Computing with cells: membrane systems - some complexity issues.

Membrane computing is a branch of natural computing which abstracts computing models from the structure and the functioning of the living cell. The main ingredients of membrane systems, called P systems, are (i) the membrane structure, which consists of a hierarchical arrangements of membranes which delimit compartments where (ii) multisets of symbols, called objects, evolve according to (iii) sets of rules which are localised and associated with compartments. By using the rules in a nondeterministic/deterministic maximally parallel manner, transitions between the system configurations can be obtained. A sequence of transitions is a computation of how the system is evolving. Various ways of controlling the transfer of objects from one membrane to another and applying the rules, as well as possibilities to dissolve, divide or create membranes have been studied. Membrane systems have a great potential for implementing massively concurrent systems in an efficient way that would allow us to solve currently intractable problems once future biotechnology gives way to a practical bio-realization. In this paper we survey some interesting and fundamental complexity issues such as universality vs. nonuniversality, determinism vs. nondeterminism, membrane and alphabet size hierarchies, characterizations of context-sensitive languages and other language classes and various notions of parallelism

Genetic and genomic resources, and breeding for accelerating improvement of small millets: current status and future interventions

Current agricultural and food systems encourage research and development on major crops, neglecting regionally important minor crops. Small millets include a group of small- seeded cereal crops of the grass family Poaceae. This includes finger millet, foxtail millet, proso millet, barnyard millet, kodo millet, little millet, teff, fonio, job’s tears, guinea millet, and browntop millet. Small millets are an excellent choice to supplement major staple foods for crop and dietary diversity because of their diverse adaptation on marginal lands, less water requirement, lesser susceptibility to stresses, and nutritional superiority compared to major cereal staples. Growing interest among consumers about healthy diets together with climate-resilient features of small millets underline the necessity of directing more research and development towards these crops. Except for finger millet and foxtail millet, and to some extent proso millet and teff, other small millets have received minimal research attention in terms of development of genetic and genomic resources and breeding for yield enhancement. Considerable breeding efforts were made in finger millet and foxtail millet in India and China, respectively, proso millet in the United States of America, and teff in Ethiopia. So far, five genomes, namely foxtail millet, finger millet, proso millet, teff, and Japanese barnyard millet, have been sequenced, and genome of foxtail millet is the smallest (423-510 Mb) while the largest one is finger millet (1.5 Gb). Recent advances in phenotyping and genomics technologies, together with available germplasm diversity, could be utilized in small millets improvement. This review provides a comprehensive insight into the importance of small millets, the global status of their germplasm, diversity, promising germplasm resources, and breeding approaches (conventional and genomic approaches) to accelerate climate-resilient and nutrient-dense small millets for sustainable agriculture, environment, and healthy food systems

The Nondeterministic Waiting Time Algorithm: A Review

We present briefly the Nondeterministic Waiting Time algorithm. Our technique for the simulation of biochemical reaction networks has the ability to mimic the Gillespie Algorithm for some networks and solutions to ordinary differential equations for other networks, depending on the rules of the system, the kinetic rates and numbers of molecules. We provide a full description of the algorithm as well as specifics on its implementation. Some results for two well-known models are reported. We have used the algorithm to explore Fas-mediated apoptosis models in cancerous and HIV-1 infected T cells

Pharmacologic prophylaxis for atrial fibrillation following cardiac surgery: a systematic review

Atrial Fibrillation (AF) is the most common arrhythmia occurring after cardiac surgery. Its incidence varies depending on type of surgery. Postoperative AF may cause hemodynamic deterioration, predispose to stroke and increase mortality. Effective treatment for prophylaxis of postoperative AF is vital as reduces hospitalization and overall morbidity. Beta - blockers, have been proved to prevent effectively atrial fibrillation following cardiac surgery and should be routinely used if there are no contraindications. Sotalol may be more effective than standard b-blockers for the prevention of AF without causing an excess of side effects. Amiodarone is useful when beta-blocker therapy is not possible or as additional prophylaxis in high risk patients. Other agents such as magnesium, calcium channels blocker or non-antiarrhythmic drugs as glycose-insulin - potassium, non-steroidal anti-inflammatory drugs, corticosteroids, N-acetylcysteine and statins have been studied as alternative treatment for postoperative AF prophylaxis

Metabolic Syndrome and Acute Respiratory Distress Syndrome in Hospitalized Patients With COVID-19

