Conformational Heterogeneity of Unbound Proteins Enhances Recognition in Protein–Protein Encounters

To understand cellular processes at the molecular level we need to improve our knowledge of protein−protein interactions, from a structural, mechanistic, and energetic point of view. Current theoretical studies and computational docking simulations show that protein dynamics plays a key role in protein association and support the need for including protein flexibility in modeling protein interactions. Assuming the conformational selection binding mechanism, in which the unbound state can sample bound conformers, one possible strategy to include flexibility in docking predictions would be the use of conformational ensembles originated from unbound protein structures. Here we present an exhaustive computational study about the use of precomputed unbound ensembles in the context of protein docking, performed on a set of 124 cases of the Protein−Protein Docking Benchmark 3.0. Conformational ensembles were generated by conformational optimization and refinement with MODELLER and by short molecular dynamics trajectories with AMBER. We identified those conformers providing optimal binding and investigated the role of protein conformational heterogeneity in protein−protein recognition. Our results show that a restricted conformational refinement can generate conformers with better binding properties and improve docking encounters in medium-flexible cases. For more flexible cases, a more extended conformational sampling based on Normal Mode Analysis was proven helpful. We found that successful conformers provide better energetic complementarity to the docking partners, which is compatible with recent views of binding association. In addition to the mechanistic considerations, these findings could be exploited for practical docking predictions of improved efficiency.Peer ReviewedPostprint (author's final draft

A Bi-Objective Scheduling Problem in a Home Care Business

Presented at the 4th XoveTIC Conference, A Coruña, Spain, 7–8 October 2021.[Abstract] In this work we study a routing and scheduling problem for a home care business. The problem is composed of two conflicting objectives, therefore we study it as a bi-objective one. We obtain the Pareto frontier for small size instances using the AUGMECON2 method and, for bigger cases, we developed an heuristic algorithm. We also obtained some preliminary results that show the algorithm has good behaviour.This research/work has been supported by MINECO grant MTM2017-87197-C3-1-P, and by the Xunta de Galicia through the ERDF (Grupos de Referencia Competitiva ED431C-2016-015 and ED431C-2020-14 and Centro de Investigación del Sistema universitario de Galicia ED431G 2019/01).Xunta de Galicia; ED431C-2016-015Xunta de Galicia; ED431C-2020-14Xunta de Galicia; ED431G 2019/0

EFFECTS OF LOUVERS SHADING DEVICES ON VISUAL COMFORT AND ENERGY DEMAND OF AN OFFICE BUILDING. A CASE OF STUDY

This paper evaluates the building energy demand and visual comfort of a real case with a glazed façade office building placed in Málaga (Mediterranean city in the south of Spain). South oriented facades receive such a high solar gain that cooling demand cannot be handled by the current HVAC system. As an environmental friendly solution, a shading control strategy based on vertical and horizontal louvers is proposed. The study consists of a comparison between the actual and the refurbished building with shading devices. Daylighting simulation is done with Daysim (Daysim, 2016). A group of offices with south, east and north oriented facades is chosen for the study. Horizontal louvers in the south façade and vertical louvers in the east facade are modelled and simulated. The simulation changes the angle of the louver: 0º (perpendicular to the glazing), -30º, 30º, -60º, 60º. Visual comfort parameters analyzed are: illuminance, daylight autonomy (DA) and useful daylight index (UDI). With respect to the thermal comfort, not only louvers orientation try to provide solar protection for glazed areas in cooling period but also maximize solar gains in heating period. However, an excessive daylight could affect discomfort glare. Shading control strategy must provide the equilibrium between both aspects. Thermal demand is calculated with Trnsys (TRNSYS, 2016).Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

ANALYSIS OF THE L AW OF FALLING RATE OF PROFIT: EUROPEAN CASE

This work aims to analyse the existence or non-existence of a decreasing rate of profit in Europe and determine the factors influencing it according to the Marxist theory of profitability. To do so, a panel data model was estimated for seven European countries over more than 60 years (from 1960 to 2021, inclusive). The results obtained allow us to verify the tendency for profitability to fall, which could lead the capitalist system to fail

