Characterizing black carbon in rain and ice cores using coupled tangential flow filtration and transmission electron microscopy

Antarctic ice cores have been used to study the history of black carbon (BC), but little is known with regards to the physical and chemical characteristics of these particles in the remote atmosphere. Characterization remains limited by ultra-trace concentrations in ice core samples and the lack of adequate methods to isolate the particles unaltered from the melt water. To investigate the physical and chemical characteristics of these particles, we have developed a tangential flow filtration (TFF) method combined with transmission electron microscopy (TEM). Tests using ultrapure water and polystyrene latex particle standards resulted in excellent blanks and significant particle recovery. This approach has been applied to melt water from Antarctic ice cores as well as tropical rain from Darwin, Australia with successful results: TEM analysis revealed a variety of BC particle morphologies, insoluble coatings, and the attachment of BC to mineral dust particles. The TFF-based concentration of these particles has proven to give excellent results for TEM studies of BC particles in Antarctic ice cores and can be used for future studies of insoluble aerosols in rainwater and ice core samples

Structure of eukaryotic purine/H(+) symporter UapA suggests a role for homodimerization in transport activity

The uric acid/xanthine H(+) symporter, UapA, is a high-affinity purine transporter from the filamentous fungus Aspergillus nidulans. Here we present the crystal structure of a genetically stabilized version of UapA (UapA-G411VΔ1-11) in complex with xanthine. UapA is formed from two domains, a core domain and a gate domain, similar to the previously solved uracil transporter UraA, which belongs to the same family. The structure shows UapA in an inward-facing conformation with xanthine bound to residues in the core domain. Unlike UraA, which was observed to be a monomer, UapA forms a dimer in the crystals with dimer interactions formed exclusively through the gate domain. Analysis of dominant negative mutants is consistent with dimerization playing a key role in transport. We postulate that UapA uses an elevator transport mechanism likely to be shared with other structurally homologous transporters including anion exchangers and prestin

Individual particle morphology, coatings, and impurities of black carbon aerosols in Antarctic ice and tropical rainfall

© 2016 American Geophysical Union. All Rights Reserved. Black carbon (BC) aerosols are a large source of climate warming, impact atmospheric chemistry, and are implicated in large-scale changes in atmospheric circulation. Inventories of BC emissions suggest significant changes in the global BC aerosol distribution due to human activity. However, little is known regarding BC's atmospheric distribution or aged particle characteristics before the twentieth century. Here we investigate the prevalence and structural properties of BC particles in Antarctic ice cores from 1759, 1838, and 1930 Common Era (C.E.) using transmission electron microscopy and energy-dispersive X-ray spectroscopy. The study revealed an unexpected diversity in particle morphology, insoluble coatings, and association with metals. In addition to conventionally occurring BC aggregates, we observed single BC monomers, complex aggregates with internally, and externally mixed metal and mineral impurities, tar balls, and organonitrogen coatings. The results of the study show BC particles in the remote Antarctic atmosphere exhibit complexity that is unaccounted for in atmospheric models of BC

Discovery of Novel Adenosine Receptor Antagonists through a Combined Structure- and Ligand-Based Approach Followed by Molecular Dynamics Investigation of Ligand Binding Mode

An intense effort is made by pharmaceutical and academic research laboratories to identify and develop selective antagonists for each adenosine receptor (AR) subtype as potential clinical candidates for "soft" treatment of various diseases. Crystal structures of subtypes A2A and A1ARs offer exciting opportunities for structure-based drug design. In the first part of the present work, Maybridge HitFinderTM library of 14400 compounds was utilized to apply a combination of structure-based against the crystal structure of A2AAR and ligand-based methodologies. The docking poses were rescored by CHARMM energy minimization and calculation of the desolvation energy using PoissonBoltzmann equation electrostatics. Out of the eight selected and tested compounds, five were found positive hits (63% success). Although the project was initially focused on targeting the A2AAR, the identified antagonists exhibited low micromolar or micromolar affinity against A2A/A3 ARs or A3AR, respectively. Based on these results, 19 compounds characterized by novel chemotypes were purchased and tested. Sixteen of them were identified as AR antagonists with affinity towards combinations of the AR family isoforms (A2A/A3, A1/A3, A1/A2A/A3 and A3). The second part of this work involves the performance of hundreds of molecular dynamics (MD) simulations of complexes between the ARs and the total of 27 ligands to resolve the binding interactions of the active compounds, which were not achieved by docking calculations alone. This computational work allowed the prediction of stable and unstable complexes which agree with the experimental results of potent and inactive compounds respectively. Of particular interest is that the 2-amino-thiophene-3- carboxamides, 3-acylamino-5-aryl-thiophene-2-carboxamides and carbonyloxycarboximidamide derivatives were found to be selective and possess a micromolar to low micromolar affinity for A3 receptor

