Proton Distribution Radii of

The root mean square radii of the proton density distribution in ^{16-24}O derived from measurements of charge changing cross sections with a carbon target at ∼900A MeV together with the matter radii portray thick neutron skin for ^{22-24}O despite ^{22,24}O being doubly magic. Imprints of the shell closures at N=14 and 16 are reflected in local minima of their proton radii that provide evidence for the tensor interaction causing them. The radii agree with ab initio calculations employing the chiral NNLO_{sat} interaction, though skin thickness predictions are challenged. Shell model predictions agree well with the data.

[DNA Bearing Bulky Fluorescent and Photoreactive Damage in Both Strands as Substrates of the Nucleotide Excision Repair System].

Model DNA molecules that contain bulky lesions in both strands have been created, and their properties as substrates of the nucleotide excision repair (NER) system have been analyzed. The modified nucleoside, 5-[3-(4-azido-2,3,5,6-tetrafluorobenzamido)-1-propoxypropyl]-2'-deoxycytidine (dC^(FAB)), or the nonnucleoside fragment, N-[6-(9-anthracenylcarbamoyl)hexanoyl]-3-amino-1,2-propanediol (nAnt), have been inserted as damage in certain positions of the first DNA strand ("0"). The position of N-[6-5(6)-fluoresceinylcarbamoyl]hexanoyl] -3-amino-1,2-propanediol (nFlu) has been varied within the second DNA strand. This residue has been located opposite the removable damaging fragment of the first strand at positions -20, -10, -4, 0, +3, and +8 relative to the first lesion. It has been demonstrated that the presence of nFlu at the -4, 0, or +3 position of the second strand significantly reduces the thermostability of DNA duplexes, especially in the case of nAnt-DNA and completely excludes the possibility of NER-catalyzed excision from dC^(FAB)- and nAnt-containing 137-meric DNA with the second lesion at these positions. The introduction of nFlu at positions -20, -10, or +8 differently affects the excision efficiency of dC^(FAB)- and nAnt-containing fragments from the first strand. The excision efficiency of dC^(FAB)-containing fragments from extended double-damaged DNA is as high as from DNA that contains a single dC^(FAB) damage, while the excision of nAnt-containing fragments occurs with 80-90% lower efficiency from double-damaged DNA occurs from DNA that contains the single nAnt insert. The nFlu insert differently affects the interaction of the sensory XPC-HR23B dimer with dC^(FAB)- and nAnt-containing DNAs, although in all cases, this interaction occurs with increased efficiency compared to that with single-damaged DNAs. No direct correlation between the thermostability of the DNA duplex and XPC-DNA affinity on the one hand, and the excision efficiency of lesions on the other hand has been shown. The absence of the correlation may be caused by both functional features of variable multiprotein complexes involved in the recognition and verification of damage during NER and the sensitivity of the complexes to the structure of the damage and damage-surrounding DNA. The results are important for understanding the NER mechanism of elimination of bulky damage located in both DNA strands.

Proton Distribution Radii of

Proton radii of ^{12-19}C densities derived from first accurate charge changing cross section measurements at 900A MeV with a carbon target are reported. A thick neutron surface evolves from ∼0.5 fm in ^{15}C to ∼1 fm in ^{19}C. The halo radius in ^{19}C is found to be 6.4±0.7 fm as large as ^{11}Li. Ab initio calculations based on chiral nucleon-nucleon and three-nucleon forces reproduce the radii well.

First Measurement of Several ß-Delayed Neutron Emitting Isotopes Beyond N=126.

The ß-delayed neutron emission probabilities of neutron rich Hg and Tl nuclei have been measured together with ß-decay half-lives for 20 isotopes of Au, Hg, Tl, Pb, and Bi in the mass region N≳126. These are the heaviest species where neutron emission has been observed so far. These measurements provide key information to evaluate the performance of nuclear microscopic and phenomenological models in reproducing the high-energy part of the ß-decay strength distribution. This provides important constraints on global theoretical models currently used in r-process nucleosynthesis.

DNA with Damage in Both Strands as Affinity Probes and Nucleotide Excision Repair Substrates.

