Distribution of legionellae in a hospital water system: prevalence of immunologically and genetically related Legionella pneumophila serogroup 6 isolates

A hospital warm water system was monitored for the presence and distribution of legionellae. Subtyping of ten selected Legionella pneumophila isolates, originating from four different sites in the system by using serogroup specific antisera in an indirect immunofluorescence test, revealed that nine of the ten isolates belong to serogroup 6, while the remaining one was serogroup 10. Two monoclonal antibodies (mAbs) specific for a subgroup of serogroup 6 strains were further used for characterization. None of the strains reacted with these mAbs. Genome analysis by elaborating NotI profiles using the pulsed field gel electrophoresis (PFGE) technique revealed that nearly all serogroup 6 isolates derived from different sites, including a new building connected by a ring pipe, were identical according to restriction fragment patterns. The patterns were distinguishable from those of the two L. pneumophila serogroup 6 reference strains, and from that of the L. pneumophila serogroup 10 isolate. These data argue for a relatively homogeneous L. pneumophila serogroup 6 population in the entire water system.     

Synthesis,molecular docking,and biological activity of 2-vinyl chromones: Toward selective butyrylcholinesterase inhibitors for potential Alzheimer's disease therapeutics

We investigated the biological activity of a series of substituted chromeno[3,2-c]pyridines, including compounds previously synthesized by our group and novel compounds whose syntheses are reported here. Tandem transformation of their tetrahydropyridine ring under the action of activated alkynes yielding 2-vinylsubstituted chromones was used to prepare nitrogen-containing derivatives of a biologically active chromone system. The inhibitory activity of these chromone derivatives against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and carboxylesterase (CaE) was investigated using the methods of enzyme kinetics and molecular docking. Antioxidant (antiradical) activity of the compounds was assessed in the ABTS assay. The results demonstrated that a subset of the studied chromone derivatives selectively inhibit BChE but do not exhibit antiradical activity. In addition, the results of molecular docking effectively explained the observed features in the efficacy, selectivity, and mechanism of BChE inhibition by the chromone derivatives.     

A membrane fusion protein,Ykt6, regulates epithelial cell migration via microRNA-mediated suppression of Junctional Adhesion Molecule A

Vesicle trafficking regulates epithelial cell migration by remodeling matrix adhesions and delivering signaling molecules to the migrating leading edge. Membrane fusion, which is driven by soluble N-ethylmaleimide-sensitive factor associated receptor (SNARE) proteins, is an essential step of vesicle trafficking. Mammalian SNAREs represent a large group of proteins, but few have been implicated in the regulation of cell migration. Ykt6 is a unique SNARE existing in equilibrium between active membrane-bound and inactive cytoplasmic pools, and mediating vesicle trafficking between different intracellular compartments. The biological functions of this protein remain poorly understood. In the present study, we found that Ykt6 acts as a negative regulator of migration and invasion of human prostate epithelial cells. Furthermore, Ykt6 regulates the integrity of epithelial adherens and tight junctions. The observed anti-migratory activity of Ykt6 is mediated by a unique mechanism involving the expressional upregulation of microRNA 145, which selectively decreases the cellular level of Junctional Adhesion Molecule (JAM) A. This decreased JAM-A expression limits the activity of Rap1 and Rac1 small GTPases, thereby attenuating cell spreading and motility. The described novel functions of Ykt6 could be essential for the regulation of epithelial barriers, epithelial repair, and metastatic dissemination of cancer cells.     

Effect of bacterial lipopolysaccharides on morphogenetic activity in wheat somatic calluses

We evaluated the effect of lipopolysaccharides from the plant-growth-promoting associative bacterium Azospirillum brasilense Sp245 and from the enteric bacterium Escherichia coli K12 on the morphogenic potential of in vitro-growing somatic calluses of soft spring wheat (Triticum aestivum L. cv. Saratovskaya 29). A genetic model was used that included two near-isogenic lines of T. aestivum L. cv. Saratovskaya 29 with different embryogenic capacities; one of these lines carries the Rht-B1 dwarfing gene, whereas the other lacks it. When added to the nutrient medium, the lipopolysaccharide of A. brasilense Sp245 promoted the formation of calluses with meristematic centers and stimulated the regeneration ability of the cultured tissues in both lines. By contrast, the lipopolysaccharide of the enteric bacterium E. coli K12 barely affected the morphogenetic activity of callus cells and the yield of morphogenic calluses and regenerated plants. These findings indicate that the lipopolysaccharide of the plant-growth-promoting associative bacterium A. brasilense Sp245 specifically enhances the morphogenetic activity of wheat somatic tissues, which increases the efficacy of culturing of genotypes with a relatively low morphogenic potential. The results of the study may contribute to the improvement of the efficacy of plant cell selection and gene engineering and to a better understanding of the mechanisms responsible for plant recognition of lipopolysaccharides of associative bacteria.     

