Prevalence of ColE1-Like Plasmids and Colicin K Production among Uropathogenic Escherichia coli Strains and Quantification of Inhibitory Activity of Colicin K

Colicin K exhibited pronounced inhibitory activity against uropathogenic Escherichia coli (UPEC) strains. Low prevalence of colicin K production and a relatively high prevalence of ColE1-like plasmids were determined among 215 UPEC strains from Slovenia. Sequencing of the colicin K-encoding pColK-K235 revealed a mosaic structure and the presence of the insertion sequence IS2.     

1,2,3,4-Tetrahydroisoquinoline Derivatives as a Novel Deoxyribonuclease I Inhibitors

Herein we report an assessment of 24 1,2,3,4-tetrahydroisoquinoline derivatives for potential DNase I (deoxyribonuclease I) inhibitory properties in vitro. Four of them inhibited DNase I with IC₅₀ values below 200 μM. The most potent was 1-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)propan-2-one ( 2 ) (IC₅₀=134.35±11.38 μM) exhibiting slightly better IC₅₀ value compared to three other active compounds, 2-[2-(4-fluorophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]-1-phenylethan-1-one ( 15 ) (IC₅₀=147.51±14.87 μM), 2-[2-(4-fluorophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]cyclohexan-1-one ( 18 ) (IC₅₀=149.07±2.98 μM) and 2-[6,7-dimethoxy-2-(p-tolyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]cyclohexan-1-one ( 22 ) (IC₅₀=148.31±2.96 μM). Cytotoxicity assessment of the active DNase I inhibitors revealed a lack of toxic effects on the healthy cell lines MRC-5. Molecular docking and molecular dynamics simulations suggest that interactions with Glu 39, His 134, Asn 170, Tyr 211, Asp 251 and His 252 are an important factor for inhibitors affinity toward the DNase I. Observed interactions would be beneficial for the discovery of new active 1,2,3,4-tetrahydroisoquinoline-based inhibitors of DNase I, but might also encourage researchers to further explore and utilize potential therapeutic application of DNase I inhibitors, based on a versatile role of DNase I during apoptotic cell death.     

Immunohistochemical and stereological study of neuroendocrine cells in human antrum during the perinatal period.

A correlative immunohistochemical and stereological study of neuroendocrine cells (NEC) was carried out in the antrum of twenty human fetuses with gestational ages from 18 to 42 weeks and of two specimens postnatally. Neuron-specific enolase (NSE) as a common marker of neurons and NEC, as well as gastrin (G-) and somatostatin (D-) immunoreactive cells served for evaluation of volume density, which proved to be the most convenient method for quantitative analysis of NEC. It was observed that a considerable frequency of NEC appeared at 23-24 weeks of gestation (8% of NSE- and 6% of G- cells) and coincided with the adult pattern of intramural innervation. After a repeated increase of NEC in the 26-week-old fetus, the frequency of NEC remained persistant during the perinatal period (10-12% of NSE- and 7-8% of G- cells). An exception was a specimen with a prolonged pregnancy (42 weeks) in which the percentage of NSE- (17%) and G- (10%) cells was almost the same as at 6 weeks postnatally. The maximal quantitative difference of NEC was noted between 6- and 8-week specimens postnatally, e.g. 9% to 22% of G- cells, respectively. Observations obtained by NSE and S-100 protein were also demonstrated in lymphoid cells of gut associated and mesenteric lymphoid tissue.     

Evidence for a widely distributed peripheral dopaminergic system

The hypothesis presented in this paper is that dopamine (DA) is a widely distributed neurotransmitter and/or cotransmitter in the autonomic nervous system. This hypothesis is based on the following evidence. Morphologically, DA-containing neurons have been demonstrated in autonomic ganglia, and dopaminergic axons have been identified in kidney and canine paw pad. On the basis of pharmacological experiments, the existence of dopaminergic nerves was suggested in vas deferens, stomach, and mesenteric artery. Biochemically, we found intensive catabolism of DA in different peripheral tissues of the rat and human. Furthermore, dopaminergic receptors have a widespread distribution in the body, and a high concentration of DA occurs in plasma with only some originating from the adrenal gland. The concentration of plasma DA closely reflects the activity of the autonomic nervous system. These observations together with our finding of relatively high concentrations of DA and its metabolites in several peripheral nerves suggest the possibility of a widely distributed peripheral dopaminergic system.     

Hematology and serum biochemistry of European mouflon (<Emphasis Type="Italic">Ovis orientalis musimon</Emphasis>) in Croatia

The aim of the present study was to determine the reference intervals for the most commonly used hematological and biochemical parameters of European mouflon from a closed hunting ground in the eastern part of the Republic of Croatia. Blood samples were collected from 39 live, physically restrained, clinically normal European mouflon, as well as from 50 domestic sheep. The distribution of values within each parameter was determined and statistical differences in values between sexes were also determined. For each sample, 14 hematological and 18 biochemical parameters were analyzed. Hematology and biochemistry values of the European mouflon were also compared with the values of domestic sheep. In further studies, the established values might be useful for the health assessment of mouflon.     

Crosstalk between H2A variant-specific modifications impacts vital cell functions

Selection of C-terminal motifs participated in evolution of distinct histone H2A variants. Hybrid types of variants combining motifs from distinct H2A classes are extremely rare. This suggests that the proximity between the motif cases interferes with their function. We studied this question in flowering plants that evolved sporadically a hybrid H2A variant combining the SQ motif of H2A.X that participates in the DNA damage response with the KSPK motif of H2A.W that stabilizes heterochromatin. Our inventory of PTMs of H2A.W variants showed that in vivo the cell cycle-dependent kinase CDKA phosphorylates the KSPK motif of H2A.W but only in absence of an SQ motif. Phosphomimicry of KSPK prevented DNA damage response by the SQ motif of the hybrid H2A.W/X variant. In a synthetic yeast expressing the hybrid H2A.W/X variant, phosphorylation of KSPK prevented binding of the BRCT-domain protein Mdb1 to phosphorylated SQ and impaired response to DNA damage. Our findings illustrate that PTMs mediate interference between the function of H2A variant specific C-terminal motifs. Such interference could explain the mutual exclusion of motifs that led to evolution of H2A variants.     

Isolation and characterization of Tn917-generated bacitracin deficient mutants of Bacillus licheniformis

Abstract Two Tn917-generated bacitracin deficient mutants of Bacillus licheniformis were isolated. Southern blot analysis of chromosomal DNA extracted from both insertional mutants showed that Tn917 inserted in the vicinity of the gene coding for the enzyme BA2 of the bacitracin synthetase enzyme complex. Measurements of bacitracin synthetase activity in cell-free extracts and positive hybridization signals in the vicinity of the BA2 gene indicate that in both bacitracin deficient mutants Tn917 could be inserted in the BA1 gene or in segments involved in regulation. Thus, it could be possible that the genes for bacitracin synthetase are clustered in the B. licheniformis genome.     

Inducible resistance to zinc ions in Bacillus subtilis 168

Abstract Chromosomally determined resistance to Zn²⁺ ions is a property of Bacillus subtilis 168. Resistance is inducible and is not connected with Cd²⁺ resistance, characteristics of plasmid determined resistance in bacteria. A few proteins were shown to respond to inducible levels of the cation.