A collagen-targeted biomimetic RGD peptide to promote osteogenesis

Osteogenesis is a complex, multifactorial process in which many different signals interact. The bone morphogenetic proteins (BMPs) are the most potent inducers of osteoblastic differentiation, although very high doses of BMPs in combination with collagen type I formulations have to be used for clinical applications. Although integrin-binding arginine-glycine-aspartic acid (RGD) biomimetic peptides have shown some promising abilities to promote the attachment of cells to biomaterials and to direct their differentiation, the linking of these peptides to collagen sponges usually implies chemical manipulation steps. In this study, we describe the design and characterization of a synthetic collagen-targeted RGD biomimetic (CBD-RGD) peptide formed from a collagen-binding domain derived from the von Willebrand factor and the integrin-binding RGD sequence. This peptide was demonstrated to bind to absorbable collagen type I sponges (ACSs) without performing any chemical linking, and to induce the differentiation of MC3T3-E1 mouse preosteoblasts and rat bone marrow-derived mesenchymal stem cells. Furthermore, in vivo experiments showed that ACSs functionalized with CBD-RGD and loaded with a subfunctional dose of BMP-2-formed ectopic bone in rats, while nonfunctionalized sponges loaded with the same amount of BMP-2 did not. These results indicate that the combination of this biomimetic peptide with the currently used collagen+BMP system might be a promising approach to improve osteogenesis and to reduce the doses of BMPs needed in clinical orthopedics.MICINN (BIO2009-13903-C01-01) MINECO (BIO2012-34960) Junta de Andalucía (P07-CVI-2781) ISCiii, RETICS, Red Española de Terapia Celular (TerCel) (RD12/0019/0032) ISCiii, CIBER-BBN (CB06/01/1015

Post-treatment of real municipal wastewater effluents by means of granular activated carbon (GAC) based catalytic processes: A focus on abatement of pharmaceutically active compounds

Pharmaceutically active compounds (PhACs) widely present in urban wastewater effluents pose a threat to ecosystems in the receiving aquatic environment. In this work, efficiency of granular activated carbon (GAC) - based catalytic processes, namely catalytic wet peroxide oxidation (CWPO), peroxymonosulfate oxidation (PMS/GAC) and peroxydisulfate oxidation (PDS/GAC) at ambient temperature and pressure were studied for removal of 22 PhACs (ng L-1 level) that were present in secondary effluents of real urban wastewater. Concentrations of PhACs were measured using Ultra Performance Liquid Chromatography - Triple Quadrupole Mass Spectrometry (UPLC-QqQ-MS/MS). Catalytic experiments were conducted in discontinuous mode using up-flow fixed bed reactors with granular activated carbon (GAC) as a catalyst. The catalyst was characterized by means of N-2 adsorption-desorption isotherm, mercury intrusion porosimetry (MIP), elemental analysis, X-ray fluorescence spectroscopy (WDXRF), X-ray diffraction (XRD), thermal gravimetry and differential temperature analyses coupled mass spectrometry (TGA-DTA-MS). Results indicate that the highest efficiency in terms of TOC removal was achieved during CWPO performed at optimal operational conditions (stoichiometric dose of H2O2; TOC removal similar to 82%) followed by PMS/GAC (initial PMS concentration 100 mg L-1; TOC removal similar to 73.7%) and PDS/GAC (initial PDS concentration 100 mg L-1; TOC removal similar to 67.9%) after 5 min of contact time. Full consumption of oxidants was observed in all cases for CWPO and PDS/GAC at contact times of 2.5 min, while for PMS/GAC it was 1.5 min. In general, for 18 out of 22 target PhACs, very high removal efficiencies (> 92%) were achieved in all tested processes (including adsorption) performed at optimal operational conditions during 5 min of contact time. However, moderate (40 - 70%) and poor (< 40%) removal efficiencies were achieved for salicylic acid, ofloxacin, norfloxacin and ciprofloxacin, which can be possibly attributed to insufficient contact time. Despite high efficiency of all studied processes for PhACs elimination from urban wastewater effluent, CWPO seems to be more promising for continuous operation. (C) 2021 Elsevier Ltd. All rights reserved.Authors are grateful to staffmembers of Viikinmaki Wastewater Treatment Plant (Helsinki, Finland) for collaboration. D.Sc. Juan Jose Rueda-Marquez is thankful for financial support from Academy of Finland within the project "Combination of Advanced Oxidation Processes and Photobiotreatment for Sustainable Resource Recovery and Wastewater Reuse". D.Sc. Irina Levchuk is grateful for financial support obtained from KAUTE saatio(grant number: 201800116). D.Sc. Ana Rey is grateful for financial support from Ministerio de Economia y Competitividad (MINECO)Agencia Estatal de Investigacion (AEI) of Spain through the project CTQ2015-73168-JIN, co-financed by the European Funds for Regional Development (FEDER, UE). D. Sc. Javier Moreno-Andres is grateful for the financial support by the European Union under the 2014-2020 ERDF Operational Programme and by the Department of Economy, Knowledge, Business and University of the Regional Government of Andalusia. Project reference: FEDER-UCA18-108023