Importance: Obesity, diabetes, and hypertension are common comorbidities in patients with severe COVID-19, yet little is known about the risk of acute respiratory distress syndrome (ARDS) or death in patients with COVID-19 and metabolic syndrome. Objective: To determine whether metabolic syndrome is associated with an increased risk of ARDS and death from COVID-19. Design, setting, and participants: This multicenter cohort study used data from the Society of Critical Care Medicine Discovery Viral Respiratory Illness Universal Study collected from 181 hospitals across 26 countries from February 15, 2020, to February 18, 2021. Outcomes were compared between patients with metabolic syndrome (defined as ≥3 of the following criteria: obesity, prediabetes or diabetes, hypertension, and dyslipidemia) and a control population without metabolic syndrome. Participants included adult patients hospitalized for COVID-19 during the study period who had a completed discharge status. Data were analyzed from February 22 to October 5, 2021. Exposures: Exposures were SARS-CoV-2 infection, metabolic syndrome, obesity, prediabetes or diabetes, hypertension, and/or dyslipidemia. Main outcomes and measures: The primary outcome was in-hospital mortality. Secondary outcomes included ARDS, intensive care unit (ICU) admission, need for invasive mechanical ventilation, and length of stay (LOS). Results: Among 46 441 patients hospitalized with COVID-19, 29 040 patients (mean [SD] age, 61.2 [17.8] years; 13 059 [45.0%] women and 15713 [54.1%] men; 6797 Black patients [23.4%], 5325 Hispanic patients [18.3%], and 16 507 White patients [57.8%]) met inclusion criteria. A total of 5069 patients (17.5%) with metabolic syndrome were compared with 23 971 control patients (82.5%) without metabolic syndrome. In adjusted analyses, metabolic syndrome was associated with increased risk of ICU admission (adjusted odds ratio [aOR], 1.32 [95% CI, 1.14-1.53]), invasive mechanical ventilation (aOR, 1.45 [95% CI, 1.28-1.65]), ARDS (aOR, 1.36 [95% CI, 1.12-1.66]), and mortality (aOR, 1.19 [95% CI, 1.08-1.31]) and prolonged hospital LOS (median [IQR], 8.0 [4.2-15.8] days vs 6.8 [3.4-13.0] days; P \u3c .001) and ICU LOS (median [IQR], 7.0 [2.8-15.0] days vs 6.4 [2.7-13.0] days; P \u3c .001). Each additional metabolic syndrome criterion was associated with increased risk of ARDS in an additive fashion (1 criterion: 1147 patients with ARDS [10.4%]; P = .83; 2 criteria: 1191 patients with ARDS [15.3%]; P \u3c .001; 3 criteria: 817 patients with ARDS [19.3%]; P \u3c .001; 4 criteria: 203 patients with ARDS [24.3%]; P \u3c .001). Conclusions and relevance: These findings suggest that metabolic syndrome was associated with increased risks of ARDS and death in patients hospitalized with COVID-19. The association with ARDS was cumulative for each metabolic syndrome criteria present

A membrane computing simulator of trans-hierarchical antibiotic resistance evolution dynamics in nested ecological compartments (ARES)

