Towards Anion Recognition and Precipitation with Water-Soluble 1,2,4-Selenodiazolium Salts: Combined Structural and Theoretical Study

The synthesis and structural characterization of a series of supramolecular complexes of bicyclic cationic pyridine-fused 1,2,4-selenodiazoles with various anions is reported. The binding of trifluoroacetate, tetrachloroaurate, tetraphenylborate, perrhenate, and pertechnetate anions in the solid state is regarded. All the anions interact with selenodiazolium cations exclusively via a pair of “chelating” Se⋯O and H⋯O non-covalent interactions, which make them an attractive, novel, non-classical supramolecular recognition unit or a synthon. Trifluoroacetate salts were conveniently generated via novel oxidation reaction of 2,2′-dipyridyl diselenide with bis(trifluoroacetoxy)iodo)benzene in the presence of corresponding nitriles. Isolation and structural characterization of transient 2-pyridylselenyl trifluoroacetate was achieved. X-ray analysis has demonstrated that the latter forms dimers in the solid state featuring very short and strong Se⋯O and Se⋯N ChB contacts. 1,2,4-Selenodiazolium trifluoroacetates or halides show good solubility in water. In contrast, (AuCl₄)⁻, (ReO₄)⁻, or (TcO₄)⁻ derivatives immediately precipitate from aqueous solutions. Structural features of these supramolecular complexes in the solid state are discussed. The nature and energies of the non-covalent interactions in novel assembles were studied by the theoretical methods. To the best of our knowledge, this is the first study that regards perrhenate and pertechnetate as acceptors in ChB interactions. The results presented here will be useful for further developments in anion recognition and precipitation involving cationic 1,2,4-selenodiazoles.     

Elektrochemische Bestimmung der Sauerstoffpartialdrücke in Wasserdampf-Wasserstoff-Gemischen und sauerstoffhaltigen Eisenschmelzen

Die Sauerstoffionenleitung in stabilisiertem Zirkondioxyd. CaO-stabilisiertes Zirkondioxyd als Elektrolyt in Sauerstoffkonzentrationsketten. Elektrochemische Bestimmung der Sauerstoffpartialdrücke in H₂O-H₂-Gasgemischen an der Kette Luft/ZrO₂ + CaO/H₂O, H₂ bei 800 bis 1750 °C und in sauerstoffhaltigen Eisenschmelzen an der Kette H₂O, H₂/ZrO₂ + CaO/[O]_Fe bei 1550 bis 1750 °C. Ermittlung der Temperaturabhängigkeit der Freien Enthalpie für die Reaktionen {H₂} + 1/2 {O₂} = {H₂O} und 1/2 {O₂} = [O]_Fe. Berechnung der Überführungszahlen der Ionen und der kritischen Sauerstoffdrücke der beginnenden Elektronenleitung für den ZrO₂-CaO-Elektrolyten.     

Proceedings of the American Psychological Association for the legislative year 2008: Minutes of the annual meeting of the Council of Representatives, February 22–24, 2008, Washington, DC, and August 13 and 17, 2008, Boston, MA, and minutes of the February, June, August, and December 2008 meetings of the Board of Directors.

These minutes are the official record of the actions of the Association taken during the year by both the Board of Directors (the Board) and the Council of Representatives (Council). The roll of representatives was called at each Council meeting, and more than a quorum answered to their names. Reference is made in these minutes to various reports, some of which will be published elsewhere. Copies of these reports were distributed to Council and are on file in the Central Office. As long as the supply lasts, extra copies of many of the reports are available from the Central Office. These minutes are arranged in topical rather than chronological order, and subheadings are used when appropriate. The main topical headings are I. Minutes of Meetings; II. Elections, Awards, Membership, and Human Resources; III. Ethics; IV. Board of Directors; V. Divisions and State, Provincial, and Territorial Psychological Associations; VI. Organization of the APA; VII. Publications and Communications; VIII. Convention Affairs; IX. Educational Affairs; X. Professional Affairs; XI. Scientific Affairs; XII. Public Interest; XIII. Ethnic Minority Affairs; XIV. International Affairs; XV. Central Office; and XVI. Financial Affairs. Changes to the language of the American Psychological Association (APA) Bylaws, Association Rules, or motions of the items are noted as follows throughout these proceedings: Bracketed material is to be deleted; underlined material is to be added. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Proceedings of the American Psychological Association for the legislative year 2010: Minutes of the annual meeting of the Council of Representatives, February 19–21, 2010, Washington, DC, and August 11 and 15, 2010, San Diego, California, and minutes of the February, June, August, September, and December 2010 meetings of the Board of Directors.

