Dynamics and Energetics of a Bromodomain in complex with bromosporine from Leishmania donovani

Leishmaniasis continues to be a neglected tropical disease, affecting people and animals and causing significant economic losses. Therefore, there is interest in the study and evaluation of new drug targets. In fact, it has been shown that by interfering with lysine-reading proteins such as bromodomain (BMD) there is a decrease in parasite survival. In this study, we researched the dynamics and energetics of the Leishmania donovani BMD in complex with bromosporin, which is considered to be a pan-inhibitor of BMDs, with the aim of understanding the molecular recognition mechanism. Molecular dynamics (MD) and non-equilibrium free energy calculation guided by steered molecular dynamics (SMD) simulations showed that the BMD has three flexible amino acid regions and bromosporin exhibiting various recognition states during the interaction. These results corroborate the promiscuity of bromosporin for energetically favourable sites, with the possibility of expanding its inhibition to other bromodomains. Furthermore, these results suggest that Van der Waals interactions have more relevance for complex recognition and residues ASN-87 and TRP-93 are key in forming hydrophobic and H-bond interactions, respectively. This research provides new insights for understanding the recognition mechanism, dynamics and energetics of the complex for the development of new therapeutic strategies.

La leishmaniasis sigue siendo una enfermedad tropical desatendida, que afecta a personas y animales y causa importantes pérdidas económicas. De ahí el interés por estudiar y evaluar nuevas dianas farmacológicas. De hecho, se ha demostrado que al interferir con proteínas lectoras de lisina como el bromodominio ("bromodomain", BMD) se produce una disminución de la supervivencia del parásito. En este artículo estudiamos la dinámica y la energética del BMD de Leishmania donovani en complejo con bromosporina, que se considera un pan-inhibidor de BMD, con el objetivo de comprender el mecanismo de reconocimiento molecular. Las simulaciones de dinámica molecular (DM) y el cálculo de energía libre de no-equilibrio guiado por dinámica molecular de estiramiento (DMS) mostraron que BMD tiene tres regiones de aminoácidos flexibles y la bromosporina presenta varios estados de reconocimiento durante la interacción. Estos resultados corroboran la promiscuidad de la bromosporina por sitios energéticamente favorables, siendo posible expandir su inhibición a otros bromodominios. Además, los resultados sugieren que las interacciones de Van der Waals tienen más relevancia para el reconocimiento del complejo y los residuos ASN-87 y TRP-93 son clave en la formación de interacciones hidrofóbicas y de puentes de hidrógeno, respectivamente. Esta investigación proporciona nuevos conocimientos para comprender el mecanismo de reconocimiento molecular, la dinámica y la energética del complejo para el desarrollo de nuevas estrategias terapéuticas.

A leishmaniose continua a ser uma doença tropical negligenciada, que afeta os seres humanos e os animais e causa perdas econômicas significativas. Daí o interesse em estudar e avaliar novos alvos de medicamentos. De fato, a interferência com proteínas leitoras de lisina, como o bromo domínio ("bromodomain", BMD), tem demonstrado diminuir a sobrevivência do parasita. Neste trabalho, estudamos a dinâmica e a energética do BMD de Leish-mania donovani em complexo com a bro-mosporina, considerada um pan-inibidor da BMDs, com o objetivo de compreender o mecanismo de reconhecimento molecular. As simulações de dinâmica molecular (MD) e cálculo de energia livre de não-equilíbrio guiada por dinâmica molecular esticamento (MDS) mostraram que o BMD tem três regiões de aminoácidos flexíveis e que a bromosporina apresenta vários estados de reconhecimento durante a interação. Esses resultados corroboram a promiscuidade da bromosporina para locais energeticamente favoráveis, possibilitando a expansão de sua inibição para outros bromodomínios. Além disso, os resultados sugerem que as interações de Van der Waals são mais relevantes no momento do reconhecimento do complexo e os resíduos ASN-87 e TRP-93 são fundamentais na formação de interações hidrofóbicas e de ligações de hidrogênio, respectivamente. Essa pesquisa fornece novos insights para compreender o mecanismo de reconhecimento, a dinâmica e a energética do complexo para o desenvolvimento de novas estratégias terapêuticas.

