Dynamical complexity of discrete time regulatory networks

Genetic regulatory networks are usually modeled by systems of coupled differential equations and by finite state models, better known as logical networks, are also used. In this paper we consider a class of models of regulatory networks which present both discrete and continuous aspects. Our models consist of a network of units, whose states are quantified by a continuous real variable. The state of each unit in the network evolves according to a contractive transformation chosen from a finite collection of possible transformations, according to a rule which depends on the state of the neighboring units. As a first approximation to the complete description of the dynamics of this networks we focus on a global characteristic, the dynamical complexity, related to the proliferation of distinguishable temporal behaviors. In this work we give explicit conditions under which explicit relations between the topological structure of the regulatory network, and the growth rate of the dynamical complexity can be established. We illustrate our results by means of some biologically motivated examples.Comment: 28 pages, 4 figure

Geographical variation in antimicrobial use and multiresistant pathogens in Brazilian intensive care units: a nationwide study

Introduction: Geographical analyses of antibiotic use identify regions with the highest consumption and help design policies for strategic patient groups.Methodology: We conducted a cross-sectional study based on official data available in July 2022 from Brazilian Health Surveillance Agency (Anvisa). Antibiotics are reported as a defined daily dose (DDD) per 1,000 patient-days, and central line-associated bloodstream infection (CLABSI) is defined according to Anvisa criteria. We also considered multi-drug resistant (MDR) as the critical pathogens the World Health Organization listed. We measured antimicrobial use and CLABSI trends per ICU bed using the compound annual growth rate (CAGR). Results: we evaluated the regional variation in CLABSI by multidrug-resistant pathogens and the antimicrobial use in 1,836 hospital intensive care units (ICUs). In 2020, the leader in use in intensive care units (ICUs) in the North was piperacillin/tazobactam (DDD = 929.7) in the Northeast. Midwest and South were meropenem (DDD = 809.4 and DDD = 688.1, respectively), and Southeast was ceftriaxone (DDD = 751.1). The North has reduced polymyxin use (91.1%), and ciprofloxacin increased (439%) in the South. There was an increase in CLABSI by carbapenem-resistant Pseudomonas aeruginosa in the North region (CAGR = 120.5%). Otherwise, CLABSI by vancomycin-resistant Enterococcus faecium (VRE) increased in all regions except the North (CAGR =-62.2%), while that carbapenem-resistant Acinetobacter baumannii increased in the Midwest (CAGR = 27.3%). Conclusions: we found heterogeneity in antimicrobial use patterns and CLABSI etiology among Brazilian ICUs. Although Gram-negative bacilli were the primary responsible agent, we observed a notable increase trend of CLABSI by VRE

Fostering Awareness on Environmentally Sustainable Technological Solutions for the Post-Harvest Food Supply Chain

This study presents a current status and future trends of innovative and environmentally sustainable technological solutions for the post-harvest food supply chain and the food industry, in terms of ecological packaging, active, and/or intelligent packaging. All these concerns are currently highlighted due to the strong increase in the purchase/sale of products on online platforms, as well as the requirements for stricter food security and safety. Thus, this study aims to increase the global awareness of agro-industrial micro, small, and medium size enterprises for the adoption of innovative food solutions though industry digitalization (Industry 4.0), associated logistics and circular economy, with a concern for cybersecurity and products information, communication and shelf-life extension. The adoption of these guidelines will certainly foster along the complete food chain (from producer to consumer, with all intermediary parties) the awareness on environmentally sustainable technological solutions for the post-harvest food supply chain, and thus, promoting the future food sustainability required by the population increase, the climate change, the exodus of rural population to urban areas, and food loss and waste.This study is within the activities of project S4Agro-Soluções Sustentáveis para o Setor Agroindustrial (Sustainable Solutions for the Agro-industrial sector) promoted by COMPETE 2020– POCI–SIAC: 02/SIAC/2019 (POCI-02-0853-FEDER-046425) and co-financed by FEDER under the Portugal 2020 initiative.info:eu-repo/semantics/publishedVersio

