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11.
Alexander Y. Сhurbanov Tatiana M. Karafet Igor V. Morozov Valeriia Yu. Mikhalskaia Marina V. Zytsar Alexander A. Bondar Olga L. Posukh 《PloS one》2016,11(4)
Hearing loss (HL) is one of the most common sensorineural disorders and several dozen genes contribute to its pathogenesis. Establishing a genetic diagnosis of HL is of great importance for clinical evaluation of deaf patients and for estimating recurrence risks for their families. Efforts to identify genes responsible for HL have been challenged by high genetic heterogeneity and different ethnic-specific prevalence of inherited deafness. Here we present the utility of whole exome sequencing (WES) for identifying candidate causal variants for previously unexplained nonsyndromic HL of seven patients from four unrelated Altaian families (the Altai Republic, South Siberia). The WES analysis revealed homozygous missense mutations in three genes associated with HL. Mutation c.2168A>G (SLC26A4) was found in one family, a novel mutation c.1111G>C (OTOF) was revealed in another family, and mutation c.5254G>A (RAI1) was found in two families. Sanger sequencing was applied for screening of identified variants in an ethnically diverse cohort of other patients with HL (n = 116) and in Altaian controls (n = 120). Identified variants were found only in patients of Altaian ethnicity (n = 93). Several lines of evidences support the association of homozygosity for discovered variants c.5254G>A (RAI1), c.1111C>G (OTOF), and c.2168A>G (SLC26A4) with HL in Altaian patients. Local prevalence of identified variants implies possible founder effect in significant number of HL cases in indigenous population of the Altai region. Notably, this is the first reported instance of patients with RAI1 missense mutation whose HL is not accompanied by specific traits typical for Smith-Magenis syndrome. Presumed association of RAI1 gene variant c.5254G>A with isolated HL needs to be proved by further experimental studies. 相似文献
12.
Morozov I. A. Kamenetskikh A. S. Beliaev A. Yu. Scherban M. G. Lemkina L. M. Eroshenko D. V. Korobov V. P. 《Biophysics》2019,64(3):410-415
Biophysics - Abstract—Elastic polyurethanes are flexible materials used in biomedical products. Plasma treatment is a promising method of surface modification. However, external deformation... 相似文献
13.
Epitope mapping of the major capsid protein of type 2 porcine circovirus (PCV2) by using chimeric PCV1 and PCV2 总被引:13,自引:0,他引:13 下载免费PDF全文
Lekcharoensuk P Morozov I Paul PS Thangthumniyom N Wajjawalku W Meng XJ 《Journal of virology》2004,78(15):8135-8145
Type 2 porcine circovirus (PCV2) is associated with postweaning multisystemic wasting syndrome in pigs, whereas the genetically related type 1 PCV (PCV1) is nonpathogenic. In this study, seven monoclonal antibodies (MAbs) against PCV2-ORF2 capsid protein were generated, biologically characterized, and subsequently used to map the antigenic sites of PCV2 capsid protein by using infectious PCV DNA clones containing PCV1/PCV2-ORF2 chimeras. The PCV1/PCV2-ORF2 chimeras were constructed by serial deletions of PCV2-ORF2 and replacement with the corresponding sequences of the PCV1-ORF2. The reactivities of chimeric PCV1/PCV2 clones in transfected PK-15 cells with the seven MAbs were detected by an immunofluorescence assay (IFA). The chimera (r140) with a deletion of 47 amino acids at the N terminus of PCV2-ORF2 reacted strongly to all seven MAbs. Expanding the deletion of PCV2-ORF2 from residues 47 to 57 (r175) abolished the recognition of MAb 3B7, 3C11, 4A10, 6H2, or 8F6 to the chimera. Further deletion of PCV2-ORF2 to 62 residues disrupted the binding of this chimera to all seven MAbs. IFA reactivities with all MAbs were absent when residues 165 to 233 at the C terminus of PCV2-ORF2 was replaced with that of PCV1-ORF2. Extending the sequence of PCV2-ORF2 from residues 165 (r464) to 185 (r526), 200 (r588), or 224 (r652) restored the ability of the three chimeras to react with MAbs 3C11, 6H2, 9H7, and 12G3 but not with 8F6, 3B7, or 4A10. When the four amino acids at the C terminus of r588 were replaced with that of PCV2-ORF2, the resulting chimera (r588F) reacted with all seven MAbs. The results from this study suggest that these seven MAbs recognized at least five different but overlapping conformational epitopes within residues 47 to 63 and 165 to 200 and the last four amino acids at the C terminus of the PCV2 capsid protein. 相似文献
14.
