Efficient degradation of various emerging pollutants by wild type and evolved fungal DyP4 peroxidases

The accumulation of emerging pollutants in the environment remains a major concern as evidenced by the increasing number of reports citing their potential risk on environment and health. Hence, removal strategies of such pollutants remain an active area of investigation. One way through which emerging pollutants can be eliminated from the environment is by enzyme-mediated bioremediation. Enzyme-based degradation can be further enhanced via advanced protein engineering approaches. In the present study a sensitive and robust bioanalytical liquid chromatography-tandem mass spectrometry (LCMSMS)-based approach was used to investigate the ability of a fungal dye decolorizing peroxidase 4 (DyP4) and two of its evolved variants—that were previously shown to be H2O2 tolerant—to degrade a panel of 15 different emerging pollutants. Additionally, the role of a redox mediator was examined in these enzymatic degradation reactions. Our results show that three emerging pollutants (2-mercaptobenzothiazole (MBT), paracetamol, and furosemide) were efficiently degraded by DyP4. Addition of the redox mediator had a synergistic effect as it enabled complete degradation of three more emerging pollutants (methyl paraben, sulfamethoxazole and salicylic acid) and dramatically reduced the time needed for the complete degradation of MBT, paracetamol, and furosemide. Further investigation was carried out using pure MBT to study its degradation by DyP4. Five potential transformation products were generated during the enzymatic degradation of MBT, which were previously reported to be produced during different bioremediation approaches. The current study provides the first instance of the application of fungal DyP4 peroxidases in bioremediation of emerging pollutants

The Discovery of Potent SHP2 Inhibitors with Anti-Proliferative Activity in Breast Cancer Cell Lines

Despite available treatments, breast cancer is the leading cause of cancer-related death. Knowing that the tyrosine phosphatase SHP2 is a regulator in tumorigenesis, developing inhibitors of SHP2 in breast cells is crucial. Our study investigated the effects of new compounds, purchased from NSC, on the phosphatase activity of SHP2 and the modulation of breast cancer cell lines’ proliferation and viability. A combined ligand-based and structure-based virtual screening protocol was validated, then performed, against SHP2 active site. Top ranked compounds were tested via SHP2 enzymatic assay, followed by measuring IC50 values. Subsequently, hits were tested for their anti-breast cancer viability and proliferative activity. Our experiments identified three compounds 13030, 24198, and 57774 as SHP2 inhibitors, with IC50 values in micromolar levels and considerable selectivity over the analogous enzyme SHP1. Long MD simulations of 500 ns showed a very promising binding mode in the SHP2 catalytic pocket. Furthermore, these compounds significantly reduced MCF-7 breast cancer cells’ proliferation and viability. Interestingly, two of our hits can have acridine or phenoxazine cyclic system known to intercalate in ds DNA. Therefore, our novel approach led to the discovery of SHP2 inhibitors, which could act as a starting point in the future for clinically useful anticancer agents

An Ontology Based Approach for Data Leakage Prevention Against Advanced Persistent Threats

13th International Conference on Metadata and Semantic Research, MTSR 2019 -- 28 October 2019 through 31 October 2019 -- -- 235199Advanced Persistent Threats (APTs) are increasingly being a risk for companies and institutions because of their distributed, complicated, multi-step and targeted behaviors. The amount of sensitive data in organizations are increasing and APTs threaten organizations by exfiltrating these data from the organization. The sensitive data not only include structured data such as credit card numbers but also unstructured data such as a private report created by the company. Although Data Leakage Prevention (DLP) systems are improving in terms of detecting the leakage of sensitive data, APTs’ sophisticated methods are still successful against DLP systems. The characteristics of APTs require a prevention system that can semantically and hierarchically correlate basic elements and actions in the system with behaviors of an APT across the organization. Among many effort to classify APT behavior, MITRE’s ATT&CK matrix for enterprise is widely accepted as an effective topology for the APT behavior. In this paper, an ontology based approach to achieve data leakage prevention against APTs is proposed. The proposed approach correlates low-level event details with APT techniques and tactics defined in MITRE’s ATT&CK matrix. © 2019, Springer Nature Switzerland AG.Türkiye Bilimsel ve Teknolojik Araştirma Kurumu, TÜBITAK: 117E100This work was supported by TUBITAK, the Scientific and Technological Research Council of Turkey (Grant No. 117E100)

Effect of Gestational Diabetes Mellitus History on Future Pregnancy Behaviors: The Mutaba’ah Study

