Catalog of dessins d'enfants with \le 4 edges

In this work all the dessins d'enfant with no more than 4 edges are listed and their Belyi pairs are computed. In order to enumerate all dessins the technique of matrix model computations was used. The total number of dessins is 134; among them 77 are spherical, 53 of genus 1 and 4 of genus 2. The orders of automorphism groups of all the dessins are also found. Dessins are listed by the number of edges. Dessins with the same number of edges are ordered lexicographically by their lists of 0-valencies. The corresponding matrix model for any list of 0-valencies is given and computed. Complex matrix models for dessins with 1 -- 3 edges are used. For the dessins with 4 edges we use Hermitian matrix model, correlators for which are computed in [1].Comment: 64 pages, 134 figure

Взаимодействие аниона [2-В10Н9О(СН2)4О]− с вторичными аминами

Objectives. One of the most promising methods of treating malignant tumors is 10B-neutron capture therapy. While compounds based on cluster boron anions [BnHn]2− (n = 10, 12) are often used as boron-containing agents due to the very high specific concentration of boron atoms per particle, the use of such compounds is associated with the need to develop new methods for the functionalization of boron clusters associated with the production of boron-containing derivatives containing biologically active functional groups. One of the most convenient methods of modification of [BnHn]2− (n = 10, 12) anions is the interaction of their derivatives containing cyclic oxonium-type substituents with negatively charged or neutral nucleophilic reagents. The disclosure of substituents of this type leads to the formation of closo-borates with functional groups separated from the cluster by an alkoxyl spacer chain. The purpose of this study is to develop methods for the synthesis of derivatives of the closo-decaborate anion [B10H10]2− with pendant nitrogen-containing groups.Methods. The general control of the reactions of the disclosure of cyclic substituents was carried out on the basis of 11B nuclear magnetic resonance (NMR) spectroscopy data. The structure of the obtained derivatives, including the nature of the attached functional groups, was determined using 1H, 13C attached proton test (APT) NMR and infrared (IR) spectroscopy data. The molecular weight of the synthesized compounds was confirmed by electrospray ionization mass-spectrometry (ESI–MS).Results. The interaction of the anion [2-B10H9O(CH2)4O]− with secondary amines (dimethylamine, dipropylamine, diallylamine, dibutylamine, diisobutylamine, morpholine, di-sec-butylamine) in an ethanol environment is investigated. As a result of the reactions, a cyclic substituent is shown to expand with the addition of a nucleophilic reagent. Seven new derivatives of the closodecaborate anion with pendant nitrogen-containing groups have been synthesized.Conclusions. A developed method for obtaining closo-decaborates with ammonium groups separated from the boron cluster by an alkoxyl spacer group is presented. It is shown that the use of amines of various structures does not fundamentally affect the course of the reactions, allowing the composition and structure of the target derivatives to be effectively regulated. The resulting compounds can be involved in further modification reactions due to a reactive pendant group, as well as being suitable for use as effective polydentate ligands. Closo-decaborates with pendant nitrogen-containing groups and their derivatives are of considerable interest in the synthesis of compounds for use in 10B-neutron capture therapy of malignant tumors.Цели. 10B-нейтронозахватная терапия является одним из наиболее перспективных методов лечения злокачественных опухолей. В качестве борсодержащих агентов нередко применяются соединения на основе кластерных анионов бора [BnHn]2− (n = 10, 12), как имеющие очень высокую удельную концентрацию атомов бора в расчете на одну частицу. Однако использование таких соединений связано с необходимостью разработки новых методов функционализации борных кластеров, связанных с получением борсодержащих производных с биологически активными функциональными группами. Одним из наиболее удобных методов модификации анионов [BnHn]2− (n = 10, 12) является взаимодействие их производных, содержащих циклические заместители оксониевого типа, с отрицательно заряженными или нейтральными нуклеофильными реагентами. Раскрытие заместителей данного типа приводит к образованию клозо-боратов с функциональными группами, отделенными от кластера алкоксильной спейсерной цепочкой. Целью настоящего исследования является разработка методов синтеза производных клозо-декаборатного аниона [B10H10]2− с пендантными азотсодержащими группами.Методы. Общий контроль протекания реакций раскрытия циклических заместителей осуществлялся на основании данных 11B спектроскопии ядерного магнитного резонанса (ЯМР). Строение полученных производных, в том числе природу присоединенных функциональных групп определяли на основании данных 1H, 13C ЯМР с тестом на присоединенные протоны (APT) и инфракрасной спектроскопии (ИК). Молекулярную массу синтезированных соединений подтверждали методом масс-спектрометрии с ионизацией электрораспылением (ИЭР-МС).Результаты. Исследовано взаимодействие аниона [2-B10H9O(CH2)4O]− с вторичными аминами (диметиламин, дипропиламин, диаллиламин, дибутиламин, диизобутиламин, морфолин, ди-втор-бутиламин) в среде этанола. Показано, что в результате реакций происходит раскрытие циклического заместителя с присоединением нуклеофильного реагента. Синтезированы семь новых производных клозо-декаборатного аниона с пендантными азотсодержащими группами.Выводы. Разработан новый метод получения клозо-декаборатов с аммониевыми группами, отделенными от борного кластера алкоксильной спейсерной группой. Показано, что применение аминов различного строения принципиально не влияет на ход протекающих реакций и позволяет эффективно регулировать состав и строение целевых производных. Полученные соединения могут быть вовлечены в дальнейшие реакции модификации за счет реакционноспособной пендантной группы, а также могут быть использованы в роли эффективных полидентатных лигандов. Клозо-декабораты с пендантными азотсодержащими группами и их производные представляют значительный интерес в синтезе соединений, перспективных для применения в 10B-нейтронозахватной терапии злокачественных опухолей

