КІРЛІАНОГРАФІЧНЕ ОЦІНЮВАННЯ БІОДОСТУПНОСТІ РЕЧОВИНИ

The ratio between water molecules associated to the clusters in cell structures, which is the conformational catalyst for the exchange processes, and non-associated or free water participating in free-radical reactions is very important for the normal functioning of the organs of living beings.The aim of the study was to compare Kirlian glow of apple samples before and after t h e sanctification during the Christian holiday The Saviour to detect the possibility of the bioavailability signs establishing of the product for the body.The kirlianographic study of 10 samples of whole and cut apples with the same sort and size before and after the sanctification was made. Radiographic film and standard methods of its development as well as the instrument “REK-1”, designed by Ukrainian Research Institute of Machine Building Technology (D nepropetrovsk) were used. Mathematical processing of scanned Kirlianograms was performed using standard software package for th e construction of histograms and pixel brightness profile of the picture.The method of classical kirlianography with X ray film allows assessing the bioavailability condition, which is important for the prediction of absorption and physiological effects of a man consumed food and phytomedicines. Therefore, these studies are relevant and require further development. Used such standard methods of mathematical processing as histograms and pixel brightness profile for the analysis of Kirlian images are informative enough for the individual samples, and can be the basis for the batch processing of data.Важным для нормального функционирования органов живых существ является соотношение в клеточных структурах связанной в биополимерах и свободной воды. Степень усвоения организмом любых веществ, принимаемых вовнутрь, зависит от их биодоступности, то есть физиологичности, определяемой состоянием воды. Однако до последнего времени роль электронно-возбужденных состояний в жидкофазных системах организма во внимание не принималась. Известно, что в водных растворах систем, близких к физиологическим условиям, возникает колебательный режим излучения. Свободнорадикальные реакции сопровождаются излучением фотонов в ультрафиолетовой части спектра, к которой относится и кирлиановское свечение. Изучили возможность использования метода классической кирлианографии на рентгеновской пленке в оценке состояния природной биоэнергетики. Исследовали свечение образцов яблок до и после освящения. Анализировали гистограммы и профиль яркостей пикселей их кирлиановских изображений, отражающих их природную структуру и энергетику. Выявили улучшение структуры яблок после освящения, как целых, так и в разрезе, что связано с переструктурированием воды в них. В частности, внешнее кирлиановское свечение освященных яблок более интенсивное, по сравнению с не освященными, что свидетельствует о большей у них биоэнергии. В то же время, свечение внутреннего строения свидетельствует о большем содержании связанной воды, что ближе к физиологическому состоянию клеток организма. Таким образом, метод классической кирлианографии на рентгеновской пленке позволяет оценить внутреннее энергетическое и структурное состояние продукта, определяющие его биодоступность.Важливим для нормального функціонування органів живих істот є співвідношення в структурах клітин зв’язаної в біополімерах та вільної води. Ступінь засвоєння організмом різних речовин залежить від їх біодоступності, тобто фізіологічності, що визначається станом води. Проте до останнього часу роль електронозбуджених станів у ріди- нофазних системах організму до уваги не бралася. Звісно, що у водних розчинах систем, близьких до фізіологіч­них умов, виникає режим коливання випромінювання. Вільнорадикальні реакції супроводжуються випромінюван­ням фотонів в ультрафіолетовій частині спектра, до якої належить й кірліанівське світіння. Вивчали можливість використання класичної кірліанографії на рентгенівській плівці для оцінки стану природної біоенергетики речови­ни. Досліджували кірліанівське випромінювання зразків яблук до та після їх освячення на християнське свято. Аналізували гістограми та профіль яскравості пікселів їх кірліанівських зображень, що віддзеркалюють їх природну структуру і енергетику. Виявили поліпшення структури яблук після освячення, як цілих, так і розрізаних, що пов’я­зано з переструктуруванням у них води. З овнішнє кірліанівське випромінювання освячених яблук більш інтенсив­не, порівняно з не освяченими, що свідчить про більшу біоенергію у перших. В той же час, світіння внутрішньої будови освячених яблук свідчить про більший вміст зв’язаної води, що ближче до фізіологічного стану клітин організму. Таким чином, метод класичної кірліанографії на рентгенівській плівці дозволяє оцінити стан енергетики та структури речовини для вживання людиною, від чого залежить його засвоєння організмом, тобто біодоступність

Hamiltonians for Reduced Gravity

A generalised canonical formulation of gravity is devised for foliations of spacetime with codimension $n\ge1$. The new formalism retains n-dimensional covariance and is especially suited to 2+2 decompositions of spacetime. It is also possible to use the generalised formalism to obtain boundary contributions to the 3+1 Hamiltonian.Comment: 18 pages, revtex, 3 postscript figures include

Structural basis for hijacking of the host ACBD3 protein by bovine and porcine enteroviruses and kobuviruses