Nucleotide excision repair (NER) is a multistep process of recognition and elimination of a wide spectrum of damages that cause significant distortions in DNA structure, such as UV-induced damage and bulky chemical adducts. A series of model DNAs containing new bulky fluoro-azidobenzoyl photoactive lesion dC(FAB) and well-recognized nonnucleoside lesions nFlu and nAnt have been designed and their interaction with repair proteins investigated. We demonstrate that modified DNA duplexes dC(FAB)/dG (probe I), dC(FAB)/nFlu+4 (probe II), and dC(FAB)/nFlu-3 (probe III) have increased (as compared to unmodified DNA, umDNA) structure-dependent affinity for XPC-HR23B (Kdum > KdI > KdII ≈ KdIII) and differentially crosslink to XPC and proteins of NER-competent extracts. The presence of dC(FAB) results in (i) decreased melting temperature (ΔTm = -3°C) and (ii) 12° DNA bending. The extended dC(FAB)/dG-DNA (137 bp) was demonstrated to be an effective NER substrate. Lack of correlation between the affinity to XPC-HR23B and substrate properties of the model DNA suggests a high impact of the verification stage on the overall NER process. In addition, DNAs containing closely positioned, well-recognized lesions in the complementary strands represent hardly repairable (dC(FAB)/nFlu+4, dC(FAB)/nFlu-3) or irreparable (nFlu/nFlu+4, nFlu/nFlu-3, nAnt/nFlu+4, nAnt/nFlu-3) structures. Our data provide evidence that the NER system of higher eukaryotes recognizes and eliminates damaged DNA fragments on a multi-criterion basis.

[Application of GLAD-PCR analysis for the methylation sites detection in the regulatory areas of tumor-suppressor genes ELMo1 and EsR1 in colorectal cancer].

Aberrant methylation of regulation regions of tumorsuppressor genes is showed for many cancer diseases. In course of this modification an enzyme DNMT3 methylates RCGY sites in CpG-islands of regulation regions producing R(5mC)GY sites. Earlier we developed GLAD-PCR assay to determine R(5mC)GY site in a definite position of human genome. In this work we have applied GLAD-PCR assay to determine R(5mC)GY sites in regulation regions of ESR1 and ELMO1 tumor-suppressor genes. We have studied a fragment of first exon of ELMO1 gene and a part of ESR1 promoter region in DNA preparations from malignant cell line SW837 and colorectal tumor samples. We have checked four sites in each region and found two highly methylated sites: GCGC in first exon of ELMO1 gene and GCGT in promoter region of ESR1 gene. Site GCGT is weakly methylated in healthy tissues and more methylated in the most of colorectal samples. Site GCGC is not methylated in healthy tissues and significantly methylated in 60% of colorectal samples. A possibility to use GLAD-PCR assay for cancer diagnostics is discussed.

[DISTRIBUTION OF TWO-LOCUS HAPLOTYPES OF MICROBIAL COMPONENT SENSOR GENES TLR1 AND TLR6 IN MAJOR POPULATIONS OF SOUTH URALS].

AIM: Evaluate the fraction of various TLR1-TLR6 haplotypes in populations of Russians Bashkir and Nagaybak of Chelyabinsk Region. MATERIALS AND METHODS: Potential donors of stem cells from Chelyabinsk Region Station of Blood Transfusion registry were included into the study and split into 3 populations: Russians (81), Bashkir (78) and Nagaybak (84). Genotyping by 2 polymorphisms of TLR1 and TLR6 genes was carried out in all the 3 groups. Point polymorphism of TLR1 gene 1805T>G was determined by polymorphism analysis of length of restriction fragments, and polymorphism of TLR6 gene 745C>T by PCR using sequence-specific primers. RESULTS: TLR1 1805*G-TLR6 745*T haplotype occurs in population of Russians (42%) and relatively rare--among Bashkir (17%). An inverse picture is observed for TLR1 1805*T-TLR6 745*C haplotype: a more frequent spread among Bashkir (65%) and relatively rare occurrence in Russians (23%). Frequencies of the mentioned haplotypes, that occupy intermediate position compared with corresponding parameters for populations of Russians and Bashkir, were detected for Nagaybak, that, probably, reflects complex pathways of settling of their ancestors and effects of other non-adaptation factors. CONCLUSION: Frequencies of TLR1-TLR6 two-locus haplotypes in major populations of South Urals were determined for the first time. Further studies in this field will allow better understanding of features of immune response and sensitivity to infections in various populations.

[Inflammatory diseases of scrotal organs in patients with brucellosis: Improvement of therapy].

AIM: To evaluate the efficacy of cycloferon used in the combination treatment of scrotal inflammatory diseases (SID) in patients with brucellosis. SUBJECTS AND METHODS: A total of 150 male patients with chronic brucellosis (CB) were examined. Inquiry, questioning, physical and ultrasound examinations, and spermiogram analysis were used to detect of diseases of the reproductive system. Twenty-two CB patients with SID were examined over time (before and after cycle therapy). In Group 1, combination therapy included 2 cycles of five intramuscular injections of cycloferon 0.25 g in each at a 10-day interval. In Group 2, a package of therapeutic measures meets the generally accepted standards. and Incorporation of cycloferon into the combination therapy of SID patients with CB positively affected the time course of clinical changes and spermatogenesis, declines the number of SID exacerbations, improved quality of life, and failed to cause side effects. CONCLUSION: The findings allow us to recommend cycloferon as the drug of choice in treating CB patients with SID.