Some bis (3-(4-nitrophenyl)acrylamide derivatives: Synthesis, characterization, DFT, antioxidant, antimicrobial properties, molecular docking and molecular dynamics simulation studies-Supplemenntary data

Alzheimer's disease, which is a progressive neurologic disorder, is the most common form of dementia. Although there are various treatment options for Alzheimer’s disease, there is no definite treatment for this disease yet. In this study it was aimed to investigate the treatment potentials of three bis(3-(4-nitrophenyl)acrylamide) derivatives, two of which are known and one is new, for Alzheimer's disease. The study consists of three parts; in the first part of the study, synthesis and characterization studies of the investigated compounds were carried out. In the characterization of the compounds, IR, 1H-NMR, 13C-NMR, LC-MS and elemental analysis techniques were used. In the second part of the study, the compounds were investigated computationally with the assistance of various computational techniques including density functional theory (DFT) calculations, molecular docking and molecular dynamics simulations. In this part, binding free energy calculations were also performed on the investigated compounds. Results of computational studies showed that synthesized compounds interacted with AChE effectively and can be promising structures as AChE inhibitors. In the last part of the study, antioxidant and antimicrobial properties of the compounds were investigated. Antioxidant activities were determined by DPPH? and ABTS?? radical scavenging methods. According to the DPPH? test, the most active compound was found to be 2, while the most active compound was found to be 3 according to the ABTS? test, showing that these methods for antioxidant assay were not significantly correlated with each other. On the other hand, the results of the antimicrobial activity tests showed that compound 3 was the most active compound, which exhibited both antioxidant and antimicrobial activity.

Some bis (3-(4-nitrophenyl)acrylamide derivatives: Synthesis, characterization, DFT, antioxidant, antimicrobial properties, molecular docking and molecular dynamics simulation studies

Alzheimer's disease, which is a progressive neurologic disorder, is the most common form of dementia. Although there are various treatment options for Alzheimer’s disease, there is no definite treatment for this disease yet. In this study it was aimed to investigate the treatment potentials of three bis(3-(4-nitrophenyl)acrylamide) derivatives, two of which are known and one is new, for Alzheimer's disease. The study consists of three parts; in the first part of the study, synthesis and characterization studies of the investigated compounds were carried out. In the characterization of the compounds, IR, 1H-NMR, 13C-NMR, LC-MS and elemental analysis techniques were used. In the second part of the study, the compounds were investigated computationally with the assistance of various computational techniques including density functional theory (DFT) calculations, molecular docking and molecular dynamics simulations. In this part, binding free energy calculations were also performed on the investigated compounds. Results of computational studies showed that synthesized compounds interacted with AChE effectively and can be promising structures as AChE inhibitors. In the last part of the study, antioxidant and antimicrobial properties of the compounds were investigated. Antioxidant activities were determined by DPPH? and ABTS?? radical scavenging methods. According to the DPPH? test, the most active compound was found to be 2, while the most active compound was found to be 3 according to the ABTS? test, showing that these methods for antioxidant assay were not significantly correlated with each other. On the other hand, the results of the antimicrobial activity tests showed that compound 3 was the most active compound, which exhibited both antioxidant and antimicrobial activity.

Free energy perturbation (FEP)-guided scaffold hopping

Scaffold hopping refers to computer-aided screening for active compounds with different structures against the same receptor to enrich privileged scaffolds, which is a topic of high interest in organic and medicinal chemistry. However, most approaches cannot efficiently predict the potency level of candidates after scaffold hopping. Herein, we identified potent PDE5 inhibitors with a novel scaffold via a free energy perturbation (FEP)-guided scaffold-hopping strategy, and FEP shows great advantages to precisely predict the theoretical binding potencies ΔG FEP between ligands and their target, which were more consistent with the experimental binding potencies ΔG EXP (the mean absolute deviations | Δ G FEP - Δ G EXP |  < 2 kcal/mol) than those ΔG MM-PBSA or ΔG MM-GBSA predicted by the MM-PBSA or MM-GBSA method. Lead L12 had an IC50 of 8.7 nmol/L and exhibited a different binding pattern in its crystal structure with PDE5 from the famous starting drug tadalafil. Our work provides the first report via the FEP-guided scaffold hopping strategy for potent inhibitor discovery with a novel scaffold, implying that it will have a variety of future applications in rational molecular design and drug discovery.

