Utilization of a sewage sludge for rehabilitating the soils degraded by the metallurgical industry and a possible environmental risk involved

Soils collected in the proximity of a steel plant in Krakow were analyzed for their pH, the content of total organic carbon, and the total contents of metals and metalloids. Applying the Commission of European Communities Bureau of Reference (BCR) extraction of selected metals: Cd, Fe, Pb, and Zn, their forms of binding in soils have been determined. The results of the soil analyses of the samples taken in 1996 and 2016 were compared, and then the soil contamination changes were assessed using the GI, contamination factor (CF), and PLI indicators. A rehabilitation of the degraded soils was tested using the communal sewage sludge, which was added into the soil at four various ratios. The sewage sludge applied meets the environmental standards as a material for rehabilitating soils for non-agricultural needs but cannot be used for upgrading strongly contaminated soils. The reason is that the sludge addition increases the soil As, Ca, Cr, Mn, and Zn quantities as well as the easily mobilized fractions of the sludge/soil mixtures that contain Cd, Cr, Mg, Mn, Pb, and Tl. The addition of the communal sludge into soils increases the value of the environmental risk in the case of Pb, Mn, Mg, Fe, Cr, Zn, and Ca, but within the same risk classification ranges.     

Radiotherapy alone as a method of treatment for sinonasal mucosal melanoma: A report based on six cases and a review of current opinion

Objectives

Radiotherapy in patients with sinonasal mucosal melanoma (SNMM) was given as alternative treatment to surgery in cases with advanced, inoperable tumors or those not eligible for surgery. We presented the outcomes for patients with SNMM treated with radiotherapy alone.

Allosteric Inhibition of Serotonin 5-HT<Subscript>7</Subscript> Receptors by Zinc Ions

The allosteric regulation of G protein-coupled receptors (GPCRs) is a well-known phenomenon, but there are only a few examples of allosteric modulation within the metabotropic serotonergic receptor family. Recently, we described zinc non-competitive interactions toward agonist binding at serotonin 5-HT_1A receptors, in which biphasic effects, involving potentiation at sub-micromolar concentrations (10 μM) and inhibition at sub-millimolar concentrations (500 μM) of Zn²⁺ in radioligand binding assays, were consistent with both the agonist and antagonist-like effects of zinc ions observed in in vivo studies. Here, we showed new data demonstrating zinc allosteric inhibition of both agonist and antagonist binding at human recombinant 5-HT₇ receptors stably expressed in HEK293 cells as observed by radioligand binding studies as well as zinc neutral antagonism displayed by the concentration of 10 μM in the functional LANCE assay. The allosteric nature of the effect of Zn on 5-HT₇ receptors was confirmed (1) in saturation studies in which zinc inhibited the binding of potent orthosteric 5-HT₇ receptor radioligands, the agonist [³H]5-CT, and the two antagonists [³H]SB-269970 and [³H]mesulergine, showing ceiling effect and differences in the magnitude of negative cooperativity (α = 0.15, 0.06, and 0.25, respectively); (2) in competition experiments in which 500 μM of zinc inhibited all radioligand displacements by non-labeled orthosteric ligands (5-CT, SB-269970, and clozapine), and the most significant reduction in affinity was observed for the 5-CT agonist (4.9–16.7-fold) compared with both antagonists (1.4–3.9-fold); and (3) in kinetic experiments in which 500 μM zinc increased the dissociation rate constants for [³H]5-CT and [³H]mesulergine but not for [³H]SB-269970. Additionally, in the functional LANCE test using the constitutively active HEK293 cell line expressing the 5-HT₇ receptor, 10 μM zinc had features of neutral antagonism and increased the EC₅₀ value of the 5-CT agonist by a factor of 3.2. Overall, these results showed that zinc can act as a negative allosteric inhibitor of 5-HT₇ receptors. Given that the inhibiting effects of low concentrations of zinc in the functional assay represent the most likely direction of zinc activity under physiological conditions, among numerous zinc-regulated proteins, the 5-HT₇ receptor can be considered a serotonergic target for zinc modulation in the CNS.     

Synthesis and pharmacological evaluation of new arylpiperazines. 3-[4-[4-(3-chlorophenyl)-1-piperazinyl]butyl]-quinazolidin-4-one - a dual serotonin 5-HT(1A)/5-HT(2A) receptor ligand with an anxiolytic-like activity

On the basis of systematic studies on the structure–activity relationships in arylpiperazine group of serotonin ligands, 12 new derivatives containing quinazolidin-4(3H)-one (1–4), 2-phenyl-2,3-dihydrophthalazine-1,4-dione (5–8) or 1-phenyl-1,2-dihydropyridazine-3,6-dione (9–12) fragments were synthesized. The majority of the tested compounds (2, 4, 7, 8 and 10–12) showed a high affinity for 5-HT_1A receptors (K_i=11–54 nM) and two (1, 2) were found active at 5-HT_2A sites (16 and 68 nM, respectively). All the new 5-HT_1A ligands tested in vivo revealed an antagonistic activity at postsynaptic 5-HT_1A receptors, and three of them behaved as agonists at presynaptic ones. Additionally, both the meta-chlorophenylpiperazine derivatives containing quinazolidin-4-one fragment showed features of 5-HT_2A receptor antagonists. The dual 5-HT_1A/5-HT_2A receptor ligand (2) was further tested for its potential psychotropic activity. It showed a distinct anxiolytic-like activity in a conflict drinking test in rats and the observed effect was more potent in terms of the active dose, than that produced by diazepam (used as a reference drug).     

