Subjective method of refractometry and depth of focus

AbstractPurposeTo study the impact of the depth of focus on subjective refraction and distribution of myopic and hyperopic refractions.MethodsA total of 450 eyes of 305 subjects in the age range of 23–34 years were recruited for the study. A distribution of refractions was examined using a traditional method of the subjective refractometry on the basis of point-like posterior focus notion. Correction of the results was made on the assumption that the emmetropic eye retains high visual acuity when applying convex lenses with values which are fewer or equal to the depth of focus values. The following values of the depth of focus were used: ±0.55D, ±0.35D and ±0.2D for visual acuity 1.0, 1.5 and 2.0, respectively.ResultsApplication of the traditional method of refractometry produced the following occurrence of refractions: hypermetropia 59.3%, myopia 22% and emmetropia 18.7%. After correction of the initial results of values of the depth of focus the distribution of refractions was as follows: hypermetropia 12.7%, myopia 22% and emmetropia 65.3%.ConclusionThe traditional method of subjective refractometry with application of trial lenses was developed on the basis of data of large optical aberrations and significant depth of focus which values should be taken into account during interpretation of results of subjective refractometry. Our data regarding to prevalence of emmetropic refraction falls in line with basic science provisions in respect of the physiology of the eye

Influence of social-economic institutions on innovative environment development: Russian case study

One of the important questions for innovative environment development is social-economic institutions, which help to decrease transaction cost and risks in small and medium size enterprises (SMEs). Basic institutional framework is represented by a set of specific institutions, which form the innovation environment of the region and have an impact on the activities of the innovation system actors. The proposed set of institutions is divided into two groups: those institutions that directly affect the development of innovative environment and institutions, which influence is indirect, but nevertheless important. The result of analysis of institutions development of Tomsk region and five more innovation-oriented areas of the Russian Federation is given in the article

Influence of social-economic institutions on innovative environment development: Russian case study

One of the important questions for innovative environment development is social-economic institutions, which help to decrease transaction cost and risks in small and medium size enterprises (SMEs). Basic institutional framework is represented by a set of specific institutions, which form the innovation environment of the region and have an impact on the activities of the innovation system actors. The proposed set of institutions is divided into two groups: those institutions that directly affect the development of innovative environment and institutions, which influence is indirect, but nevertheless important. The result of analysis of institutions development of Tomsk region and five more innovation-oriented areas of the Russian Federation is given in the article

Physical and chemical processes and the morphofunctional characteristics of human erythrocytes in hyperglycaemia

Background: This study examines the effect of graduated hyperglycaemia on the state and oxygen-binding ability of hemoglobin, the correlation of phospholipid fractions and their metabolites in the membrane, the activity of proteolytic enzymes and the morphofunctional state of erythrocytes. Methods: Conformational changes in the molecule of hemoglobin were determined by Raman spectroscopy. The structure of the erythrocytes was analyzed using laser interference microscopy (LIM). To determine the activity of NADN-methemoglobinreductase, we used the P.G. Board method. The degree of glycosylation of the erythrocyte membranes was determined using a method previously described by Felkoren et al. Lipid extraction was performed using the Bligh and Dyer method. Detection of the phospholipids was performed using V. E. Vaskovsky method. Results: Conditions of hyperglycaemia are characterized by a low affinity of hemoglobin to oxygen, which is manifested as a parallel decrease in the content of hemoglobin oxyform and the growth of deoxyform, methemoglobin and membrane-bound hemoglobin. The degree of glycosylation of membrane proteins and hemoglobin is high. For example, in the case of hyperglycaemia, erythrocytic membranes reduce the content of all phospholipid fractions with a simultaneous increase in lysoforms, free fatty acids and the diacylglycerol (DAG). Step wise hyperglycaemia in incubation medium and human erythrocytes results in an increased content of peptide components and general trypsin-like activity in the cytosol, with a simultaneous decreased activity of µ-calpain and caspase 3. Conclusions: Metabolic disorders and damage of cell membranes during hyperglycaemia cause an increase in the population of echinocytes and spherocytes. The resulting disorders are accompanied with a high probability of intravascular haemolysis.</p

Functional Analysis of DNMT3A DNA Methyltransferase Mutations Reported in Patients with Acute Myeloid Leukemia

