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• G4 DNA wires mediate electron transfer (ET) between gold and G4-bound methylene blue (MB). • G4 DNA wires were tethered to gold electrodes via 4 phosphorothioated adenosine tags. • ET rate constant k s of 155 s−1 beats 74 s−1 shown for (dGdC) 20 , approaching 184 s−1 of (dAdT) 25. • This k s is well below 108 s−1 determined by the current-voltage measurements with no MB. • Complex H+/2e− electrochemistry of MB obstructed kinetic analysis of ET along G4 wires. G-quadruplex (G4) DNA wires are perspective highly-conductive building blocks for self-assembling bioelectronic nanocircuits. Here, we interrogated electrochemically G4-mediated electron transfer (ET) reaction between the gold electrodes and redox indicator methylene blue (MB) intercalated into ten-tetrade G4 DNA tethered to the gold electrode via four phosphorothioated adenosine tags. The efficiency of DNA-mediated ET evaluated by kinetic analysis of MB redox transformations was characterized by the k s of 155 s−1. This value was well below 108 s−1 per ten tetrades determined by the current-voltage measurements in the absence of any redox active species, primarily. Due to the complex 2e−/1H+ electrochemistry of MB that apparently gated the overall ET reaction. However, it was superior to 74 s−1 found for MB intercalated into (dGdC) 20 duplexes and close to 184 s−1 estimated for MB groove-bound to (dAdT) 25. The ET-mediating efficiency of highly hydrated G4 wires was thus superior to the electronically-corrupted and water-poor dGdC duplexes and approaching that of dAdT-rich DNA. We show that the electrical properties of G4 DNA wires assessed electrochemically with MB as a redox probe differ essentially from those measured in the absence of redox indicators, indicating that the electrochemical reaction of the redox probe intercalating/interacting with the G4 DNA wires limits the overall kinetics of ET through the wire. [Display omitted] [ABSTRACT FROM AUTHOR]

The evolution of multicellularity has been one of the major transitions in the history of life. In contrast to animals and plants, how multicellularity evolved in fungi and how it compares to the general principles distilled from the study of more widely studied model systems, has received little attention. This review broadly discusses multicellular functioning and evolution in fungi. We focus on how fungi solved some of the common challenges associated with the evolution of multi-celled organisms and what unique challenges follow from the peculiar, filamentous growth form of fungi. We identify and discuss seven key challenges for fungal multicellular growth: apical growth, compartmentalization, long-distance mass transport, controlling mutational load, cell-to-cell communication, differentiation and adhesion. Some of these are characteristic of all multicellular transitions, whereas others are unique to fungi. We hope this review will facilitate the interpretation of fungal multicellularity in comparison with that of other multicellular lineages and will prompt further research into how fungi solved fundamental challenges in one of the major transitions in their evolutionary history. - Fungi evolved multicellularity via unique mechanisms compared to other lineages - Fungi had to overcome 7 key obstacles during the evolution of multicellularity - Fungal hyphae are different from most other forms of multicellularity - Both simple and complex multicellularity occur in fungi [ABSTRACT FROM AUTHOR]

DNA-mediated electron transfer (ET) underlies a variety of bioelectronics applications, and, thus, simple approaches for its kinetic analysis are required. Here, electrocatalysis of a ferricyanide reduction catalyzed by methylene blue (MB) bound to either (dGdC) 20 or (dAdT) 25 duplexes tethered to gold via an alkanethiol linker was voltammetrically studied at stationary electrodes, and its kinetics was analyzed by two theoretical models. A thin layer voltammetry analysis, assuming that the reaction occurs within the l -nm thick layer formed by the DNA duplexes of the length l , yielded the electrocatalytic rate constant k 1 of (2.1 ± 0.4)105 and (2.4 ± 0.5)106 M−1 s−1, for (dGdC) 20 and (dAdT) 25. The sequence-specific k 1 values were consistent with structural differences of (dGdC) 20 or (dAdT) 25 at the negatively polarized interface and approached the k 1 previously reported for the rotating disk electrode system (Angew. Chemie Int. Ed. 58 (2019) 3048). These results offer new tools for immediate kinetic analysis of electrocatalytic reactions involving long-range ET along the DNA duplexes, the tools that allow differentiating electrical properties of nucleic acids in the most convenient and simple way. Image 1 • Electrocatalysis of [Fe(CN) 6 ]3- reduction by DNA-bound methylene blue was studied. • Kinetics of electrocatalysis was assessed by thin-layer voltammetry at stationary electrodes. • Theoretical approach allowed evaluation of DNA-mediated electron transfer (ET) rates. • Evaluated reaction rates were consistent with those obtained in the rotating disk electrode system. • Results offer simple tools for kinetic analysis of electrocatalysis involving DNA-mediated ET. [ABSTRACT FROM AUTHOR]

