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M A Livshits

Publications and source records attributed to M A Livshits.

At least 19 recordsLinked to original sources
PubMed2003

Analysis of binding specificity of disulfide bonded dimeric lambda-Cro V55C protein with generic hexamer oligonucleotide microchip.

Binding specificity of mutant V55C disulfide bonded dimeric lambda-Cro protein (CroVC) to double-stranded DNA (dsDNA) was studied using generic hexamer oligonucleotide microchip. The curves of dissociation of hybridized DNA in the presence and absence of CroVC were converted into the effective discriminant constants to assess the relevant thermodynamic equilibrium binding constants for dsDNA-protein complexes. Then, tiling of longer oligonucleotides with shorter oligomers was used to search for sequence motifs with the highest binding specificity similarly to sequencing by hybridization. The comparison of the deduced sequences with the known natural operator half-sites demonstrated the principal ability to discern and reconstruct the major parts of 7-mer motifs corresponding to the strongest binding of CroVC subunits. Our results show the applicability of generic microchips to the analysis of binding specificity in the case of multi-subunit DNA-binding proteins.

Bacteriophage lambda↗
PubMed2001

The telomeric dG(GT)4G sequence can adopt a parallel-stranded double helical conformation.

Oligonucleotides 3'-d(GTGTGTGTGG)-L-d(GGTGTGTGTG)-3' (hp-GT) and 3'-d(G4STG4TG4STG4STGG)-L-d(GGTGTGTGTG)-3' (hp-SGT), (L=(CH2CH2O)3), were shown by use of several optical techniques to form a novel parallel-stranded (ps) intramolecular double helix with purine-purine and pyrimidine-pyrimidine base pairing. The rotational relaxation time of hp-GT was similar to that of a 10-bp reference duplex, and the fraction of unpaired bases was determined to be approximately 7%, testifying to the formation of an intramolecular double helical hairpin by the sequence under the given experimental conditions. A quasi-two-state mode of ps-double helix formation was validated, yielding a helix-coil transition enthalpy of -135 +/- 5 kJ/mol. The G x G and T x T (or 4ST x T) base pair configurations and conformational parameters of the double helix were derived with molecular modeling by force field techniques. Repetitive d(GT) sequences are abundant in telomers of different genomes and in the regulatory regions of genes. Thus, the observed conformational potential of the repetitive d(GT) sequence may be of importance in the regulation of cell processes.

Base Pairing↗
PubMed2000

Parallel-stranded DNA with mixed AT/GC composition: role of trans G.C base pairs in sequence dependent helical stability.

Parallel-stranded (ps) DNAs with mixed AT/GC content comprising G.C pairs in a varying sequence context have been investigated. Oligonucleotides were devised consisting of two 10-nt strands complementary either in a parallel or in an antiparallel orientation and joined via nonnucleotide linkers so as to form 10-bp ps or aps hairpins. A predominance of intramolecular hairpins over intermolecular duplexes was achieved by choice of experimental conditions and verified by fluorescence determinations yielding estimations of rotational relaxation times and fractional base pairing. A multistate mode of ps hairpin melting was revealed by temperature gradient gel electrophoresis (TGGE). The thermal stability of the ps hairpins with mixed AT/GC content depends strongly on the specific sequence in a manner peculiar to the ps double helix. The thermodynamic effects of incorporating trans G.C base pairs into an AT sequence are context-dependent: an isolated G. C base pair destabilizes the duplex whereas a block of > or =2 consecutive G.C base pairs exerts a stabilizing effect. A multistate heterogeneous zipper model for the thermal denaturation of the hairpins was derived and used in a global minimization procedure to compute the thermodynamic parameters of the ps hairpins from experimental melting data. In 0.1 M LiCl at 3 degrees C, the formation of a trans G.C pair in a GG/CC sequence context is approximately 3 kJ mol(-)(1) more favorable than the formation of a trans A.T pair in an AT/TA sequence context. However, GC/AT contacts contribute a substantial unfavorable free energy difference of approximately 2 kJ mol(-)(1). As a consequence, the base composition and fractional distribution of isolated and clustered G.C base pairs determine the overall stability of ps-DNA with mixed AT/GC sequences. Thus, the stability of ps-DNA comprising successive > or =2 G.C base pairs is greater than that of ps-DNA with an alternating AT sequence, whereas increasing the number of AT/GC contacts by isolating G.C base pairs exerts a destabilizing effect on the ps duplex. Molecular modeling of the various helices by force field techniques provides insight into the structural basis for these distinctions.

Base Composition↗
PubMed1998

["Second-look" surgery and diagnostic laparoscopy in the combined and comprehensive therapy of patients with ovarian cancer].