In mammals, DNA methylation is necessary for the maintenance of genomic stability, gene expression regulation, and other processes. During malignant diseases progression, changes in both DNA methylation patterns and DNA methyltransferase (MTase) genes are observed. Human de novo MTase DNMT3A is most frequently mutated in acute myeloid leukemia (AML) with a striking prevalence of R882H mutation, which has been extensively studied. Here, we investigate the functional role of the missense mutations (S714C, R635W, R736H, R771L, P777R, and F752V) found in the catalytic domain of DNMT3A in AML patients. These were accordingly mutated in the murine Dnmt3a catalytic domain (S124C, R45W, R146H, R181L, P187R, and F162V) and in addition, one-site CpG-containing DNA substrates were used as a model system. The 3-15-fold decrease (S124C and P187R) or complete loss (F162V, R45W, and R146H) of Dnmt3a-CD methylation activity was observed. Remarkably, Pro 187 and Arg 146 are not located at or near the Dnmt3a functional motives. Regulatory protein Dnmt3L did not enhance the methylation activity of R45W, R146H, P187R, and F162V mutants. The key steps of the Dnmt3a-mediated methylation mechanism, including DNA binding and transient covalent intermediate formation, were examined. There was a complete loss of DNA-binding affinity for R45W located in the AdoMet binding region and for R146H. Dnmt3a mutants studied in vitro suggest functional impairment of DNMT3A during pathogenesis

The effect of experimental hyperoxia on erythrocytes’ oxygen-transport function

The aim of this study was to investigate the effect of hyperoxia, calcium ions and pH value on the composition of major phospholipids in human erythrocyte membranes and erythrocytes’ oxygen-transport function. To create a model of hyperoxia, we saturated the incubated mixture with oxygen by constant passing of oxygen–air mixture through the incubation medium. To assess the effect of elevated calcium ion concentrations, CaCl2 was added to the incubation medium. An incubation medium with different pH was used to study the effect of various pH values. Lipids were extracted from erythrocytes and chromatographic separation was carried out in a thin layer of silica gel deposited on a glass plate. The thiobarbituric acid (TBA)-active products and the content of diene conjugates (DC) in erythrocytes were determined. The oxygen-binding capacity of haemoglobin was evaluated using Raman spectroscopy. The obtained results indicated that hyperoxia causes deep changes both in the composition and character of bilayer lipids of erythrocyte membranes, which affects the functional characteristics of erythrocytes, primarily the oxygen-transport properties of erythrocyte haemoglobin. It should be noted that a combination of Ca2+ ions and change in the pH value intensify the processes associated with disruption of phospholipids’ composition. The findings indicate that the lipid phase is one of the key elements in the functioning of erythrocytes in norm as well as during development of various pathological processes

Pannexin 1 regulates skeletal muscle regeneration by promoting bleb-based myoblast migration and fusion through a novel lipid based signaling mechanism

Adult skeletal muscle has robust regenerative capabilities due to the presence of a resident stem cell population called satellite cells. Muscle injury leads to these normally quiescent cells becoming molecularly and metabolically activated and embarking on a program of proliferation, migration, differentiation, and fusion culminating in the repair of damaged tissue. These processes are highly coordinated by paracrine signaling events that drive cytoskeletal rearrangement and cell-cell communication. Pannexins are a family of transmembrane channel proteins that mediate paracrine signaling by ATP release. It is known that Pannexin1 (Panx1) is expressed in skeletal muscle, however, the role of Panx1 during skeletal muscle development and regeneration remains poorly understood. Here we show that Panx1 is expressed on the surface of myoblasts and its expression is rapidly increased upon induction of differentiation and that Panx1-/- mice exhibit impaired muscle regeneration after injury. Panx1-/- myoblasts activate the myogenic differentiation program normally, but display marked deficits in migration and fusion. Mechanistically, we show that Panx1 activates P2 class purinergic receptors, which in turn mediate a lipid signaling cascade in myoblasts. This signaling induces bleb�driven amoeboid movement that in turn supports myoblast migration and fusion. Finally, we show that Panx1 is involved in the regulation of cell-matrix interaction through the induction of ADAMTS (Disintegrin-like and Metalloprotease domain with Thrombospondin-type 5) proteins that help remodel the extracellular matrix. These studies reveal a novel role for lipid-based signaling pathways activated by Panx1 in the coordination of myoblast activities essential for skeletal muscle regeneration

