Biomedical subjects
Publications and source records attributed to O V Matveeva.
The authors analyzed prevalence of individual types of upper limb compression neuropathy in miners of coal and iron-ore mines. Medical examination covered main mining occupations exposed to suchhazards as local vibration, cooling microclimate, functional overstrain. Some types of compression neuropathies appeared to depend on duration of exposure to the hazards and on the occupation hands disease stage.
The authors studied prevalence of bone congenital malformations including congenital vertebral canal stenosis, of acquired vertebral canal stenosis due to intervertebral disc prolapse, yellow ligament hypertrophy, and combinations of those two in patients with occupational and general vertebral diseases.
Antisense oligonucleotides are used for therapeutic applications and in functional genomic studies. In practice, however, many of the oligonucleotides complementary to an mRNA have little or no antisense activity. Theoretical strategies to improve the 'hit rate' in antisense screens will reduce the cost of discovery and may lead to identification of antisense oligonucleotides with increased potency. Statistical analysis performed on data collected from more than 1000 experiments with phosphorothioate-modified oligonucleotides revealed that the oligo-probes, which form stable duplexes with RNA (DeltaG(o)37 < or = -30 kcal/mol) and have small self-interaction potential, are more frequently efficient than molecules that form less stable oligonucleotide-RNA hybrids or more stable self-structures. To achieve optimal statistical preference, the values for self-interaction should be (DeltaG(o)37) > or = -8 kcal/mol for inter-oligonucleotide pairing and (DeltaG(o)37) > or = -1.1 kcal/mol for intra-molecular pairing. Selection of oligonucleotides with these thermodynamic values in the analyzed experiments would have increased the 'hit rate' by as much as 6-fold.
Optimization of probe design for array-based experiments requires improved predictability of oligonucleotide hybridization behavior. Currently, designing oligonucleotides capable of interacting efficiently and specifically with the relevant target is not a routine procedure. Multiple examples demonstrate that oligonucleotides targeting different regions of the same RNA differ in their hybridization ability. The present work shows how thermodynamic evaluations of oligo-target duplex or oligo self-structure stabilities can facilitate probe design. Statistical analysis of large sets of hybridization data reveals that thermodynamic evaluation of oligonucleotide properties can be used to avoid poor RNA binders. Thermodynamic criteria for the selection of 20 and 21mers, which, with high probability, interact efficiently and specifically with their targets, are suggested. The design of longer oligonucleotides can also be facilitated by the same calculations of DeltaG(o) (T) values for oligo-target duplex or oligo self-structure stabilities and similar selection schemes.
Prevalence of neurologic cervical and lumbar disorders among workers does not depend upon hardness of work conditions. First diagnosed occupational vertebral syndromes were clinically divided into reflectory and compression ones. Length of service, age and X-ray signs appeared not to differ significantly between the groups.
Occupational medical examinations and hospital studies considered prevalence and clinical features of compression neuropathies of lower limbs in workers subjected to static and dynamic overload of legs. Findings are locomotory and vascular disorders causing compression of peripheral nerves.
Design of antisense oligonucleotides targeting any mRNA can be much more efficient when several activity-enhancing motifs are included and activity-decreasing motifs are avoided. This conclusion was made after statistical analysis of data collected from >1000 experiments with phosphorothioate-modified oligonucleotides. Highly significant positive correlation between the presence of motifs CCAC, TCCC, ACTC, GCCA and CTCT in the oligonucleotide and its antisense efficiency was demonstrated. In addition, negative correlation was revealed for the motifs GGGG, ACTG, AAA and TAA. It was found that the likelihood of activity of an oligonucleotide against a desired mRNA target is sequence motif content dependent.
SUMMARY: ODNBase is a database of antisense oligodeoxynucleotides targeted to mammalian mRNAs that were reported in the literature. It includes the oligo sequences tested, the measured effectiveness, the RNA that was targeted, the type of measurement assay used, the oligo concentration applied, and the reference for each oligo. It provides a searchable interface by motif content, activity level, applied concentration and RNA name. Oligo lists matching search criteria can be downloaded in a spreadsheet compatible format.
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Intermolecular hybridization experiments show that murine 18S rRNA and 28S rRNA are capable of forming stable hybrid structures with mRNA from genes p53, c-myc and c-mos from the same species. Both 5'-uncoding and coding oncogene p53 mRNA regions contain fragments interacting with rRNA. Computer analysis revealed 18S rRNA fragments complementary to oligonucleotides frequently met in mRNA, which are potential hybridization regions (clinger-fragments). The distribution of clinger-fragments along 18S rRNA sequence is universal at least for one hundred murine mRNA sequences analyzed. Maximal frequencies of oligonucleotides complementary to 18S rRNA clinger-fragments are reliably (2-3 times) higher for mRNA than for intron sequences and randomly generated sequences. The results obtained suggest a possible role of clinger-fragments in translation processes as universal regions of mRNA binding.
By blot hybridization we found that DNA fragments of eukaryotic 18 and 28S rRNAs bind specifically with mRNA. In these experiments the in vitro transcribed mRNA of mouse gene p53 was used. In addition we found that both 18 and 28S rRNAs were able to form intermolecular complexes with mRNAs of several genes 18S rRNA-mRNA; 28S rRNA-mRNA, but fail to bind the antisense RNAs of the same genes. The experimental data allow to suppose that 18S and 28S rRNAs carry several fragments that are complementary to some fragments in the mRNA sequences.
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A model describing the interaction of a short oligonucleotide with long polynucleotide matrix has been developed. The model allows to calculate possibilities of oligonucleotide binding with different matrix sites on the basis of thermodynamic parameters of duplex formation. The model has been used for description of messenger RNA interaction with "clinger-fragment" sites on ribosomal RNA, which are potential sites of hybridization with mRNA. A possibility of rRNA interaction with mRNA by means of multiple duplex formation between "clinger-fragments" and numerous complementary short mRNA sites is discussed.