Diversity and Prevalence of Hereditary Diseases among Nogais of the Karachay-Cherkess Republic

The diversity and prevalence of hereditary diseases (HDs) among Nogais of the Karachay-Cherkess Republic (KChR) are described. The size of the surveyed KChR population was 387231 individuals, including 3.81% Nogais (14741 individuals). We revealed 36 nosological forms of HDs (110 patients from 81 families): 22 with autosomal dominant (AD) inheritance, 10 with autosomal recessive (AR) inheritance, and 4 with X-linked inheritance. The prevalence of HDs in Nogais was 1: 134. The features of HD diversity in Nogais were determined in comparison with the previously surveyed populations of Russia. The accumulation of Ehlers–Danlos syndrome (1: 388), AD amelogenesis imperfecta (1: 3685), AD ichthyosis (1: 4914), AR nonsyndromic mental retardation (1: 1340), AR Gilbert syndrome (1: 4914), and X-linked inherited deficit of glucose-6-dehydrogenase (1: 1774 males) was established. The analysis of heterozygous carriage of mutations “major” for Russia in the genes of the four following AR diseases in 118 unrelated clinically healthy Nogais (236 analyzed chromosomes) was performed: cystic fibrosis (13 mutations in the CFTR gene: CFTRdele2,3 (21 kb), F508del, I507del, 1677delTA, 2184insA, 2143delT, 2183AA>G, 2184delA, 394delTT, 3821delT, L138ins, E92K, W1282X); phenylketonuria (six frequent mutations in the PAH gene: R261X, R408W, R413P, F331S, P211T, P211L); nonsyndromic sensorineural hearing loss (35delG mutation in the GJB2 gene); and Gilbert syndrome (an increase in the number of TA repeats in the UGT1A1 gene). Allelic specificity for all studied genes in the Nogai people was revealed.     

Carotenoids as antioxidants: spin trapping EPR and optical study.

The role of several natural and synthetic carotenoids as scavengers of free radicals was studied in homogeneous solutions. A set of free radicals: *OH, *OOH, and *CH(3) were generated by using the Fenton reaction in dimethyl sulfoxide. It was shown that the spin trapping technique is more informative than optical methods for the experimental conditions under study. 5,5-Dimethyl-pyrroline-N-oxide (DMPO) and N-tert-butyl-alpha-phenylnitrone (PBN) were used as spin traps for the EPR studies. The results show that the scavenging ability of the carotenoids towards radical *OOH correlates with their redox properties.     

Structural–functional characteristics of brachiocephalic vessels in hypertensive patients under changed atmospheric pressure

The ultrasonic location technique was used to measure the intima-media thickness (IMT) as well as the internal systolic diameter of and the linear blood velocity (LBV) in the cervical arteries in subjects with initial stages of hypertension. Correlation analysis elicited a temporal contingency between these parameters and daily average values of atmospheric pressure. Thus, the common carotid artery IMT tended to increase on high-pressure days. In addition, diameters of the common and internal carotid arteries and vertebral artery were narrowed and, consequently, LBV in these vessels increased. This relationship is more evident in men than women and in elderly subjects than young. These results are suggestive of a vasoconstrictive effect of high atmospheric pressure on these arteries. The relationship is not universal, as it is nonlinear for the diameter of the internal carotid artery and inverse for the external one. This implies different sensitivity of arteries to the factor under study and possible blood redistribution in the arterial tree depending on external pressure. The relationship was observed equally on the day of investigation and previous days, which points to its temporal stability.     

Pond smelt <Emphasis Type="Italic">Hypomesus olidus</Emphasis>, a new species of the ichthyofauna of the Commander Islands

The population of pond smelt Hypomesus olidus has been registered for the first time in the water bodies of Bering Island (Commander Islands). The spawning of this species has been observed in the Sarannoe Lake system, and the maturing breeders have been caught in the freshwater-brackish Gavanskoe Lake system. The spawning grounds, the spawning period, the environment, and the morphology of the breeders have been described. The ratio of Ca and Sr isotopes in the otoliths of the pond smelt inhabiting the Sarannoe Lake system evidenced that this species here was presented by the resident ecotype. The problem of the smelt phylogeny and resettlement in the northern Pacific Ocean is discussed.     

