Modulating membrane shape and mechanics of minimal cells by light: area increase, softening and interleaflet coupling of membrane models doped with azobenzene-lipid photoswitches

Light can effectively interrogate biological systems providing control over complex cellular processes. Particularly advantageous features of photo-induced processes are reversibility, physiological compatibility, and spatiotemporal precision. Understanding the underlying biophysics of light-triggered changes in bio-systems is crucial for cell viability and optimizing clinical applications of photo-induced processes in biotechnology, optogenetics and photopharmacology. Employing membranes doped with the photolipid azobenzene-phosphatidylcholine (azo-PC), we provide a holistic picture of light-triggered changes in membrane morphology, mechanics and dynamics. We combine microscopy of giant vesicles as minimal cell models, Langmuir monolayers, and molecular dynamics simulations. We employ giant vesicle elelctrodeformation as a facile and accurate approach to quantify the magnitude, reversibility and kinetics of light-induced area expansion/shrinkage as a result of azo-PC photoisomerization and content. Area increase as high as ~25% and a 10-fold decrease in the membrane bending rigidity is observed upon trans-to-cis azo-PC isomerization. These results are in excellent agreement with simulations data and monolayers. Simulations also show that trans-to-cis isomerization of azo-PC decreases the membrane leaflet coupling. We demonstrate that light can be used to finely manipulate the shape and mechanics of photolipid-doped minimal cell models and liposomal drug carriers, thus, presenting a promising therapeutic alternative for the repair of cellular disorders.Competing Interest StatementThe authors have declared no competing interest

Luminescence and radiation defects in irradiated ruby

The excitations of luminescence in irradiated and non-irradiated ruby crystals are investigated by means of highly polarized synchrotron radiation. In the VUV luminescence spectra the existence of quick and slow emission was observed in irradiated and nonirradiated crystals. The luminescence bands with maximum at 3.8 eV are produced by F+ centers. A new type of quick luminescence was established for the band at 4.6 eV. It is called cross-luminescence and is connected with the recombination of valence band electrons with holes in low-lying core levels. It is shown that the band at 3.0 eV is not due to anionic centers (F-centers), but is determined by a short lifetime emission center

Test Educational Materials in Pdf Format Development for Interactive Learning

Рассмотрен автоматизированный способ формирования интерактивных заданий с применением системы LuaLaTeX для самостоятельной проработки и закрепления материала обучающимися. Предлагаемый подход позволяет синтезировать задания, отличающиеся порядком вопросов и вариантов ответов из заданного перечня для одного исходного документа. Результат работы может быть применен в различных системах управления обучением.Forming interactive tasks automated method using the LuaLaTeX system for independent study and material consolidation by students is considered. The proposed approach allows you to synthesize tasks that differ in the questions and answers order from a given list from one source document. The result of the work can be applied in various learning management systems

Heart myxoma under the mask of interstitial lung lesion: a difficult case from practice

The aim of the investigation was to describe a clinical case of the development of interstitial lung lesions in a 57-year-old man with a large left atrial myxoma, which had a reverse development after myxomectomy.Materials and methods. Patient V., 57 years old, was hospitalized in the therapeutic department of the City Clinical Hospital No. 1 named after N. I. Pirogov in connection with bilateral polysegmental pneumonia. A month before hospitalization, he underwent an outpatient examination for progressive dyspnea. Myxoma of the heart was diagnosed. Due to the progression of respiratory failure and the appearance of fever, he was hospitalized. Amidst the multistage antibiotic therapy, there was a torpid course of lung pathology with syndromes of bilateral dissemination and “ground glass”, bilateral lymphadenopathy of the mediastinum, high pulmonary hypertension, and systemic inflammatory reaction syndrome. Thromboembolism of the branches of the pulmonary artery, tuberculosis, sepsis, infective endocarditis, neoplastic processes of pulmonary and other localization were excluded.Results. The clinical picture corresponded to interstitial lung lesions within the framework of paraneoplastic syndrome in heart myxoma. It was decided to urgently carry out myxomectomy.Conclusion. The clinical case demonstrates the development of a rare variant of paraneoplastic syndrome in left atrial myxoma, which was suspected during the patient’s treatment for bilateral polysegmental pneumonia. The progression of the pulmonary lesion was explained by active interstitial inflammation and was supported by the immunological activity of the heart tumor.The performed myxomectomy, despite the persisting syndrome of systemic inflammatory reaction and infiltration of the lung tissue, led in 2 weeks to complete resolution of interstitial lung lesions and pulmonary hypertension, which confirmed the causal relationship between myxoma of the heart and involvement in the pathological process of the lungs

