COMBINE analysis of nuclear receptor-DNA binding specificity: Comparison of two sets of data

To identify the major determinants of the DNA binding specificity of nuclear transcription factors, the Comparative Binding Energy (COMBINE) analysis has been performed for two datasets. In Tomic et al.,l COMBINE QSAR models were derived for a set of 320 complexes of DNA and glucocorticoid receptor mutants. Here, we derive COMBINE QSAR models for a set of 32 complexes. This set differs from the larger one in two aspects. The complexes have additional mutation sites in the DNA binding domain and, instead of just activity measurements, both activity and binding affinity measurements are available. Models of better predictive ability were obtained with the smaller, but experimentally better characterized, dataset. The parameters important for determining binding specificity are nevertheless similar for both datasets: the electrostatic interaction energies between the mutated nucleotides and mutated residue(s) as well as some charged amino acid residues (Arg-447, Arg-470, Arg-477), and the solvation free energies of the mutated base(s). However, the relative importance of these parameters is different in the two datasets

COMBINE Analysis of Nuclear Receptor-DNA Binding Specificity: Comparison of Two Sets of Data

To identify the major determinants of the DNA binding specificity of nuclear transcription factors, the Comparative Binding Energy (COMBINE) analysis has been performed for two datasets. In Tomić et al.,1 COMBINE QSAR models were derived for a set of 320 complexes of DNA and glucocorticoid receptor mutants. Here, we derive COMBINE QSAR models for a set of 32 complexes. This set differs from the larger one in two aspects. The complexes have additional mutation sites in the DNA binding domain and, instead of just activity measurements, both activity and binding affinity measurements are available. Models of better predictive ability were obtained with the smaller, but experimentally better characterized, dataset. The parameters important for determining binding specificity are nevertheless similar for both datasets: the electrostatic interaction energies between the mutated nucleotides and mutated residue(s) as well as some charged amino acid residues (Arg-447, Arg-470, Arg-477), and the solvation free energies of the mutated base(s). However, the relative importance of these parameters is different in the two datasets

Aberrant Disgust Responses and Immune Reactivity in Cocaine-Dependent Men

Background: Infectious diseases are the most common and cost-intensive health complications associated with drug addiction. There is wide belief that drug-dependent individuals expose themselves more regularly to disease-related pathogens through risky behaviors such as sharing pipes and needles, thereby increasing their risk for contracting an infectious disease. However, evidence is emerging indicating that not only lifestyle but also the immunomodulatory effects of addictive drugs, such as cocaine, may account for their high infection risk. As feelings of disgust are thought to be an important psychological mechanism in avoiding the exposure to pathogens, we sought to investigate behavioral, physiological, and immune responses to disgust-evoking cues in both cocaine-dependent and healthy men. Methods: All participants (N = 61) were exposed to neutral and disgust-evoking photographs depicting food and nonfood images while response accuracy, latency, and skin conductivity were recorded. Saliva samples were collected before and after exposure to neutral and disgusting images, respectively. Attitudes toward disgust and hygiene behaviors were assessed using questionnaire measures. Results: Response times to disgust-evoking photographs were prolonged in all participants, and specifically in cocaine-dependent individuals. While viewing the disgusting images, cocaine-dependent individuals exhibited aberrant skin conductivity and increased the secretion of the salivary cytokine interleukin-6 relative to control participants. Conclusion: Our data provide evidence of a hypersensitivity to disgusting stimuli in cocaine-dependent individuals, possibly reflecting conditioned responses to noningestive sources of infection. Coupled with a lack of interoception of bodily signals, aberrant disgust responses might lead to increased infection susceptibility in affected individuals

Software Support for Irregular and Loosely Synchronous Problems

A large class of scientific and engineering applications may be classified as irregular and loosely synchronous from the perspective of parallel processing. We present a partial classification of such problems. This classification has motivated us to enhance Fortran D to provide language support for irregular, loosely synchronous problems. We present techniques for parallelization of such problems in the context of Fortran D

Supercritical CO2 Extracts of Satureja montana Dispersed in Deep Eutectic Solvents