This study is the first pharmacological characterization of the novel chemical entity, ORM-3819 ( L -6-{4-[N'-(4-Hydroxi-3-methoxy-2-nitro-benzylidene)-hydrazino]-phenyl}-5-methyl-4,5-dihydro-2 H-pyridazin-3-one), focusing primarily on its cardiotonic effects. ORM-3819 binding to cardiac troponin C (cTnC) was confirmed by nuclear magnetic resonance spectroscopy, and a selective inhibition of the phosphodiesterase III (PDE III) isozyme (IC 50 =3.88±0.3 nM) was revealed during in vitro enzyme assays. The Ca 2+ -sensitizing effect of ORM-3819 was demonstrated in vitro in permeabilized myocyte-sized preparations from left ventricles (LV) of guinea pig hearts (ΔpCa 50 =0.12±0.01; EC 50 =2.88±0.14 µM). ORM-3819 increased the maximal rate of LV pressure development (+dP/dt max ) (EC 50 =8.9±1.7 nM) and LV systolic pressure (EC 50 =7.63±1.74 nM) in Langendorff-perfused guinea pig hearts. Intravenous administration of ORM-3819 increased LV+dP/dt max (EC 50 =0.13±0.05 µM/kg) and improved the rate of LV pressure decrease (−dP/dt max ); (EC 50 =0.03±0.02 µM/kg) in healthy guinea pigs. In an in vivo dog model of myocardial stunning, ORM-3819 restored the depressed LV+dP/dt max and improved % segmental shortening (%SS) in the ischemic area (to 18.8±3), which was reduced after the ischaemia-reperfusion insult (from 24.1±2.1 to 11.0±2.4). Our data demonstrate ORM-3819 as a potent positive inotropic agent exerting its cardiotonic effect by a cTnC-dependent Ca 2+ -sensitizing mechanism in combination with the selective inhibition of the PDE III isozyme. This dual mechanism of action results in the concentration-dependent augmentation of the contractile performance under control conditions and in the postischemic failing myocardium. [ABSTRACT FROM AUTHOR]

Platelet derived growth factor receptors (PDGFR) play an important role in tumor pathogenesis and are frequently overexpressed in glioblastoma. Earlier we have shown that only confluent glioblastoma cell cultures exhibit a biphasic calcium transient upon PDGF stimulation. Here, we examined how the change in cell density leads to differential cellular responses to the same PDGF stimulus. PDGF beta receptors and their specific phosphotyrosine residues were fluorescently co-labeled on A172 and T98G glioblastoma cells. The distribution in cell membrane microdomains (lipid rafts) and the phosphorylation state of PDGFR was measured by confocal microscopy and quantitated by digital image processing. Corresponding bulk data were obtained by Western blotting. Activation of relevant downstream signaling pathways was assessed by immunofluorescence in confocal microscopy and by Western blot analysis. Functional outcomes were confirmed with bulk and single cell proliferation assays and motility measurements. In non-confluent (sparse) cultures PDGF-BB stimulation significantly increased phosphorylation of Tyr716 specific for the Ras/MAPK pathway and Tyr751 specific for the phosphoinositide 3-kinase/Akt pathway. As cell monolayers reached confluence, Tyr771 and Tyr1021 were the prominently phosphorylated residues. Tyr771 serves as adaptor for Ras-GAP, which inactivates the MAPK pathway, and Tyr1021 feeds into the phospholipase C-gamma/PKC pathway. Coherent with this, MAPK phosphorylation, Ki-67 positivity and proliferation dominated in dispersed cells, and could be abolished with inhibitors of the MAPK pathway. At the same time, RhoA activation, redistribution of cortactin to leading edges, and increased motility were the prominent output features in confluent cultures. Importantly, the stimulus-evoked confluence-specific changes in the phosphorylation of tyrosine residues occurred mainly in GM1-rich lipid microdomains (rafts). These observations suggest that the same stimulus is able to promote distinctly relevant signaling outputs through a confluence dependent, lipid raft-based regulatory mechanism. In particular, cell division and survival in sparse cultures and inhibition of proliferation and promotion of migration in confluent monolayers. In our model, the ability to switch the final output of the same stimulus as a function of cell density could be a key to the balance of proliferation and invasion in malignant glioblastoma. [ABSTRACT FROM AUTHOR]