Structure-based discovery of orally efficient inhibitors via unique interactions with H-pocket of PDE8 for the treatment of vascular dementia

Our previous study demonstrated that phosphodiesterase 8 (PDE8) could work as a potential target for vascular dementia (VaD) using a chemical probe 3a. However, compound 3a is a chiral compound which was obtained by chiral resolution on HPLC, restricting its usage in clinic. Herein, a series of non-chiral 9-benzyl-2-chloro-adenine derivatives were discovered as novel PDE8 inhibitors. Lead 15 exhibited potent inhibitory activity against PDE8A (IC50 = 11 nmol/L), high selectivity over other PDEs, and remarkable drug-like properties (worthy to mention is that its bioavailability was up to 100%). Oral administration of 15 significantly improved the cAMP level of the right brain and exhibited dose-dependent effects on cognitive improvement in a VaD mouse model. Notably, the X-ray crystal structure of the PDE8A-15 complex showed that the potent affinity and high selectivity of 15 might come from the distinctive interactions with H-pocket including T-shaped π-π interactions with Phe785 as well as a unique H-bond network, which have never been observed in other PDE-inhibitor complex before, providing new strategies for the further rational design of novel selective inhibitors against PDE8.

The Dependency of Thermal Expansion Coefficient of DNA Adsorption Film on Environmental Conditions / 医用生物力学

Objective To investigate the dependency of thermal expansion coefficient of DNA adsorption film on environmental conditions. Methods By treating DNA adsorption film as a macroscopic continuum film with prestrain, an equivalent composite beam model of DNA film-substrate was established to calculate the deflection of DNA-microcantilever beam under temperature loading. By adopting Parsegian’s empirical potential which described the mesoscopic free energy of DNA adsorption film, the DNA liquid crystal-substrate multi-scale deflection model, the thought experiment method and the equivalent deformation method were combined to establish the trans-scale relationship between the microstructure of DNA adsorption film and its macro-scale mechanical properties. The thermal expansion coefficient of DNA adsorption film was predicted. ResultsGiven the ionic strength, the thermal expansion coefficient of double-stranded DNA adsorption film ranged from 0.3×10-4/K to 8.05×10-4/K, and that of single-stranded DNA adsorption film ranged from 1.28×10-4/K to 9.33×10-4/K. Conclusions As a leading role in the competition of micro-interactions, the change of configurational entropy determines the dependency of thermal expansion coefficient of DNA adsorption film on environmental conditions; the thermal expansion coefficient of DNA adsorption film decreases with the increase of temperature or ion concentration or DNA packing density. These results are useful for gene detection and its regulation, and provide reference for the evaluation of tissue organ performance in tissue engineering.

Cinética de la adsorción de fluoruro y arsénico usando nano-fibras de alúmina / Kinetics of the fluoride and arsenic adsorption using alumina nanofibers

Resumen En muchos países del mundo, incluido México, la presencia de elementos tóxicos, como el arsénico y flúor por encima de los niveles máximos permitidos en el agua potable (0.01 mg/L y 1.5 mg/L), respectivamente está generando problemas a la salud, como el cáncer y la fluorosis esquelética, respectivamente. El objetivo de este trabajo fue determinar la cinética del proceso de adsorción del fluoruro y arsénico en soluciones sintéticas, utilizando gamma alúmina (γ-Al2O3) para establecer si el proceso se desarrolla espontáneamente. Se sintetizó γ-Al2O3 nano-fibrilar, con alta área superficial /g), por precipitación homogénea, y se (352 m2 secó por espray. El nanomaterial adsorbente obtenido se usó para eliminar el fluoruro y el arsénico total de soluciones sintéticas. La morfología de la nano-fibra de γ-Al2O3 mesoporosa se analizó usando microscopía electrónica de transmisión y de barrido. El área superficial se determinó por adsorción-desorción a pH 7 de nitrógeno. Las isotermas de adsorción del proceso de remoción coincidieron con el modelo de Langmuir para ambos elementos. La γ-Al2O3 eliminó hasta 96 % de iones flúor y 92 % de arsénico total a pH 5, mientras que a pH 7 se alcanzó una remoción del 90 % y 94.2 % de fluoruro y arsénico, respectivamente. La cinética de remoción siguió el modelo de seudo-segundo orden, y el parámetro de equilibrio adimensional y la energía libre estándar de Gibbs confirmaron que el proceso se desarrolló espontáneamente. La gamma alúmina nano-fibrilar permitió la remoción natural y espontánea de arsénico y fluoruro presente en las soluciones utilizadas en este estudio.