[Clinical and ultrasonic predictors of postoperative complications after carotid endarterectomy].

For the period from 2007 to 2012 carotid endarterectomy was performed in 150 patients with cerebrovascular insufficiency I-IV degrees and atherosclerotic lesion of carotid arteries. Dynamic observation was performed by using of duplex scanning of brachiocephalic arteries, transcranial duplex scanning, multislice CT with contrast study of extracranial and intracranial arteries. Different degrees of vascular wall thickening of operated internal carotid artery including neo- and myointimal hyperplasia, restenosis and other complications were observed in 19 (12.6%) patients after carotid endarterectomy on background of cerebrovascular insufficiency progressing. It was revealed that transient ischemic attack or stroke, acute heart failure in early postoperative period, arterial hypertension with crisis course predominantly, diabetes mellitus 2 type, obesity, male sex, elderly age and smoking were clinical markers for complications after carotid endarterectomy. Ultrasonic markers of complications after carotid endarterectomy included terms of development and degree of vascular wall thickening in case of neointimal hyperplasia and restenosis, hyperperfusion syndrome and stroke, significant changes of blood flow velocity and indexes of peripheral vascular resistance.

Proton radii of (12-17)B define a thick neutron surface in ¹7B.

The first determination of radii of point proton distribution (proton radii) of (12-17)B from charge-changing cross sections (σ(CC)) measurements at the FRS, GSI, Darmstadt is reported. The proton radii are deduced from a finite-range Glauber model analysis of the σ(CC). The radii show an increase from ¹³B to ¹7B and are consistent with predictions from the antisymmetrized molecular dynamics model for the neutron-rich nuclei. The measurements show the existence of a thick neutron surface with neutron-proton radius difference of 0.51(0.11) fm in ¹7B.

[Design of deoxyribozymes for inhibition of influenza A virus].

Influenza A viruses take a significant place in human and animal pathology causing epidemics and epizootics. Therefore, the development of new antiflu drugs has become more and more urgent. Deoxyribozymes can be considered as promising antiviral agents due to their ability to efficiently and highly specifically cleave RNA molecules. In this study, a number ofgenomic sequences of the most relevant influenza A virus subtypes, H5N1, H3N2, and H1N1, were analyzed. Conservative regions were revealed in five the least variable segments of the fragmented viral RNA genome, and potential sites of their cleavage with "10-23" deoxyribozymes were determined. 46 virus-specific 33-mer deoxyribozymes with the general structure of 5'N8AGGCTAGCTACAACGAN9 were designed and synthesized. Screening of the antiviral activity of these agents in conjugation with lipofectin on the Madin-Darby Canine Kidney cells infected with highly pathogenic avian influenza virus A/chicken/Kurgan/05/2005 (H5N1) revealed 17 deoxyribozymes, which suppressed the titer of virus cytopathicity by more than 2.5 IgTCID50/mL (i.e. the virus neutralization index was more than 300), with five of them suppressing the virus titer by a factor of 1000 and more. The most active deoxyribozymes appeared to be specific to segment 5 of the influenza A virus genome, which encoded nucleoprotein (NP).

[Surgical treatment of hemodynamically significant kinking of internal carotid arteries].

38 patients with different forms of vascular cerebral insufficiency, caused by kinking and atherosclerotic changes of internal carotid arteries were operated on. Various types of reconstructive operation on extracranial carotid arteries were performed. The color duplex ultrasound scanning and computed tomography proved to be highly informative noninvasive means for detecting carotid pathology in patients with vascular cerebral insufficiency. Reconstructive operations on internal carotid arteries can serve as prophylactic and treatment measure of chronic cerebral insufficiency. Authors propose the principle of "six types" of reconstructive operations which individualizes the surgical approach. Carotid surgery for asympomatic patients should be performed on strict indications.

[Effectiveness of cycloferon in complex treatment of brucellosis patients with lesions of the scrotum].

The article presents the results of urological examination (spermograms and data of ultrasound examination) of 22 patients with chronic brucellosis and diseases of the scrotum (6 patients with orchitis, 16 with orchiepididymitis) before and after conventional therapy (10 patients) and combined treatment with the inclusion of cycloferon (2 courses of 5 intramuscular injection [0.25 g] with an interval of 10 days)--12 patients. It is shown that the administration of cycloferon leads to more effective relief of intoxication symptoms and inflammation in the testes and appendages (reduction of scrotal wall thickness, size of testes and/or adjuncts, and the incidence and severity of hydrocele), and has a positive effect on spermatogenesis (reduction of semen viscosity, the number of white blood cells in semen, sperm agglutination associated with the formation of sperm antibodies in most patients after treatment), as well as reduces the number of exacerbations of chronic orchitis/orchiepididymitis by 2.4 times.