These minutes are the official record of the actions of the Association taken during the year by both the Board of Directors (the Board) and the Council of Representatives (Council). The roll of representatives was called at each Council meeting, and more than a quorum answered to their names. Reference is made in these minutes to various reports, some of which will be published elsewhere. Copies of these reports were distributed to Council and are on file in the Central Office. As long as the supply lasts, extra copies of many of the reports are available from the Central Office. These minutes are arranged in topical rather than chronological order, and subheadings are used when appropriate. The main topical headings are I. Minutes of Meetings; II. Elections, Awards, Membership, and Human Resources; III. Ethics; IV. Board of Directors; V. Divisions and State, Provincial, and Territorial Associations; VI. Organization of the APA; VII. Publications and Communications; VIII. Convention Affairs; IX. Educational Affairs; X. Professional Affairs; XI. Scientific Affairs; XII. Public Interest; XIII. Ethnic Minority Affairs; XIV. International Affairs; XV. Central Office; and XVI. Financial Affairs. Changes to the language of the American Psychological Association (APA) Bylaws, Association Rules, or motions of the items are noted as follows throughout these proceedings: Bracketed material is to be deleted; underlined material is to be added. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Festelektrolytzellen mit gasförmigen Vergleichselektroden zur Messung der Sauerstoffaktivität in Eisenschmelzen

Kritische Überprüfung des Anwendungsbereichs von stabilisiertem Zirkonoxid, Mullit und Magnesiumoxid in einer Festelektrolytzelle mit Luft als Sauerstoffvergleichspotential. Nachweis der Sauerstoffdurchlässigkeit fester Elektrolyte und der Ausbildung von Sauerstoffdiffusionsschichten an der Phasengrenze Festelektrolyt/Eisenschmelze. Voraussetzungen für eine korrekturfreie elektrochemische Sauerstoffbestimmung in Eisenschmelzen bei Verwendung von gasförmigen Sauerstoffvergleichspotentialen.     

Excessive Adventitial and Perivascular Vascularisation Correlates with Vascular Inflammation and Intimal Hyperplasia

Albeit multiple studies demonstrated that vasa vasorum (VV) have a crucial importance in vascular pathology, the informative markers and metrics of vascular inflammation defining the development of intimal hyperplasia (IH) have been vaguely studied. Here, we employed two rat models (balloon injury of the abdominal aorta and the same intervention optionally complemented with intravenous injections of calciprotein particles) and a clinical scenario (arterial and venous conduits for coronary artery bypass graft (CABG) surgery) to investigate the pathophysiological interconnections among VV, myeloperoxidase-positive (MPO⁺) clusters, and IH. We found that the amounts of VV and MPO⁺ clusters were strongly correlated; further, MPO⁺ clusters density was significantly associated with balloon-induced IH and increased at calciprotein particle-provoked endothelial dysfunction. Likewise, number and density of VV correlated with IH in bypass grafts for CABG surgery at the pre-intervention stage and were higher in venous conduits which more frequently suffered from IH as compared with arterial grafts. Collectively, our results underline the pathophysiological importance of excessive VV upon the vascular injury or at the exposure to cardiovascular risk factors, highlight MPO⁺ clusters as an informative marker of adventitial and perivascular inflammation, and propose another mechanistic explanation of a higher long-term patency of arterial grafts upon the CABG surgery.     

Using a Polygenic Score to Predict the Risk of Developing Primary Osteoporosis

Osteoporosis (OP) is a multifactorial bone disease belonging to the metabolic osteopathies group. Using the polygenic score (PGS) approach, we combined the effects of bone mineral density (BMD) DNA loci, affecting osteoporosis pathogenesis, based on GEFOS/GENOMOS consortium GWAS meta-analysis. We developed models to predict the risk of low fractures in women from the Volga-Ural region of Russia with efficacy of 74% (AUC = 0.740; OR (95% CI) = 2.9 (2.353–3.536)), as well as the formation of low BMD with efficacy of 79% (AUC = 0.790; OR (95% CI) = 3.94 (2.993–5.337)). In addition, we propose a model that predicts fracture risk and low BMD in a comorbid condition with 85% accuracy (AUC = 0.850; OR (95% CI) = 6.6 (4.411–10.608)) in postmenopausal women.     