Low-level ectopic expression of Fushi tarazu in Drosophila melanogaster results in ftz(Ual/Rpl)-like phenotypes and rescues ftz phenotypes

The protein encoded by the Drosophila pair-rule gene fushi tarazu (ftz) is required for the formation of the even-numbered parasegments. Here we analyze the phenotypes of ectopic expression of FTZ and FTZ protein deletions from the Tubulin 1 (Tub1) promoter. Fusion of ftz to the Tub1 promoter resulted in low-level ectopic expression of FTZ relative to FTZ expressed from the endogenous ftz gene. The effects of ectopic expression of four FTZ proteins, FTZ^1–413 (full length wild-type FTZ), FTZ^Δ257–316 (a complete deletion of the HD), FTZ^Δ101–150 (a deletion that includes the major FTZ-F1 binding site) and FTZ^Δ151–209 were determined. Ectopic expression of FTZ^1–413, FTZ^Δ257–316 and FTZ^Δ101–151 did not result in an anti-ftz phenotype; however, ectopic expression of FTZ^1–413, and FTZ^Δ257–316 did result in a ftz^Ual/Rpl-like phenotype. In addition, low-level ectopic expression of FTZ^1–413 and FTZ^Δ257–316 rescued ftz phenotypes. This was an important observation because the even-numbered parasegment pattern of FTZ expression is considered important for normal segmentation. Therefore, the rescue of ftz phenotypes by low-level FTZ expression in all cells of the embryo suggests that the even-numbered parasegment expression pattern of FTZ is not the sole factor restricting FTZ action. Low-level ectopic expression of FTZ^Δ151–209 resulted in the anti-ftz phenotype and rescued hypomorphic ftz-f1 phenotypes indicating that FTZ^Δ151–209 is a hyperactive FTZ molecule. Therefore, the region encompassing amino acids 151–209 of FTZ is required in some manner for repression of FTZ activity. These results are discussed in relation to the current understanding of the mechanism of FTZ action.     

Temporin A and its retro-analogues: synthesis, conformational analysis and antimicrobial activities.

Temporin A (TA) is a hydrophobic peptide isolated from the skin of the European red frog Rana temporaria. Strong antimicrobial activity against gram-positive cocci and Candida, as well as its small molecular weight (10-13 aa residues), makes TA an interesting antimicrobial compound. However, its synthesis is rather problematic. Here, the synthesis of two retro-analogues of TA--retro-TA and (6-1)(7-13)-TA--is reported. The synthesis of retro-TA was performed without any problems, while during the synthesis of (6-1)(7-13)-TA problems similar to those encountered during the synthesis of TA were faced. Antimicrobial assays showed minimal inhibitory concentration (MIC) values of retro-TA to be, in most cases, only one dilution higher than those of original TA, but still remained relatively low. An analysis of the circular dichroism spectra of the peptides shows that TA and (6-1)(7-13)-TA adopt an alpha-helical structure in a hydrophobic environment, while retro-TA forms mainly unordered conformation under both hydrophobic and hydrophilic conditions. One can postulate that differences in conformation of the peptide chain might be responsible for the lower antimicrobial activity of retro-TA as compared to that of the parent molecule. In any case, retro-TA can be interesting owing to its simple and nonproblematic synthesis.     

Redox reaction between amino-(3,4-dihydroxyphenyl)methyl phosphonic acid and dopaquinone is responsible for the apparent inhibitory effect on tyrosinase.

Amino-(3,4-dihydroxyphenyl)methyl phosphonic acid, the phosphonic analog of 3,4-dihydroxyphenylglycine, had been previously reported as a potent inhibitor of tyrosinase. The mechanism of the apparent enzyme inhibition by this compound has now been established. Amino-(3,4-dihydroxyphenyl)methyl phosphonic acid turned out to be a substrate and was oxidized to o-quinone, which evolved to a final product identified as 3,4-dihydroxybenzaldehyde, the same as for 3,4-dihydroxyphenylglycine. Monohydroxylated compounds (amino-(3-hydroxyphenyl)methyl phosphonic acid and amino-(4-hydroxyphenyl)methyl phosphonic acid) were not oxidized, neither was 4-hydroxy-l-phenylglycine. However, the relatively high Km for amino-(3,4-dihydroxyphenyl)methyl phosphonic acid (0.52 mm) indicated that competitive inhibition could not entirely explain the previously reported strong inhibitory effect (Ki = 50 and 97 micro m for tyrosine and 3-(3,4-dihydroxyphenyl)alanine (Dopa) as substrates, respectively). Neither was the enzyme covalently inactivated to a significant degree. Spectroscopic and electrochemical analysis of the oxidation of a mixture of Dopa and the inhibitor demonstrated that the phosphonic compound reduced dopaquinone back to Dopa, thus diminishing and delaying the formation of dopachrome. This produces an apparent strong inhibitory effect when the reaction is monitored spectrophotometrically at 475 nm. In this peculiar case Dopa acts as a redox shuttle mediating the oxidation of the shorter phosphonic homolog. Decomposition of the phosphonic o-quinone to 3,4-dihydroxybenzaldehyde drives the reaction against the slightly unfavorable difference in redox potentials.     

Visible‐Light Microscopic Discovery of Up to 150 μm Long Helical Amyloid Fibrils Built of the Dodecapeptide H‐(Val‐Ala‐Leu)4‐OH and of Decapeptides Derived from Insulin

In the formation of amyloid fibrils from small peptides, the appearance of superhelices of (P)‐ or (M)‐helicity has been observed for the first time; high concentrations of the peptides and extended periods of incubation at physiological pH appear to be important for this phenomenon. In view of the general importance of peptide and protein aggregation, we give a brief overview with selected examples for demonstration.