Синтез та біологічна активність нових четвертинних солей адамантановмісних діалкіламінопропанолів

The emergence and spread of multidrug-resistant pathogens leads to a decrease in efficacy of antibiotic therapy, prolongation of the length of patient’s hospital stay and an increase in treatment costs. The screening of potential antimicrobial agents among the new classes of chemical compounds is one of the promising methods to overcome the problem of resistance.Objectives. The synthesis and screening studies of antimicrobial activity of quaternary salts of adamantane derivatives (3a – 3l) with the aim to find of new prospective compound with good activityMaterials and methods. The synthesis and investigation of physicochemical properties of new adamantan-based dialkylaminopropanol quaternary salts were carried out. The evaluation of antimicrobial action against S. aureus, E. coli and C. albicans strains were performed.Results and discussion. The results showed that the inhibitory activities of quaternary salts with 1-adamantylethyl radical in their alkoxy group were significantly higher than those of the compounds with 1-adamantyl and 1-adamantyloxyethyl radicals in their alkoxy group.Conclusions. 3c was the most active compound tested against all strains, with MIC between 1.56 and 3.12 µg/mL, and its antimicrobial activity was similar to that of myramistin.Актуальность. Появление и распространение устойчивых штаммов возбудителей инфекционных заболеваний приводит к снижению эффективности антибиотикотерапии, способствует увеличению срока госпитализации пациентов и расходов на их лечение. Одним из путей борьбы с резистентностью является поиск активных соединений среди новых химических классов и разработка на их основе эффективных препаратов.Цель работы. Синтез и скрининговые исследования антимикробного действия четвертичных солей адамантансодержащих диалкиламинопропанолов с целью поиска новых перспективных активных соединений.Материалы и методы. Осуществлен синтез и изучены физико-химические свойства четвертичных солей адамантансодержащих диалкиламинопропанолов. Была проведена оценка их антимикробного действия в отношении S. aureus, E. coli и C. albicans.Результаты и их обсуждение. Показано, что ингибирующая активность четвертичных солей с 1-адамантилэтильным радикалом в алкоксигруппе была значительно выше, чем у соединений с 1-адамантильным и 1-адамантилоксиэтильным радикалами.Выводы. Наиболее выраженная активность в отношении всех штаммов была установлена у соединения 3с, которое по показателю антимикробной активности не уступает препарату сравнения мирамистину (МПК был в диапазоне 1,56-3,12 мкг/мл).Актуальність. Поява та розповсюдження стійких штамів збудників інфекційних хвороб призводить до зниження ефективності антибіотикотерапії, спричиняє збільшення терміну госпіталізації пацієнтів та витрат на їх лікування. Одним із шляхів протидії резистентності є пошук активних сполук серед нових хімічних класів та розробка на їх основі ефективних препаратів. Мета роботи. Синтез та скринінгові дослідження антимікробної дії четвертинних солей адамантановмісних діалкіламінопропанолів (3a-3l) з метою пошуку нових перспективних активних сполук.Матеріали та методи. Здійснено синтез та вивчені фізико-хімічні властивості четвертинних солей адамантановмісних діалкіламінопропанолів. Було оцінено їх антимікробну дію відносно S. aureus, E. coli та C. albicans.Результати та їх обговорення. Було встановлено, що інгібуюча активність четвертинних солей з 1-адамантилетиловим радикалом у алкоксигрупі була значно вищою, ніж у сполук з 1-адамантиловим та 1-адаман-тилоксіетильним радикалами.Висновки. Найбільш виражену інгібуючу активність по відношенню до всіх штамів показала сполука 3с, яка за антимікробною активністю не поступалась препарату порівняння мірамістину (МІК був в інтервалі 1,56-3,12 мкг/мл)

Apoptosis is not conserved in plants as revealed by critical examination of a model for plant apoptosis-like cell death

