85 research outputs found
Some models of the Geminids meteor stream formation
Further development of methods of investigations of meteor shower structure and a great deal of observational data have made it possible to obtain a precise flux density profile along the Earth's orbit for the Geminids meteor shower. This curve proved to be adequately described by a exponential law. Examined are: (1) which ejection model will fit the observed shower structure; and (2) to what extent the subsequent process of evolution modifies the formed structure. The following conclusions are drawn: (1) When studying the mechanism of formation of meteor streams, it is necessary to take into consideration the velocity distribution of particles that have been ejected from the parent body; (2) On the basis of the observed density variations, it is possible to determine what kind of ejection takes place (a single ejection or that around an orbital arch); and (3) The original structure of the Geminids cross section persists for no more than 1,500 to 2,000 years
Selective staining and eradication of cancer cells by protein-carrying DARPin-functionalized liposomes
Since their discovery, liposomes have been widely employed in biomedical research. These nano-size spherical vesicles consisting one or few phospholipid bilayers surrounding an aqueous core are capable of carrying a wide variety of bioactive compounds, including drugs, peptides, nucleic acids, proteins and others. Despite considerable success achieved in synthesis of liposome constructs containing bioactive compounds, preparation of ligand-targeted liposomes comprising large quantities of encapsulated proteins that are capable of affecting pathological cells still remains a big challenge. Here we described a novel method for preparation of small (80\u201390 nm in diameter) unilamellar liposomes containing very large quantities (thousands of protein molecules per liposome) of heme-containing cytochrome c, highly fluorescent mCherry and highly toxic PE40 (Pseudomonas aeruginosa Exotoxin A domain). Efficient encapsulation of the proteins was achieved through electrostatic interaction between positively charged proteins (at pH lower than pI) and negatively charged liposome membrane. The proteoliposomes containing large quantities of mCherry or PE40 and functionalized with designed ankyrin repeat protein (DARPin)_9-29, which targets human epidermal growth factor receptor 2 (HER2) were shown to specifically stain and kill in sub-nanomolar concentrations HER2-positive cells, overexpressing HER2, respectively. Specific staining and eradication of the receptor-positive cells demonstrated here makes the DARPin-functionalized liposomes carrying large quantities of fluorescent and/or toxic proteins a promising candidate for tumor detection and therapy
Concurrent thermochemoradiotherapy for brain high-grade glioma
Despite the achievements in the current strategies for treatment, the prognosis in malignant glioma patients remains unsatisfactory. Hyperthermia is currently considered to be the most effective and universal modifier of radiotherapy and chemotherapy. Preliminary treatment outcomes for 28 patients with newly diagnosed (23) and recurrent (5) high-grade gliomas were presented. All the patients received multimodality treatment including surgery, thermoche-moradiotherapy followed by 4 cycles of adjuvant chemotherapy. All the patients endured thermochemoradiotherapy well. A complication, limited skin burn (II stage), was diagnosed in two cases and treated conservatively without treatment interruption. A month after thermochemoradiotherapy the results were as follows: complete regression was achieved in 4 cases, partial regression in 4 cases, stable disease in 14 cases and disease progression in 6 cases (one of them is pseudo-progression). After completing the adjuvant chemotherapy 2 more patients demonstrated complete response and 1 patient had disease progression. Introduction of local hyperthermia in multimodal therapy of malignant glioma does not impair the combined modality treatment tolerability of patients with malignant gliomas. A small number of studied patients and short follow-up time do not allow making reliable conclusions about the impact of local hyperthermia on the treatment outcomes; however, there is a tendency towards the increase in disease-free survival in the patients with newly diagnosed malignant gliomas
