Electrophysiological Correlates of Major Depression Disorder with Anxious Distress in Patients of Different Age Groups

The electrophysiological correlates of major depression disorder with anxious distress in patients of different age groups have been investigated. The spectral characteristics of 19-channel background EEG were analyzed and the power spectra recorded with the eyes closed vs. eyes open in 64 patients with anxiety–depressive disorder and in 194 healthy subjects were compared. The subjects were divided into the two age groups: 18–39 and 40–76 years old. The spectral parameters were calculated for 5 main EEG frequency bands: θ (4–8 Hz), α (8–12 Hz), β₁ (12–20 Hz), β₂ (20–30 Hz), and γ (30–40 Hz). The most statistically significant differences between the groups were found in the α, β, and γ bands. Lower values of spectral power of the α rhythm in occipital areas and the higher values of spectral power of the β and γ rhythms in the frontocentral region were recorded in the group of 18-to-39-year-old patients with the eyes closed. Higher values of spectral power of the β rhythm in the fronto-central region and in the left temporal lobe were recorded in the group of 40-to-76-year-old patients with both the eyes closed and the eyes open. The higher β-activity in the fronto-central regions in both groups of patients may be caused by increased excitability of the cerebral cortex and decreased activity of inhibitory processes. Increased activation of the left temporal lobe in older subjects is probably associated with the severity of anxiety symptoms and may be a distinctive marker of mixed anxiety and depressive disorder. The lower values of α-power revealed only in the group of younger subjects are probably associated with age-related reorganization of EEG in older subjects.     

Quantitative and ultrastructural analysis of the chondriome in ovogenesis and embryogenesis of the sea urchin Paracentrotus lividus.

The dynamics of chondriome in the ovogenesis of the sea urchin Paracentrotus lividus was studied. Growing oocytes 20-30, 50-60 and 90-100 microm in diameter ("small", "medium-sized" and "large", respectively) and mature eggs were used for the ultrastructural and stereological analysis of mitochondria. Linear parameters of mitochondria (length and thickness) were measured on 3-D reconstructions of serial ultrathin sections using the software developed in the laboratory. The following transformations of chondriome structure were shown to occur during ovogenesis: (1) the number of mitochondria (MT) increases with the growth of cytoplasmic compartment; (2) the modal length of MT increases from 0.5 microm in small oocytes to 1 microm in large ones and decreases again to 0.5 microm in the egg; this process is accompanied by changes in the relative number of spherical MT which decreases in medium-sized oocytes and subsequently rises again in the egg; (3) in medium-sized oocytes, dumbbell-shaped MT appear first, the number of these MT reaching the maximum to the stage of large oocytes. In mature eggs, the dumb-bell-shaped MT are absent; (4) in small and medium-sized oocytes, the orthodox conformation of MT is observed, in contrast to MT with a condensed matrix in large oocytes and eggs; (5) in mature eggs, mitochondrial clusters containing 10 to 20 MT of various size are formed. Based on the data obtained, we suggested that during ovogenesis of the sea urchin, specific differentiation of the chondriome is induced which leads to the increase in the quantity of MT via multiple division acts, while restricting the MT growth and variability of their shape.     

Sarcoglycanopathies: Clinical,Molecular and Genetic Characteristics,Epidemiology, Diagnostics and Treatment Options

Sarcoglycanopathies are a group of autosomal recessive limb-girdle muscular dystrophies (LGMD) caused by mutations in sarcoglycan genes: SGCA (LGMD 2D, MIM 600119), SGCB (LGMD 2E, MIM 604286), SGCG (LGMD 2C, MIM 353700), and SGCD (LGMD 2F, MIM 601287). These genes encode four transmembrane sarcoglycan subunits participating in formation of the large sarcolemmal dystrophin- glycoprotein complex. Clinical symptoms of sarcoglycanopathies resemble the ones in Duchenne/Becker muscular dystrophy and several autosomal recessive LGMD, which causes difficulties in the differential diagnostics between these diseases. This review covers the main aspects of sarcoglycanopathies, such as etiology, spectrum of mutations, clinical features and diagnostics. In addition, we review the fundamental pathogenesis mechanisms leading to sarcoglycanopathies, which can also help to understand the potential options for treatment for patients with muscular dystrophies.     

Mutation spectrum of the <Emphasis Type="Italic">PAH</Emphasis> gene in phenylketonuria patients in the Karachay-Cherkess Republic (Russia)

A comprehensive population and medical-genetic study was carried out in ten districts and two cities in the Karachay-Cherkess Republic (Russia). As a result, 57 patients with phenylketonuria were revealed. PAH gene genotypes for 40 probands and their diseased and healthy relatives were determined. The mutation spectrum of the PAH gene in the Karachay-Cherkess Republic was investigated. The major mutation in this region is R261X with allelic frequency of 68.4%. We elaborated a convenient system for detection of six PAH gene mutations common in the Karachay-Cherkess Republic, with the total information content of the system being 89.9%. As a result of processing the clinical data, association of the diet and phenylalanine levels in the blood was verified. Genophenotypic analysis confirms the association of the residual activity of phenylalanine hydroxylase and the severity of the disease. It is shown that common mutation R261X is severe and that patients who are homozygous for this mutation have classical phenylketonuria (PKU).     