Abstract In many countries of the world including Mexico, the presence of toxic elements such as arsenic and fluoride on the maximum levels permitted in drinking water (0.01 mg/L and 1.5 mg/L) is causing health problems such as cancer and skeletal fluorosis, respectively. For this reason, the objective of this work was to determine the kinetics of adsorption process of the fluoride and arsenic in synthetic water using gamma alumina (γ-Al2O3) and to determine whether the process develops spontaneously. Nanofiber γ-Al2O3 with high surface area was synthesized by homogeneous precipitation and spray dry method. This adsorbent nanomaterial was used to remove fluoride and total arsenic from synthetic water. Nanofiber morphology of the mesoporous γ-Al2O3 was analyzed by transmission and scanning electron microscopy. The high surface area (352 m2/g) was determined by nitrogen adsorption-desorption. The adsorption isotherms of the removal process concur by the Langmuir model for both toxic elements. γ-Al2O3 removes up to 96 % of fluoride ions and 92 % of total arsenic at pH5, while a removal of 90 % and 94.2 % at pH7 of fluoride and arsenic, respectively, is achieved. The removal kinetics follows the pseudo-second order model, and the dimensionless equilibrium parameter and Gibbs standard free energy confirm that the process is performed spontaneously. The gamma nano-fibrillar alumina is a good material for the natural and spontaneous removal of arsenic and fluoride present in synthetic water used in this study.

Integrated project of a smart microgrid allied with energy management: An initiative to reduce electrical energy costs

Abstract Electricity is undoubtedly one of the most important resources in the modern world. As the demand for electric energy increases, conventional resources that are transformed into electric energy are being exhausted, generating a need to search for alternative sources, resulting in a significant increase in energy costs. This study presents an integrated project of an intelligent microgrid and energy management aimed at reducing energy costs. At the Federal University of Paraná (UFPR), electricity represents an annual cost of over BRL 13 million, which is the third largest operating expense of the university. In addition, the public education budget in Brazil has been decreased in recent years. Therefore, this study was conducted within the scope of UFPR and aimed to analyze three alternatives to reduce electric energy costs: i) demand management through an analysis of energy bills, ii) migration to the free energy market, and iii) the development of an in-house photovoltaic generation facility. A computational tool to optimize the contracted demand and simulate the annual savings with the free market and distributed generation projects was developed using Microsoft Excel. Payback, the net present value, and the internal rate of return were calculated. Finally, the economic viability of all alternatives was proven, with demand management demonstrating an economic potential of greater than BRL 500,000 per year, use of the free market saving more than BRL 300,000, and the developed in-house photovoltaic generation system achieving an economic impact of more than BRL 600,000 per year.

Application Status of Properties of Surface and Interface in Research on Pharmaceutical Preparations / 中国实验方剂学杂志

The surface and interface,as the transition region between two phases,belongs to the category of physical chemistry.At present,it is widely used in materials and other scientific fields.Meanwhile,this property also plays an important role in pharmaceutical research.The interface layer involved in the progress of pharmaceutical preparations is connected with the two-phase or three-phase between gas,liquid and solid closely.The interface effect will affect the final shaping of pharmaceutical preparations and the dissolution and absorption of drugs in the human body.In this paper,the surface and interface characteristics(specific surface area,surfacial and interfacial tension and surface Gibbs free energy) were compared,and the application of interface phenomena(wetting,solubilization and emulsification) in pharmaceutical research were introduced.From the points of view of the progress control of pharmaceutical preparations and the effectiveness of their products,the article expounds the important role of properties of surface and interface in the field of pharmaceutical preparations.Therefore,it is necessary to pay attention to the properties of surface and interface,one of the key physical properties of drugs,and to apply them in the pharmaceutical research.

