Halogen bonds involved in binding of halogenated ligands by protein kinases.

Analysis of 664 known structures of protein kinase complexes with halogenated ligands revealed 424 short contacts between a halogen atom and a potential protein X-bond acceptor, the topology and geometry of which were analyzed according to the type of a halogen atom (X = Cl, Br, I) and a putative protein X-bond acceptor. Among 236 identified halogen bonds, the most represented ones are directed to backbone carbonyls of the hinge region and may replace the pattern of ATP-like hydrogen bonds. Some halogen-π interactions with either aromatic residues or peptide bonds, that accompany the interaction with the hinge region, may possibly enhance ligand selectivity. Interestingly, many of these halogen-π interactions are bifurcated. Geometrical preferences identify iodine as the strongest X-bond donor, less so bromine, while virtually no such preferences were observed for chlorine; and a backbone carbonyl as the strongest X-bond acceptor. The presence of a halogen atom in a ligand additionally affects the properties of proximal hydrogen bonds, which according to geometrical parameters get strengthened, when a nitrogen of a halogenated ligand acts as the hydrogen bond donor

Combined in silico and 19F NMR analysis of 5-fluorouracil metabolism in yeast at low ATP conditions.

The cytotoxic effect of 5-fluorouracil (5-FU) on yeast cells is thought to be mainly via a misincorporation of fluoropyrimidines into both RNA and DNA, not only DNA damage via inhibition of thymidylate synthase (TYMS) by fluorodeoxyuridine monophosphate (FdUMP). However, some studies on Saccharomyces cerevisiae show a drastic decrease in ATP concentration under oxidative stress, together with a decrease in concentration of other tri- and diphosphates. This raises a question if hydrolysis of 5-fluoro-2-deoxyuridine diphosphate (FdUDP) under oxidative stress could not lead to the presence of FdUMP and the activation of so-called ‘thymine-less death’ route. We attempted to answer this question with in silico modeling of 5-FU metabolic pathways, based on new experimental results, where the stages of intracellular metabolism of 5-FU in Saccharomyces cerevisiae were tracked by a combination of 19F and 31P NMR spectroscopic study. We have identified 5-FU, its nucleosides and nucleotides, and subsequent di- and/or triphosphates. Additionally, another wide 19F signal, assigned to fluorinated unstructured short RNA, has been also identified in the spectra. The concentration of individual metabolites was found to vary substantially within hours,however,theinitialsteady-statewaspreservedonlyforanhour,untiltheATPconcentration dropped by a half, which was monitored independently via 31P NMR spectra. After that, the catabolic process leading from triphosphates through monophosphates and nucleosides back to 5-FU was observed. These results imply careful design and interpretation of studies in 5-FU metabolism in yeast

Encapsulation of iron-saturated lactoferrin for proteolysis protection with preserving iron coordination and sustained release

Lactoferrin (Lf) is a globular glycoprotein found mainly in milk. It has a very high affinity for iron(III) ions, and its fully saturated form is called holoLf. The antimicrobial, antiviral, anticancer, and immunomodulatory properties of Lf have been studied extensively for the past two decades. However, to demonstrate therapeutic benefits, Lf has to be efficiently delivered to the intestinal tract in its structurally intact form. This work aimed to optimize the encapsulation of holoLf in a system based on the versatile Eudragit® RS polymer to protect Lf against the proteolytic environment of the stomach. Microparticles (MPs) with entrapped holoLf were obtained with satisfactory entrapment efficiency (90–95%), high loading capacity (9.7%), and suitable morphology (spherical without cracks or pores). Detailed studies of the Lf release from the MPs under conditions that included simulated gastric or intestinal fluids, prepared according to the 10th edition of the European Pharmacopeia, showed that MPs partially protected holoLf against enzymatic digestion and ionic iron release. The preincubation of MPs loaded with holoLf under conditions simulating the stomach environment resulted in the release of 40% of Lf from the MPs. The protein released was saturated with iron ions at 33%, was structurally intact, and its iron scavenging properties were preserved

Is there the gap in public health literature in Europe?