Finding of the Low Molecular Weight Inhibitors of Resuscitation Promoting Factor Enzymatic and Resuscitation Activity
Background: Resuscitation promoting factors (RPF) are secreted proteins involved in reactivation of dormant actinobacteria, including Mycobacterium tuberculosis. They have been considered as prospective targets for the development of new antituberculosis drugs preventing reactivation of dormant tubercle bacilli, generally associated with latent tuberculosis. However, no inhibitors of Rpf activity have been reported so far. The goal of this study was to find low molecular weight compounds inhibiting the enzymatic and biological activities of Rpfs. Methodology/Principal Findings: Here we describe a novel class of 2-nitrophenylthiocyanates (NPT) compounds that inhibit muralytic activity of Rpfs with IC50 1–7 mg/ml. Fluorescence studies revealed interaction of active NPTs with the internal regions of the Rpf molecule. Candidate inhibitors of Rpf enzymatic activity showed a bacteriostatic effect on growth of Micrococcus luteus (in which Rpf is essential for growth protein) at concentrations close to IC50. The candidate compounds suppressed resuscitation of dormant (‘‘non-culturable’’) cells of M. smegmatis at 1 mg/ml or delayed resuscitation of dormant M. tuberculosis obtained in laboratory conditions at 10 mg/ml. However, they did not inhibit growth of active mycobacteria under these concentrations. Conclusions/Significance: NPT are the first example of low molecular weight compounds that inhibit the enzymatic an
Dissemination of Invasive Mosquito Species, Aedes (Stegomyia) aegypti (L., 1762) and Aedes (Stegomyia) albopictus (Skuse, 1895) in the South of Krasnodar Region, Russia
Objective of the study was to investigate the current borders of the invasive species Ae. aegypti and Ae. albopictus distribution in the south of the Krasnodar Region and climatic factors limiting their expansion. Material and methods. Mosquito larvae, pupa and imago were collected in 21 inhabited localities in August–September, 2017, using conventional entomological methods, and identified through standard morphological keys. Climatic data found on the website pogoda. ru were analyzed using SPSS program. Results and conclusions. Ae. albopictus is widely spread along the Black Sea coast, from Adler to Novorossiysk (Ozereyevka), as well as on the north slopes of Caucasus up to Maikop. Additional investigations are required to specify the northern border of species distribution and to evidence the existence of established populations here. Ae. aegypti were not found in the south of the Krasnodar Region. The obtained data suggest a possibility of much wider spreading of dengue, Chikungunya and Zika fevers in case of pathogen importation to the south of Krasnodar Region, than was assumed earlier
Impact of toxicity effects of zinc oxide nanoparticles in rats within acute and subacute experiments
Introduction. Occupational air is contaminated with zinc oxide nanoparticles in the copper smelting industry, especially in the smelting of brass and copper. A wide range of toxic effects with varied clinical symptomatology is observed in zinc and its compounds. Competitive relations with many other metals, including calcium, copper, and iron, are the foundation of most cases of zinc intoxication. Long-term administration of zinc or its compounds to laboratory rodents affects enzymes, carbohydrates and mineral metabolism. Materials and methods. Subchronic intoxication with repeated intraperitoneal injections and acute low respiratory tract reaction to a single intratracheal injection of zinc nanoparticles were simulated in outbred white rats. Water suspensions of zinc oxide nanoparticles with a 30-80 nm diameter were applied in both experimental models. Upon completion of the exposure, the condition of the rats in all groups was evaluated in many generally accepted criteria for toxicity. The student’s t-test was applied for statistical analysis of the obtained data. Results. Moderate intoxication development in a subchronic experiment is demonstrated. Homogeneous ultrastructural changes in the spleen tissue were revealed. Mitochondrial damage with partial or complete loss of crista is the most common. The fragmentation ratio of DNA was found by a statistically significant increase. A single intratracheal injection of zinc oxide nanoparticles revealed the increase in the attraction of cells capable of their phagocytosis (mainly neutrophils) into the low respiratory tract. This shows their cytotoxicity. Conclusion. Moderate general toxic and cytotoxic effects of zinc oxide nanoparticles on the rat body were identified. © 2021 Izdatel'stvo Meditsina. All rights reserved
