Original research Analysis of phenotype expressions of deletions in the dystrophin gene in terms of efficiency of exon skipping as a method for treatment of hereditary dystrophinopathies
Zotova ED, Reshetov DA, Zhernovkov VE, Vlodavets DV, Dimitrieva TV, Deykin AV
Duchenne muscular dystrophy (DMD) is a common genetic disease caused by a mutation of the dystrophin gene. It leads to death in childhood. At the time of writing this paper, patients had access to supportive therapy only. However, DMD treatment methods are actively being developed. Exon skipping is a promising method. Exon skipping involves restoration of the reading frame within a gene by inducing alternative splicing. This leads to synthesis of truncated but still functional dystrophin. The paper assesses the functionality of the truncated forms of dystrophin resulting from correction of nonsense mutations and internal exon indels by exon-skipping technique. The assessment was made based on data on the phenotype of carriers of mutations in the dystrophin gene taken from the Leiden Open Variation Database (LOVD). It was revealed that the same mutation could manifest itself as a variety of phenotypes. This, perhaps, is as a result of the patients having different genetic background. For example, deletion of exon 48, for which there is 97 records in LOVD, resulted in asymptomatic diseases in 2 % of cases, Duchenne muscular dystrophy in 60 %, Becker muscular dystrophy (characterized by milder symptoms than DMD) in 12 % and intermediate phenotype in 26 % of cases. High phenotypic variability of mutations of the dystrophin gene raises the issue of limits of applying exon skipping for treatment of inherited myopathies.
Received: 2016-06-17
Published online: 2017-01-05
DOI: 10.24075/brsmu.2016-03-03
Comments 1
VIEWS 5735
Method Gadolinium- and curcumin-loaded micelles based on α-fetoprotein functionalized amphiphilic block copolymers
Pozdniakova NV, Grigorieva EYu, Shevelev AB
This article describes a method of obtaining curcumin- and gadolinium-loaded micelles based on triblock amphiphilic polyethylene glycol and polypropylene glycol copolymers Pluronic F-127 and Pluronic P-123 (Sigma-Aldrich, USA) superficially functionalized with recombinant human -fetoprotein. The size of nanoparticles was measured using dynamic light scattering and amounted to an average of 50 to 100 nm. The micelles were stable: stored at +4 °С for 10 days, they exhibited no changes in their properties that would not fall within the standard error of measurement for the methods used for the analysis. Preliminary in vivo experiments conducted on mice showed no conspicuous toxicity of micelles with the maximum possible concentration of gadolinium, which enables their use in tumor tissue imaging in vivo.
Received: 2016-06-23
Published online: 2017-01-05
DOI: 10.24075/brsmu.2016-03-04
Comments 0
VIEWS 5385
Original research Studying the ability to control human phantom fingers in P300 brain-computer interface
Kaplan AYa, Zhigulskaya DD, Kiriyanov DA
In this work we have tested the assumption that an individual can control a target finger of a phantom by voluntarily focusing his attention on the luminous marker located on that finger in the complex of a P300 wave–based brain-computer interface (P300 BCI) and an anthropomorphic phantom. Because each correct movement of phantom fingers indicates a sufficient mental effort aimed at this action, creating a new ideomotor training simulator of smaller movements of the hand becomes possible. Our study included 21 volunteer subjects of both sexes aged 18–25. It was shown that with P300 BCI complex the subjects learned to control phantom fingers on the first day of the experiment, the percentage of successful attempts being no less than 69 %. Failures were mainly related to the insufficient attention focus on luminous markers on the target phantom fingers. We hypothesize that P300 BCI — Hand Phantom complex can be a basis for developing a fine motor skills simulator.
Received: 2016-04-11
Published online: 2017-01-05
DOI: 10.24075/brsmu.2016-02-03
Comments 0
VIEWS 4838
Original research Two HMG domains of yeast mitochondrial protein Abf2p have different affinity to DNA
Kurashenko AV, Samoilova EO, Balaeva MV, Chicherin IV, Petrov DYu, Kamenski P, Levitskii SA
Maintaining mitochondrial genome integrity is essential for the viability of the whole organism. Mitochondrial genome mutations lead to muscular dystrophies, neurodegenerative diseases, and are associated with aging. In this work a baker’s yeast (Saccharomyces cerevisiae) mitochondria model was used to investigate DNA-binding abilities of different domains of a mitochondrial Abf2p protein which participates in homologous recombination and reparation. A weak non-specific HMG1 binding to linear DNA and a specific HMG1 binding to a branched DNA with a dissociation constant of 510 nM have been discovered. The HMG2 domain itself does not bind to any DNA and either has other functions or demonstrates its DNA-binding activity in a full-length protein only.
