Transient Dynamics Inside Periodic Windows and in Their Vicinity I. Logistic Maps

The paper contains results of numerical experiments on evolution generated by logistic maps inside periodic windows and in their vicinity. We study properties of dynamics in terms of rambling time inside periodic windows and duration of the non-laminar phase in their proximity, showing that a close relation between these two notions exists. We also give results of numerical experiments on map-generated evolution of measure on the unit interval.     

Spectrophotometric assay for copper and iron in transformer oil using partial least squares regression (PLS2)

A simple and low cost spectrophotometric assay is proposed in this work for simultaneous determination of copper and iron levels in insulating oils. The procedure requires minimum sample volume (250 muL), it is carried out in disposable micro tubes (1.5 mL) and aqueous standards are used for calibration. In brief, after dilution with n-propanol, the wear metals are extracted with hydrochloric acid and, after neutralization, the analytes are reduced to the oxidation states Cu(I) and Fe(II) respectively. Finally, the mixture of bathocuproine-disulfonic acid and bathophenantroline-disulfonic acid is added for selective formation of copper and iron complexes. Then, chloroform and methanol are added, the sample is centrifuged and absorption spectra are registered in the upper-aqueous layer (470-550 nm). Multivariate calibration, covering concentration range 0-4 mug/mL of each analyte in oil is performed using partial least squares regression. The test solutions are prepared by spiking the aqueous standards of copper and iron to metal-free oil diluted with n-propanol (1:1). The prediction results were in agreement with those obtained using univariate spectrophotometric assay (one ligand) and those obtained by electrothermal atomic absorption spectrometry (after dissolution of wear metals and dilution with n-propanol)     

The CD200 Regulates Inflammation in Mice Independently of TNF-α Production

Inflammatory bowel disease is characterized by the infiltration of immune cells and chronic inflammation. The immune inhibitory receptor, CD200R, is involved in the downregulation of the activation of immune cells to prevent excessive inflammation. We aimed to define the role of CD200R ligand-CD200 in the experimental model of intestinal inflammation in conventionally-reared mice. Mice were given a dextran sodium sulfate solution in drinking water. Bodyweight loss was monitored daily and the disease activity index was calculated, and a histological evaluation of the colon was performed. TNF-α production was measured in the culture of small fragments of the distal colon or bone marrow-derived macrophages (BMDMs) cocultured with CD200⁺ cells. We found that Cd200^−/− mice displayed diminished severity of colitis when compared to WT mice. Inflammation significantly diminished CD200 expression in WT mice, particularly on vascular endothelial cells and immune cells. The co-culture of BMDMs with CD200⁺ cells inhibited TNF-α secretion. In vivo, acute colitis induced by DSS significantly increased TNF-α secretion in colon tissue in comparison to untreated controls. However, Cd200^−/− mice secreted a similar level of TNF-α to WT mice in vivo. CD200 regulates the severity of DSS-induced colitis in conventionally-reared mice. The presence of CD200⁺ cells decreases TNF-α production by macrophages in vitro. However, during DDS-induced intestinal inflammation secretion of TNF-α is independent of CD200 expression.     

Suppression of NtZIP4A/B Changes Zn and Cd Root-to-Shoot Translocation in a Zn/Cd Status-Dependent Manner

In tobacco, the efficiency of Zn translocation to shoots depends on Zn/Cd status. Previous studies pointed to the specific contribution of root parts in the regulation of this process, as well as the role of NtZIP4A/B (from the ZIP family; Zrt Irt-like Proteins). Here, to verify this hypothesis, NtZIP4A/B RNAi lines were generated. Then, in plants exposed to combinations of Zn and Cd concentrations in the medium, the consequences of NtZIP4A/B suppression for the translocation of both metals were determined. Furthermore, the apical, middle, and basal root parts were examined for accumulation of both metals, for Zn localization (using Zinpyr-1), and for modifications of the expression pattern of ZIP genes. Our results confirmed the role of NtZIP4A/B in the control of Zn/Cd-status-dependent transfer of both metals to shoots. Furthermore, they indicated that the middle and basal root parts contributed to the regulation of this process by acting as a reservoir for excess Zn and Cd. Expression studies identified several candidate ZIP genes that interact with NtZIP4A/B in the root in regulating Zn and Cd translocation to the shoot, primarily NtZIP1-like in the basal root part and NtZIP2 in the middle one.     