Pharmacogenetics of cardiovascular drugs.

Pharmacogenetics is a field aimed at understanding the genetic contribution to inter-patient variability in drug efficacy and toxicity. Treatment of cardiovascular disease is, in most cases, guided by evidence from well-controlled clinical trials. Given the solid scientific basis for the treatment of most cardiovascular diseases, it is common for patients with a given disease to be treated in essentially the same manner. Thus, the clinical trials have been very informative about treating large groups of patients with a given disease, but are slightly less informative about the treatment of individual patients. Pharmacogenetics and pharmacogenomics have the potential of taking the information derived from large clinical trials and further refining it to select the drugs with the greatest likelihood for benefit, and least likelihood for harm, in individual patients, based on their genetic make-up. In this paper, the current literature on cardiovascular pharmacogenetics is emphasised, and how the use of pharmacogenetic/pharmacogenomic information may be particularly useful in the future in the treatment of cardiovascular diseases is also highlighted.     

The Effects of Insulin-Induced Hypoglycaemia on Tyrosine Hydroxylase Phosphorylation in Rat Brain and Adrenal Gland

In this study we investigated the effects of insulin-induced hypoglycaemia on tyrosine hydroxylase (TH) protein and TH phosphorylation in the adrenal gland, C1 cell group, locus coeruleus (LC) and midbrain dopaminergic cell groups that are thought to play a role in response to hypoglycaemia and compared the effects of different concentrations of insulin in rats. Insulin (1 and 10 U/kg) treatment caused similar reductions in blood glucose concentration (from 7.5–9 to 2–3 mmol/L); however, plasma adrenaline concentration was increased 20–30 fold in response to 10 U/kg insulin and only 14 fold following 1 U/kg. Time course studies (at 10 U/kg insulin) revealed that in the adrenal gland, Ser31 phosphorylation was increased between 30 and 90 min (4–5 fold), implying that TH was activated to increase catecholamine synthesis in adrenal medulla to replenish the stores. In the brain, Ser19 phosphorylation was limited to certain dopaminergic groups in the midbrain, while Ser31 phosphorylation was increased in most catecholaminergic regions at 60 min (1.3–2 fold), suggesting that Ser31 phosphorylation may be an important mechanism to maintain catecholamine synthesis in the brain. Comparing the effects of 1 and 10 U/kg insulin revealed that Ser31 phosphorylation was increased to similar extent in the adrenal gland and C1 cell group in response to both doses whereas Ser31 and Ser19 phosphorylation were only increased in response to 1 U/kg insulin in LC and in response to 10 U/kg insulin in most midbrain regions. Thus, the adrenal gland and some catecholaminergic brain regions become activated in response to insulin administration and brain catecholamines may be important for initiation of physiological defences against insulin-induced hypoglycaemia.     

Azospirillum brasilense glutamine synthetase: influence of the activating metal ions on the enzyme properties

The kinetic properties of the Mg²⁺-activated and Mn²⁺-activated glutamine synthetase (GS) of Azospirillum brasilense in the biosynthetic reaction were studied. The Mg²⁺-supported and Mn²⁺-supported GSs in an average state of adenylylation varied in pH optimum, maximum activity, saturation functions for ammonium and glutamate, affinity to substrates, and in the Me²⁺-ATP ratio required for the optimal enzyme activity. Seventeen other cations were tested for the maintenance of GS activity. The level of the latter and the kinetic behavior of the GS in A.brasilense is suggested to depend essentially on the concentrations of Mg²⁺, Mn²⁺ and Co²⁺, as well as on their ratio     

