BRAHMS: Novel middleware for integrated systems computation

Biological computational modellers are becoming increasingly interested in building large, eclectic models, including components on many different computational substrates, both biological and non-biological. At the same time, the rise of the philosophy of embodied modelling is generating a need to deploy biological models as controllers for robots in real-world environments. Finally, robotics engineers are beginning to find value in seconding biomimetic control strategies for use on practical robots. Together with the ubiquitous desire to make good on past software development effort, these trends are throwing up new challenges of intellectual and technological integration (for example across scales, across disciplines, and even across time) - challenges that are unmet by existing software frameworks. Here, we outline these challenges in detail, and go on to describe a newly developed software framework, BRAHMS. that meets them. BRAHMS is a tool for integrating computational process modules into a viable, computable system: its generality and flexibility facilitate integration across barriers, such as those described above, in a coherent and effective way. We go on to describe several cases where BRAHMS has been successfully deployed in practical situations. We also show excellent performance in comparison with a monolithic development approach. Additional benefits of developing in the framework include source code self-documentation, automatic coarse-grained parallelisation, cross-language integration, data logging, performance monitoring, and will include dynamic load-balancing and 'pause and continue' execution. BRAHMS is built on the nascent, and similarly general purpose, model markup language, SystemML. This will, in future, also facilitate repeatability and accountability (same answers ten years from now), transparent automatic software distribution, and interfacing with other SystemML tools. (C) 2009 Elsevier Ltd. All rights reserved

Lepiniopsis ternatensis sap stimulates fibroblast proliferation and down regulates macrophage TNF-α secretion

Christensen Fund for Melanesi

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 × 10-19 and 2.35 × 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group

BacHBerry: BACterial Hosts for production of Bioactive phenolics from bERRY fruits

BACterial Hosts for production of Bioactive phenolics from bERRY fruits (BacHBerry) was a 3-year project funded by the Seventh Framework Programme (FP7) of the European Union that ran between November 2013 and October 2016. The overall aim of the project was to establish a sustainable and economically-feasible strategy for the production of novel high-value phenolic compounds isolated from berry fruits using bacterial platforms. The project aimed at covering all stages of the discovery and pre-commercialization process, including berry collection, screening and characterization of their bioactive components, identification and functional characterization of the corresponding biosynthetic pathways, and construction of Gram-positive bacterial cell factories producing phenolic compounds. Further activities included optimization of polyphenol extraction methods from bacterial cultures, scale-up of production by fermentation up to pilot scale, as well as societal and economic analyses of the processes. This review article summarizes some of the key findings obtained throughout the duration of the project

Disrupting iron homeostasis can potentiate colistin activity and overcome colistin resistance mechanisms in Gram-Negative Bacteria

Data availability: Transcriptomics datasets obtained through this work have been deposited at the Gene Expression Omnibus (GEO) repository of National Centre for Biotechnology Information (NCBI) under the accession number GSE212989. Numerical source data is available in the Supplementary Data 3 file and all other data are available from the corresponding author on reasonable request.Supplementary information is available online at https://www.nature.com/articles/s42003-023-05302-2#Sec30 .Copyright © The Author(s) 2023. Acinetobacter baumannii is a Gram-negative priority pathogen that can readily overcome antibiotic treatment through a range of intrinsic and acquired resistance mechanisms. Treatment of carbapenem-resistant A. baumannii largely relies on the use of colistin in cases where other treatment options have been exhausted. However, the emergence of resistance against this last-line drug has significantly increased amongst clinical strains. In this study, we identify the phytochemical kaempferol as a potentiator of colistin activity. When administered singularly, kaempferol has no effect on growth but does impact biofilm formation. Nonetheless, co-administration of kaempferol with sub-inhibitory concentrations of colistin exposes bacteria to a metabolic Achilles heel, whereby kaempferol-induced dysregulation of iron homeostasis leads to bacterial killing. We demonstrate that this effect is due to the disruption of Fenton’s reaction, and therefore to a lethal build-up of toxic reactive oxygen species in the cell. Furthermore, we show that this vulnerability can be exploited to overcome both intrinsic and acquired colistin resistance in clinical strains of A. baumannii and E. coli in vitro and in the Galleria mellonella model of infection. Overall, our findings provide a proof-of-principle demonstration that targeting iron homeostasis is a promising strategy for enhancing the efficacy of colistin and overcoming colistin-resistant infections.R.R.M.C. and R.D. are supported by a BBSRC New Investigator Award BB/V007823/1. R.R.M.C. is also supported by the Academy of Medical Sciences/the Wellcome Trust/ the Government Department of Business, Energy and Industrial Strategy/the British Heart Foundation/Diabetes UK Springboard Award [SBF006\1040]. D.A.I.M. was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number R01AI15875