Predicting complexation performance between cyclodextrins and guest molecules by integrated machine learning and molecular modeling techniques

Most pharmaceutical formulation developments are complex and ideal formulations are generally obtained after extensive experimentation. Machine learning is increasingly advancing many aspects in modern society and has achieved significant success in multiple subjects. Current research demonstrated that machine learning can be adopted to build up high-accurate predictive models in drugs/cyclodextrins (CDs) systems. Molecular descriptors of compounds and experimental conditions were employed as inputs, while complexation free energy as outputs. Results showed that the light gradient boosting machine provided significantly improved predictive performance over random forest and deep learning. The mean absolute error was 1.38 kJ/mol and squared correlation coefficient was 0.86. The evaluation of relative importance of molecular descriptors further demonstrated the key factors affecting molecular interactions in drugs/CD systems. In the specific ketoprofen-CD systems, machine learning model showed better predictive performance than molecular modeling calculation, while molecular simulation could provide structural, dynamic and energetic information. The integration of machine learning and molecular simulation could produce synergistic effect for interpreting and predicting pharmaceutical formulations. In conclusion, the developed predictive models were able to quickly and accurately predict the solubilizing capacity of CD systems. Current research has taken an important step toward the application of machine learning in pharmaceutical formulation design.

Novel ligand-based docking; molecular dynamic simulations; and absorption, distribution, metabolism, and excretion approach to analyzing potential acetylcholinesterase inhibitors for Alzheimer's disease / 药物分析学报

Acetylcholinesterase (AChE) plays an important role in Alzheimer's disease (AD). The excessive activity of AChE causes various neuronal problems, particularly dementia and neuronal cell deaths. Generally, anti- AChE drugs induce some serious neuronal side effects in humans. Therefore, this study sought to identify alternative drug molecules from natural products with fewer side effects than those of conventional drugs for treating AD. To achieve this, we developed computational methods for predicting drug and target binding affinities using the Schrodinger suite. The target and ligand molecules were retrieved from established databases. The target enzyme has 539 amino acid residues in its sequence alignment. Ligand molecules of 20 bioactive molecules were obtained from different kinds of plants, after which we performed critical analyses such as molecular docking; molecular dynamic (MD) simulations; and absorption, distribution, metabolism, and excretion (ADME) analysis. In the docking studies, the natural compound rutin showed a superior docking score of -12.335 with a good binding energy value of -73.313 kcal/mol. Based on these findings, rutin and the target complex was used to perform MD simulations to analyze rutin stability at 30 ns. In conclusion, our study demonstrates that rutin is a superior drug candidate for AD. Therefore, we propose that this molecule is worth further investigation using in vitro studies.

Garlic: kinetic drying and thermodynamic properties / Alho: cinética de secagem e propriedades termodinâmicas

Dehydrated garlic is an importance spice in pre-cooked and processed food products, but studies of the drying variables of this product are scarce. Thus, this work aimed to model and study the kinetics of garlic drying at three different temperatures (40, 50 and 60 °C) and analyze the thermodynamic parameters during the process. The drying was analyzed using pre-established mathematical models for agricultural products and equations that describe the thermodynamics of product dehydration. The best mathematical adjustment for all drying temperatures was the Midilli equation. The moisture ratio was seen to decrease during the process for all situations. The effective diffusivity increased with increasing temperature. The enthalpy change was positive during the process and decreased with increasing temperature. The study entropy was negative, indicating a non-spontaneous reaction. In addition, the Gibbs free energy increased with increasing drying temperature. The thermodynamic standards were satisfactory and correctly described the moisture loss by the garlic samples.

