Technology for Creation and Detailed Analysis of Polymer Composites with Uniform Distribution of Quantum Dots and Liquid Crystals

One of the most actual tasks in biotechnology is the creation of a new generation of nanobiosensors with improved brightness, photo stability, and sensitivity. Compositions of polymers and colloidal quantum dots (QDs) are the most promising base to develop such sensors. This work presents the technology for creation and detailed analysis of nanostructured composite films based on polypropylene matrices with uniformly distributed CdSe/ZnS quantum dots and liquid crystals. Methods of optical microscopy, scanning probe microscopy and confocal fluorescen tmicrospectroscopy were used. The presence of liquid crystals in the composite allows additional control of QDs fluorescence. The methodology proposed is applicable not only to polypropylene, but also to other porous polymers. The results of this work indicate the possibility of creating high-quality polymer/QDs composite materials and open the way to the development of nanomaterials (nanosensors) with optical properties sensitive to various environmental parameters (electric field, photo irradiation, mechanical action, etc.). Keywords: quantum dot-polymer composites, nanoporous polypropylene, fluorescenc

The Effect of Focusing and Caustics on Exit Phenomena in Systems Lacking Detailed Balance

We study the trajectories followed by a particle subjected to weak noise when escaping from the domain of attraction of a stable fixed point. If detailed balance is absent, a _focus_ may occur along the most probable exit path, leading to a breakdown of symmetry (if present). The exit trajectory bifurcates, and the exit location distribution may become `skewed' (non-Gaussian). The weak-noise asymptotics of the mean escape time are strongly affected. Our methods extend to the study of skewed exit location distributions in stochastic models without symmetry.Comment: REVTEX macros (latest version). Two accompanying PS figures, one of which is large (over 600K unpacked

Structural insights into thrombolytic activity of destabilase from medicinal leech

Destabilase from the medical leech Hirudo medicinalis belongs to the family of i-type lysozymes. It has two different enzymatic activities: microbial cell walls destruction (muramidase activity), and dissolution of the stabilized fibrin (isopeptidase activity). Both activities are known to be inhibited by sodium chloride at near physiological concentrations, but the structural basis remains unknown. Here we present two crystal structures of destabilase, including a 1.1 Å-resolution structure in complex with sodium ion. Our structures reveal the location of sodium ion between Glu34/Asp46 residues, which were previously recognized as a glycosidase active site. While sodium coordination with these amino acids may explain inhibition of the muramidase activity, its influence on previously suggested Ser49/Lys58 isopeptidase activity dyad is unclear. We revise the Ser49/Lys58 hypothesis and compare sequences of i-type lysozymes with confirmed destabilase activity. We suggest that the general base for the isopeptidase activity is His112 rather than Lys58. pKa calculations of these amino acids, assessed through the 1 μs molecular dynamics simulation, confirm the hypothesis. Our findings highlight the ambiguity of destabilase catalytic residues identification and build foundations for further research of structure–activity relationship of isopeptidase activity as well as structure-based protein design for potential anticoagulant drug development.</p

Manifestation of Huntington's disease pathology in human induced pluripotent stem cell-derived neurons

© 2016 Nekrasov et al.Background: Huntington's disease (HD) is an incurable hereditary neurodegenerative disorder, which manifests itself as a loss of GABAergic medium spiny (GABA MS) neurons in the striatum and caused by an expansion of the CAG repeat in exon 1 of the huntingtin gene. There is no cure for HD, existing pharmaceutical can only relieve its symptoms. Results: Here, induced pluripotent stem cells were established from patients with low CAG repeat expansion in the huntingtin gene, and were then efficiently differentiated into GABA MS-like neurons (GMSLNs) under defined culture conditions. The generated HD GMSLNs recapitulated disease pathology in vitro, as evidenced by mutant huntingtin protein aggregation, increased number of lysosomes/autophagosomes, nuclear indentations, and enhanced neuronal death during cell aging. Moreover, store-operated channel (SOC) currents were detected in the differentiated neurons, and enhanced calcium entry was reproducibly demonstrated in all HD GMSLNs genotypes. Additionally, the quinazoline derivative, EVP4593, reduced the number of lysosomes/autophagosomes and SOC currents in HD GMSLNs and exerted neuroprotective effects during cell aging. Conclusions: Our data is the first to demonstrate the direct link of nuclear morphology and SOC calcium deregulation to mutant huntingtin protein expression in iPSCs-derived neurons with disease-mimetic hallmarks, providing a valuable tool for identification of candidate anti-HD drugs. Our experiments demonstrated that EVP4593 may be a promising anti-HD drug