Characteristics of insulin therapy of diabetes mellitus type 1 in children and adolescents receiving glucocorticoids

BACKGROUND: In coexistence of diabetes mellitus type 1 (DM1) with severe autoimmune and inflammatory diseases some patients need simultaneous administration of insulin and glucocorticoids (GC). GC therapy in patients with DM1 can worsen glycemic control. AIM: To determine characteristics of insulin therapy of DM1 in children and adolescents receiving GC. DESCRIPTION OF CLINICAL CASES: We observed 5 patients with DM1 receiving GC for juvenile idiopathic arthritis (JIA), juvenile systemic sclerosis (JSS), juvenile dermatomyositis (JDM), ulcerative colitis (UC), and reactive arthritis (RA). Intra-articular administration of GC did not significantly influence glycemic control. In case of GC pulse therapy hyperglycemia and increased insulin requirements were recognized in 3–6 hours after GC receipt, persisted from few hours up to 3 days after each administration. While therapy with oral GC in high doses the worst glycemic control was registered in daylight hours. To overcome insulin resistance change of time of injection and 10%-increase of long-acting insulin analogue, additional injections of ultrashort-acting insulin analogues, temporal prescription of short-acting human insulin were used. While GC therapy insulin daily dose was individual and could reach 2.0 U/kg. After transition to maintaining doses of GC or discontinuation of GC therapy patients returned to standard or relatively low insulin requirements. Levels of glycosylated hemoglobin differed significantly among patients at different stages of treatment, were maximal while long-term therapy with high doses of oral GC, but mostly depended on patient’s compliance. CONCLUSION: Bettering of glycemic control while receiving GC can be reached by timely dose correction of insulin therapy, selection of individual schemes, taking into account time of receipt and pharmacokinetic characteristics of GC. Adherence of the patient and his family to treatment of DM1 plays an important role in glycemic control

Интерферон-γ и опухолевый рост

Purpose of the study: to analyze published data on the mechanisms of action of interferon gamma (IFN-γ) in tumor growth and to evaluate the possibility of its use in the treatment of solid tumors. Material and Methods. More than 200 publications were found in the Scopus, Pubmed, eLibrary and other databases, the search keywords were: interferon gamma, tumor growth, cancer therapy. This review includes 54 papers. Results. IFN-γ is a pleiotropic cytokine with antiviral, antitumor, and immunomodulatory functions and plays an important role in coordinating the innate and adaptive immune response. The success of immuno-oncology drugs and chemotherapy in the treatment of malignant tumors depends on the stimulation of the production and adequate signaling of IFN-γ. Suppression and loss of IFN-γ receptor and downstream signaling mediators, and amplifcation of molecules that inhibit the IFN-γ signaling pathway are common mechanisms for tumor cells to escape from the immune system. The development of malignant processes is accompanied by a change, more often a decrease, in the secretion of IFN-γ, which attracts the attention of researchers to its exogenous administration. Determination of the IFN-γ signature may be a predictive marker of clinical response to anticancer drug therapy. The antitumor properties of IFN-γ are largely dose-dependent, which has been clearly shown in clinical and experimental studies. Low doses of the drug often promote tumor growth. On the contrary, the use of high doses is usually accompanied by an antitumor effect. IFN-γ or its inducers remain promising agents for cancer therapy. Combinatorial strategies involving IFN-γ may be a rational option to overcome tumor resistance to blockade of immune checkpoints. Conclusion. It is necessary to continue fundamental and applied research to study the feasibility of using interferon gamma as a therapeutic agent in tumor growth.Цель исследования – проанализировать опубликованные данные о механизмах действия интерферона гамма (IFN-γ) при опухолевом росте и оценить возможности его применения для лечения солидных опухолей. Материал и методы. По теме найдено более 200 зарубежных и российских публикаций, представленных в базах данных Scopus, Pubmed, eLibrary и других; ключевые слова поиска: интерферон гамма, опухолевый рост, терапия рака. В данный обзор включено 54 работы. Результаты. IFN-γ – плейотропный цитокин, обладающий противовирусной, противоопухолевой и иммуномодулирующей функциями и играющий важную роль в координации врожденного и адаптивного иммунного ответа. Успешность применения в лечении злокачественных опухолей иммуноонкологических препаратов и химиотерапии зависит, в том числе, от стимулирования выработки и адекватной передачи сигналов IFN-γ. Подавление и потеря рецептора IFN-γ и нижестоящих сигнальных медиаторов, амплификация молекул, ингибирующих сигнальный путь IFN-γ, являются обычными механизмами ускользания опухолевых клеток от иммунной системы. Развитие злокачественных процессов сопровождается изменением (чаще снижением), секреции IFN-γ, что привлекает внимание исследователей к его экзогенному введению. Определение сигнатуры IFN-γ может являться прогностическим маркером клинического ответа на противоопухолевую лекарственную терапию. Противоопухолевые свойства IFN-γ во многом дозозависимы, что наглядно показано в клинических и экспериментальных исследованиях. Низкие дозы препарата чаще способствуют росту опухоли, напротив, использование высоких доз обычно сопровождается противоопухолевым действием. IFN-γ или его индукторы остаются многообещающими агентами для терапии злокачественных новообразований. Комбинаторные стратегии с включением IFN-γ могут быть рациональным вариантом для преодоления резистентности опухолей к блокаде иммунных контрольных точек. Заключение. Необходимо продолжать фундаментальные и прикладные исследования по изучению возможностей применения интерферона гамма в качестве лечебного агента при опухолевом росте