Key role of barstar Cys-40 residue in the mechanism of heat denaturation of bacterial ribonuclease complexes with barstar

The mechanism by which barnase and binase are stabilized in their complexes with barstar and the role of the Cys-40 residue of barstar in that stabilization have been investigated by scanning microcalorimetry. Melting of ribonuclease complexes with barstar and its Cys-82-Ala mutant is described by two 2-state transitions. The lower-temperature one corresponds to barstar denaturation and the higher-temperature transition to ribonuclease melting. The barstar mutation Cys-40-Ala, which is within the principal barnase-binding region of barstar, simplifies the melting to a single 2-state transition. The presence of residue Cys-40 in barstar results in additional stabilization of ribonuclease in the complex.     

Carotenoids as scavengers of free radicals in a Fenton reaction: antioxidants or pro-oxidants?

The spin trapping EPR technique was used to study the influence of carotenoids (beta-carotene, 8'-apo-beta-caroten-8'-al, canthaxanthin, and ethyl 8'-apo-beta-caroten-8'-oate) on the yield of free radicals in the Fenton reaction (Fe(2+) + H(2)O(2) --> Fe(3+) + .OH + -OH) in the organic solvents, DMSO, and methanol. DMPO and PBN were used as spin trapping agents. It was demonstrated that carotenoids could increase or decrease the total yield of free radicals depending on the oxidation potential of the carotenoids and the nature of the radicals. A reaction mechanism is suggested which includes the reduction of Fe(3+) to Fe(2+) by carotenoids. The effectiveness of this carotenoid-driven Fenton reaction increases with a decrease of the scavenging rates for free radicals and with decreasing oxidation potentials of carotenoids.     

Changes in a late positive component of evoked potentials in the <Emphasis Type="Italic">GO/NOGO</Emphasis> test after cryocingulotomy

The influence of cingulotomy on the components of brain evoked potentials detected by a modified GO/NOGO paradigm was investigated. Patients with a diagnosis of heroin dependence (13 subjects) participated in the study. For medical indications, patients were treated with stereotaxic anterior cryocingulotomy in order to reduce the compulsive need that makes the drug dependence intractable. A two-stimulus modification of the GO/NOGO paradigm developed in our laboratory was used in this study. Cingulotomy did not change significantly the early (in the 100-to 200-ms range) components evoked by visual or auditory stimuli. The positive component evoked by the GO stimuli also did not change. This component corresponds to the P3b component observed in the ODD BALL paradigm. The only component that changed after the anterior cingulotomy was a late component generated by the NOGO stimuli in the 400-ms range, which was distributed in the medial frontocentral area. Thus, we have obtained a direct confirmation of the relationship between this component and the activity of the anterior cingulate gyrus. Analysis of the individual evoked potentials allows us to conclude that the suggested modification of the GO/NOGO test and methods for correcting artifacts in the statistical analysis of differences may be regarded as a reliable approach to the assessment of the functional activity of the anterior cingulate gyrus in humans.     

Substrate specificity of Escherichia coli thymidine phosphorylase

Substrate specificity of Escherichia coli thymidine phosphorylase to thymidine derivatives modified at 5' -, 3' -, and 2' ,3' - positions of the sugar moiety was studied. Equilibrium and kinetic constants (K(m), K(I), k(cat)) of the phosphorolysis reaction have been determined for 20 thymidine analogs. The results are compared with X-ray and molecular dynamics data. The most important hydrogen bonds in the enzyme-substrate complex are revealed.     

Hydrogel microchip as a tool for studying exosomes in human serum

Exosomes are cell-derived vesicles that are secreted by both normal and cancer cells. Over the last decade, a few studies have revealed that exosomes cross talk and/or influence major tumor-related pathways such as angiogenesis and metastasis involving many cell types within the tumor microenvironment. The protein composition of the membrane of an exosome reflects that of the membrane of the cell of origin. Because of this, tumor-derived exosomes differ from exosomes that are derived from normal cells. The detection of tumor exosomes and analysis of their molecular composition hold promise for diagnosis and prognosis of cancer. Here, we present hydrogel microarrays (biochips), which contain a panel of immobilized antibodies that recognize tetraspanins (CD9, CD63, CD81) and prognostic markers for colorectal cancer (A33, CD147). These biochips make it possible to analyze the surface proteins of either isolated exosomes or exosomes that are present in the serum samples without isolation. These biochips were successfully used to analyze the surface proteins of exosomes from serum that was collected from a colorectal cancer patient and healthy donor. Biochip-guided immunofluorescent analysis of the exosomes has made it possible for us to detect the A33 antigen and CD147 in the serum sample of the colorectal cancer patient with normal levels of CEA and CA19-9.