Picornaviruses infect a wide range of mammals including livestock such as cattle and swine. As with other picornavirus genera such as Aphthovirus, there is emerging evidence of a significant economic impact of livestock infections caused by members of the genera Enterovirus and Kobuvirus. While the human infecting enteroviruses and kobuviruses have been intensively studied during the past decades in great detail, research on livestock infecting viruses has been mostly limited to the genomic characterization of the viral strains identified worldwide. Here, we extend our previous studies of the structure and function of the complexes composed of the non structural 3A proteins of human infecting enteroviruses and kobuviruses and the host ACBD3 protein and present a structural and functional characterization of the complexes of the following livestock infecting picornaviruses bovine enteroviruses EV E and EV F, porcine enterovirus EV G, and porcine kobuvirus AiV C. We present a series of crystal structures of these complexes and demonstrate the role of these complexes in facilitation of viral replicatio

Structures of kobuviral and siciniviral polymerases reveal conserved mechanism of picornaviral polymerase activation

RNA dependent RNA polymerase 3Dpol is a key enzyme for the replication of picornaviruses. The viral genome is translated into a single polyprotein that is subsequently proteolytically processed into matured products. The 3Dpol enzyme arises from a stable 3CD precursor that has high proteolytic activity but no polymerase activity. Upon cleavage of the precursor the newly established N terminus of 3Dpol is liberated and inserts itself into a pocket on the surface of the 3Dpol enzyme. The essential residue for this mechanism is the very first glycine that is conserved among almost all picornaviruses. However, kobuviruses and siciniviruses have a serine residue instead. Intrigued by this anomaly we sought to solve the crystal structure of these 3Dpol enzymes. The structures revealed a unique fold of the 3Dpol N termini but the very first serine residues were inserted into a charged pocket in a similar manner as the glycine residue in other picornaviruses. These structures revealed a common underlying mechanism of 3Dpol activation that lies in activation of the amp; 945;10 helix containing a key catalytical residue Asp238 that forms a hydrogen bond with the 2 amp; 8242; hydroxyl group of the incoming NTP nucleotid

Development of small bisquaternary cholinesterase inhibitors as drugs for pre-treatment of nerve agent poisonings

Kamil Kuca,1,2 Jana Zdarova Karasova,2,3 Ondrej Soukup,2 Jiri Kassa,3 Eva Novotna,2 Vendula Sepsova,2,3 Anna Horova,2 Jaroslav Pejchal,3 Martina Hrabinova,2,3 Eva Vodakova,2 Daniel Jun,2,3 Eugenie Nepovimova,1,2 Martin Valis,4 Kamil Musilek1,2 1Department of Chemistry, Faculty of Science, University of Hradec Kralove, 2Biomedical Research Center, University Hospital Hradec Kralove, 3Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defence, 4Department of Neurology, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic Background: Intoxication by nerve agents could be prevented by using small acetylcholinesterase inhibitors (eg, pyridostigmine) for potentially exposed personnel. However, the serious side effects of currently used drugs led to research of novel potent molecules for prophylaxis of organophosphorus intoxication. Methods: The molecular design, molecular docking, chemical synthesis, in vitro methods (enzyme inhibition, cytotoxicity, and nicotinic receptors modulation), and in vivo methods (acute toxicity and prophylactic effect) were used to study bispyridinium, bisquinolinium, bisisoquinolinium, and pyridinium-quinolinium/isoquinolinium molecules presented in this study. Results: The studied molecules showed non-competitive inhibitory ability towards human acetylcholinesterase in vitro that was further confirmed by molecular modelling studies. Several compounds were selected for further studies. First, their cytotoxicity, nicotinic receptors modulation, and acute toxicity (lethal dose for 50% of laboratory animals [LD50]; mice and rats) were tested to evaluate their safety with promising results. Furthermore, their blood levels were measured to select the appropriate time for prophylactic administration. Finally, the protective ratio of selected compounds against soman-induced toxicity was determined when selected compounds were found similarly potent or only slightly better to standard pyridostigmine. Conclusion: The presented small bisquaternary molecules did not show overall benefit in prophylaxis of soman-induced in vivo toxicity. Keywords: AChE inhibitors, prophylaxis, pre-treatment, nerve agents, toxicity, soma

Insights into the karyotype and genome evolution of haplogyne spiders indicate a plyploid origin of lineage with holokinetic chromosomes.

Spiders are an ancient and extremely diverse animal order. They show a considerable diversity of genome sizes, karyotypes and sex chromosomes, which makes them promising models to analyse the evolution of these traits. Our study is focused on the evolution of the genome and chromosomes in haplogyne spiders with holokinetic chromosomes. Although holokinetic chromosomes in spiders were discovered a long time ago, information on their distribution and evolution in these arthropods is very limited. Here we show that holokinetic chromosomes are an autapomorphy of the superfamily Dysderoidea. According to our hypothesis, the karyotype of ancestral Dysderoidea comprised three autosome pairs and a single X chromosome. The subsequent evolution has frequently included inverted meiosis of the sex chromosome and an increase of 2n. We demonstrate that caponiids, a sister clade to Dysderoidea, have enormous genomes and high diploid and sex chromosome numbers. This pattern suggests a polyploid event in the ancestors of caponiids. Holokinetic chromosomes could have arisen by subsequent multiple chromosome fusions and a considerable reduction of the genome size. We propose that spider sex chromosomes probably do not pose a major barrier to polyploidy due to specific mechanisms that promote the integration of sex chromosome copies into the genome