Identification of a conserved N-terminal domain in the first module of ACV synthetases

Abstract The l‐δ‐(α‐aminoadipoyl)‐l‐cysteinyl‐d‐valine synthetase (ACVS) is a trimodular nonribosomal peptide synthetase (NRPS) that provides the peptide precursor for the synthesis of β‐lactams. The enzyme has been extensively characterized in terms of tripeptide formation and substrate specificity. The first module is highly specific and is the only NRPS unit known to recruit and activate the substrate l‐α‐aminoadipic acid, which is coupled to the α‐amino group of l‐cysteine through an unusual peptide bond, involving its δ‐carboxyl group. Here we carried out an in‐depth investigation on the architecture of the first module of the ACVS enzymes from the fungus Penicillium rubens and the bacterium Nocardia lactamdurans. Bioinformatic analyses revealed the presence of a previously unidentified domain at the N‐terminus which is structurally related to condensation domains, but smaller in size. Deletion variants of both enzymes were generated to investigate the potential impact on penicillin biosynthesis in vivo and in vitro. The data indicate that the N‐terminal domain is important for catalysis

Main Results of Phase IV BEMUSE Project: Simulation of LBLOCA in an NPP

Phase IV of BEMUSE Program is a necessary step for a subsequent uncertainty analysis. It includes the simulation of the reference scenario and a sensitivity study. The scenario is a LBLOCA and the reference plant is Zion 1 NPP, a 4 loop PWR unit. Thirteen participants coming from ten different countries have taken part in the exercise. The BEMUSE (Best Estimate Methods plus Uncertainty and Sensitivity Evaluation) Programhas been promoted by theWorking Group on AccidentManagement and Analysis (WGAMA) and endorsed by the Committee on the Safety of Nuclear Installations (CSNI). The paper presents the results of the calculations performed by participants and emphasizes its usefulness for future uncertainty evaluation, to be performed in next phase. The objectives of the activity are basically to simulate the LBLOCA reproducing the phenomena associated to the scenario and also to build a common, well-known, basis for the future comparison of uncertainty evaluation results among different methodologies and codes. The sensitivity calculations performed by participants are also presented. They allow studying the influence of different parameters such as material properties or initial and boundary conditions, upon the behaviour of the most relevant parameters related to the scenario

GOBLET: the Global Organisation for Bioinformatics Learning, Education and Training

In recent years, high-throughput technologies have brought big data to the life sciences. The march of progress has been rapid, leaving in its wake a demand for courses in data analysis, data stewardship, computing fundamentals, etc., a need that universities have not yet been able to satisfy--paradoxically, many are actually closing "niche" bioinformatics courses at a time of critical need. The impact of this is being felt across continents, as many students and early-stage researchers are being left without appropriate skills to manage, analyse, and interpret their data with confidence. This situation has galvanised a group of scientists to address the problems on an international scale. For the first time, bioinformatics educators and trainers across the globe have come together to address common needs, rising above institutional and international boundaries to cooperate in sharing bioinformatics training expertise, experience, and resources, aiming to put ad hoc training practices on a more professional footing for the benefit of all

GOBLET: The Global Organisation for Bioinformatics Learning, Education and Training

In recent years, high-throughput technologies have brought big data to the life sciences. The march of progress has been rapid, leaving in its wake a demand for courses in data analysis, data stewardship, computing fundamentals, etc., a need that universities have not yet been able to satisfy—paradoxically, many are actually closing “niche” bioinformatics courses at a time of critical need. The impact of this is being felt across continents, as many students and early-stage researchers are being left without appropriate skills to manage, analyse, and interpret their data with confidence. This situation has galvanised a group of scientists to address the problems on an international scale. For the first time, bioinformatics educators and trainers across the globe have come together to address common needs, rising above institutional and international boundaries to cooperate in sharing bioinformatics training expertise, experience, and resources, aiming to put ad hoc training practices on a more professional footing for the benefit of all

The Complete Genome Sequence of ‘Candidatus Liberibacter solanacearum’, the Bacterium Associated with Potato Zebra Chip Disease

