Biomedical subjects

N Morozova

Publications and source records attributed to N Morozova.

8 recordsLinked to original sources

PubMed2006

Protein-RNA interactions: exploring binding patterns with a three-dimensional superposition analysis of high resolution structures.

MOTIVATION: The recognition of specific RNA sequences and structures by proteins is critical to our understanding of RNA processing, gene expression and viral replication. The diversity of RNA structures suggests that RNA recognition is substantially different than that of DNA. RESULTS: The atomic coordinates of 41 protein-RNA complexes have been used to probe composite nucleoside binding pockets that form the structural and chemical underpinnings of base recognition. Composite nucleoside binding pockets were constructed using three-dimensional superpositions of each RNA nucleoside. Unlike protein-DNA interactions which are dominated by accessibility, RNA recognition frequently occurs in non-canonical and single-strand-like structures that allow interactions to occur from a much wider set of geometries and make fuller use of unique base shapes and hydrogen-bonding ability. By constructing composites that include all van der Waals, hydrogen-bonding, stacking and general non-polar interactions made to a particular nucleoside, the strategies employed are made readily visible. Protein-RNA interactions can result in the formation of a glove-like tight binding pocket around RNA bases, but the size, shape and non-polar binding patterns differ between specific RNA bases. We show that adenine can be distinguished from guanine based on the size and shape of the binding pocket and steric exclusion of the guanine N2 exocyclic amino group. The unique shape and hydrogen-bonding pattern for each RNA base allow proteins to make specific interactions through a very small number of contacts, as few as two in some cases. AVAILABILITY: The program ENTANGLE is available from http://www.bioc.rice.edu/~shamoo

Algorithms↗

PubMed2005

Prospective study of occupation and amyotrophic lateral sclerosis mortality.

Occupational exposures are suspected of contributing to the risk of amyotrophic lateral sclerosis (ALS), but results of epidemiologic studies have been inconsistent. The authors prospectively assessed the relation between occupation and ALS mortality among more than 1 million participants in the Cancer Prevention Study II of the American Cancer Society. Follow-up from 1989 through 2002 identified 507 ALS deaths among men and 430 among women. Adjusted rate ratios were calculated by using Mantel-Haenszel weights and Cox proportional hazards. Among men, elevated ALS mortality was found for programmers (rate ratio = 4.55, 95% confidence interval: 1.46, 14.2; p = 0.009) and laboratory technicians (rate ratio = 1.96, 95% confidence interval: 1.04, 3.66; p = 0.04). Occupations previously associated with increased risk of ALS for which no increased risk was found included farmers, electricians, and welders, although the numbers of electricians (eight ALS deaths) and welders (two ALS deaths) were small. Among women, only machine assemblers had significantly increased ALS mortality (rate ratio = 2.81, 95% confidence interval: 1.05, 7.53; p = 0.04). Results, which suggest that male programmers and laboratory technicians and female machine assemblers may be at increased risk of death from ALS, should be interpreted cautiously, however, because they are based on small numbers.

Amyotrophic Lateral Sclerosis↗

PubMed2001

Functional analysis of capsaicin receptor (vanilloid receptor subtype 1) multimerization and agonist responsiveness using a dominant negative mutation.

The recently cloned vanilloid receptor subtype 1 (VR1) is a ligand-gated channel that is activated by capsaicin, protons, and heat. We have attempted to develop a dominant negative isoform by targeting several mutations of VR1 at highly conserved amino acids or at residues of potential functional importance and expressing the mutants in Chinese hamster ovary cells. Mutation of three highly conserved amino acid residues in the putative sixth transmembrane domain disrupts activation of the VR1 receptor by both capsaicin and resiniferatoxin. The vanilloid binding site in this mutant is intact, although the affinity for [(3)H]resiniferatoxin (RTX) is diminished by nearly 40-fold. Interestingly, this mutant retains a significant but diminished response to protons, supporting the existence of multiple gating mechanisms for different stimuli. The mutant appears to function by interfering with the gating induced by vanilloids rather than the expression level or permeability of the receptor. In addition, this mutant was found to function as a strong dominant negative mutation when coexpressed with wild-type VR1, providing functional evidence that the VR1 receptor forms a multimeric complex. Analysis of both current density and [(3)H]RTX affinity in cells cotransfected with different ratios of wild-type and mutant VR1 is consistent with tetrameric stoichiometry for the native capsaicin receptor.

