Bigraphical Refinement

We propose a mechanism for the vertical refinement of bigraphical reactive systems, based upon a mechanism for limiting observations and utilising the underlying categorical structure of bigraphs. We present a motivating example to demonstrate that the proposed notion of refinement is sensible with respect to the theory of bigraphical reactive systems; and we propose a sufficient condition for guaranteeing the existence of a safety-preserving vertical refinement. We postulate the existence of a complimentary notion of horizontal refinement for bigraphical agents, and finally we discuss the connection of this work to the general refinement of Reeves and Streader.Comment: In Proceedings Refine 2011, arXiv:1106.348

Potential role of endocrine gastrin in the colonic adenoma carcinoma sequence

The role of hyper-gastrinaemia in the incidence of colonic cancer remains to be clarified. The aim of this study was to determine whether cholecystokinin-2 (CCK-2) receptor expression predicts the sensitivity of human colonic adenomas to the proliferative effects of serum hyper-gastrinaemia. Gene expression of the classical (74 kDa) CCK-2 receptor in human colonic adenoma specimens and cell lines, was quantified by real-time PCR. Western blotting, using a CCK-2 receptor antiserum, confirmed protein expression. A transformed human colonic adenoma was grown in SCID mice, with hyper-gastrinaemia induced by protein pump inhibitors. CCK-2 receptor blockade was achieved by using neutralising antiserum. Both human colonic adenoma cell lines and biopsies expressed CCK-2 receptor mRNA at levels comparable with CCK-2 receptor transfected fibroblasts and oxyntic mucosa. Western blotting confirmed immunoreactive CCK-2 receptor bands localised to 45, 74 and 82.5 kDa. Omeprazole and lansoprazole-induced hyper-gastrinaemia (resulting in serum gastrin levels of 34.0 and 153.0 pM, respectively) significantly increased the weight of the human adenoma grafts (43% (P=0.016) and 70% (P=0.014), respectively). The effect of hypergastrinaemia on tumour growth was reversed by use of antiserum directed against the CCK-2 receptor. Hyper-gastrinaemia may promote proliferation of human colonic adenomas that express CCK-2 receptor isoforms

PARP14 is a PARP with both ADP-ribosyl transferase and hydrolase activities

This is the final version. Available on open access from the American Association for the Advancement of Science via the DOI in this recordData availability: The MS proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (92) partner repository with the dataset identifier PXD043452.PARP14 is a mono-ADP-ribosyl transferase involved in the control of immunity, transcription, and DNA replication stress management. However, little is known about the ADP-ribosylation activity of PARP14, including its substrate specificity or how PARP14-dependent ADP-ribosylation is reversed. We show that PARP14 is a dual-function enzyme with both ADP-ribosyl transferase and hydrolase activity acting on both protein and nucleic acid substrates. In particular, we show that the PARP14 macrodomain 1 is an active ADP-ribosyl hydrolase. We also demonstrate hydrolytic activity for the first macrodomain of PARP9. We reveal that expression of a PARP14 mutant with the inactivated macrodomain 1 results in a marked increase in mono(ADP-ribosyl)ation of proteins in human cells, including PARP14 itself and antiviral PARP13, and displays specific cellular phenotypes. Moreover, we demonstrate that the closely related hydrolytically active macrodomain of SARS2 Nsp3, Mac1, efficiently reverses PARP14 ADP-ribosylation in vitro and in cells, supporting the evolution of viral macrodomains to counteract PARP14-mediated antiviral response.Biotechnology and Biological Sciences Research Council (BBSRC)Wellcome TrustOxford University Challenge Seed FundEdward Penley Abraham Research FundOvarian Cancer Research AllianceResearch Council of NorwaySwedish Research CouncilMedical Research Council (MRC)Novo Nordisk Foundation Center for Protein ResearchDanish Council of Independent ResearchDanish Cancer Societ

Setting a baseline for global urban virome surveillance in sewage

The rapid development of megacities, and their growing connectedness across the world is becoming a distinct driver for emerging disease outbreaks. Early detection of unusual disease emergence and spread should therefore include such cities as part of risk-based surveillance. A catch-all metagenomic sequencing approach of urban sewage could potentially provide an unbiased insight into the dynamics of viral pathogens circulating in a community irrespective of access to care, a potential which already has been proven for the surveillance of poliovirus. Here, we present a detailed characterization of sewage viromes from a snapshot of 81 high density urban areas across the globe, including in-depth assessment of potential biases, as a proof of concept for catch-all viral pathogen surveillance. We show the ability to detect a wide range of viruses and geographical and seasonal differences for specific viral groups. Our findings offer a cross-sectional baseline for further research in viral surveillance from urban sewage samples and place previous studies in a global perspective

Multi-agent Systems Design and Prototyping with Bigraphical Reactive Systems

International audienceSeveral frameworks and methodologies have been proposed to ease the design of Multi Agent Systems (MAS), but the vast majority of them is tightly tied to specific implementation platforms. In this paper, we outline a methodology for MAS design and prototyping in the more abstract framework of Bigraphical Reactive Systems (BRS). In our approach, components and elements of the application domain are modelled as bigraphs, and their dynamics as graph rewriting rules. Desiderata can be encoded by means of type systems or logical formulae. Then, the BDI agents (i.e., their beliefs, desires and intentions) are identified and extracted from the BRS. This yield a prototype which can be run as distributed bigraphical system, evolving by means of distributed transactional rewritings triggered by cooperating agents depending on their internal intentions and beliefs.This methodology allows the designer to benefit from the results and tools from the theory of BRS, especially in the requirement analysis and validation phases. Among other results, we mention behavioural equivalences, temporal/spatial logics, visual tools for editing, for simulation and for model checking, etc. Moreover, bigraphs can be naturally composed, thus allowing for modular design of MAS