Introduction and objective: The growing expectations for the effectiveness of public health increase the demand for scientific literature, concerning research, reviews and other forms of information. The bibliographic databases are of crucial importance for researchers and policy makers. The objective of this study is to estimate the supply of scientific literature related to public health in selected European countries, which are available to a wide range of users. Material and Methods: Analysis of the number of bibliographic records on topics related to public health was based on searches in Ovid MEDLINE ( R) in May and June 2011. According to MeSH terms, 11 keywords and names of 13 European countries were used in the search. Publications from the years 2001–2010 were analyzed. A number of publications indexed under ‘public health’, and related to selected countries were compared with the size of the population of those countries, GDP, total expenditure on health and burden of disease (DALYS’s). Results: The most popular topic was ‘health policy’, whereas the topics ‘occupational health’ and ‘environmental health’ were less prevalent. There were no significant changes in the number of publications in 2001–2010. The number of articles indexed under ‘public health’ had significant positive correlation with national GDP, expenditure on health and population size, and negative with DALY’s. Conclusions: According to the criteria accepted in this study, the Nordic countries – Finland, Sweden and Norway – were very productive in this respect. Poland and other Central European Countries were less productive

Pielęgniarstwo na rzecz milenijnych celów rozwoju. Cz. 2

Praca recenzowana / Peer-reviewed paperZ przyjemnością oddajemy w Państwa ręce drugi tom monografii wydanej z okazji XII Kongresu Pielęgniarek Polskich w Krakowie, w którym udział wzięło blisko 500 pielęgniarek, zaprezentowano 160 prac w 9 sesjach. Ta kolejna już publikacja świadczy o dynamicznym rozwoju badań naukowych w pielęgniarstwie. Dowodzi, że pielęgniarstwo to nie tylko zawód, ale i interdyscyplinarna nauka

Rodzina w zdrowiu i w chorobie. Wybrane aspekty opieki nad przewlekle chorym

Praca recenzowana / peer-reviewed pape

Selected methods of evaluation of investment ventures

Jednym z najważniejszych czynników rozwoju gospodarczego są na pewno inwestycje. Mają one istotne znaczenie w strategii każdego podmiotu, który chce utrzymać się w swoim obszarze działalności. Są one determinantem postępu, nowoczesności i dynamizmu. Na ważność inwestycji wpływa kilka elementów. Pociągają za sobą zaangażowanie zazwyczaj znacznych kwot środków finansowych, co przemawia za wyborem racjonalnego źródła finansowania, a także dotyczą istotnych obszarów decyzyjnych, zarówno w kwestii wyboru efektywnego wariantu projektu, jak i wyodrębnienia ośrodków odpowiedzialności. Poszczególne opcje decyzyjne, poddane są analizie, która bada ich efektywność, wykorzystuje ona metody zróżnicowane na proste i dyskontowe. Artykuł jest poświęcony tematyce inwestycji, towarzyszącej temu zagadnieniu podstawowej terminologii. Wyszczególniono definicje i główne rodzaje inwestycji. Ponadto objęto charakterystyką pojęcie ryzyka. Omówiono także narzędzie oceny efektywności inwestycji – rachunek ekonomicznej efektywności.One of the most important factors of economic development are definitely investments. Investments have fundamental consequences in strategy of each entity, which wants to survive in its area of activity. They determine the progress, modernity and dynamism. Investments are important due to several determinants. For example: they require quite a lot of money, that is why we should choose sensible source of financing. They also refer to important decision areas both in the matter of choosing an effective variant of a project and distinguishing centers of responsibility. The decisions are exposed to analysis and their effectiveness is evaluated, while different methods are used, which are diversified into simple and complex ones. The article is dedicated to an investment and its relevant terminology. Particular attention has been paid to its definition and main types of investment. The idea of assessment of efficiency of an investment project has also been discussed here - that is the economic calculation efficiency

Tax strategy of the company

Artykuł poświęcony jest zagadnieniu strategii podatkowej. Pierwsza część opisuje istotę oraz funkcje podatków. Część druga poświęcona jest polityce podatkowej przedsiębiorstwa jako jednej ze strategii funkcjonalnych. W artykule zaprezentowano rodzaje ryzyka podatkowego oraz sposoby minimalizacji wydatków podatkowych. Przedstawiono również etapy formułowania strategii podatkowej.The article addresses the issue of tax strategies. The first part describes the essence and functions of taxes. The second part is devoted to the fiscal policy of the company as one of the functional strategy. This paper presents the risks and ways to minimize the tax expenditure. The stages of formulation tax strategies have also been included into the paper