Perichromosomal layer proteins associate with chromosome scaffold and nuclear matrix throughout the cell cycle

According to the radial loop model of chromosome organization, a major role in the formation and maintenance of chromosomes is played by the residual structures (the nuclear matrix in interphase nuclei and the chromosome scaffold in metaphase chromosomes). However, in vivo microscopy has recently revealed that the components of these “static” structures are highly mobile and continuously exchanged between specific target sites and the nucleoplasm or cytoplasm. This contradiction between predicted stability and observed dynamics led us to reexamine the principles underlying the association of proteins with residual structures. In the present paper, we have analyzed the association of two perichromosomal layer proteins, pKi-67 and B23, with the residual structures. The results show that these two proteins are associated with residual structures throughout the cell cycle; only those structures change that contain proteins precipitated by 2 M NaCl (nucleoli, perichromosomal layer, prenucleolar bodies, cytoplasm of mitotic cells). Both pKi-67 and B23 remain associated with the nuclear matrix even when they are translocated to nucleoplasmic foci due to inhibitor action or hypotonic treatment. However, in most cases it remains possible to extract a structurally visible protein fraction with 2 M NaCl (protein distributed in nucleoplasm). One may suppose that the protein fraction associated with residual structures includes molecules interacting with their binding sites at the moment of permeabilization, while the free proteins are extracted (i.e., during the interaction with binding sites, these proteins form salt-resistant complexes; however, on diffusion the same proteins are extractable by the high-salt solution). The residual structures may be considered as a “snapshot” of all proteins transiently (or statically) bound to their target sites at the moment of permeabilization. The article is published in the original.     

Self-organization of endoplasmic reticulum aggregates in cells with overexpression of nucleoporin POM121

The nuclear pore complexes are complex protein structures located in the nuclear envelope, where they control the nuclear-cytoplasmic transport, and inside the stacks of endoplasmic reticulum cisternae, annulate lamellae. After overexpression of some nucleoporins, numerous granules are visible in the cytoplasm. According to the published data, these granules are the annulate lamellae. In the current paper, the structural organization of POM121-containing granules was analyzed using correlative light and electron microscopy. The ultrastructural study demonstrates that POM121-containing granules are not annulate lamellae but aggregates of endoplasmic reticulum membranes. Thus, overexpressed POM121 is not able to induce the annulate lamella formation. The mechanisms of self-organization of non-functional structures (such as the aggregates of endoplasmic reticulum membranes described here) and possible involvement of these mechanisms in the formation of cellular structures are discussed.     

Proteomic analysis of mitochondria from the Bos taurus heart. II. Identification of mitochondrial soluble proteins

A fraction of the so-called mitochondrial soluble proteins was obtained after the destruction of purified mitochondria by sonication according to the previously found approach to the identification of protein subsets of the Bos taurus heart proteome. A tryptic destruction of these proteins was achieved. Approximately half of the tryptic hydrolysate was separated into two fractions of cysteine-containing and cysteine-free peptides by covalent chromatography on Thiopropyl Sepharose 4B. The cysteine-containing peptides were modified by iodoacetamide. The peptides were mass-spectrometrically identified in all the three fractions of tryptic hydrolysate, and the proteins were searched for in the amino acid sequence databases. There were 213 unique proteins reliably identified.     

The spectrum of mutations in the <Emphasis Type="Italic">PAH</Emphasis> gene in patients with hyperphenylalaninemia from the Karachay-Cherkess Republic

According to the neonatal screening conducted during the last nine years in Karachay-Cherkessia, the frequency of hyperphenylalaninemia (including PKU) was 1: 850 newborns, which significantly exceeded the average frequency of 1: 7000 in Russia. Analysis of DNA obtained from 25 patients with a diagnosis of “hyperphenylalaninemia” (HPA) from the Karachay-Cherkess Republic was performed to search for mutations in the PAH gene. Mutations were identified on 90% of the studied chromosomes, while at least one mutation in the PAH gene was observed in all patients. The allele frequency of a major mutation R261X was 32.5%. A correlation between genotype and phenotype was confirmed in patients with HPA.     

Geneticl and clinical characteristics of 22q11.2 deletion syndrome

In a group of 140 patients with typical phenotype, the 22q11.2 microdeletion was detected in 43 patients (32%) using FISH and MLPA methods. There were no deletions of other chromosomal loci causing to phenotypes similar to the 22q11.2 deletion syndrome (22q11.2DS). Sequencing of the TBX1 gene did not detect any mutations, except for some common neutral polymorphisms. For the first time in the Russian Federation, the diagnostic efficiency of 22q11.2DS appeared to be 32%, as a result of the application of a combination of genetic approaches for a large group of patients with suspected 22q11.2DS.