Background: Animals and plants diverged over one billion years ago and evolved unique mechanisms for many cellular processes, including cell death. One of the most well-studied cell death programmes in animals, apoptosis, involves gradual cell dismantling and engulfment of cellular fragments, apoptotic bodies, through phagocytosis. However, rigid cell walls prevent plant cell fragmentation and thus apoptosis is not applicable for executing cell death in plants. Furthermore, plants are devoid of the key components of apoptotic machinery, including phagocytosis as well as caspases and Bcl-2 family proteins. Nevertheless, the concept of plant "apoptosis-like programmed cell death" (AL-PCD) is widespread. This is largely due to superficial morphological resemblances between plant cell death and apoptosis, and in particular between protoplast shrinkage in plant cells killed by various stimuli and animal cell volume decrease preceding fragmentation into apoptotic bodies.Results: Here, we provide a comprehensive spatio-temporal analysis of cytological and biochemical events occurring in plant cells subjected to heat shock at 40-55 degrees C and 85 degrees C, the experimental conditions typically used to trigger AL-PCD and necrotic cell death, respectively. We show that cell death under both conditions was not accompanied by membrane blebbing or formation of apoptotic bodies, as would be expected during apoptosis. Instead, we observed instant and irreversible permeabilization of the plasma membrane and ATP depletion. These processes did not depend on mitochondrial functionality or the presence of Ca2+ and could not be prevented by an inhibitor of ferroptosis. We further reveal that the lack of protoplast shrinkage at 85 degrees C, the only striking morphological difference between cell deaths induced by 40-55 degrees C or 85 degrees C heat shock, is a consequence of the fixative effect of the high temperature on intracellular contents.Conclusions: We conclude that heat shock-induced cell death is an energy-independent process best matching definition of necrosis. Although the initial steps of this necrotic cell death could be genetically regulated, classifying it as apoptosis or AL-PCD is a terminological misnomer. Our work supports the viewpoint that apoptosis is not conserved across animal and plant kingdoms and demonstrates the importance of focusing on plant-specific aspects of cell death pathways

Frequency of rare recessive mutations in unexplained late onset cerebellar ataxia.

Sporadic late onset cerebellar ataxia is a well-described clinical presentation with a broad differential diagnosis that adult neurologists should be familiar with. However, despite extensive clinical investigations, an acquired cause is identified in only a minority of cases. Thereafter, an underlying genetic basis is often considered, even in those without a family history. Here we apply whole exome sequencing to a cohort of 12 patients with late onset cerebellar ataxia. We show that 33% of 'idiopathic' cases harbor compound heterozygous mutations in known ataxia genes, including genes not included on multi-gene panels, or primarily associated with an ataxic presentation

Immunolocalization of dually phosphorylated MAPKs in dividing root meristem cells of Vicia faba, Pisum sativum, Lupinus luteus and Lycopersicon esculentum

Key message In plants, phosphorylated MAPKs display constitutive nuclear localization; however, not all studied plant species show co-localization of activated MAPKs to mitotic microtubules. Abstract The mitogen-activated protein kinase (MAPK) signaling pathway is involved not only in the cellular response to biotic and abiotic stress but also in the regulation of cell cycle and plant development. The role of MAPKs in the formation of a mitotic spindle has been widely studied and the MAPK signaling pathway was found to be indispensable for the unperturbed course of cell division. Here we show cellular localization of activated MAPKs (dually phosphorylated at their TXY motifs) in both interphase and mitotic root meristem cells of Lupinus luteus, Pisum sativum, Vicia faba (Fabaceae) and Lycopersicon esculentum (Solanaceae). Nuclear localization of activated MAPKs has been found in all species. Colocalization of these kinases to mitotic microtubules was most evident in L. esculentum, while only about 50 % of mitotic cells in the root meristems of P. sativum and V. faba displayed activated MAPKs localized to microtubules during mitosis. Unexpectedly, no evident immunofluorescence signals at spindle microtubules and phragmoplast were noted in L. luteus. Considering immunocytochemical analyses and studies on the impact of FR180204 (an inhibitor of animal ERK1/2) on mitotic cells, we hypothesize that MAPKs may not play prominent role in the regulation of microtubule dynamics in all plant species

Differential Dynamic Changes of Reduced Trait Model for Analyzing the Plastic Response to Drought Phases: A Case Study in Spring Wheat

