by using AM is a promising and emerging method that has a great potential to improve public health. Lost wax casting or investment casting is currently used to produce acetabular shells followed by lengthy and complex secondary processes such as machining and polishing. Living organs and medical models have intricate 3D shapes that are challenging to identity in X-ray CT images. These images are used for preparing treatment plans to improve the quality of the surgeries regarding waiting and surgery time per procedure and care regime. For instance, a limited number of hip replacement procedures can be carried out on each acetabulum due to a decrease of bone thickness. Rapid prototyping is a suitable treatment planning tool in complex cases to enhance the quality of surgical procedure and provide long-term stability that can be used to customize the shape and size of the acetabular shell. In this paper, to analyse the manufacturing of a prosthetic acetabular shell, built-up lines resulting from a thermal stress flow and process stopping during the selective laser melting (SLM) AM process, with regarding Gibbs free energy, interfacial energy, and equilibrium temperature will be discussed. Geometrical measurements showed 1.59% and 0.27% differences between the designed and manufactured prototype for inside and outside diameter respectively. Experimental results showed that thermal stress flow in outer surfaces are compressive, but for inner surfaces are tensile, so built-up lines in inner and outer surfaces appear as a groove and dent respectively. The results also indicate that SLM is an accurate and promising method for fabrication of acetabular cup

The ORCA2 transcription factor plays a key role in regulation of the terpenoid indole alkaloid pathway

Background: The terpenoid indole alkaloid (TIA) pathway leads to the production of pharmaceutically important drugs, such as the anticancer compounds vinblastine and vincristine. Unfortunately, these drugs are produced in trace amounts, causing them to be very costly. To increase production of these drugs, an improved understanding of the TIA regulatory pathway is needed. Towards this end, transgenic Catharanthus roseus hairy roots that overexpress the ORCA2 TIA transcriptional activator were generated and characterized.Results: Transcriptional profiling experiments revealed that overexpression of ORCA2 results in altered expression of key genes from the indole and terpenoid pathways, which produce precursors for the TIA pathway, and from the TIA pathway itself. In addition, metabolite-profiling experiments revealed that overexpression of ORCA2 significantly affects the levels of several TIA metabolites. ORCA2 overexpression also causes significant increases in transcript levels of several TIA regulators, including TIA transcriptional repressors.Conclusions: Results presented here indicate that ORCA2 plays a critical role in regulation of TIA metabolism. ORCA2 regulates expression of key genes from both feeder pathways, as well as the genes (STR and SGD) encoding the enzymes that catalyze the first two steps in TIA biosynthesis. ORCA2 may play an especially important role in regulation of the downstream branches of the TIA pathway, as it regulates four out of five genes characterized from this part of the pathway. Regulation of TIA transcriptional repressors by ORCA2 may provide a mechanism whereby increases in TIA metabolite levels in response to external stimuli are transient and limited in magnitude

Antifreeze protein mimetic metallohelices with potent ice recrystallization inhibition activity

Antifreeze proteins are produced by extremophile species to control ice formation and growth, and they have potential applications in many fields. There are few examples of synthetic materials which can reproduce their potent ice recrystallization inhibition property. We report that self-assembled enantiomerically pure, amphipathic metallohelicies inhibited ice growth at just 20 μM. Structure-property relationships and calculations support the hypothesis that amphipathicity is the key motif for activity. This opens up a new field of metallo-organic antifreeze protein mimetics and provides insight into the origins of ice-growth inhibition

Daily Preventive Zinc Supplementation Decreases Lymphocyte and Eosinophil Concentrations in Rural Laotian Children from Communities with a High Prevalence of Zinc Deficiency: Results of a Randomized Controlled Trial.

BACKGROUND:Zinc deficiency impairs immune function and is common among children in South-East Asia. OBJECTIVES:The effect of zinc supplementation on immune function in young Laotian children was investigated. METHODS:Children (n = 512) aged 6-23 mo received daily preventive zinc tablets (PZ; 7 mg Zn/d), daily multiple micronutrient powder (MNP; 10 mg Zn/d, 6 mg Fe/d, plus 13 other micronutrients), therapeutic dispersible zinc tablets only in association with diarrhea episodes (TZ; 20 mg Zn/d for 10 d after an episode), or daily placebo powder (control). These interventions continued for 9 mo. Cytokine production from whole blood cultures, the concentrations of T-cell populations, and a complete blood count with differential leukocyte count were measured at baseline and endline. Endline means were compared via ANCOVA, controlling for the baseline value of the outcome, child age and sex, district, month of enrollment, and baseline zinc status (below, or above or equal to, the median plasma zinc concentration). RESULTS:T-cell cytokines (IL-2, IFN-γ, IL-13, IL-17), LPS-stimulated cytokines (IL-1β, IL-6, TNF-α, and IL-10), and T-cell concentrations at endline did not differ between intervention groups, nor was there an interaction with baseline zinc status. However, mean ± SE endline lymphocyte concentrations were significantly lower in the PZ than in the control group (5018 ± 158 compared with 5640 ± 160 cells/μL, P = 0.032). Interactions with baseline zinc status were seen for eosinophils (Pixn = 0.0036), basophils (Pixn = 0.023), and monocytes (P = 0.086) but a significant subgroup difference was seen only for eosinophils, where concentrations were significantly lower in the PZ than in the control group among children with baseline plasma zinc concentrations below the overall median (524 ± 44 compared with 600 ± 41 cells/μL, P = 0.012). CONCLUSIONS:Zinc supplementation of rural Laotian children had no effect on cytokines or T-cell concentrations, although zinc supplementation affected lymphocyte and eosinophil concentrations. These cell subsets may be useful as indicators of response to zinc supplementation.This trial was registered at clinicaltrials.gov as NCT02428647

ORC-13661 protects sensory hair cells from aminoglycoside and cisplatin ototoxicity

Aminoglycoside (AG) antibiotics are widely used to prevent life-threatening infections, and cisplatin is used in the treatment of various cancers, but both are ototoxic and result in loss of sensory hair cells from the inner ear. ORC-13661 is a new drug that was derived from PROTO-1, a compound first identified as protective in a large-scale screen utilizing hair cells in the lateral line organs of zebrafish larvae. Here, we demonstrate, in zebrafish larvae and in mouse cochlear cultures, that ORC-13661 provides robust protection of hair cells against both ototoxins, the AGs and cisplatin. ORC-13661 also prevents both hearing loss in a dose-dependent manner in rats treated with amikacin and the loading of neomycin-Texas Red into lateral line hair cells. In addition, patch-clamp recordings in mouse cochlear cultures reveal that ORC-13661 is a high-affinity permeant blocker of the mechanoelectrical transducer (MET) channel in outer hair cells, suggesting that it may reduce the toxicity of AGs by directly competing for entry at the level of the MET channel and of cisplatin by a MET-dependent mechanism. ORC-13661 is therefore a promising and versatile protectant that reversibly blocks the hair cell MET channel and operates across multiple species and toxins