The data on 503 cases of ovarian malignancies were evaluated to work out indications for and clinical assessment of revision laparotomies. Second-look surgery was carried out in the following situations: (1) tumor elements found in the washings of the peritoneum in Douglas' space and high blood-serum levels of CA-125 (8 patients with stage I-II tumors, in clinical remission); (2) during remission, after 6-10 courses of polychemotherapy (13 patients with stage III-IV tumors); (3) during remission, after non-radical primary surgery (117); (4) suspected recurrence (144); (5) recurrence-free surgical pathology, e.g. ventral hernia, requiring laparotomy (22). Patients without repeated laparotomy (199) were in control. During remission, surveillance can be carried out using cytologic, ultrasound and immunoradiologic techniques since laparoscopy fails. The latter is useful, for diagnostic purposes, in case of discrepancy between clinical and ultrasound evidence as well as during monitoring in patients in clinical remission who show unfavorable levels of CA-125 and poor results of sonographic. Laparotomy is indicated prior to chemotherapy of inoperable tumors for morphologic verification of diagnosis. Indications for second-look operations can be significantly decreased considering the latest improvements in non-invasive monitoring technique. Laparoscopic examination can effectively serve the same purposes.

Adult↗
PubMed1996

Theoretical analysis of the kinetics of DNA hybridization with gel-immobilized oligonucleotides.

A new method of DNA sequencing by hybridization using a microchip containing a set of immobilized oligonucleotides is being developed. A theoretical analysis is presented of the kinetics of DNA hybridization with deoxynucleotide molecules chemically tethered in a polyacrylamide gel layer. The analysis has shown that long-term evolution of the spatial distribution and of the amount of DNA bound in a hybridization cell is governed by "retarded diffusion," i.e., diffusion of the DNA interrupted by repeated association and dissociation with immobile oligonucleotide molecules. Retarded diffusion determines the characteristic time of establishing a final equilibrium state in a cell, i.e., the state with the maximum quantity and a uniform distribution of bound DNA. In the case of cells with the most stable, perfect duplexes, the characteristic time of retarded diffusion (which is proportional to the equilibrium binding constant and to the concentration of binding sites) can be longer than the duration of the real hybridization procedure. This conclusion is indirectly confirmed by the observation of nonuniform fluorescence of labeled DNA in perfect-match hybridization cells (brighter at the edges). For optimal discrimination of perfect duplexes from duplexes with mismatches the hybridization process should be brought to equilibrium under low-temperature nonsaturation conditions for all cells. The kinetic differences between perfect and nonperfect duplexes in the gel allow further improvement in the discrimination through additional washing at low temperature after hybridization.

DNA↗
PubMed1996

[Specifics of reproductive disorders and hormonal sensitivity of tumors in patients with "hormone-related neoplastic syndrome"].

Blood-serum levels of gonadotrophins and estradiol were assayed alongside with those of estradiol and progesterone receptors in the tissue of tumors of the breast, uterus, ovary and large bowel to establish general regularities of reproductive homeostasis in patients. The study was based on the assumption that risk of secondary tumor development is considerable in a patient who bears one of said malignancies. The effect of estrogen hormones was shown to be one of general causes of tumorigenesis. This is corroborated by enhanced hyperestrinism observed in cases of carcinoma of the corpus uteri as well as by certain data pointing to a reliable correlation between estrogen-stimulated synthesis of progesterone receptors and prognosis in patients with tumors of the breast, uterus and ovary. No estrogen dependence, however, was registered in patients with tumors of the bowel. Pathogenetic features shared by tumors of the large bowel and those of the reproductive system should probably be accounted for by disorders in metabolism.

Adult↗
PubMed1994

Dissociation of duplexes formed by hybridization of DNA with gel-immobilized oligonucleotides.

The method of DNA sequencing by hybridization with oligonucleotides matrix (SHOM) developed in this laboratory (1.2) uses the matrix of oligonucleotides immobilized within polyacrylamide gel. The particular feature of this matrix is that the apparent thermostability of the duplexes depends on the concentration of gel-immobilized oligonucleotides. This dependence is specific for oligonucleotides immobilized in the gel volume (3-D-immobilization) rather than on a flat surface of a filter or glass (2-D-immobilization). The theory has been developed that provides a quantitative description of temperature-dependent duplex dissociation within gel. The theory takes into account that the diffusion of dissociated DNA out of the gel is retarded by multiple acts of association-dissociation of DNA with immobilized oligonucleotides. It allows to calculate the apparent dissociation temperature of duplexes and describes quantitatively its growth upon increase in the enthalpy of duplex dissociation, concentration of immobilized oligonucleotides, gel thickness and decrease of dissociation entropy and washing time. Concentration of gel-immobilized oligonucleotides can be calculated for a normalized matrix in which GC-rich and AT-rich duplexes exhibit the same apparent thermostabilities and are washed off at the same temperature. This simplifies identification of perfect duplexes formed on the matrix which can be carried out for all duplexes at the same temperature. The gel-immobilized oligonucleotide matrix provides also a higher capacity for immobilization and therefore a higher sensitivity of measurements, resulting in a higher discrimination power for identification of perfect duplexes as compared with matrixes of oligonucleotides immobilized on a surface.