• Electrochemical synthesis of struvite used a pure Mg anode. • Synthetic wastewater with Cl− background was used as test solution. • Pitting potential saturates to a minimum at Cl− ≥ 1000 mM. • Higher corrosion rate was obtained at pH 8. • 98% phosphate recovery was achieved in Cl− ≥1000 mM at pH 8. Electrochemical recovery of phosphorus from synthetic wastewater using a sacrificial Mg anode has been explored as a function of key parameters, including pH, voltage, and salinity. The effect of chloride (NaCl) concentrations in the range of 0–1500 mM on both Mg corrosion and phosphate precipitation was investigated in acidic and alkaline (i.e., pH 4 and 8) solutions of dihydrogen ammonium phosphate. The primary phosphate precipitate was expected to be struvite (MgNH 4 PO 4 ·6H 2 O), and collected precipitates were characterized to determine composition and phase. Batch experiments were run at selected potentials identified by linear sweep voltammetry experiments. Higher corrosion current densities (j corr), which indicated higher Mg dissolution and corrosion rates (υ corr), were achieved in solutions with higher pH and salt concentrations. Both Mg corrosion and phosphate recovery were proportional to [Cl−], so 1500 mM Cl− at pH 8 resulted in increased Mg dissolution and phosphate recovery by ∼5x and 2x, respectively, compared to the solution without chloride. Elemental composition analysis (ion chromatography), crystallography (X-ray diffraction), surface chemical composition analysis (Fourier-transform infrared spectrometry) and characterization (scanning electron microscopy images) of precipitates suggested the presence of struvite. The Mg/P composition of precipitates formed in 1000 mM Cl− solution showed a greater extent of deviation from the theoretical molar ratio in struvite when the electrochemical cell was operated at more positive anodic overpotential and low initial solution pH. The elevated Mg/P ratio could indicate the presence of mixed precipitates. Simulation of product distribution analysis and specific energy requirement results suggest optimum electrochemical struvite production in the pH range of 8–10 in the presence of chloride. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: The architectural high mobility group box 1 (Hmgb1) protein acts as both a nuclear and an extracellular regulator of various biological processes, including skeletogenesis. Here we report its contribution to the evolutionarily conserved, distinctive regulation of the matrilin-1 gene (Matn1) expression in amniotes. We previously demonstrated that uniquely assembled proximal promoter elements restrict Matn1 expression to specific growth plate cartilage zones by allowing varying doses of L-Sox5/Sox6 and Nfi proteins to fine-tune their Sox9-mediated transactivation. Here, we dissected the regulatory mechanisms underlying the activity of a conserved distal promoter element 1. We show that this element carries three Sox-binding sites, works as an enhancer in vivo, and allows promoter activation by the Sox5/6/9 chondrogenic trio. In early steps of chondrogenesis, declining Hmgb1 expression overlaps with the onset of Sox9 expression. Unlike repression in late steps, Hmgb1 overexpression in early chondrogenesis increases Matn1 promoter activation by the Sox trio, and forced Hmgb1 expression in COS-7 cells facilitates induction of Matn1 expression by the Sox trio. The conserved Matn1 control elements bind Hmgb1 and SOX9 with opposite efficiency in vitro. They show higher HMGB1 than SOX trio occupancy in established chondrogenic cell lines, and HMGB1 silencing greatly increases MATN1 and COL2A1 expression. Together, these data thus suggest a model whereby Hmgb1 helps recruit the Sox trio to the Matn1 promoter and thereby facilitates activation of the gene in early chondrogenesis. We anticipate that Hmgb1 may similarly affect transcription of other cartilage-specific genes. [Copyright &y& Elsevier]