Synthesis and Anticancer Activity of Mitotic-Specific 3,4-Dihydropyridine-2(1H)-thiones

Most anticancer drugs target mitosis as the most crucial and fragile period of rapidly dividing cancer cells. However the limitations of classical chemotherapeutics drive the search for new more effective and selective compounds. For this purpose structural modifications of the previously characterized pyridine analogue (S1) were incorporated aiming to obtain an antimitotic inhibitor of satisfactory and specific anticancer activity. Structure-activity relationship analysis of the compounds against a panel of cancer cell lines allowed to select a compound with a thiophene ring at C5 of a 3,4-dihydropyridine-2(1H)-thione (S22) with promising antiproliferative activity (IC₅₀ equal 1.71 ± 0.58 µM) and selectivity (SI = 21.09) against melanoma A375 cells. Moreover, all three of the most active compounds from the antiproliferative study, namely S1, S19 and S22 showed better selectivity against A375 cells than reference drug, suggesting their possible lower toxicity and wider therapeutic index. As further study revealed, selected compounds inhibited tubulin polymerization via colchicine binding site in dose dependent manner, leading to aberrant mitotic spindle formation, cell cycle arrest and apoptosis. Summarizing, the current study showed that among obtained mitotic-specific inhibitors analogue with thiophene ring showed the highest antiproliferative activity and selectivity against cancer cells.     

Functionalized Peptide Fibrils as a Scaffold for Active Substances in Wound Healing

Technological developments in the field of biologically active peptide applications in medicine have increased the need for new methods for peptide delivery. The disadvantage of peptides as drugs is their low biological stability. Recently, great attention has been paid to self-assembling peptides that can form fibrils. Such a formulation makes bioactive peptides more resistant to enzymatic degradation and druggable. Peptide fibrils can be carriers for peptides with interesting biological activities. These features open up prospects for using the peptide fibrils as long-acting drugs and are a valid alternative to conventional peptidic therapies. In our study, we designed new peptide scaffolds that are a hybrid of three interconnected amino acid sequences and are: pro-regenerative, cleavable by neutrophilic elastase, and fibril-forming. We intended to obtain peptides that are stable in the wound environment and that, when applied, would release a biologically active sequence. Our studies showed that the designed hybrid peptides show a high tendency toward regular fibril formation and are able to release the pro-regenerative sequence. Cytotoxicity studies showed that all the designed peptides were safe, did not cause cytotoxic effects and revealed a pro-regenerative potential in human fibroblast and keratinocyte cell lines. In vivo experiments in a dorsal skin injury model in mice indicated that two tested peptides moderately promote tissue repair in their free form. Our research proves that peptide fibrils can be a druggable form and a scaffold for active peptides.     

A convenient access to 1,2-diferrocenyl-substituted ethylenes via [3 + 2]-cycloelimination of 2-silylated 4,4,5,5-tetrasubstituted 1,3-dithiolanes

Ferrocenyl thioketones bearing a hetaryl, phenyl or alkyl group as the second substituent react with (trimethylsilyl)diazomethane at ca. ?30°C in THF solution without formation of a stable [3?+?2]-cycloadduct. After the spontaneous evolution of N₂, the corresponding sterically crowded 4,4,5,5-tetrasubstituted 2-silylated 1,3-dithiolanes are formed as products of the second [3?+?2]-cycloaddition of the intermediate thiocarbonyl S-methanide with the starting thioketone. After desilylation by treatment with TBAF, they are converted into the corresponding carbanions, which display different stability depending on the type of substituent. The presence of hetaryl and phenyl groups results in the exclusive formation of 1,2-diferrocenyl ethylenes. In contrast, the presence of methyl groups significantly enhances the stability of the carbanion, which by protonation yields trans-4,5-diferrocenyl-4,5-dimethyl-1,3-dithiolane.     