Uso comum de recursos em organizações coletivistas: caso Bendita Colab

The present study aims to analyze how the common use of resources occurs in collectivist organizations. Specifically seeks to describe the logic of collectivist work, identify what are the shared resources, which mechanisms of sharing, and thus better understand the practices of common use of resources in a collectivist environment from the perspectives of reciprocity, reputation and trust. The object studied in this dissertation research is the Bendita Colab Collaborative Shop, which approaches the characteristics of collectivist organization in addition to exercising the sharing of resources. This is a unique case study of intrinsic value and of a qualitative, descriptive and exploratory nature. In which, first, the chosen organization, Bendita Colab, was described, where it was identified that this is a collectivist organization with the common use of resources, before the mechanisms of reciprocity, reputation and trust. All theoretical basis comes from studies of collectivist organizations and the common use of resources in collective actions, which are organizations that establish contradictions to the utilitarian logic, unlimited growth and the search for maximum efficiency, dominant in the market economy. We recognize in this study that the blessed owners are catalysts in the common use of resources, thus playing a central role within this organization. The results allow us to point out that several times there is an oscillation between a traditional bureaucratic model and the collectivist model within the Bendita Colab. These oscillations are evidenced in relation to Blendita's mode of organization as well as the common use of resources. Evidence of this oscillation is found in rational (formal) and non-rational (affective) relationships, where depending on the trust, reputation and reciprocity achieved by the craftsman in the house, he may have greater or lesser autonomy. Thus the more the mechanisms that regulate the common use of resources lean towards the non-rational (affective) pole, the greater the autonomy of artisans in the common use of resources. On the other hand, how much, but the mechanisms of trust, reputation and reciprocity lean towards the rational (formal) pole less the degree of autonomy.O presente estudo objetiva analisar como se dá o uso comum de recursos em organizações coletivistas. Especificamente busca descrever a lógica de trabalho coletivista, identificar quais são os recursos compartilhados, quais os mecanismos de compartilhamento, e assim melhor compreender as práticas do uso comum de recursos em um ambiente coletivista sobre as perspectivas de reciprocidade, reputação e confiança. O objeto estudado nesta pesquisa de dissertação é a Loja Colaborativa Bendita Colab, que se aproxima das características de organização coletivista além de exercer o compartilhamento de recursos. Trata-se de um estudo de caso único, de valor intrínseco, e de natureza qualitativa, descritiva e exploratória. Em que, primeiro descreveu-se a organização escolhida, Bendita Colab, onde identificou-se que esta é uma organização coletivista com o uso comum de recursos, perante os mecanismos de reciprocidade, reputação e confiança. Todo embasamento teórico advém dos estudos sobre as organizações coletivistas e sobre o uso comum de recursos em ações coletivas, sendo estas, organizações que estabelecem contradições à lógica utilitarista, ao crescimento ilimitado e à busca pela máxima eficiência, dominante na economia de mercado. Reconhecemos neste estudo que as sócias proprietárias da bendita são como catalizadoras no uso comum de recursos, tendo assim papel central dentro desta organização. Os resultados permitem apontar que por diversas vezes existe uma oscilação entre um modelo burocrático tradicional e o modelo coletivista dentro da Bendita Colab. Estas oscilações são evidenciadas com relação ao modo de organização da Bendita bem como o uso comum de recursos. Encontram-se evidencias desta oscilação nas relações racionais (formais) e não racionais (afetivas), onde dependendo da confiança, reputação e reciprocidade alcançadas pelo artesão na casa, o mesmo pode possuir maior, ou menor autonomia. Assim quanto mais os mecanismos que regulam o uso comum de recursos penderem para o polo não racional (afetivo), maior a autonomia dos artesãos no uso comum de recursos. Em contrapartida, quanto, mas os mecanismos de confiança, reputação e reciprocidade pendem para o polo racional (formal) menor o grau de autonomia

Biochemical Basis of Topoisomerase I Relaxation Activity Reduction by Nonenzymatic Lysine Acetylation

The relaxation activity of topoisomerase I is required for regulation of global and local DNA supercoiling. The in vivo topoisomerase I enzyme activity is sensitive to lysine acetylation⁻deacetylation and can affect DNA supercoiling and growth as a result. Nonenzymatic lysine acetylation by acetyl phosphate has been shown to reduce the relaxation activity of topoisomerase I. In this work, the biochemical consequence of topoisomerase I modification by acetyl phosphate with enzymatic assays was studied. Results showed that noncovalent binding to DNA and DNA cleavage by the enzyme were reduced as a result of the acetylation, with greater effect on DNA cleavage. Four lysine acetylation sites were identified using bottom-up proteomics: Lys13, Lys45, Lys346, and Lys488. The Lys13 residue modified by acetyl phosphate has not been reported previously as a lysine acetylation site for topoisomerase I. We discuss the potential biochemical consequence of lysine acetylation at this strictly conserved lysine and other lysine residues on the enzyme based on available genetic and structural information

Synthesis of temperature-responsive Dextran-MA/PNIPAAm particles for controlled drug delivery using superhydrophobic surfaces