Received: 2015-09-29
Published online: 2017-01-05
DOI: 10.24075/brsmu.2016-01-11
Comments 0
VIEWS 4944
Original research Stability of gadolinium-based contrast agents in the presence of zinc and calcium ions in different media
Kharlamov VG, Kulakov VN, Lipengolts AA, Shimanovskii NL
To improve the safety of Gd3<sup>+</sup>-based contrast agents (GBCA) in clinical practice, it is recommended to use the most stable substances and to consider conditions determining their stability. The aim of this study was to compare the stability of GBCAs for magnetic resonance imaging in the presence of zinc and calcium ions and polyvinylpyrrolidone (PVP) in water, phosphate buffer solution and blood serum using proton NMR relaxometry. The study demonstrated that macrocyclic gadobutrol is more stable than all linear contrast agents. The addition of PVP (10 mg/ml) improved the stability of linear GBCAs in phosphate buffer solution and blood serum. Calcium ions have a much weaker destabilizing effect on GBCAs than zinc ions.
Received: 2015-09-29
Published online: 2017-01-05
DOI: 10.24075/brsmu.2016-01-12
Comments 0
VIEWS 4493
Opinion Approaches to improving tuberculosis care in HIV-infected patients and criteria for its evaluation
Frolova OP, Schukina IV, Novoselova OA, Stakhanov VA, Kazennyi AB
Despite various anti-tuberculosis measures in the setting of HIV infection, the epidemiological situation of tuberculosis in Russia is deteriorating. We have analyzed the data of statistical report form no. 61 for years 2004–2014, surveillance data on individual TB cases with HIV coinfection for years 2004–2014 (personal data) and TB care arrangements for patients with HIV in 20 regions. The main causes of the deteriorating epidemiological situation are the growing immunodeficiency in patients with TB coinfection, unseparated epidemiologically dangerous patient flows (patients with tuberculosis and HIV-infected patients) and low quality preventative measures in special care medical facilities. Chemoprophylaxis can be an effective method of controlling the spread of tuberculosis among HIV-infected patients if it is recommended by a qualified tuberculosis therapist to patients adhering to regular drug intake under supervision of medical personnel. Otherwise a large scale chemoprophylaxis can result in an increased proportion of patients with drug-resistant tuberculosis. This works suggests criteria for the evaluation of tuberculosis care effectiveness considering the pathogenesis of the disease during late stages of HIV.
Received: 2015-12-06
Published online: 2017-01-05
DOI: 10.24075/brsmu.2016-01-13
Comments 0
VIEWS 4566
Review Comparative analysis of modern approaches to the performance assessment of scientific medical organizations in Russia and abroad
Aniskevich AS, Halfin RA, Tatarinova LV
The article reviews basic methods of performance assessment of scientific medical organizations in Russia. Qualitative and quantitative effectiveness criteria are provided. International practices are described; a comparative analysis of assessment methods used in Russia and abroad is carried out. Global trends in the development of approaches to analyzing the effectiveness of scientific organizations are reviewed. Based on our analysis, a compelling rationale for developing more up-to-date criteria for evaluating the performance of scientific medical organizations is given.
Received: 2016-02-20
Published online: 2017-01-05
DOI: 10.24075/brsmu.2016-01-14
Comments 0
VIEWS 4745
Review Brain-computer interface: the future in the present
Levitskaya OS, Lebedev MA
Brain-computer interfaces (BCIs) are a promising technology intended for the treatment of diseases and trauma of the nervous system. BCIs establish a direct connection between the brain areas that remain functional and assistive devices, such as powered prostheses and orthoses for the arms and legs, motorized wheelchairs, artificial sensory organs and other technologies for restoration of motor and sensory functions. BCIs of various kinds are currently developing very rapidly, aided by the progress in computer science, robotic applications, neurophysiological techniques for recording brain activity and mathematical methods for decoding neural information. BCIs are often classified as motor BCIs (the ones that reproduce movements), sensory BCIs (the ones that evoke sensations), sensorimotor BCIs (the ones that simultaneously handle motor and sensory functions), and cognitive BCIs intended to regulate the higher brain functions. All these BCI classes can be either invasive (i. e. penetrating the body and/or the brain) or noninvasive (i.e. making no o little contact with the body surface). Noninvasive BCI are safe to use and easy to implement, but they suffer from signal attenuation by scalp and skin, its contamination with noise and artifacts, and an overall low information transfer rate. Invasive BCIs are potentially more powerful because they utilize implanted grids that can both record neural signals in high-resolution and apply stimulation to the nervous tissue locally to deliver information back to the brain. BCI technologies are being developed not only for individual use, but also for collective tasks performed by multiple interconnected brains.
Received: 2016-03-11
Published online: 2017-01-05
DOI: 10.24075/brsmu.2016-02-01
Comments 0
VIEWS 5320