Funding Information: This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 101003396. Publisher Copyright: © 2023 by the authors.The aim of this work was to establish the potential of natural deep eutectic solvents (NADES) for the stabilization of aroma volatile organic compounds from a natural source. Satureja montana was used as a source of volatile components, as it is rich in terpenes of great commercial and biological importance, such as carvacrol, thymol, and thymoquinone, among others. Supercritical CO2 was used to extract the lipophilic fraction of S. montana, which was further directly dispersed in NADES. The stabilizing capacity of seven different NADES based on betaine and glycerol was analyzed. The stability of the components in NADES was monitored by analyzing the headspace profile during 6 months of storage at room temperature. The changes in the headspace profile over time were analyzed by using different statistical and chemometric tools and the Wilcoxon matched pair test. It was determined that alterations over time occurred such as degradation and oxidation, and they were the most prominent in the control. In addition, the indicator of decreased stability of the control was the formation of the new compounds that could compromise the quality of the product. In the stabilized NADES samples, the changes were significantly less prominent, indicating that the NADES had a stabilizing effect on the volatile compounds. According to Wilcoxon matched pair test, the most efficient stability was achieved by using betaine/ethylene glycol, glycerol/glucose, and betaine/sorbitol/water. Therefore, by applying two green solvents, a sustainable approach for obtaining pure and high-quality S. montana extracts with extended stability at room temperature was established.publishersversionpublishe

Ruthenacarborane and Quinoline: A Promising Combination for the Treatment of Brain Tumors

Gliomas and glioblastomas are very aggressive forms of brain tumors, prone to the development of a multitude of resistance mechanisms to therapeutic treatments, including cytoprotective autophagy. In this work, we investigated the role and mechanism of action of the combination of a ruthenacarborane derivative with 8-hydroxyquinoline (8-HQ), linked via an ester bond (complex 2), in rat astrocytoma C6 and human glioma U251 cells, in comparison with the two compounds alone, i.e., the free carboxylic acid (complex 1) and 8-HQ, and their non-covalent combination ([1 + 8-HQ], in 1:1 molar ratio). We found that only complex 2 was able to significantly affect cellular viability in glioma U251 cells (IC50 11.4 μM) via inhibition of the autophagic machinery, most likely acting at the early stages of the autophagic cascade. Contrary to 8-HQ alone, complex 2 was also able to impair cellular viability under conditions of glucose deprivation. We thus suggest different mechanisms of action of ruthenacarborane complex 2 than purely organic quinoline-based drugs, making complex 2 a very attractive candidate for evading the known resistances of brain tumors to chloroquine-based therapies

Determinants of residents’ support for sustainable tourism development: an empirical study in Midyat, Turkey

The purpose of this study is to examine the extent to which residents’ perceptions of their place image can predict their perceptions of the impacts of tourism, and ultimately, to elucidate their support for sustainable tourism development in Midyat, Turkey. This city currently faces a range of negative impacts associated with tourism, such as inflation, high leakage, threats to family structures, environmental degradation, pollution, and crowding. At the same time, Midyat seeks to maximize the positive impacts of tourism, including job creation and employment, environmental protection, cultural and educational enrichment, and recreational opportunities. Therefore, there is an urgent need for a strategic shift in development. The study population consists of residents residing in Midyat, Turkey, from whom three hundred and fifty-six questionnaires were collected. PLS (Partial Least Squares) path analysis was utilized to analyze the research model constructed based on the literature. The results demonstrated that residents’ place image significantly predicted two out of three impacts of tourism, namely, socio-cultural and economic impacts. Additionally, residents’ perceptions of environmental and socio-cultural impacts were significant predictors of their support or opposition to sustainable tourism. While perceived environmental impacts have a positive effect on support for sustainable tourism, perceived economic impacts have a negative effect. This finding can guide tourism planners and professionals to make more informed decisions and take stronger steps toward sustainable tourism development. This study revealed that the quality of life, job opportunities, infrastructure, and economic income of Midyat’s residents are insufficient. However, the city is characterized by social attributes, such as friendliness, trust, and supportiveness. The results are limited to local residents, and using only one tourist stakeholder to assess sustainable tourism development is insufficient. Therefore, additional research must be performed to guarantee the involvement of other tourism stakeholders.info:eu-repo/semantics/publishedVersio

Metal-support interaction: The key factor governing activity of Pd/SnO2 catalyst for denitration of ground water

Two mesoporous nanocristalline Pd/SnO2 catalysts were prepared by modified solgel technique differing in the pH conditions (pH = 2 and 9.5) of the synthesis of their supports. Samples achieved different activity and selectivity in water denitration reaction using hydrogen. XPS results of reduced samples indicate a strong interaction between the Pd and the Sn possibly as a result of electron shift from Sn to Pd. The solid solution of Pd2+ and SnO2 is formed by taking O from the surface of the support. In such a way some SnO2-X species may stay onto the surface and be responsible for its pronounced activity