Amino Acid Substitution↗

PubMed2001

Two phases of chromatin decondensation during dedifferentiation of plant cells: distinction between competence for cell fate switch and a commitment for S phase.

Cellular dedifferentiation is the major process underlying totipotency, regeneration, and formation of new stem cell lineages in multicellular organisms. In animals it is often associated with carcinogenesis. Here, we used tobacco protoplasts (plant cells devoid of cell wall) to study changes in chromatin structure in the course of dedifferentiation of mesophyll cells. Using flow cytometry and micrococcal nuclease analyses, we identified two phases of chromatin decondensation prior to entry of cells into S phase. The first phase takes place in the course of protoplast isolation, following treatment with cell wall degrading enzymes, whereas the second occurs only after protoplasts are induced with phytohormones to re-enter the cell cycle. In the absence of hormonal application, protoplasts undergo cycles of chromatin condensation/decondensation and die. The ubiquitin proteolytic system was found indispensable for protoplast progression into S phase, being required for the second but not the first phase of chromatin decondensation. The emerging model suggests that cellular dedifferentiation proceeds by two functionally distinct phases of chromatin decondensation: the first is a transitory phase that confers competence for cell fate switch, which is followed, under appropriate conditions, by a second proteasome-dependent phase representing a commitment for the mitotic cycle. These findings might have implications for a wide range of dedifferentiation-driven cellular processes in higher eukaryotes.

Base Sequence↗

PubMed2001

In silico identification of novel selenoproteins in the Drosophila melanogaster genome.

In selenoproteins, incorporation of the amino acid selenocysteine is specified by the UGA codon, usually a stop signal. The alternative decoding of UGA is conferred by an mRNA structure, the SECIS element, located in the 3'-untranslated region of the selenoprotein mRNA. Because of the non-standard use of the UGA codon, current computational gene prediction methods are unable to identify selenoproteins in the sequence of the eukaryotic genomes. Here we describe a method to predict selenoproteins in genomic sequences, which relies on the prediction of SECIS elements in coordination with the prediction of genes in which the strong codon bias characteristic of protein coding regions extends beyond a TGA codon interrupting the open reading frame. We applied the method to the Drosophila melanogaster genome, and predicted four potential selenoprotein genes. One of them belongs to a known family of selenoproteins, and we have tested experimentally two other predictions with positive results. Finally, we have characterized the expression pattern of these two novel selenoprotein genes.

Amino Acid Sequence↗

PubMed2000

Clausa, a tomato mutant with a wide range of phenotypic perturbations, displays a cell type-dependent expression of the homeobox gene LeT6/TKn2.

Class I knox genes play an important role in shoot meristem function and are thus involved in the ordered development of stems, leaves, and reproductive organs. To elucidate the mechanism underlying the expression pattern of these homeobox genes, we studied a spontaneous tomato (Lycopersicon esculentum) mutant that phenotypically resembles, though is more extreme than, transgenic plants misexpressing class I knox genes. This mutant was found to carry a recessive allele, denoted clausa:shootyleaf (clau:shl)-a newly identified allele of clausa. Mutant plants exhibited abnormal leaf and flower morphology, epiphyllus inflorescences, fusion of organs, calyx asymmetry, and navel-like fruits. Analysis by scanning electron microscopy revealed that such fruits carried ectopic ovules, various vegetative primordia, as well as "forests" of stalked glandular trichomes. In situ RNA hybridization showed a peculiar expression pattern of the class I knox gene LeT6/TKn2; expression was restricted to the vascular system and palisade layer of mature leaves and to the inner part of ovules integuments. We conclude that CLAUSA regulates various aspects of tomato plant development, at least partly, by rendering the LeT6/TKn2 gene silent in specific tissues during development. Considering the expression pattern of LeT6/TKn2 in the clausa mutant, we suggest that the control over a given homeobox gene is maintained by several different regulatory mechanisms, in a cell type-dependent manner.