In this article, we introduce ARES (Antibiotic Resistance Evolution Simulator) a software device that simulates P-system model scenarios with five types of nested computing membranes oriented to emulate a hierarchy of eco-biological compartments, i.e. a) peripheral ecosystem; b) local environment; c) reservoir of supplies; d) animal host; and e) host's associated bacterial organisms (microbiome). Computational objects emulating molecular entities such as plasmids, antibiotic resistance genes, antimicrobials, and/or other substances can be introduced into this framework and may interact and evolve together with the membranes, according to a set of pre-established rules and specifications. ARES has been implemented as an online server and offers additional tools for storage and model editing and downstream analysisThis work has also been supported by grants BFU2012-39816-C02-01 (co-financed by FEDER funds and the Ministry of Economy and Competitiveness, Spain) to AL and Prometeo/2009/092 (Ministry of Education, Government of Valencia, Spain) and Explora Ciencia y Explora Tecnologia/SAF2013-49788-EXP (Spanish Ministry of Economy and Competitiveness) to AM. IRF is recipient of a "Sara Borrell" postdoctoral fellowship (Ref. CD12/00492) from the Ministry of Economy and Competitiveness (Spain). We are also grateful to the Spanish Network for the Study of Plasmids and Extrachromosomal Elements (REDEEX) for encouraging and funding cooperation among Spanish microbiologists working on the biology of mobile genetic elements (Spanish Ministry of Science and Innovation, reference number BFU2011-14145-E).Campos Frances, M.; Llorens, C.; Sempere Luna, JM.; Futami, R.; Rodríguez, I.; Carrasco, P.; Capilla, R.... (2015). A membrane computing simulator of trans-hierarchical antibiotic resistance evolution dynamics in nested ecological compartments (ARES). Biology Direct. 10(41):1-13. https://doi.org/10.1186/s13062-015-0070-9S1131041Baquero F, Coque TM, Canton R. Counteracting antibiotic resistance: breaking barriers among antibacterial strategies. Expert Opin Ther Targets. 2014;18:851–61.Baquero F, Lanza VF, Canton R, Coque TM. Public health evolutionary biology of antimicrobial resistance: priorities for intervention. Evol Appl. 2014;8:223–39.Baquero F, Coque TM, de la Cruz F. Ecology and evolution as targets: the need for novel eco-evo drugs and strategies to fight antibiotic resistance. Antimicrob Agents Chemother. 2011;55:3649–60.Carlet J, Jarlier V, Harbarth S, Voss A, Goossens H, Pittet D, et al. Ready for a world without antibiotics? The pensieres antibiotic resistance call to action. Antimicrob Resist Infect Control. 2012;1:11.Laxminarayan R, Duse A, Wattal C, Zaidi AK, Wertheim HF, Sumpradit N, et al. Antibiotic resistance-the need for global solutions. Lancet Infect Dis. 2013;13:1057–98.G8-Science-Ministers-Statement. 2013. https://www.gov.uk/government/news/g8-science-ministers-statement .Levy SB, Marshall B. Antibacterial resistance worldwide: causes, challenges and responses. Nat Med. 2004;10:S122–9.Wellington EM, Boxall AB, Cross P, Feil EJ, Gaze WH, Hawkey PM, et al. The role of the natural environment in the emergence of antibiotic resistance in gram-negative bacteria. Lancet Infect Dis. 2013;13:155–65.Marshall BM, Levy SB. Food animals and antimicrobials: impacts on human health. Clin Microbiol Rev. 2011;24:718–33.Marshall BM, Ochieng DJ, Levy SB. Commensals: underappreciated reservoir of antibiotic resistance. Microbe. 2009;4:231–8.Forsberg KJ, Reyes A, Wang B, Selleck EM, Sommer MO, Dantas G. The shared antibiotic resistome of soil bacteria and human pathogens. Science. 2012;337:1107–11.Heuer H, Schmitt H, Smalla K. Antibiotic resistance gene spread due to manure application on agricultural fields. Curr Opin Microbiol. 2011;14:236–43.Teillant A, Laxminarayan R. Economics of Antibiotic Use in U.S. Swine and Poultry Production. Choices. 2015;30:1. 1st Quarter 2015.ANTIBIOTIC RESISTANCE THREATS in the United States. http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf .Gillings MR. Evolutionary consequences of antibiotic use for the resistome, mobilome and microbial pangenome. Front Microbiol. 2013;4:4.Davies J, Davies D. Origins and evolution of antibiotic resistance. Microbiol Mol Biol Rev. 2010;74:417–33.Palmer AC, Kishony R. Understanding, predicting and manipulating the genotypic evolution of antibiotic resistance. Nat Rev Genet. 2013;14:243–8.Baquero F, Tedim AP, Coque TM. Antibiotic resistance shaping multi-level population biology of bacteria. Front Microbiol. 2013;4:15.Partridge SR. Analysis of antibiotic resistance regions in Gram-negative bacteria. FEMS Microbiol Rev. 2011;35:820–55.Baquero F, Coque TM. Multilevel population genetics in antibiotic resistance. FEMS Microbiol Rev. 2011;35:705–6.Martinez JL, Baquero F, Andersson DI. Predicting antibiotic resistance. Nat Rev Microbiol. 