Zebra Chip (ZC) is an emerging plant disease that causes aboveground decline of potato shoots and generally results in unusable tubers. This disease has led to multi-million dollar losses for growers in the central and western United States over the past decade and impacts the livelihood of potato farmers in Mexico and New Zealand. ZC is associated with ‘Candidatus Liberibacter solanacearum’, a fastidious alpha-proteobacterium that is transmitted by a phloem-feeding psyllid vector, Bactericera cockerelli Sulc. Research on this disease has been hampered by a lack of robust culture methods and paucity of genome sequence information for ‘Ca. L. solanacearum’. Here we present the sequence of the 1.26 Mbp metagenome of ‘Ca. L. solanacearum’, based on DNA isolated from potato psyllids. The coding inventory of the ‘Ca. L. solanacearum’ genome was analyzed and compared to related Rhizobiaceae to better understand ‘Ca. L. solanacearum’ physiology and identify potential targets to develop improved treatment strategies. This analysis revealed a number of unique transporters and pathways, all potentially contributing to ZC pathogenesis. Some of these factors may have been acquired through horizontal gene transfer. Taxonomically, ‘Ca. L. solanacearum’ is related to ‘Ca. L. asiaticus’, a suspected causative agent of citrus huanglongbing, yet many genome rearrangements and several gene gains/losses are evident when comparing these two Liberibacter. species. Relative to ‘Ca. L. asiaticus’, ‘Ca. L. solanacearum’ probably has reduced capacity for nucleic acid modification, increased amino acid and vitamin biosynthesis functionalities, and gained a high-affinity iron transport system characteristic of several pathogenic microbes

Computing with bacterial constituents, cells and populations: from bioputing to bactoputing

The relevance of biological materials and processes to computing—aliasbioputing—has been explored for decades. These materials include DNA, RNA and proteins, while the processes include transcription, translation, signal transduction and regulation. Recently, the use of bacteria themselves as living computers has been explored but this use generally falls within the classical paradigm of computing. Computer scientists, however, have a variety of problems to which they seek solutions, while microbiologists are having new insights into the problems bacteria are solving and how they are solving them. Here, we envisage that bacteria might be used for new sorts of computing. These could be based on the capacity of bacteria to grow, move and adapt to a myriad different fickle environments both as individuals and as populations of bacteria plus bacteriophage. New principles might be based on the way that bacteria explore phenotype space via hyperstructure dynamics and the fundamental nature of the cell cycle. This computing might even extend to developing a high level language appropriate to using populations of bacteria and bacteriophage. Here, we offer a speculative tour of what we term bactoputing, namely the use of the natural behaviour of bacteria for calculating

The BEMUSE programme (Best-Estimate Methods – Uncertainty and Sensitivity Evaluation)

The BEMUSE [1] (Best Estimate Methods – Uncertainty and Sensitivity Evaluation) Programme has been promoted by the Working Group on Accident Management and Analysis (GAMA) and endorsed by the Committee on the Safety of Nuclear Installations (CSNI). The high-level objectives of the work are: • to evaluate the practicability, the quality and the reliability of Best-Estimate (BE) methods including uncertainty evaluation in applications relevant to nuclear reactor safety; • to promote the use of BE-Methods by the regulatory bodies and the industry. Operational objectives include an assessment of the applicability of best-estimate and uncertainty methods to integral tests and their use in reactor applications. The scope of the Programme is to perform Large Break Loss-Of-Coolant Accident (LBLOCA) analyses making reference to experimental data and to a Nuclear Power Plant (NPP) in order to address the issue of “the capabilities of computational tools” including scaling/uncertainty analysis. The justification for such an activity comes from the consideration that a wide spectrum of uncertainty methods applied to BE codes exist and are used in research laboratories, but their practicability and/or validity is not sufficiently established to support general use of the codes and acceptance by industry and safety authorities. The consideration of the BE codes and uncertainty evaluation for Design Basis Accident (DBA), by itself, shows the safety significance of the proposed activity. End users for the results are expected to be the industry, the safety authorities and the research laboratories. Participants coming from more than 10 organizations will take part in the Programme