Antimicrobial and Cytotoxic Properties of Bisquaternary Ammonium Bromides of Different Spacer Length

A group of cationic gemini surfactants (bisquaternary ammonium bromides) with different spacer chain lengths (8–6–8, 8–7–8, 8–8–8, 8–9–8) was investigated, paying special attention to antimicrobial and the cytotoxic properties as well as their antimicrobial activity during long‐term storage. It was shown that the compounds investigated exhibit excellent antimicrobial activity against Gram‐positive bacteria (Staphylococcus aureus) and Gram‐negative bacteria (Pseudomonas aeruginosa) as well as antifungal properties (Candida albicans). The gemini surfactants tested had the differential level of cytotoxicity against normal lymphocytes. It was shown that the spacer chain length plays an important role in antibacterial activity and influences the cytotoxicity. The gemini surfactants with shorter spacer chain length, that had higher critical micelle concentration, showed generally weaker antibacterial properties, but on the other hand, these exhibited lower level of cytotoxicity. Furthermore, the aqueous solution of gemini surfactants exhibited the same antimicrobial activity even after 3 months.     

Enzymatic Synthesis of Halogen Derivatives of Aromatic Amino Acids Labeled with Hydrogen Isotopes

The isotopomers of halogenated amino acids （2＇-F-L-phenylalanine, 3＇-F- and 3＇-Cl-L-tyrosine, as well as 5＇-F-, 5＇-Br-and 6＇-F-L-tryptophan） specifically labeled with deuterium at α- and 13-carbon atom of the side chain were synthesized by enzymatic catalyzed H/D exchange in fully deuteriated incubation medium. The extent and site of deuterium incorporation were confirmed by ^1H NMR （proton nuclear magnetic resonance） spectra.     

Incidence of the enterococcal surface protein (esp) gene in human and animal fecal sources

The occurrence of the enterococcal surface protein (esp) gene in the opportunistic pathogens Enterococcus faecalis and E. faecium is well-documented in clinical research. Recently, the esp gene has been proposed as a marker of human pollution in environmental waters; however, information on its relative incidence in various human and animal fecal sources is limited. We have determined the occurrence of the esp gene in enterococci from human (n=64) and animal (n=233) fecal samples by polymerase chain reaction using two primer sets: one presumably specific for E. faecium (esp(fm)) and the other for both E. faecalis and E. faecium (esp(fs/fm)). We believe that this research is the first to explore the use of esp(fs/fm) for the detection of human waste in natural environmental settings. The incidence in human sources was 93.1% esp(fm) and 100% esp(fs/fm) in raw sewage influent; 30% for both esp(fm) and esp(fs/fm) in septic waste; and 0% esp(fm) and 80% esp(fs/fm) in active pit toilets. The overall occurrence of the gene in animal feces was 7.7% (esp(fs/fm)) and 4.7% (esp(fm)); animal types with positive results included dogs (9/43, all esp(fm)), gulls (10/34, esp(fs/fm); 2/34, esp(fm)), mice (3/22, all esp(fs/fm)), and songbirds (5/55, all esp(fs/fm)). The esp gene was not detected in cat (0/34), deer (0/4), goose (0/18), or raccoon (0/23) feces. The inconsistent occurrence, especially in septic and pit toilet sewage, suggests a low statistical power of discrimination between animal and human sources, which means a large number of replicates should be collected. Both esp(fm) and esp(fs/fm) were common in raw sewage, but neither one efficiently differentiated between animal and other human sources.