Beak from the body chamber of an Early Carboniferous shelled longiconic coleoid cephalopod from Arkansas,USA

Here we report the discovery of an Early Carboniferous (Late Visean) 3D cephalopod beak displaying significant similarity to the lower beak of Recent coleoids. It was uncovered in a fragmentarily preserved, longiconic shell from the Moorefield Formation in Arkansas, USA. This shell comprises a fractured 29‐mm‐long body chamber having a maximum diameter of ~14 mm and showing an indistinct pro‐ostracum‐like structure. The beak‐bearing shell could easily have been mistaken for a bactritid or orthocerid if it were not for a coleoid‐type, weakly mineralized, evidently organic‐rich shell wall which shows a lamello‐columnar ultrastructure of a bulk of shell wall thickness and plate ultrastructure of thin outer layer. The specimen is assigned to an as‐yet unnamed shelled coleoid of a so far unknown high‐level taxonomic group. A partially exposed, 4.0‐mm‐long portion of the beak is the lower beak in oblique view from its left side. It exhibits fractured anthracite‐like black, apparently originally chitin material, helmet‐like general shape, broad hood with narrow shallow median groove and small notch posteriorly, pronounced pointed, non‐biomineralized upside belt rostrum, high shoulder and about a 90–100 degrees jaw angle. A broad hood and massive rostrum emphasize its similarity to the lower mandible of Recent Vampyroteuthis and signify that its unique, among living coleoids, structure has been existed for at least since Late Visean time (~333 my).     

Microcystins in Cyanobacterial Biofilms from the Littoral Zone of Lake Baikal

Some species of cyanobacteria synthesize toxins whose concentration during water bloom can reach values dangerous for human and animal health. Planktonic cyanobacteria are the most common and well-studied microcystins producers, hepatotoxic cyclic heptapeptides, whereas microcystin-producing benthic cyanobacteria are less known. In recent years, the mass development of benthic cyanobacteria forming extensive fouling on different substrates has been detected in the littoral zone of Lake Baikal. We found microcystins produced by benthic cyanobacteria in the biofouling on different natural and artificial substrates, including diseased and dead endemic sponges Lubomirskia baicalensis and Baikalospongia spp. collected from the littoral area of Lake Baikal. Microscopic analysis of the biofouling revealed prevalence of representatives of Nostocales and Oscillatoriales with predominance of Tolypothrix distorta that is likely the main microcystin producer in Lake Baikal. According to enzyme-linked immunosorbent assay (ELISA), microcystin concentrations in biofouling were 29.8–3050 μg/kg dry weight. We identified eight microcystin variants using MALDI-TOF/TOF; [Dha7]MC-YR was detected in most samples. The presence of microcystins in biofilms formed on the surface of the artificial substrate by Phormidium autumnale was also recorded. The data obtained demonstrated the necessity to monitor potentially toxic species and concentrations of cyanotoxins in plankton and benthos in the littoral zone of Lake Baikal, especially in the regions with intense tourist and recreational activities.     

High‐Temperature Treatment of Li‐Rich Cathode Materials with Ammonia: Improved Capacity and Mean Voltage Stability during Cycling

Li‐rich electrode materials of the family x Li₂MnO₃·(1?x )LiNi_a Co_b Mn_c O₂ (a + b + c = 1) suffer a voltage fade upon cycling that limits their utilization in commercial batteries despite their extremely high discharge capacity, ≈250 mA h g^?1. Li‐rich, 0.35Li₂MnO₃·0.65LiNi_0.35Mn_0.45Co_0.20O₂, is exposed to NH₃ at 400 °C, producing materials with improved characteristics: enhanced electrode capacity and a limited average voltage fade during 100 cycles in half cells versus Li. Three main changes caused by NH₃ treatment are established. First, a general bulk reduction of Co and Mn is observed via X‐ray photoelectron spectroscopy and X‐ray absorption near edge structure. Next, a structural rearrangement lowers the coordination number of Co? O and Mn? O bonds, as well as formation of a surface spinel‐like structure. Additionally, Li⁺ removal from the bulk causes the formation of surface LiOH, Li₂CO₃, and Li₂O. These structural and surface changes can enhance the voltage and capacity stability of the Li‐rich material electrodes after moderate NH₃ treatment times of 1–2 h.