Práctica y formulario de la Chancillería de Valladolid dirigido a la Real Chancillería, Presidente y jueces della

Sign.: [ ]4, A-N4, O2, A-T4, [calderón]2.En port. esc. xil. realLas ultimas 78 h. corresponden al libro segundoCopia digital. Valladolid : Junta de Castilla y León. Consejería de Cultura y Turismo, 2009-201

Effect of Punicalagin and Ellagic Acid on Human Fibroblasts In Vitro: A Preliminary Evaluation of Their Therapeutic Potential

Background: Pomegranate is a fruit that contains various phenolic compounds, including punicalagin and ellagic acid, which have been attributed to anti-inflammatory, antioxidant, and anticarcinogenic properties, among others. Objective: To evaluate the effect of punicalagin and ellagic acid on the viability, migration, cell cycle, and antigenic profile of cultured human fibroblasts (CCD-1064Sk). MTT spectrophotometry was carried out to determine cell viability, cell culture inserts were used for migration trials, and flow cytometry was performed for antigenic profile and cell cycle analyses. Cells were treated with each phenolic compound for 24 h at doses of 10−5 to 10−9 M. Results: Cell viability was always significantly higher in treated versus control cells except for punicalagin at 10−9 M. Doses of punicalagin and ellagic acid in subsequent assays were 10−6 M or 10−7 M, which increased the cell migration capacity and upregulated fibronectin and α-actin expression without altering the cell cycle. Conclusions: These in vitro findings indicate that punicalagin and ellagic acid promote fibroblast functions that are involved in epithelial tissue healing.FEDER/Junta de Andalucía-Consejería de Universidad, Investigación e Innovación/B-CTS-134-UGR20 Projec

Simulation and Optimization Models of Steady-state Gas Transmission Networks

Managing a gas transport network is a complex problem because of the number of possibilities of routing the gas through the pipes. The most important aim in this kind of systems is to fulfill the demand within the pressure bounds, independently of its associated costs. However, in the present work some cost drivers are also taken into account by means of different objective functions in order to manage the network in an efficient way. This work deals with mathematical modeling and optimization of gas transport networks, where a two-stage procedure is proposed. In the first stage, optimization algorithms based on mathematical programming are applied to make some decisions (whether to activate compressor stations, control valves and other control elements) and gives an initial solution to the second stage. This last stage, which is based on control theory techniques, refines the solution to obtain more accurate results. Due to the reduced complexity in each stage, both can be solved within reasonable runtimes for relatively large gas networks. Based on the mathematical methods involved, a software called GANESOTM has been developedThe authors would like to acknowledge the support of Reganosa LNG Company and also Ministerio de Economía y Competitividad (Spain) under research project MTM2008-02483 and Xunta de Galicia (Spanish region) under research project EM2012/111S

Effect of the most common wound antiseptics on human skin fibroblasts

Background. Antiseptics are used for the cleansing of acute or chronic wounds to eliminate micro-organisms from the wound bed. However, they have effects on the skin cells. Aim. To determine the effects of hexetidine, povidone–iodine (PI), undecylenamidopropyl-betaine/polyhexanide (UBP), chlorhexidine, disodium eosin and hydrogen peroxide on human skin fibroblasts. Methods. CCD-1064Sk cells were treated with hexetidine, PI, UBP, chlorhexidine, disodium eosin or hydrogen peroxide. Spectrophotometry was used to measure cell viability and flow cytometry was used to study apoptosis and necrosis after the treat- ment. In vitro wound scratch assays were performed to determine the gap closure. Results. All antiseptics significantly reduced the viability of human skin fibroblasts compared with controls. The percentage wound closure was lower with hexetidine, PI and UBP. The scratch assay could not be measured after treatments with chlorhexidine, disodium eosin or hydrogen peroxide, owing to their cytotoxicity. The apoptosis/necrosis experiments evidenced a significant reduction in viable cells com- pared with controls. An increased percentage of apoptotic cells was observed after treatment with all antiseptics. Compared with controls, the percentage of necrotic cells was significantly increased with all antiseptics except for hexetidine. Conclusion. The proliferation, migration and viability of human skin fibroblasts are reduced by treatment with hexetidine, PI, UBP, chlorhexidine, disodium eosin and hydrogen peroxide.This research received funding for open access charge from the University of Granada/CBUA