Current limited water availability due to climate changes results in severe drought stress and desiccation in plants. Phenotyping drought tolerance remains challenging. In particular, our knowledge about the discriminating power of traits for capturing a plastic phenotype in high-throughput settings is scant. The study is designed to investigate the differential performance and broad-sense heritability of a battery set of morphological, physiological, and cellular traits to understand the adaptive phenotypic response to drought in spring wheat during the tillering stage. The potential of peroxisome abundance to predict the adaptive response under severe drought was assessed using a high-throughput technique for peroxisome quantification in plants. The research dissected the dynamic changes of some phenological traits during three successive phases of drought using two contrasting genotypes of adaptability to drought. The research demonstrates 5 main findings: (1) a reduction of the overall dimension of the phenological traits for robust phenotyping of the adaptive performance under drought; (2) the abundance of peroxisomes in response to drought correlate negatively with grain yield; (3) the efficiency of ROS homeostasis through peroxisome proliferation which seems to be genetically programmed; and (4) the dynamics of ROS homeostasis seems to be timing dependent mechanism, the tolerant genotype response is earlier than the susceptible genotype. This work will contribute to the identification of robust plastic phenotypic tools and the understanding of the mechanisms for adaptive behavior under drought conditions.Summary statementThis study presents the estimated broad-sense heritability of 24 phenological traits under drought compared with non-stressed conditions. The results demonstrated a reduced model of the overall dimension of the phenological traits for phenotyping drought tolerant response including a novel trait (peroxisome abundance). Also, it displays that the adaptive mechanism through peroxisomes proliferation that is a genetic-dependent manner and related to the stress phase, since tolerant plants can sense the stress and maintain the cellular balance earlier than the sensitive plants

Eco-friendly Synthesis of Gold Nanoparticles Using Camellia sinensis Phytoextracts

Biosynthesis of metal nanoparticles using plant materials involves a fairly rapid reduction of metallic materials. The reduction potential of phytochemicals in a tea extract to reduce gold salt (NaAuCl4) to the highly homogenous gold nanoparticles is presented. Phytoextracts were derived from the mixture of Camellia sinensis var. sinensis and Camellia sinensis var. assamica (green tea) leaves. The appearance of the phytoextract's sloping absorption peak with Au salt at the wavelength range 530-550 nm corresponded to the absorption of gold nanoparticles. Obtained nanoparticles were purified from phytoextract excess by centrifugation. Then they were studied by Raman and FTIR spectroscopy and AFM. It was found that the size of produced gold nanoparticles was in the range from 3 nm to 10 n

Differential regulation of Knotted1-like genes during establishment of the shoot apical meristem in Norway spruce (Picea abies)

Establishment of the shoot apical meristem (SAM) in Arabidopsis embryos requires the KNOXI transcription factor SHOOT MERISTEMLESS. In Norway spruce (Picea abies), four KNOXI family members (HBK1, HBK2, HBK3 and HBK4) have been identified, but a corresponding role in SAM development has not been demonstrated. As a first step to differentiate between the functions of the four Norway spruce HBK genes, we have here analyzed their expression profiles during the process of somatic embryo development. This was made both under normal embryo development and under conditions of reduced SAM formation by treatment with the polar auxin transport inhibitor NPA. Concomitantly with the formation of an embryonic SAM, the HBK2 and HBK4 genes displayed a significant up-regulation that was delayed by NPA treatment. In contrast, HBK1 and HBK3 were up-regulated prior to SAM formation, and their temporal expression was not affected by NPA. Ectopic expression of the four HBK genes in transgenic Arabidopsis plants further supported similar functions of HBK2 and HBK4, distinct from those of HBK1 and HBK3. Together, the results suggest that HBK2 and HBK4 exert similar functions related to the SAM differentiation and somatic embryo development in Norway spruce, while HBK1 and HBK3 have more general functions during embryo development

Injection Spectroscopy of Deep Traps in Nanostructured Films of Cadmium Sulfide

Nanocrystallin CdS films with controlled stoichiometry deposited by CSVS were investigated by meth- od of the current-voltage characteristics in ITO/CdS /In structures. It was shown that in the case of cadmi- um excess (S <Cd) charge flow mechanism both in the dark and under illumination is determined by bimo- lecular recombination in the material. In the case of excess sulfur (S>Cd) charge flow mechanism is deter- mined by monomolecular recombination. In the band gap of CdS with excess of cadmium there was detected localized states with energy Et = 0.514 ± 0.026 eV, while in the material with Excess sulfur there are two localized states with energy Et1 = 0.514 ± 0.026 eV and Et2 = 0.700 ± 0.026 eV. Full concentration of localized states is more than 2·1021 m-3 – 5·1022 m-3. Dependence of injection in parameters and nature of injection in the structures based on nanostructured CdS films on their stoichiometry was determined. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/3390