New Measurement of the π0 radiative decay width.

High precision measurements of the differential cross sections for π0 photoproduction at forward angles for two nuclei, 12C and 208Pb, have been performed for incident photon energies of 4.9-5.5 GeV to extract the π0→γγ decay width. The experiment was done at Jefferson Lab using the Hall B photon tagger and a high-resolution multichannel calorimeter. The π0→γγ decay width was extracted by fitting the measured cross sections using recently updated theoretical models for the process. The resulting value for the decay width is Γ(π0→γγ)=7.82±0.14(stat)±0.17(syst) eV. With the 2.8% total uncertainty, this result is a factor of 2.5 more precise than the current Particle Data Group average of this fundamental quantity, and it is consistent with current theoretical predictions.

Photoactivated DNA analogs of substrates of the nucleotide excision repair system and their interaction with proteins of NER-competent extract of HeLa cells. Synthesis and application of long model DNA.

Long linear DNA analogs of nucleotide excision repair (NER) substrates have been synthesized. They are 137-mer duplexes containing in their internal positions nucleotides with bulky substitutes imitating lesions with fluorochloroazidopyridyl and fluorescein groups introduced using spacer fragments at the 4N and 5C positions of dCMP and dUMP (Fap-dC- and Flu-dU-DNA) and DNA containing a (+)-cis-stereoisomer of benzo[a]pyrene-N2-deoxyguanidine (BP-dG-DNA, 131 bp). The interaction of the modified DNA duplexes with the proteins of NER-competent HeLa extract was investigated. The substrate properties of the model DNA in the reaction of specific excision were shown to vary in the series Fap-dC-DNA << Flu-dU-DNA < BP-dG-DNA. During the experiments on affinity modification of the proteins of NER-competent extract, Fap-dC-DNA (137 bp) containing a (32)P-label in the photoactive nucleotide demonstrated properties of a highly efficient and selective probe. The set of the main targets of labeling included polypeptides of the extract with the same values of apparent molecular weights (35-90 kDa) as when using the shorter (48 bp) Fap-dC-DNA. Besides, some of the extract proteins were shown capable of specific and effective interaction with the long analog of NER substrate. Electrophoretic mobility of these proteins coincided with the mobilities of DNA-binding subunits of XPC-HR23B and PARP1 (~127 and ~115 kDa, respectively). The 115-kDa target protein was identified as PARP1 using NAD+-based functional testing. The results suggest that the linear Fap-dC-DNA is an unrepairable substrate analog that can compete with effective NER substrates in the binding of the proteins responsible for lesion recognition and excision.

[The use of cytoflavin for the treatment of chronic brucellosis].

Clinical and pathogenetic efficacy of cytoflavin as a component of combined therapy of chronic brucellosis was tested in 50 patients who repeated its beneficial effect on the quality of life. The mechanism of cytoflavin action consists of lowering severity of endogenous intoxication and systemic inflammation.

A Method for Assessing the Efficiency of the Nucleotide Excision Repair System Ex Vivo.

The nucleotide excision repair (NER) is one of the main repair systems present in the cells of living organisms. It is responsible for the removal of a wide range of bulky DNA lesions. We succeeded in developing a method for assessing the efficiency of NER in the cell (ex vivo), which is a method based on the recovery of TagRFP fluorescent protein production through repair of the damage that blocks the expression of the appropriate gene. Our constructed plasmids containing bulky nFlu or nAnt lesions near the tagrfp gene promoter were shown to undergo repair in eukaryotic cells (HEK 293T) and that they can be used to analyze the efficiency of NER ex vivo. A comparative analysis of the time dependence of fluorescent cells accumulation after transfection with nFlu- and nAnt-DNA revealed that there are differences in how efficient their repair by the NER system of HEK 293T cells can be. The method can be used to assess the cell repair status and the repair efficiency of different structural damages.

[Experience in treating severe viral respiratory infection caused by influenza A (H1N1)].

The authors present their experience in treating 142 patients with severe viral respiratory infection caused by influenza A (H1N1), describe its clinical picture, and identify major syndromes observed in the treatment of these patients at an intensive care unit. A rapid development of acute respiratory distress syndrome, significant hypoxemia and hypercapnia with the low efficiency of various therapeutic measures and hence progressive organ dysfunction determine the essence of the severe course of the disease. Uniform guidelines for intensive care in this patient population are presented.