Deficiency of a Niemann-Pick, Type C1-related Protein in Toxoplasma Is Associated with Multiple Lipidoses and Increased Pathogenicity

Several proteins that play key roles in cholesterol synthesis, regulation, trafficking and signaling are united by sharing the phylogenetically conserved ‘sterol-sensing domain’ (SSD). The intracellular parasite Toxoplasma possesses at least one gene coding for a protein containing the canonical SSD. We investigated the role of this protein to provide information on lipid regulatory mechanisms in the parasite. The protein sequence predicts an uncharacterized Niemann-Pick, type C1-related protein (NPC1) with significant identity to human NPC1, and it contains many residues implicated in human NPC disease. We named this NPC1-related protein, TgNCR1. Mammalian NPC1 localizes to endo-lysosomes and promotes the movement of sterols and sphingolipids across the membranes of these organelles. Miscoding patient mutations in NPC1 cause overloading of these lipids in endo-lysosomes. TgNCR1, however, lacks endosomal targeting signals, and localizes to flattened vesicles beneath the plasma membrane of Toxoplasma. When expressed in mammalian NPC1 mutant cells and properly addressed to endo-lysosomes, TgNCR1 restores cholesterol and GM1 clearance from these organelles. To clarify the role of TgNCR1 in the parasite, we genetically disrupted NCR1; mutant parasites were viable. Quantitative lipidomic analyses on the ΔNCR1 strain reveal normal cholesterol levels but an overaccumulation of several species of cholesteryl esters, sphingomyelins and ceramides. ΔNCR1 parasites are also characterized by abundant storage lipid bodies and long membranous tubules derived from their parasitophorous vacuoles. Interestingly, these mutants can generate multiple daughters per single mother cell at high frequencies, allowing fast replication in vitro, and they are slightly more virulent in mice than the parental strain. These data suggest that the ΔNCR1 strain has lost the ability to control the intracellular levels of several lipids, which subsequently results in the stimulation of lipid storage, membrane biosynthesis and parasite division. Based on these observations, we ascribe a role for TgNCR1 in lipid homeostasis in Toxoplasma

RENAL AND CORONARY PREDICTORS OF POST-MYOCARDIAL REVASCULARISATION PROGNOSIS IN PATIENTS WITH CORONARY HEART DISEASE

Aim. To assess the impact of renal and local coronary risk factors (RFs) on cardiovascular survival in patients with coronary heart disease (CHD) before and after myocardial revascularisation. Material and methods. The study included 90 CHD patients with indications for myocardial revascularisation. In all participants, the presence of renal RFs (microalbuminuria (MAU) and increased levels of β2 -microglobulin (β2 -MG)) was assessed at different intervention stages. In addition, the number of coronary arteries (CA) affected by atherosclerosis, as well as CA atherosclerosis severity, was assessed. Results. Among the majority of CHD patients with myocardial revascularisation indications, MAU was observed at all intervention stages. The endpoint incidence was associated with MAU, β2 -MG levels, the number of CA affected by atherosclerosis and CA with hemodynamically non-significant stenosis. The levels of β2 -MG significantly correlated with atherosclerotic plaque growth rate. Conclusion. The increased risk of coronary events was associated with elevated levels of MAU and β2 -MG and the increased number of CA affected by atherosclerosis and CA with hemodynamically non-significant stenosis. Elevated CV risk was linked to β2 -MG levels of ≥0,1 ng/ml. The levels of β2 -MG increased in parallel with the CHD progression

Comparative analysis of Mycobacterium tuberculosis pe and ppe genes reveals high sequence variation and an apparent absence of selective constraints.

Contains fulltext : 110619.pdf (publisher's version ) (Open Access)Mycobacterium tuberculosis complex (MTBC) genomes contain 2 large gene families termed pe and ppe. The function of pe/ppe proteins remains enigmatic but studies suggest that they are secreted or cell surface associated and are involved in bacterial virulence. Previous studies have also shown that some pe/ppe genes are polymorphic, a finding that suggests involvement in antigenic variation. Using comparative sequence analysis of 18 publicly available MTBC whole genome sequences, we have performed alignments of 33 pe (excluding pe_pgrs) and 66 ppe genes in order to detect the frequency and nature of genetic variation. This work has been supplemented by whole gene sequencing of 14 pe/ppe (including 5 pe_pgrs) genes in a cohort of 40 diverse and well defined clinical isolates covering all the main lineages of the M. tuberculosis phylogenetic tree. We show that nsSNP's in pe (excluding pgrs) and ppe genes are 3.0 and 3.3 times higher than in non-pe/ppe genes respectively and that numerous other mutation types are also present at a high frequency. It has previously been shown that non-pe/ppe M. tuberculosis genes display a remarkably low level of purifying selection. Here, we also show that compared to these genes those of the pe/ppe families show a further reduction of selection pressure that suggests neutral evolution. This is inconsistent with the positive selection pressure of "classical" antigenic variation. Finally, by analyzing such a large number of genes we were able to detect large differences in mutation type and frequency between both individual genes and gene sub-families. The high variation rates and absence of selective constraints provides valuable insights into potential pe/ppe function. Since pe/ppe proteins are highly antigenic and have been studied as potential vaccine components these results should also prove informative for aspects of M. tuberculosis vaccine design