2007;5:958–65.Martinez JL, Baquero F. Emergence and spread of antibiotic resistance: setting a parameter space. Upsala Journal of Medical Sciences. Upsala J Med Sci. 2014, Early Online: 1–10, doi: 10.3109/03009734.2014.901444 ).Baquero F, Nombela C. The microbiome as a human organ. Clin Microbiol Infect. 2012;18 Suppl 4:2–4.Kumsa B, Socolovschi C, Parola P, Rolain JM, Raoult D. Molecular detection of Acinetobacter species in lice and keds of domestic animals in Oromia Regional State. Ethiopia PLoS One. 2012;7:e52377.Ahmad A, Ghosh A, Schal C, Zurek L. Insects in confined swine operations carry a large antibiotic resistant and potentially virulent enterococcal community. BMC Microbiol. 2011;11:23.Graczyk TK, Knight R, Gilman RH, Cranfield MR. The role of non-biting flies in the epidemiology of human infectious diseases. Microbes Infect. 2001;3:231–5.Limoee M, Enayati AA, Khassi K, Salimi M, Ladonni H. Insecticide resistance and synergism of three field-collected strains of the German cockroach Blattella germanica (L.) (Dictyoptera: Blattellidae) from hospitals in Kermanshah, Iran. Trop Biomed. 2011;28:111–8.Salehzadeha A, Tavacolb P, Mahjubc H. Bacterial, fungal and parasitic contamination of cockroaches in public hospitals of Hamadan, Iran. J Vect Borne Dis. 2007;44:105–10.Akinjogunla OJ, Odeyemi AT, Udoinyang EP. Cockroaches (periplaneta americana and blattella germanica): reservoirs of multi drug resistant (MDR) bacteria in Uyo, Akwa Ibom State. Scientific J Biol Sci. 2012;1:19–30.Mideo N, Alizon S, Day T. Linking within- and between-host dynamics in the evolutionary epidemiology of infectious diseases. Trends Ecol Evol. 2008;23:511–7.Gillings MR, Stokes HW. Are humans increasing bacterial evolvability? Trends EcolEvol. 2012;27:346–52.Baquero F. Environmental stress and evolvability in microbial systems. Clin Microbiol Infect. 2009;15 Suppl 1:5–10.Paun G, Rozemberg G, Salomaa A. The Oxford Handbook of Membrane Computing. Oxford, London. Oxford University Press. 2010.Paun G. Membrane Computing. An Introduction. Berlin, Heidelberg. Springer-Verlag GmbH. 2002.Paun G. Computing with membranes. J Comput Syst Sci. 2000;61:108–43.Fontana F, Biancom L, Manca V. P systems and the modeling of biochemical oscillations. Lect Notes Comput Sci. 2006;3850:199–208.Cheruku S, Paun A, Romero-Campero FJ, Perez-Jimenez MJ, Ibarra OH. Simulating FAS-induced apoptosis by using P systems. Prog Nat Sci. 2007;4:424–31.Perez-Jimenez MJ, Romero-Campero FJ. P systems, a new computational modelling tool for systems biology. Transactions on computational systems. Lect N Bioinformat. 2006;Biology VI:176–97.Romero-Campero FJ, Perez-Jimenez MJ. Modelling gene expression control using P systems: The Lac Operon, a case study. Biosystems. 2008;91:438–57.Romero-Campero FJ, Perez-Jimenez MJ. A model of the quorum sensing system in Vibrio fischeri using P systems. Artif Life. 2008;14:95–109.Besozzi D, Cazzaniga P, Pescini D, Mauri G. Modelling metapopulations with stochastic membrane systems. Biosystems. 2008;91:499–514.Cardona M, Colomer MA, Perez-Jimenez MJ, Sanuy D, Margalida A. Modelling ecosystems using P Systems: The Bearded Vulture, a case of study. Lect Notes Comput Sci. 2009;5391:137–56.Cardona M, Colomer MA, Margalida A, Perez-Hurtado I, Perez-Jimenez MJ, Sanuy D. A P system based model of an ecosystem of some scavenger birds. Lect Notes Comput Sci. 2010;5957:182–95.Frisco P, Gheorghe M, Perez-Jimenez M. Applications of Membrane Computing in Systems and Synthetic biology. Cham. Springer International Publishing. 2014.Membrane Computing Community. http://ppage.psystems.eu .P-Lingua. http://www.p-lingua.org/wiki/index.php/Main_Page .Llorens C, Futami R, Covelli L, Dominguez-Escriba L, Viu JM, Tamarit D, et al. The Gypsy Database (GyDB) of mobile genetic elements: release 2.0. Nucleic Acids Res. 2011;39:D70–4.Baquero F. From pieces to patterns: evolutionary engineering in bacterial pathogens. Nat Rev Microbiol. 2004;2:510–8.Java. http://www.java.com .Garcia-Quismondo M, Gutierrez-Escudero R, Martinez-del-Amor MA, Orejuela-Pinedo E, Pérez-Hurtado I. P-Lingua 2.0: a software framework for cell-like P systems. Int J Comput Commun. 2009;IV:234.R programming language. http://www.r-project.org .Maciel A, Sankaranarayanan G, Halic T, Arikatla VS, Lu Z, De S. Surgical model-view-controller simulation software framework for local and collaborative applications. Int J Comput Assist Radiol Surg. 2011;6:457–71.Dethlefsen L, McFall-Ngai M, Relman DA. An ecological and evolutionary perspective on human-microbe mutualism and disease. Nature. 2007;449:811–8.Ley RE, Lozupone CA, Hamady M, Knight R, Gordon JI. Worlds within worlds: evolution of the vertebrate gut microbiota. Nat Rev Microbiol. 2008;6:776–88.Pallen MJ, Wren BW. Bacterial pathogenomics. Nature. 2007;449:835–42.Carrasco P, Perez-Cobas AE, Van de Pol C, Baixeras J, Moya A, Latorre A. Succession of the gut microbiota in the cockroach Blattella germanica. Int Microbiol. 2014;17:99–109