O alho desidratado é um tempero de suma importância em produtos pré-cozidos e processados, no entanto, o estudo das variáveis de secagem desse produto é escasso. Diante disso, objetivou-se com esse trabalho estudar a cinética e a modelagem da secagem de alho, em três temperaturas distintas (40, 50 e 60 °C), e analisar os parâmetros termodinâmicos durante o processo. O estudo da secagem foi feito por meio de modelos matemáticos pré-estabelecidos para produtos agrícolas e por equações que descrevem a termodinâmica da desidratação de produtos. O melhor ajuste matemático foi à equação de Midilli para todas as temperaturas de secagem. A razão de umidade apresentou-se decrescente durante o processo para todas as situações. A difusividade efetiva aumentou com o aumento da temperatura. A variação de entalpia apresentou-se positiva durante o processo de secagem e diminui com o aumento da temperatura. A entropia estudada foi negativa, indicando uma reação não-espontânea. E a energia livre de Gibbs aumentou com a elevação da temperatura de secagem. Os padrões termodinâmicos foram satisfatórios e descreveram como ocorreu a perda de umidade pelas amostras de alho.

Recent Progress of Particle Design Engineering Based on Surface Free Energy / 中国药学杂志

Presently interests are growing in the field of surface free energy(SFE). With the further research, more particle design engineering based on SFE are summarized via characterizing the related properties of SFE during the process of particle design. SFE of materials will vary with changing the physical properties of particles via modifying the surface of particles with particle design. In this study, we summarized the application of SFE in powder micronization, particle modification, mixing, coating, pelletilization and granulation, etc. Dispersive-polar model and adhesion-cohesion model were established based on the parameters of SFE. The application of the two models were also illustrated in the particle design engineering.

Genomic Analysis of miR-21-3p and Expression Pattern with Target Gene in Olive Flounder

MicroRNAs (miRNAs) act as regulators of gene expression by binding to the 3’ untranslated region (UTR) of target genes. They perform important biological functions in the various species. Among many miRNAs, miR-21-3p is known to serve vital functions in development and apoptosis in olive flounder. Using genomic and bioinformatic tools, evolutionary conservation of miR-21-3p was examined in various species, and expression pattern was analyzed in olive flounder. Conserved sequences (5’-CAGUCG-3’) in numerous species were detected through the stem-loop structure of miR-21-3p. Thus, we analyzed target genes of miR-21-3p. Among them, 3’ UTR region of PPIL2 gene indicated the highest binding affinity with miR-21-3p based on the minimum free energy value. The PPIL2 gene showed high expression levels in testis tissue of the olive flounder, whereas miR-21-3p showed rather ubiquitous expression patterns except in testis tissue, indicating that miR-21-3p seems to control the PPIL2 gene expression in a complementary repression manner in various tissues of olive flounder. Taken together, this current study contributes to infer the target gene candidates for the miR-21-3p using bioinformatics tools. Furthermore, our data offers important information on the relationship between miR-21-3p and target gene for further functional study.

Research on compaction behavior of pharmaceutical powders based on surface free energy / 药学学报

This study was designed to establish the method of characterization of surface free energy(SFE)and evaluate the compaction properties of pharmaceutical materials based on SFE. We investigated the contact angles of materials with water and diiodomethane under different compression pressures. The contact angles of materials at 353 MPa compression pressure were utilized to calculate the related parameters of SFE ultimately. The area under tensile strength-compression pressure curve(AUTSC)and pressure yield(Py)were employed to evaluate the compactibility of material. Additionally, Pearson correlation analysis was utilized to analyze the relationship between the SFE and the compaction properties of pharmaceutical materials. The results exhibited that SFE had a significant correlation with the compaction properties of materials(P < 0.05). Moreover, the related parameters of SFE, i.e., cohesive work(Wco)and polarity index(PI)of SFE, were positively correlated with Py of Heckel equation and negatively related with AUTSC. The higher values of Wco and PI, the stronger repulsive force among the particles, led to a worse compaction behavior. In this study, we established the method for characterization of the compaction behavior of materials based on SFE initially. This study also demonstrated that SFE could evaluate the compaction behavior effectively, which provides a better understanding of compaction behavior for pharmaceutical researchers.