In this study, a suite of natural wastewater sources is tested to understand the effects of wastewater composition and source on electrochemically driven nitrogen and phosphorus nutrient removal. Kinetics, electrode behavior, and removal efficiency were evaluated during electrochemical precipitation, whereby a sacrificial magnesium (Mg) anode was used to drive precipitation of ammonium and phosphate. The electrochemical reactor demonstrated fast kinetics in the natural wastewater matrices, removing up to 54% of the phosphate present in natural wastewater within 1 min, with an energy input of only 0.04 kWh.m−3. After 1 min, phosphate removal followed a zero-order rate law in the 1 min - 30 min range. The zero-order rate constant (k) appears to depend upon differences in wastewater composition, where a faster rate constant is associated with higher Cl− and NH 4 + concentrations, lower Ca2+ concentrations, and higher organic carbon content. The sacrificial Mg anode showed the lowest corrosion resistance in the natural industrial wastewater source, with an increased corrosion rate (v corr) of 15.8 mm.y−1 compared to 1.9–3.5 mm.y−1 in municipal wastewater sources, while the Tafel slopes (β) showed a direct correlation with the natural wastewater composition and origin. An overall improvement of water quality was observed where important water quality parameters such as total organic carbon (TOC), total suspended solids (TSS), and turbidity showed a significant decrease. An economic analysis revealed costs based upon experimental Mg consumption are estimated to range from 0.19 $.m−3 to 0.30 $.m−3, but costs based upon theoretical Mg consumption range from 0.09 $.m−3 to 0.18 $.m−3. Overall, this study highlights that water chemistry parameters control nutrient recovery, while electrochemical treatment does not directly produce potable water, and that economic analysis should be based upon experimentally-determined Mg consumption data. Synopsis Statement: Magnesium-driven electrochemical precipitation of natural wastewater sources enables fast kinetics for phosphate removal at low energy input. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: The aim of our work was to examine three industrial by-products in order to determine whether the examined by- products can be potentially used for the nutrition of plants. Maize (Zea mays L.) was used in the experiments. The by- products to be involved into the experiments were grinding sludge, extruded poppy-heads remaining from morphine production and sewage sludge compost. All of the by-products involved into the experiments are generated in huge volumes; therefore, they can be suitable for solving nutrient deficiency problems in large agricultural fields. It has been confirmed by the experiments focusing on the nutritional elements of the by-products that all the by-products contain several essential elements (e.g. Ca, Fe, K, Mg, P and S) in large quantities. In the light of the experiments, we have come to the conclusion that all of the examined by-products can be used in the nutrition supply of plants, but it is essential to determine the concentrations of application accurately for field use. This statement is particularly true for grinding sludge. In summary of the results, we found that the by-products that were subjected in our experiments may be used in full or partial replacement of the costly chemicals as the case may be, though as the composition of the by-products, e.g. sewage sludge compost, may change, it is necessary to continuously monitor the by-products designed for the above use. [Copyright &y& Elsevier]

Abstract: The study area, located at the contact zone between the Harghita Mountains and the Transylvanian Basin is well known for the abundance and diversity of mineral water springs. These mineral waters are used by the local people for drinking and also as Spas. This paper focuses on the mineral waters of some traditional Spas from this area, Odorheiu Secuiesc (Seiche Spa, Kápolnás Spa or Solymossy Spa), Upper Vârghiş Valley (Selters Spa and Nádasszék Spa) and Chirui Spa. The aim of the present work is to characterize the mineral waters based on the quantification of chemical content and also to establish correlations between the geological structure and the water''s chemical composition. The geological setting and tectonics have a large influence on the chemical composition of mineral waters. Two main water types can be described, mineral waters of Na+ – Cl- type, present at Odorheiu Secuiesc, Kápolnás Spa and of HCO3- type with no dominant cation at Chirui Spa. The mineral waters located on a fault at Odorhei Seiche Spa have high CO2 values. Possible mixing zones might be identified between the two types which are present in the Upper Vârghiş Valley where mineral waters of Na+ – HCO3-– Cl- type are present except one source, which is of Na+ – Cl- type. The mixing is reflected not only by the chemical composition, but also by the quantity of dissolved CO2. The present paper deals with all the existing mineral water springs in the area providing information in a high resolution about the local hydromineral system. [Copyright &y& Elsevier]

Abstract: This review summarized the literature and own data on the parent organotin(IV) compounds and complexes formed with biologically active ligands. [Copyright &y& Elsevier]