Gestational diabetes mellitus (GDM) increases the risk of adverse pregnancy outcomes in any pregnancy and recurrence rates are high in future pregnancies. This study aims to investigate the effect of self-reported history of previous GDM on behaviors in a future pregnancy. This is an interim cross-sectional analysis of the pregnant women who participated in the Mutaba’ah Study between May 2017 and March 2020 in the United Arab Emirates. Participants completed a baseline self-administered questionnaire on sociodemographic and pregnancy-related information about the current pregnancy and previous pregnancies. Regression models assessed the relationships between self-reported history of GDM and pre-pregnancy and pregnancy behaviors in the current pregnancy. Out of 5738 pregnant parous women included in this analysis, nearly 30% (n = 1684) reported a history of GDM in a previous pregnancy. Women with a history of previous GDM were less likely to plan their current pregnancies (adjusted odds ratio (aOR): 0.84, 95% confidence interval (CI) 0.74–0.96) and more likely to be worried about childbirth (aOR: 1.18, 95% CI 1.03–1.36). They had shorter interpregnancy intervals between their previous child and current pregnancy (aOR: 0.88, 95% CI 0.82–0.94, per SD increase). There were no significant differences between women with and without a history of GDM in supplement use, sedentary behavior, or physical activity before and during this current pregnancy. Nearly a third of parous pregnant women in this population had a history of GDM in a previous pregnancy. Pregnant women with a previous history of GDM were similar to their counterparts with no history of GDM in the adopted pre-pregnancy and prenatal health behaviors. More intensive and long-term lifestyle counseling, possibly supported by e-health and social media materials, might be required to empower pregnant women with a history of GDM. This may assist in adopting and maintaining healthy prenatal behaviors early during the pregnancy or the preconception phase to minimize the risk of GDM recurrence and the consequential adverse maternal and infant health outcomes

Synthesizing covalent organic frameworks for unprecedented iodine capture performance

Nuclear energy continues to be an important supplier of electricity, but it has problems with waste management and the possibility to leak radioactive material. Iodine, a potentially harmful byproduct of uranium fission, is hazardous to both the environment and human health. Therefore, developing safe, effective, and affordable storage facilities for iodine waste is crucial. Owing to their well-controlled pore structure and substantial certain surface area, covalent organic frameworks (COFs) show promise for the adsorption of radioactive iodine. The newly developed COFs (SJ-COF, YA-COF, and AA-COF) shown amazing properties, including strong thermal and chemical stability, which made them ideal for efficient iodine capture. Notably, the ultrahigh iodine capture capacities of these COFs—8.52 g g−1, 8.12 g g−1 and 7.01 g g−1—were significantly greater than most previously reported materials. And The % removal efficiency for SJ-COF, YA-COF and AA-COF from I2/cyclohexane solutions were 87.9 %, 88.6% and 82.6 % respectively. It is noteworthy that the three COFs have high selectivity, reusability, and iodine retention abilities, maintaining iodine even after five recyclings. Based on the outcomes of the experiments, the adsorption processes of the three COFs were examined, and it was discovered that iodine was bound through physical-chemical adsorption. The findings of our work provide a ground-breaking standard for the removal of nuclear waste and demonstrate the enormous potential of COFs as adaptable porous structures that may be specifically designed to address major environmental concerns

Perspectives on the Feasibility of Using Enzymes for Pharmaceutical Removal in Wastewater

This particular chapter spotlights the growing environmental concerns and hazardous consequences of numerous organic contaminants so-called emerging contaminants (ECs). These ECs are being detected, though in different quantities, in different environmental matrices and wastewater treatment systems. With ever-increasing awareness, people are now more concerned about the wide-spread distribution of pharmaceutically related active compounds in water matrices. In turn, the free flow of ECs in water matrices poses notable adverse effects on human, aquatic animals, and naturally occurring plants, even at very small concentrations. Due to inadequacies and ineffectiveness of, in practice, physical and chemical-based remediation processes, robust treatment approaches, such as microorganisms and their novel enzyme-based degradation/removal of ECs, are of supreme interest. This chapter focuses on various pharmaceutically related ECs and their efficient mitigation from water matrices. Following a brief introduction, the focus is given to two main treatment approaches, i.e., (1) remediation of pharmaceutically active compounds by crude (pristine) and purified enzymes (i.e., lignin peroxidase, manganese peroxidase, soybean peroxidase, horseradish peroxidase, and laccases) and (2) immobilized enzyme-assisted degradation of pharmaceutically active compounds.Peer reviewe