Measurements of KL Branching Fractions and the CP Violation Parameter |eta+-|

We present new measurements of the six largest branching fractions of the KL using data collected in 1997 by the KTeV experiment (E832) at Fermilab. The results are B(KL -> pi e nu) = 0.4067 +- 0.0011 B(KL -> pi mu nu) = 0.2701 +- 0.0009 B(KL -> pi+ pi- pi0) = 0.1252 +- 0.0007 B(KL -> pi0 pi0 pi0) = 0.1945 +- 0.0018 B(KL -> pi+ pi-) = (1.975 +- 0.012)E-3, and B(KL -> pi0 pi0) = (0.865 +- 0.010)E-3, where statistical and systematic errors have been summed in quadrature. We also determine the CP violation parameter |eta+-| to be (2.228 +- 0.010)E-3. Several of these results are not in good agreement with averages of previous measurements.Comment: Submitted to Phys. Rev. D; 20 pages, 22 figure

Realization of reproductive function in patients with polycystic ovary syndrome

The aim of the study – present a clinical case of the realization of reproductive function in a patient with PCOS against the background of conservative treatmentЦель исследования – представление клинического случая реализации репродуктивной функции у пациентки с СПЯ на фоне консервативного лечения

A clinical case of a combination of Spina bifida, Arnold-Chiari anomaly and multiple congenital malformations in a child

The purpose of the study - presentation of a clinical case of a combination of Spina bifida and Arnold-Chiari type 2 anomaly.Цель исследования. Представление клинического случая сочетания Spina bifida и аномалии Арнольда-Киари 2 типа

Think globally, measure locally: The MIREN standardized protocol for monitoring plant species distributions along elevation gradients

Climate change and other global change drivers threaten plant diversity in mountains worldwide. A widely documented response to such environmental modifications is for plant species to change their elevational ranges. Range shifts are often idiosyncratic and difficult to generalize, partly due to variation in sampling methods. There is thus a need for a standardized monitoring strategy that can be applied across mountain regions to assess distribution changes and community turnover of native and non-native plant species over space and time. Here, we present a conceptually intuitive and standardized protocol developed by the Mountain Invasion Research Network (MIREN) to systematically quantify global patterns of native and non-native species distributions along elevation gradients and shifts arising from interactive effects of climate change and human disturbance. Usually repeated every five years, surveys consist of 20 sample sites located at equal elevation increments along three replicate roads per sampling region. At each site, three plots extend from the side of a mountain road into surrounding natural vegetation. The protocol has been successfully used in 18 regions worldwide from 2007 to present. Analyses of one point in time already generated some salient results, and revealed region-specific elevational patterns of native plant species richness, but a globally consistent elevational decline in non-native species richness. Non-native plants were also more abundant directly adjacent to road edges, suggesting that disturbed roadsides serve as a vector for invasions into mountains. From the upcoming analyses of time series, even more exciting results can be expected, especially about range shifts. Implementing the protocol in more mountain regions globally would help to generate a more complete picture of how global change alters species distributions. This would inform conservation policy in mountain ecosystems, where some conservation policies remain poorly implemented