КЛИНИКО-ЭПИДЕМИОЛОГИЧЕСКАЯ ХАРАКТЕРИСТИКА КОРИ У ВЗРОСЛЫХ ЖИТЕЛЕЙ АЛТАЙСКОГО КРАЯ

The aim of the study is to determine the clinical and epidemiological features of measles in the Altai territory. Materials and methods: a retrospective analysis of 92 medical histories of inpatient patients with a confirmed diagnosis of «Measles» at the age of 17 to 54 years, who were treated in the Infectious Departments of City Hospitals № 5 and №11 in Barnaul in 2015–2018, was made. Results: the epidemic situation of measles in the Altai territory is characterized by an increase of morbidity rate in 2015, as well as isolated cases in 2017–2018. The peculiarity of the outbreak of the disease was in-hospital infection of patients upon admission to medical hospitals and late diagnosis of measles, as well as the importation of infection from adjacent territories (regions of Russia and the Republic of Kazakhstan), which is confirmed by genotyping of the virus in patients. The development of the disease in 23,9% of those,who were vaccinated, was routinely observed in the age group older than 30 years. In the clinical picture of measles at the present stage, along with the classical manifestations, in 15.2% of patients in the first days of the disease gastroenteritis was marked, in 40,2% of patients the signs of hepatitis (cytolysis syndrome) were observed. Conclusion: the prevalence among the patientspersons, older than 30 years, may indicate the extinction of post-vaccination immunity. Timely immunization against measles in adulthood (after 30 years), will increase the effectiveness of measures to implement the program of elimination of measles in the Altai territory. The development of gastroenteritis up to the 5 days of the disease (on average 2,5±0.9 days), hepatitis in the period of height of the disease (in 15,2% and 40,2% of patients, respectively), determined the erroneous diagnosis of «Enterovirus infection», pseudotuberculosis, etc. and deserved the attention of practitioners.Цель: определить клинико-эпидемиологические особенности кори у взрослых на территории Алтайского края. Материалы и методы: проведен ретроспективный анализ 92 медицинских карт стационарного больного пациентов с подтвержденным диагнозом «Корь» в возрасте от 17 до 54 лет, находившихся на лечении в инфекционных отделениях КГБУЗГБ № 5 и № 11 г. Барнаула в 2015–2018 гг. Результаты: эпидемическая ситуация по кори в Алтайском крае характеризуется подъемом заболеваемости в 2015 г., а также единичными случаями в 2017– 2018 гг. Эпидемиологическими особенностями явились завоз инфекции из сопредельных территорий и из-за рубежа (Республики Казахстан, Турции, Мальдивских островов), несвоевременное установление диагноза кори при поступлении в медицинское учреждение и, как следствие, внутрибольничное инфицирование. Завозной характер инфекции подтвержден генотипированием вируса у заболевших. Развитие заболевания у 23,9% вакцинированных в плановом порядке наблюдалось в возрастной группе старше 30 лет. В клинической картине кори на современном этапе, наряду с классическими проявлениями, у 15,2% пациентов в первые дни болезни отмечены явления гастроэнтерита, у 40,2% заболевших – признаки гепатита (синдром цитолиза). Заключение: преобладание среди больных лиц старше 30 лет может свидетельствовать об угасании постпрививочного иммунитета. Дополнительное проведение иммунизации против кори в зрелом возрасте (после 30 лет) повысит эффективность мероприятий по реализации программы элиминации кори на территории Алтайского края. Развитие синдрома гастроэнтерита до 5-го дня болезни (в среднем на 2,5±0,9 сутки), гепатита в периоде разгара (у 15,2% и 40,2% больных соответственно) определяло постановку ошибочного диагноза «Энтеровирусная инфекция», «Псевдотуберкулез» и т.д. и заслуживает внимания практикующих врачей