Molecular recognition mechanism and motion of HCV NS3/4A protease with Faldaprevir analogue / 生物工程学报

Faldaprevir analogue molecule (FAM) has been reported to effectively inhibit the catalytic activity of HCV NS3/4A protease, making it a potential lead compound against HCV. A series of HCV NS3/4A protease crystal structures were analyzed by bioinformatics methods, and the FAM-HCV NS3/4A protease crystal structure was chosen for this study. A 20.4 ns molecular dynamics simulation of the complex consists of HCV NS3/4A protease and FAM was conducted. The key amino acid residues for interaction and the binding driving force for the molecular recognition between the protease and FAM were identified from the hydrogen bonds and binding free energy analyses. With the driving force of hydrogen bonds and van der Waals, FAM specifically bind to the active pocket of HCV NS3/4A protease, including V130-S137, F152-D166, D77-D79 and V55, which agreed with the experimental data. The effect of R155K, D168E/V and V170T site-directed mutagenesis on FAM molecular recognition was analyzed for their effect on drug resistance, which provided the possible molecular explanation of FAM resistance. Finally, the system conformational change was explored by using free energy landscape and conformational cluster. The result showed four kinds of dominant conformation, which provides theoretical basis for subsequent design of Faldaprevir analogue inhibitors based on the structure of HCV NS3/4A protease.

Sanitização de cenoura minimamente processada com nanopartículas de prata / Sanitization of minimally processed carrot with silver nanoparticles

A produção de cenoura em grande escala na região de Rio Paranaíba coloca essa região em posição de destaque no cenário nacional. No entanto, é relatado que ocorre significativa quantidade de sobras após a colheita. O aproveitamento do material descartado na cadeia de alimentos pode se concretizar pelo processamento mínimo, como uma alternativa de agregação de valor. A etapa de sanitização é de extrema importância durante a produção de vegetais minimamente processados. Nesse contexto, objetivou-se estudar o efeito antimicrobiano de nanopartículas de prata na sanitização de cenoura minimamente processada, obtida a partir do aproveitamento das sobras de cenouras da colheita da cidade de Rio Paranaíba, bem como o estudo da termodinâmica de adesão de diferentes estirpes bacterianas na superfície da cenoura sanitizada. Observou-se que as nanopartículas de prata (6mg L^-1)apresentaram bons resultados, quando comparadas aos sanitizantes hipoclorito de sódio (100mg L^-1) e dicloroisocianurato de sódio (150mg L^-1), na descontaminação da cenoura minimamente processada sobre microrganismos mesófilos aeróbios; Pseudomonasspp.; bactérias láticas; e coliformes a 35ºC. Verificou-se também que a superfície da cenoura apresenta características hidrofílicas que podem dificultar a adesão bacteriana. Esse fato foi confirmado na avaliação de termodinâmica de adesão, que foi desfavorável paraStaphylococcus aureus, Escherichia colie Listeria innocua, sendo mais desfavorável para as interações envolvendo as superfícies de cenoura sanitizadas com nanopartículas de prata.

The carrot production on a large scale in the region of Rio Paranaiba places the region in a prominent position on the national scene. However, it is reported that a significant amount of scraps occurs after harvest. The use of discarded material in the food chain can be realized by minimal processing, as an alternative of adding value. A sanitization step is very important during the production of minimally processed vegetables. In this context, this research aimed to study the antimicrobial effect of silver nanoparticles in the sanitization of minimal processing carrot from discarded carrot harvested at Rio Paranaiba city, as well as study the thermodynamics adhesion for different bacterial strains in sanitized carrot surface. It was observed that silver nanoparticles (6mg L^-1) showed good results when was compared to sodium hypochlorite (100mg L^-1) and sodium dichloroisocyanurate (150mg L^-1) in reducing populations of aerobic mesophilic microorganism;Pseudomonasspp. lactic acid bacteria and coliforms at 35ºC present in carrot. It was also found that the surface of carrot has hydrophilic characteristics which can prevent bacterial adhesion. This fact was confirmed that thermodynamic evaluation of adhesion that was unfavorable for Staphylococcus aureus, Escherichia coliand Listeria innocua, and more thermodynamically unfavorable for interactions involving carrot surfaces sanitized with silver nanoparticles.