The Multiplicity of Main Sequence Turnoffs in Globular Clusters
We present color-magnitude diagrams of globular clusters for models with
self-enrichment and pre-enrichment. The models with self-enrichment turn out to
have two or more main sequence turnoff points in the color-magnitude diagram if
the fraction of mass lost by the globular cluster under supernova explosions
does not exceed 95-97%. The models with pre-enrichment can have only one main
sequence turnoff point. We argue that the cluster wCen evolved according to a
self-enrichment scenario.Comment: 13 pages, 7 figure
Benzothiazinones kill Mycobacterium tuberculosis by blocking arabinan synthesis
New drugs are required to counter the tuberculosis (TB) pandemic. Here, we describe the synthesis and characterization of 1,3-benzothiazin-4-ones (BTZs), a new class of antimycobacterial agents that kill Mycobacterium tuberculosis in vitro, ex vivo, and in mouse models of TB. Using genetics and biochemistry, we identified the enzyme decaprenylphosphoryl-beta-d-ribose 2'-epimerase as a major BTZ target. Inhibition of this enzymatic activity abolishes the formation of decaprenylphosphoryl arabinose, a key precursor that is required for the synthesis of the cell-wall arabinans, thus provoking cell lysis and bacterial death. The most advanced compound, BTZ043, is a candidate for inclusion in combination therapies for both drug-sensitive and extensively drug-resistant TB
Анализ эффективности фотодинамического отбеливания зубов с использованием фотосенсибилизатора хлорин е6
Teeth whitening is one of the most sought-after procedures in aesthetic dentistry. Discolorites that are difficult to whiten, caused by dentin changes or enamel defects, can be eliminated by oxidizing the chromogens with chemical agents that penetrate to the enamel and dentin. In recent years, the method of photodynamic bleaching (PDB) is considered to be minimally invasive. It does not use hydrogen peroxide that leads to increased sensitivity of teeth, and is relatively effective over time. A convenient solution for PDB would be to use chlorin e6 as a photosensitizer, which has a high quantum yield of singlet oxygen generation, low phototoxicity, rapid elimination, on the one hand, and photobleaching capability, on the other. This paper presents quantitative data on the study of the effectiveness of PDB with chlorine e6: color change for 100 teeth after the procedure, chlorine e6 penetration into the tooth tissues, evaluation of the interstitial efficiency of the generation of singlet oxygen and photobleaching of chlorine e6 during laser exposure. It has been statistically established that for one PDB procedure, the tooth color saturation (C) varies on average by 0.5 tones on the VITA scale, and the lightness of color (L) in some cases increases by more than 10 units.Отбеливание зубов является одной из самых востребованных процедур в эстетической стоматологии. Трудно поддающиеся отбеливанию дисколориты, вызванные изменениями дентина или дефектами эмали, могут быть устранены путем окисления хромогенов с помощью химических агентов, проникающих в эмаль и дентин. В последние годы фотодинамическое отбеливание зубов (ФДОЗ) рассматривается как минимально инвазивный и относительно эффективный по времени метод, при котором не используется перекись водорода, применение которой приводит к повышенной чувствительности зубов. Для ФДОЗ может использоваться фотосенсибилизатор (ФС) хлорин е6, обладающий высоким квантовым выходом генерации синглетного кислорода, низкой фототоксичностью, быстрым выведением, с одной стороны, и способностью к фотообесцвечиванию, с другой. В настоящей работе представлены количественные данные исследования эффективности ФДОЗ с хлорином е6: изменение цвета для 100 зубов после процедуры, оценка проникновения ФС в ткани зуба, оценка внутритканевой эффективности генерации синглетного кислорода и интенсивности фотообесцвечивания ФС при лазерном воздействии. Статистически установлено, что за одну процедуру ФДОЗ насыщенность цвета зубов (С) изменяется в среднем на 0,5 тона по шкале VITA, а светлота цвета (L) в отдельных случаях повышается более чем на 10 единиц
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