Fluorescent amino acids as versatile building blocks for chemical biology

Fluorophores have transformed the way we study biological systems, enabling non-invasive studies in cells and intact organisms, which increase our understanding of complex processes at the molecular level. Fluorescent amino acids have become an essential chemical tool because they can be used to construct fluorescent macromolecules, such as peptides and proteins, without disrupting their native biomolecular properties. Fluorescent and fluorogenic amino acids with unique photophysical properties have been designed for tracking protein–protein interactions in situ or imaging nanoscopic events in real time with high spatial resolution. In this Review, we discuss advances in the design and synthesis of fluorescent amino acids and how they have contributed to the field of chemical biology in the past 10 years. Important areas of research that we review include novel methodologies to synthesize building blocks with tunable spectral properties, their integration into peptide and protein scaffolds using site-specific genetic encoding and bioorthogonal approaches, and their application to design novel artificial proteins, as well as to investigate biological processes in cells by means of optical imaging. [Figure not available: see fulltext.]

Integrin αvβ6 sets the stage for colorectal cancer metastasis

The β6 subunit of the αvβ6 integrin heterodimer has long been an enigma in cancer biology though recent research has provided many new insights into its biology. Collectively, these findings include discovery of the transcriptional, translational and cell biological mechanisms by which β6 acts, the identification of the cellular influences β6 exerts upon the cell proteome, the characterisation of multiple β6-centric pro-metastatic signalling systems and the search for pharmacological therapies (industry and academia) targeted against β6. Once expressional restriction is overcome in early colorectal cancer (CRC), epithelial cell surface restricted αvβ6 can physically interact with, and activate, known oncoproteins, and has the potential to enable the cross-talk through non-canonical signal transduction pathways, resulting in the adoption of an invasive/metastatic phenotype. This recent research has identified numerous interconnections and potential feedback loops, highlighting the fact that the expression of the β6 subunit may initiate a cascade of downstream effects on the CRC cell rather than acting through a single mechanism. We here review these recent studies and postulate that the existence of a cell surface uPAR/αvβ6/TGFβ "metastasome" interactome in/on a proportion of colorectal cancer cells, where β6 expression sequesters and activates multiple systems at the invasive front of tumour lesions, promoting cancer metastasis and hence explaining why β6 has been correlated with reduced patient survival in CRC.20 page(s

Measurement of Cyanine Dye Photobleaching in Photosensitizer Cyanine Dye Conjugates Could Help in Optimizing Light Dosimetry for Improved Photodynamic Therapy of Cancer

Photodynamic therapy (PDT) of cancer is dependent on three primary components: photosensitizer (PS), light and oxygen. Because these components are interdependent and vary during the dynamic process of PDT, assessing PDT efficacy may not be trivial. Therefore, it has become necessary to develop pre-treatment planning, on-line monitoring and dosimetry strategies during PDT, which become more critical for two or more chromophore systems, for example, PS-CD (Photosensitizer-Cyanine dye) conjugates developed in our laboratory for fluorescence-imaging and PDT of cancer. In this study, we observed a significant impact of variable light dosimetry; (i) high light fluence and fluence rate (light dose: 135 J/cm2, fluence rate: 75 mW/cm2) and (ii) low light fluence and fluence rate (128 J/cm2 and 14 mW/cm2 and 128 J/cm2 and 7 mW/cm2) in photobleaching of the individual chromophores of PS-CD conjugates and their long-term tumor response. The fluorescence at the near-infrared (NIR) region of the PS-NIR fluorophore conjugate was assessed intermittently via fluorescence imaging. The loss of fluorescence, photobleaching, caused by singlet oxygen from the PS was mapped continuously during PDT. The tumor responses (BALB/c mice bearing Colon26 tumors) were assessed after PDT by measuring tumor sizes daily. Our results showed distinctive photobleaching kinetics rates between the PS and CD. Interestingly, compared to higher light fluence, the tumors exposed at low light fluence showed reduced photobleaching and enhanced long-term PDT efficacy. The presence of NIR fluorophore in PS-CD conjugates provides an opportunity of fluorescence imaging and monitoring the photobleaching rate of the CD moiety for large and deeply seated tumors and assessing PDT tumor response in real-time