Laser-induced generation of singlet oxygen and its role in the cerebrovascular physiology

For over 55 years, laser technology has expanded from laboratory research to widespread fields, for example telecommunication and data storage amongst others. Recently application of lasers in biology and medicine presents itself as one of the emerging areas. In this review, we will outline the recent advances in using lasers for the generation of singlet oxygen, traditionally used to kill tumour cells or induce thrombotic stroke model due to damage vascular effects. Over the last two decade, completely new results on cerebrovascular effects of singlet oxygen generated during photodynamic therapy (PDT) have been shown alongside promising applications for delivery of drugs and nanoparticles into the brain for therapy of brain cancer. Furthermore, a "gold key” has been found to overcome the limitations of PDT, such as low light penetration and high toxicity of photosensitizers, by direct generation of singlet oxygen using quantum-dot laser diodes emitting in the near infrared (NIR) spectral range. It is our motivation to highlight these pioneering results in this review, to improve understanding of the biological role of singlet oxygen and to provide new perspectives for improving clinical application of laser based therapy in further research

Multimodal optical diagnostics of the microhaemodynamics in upper and lower limbs

The introduction of optical non-invasive diagnostic methods into clinical practice can substantially advance in the detection of early microcirculatory disorders in patients with different diseases. This paper is devoted to the development and application of the optical non-invasive diagnostic approach for the detection and evaluation of the severity of microcirculatory and metabolic disorders in rheumatic diseases and diabetes mellitus. The proposed methods include the joint use of laser Doppler flowmetry, absorption spectroscopy and fluorescence spectroscopy in combination with functional tests. This technique showed the high diagnostic importance for the detection of disturbances in peripheral microhaemodynamics. These methods have been successfully tested as additional diagnostic techniques in the field of rheumatology and endocrinology. The sensitivity and specificity of the proposed diagnostic procedures have been evaluated.<br/

HYDROGEN-INDUCED POLYMORPHYSM OF METALS AND HYDROGEN TREATMENT OF METALLIC MATERIALS

There are described classification of phase transformations induced with hydrogen and represented achievements of ‘hydrogen treatment of materials. technologies.Рассмотрена классификация фазовых превращений, индуцированных водородом в металлах, и представлены достижения технологий водородной обработки материалов

The influence of German legal doctrine on the formation of the principle of good faith in the civil law of the Russian Federation

The article discusses the formation of the principle of good faith in Russian civil law, influenced by German legal doctrine. It gives the main characteristics of the principle of good faith, adopted by Russian law-enforcement practice and theory from German doctrine. The paper draws the conclusion about the need for a deep understanding of the principle in order to prevent its application contrary to the objectives of this principl

METALS POLYMORPHYSM AS A SCIENTIFIC BASIS OF THE “IRON AGE” OF HUMAN CIVILIZATION AFTER CHERNOV

The outstanding discovery of the great Russian scientist and engineer D. K. Chernov predetermined the division of the “Iron Age” into two epochs “BEFORE CHERNOV” and “AFTER CHERNOV”. Discovered by Chernov polymorphism of steels allowed the development of new technologies for processing metal materials. Hydrogen treatment makes possible to improve the properties of non.polymorphic metals.Выдающееся открытие великого русского ученого и инженера Д. К. Чернова предопределило деление «века железа» на две эпохи «ДО ЧЕРНОВА» и «ПОСЛЕ ЧЕРНОВА». Открытый Черновым полиморфизм сталей позволил разработать новые технологии обработки металлических материалов. Водородная обработка позволяет улучшать свойства неполиморфных металлов

Mutational re-modeling of di-aspartyl intramembrane proteases: uncoupling physiologically-relevant activities from those associated with Alzheimer\u27s disease