Purpose: To implement a bioinspired methodology using superhydrophobic surfaces suitable for producing smart hydro- gel beads in which the bioactive substance is introduced in the particles during their formation. Methods: Several superhydrophobic surfaces, including polystyrene, aluminum and copper, were prepared. Polymeric solutions composed by photo-crosslinked dextran-methacrylated and thermal responsive poly(N-isopropylacrylamide) mixed with a protein (insulin or albumin) were dropped on the superhydrophobic surfaces, and the obtained millimetric spheres were hardened in a dry environment under UV light. Results: Spherical and non-sticky hydrogels particles were formed in few minutes on the superhydrophobic surfaces. The proteins included in the liquid formulation were homogeneously distributed in the particle network. The particles exhibited temperature-sensitive swelling, porosity and protein release rate, with the responsiveness tunable by the dextran-MA/PNIPAAm weight ratio.Conclusions: The proposed method permitted the preparation of smart hydrogel particles in one step with almost 100% encapsulation yield. The temperature-sensitive release profiles suggest that the obtained spherical-shaped biomaterials are suitable as protein carriers. These stimuli-responsive beads could have potential to be used in pharmaceutical or other biomedical applications, including tissue engineering and regenerative medicine.The authors acknowledge funding from the project: PTDC/QUI/68804/2006 (FCT), IBEROMARE-Procept, FEDER and MICINN (SAF2008-01679). The research leading to these results has also received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement #NMP4-SL-2009-229292. The authors are grateful to project DISC REGENERATION, Collaborative Project-Large-scale integrating project, NMP3-LA-2008-213904 for the use of the UV lamp

The role of functional polymorphisms in immune response genes as biomarkers of BCG Immunotherapy outcome in bladder cancer: Establishment of a predictive profile in a Southern Europe population

OBJECTIVE: To evaluate the predictive value of genetic polymorphisms in the context of BCG immunotherapy outcome and create a predictive profile that may allow discriminating the risk of recurrence. MATERIAL AND METHODS: In a dataset of 204 patients treated with BCG, we evaluate 42 genetic polymorphisms in 38 genes involved in the BCG mechanism of action, using Sequenom MassARRAY technology. Stepwise multivariate Cox Regression was used for data mining. RESULTS: In agreement with previous studies we observed that gender, age, tumor multiplicity and treatment scheme were associated with BCG failure. Using stepwise multivariate Cox Regression analysis we propose the first predictive profile of BCG immunotherapy outcome and a risk score based on polymorphisms in immune system molecules (SNPs in TNFA-1031T/C (rs1799964), IL2RA rs2104286 T/C, IL17A-197G/A (rs2275913), IL17RA-809A/G (rs4819554), IL18R1 rs3771171 T/C, ICAM1 K469E (rs5498), FASL-844T/C (rs763110) and TRAILR1-397T/G (rs79037040) in association with clinicopathological variables. This risk score allows the categorization of patients into risk groups: patients within the Low Risk group have a 90% chance of successful treatment, whereas patients in the High Risk group present 75% chance of recurrence after BCG treatment. CONCLUSION: We have established the first predictive score of BCG immunotherapy outcome combining clinicopathological characteristics and a panel of genetic polymorphisms. Further studies using an independent cohort are warranted. Moreover, the inclusion of other biomarkers may help to improve the proposed model

Changes in lipid distribution in E. coli strains in response to norfloxacin

Bacterial resistance to antibiotics has become an increasing threat, requiring not only the development of new targets in drug discovery, but more importantly, a better understanding of cellular response. In the current study, three closely related Escherichia coli strains, a wild type (MG1655), and an isogenic pair derived from the wild type (DPB635 and DPB636) are studied following exposure to sub lethal concentrations of antibiotic (norfloxacin) over time. In particular, genotype similarities between the three strains were assessed based on the lipid regulation response (e.g., presence/absence and up/down regulation). Lipid identification was performed using direct surface probe analysis (Matrix-assisted laser desorption/ionization, MALDI), coupled to high-resolution mass spectrometry (Fourier transform ion cyclotron resonance mass spectrometry, FT-ICR MS) followed by statistical analysis of variability and reproducibility across batches using internal standards. Inspection of the lipid profile showed that for the MG1655, DPB635 and DPB636 E. coli strains, a similar distribution of the altered lipids were observed after exposure to norfloxacin antibiotic (e.g., fatty acids and glycerol phospholipids are up and down regulated, respectively). Additionally, variations in the lipid distribution resemble the extent to which each strain can combat the antibiotic exposure. That is, the topA66 topoisomerase I mutation of DPB636 translates into diminished response related to antibiotic sensitivity when compared to MG1655 and the DPB635 strains