Acrylic Resins↗
PubMed1991

Directionality of evolution at molecular and organismic levels.

The molecular evolution theories of Eigen and Kimura are compared and their difference is explained. In terms of Eigen's theory for the evolution of macromolecules, the selection of genotypes occurs directly. The physical meaning of the neutral theory is the degeneracy of the correlation between a phenotype and a genotype at the molecular level. A model theory of evolution on a fitness landscape is proposed. The theory shows that the constraints of selection determined by the structure and dynamics of previous evolution stages increases its rate strongly.

Biological Evolution↗
PubMed1991

On the divergence of species.

Speciation may be considered as a kind of non-equilibrium phase transition which is caused by bifurcation at a critical point of instability. It can be shown that multiple branching of an evolutionary tree is highly improbable, since non-degenerate mathematical models describe only binary branchings.

Biological Evolution↗
PubMed1990

Flexibility difference between double-stranded RNA and DNA as revealed by gel electrophoresis.

A systematic study of agarose gel electrophoresis of double-stranded RNA in the kilobase range of sizes was performed. The dsRNA to dsDNA relative mobility was found to depend on gel concentration: in low density gels RNA moves slower and in high density gels - faster than DNA of the same molecular size. The electrophoretic differences were interpreted within the reptation theory to be mainly due to the molecular stiffness differences. The dsRNA persistence length was roughly estimated to be about twice as great as that of DNA.

Bacteriophages↗
PubMed1990

[Methods of optimizing and objective criteria for evaluating the efficacy of chemo-surgical treatment of malignant epithelial tumors of the ovaries].

In a group of 811 patients with epithelial malignancies of the ovaries, the diagnostic and therapeutic procedures used were either standard or they involved elements of optimization based on certain objective criteria. The reliability of diagnosis and treatment efficacy in the two subgroups were compared. Stage I-II tumors made up 37.1% of neoplasms diagnosed at regular check-ups and 16.9% of those identified in controls. Duration of relapse-free period was 45.0 and 11.8 months whereas five-year survival rate--42.9% and 20.5%, respectively. Clinically inapparent recurrence was cytologically detected in 29.5% of "actively" followed patients. Additional estrogen and progestin therapy assured an increase in recurrence-free period from 13.5 to 20.6 months in patients with stage III-IV tumors (9.1 and 9.5 months in controls). The efficacy of single-agent and combination chemotherapy in stage III-IV cancer was nearly the same. Adjuvant postoperative chemotherapy administered during the first 2.5-3 years of remission resulted in a 2.2--fold decrease in recurrence rate and a 21.4% rise in five-year survival rate in patients with stage Ia and Ib cancer.

Adenocarcinoma↗
PubMed1989

Speciation and bifurcations.

The interrelations of physics and biology are discussed. It is shown that Darwin can be considered as one of the founders of the important field of contemporary physics called physics of dissipative structures or synergetics. The theories of gradual and punctual evolution are presented. The contradiction between these theories can be solved on the basis of molecular theory of evolution and on the basis of the phenomenological physical treatment. The general physical properties of living systems, considered as open systems being far from equilibrium, are listed and simple non-linear mathematical models describing gradual and punctual speciation are suggested. The usual pictures which present these two kinds of speciation can possess physico-mathematical sense. Punctuated speciation means bifurcation, a kind of non-equilibrium phase transition.

Biological Evolution↗
PubMed1985

[Differential diagnosis of primary and metastatic ovarian tumors in patients treated for breast cancer].

The report deals with some problems of differential diagnosis between primary and metastatic ovarian tumors in 78 patients treated for breast cancer (without local recurrence). Clinical symptoms, results of palpation, evidence supplied by surgical intervention, data of cytological examination of exudates and even the findings of express histological analysis of bioptates fail to provide a sufficient improvement on diagnosis. Final diagnosis can be obtained by means of an all-round histological examination only. The extent of surgical procedure should match the operation of choice for primary ovarian tumor. Since ovarian involvement is rather frequent in breast cancer patients, they should be followed up by the gynecologist in the course of the whole survival time.

Breast Neoplasms↗
PubMed1983

[Clinico-morphological characteristics and results of treatment of endometrioid cystadenocarcinoma of the ovary].

Clinico-morphological peculiarities of endometrioid cystadenocarcinoma of the ovaries (105 cases) were compared with those of a more frequent serous one. Hyperestrogenism was more frequent in endometrioid cystadenocarcinoma, metastases, ascites and hydrothorax developing less frequently. Immediate and long-term results in endometrioid cystadenocarcinoma were better than in cases of serous one. When hormone-producing, both tumors metastasized less frequently and 5-year survival rates in such cases were relatively higher. Progestin treatment was effective in cases of endometrioid cystadenocarcinoma, particularly, in those of hormone-producing form.

Adenocarcinoma↗