A nuclear ribosomal DNA pseudogene in triatomines opens a new research field of fundamental and applied implications in Chagas disease

A pseudogene, designated as "ps(5.8S+ITS-2)", paralogous to the 5.8S gene and internal transcribed spacer (ITS)-2 of the nuclear ribosomal DNA (rDNA), has been recently found in many triatomine species distributed throughout North America, Central America and northern South America. Among characteristics used as criteria for pseudogene verification, secondary structures and free energy are highlighted, showing a lower fit between minimum free energy, partition function and centroid structures, although in given cases the fit only appeared to be slightly lower. The unique characteristics of "ps(5.8S+ITS-2)" as a processed or retrotransposed pseudogenic unit of the ghost type are reviewed, with emphasis on its potential functionality compared to the functionality of genes and spacers of the normal rDNA operon. Besides the technical problem of the risk for erroneous sequence results, the usefulness of "ps(5.8S+ITS-2)" for specimen classification, phylogenetic analyses and systematic/taxonomic studies should be highlighted, based on consistence and retention index values, which in pseudogenic sequence trees were higher than in functional sequence trees. Additionally, intraindividual, interpopulational and interspecific differences in pseudogene amount and the fact that it is a pseudogene in the nuclear rDNA suggests a potential relationships with fitness, behaviour and adaptability of triatomine vectors and consequently its potential utility in Chagas disease epidemiology and control.

Dynamics of the interaction between body fluid and Ti cp: the influence of surface functionalization in the first stages of osseointegration

INTRODUCTION: Regenerative therapies using biomaterials require accurate information on interactions between the implanted material and the human body. To improve the process of bone regeneration it is necessary to obtain a better understanding of the influence of the surfaces on the early stages of osseointegration. This work aims to investigate the dynamic interaction between simulated body fluid (SBF) and titanium surfaces (Ti cp) immediately after their first contact. METHODS: Ti cp samples were passed through physicochemical treatments after immersion in acid solution, alkaline solution and solutions containing TiO2 and Ca2+, to obtain three different surfaces. These were characterized by electron microscopy and free energy estimates. The evaluation of the interaction with SBF was performed by measuring the dynamic contact angles after contacting the surfaces. RESULTS: The effects of SBF wettability were more significant on surfaces according to high energy estimates. A comparative analysis of the three types of surfaces showed that fluid spreading was greater in samples with greater polar components, indicating that the surface nature influences interactions in the early stages of osseointegration. CONCLUSION: The results indicate the influence of polar interactions in the dynamic wettability of the SBF. It is possible that these interactions can also influence cellular viability on surfaces. Based on these results, new experiments are being designed to improve the presented methodology as a tool for the evaluation of biomaterials without the need for in vivo experiments.

Desenvolvimento de um revestimento bioativo de alta adesão para aplicações em Implantodontia / Development of a high adhesion bioactive coating for implant dentistry purposes

Revestimento bioativo de alta adesão foi obtido por modificações físico-químicas na superfície do titânio para formar estruturas de multicamadas contendo TiO2 e fosfatos de cálcio Ca/P. Medidas de tração foram realizadas para quantificar as forças de interfaces, observadas perto de 10 MPa. A ativação das superfícies foi evidenciada por estimativas de energia livre, cujos efeitos são atribuídos tanto à difusão atômica quanto à polarização da superfície. Os testes mostraram a bioatividade e a qualidade da superfície para a aplicação tecnológica...

This paper reports the development of a high adhesion bioactive coating promoted by increasing titanium free surface energy. Through physical-chemical modifi cations, multilayer structures with titania (TiO2) and calcium phosphates (Ca/P) were formed. Adhesion strength measurements were performed to quantify the interfacial force aspects and results were near 10MPa. Surface activation was evidenced by free energy estimates, with results attributed to the atomic diffusion process. The bioactivity tests showed the quality of this surface for technological applications...