Recognition of a Clickable Abasic Site Analog by DNA Polymerases and DNA Repair Enzymes

Azide–alkyne cycloaddition (“click chemistry”) has found wide use in the analysis of molecular interactions in living cells. 5-ethynyl-2-(hydroxymethyl)tetrahydrofuran-3-ol (EAP) is a recently developed apurinic/apyrimidinic (AP) site analog functionalized with an ethynyl moiety, which can be introduced into cells in DNA constructs to perform labeling or cross-linking in situ. However, as a non-natural nucleoside, EAP could be subject to removal by DNA repair and misreading by DNA polymerases. Here, we investigate the interaction of this clickable AP site analog with DNA polymerases and base excision repair enzymes. Similarly to the natural AP site, EAP was non-instructive and followed the “A-rule”, directing residual but easily detectable incorporation of dAMP by E. coli DNA polymerase I Klenow fragment, bacteriophage RB69 DNA polymerase and human DNA polymerase β. On the contrary, EAP was blocking for DNA polymerases κ and λ. EAP was an excellent substrate for the major human AP endonuclease APEX1 and E. coli AP exonucleases Xth and Nfo but was resistant to the AP lyase activity of DNA glycosylases. Overall, our data indicate that EAP, once within a cell, would represent a replication block and would be removed through an AP endonuclease-initiated long-patch base excision repair pathway.     

Size and Methylation Index of Cell-Free and Cell-Surface-Bound DNA in Blood of Breast Cancer Patients in the Contest of Liquid Biopsy

Aberrantly methylated circulating DNA (cirDNA) has proven to be a good cancer marker, but its detection is limited by low concentrations, fragmentation, and insufficiency. Since the methylated cirDNA was shown to be more stable in circulation than the unmethylated one and was shown to bind with the blood cell surface, we studied the concentration, representation, and fragmentation of tumor-derived methylated DNA in cell-free and cell-surface-associated DNA. We found that long DNA fragments (more than 10 kb) are mainly associated with the surface of blood cells. However, in plasma short DNA fragments (100–1000 bp) were also found along with long DNA fragments. Isolation of short fragments after separation of cirDNA in 6% PAGE followed by quantitative PCR (L1 element) has shown that short DNA fragments in healthy females represent 22% versus 0.5–4.4% in breast cancer patients. The methylated form of the RARβ2 gene was detected only in long DNA fragments by Real-time TaqMan PCR of bisulfite-converted DNA. The methylation index of cirDNA from healthy women was estimated at 0%, 9%, and 7% in plasma, PBS-EDTA, and trypsin eluates from the surface of blood cells, respectively. The methylation index of breast cancer patients’ DNA was found to be 33%, 15%, and 61% in the same fractions confirming the overrepresentation of methylated DNA in csbDNA.     

Insertion of Calcium-Permeable AMPA Receptors during Epileptiform Activity In Vitro Modulates Excitability of Principal Neurons in the Rat Entorhinal Cortex

Epileptic activity leads to rapid insertion of calcium-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (CP-AMPARs) into the synapses of cortical and hippocampal glutamatergic neurons, which generally do not express them. The physiological significance of this process is not yet fully understood; however, it is usually assumed to be a pathological process that augments epileptic activity. Using whole-cell patch-clamp recordings in rat entorhinal cortex slices, we demonstrate that the timing of epileptiform discharges, induced by 4-aminopyridine and gabazine, is determined by the shunting effect of Ca²⁺-dependent slow conductance, mediated predominantly by K⁺-channels. The blockade of CP-AMPARs by IEM-1460 eliminates this extra conductance and consequently increases the rate of discharge generation. The blockade of NMDARs reduced the additional conductance to a lesser extent than the blockade of CP-AMPARs, indicating that CP-AMPARs are a more significant source of intracellular Ca²⁺. The study’s main findings were implemented in a mathematical model, which reproduces the shunting effect of activity-dependent conductance on the generation of discharges. The obtained results suggest that the expression of CP-AMPARs in principal neurons reduces the discharge generation rate and may be considered as a protective mechanism.