Base Sequence↗

PubMed1988

Participation of serotoninergic system in neuroimmunomodulation: intraimmune mechanisms and the pathways providing an inhibitory effect.

Exogenous serotonin administration as well as its precursor 5-oxytryptophan, blockade of the ferment inactivation by MAO inhibition, impairment of the monoamine binding, in other words, all the ways of elevation of active serotonin level, result in the inhibition of the immune response. On the contrary, exclusion of the serotoninergic system by the nuclei raphe lesion and the blockade of the synthesis ferments by p-chlorphenylalanine and p-chloramphetamine stimulates it. The present analysis permits us to conclude that the nuclei raphe serotoninergic system provides an inhibitory mechanism of the immune response modulation, that is realized via the hypothalamus-hypophysis-adrenals axis. Immune response modulation by the extraimmune control system is possible only be means of the mechanisms that are present in the immunocompetent system. Investigation of the cellular basis of physiological mechanisms of serotoninergic regulation of the immune process made it possible to determine alterations in the correlation of functionally different cell populations in animals with elevated serotonin level. An inhibitory action which serotonin produces upon the immunogenesis, is based on the attenuation of suppressor cell function, an earlier than under the normal immune response development emergence of suppressor in the population of cell organs, and their longer presence, that is to some extent connected with the redistribution of cell populations in the immunocompetent organs. After serotonin administration only the antigen-nonspecific immunosuppression is activated. In evolutionary terms the mechanisms of nonspecific suppression have been formed earlier than those of specific ones (Calkins & Stutman, 1978; Mijawaki, Seki, Kubo & Tanigushi, 1979). It is quite reasonable that extraimmune modulation, and psychoneuroimmunomodulation by monoamine systems in particular, can be performed by means of this ancient antigen-nonspecific mechanism of the immune response regulation. In this case, the modulation of immunological reactivity should correspond to these endogenous and environmental influences. Thus, activation of the nonspecific suppression induced through the serotoninergic system can be considered as the universal mechanism which on the one hand completes control of the immune homeostasis and on the other may be the precondition of the development of pathological states caused by the reduction of immunological status.

Adrenalectomy↗

PubMed1986

Monoamines as immunomodulators: importance of suppressors and helpers of the bone marrow.

The intraimmune pathways and mechanisms of action of the serotoninergic and dopaminergic systems in exerting a modulating effect upon immunogenesis are presented. Experiments were carried out in mice immunized with sheep red blood cells (1 X 10(7); 5 X 10(6)). Participation of the hypothalamic-pituitary complex in the monoaminergic mechanisms of stimulation and inhibition of rosette formation was revealed. Dissection of the pituitary stalk prevented stimulation of rosette formation by apomorphine (1 mg/kg i.p) and bupropion (20 mg/kg) and the reduction of the immune response by haloperidol (1 mg/kg), 5-hydroxytryptophan (300 mg/kg) and serotonin (50 mg/kg). The results of syngeneic cellular transfer of different immunocompetent organs showed that serotonin injection induced an increase in B-suppressor activity of bone marrow cells, reaching maximal value in the inductive period (day 3 of the immune response). B-Lymphocyte suppression in donors not treated with serotonin peaked on day 5 of the immune response. Stimulation of the immune response under activation of the dopaminergic system after apomorphine administration was provided by an increase in T-helper activity in the bone marrow cells, mainly with respect to IgM-response. The suppressive activity of bone marrow T cells on IgM- and IgG-immune responses was increased in nonimmunized donors treated with serotonin or haloperidol. The mechanisms of neurochemical multichannel immunomodulation by means of redistribution of cellular populations resulting in an increase in suppressors or helpers in bone marrow are discussed.

Adjuvants, Immunologic↗