Lacrimal Gland Repair Using Progenitor Cells

Abstract In humans, the lacrimal gland (LG) is the primary contributor to the aqueous layer of the tear film. Production of tears in insufficient quantity or of inadequate quality may lead to aqueous‐deficiency dry eye (ADDE). Currently there is no cure for ADDE. The development of strategies to reliably isolate LG stem/progenitor cells from the LG tissue brings great promise for the design of cell replacement therapies for patients with ADDE. We analyzed the therapeutic potential of epithelial progenitor cells (EPCPs) isolated from adult wild‐type mouse LGs by transplanting them into the LGs of TSP ‐1−/− mice, which represent a novel mouse model for ADDE. TSP‐1−/− mice are normal at birth but progressively develop a chronic form of ocular surface disease, characterized by deterioration, inflammation, and secretory dysfunction of the lacrimal gland. Our study shows that, among c‐kit‐positive epithelial cell adhesion molecule (EpCAM+) populations sorted from mouse LGs, the c‐kit+dim/EpCAM+/Sca1−/CD34−/CD45− cells have the hallmarks of an epithelial cell progenitor population. Isolated EPCPs express pluripotency factors and markers of the epithelial cell lineage Runx1 and EpCAM, and they form acini and ducts when grown in reaggregated three‐dimensional cultures. Moreover, when transplanted into injured or “diseased” LGs, they engraft into acinar and ductal compartments. EPCP‐injected TSP‐1−/− LGs showed reduction of cell infiltration, differentiation of the donor EPCPs within secretory acini, and substantial improvement in LG structural integrity and function. This study provides the first evidence for the effective use of adult EPCP cell transplantation to rescue LG dysfunction in a model system. Stem Cells Translational Medicine 2017;6:88–9

Molecular Mechanisms of Neuromuscular Decline in Spinal and Bulbar Muscular Atrophy

Spinal and Bulbar Muscular Atrophy (SBMA) is a rare neuromuscular disorder caused by a CAG repeat expansion mutation in first exon of the Androgen Receptor (AR) gene. The mutant protein is thus referred to as polyQ-AR. AR’s natural ligand, testosterone, is required for polyQ-AR to cause neuromuscular decline, thus only men are clinically affected. Historically, SBMA has been considered a motor neuron disease, but recent works from our group and others implicate skeletal muscle as a primary site of pathogenicity caused by polyQ-AR. Given that AR is a potent facilitator of skeletal muscle hypertrophy, but polyQ-AR causes progressive muscle atrophy starting in the third of fourth decade of life despite normal male development, the differences between AR and polyQ-AR molecular activity in skeletal muscle are particularly intriguing and remain elusive. Moreover, we have previously shown that polyQ-AR expression in skeletal muscle of SBMA mice is required for motor neuron pathology, which suggests a skeletal muscle-driven mechanism for motor neuron degeneration in SBMA. The neuromuscular junction (NMJ), which is a large and highly specialized synapse between motor neurons and skeletal muscle, is likely the main site of pathogenicity driving this non-cell autonomous motor neuron demise. This dissertation first provides an overview of SBMA and a published review on what is currently known about NMJ involvement in motor neuron disease. Next, I present findings in aged muscle rescued SBMA mice that develop latent phenotypes that are highly relevant to SBMA patients but have not previously been explored in animal models. In parallel, I show that motor neuron rescued SBMA mice do not experience any notable attenuation of neuromuscular decline, definitively highlighting the central role of polyQ-AR expression in skeletal muscle in driving neuromuscular decline in SBMA. Lastly, transcriptome analysis and metabolic profiling of pre-symptomatic SBMA mice provides important clues as to how polyQ-AR could initiate muscle pathology at the molecular level. Taken together, this dissertation reinforces the timely and important paradigm shift in the field toward investigating skeletal muscle, not motor neurons, as therapeutic targets in SBMA and prompts the reclassification of this repeat expansion disorder as a neuromuscular disease or even a primary myopath