Abstract: A number of [Ph3Sn(IV)]+ complexes formed with ligands containing –OH (–Cx2013;COOH group(s) and aromatic {N} donor atom have been prepared. The binding sites of the ligands were identified by FT-IR spectroscopic measurements. In the complexes containing hydroxy and carboxylate functions, the carboxylato group is coordinated to the organotin(IV) centres in monodentate or bridging bidentate manner. It was also found that in the hydroxypyridine and -pyrimidine complexes the [Ph3Sn(IV)]+ moiety in most cases reacts with the phenolic form of the ligands. The rationalisation of the experimental 119Sn Mössbauer nuclear quadrupole splittings, |Δ exp| – according to the point charge model formalism – together with the FT-IR data support the formation of trigonal bipyramidal (Tbp) or octahedral (Oh) molecular structures. Furthermore, X-ray diffraction analysis has been performed on the triphenyltin(IV)-3-phenolato-2(1H)-pyridinone-O,O′ single crystals. The penta-coordinated tin center exhibits a Tbp geometry. In case of 2-picolinic acid, a trans-phenylation was observed during the complexation, resulting [Ph2Sn(IV)]2+ complex and Ph4Sn(IV). [Copyright &y& Elsevier]

Abstract: Nine complexes of tBu2Sn(IV)2+ were obtained in the solid state with ligands containing –COOH group(s) and aromatic {N} donor atom. The binding sites of the ligands were identified by FT-IR spectroscopic measurements. It was found that in most cases the –COO− groups are co-ordinated in monodentate manner. Nevertheless, in some of our complexes, the –COO− group forms bridges between two central {Sn} atoms resulting in the formation of an oligomeric structure, a motif that is characteristic only to the nicotinate compound. These pieces of information and the rationalisation of the experimental 119Sn Mössbauer nuclear quadrupole splittings, Δ, – according to the point charge model formalism – support the formation of octahedral (Oh) or trigonal bipyramidal (TBP) molecular structures. The X-ray diffraction analysis of one complex obtained as single crystal revealed the distortion of the TBP geometry towards square pyramidal (SP) one. This was rationalised by PM3 molecular modelling of the tBu2Sn(pdc) complex. In the asymmetric unit, the two chemically similar but symmetry independent molecules form pseudo-dimers, in which the Sn⋯Sn separation amounts to ca. 6.4 Å. The crystal lattice is stabilised by C–H⋯O hydrogen bonding between individual molecules. [Copyright &y& Elsevier]

The coordination of Me2Sn(IV)2+ (&z.dbnd6;M) to captopril {N-[(S)-3-mercapto-2-methylpropionyl]-l-proline, &z.dbnd6;H2(cap), H2L} in aqueous solution was studied by means of potentiometric titration, electrospray mass spectrometry, 1H-NMR spectroscopy and Mo¨ssbauer spectroscopy in the pH range 2–11 (I=0.1 mol dm−3 NaClO4, 298 K). The results obtained with these methods proved that only monomeric complexes are formed in solution. In the acidic pH range, species with a metal-to-ligand ratio of 1:1 exist. The neutral complex ML, similarly to the complex Me2Sn(cap) crystallized in the same pH range, adopts a tbp structure with eq &z.sbnd;S− and ax &z.sbnd;COO−, while, instead of the coordination of the amide &z.sbnd;C&z.dbnd6;O, observed in the solid state, the other ax position is occupied by a H2O molecule. With increasing pH, in the neutral and weakly basic pH range the complexes MLH−1 and ML2 are formed, in which the &z.sbnd;COO− group is displaced from the coordination sphere by an OH− and an S− of another ligand, respectively. Biological activity tests on Me2Sn(cap) and three further R2Sn(IV) captopril complexes showed that n-Bu2Sn(cap) and t-Bu2Sn(cap) exert toxic activity towards the embryos of Ciona intestinalis, while the ligand itself does not affect the development of the embryos to any significant extent; Me2Sn(cap) and Et2Sn(cap) produced normal swimming larvae. [Copyright &y& Elsevier]

The organotin(IV) cations form complexes with ligands containing {O}, {N}, {S}, or {phosphorus(O)} donor atoms with various composition and stability. The emergence of new experimental techniques (EXAFS, multinuclear 1H-, 13C-, 119Sn-NMR, 119Sn Mo¨ssbauer, etc., spectroscopic techniques) provided useful information about the structure and stabilities of the complexes formed. We reviewed the literature on these type of complexes taking into account the biological aspects of the complexes discussed. [Copyright &y& Elsevier]