The intramembrane proteolytic activities of presenilins (PSEN1/PS1 and PSEN2/PS2) underlie production of beta-amyloid, the key process in Alzheimer\u27s disease (AD). Dysregulation of presenilin-mediated signaling is linked to cancers. Inhibition of the gamma-cleavage activities of PSENs that produce Abeta, but not the epsilon-like cleavage activity that release physiologically essential transcription activators, is a potential approach for the development of rational therapies for AD. In order to identify whether different activities of PSEN1 can be dissociated, we designed multiple mutations in the evolutionary conserved sites of PSEN1. We tested them in vitro and in vivo assays and compared their activities with mutant isoforms of presenilin-related intramembrane di-aspartyl protease (IMPAS1 (IMP1)/signal peptide peptidase (SPP)). PSEN1 auto-cleavage was more resistant to the mutation remodeling than the epsilon-like proteolysis. PSEN1 with a G382A or a P433A mutation in evolutionary invariant sites retains functionally important APP epsilon- and Notch S3- cleavage activities, but G382A inhibits APP gamma-cleavage and Abeta production and a P433A elevates Abeta. The G382A variant cannot restore the normal cellular ER Ca(2+) leak in PSEN1/PSEN2 double knockout cells, but efficiently rescues the loss-of-function (Egl) phenotype of presenilin in C. elegans. We found that, unlike in PSEN1 knockout cells, endoplasmic reticulum (ER) Ca(2+) leak is not changed in the absence of IMP1/SPP. IMP1/SPP with the analogous mutations retained efficiency in cleavage of transmembrane substrates and rescued the lethality of Ce-imp-2 knockouts. In summary, our data show that mutations near the active catalytic sites of intramembrane di-aspartyl proteases have different consequences on proteolytic and signaling functions

Whole exome sequencing links dental tumor to an autosomal-dominant mutation in ANO5 gene associated with gnathodiaphyseal dysplasia and muscle dystrophies

Tumors of the jaws may represent different human disorders and frequently associate with pathologic bone fractures. In this report, we analyzed two affected siblings from a family of Russian origin, with a history of dental tumors of the jaws, in correspondence to original clinical diagnosis of cementoma consistent with gigantiform cementoma (GC, OMIM: 137575). Whole exome sequencing revealed the heterozygous missense mutation c.1067G \u3e A (p.Cys356Tyr) in ANO5 gene in these patients. To date, autosomal-dominant mutations have been described in the ANO5 gene for gnathodiaphyseal dysplasia (GDD, OMIM: 166260), and multiple recessive mutations have been described in the gene for muscle dystrophies (OMIM: 613319, 611307); the same amino acid (Cys) at the position 356 is mutated in GDD. These genetic data and similar clinical phenotypes demonstrate that the GC and GDD likely represent the same type of bone pathology. Our data illustrate the significance of mutations in single amino-acid position for particular bone tissue pathology. Modifying role of genetic variations in another gene on the severity of the monogenic trait pathology is also suggested. Finally, we propose the model explaining the tissue-specific manifestation of clinically distant bone and muscle diseases linked to mutations in one gene

Multimodal Optical Diagnostics of the Microhaemodynamics in Upper and Lower Limbs

The introduction of optical non-invasive diagnostic methods into clinical practice can substantially advance in the detection of early microcirculatory disorders in patients with different diseases. This paper is devoted to the development and application of the optical non-invasive diagnostic approach for the detection and evaluation of the severity of microcirculatory and metabolic disorders in rheumatic diseases and diabetes mellitus. The proposed methods include the joint use of laser Doppler flowmetry, absorption spectroscopy and fluorescence spectroscopy in combination with functional tests. This technique showed the high diagnostic importance for the detection of disturbances in peripheral microhaemodynamics. These methods have been successfully tested as additional diagnostic techniques in the field of rheumatology and endocrinology. The sensitivity and specificity of the proposed diagnostic procedures have been evaluated

Mathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms

Cancer cells depend on transcription of telomerase reverse transcriptase (TERT). Many transcription factors affect TERT, though regulation occurs in context of a broader network. Network effects on telomerase regulation have not been investigated, though deeper understanding of TERT transcription requires a systems view. However, control over individual interactions in complex networks is not easily achievable. Mathematical modelling provides an attractive approach for analysis of complex systems and some models may prove useful in systems pharmacology approaches to drug discovery. In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their respective promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analysed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR analysis of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3′-oxime (BIO) predicted unstable TERT repression dependent on noise and expression of JUN, corresponding with observations from a previous study. MYC expression is critical in TERT activation in the model, consistent with its well known function in endogenous TERT regulation. Loss of MYC caused complete TERT suppression in our model, substantially rescued only by co-suppression of AR. Interestingly expression was easily rescued under modelled Ets-factor gain of function, as occurs in TERT promoter mutation. RNAi targeting AR, JUN, MXD1, SP3, or TP53, showed that AR suppression does rescue endogenous TERT expression following MYC knockdown in these cells and SP3 or TP53 siRNA also cause partial recovery. The model therefore successfully predicted several aspects of TERT regulation including previously unknown mechanisms. An extrapolation suggests that a dominant stimulatory system may programme TERT for transcriptional stability