Biological control has been attracting an increasing attention over the last two decades as an environmentally friendly alternative
to the more traditional chemical-based control. In this paper, we address robustness of the biological control strategy with
respect to fluctuations in the controlling species density. Specifically, we consider a pest being kept under control by its
predator. The predator response is assumed to be of Holling type III, which makes the system’s kinetics “excitable.” The system
is studied by means of mathematical modeling and extensive numerical simulations. We show that the system response to perturbations
in the predator density can be completely different in spatial and non-spatial systems. In the nonspatial system, an overcritical
perturbation of the population density results in a pest outbreak that will eventually decay with time, which can be regarded
as a success of the biological control strategy. However, in the spatial system, a similar perturbation can drive the system
into a self-sustained regime of spatiotemporal pattern formation with a high pest density, which is clearly a biological control
failure. We then identify the parameter range where the biological control can still be successful and describe the corresponding
regime of the system dynamics. Finally, we identify the main scenarios of the system response to the population density perturbations
and reveal the corresponding structure of the parameter space of the system.
A. Morozov is on leave from Shirshov Institute of Oceanology, Russian Academy of Science, Nakhimovsky Prosp. 36, Moscow 117218,
Russia. 相似文献
15.
Pierson T Matrakas D Taylor YU Manyam G Morozov VN Zhou W van Hoek ML 《Journal of proteome research》2011,10(3):954-967
We have isolated and characterized outer membrane vesicles (OMVs) from Francisella. Transport of effector molecules through secretion systems is a major mechanism by which Francisella tularensis alters the extracellular proteome and interacts with the host during infection. Outer membrane vesicles produced by Francisella were examined using TEM and AFM and found to be 43-125 nm in size, representing another potential mechanism for altering the extracellular environment. A proteomic analysis (LC-MS/MS) of OMVs from F. novicida and F. philomiragia identified 416 (F. novicida) and 238 (F. philomiragia) different proteins, demonstrating that OMVs are an important contributor to the extracellular proteome. Many of the identified OMV proteins have a demonstrated role in Francisella pathogenesis. Biochemical assays demonstrated that Francisella OMVs possess acid phosphatase and hemolytic activities that may affect host cells during infection, and are cytotoxic toward murine macrophages in cell culture. OMVs have been previously used as a human vaccine against Neisseria meningitidis . We hypothesized that Francisella OMVs could be useful as a novel Francisella vaccine. Vaccinated BALB/C mice challenged with up to 50 LD50 of Francisella showed statistically significant protection when compared to control mice. In the context of these new findings, we discuss the relevance of OMVs in Francisella pathogenesis as well as their potential use as a vaccine. 相似文献
16.
Physical maps of the cobmtDNA region were constructed and compared between sugar beet Beta vulgarisL. plants with normal fertility and with cytoplasmic male sterility (CMS). A CMS-associated rearrangement did not affect the coding region of coband combined two mtDNA regions which are normally about 150 kb apart. Two point substitutions were found in the 3"-untranslated region of cob. 相似文献
17.
18.
Morozov AA 《Radiatsionnaia biologiia, radioecologiia / Rossi?skaia akademiia nauk》2003,43(3):363-366
While getting ultra los dosages in serial dilutions interactions between a substance and impurities of a solvent occur parallel with diminishing of concentrations. The concentration of impurities in high dilutions prevails the calculated concentration of substrate. Experiments show that different concentrations of compounds of impurities in a solvent correspond to different substances in different dilutions, including < 10(-24) mol/l. While dissolving three components--a solvent, impurities and a substance--participate in two processes: changing of concentration and changing of composition. Changed chemical composition of impurities of a solvent reflects specificity of physicochemical properties of a dissolving substance and is the molecular basis for biological activity of solutions with a concentration lower than 10(-24) mol/l. 相似文献
19.
The spectrum and frequency of mutations of exon 7 of the gene for phenylalanine hydroxylase (PAH) were studied in 34 phenylketonuria (PKU) patients living in Novosibirsk oblast. The five most prevalent mutations constituted 17.64% of defective alleles: R243Q (1.47%), R252W (1.47%), R261Q (5.88%), E280K (1.47%), and P281L (7.35%). A neutral polymorphic locus V245V was found within exon 7. 相似文献
20.
A previously unknown sequence of the human phenylalanine hydroxylase (PAH) gene intron 7 (GeneBank AN AF204239) has been reported. Screening of the group of phenylketonuria patients from Nobosibirsk region for polymorphic sites within intron 7 revealed single nucleotide substitutions at intron positions 332, 451, 574 and 791. Polymorphic site at intron position 791 corresponds to one of the eight restriction sites (MspI) utilized for haplotype construction. Analysis of the MspI allele frequencies in 29 phenylketonuria patients showed that the frequency of the MspI+ allele in this group was 79.4%. Polymorphic sites at nucleotide position +97 from the beginning of intron 10, and at nucleotide position -54 from the end of intron 5, were also described. The polymorphic sites revealed can be used as markers for identification of the PAH alleles in population genetic studies, and also serve for diagnostics of phenylketonuria (PKU). The presence of numerous nucleotide substitutions within the intronic sequences confirms highly polymorphic structure of the PAH gene. 相似文献