Ochraceopyronide, a rare α‐pyrone‐c‐lyxofuranoside from a soil‐derived fungus aspergillus ochraceopetaliformis

The fungal strain was isolated from a soil sample collected in Giza province, Egypt, and was identified as Aspergillus ochraceopetaliformis based on phenotypic and genotypic data. The ethyl acetate extract of the fungal strain exhibited promising activity levels against several pathogenic test organisms and through a series of1H NMR guided chromatographic separations, a new α‐py-rone‐C‐lyxofuranoside (1) along with four known compounds (2–5) were isolated. The planar structure of the new metabolite was elucidated by detailed analysis of its 1D/2D NMR and HRMS/IR/UV spectroscopic data, while the relative configuration of the sugar moiety was determined by a combined study of NOESY and coupling constants data, with the aid of theoretical calculations. The structures of the known compounds—isolated for the first time from A. ochraceopetaliformis—were established by comparison of their spectroscopic data with those in the literature. All isolated fungal metabolites were evaluated for their antibacterial and antifungal activities against six Gram-posi-tive and Gram‐negative bacteria as well as against three human pathogenic fungi. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Steroid sulfatase inhibiting lanostane triterpenes – Structure activity relationship and in silico insights

Steroid sulfatase (STS) transforms hormone precursors into active steroids. Thus, it represents a target of intense research regarding hormone-dependent cancers. In this study, three ligand-based pharmacophore models were developed to identify STS inhibitors from natural sources. In a pharmacophore-based virtual screening of a curated molecular TCM database, lanostane-type triterpenes (LTTs) were predicted as STS ligands. Three traditionally used polypores rich in LTTs, i.e., Ganoderma lucidum Karst., Gloeophyllum odoratum Imazeki, and Fomitopsis pinicola Karst., were selected as starting materials. Based on eighteen thereof isolated LTTs a structure activity relationship for this compound class was established with piptolinic acid D (1), pinicolic acid B (2), and ganoderol A (3) being the most pronounced and first natural product STS inhibitors with IC50 values between 10 and 16 µM. Molecular docking studies proposed crucial ligand target interactions and a prediction tool for these natural compounds correlating with experimental findings. © 2019 Elsevier Inc

Erythroidine alkaloids: A novel class of phytoestrogens

Erythrina poeppigiana is a medicinal plant which is widely used in Asia, Latin America, and Africa in traditional remedies for gynecological complications and maladies. In continuation of studies for the discovery of novel phytoestrogens, four erythroidine alkaloids, namely α-erythroidine, β-erythroidine, and their oxo-derivatives 8-oxo-α-erythroidine and 8-oxo-β-erythroidine, were isolated and structurally characterized from the methanolic extract of the stem bark of E. poeppigiana. Due to the high amounts of erythroidines in the extract and considering the widespread utilization of Erythrina preparations in traditional medicine, the exploration of their estrogenic properties was performed. The estrogenicity of the isolated erythroidines was assayed in various estrogen receptor-(ER)-dependent test systems, including receptor binding affinity, cell culture based ER-dependent reporter gene assays, and gene expression studies in cultured cells using reverse transcription polymerase chain reaction techniques. α-Erythroidine and β-erythroidine showed binding affinity values for ERα of 0.015 ± 0.010% and 0.005 ± 0.010%, respectively, whereas only β-erythroidine bound to ERβ (0.006 ± 0.010%). In reporter gene assays, both erythroidines exhibited a significant dose-dependent estrogenic stimulation of ER-dependent reporter gene activity in osteosarcoma cells detectable already at 10 nM. Results were confirmed in the MVLN cells, a bioluminescent variant of MCF-7 breast cancer cells. Further, α-erythroidine and β-erythroidine both induced the enhanced expression of the specific ERα-dependent genes trefoil factor-1 and serum/glucocorticoid regulated kinase 3 in MCF-7 cells, confirming estrogenicity. Additionally, using molecular docking simulations, a potential mode of binding on ERα, is proposed, supporting the experimental evidences. This is the first time that an estrogenic profile is reported for erythroidine alkaloids, potentially a new class of phytoestrogens. © Georg Thieme Verlag KG Stuttgart New York