Molecular basis of altered excitability in Shaker mutants of Drosophila melanogaster.

Mutations in the Shaker (Sh) locus of Drosophila melanogaster have differing effects on action potential duration and repolarization in neurons as well as on A-type K+ channels (I(A)) in muscle. The molecular basis of three exemplary Sh alleles (Sh(KS133), Sh(E62) and Sh5) has been identified. They are point mutation in the Sh transcription unit expressing aberrant voltage-gated A-type K+ channels. Replicas of each mutation have been introduced by in vitro mutagenesis into Sh cDNA. The expression of in vitro transcribed mutant Sh cRNA in Xenopus laevis oocytes reproduced the specific phenotypic traits of each Sh allele. The lack of I(A) in Sh(KS133) is due to a missense mutation within a sequence motif occurring in all hitherto characterized voltage-gated K+ channel forming proteins. The reduction of I(A) in Sh(E62) is due to a mutation in an AG acceptor site. The intervening sequence between exon 19 and 20 is not spliced in Sh(E62) RNA. As a consequence Sh(E62) flies do not contain the full complement of Sh K+ forming proteins. Finally, the Sh5 mutation leads to an altered voltage dependence of K+ channel activation and inactivation as well as to an accelerated rate of recovery from inactivation. This is due to a missense mutation altering the amino acid sequence of the proposed transmembrane segment S5 of the Sh K+ channels. Segment S5 is located adjacently to the presumed voltage sensor of voltage-gated ion channels. The results explain the altered properties of excitable cells in Sh mutants and provide a general model for the possible role of A-type K+ channels in modulation action potential profiles

Предопухолевая патология молочных желез в различных этнических популяциях населения Крыма

Серед жіночого населення АРК виявлені популяції із украй високою захворюваністю РМЖ (армянки - 114,25); з високою захворюваністю (слов’янки - 65,21); а також з відносно низькою захворюваністю (кримські татарки - 41,99 на 100 тис. відповідного жіночого населення; р < 0,001). Порівняльний аналіз поширеності доброякісної патології в 531 пацієнтки (399 слов’янок, 69 татарок, 63 армянки) показав, що вірогідно найбільш частими захворюваннями у вірменській популяції з високою захворюваністю РМЖ є кисты молочних залоз (Р=0,033) і вузлова форма фиброзно-кистозной хвороби (Р=0,040), які, очевидно, можна відносити до предраковой патології.In Crimean woman there are populations with very high Breast Cancer incidence (Armenians - 114,25); with high incidence (Slavs - 65,21); and with lowest incidence (Tatars - 41,99 in 100 000 woman populations; р < 0,001). In 531 patients (399 Slavs, 69 Tatars, 63 Armenians) more freqwently was diagnosed Breast Cysts (Р=0,033) and Nodular Fibrocystic disease (Р=0,040) in Armenian ethnic group with very high Breast Cancer incidence. Breast Cysts and Nodular Fibrocystic disease only are precancerous diseases of the Breast

Active sites in Escherichia coli ribosomes

AbstractIn the figure, 30 S ribosomal proteins have been arranged according to their functional role: Protein S1 is required for mRNA binding. Proteins S3, S4, S5, S11 and S12 are involved in cistron and/or codon—anticodon recognition. They must be close to the decoding sites on the 30 S subunit. Furthermore proteins S2, S3, S10, S14, S19 and S21 function in f-Met-tRNA binding. Proteins S1, S2, S3, S10, S14, S19, S20 and S21 are important for the function of both decoding sites, whereas proteins S9, S11 and S18 are only needed for EF—Tu-dependent aminoacyl-tRNA binding. Proteins S2, S5, S9 and S11 would be close to the GTPase center of the 50 S subunit, since they are important for this activity.The present available data concerning the 50 S subunit allow the following picture to be drawn: Protein L16 is involved in binding the 3′-terminus of aminoacyl-tRNA in the A-site. Next to it in the A-site, there is protein L6. The P-site is located adjacent to the A-site of the peptidyltransferase center. Accordingly, protein L2 is near protein L6 and is located in the P-site as well as proteins L27 and L4. Protein L11, which is intimately involved in peptide bond formation, would have to border parts of both A- and P-sites. Proteins L6 and L2 stimulate binding of 5 S RNA—protein complexes to 23 S RNA. The 5 S RNA—protein complex has GTPase and ATPase activities. The proteins in this complex (L5, L18, L20, L25 and L30) seem to be located close to the A-site of the peptidyltransferase center. These proteins together with protein L11 are involved in GDP binding. Proteins L10 and L6 are implicated in reconstitution of protein L7 and L12 mediated EF—G-dependent ribosomal GTP hydrolysis. This observation is supported by the fact that the aminoacyl-tRNA binding site, e.g. proteins L16 and L6, is connected with EF—G and EF—Tu binding site, e.g. proteins L7 and L12, as well as the GTPase center. Furthermore, if one of the functional roles of 5 S RNA is to bind aminoacyl-tRNA via T—Ψ—C, then those ribosomal proteins which bind to 5 S RNA (or are close to it) would be located near or at the A-site.The model of active sites in E. coli ribosome illustrated in the figure is based on the presently available experimental results. It is far from being complete and should not be overinterpreted as an accurate topographical model. More data on the functional role of ribosomal components and on the topography of the subunits can be expected in the near future and will add to the knowledge on the active sites in ribosomes

Реструктуризация предприятия (на примере ООО «Передвижная механизированная колонна-Томь»)

В процессе исследования определено экономическое содержание процесса реструктуризации предприятия; представлен механизм реализации реструктуризации предприятий; охарактеризованы основные методы оценки эффективности процесса реструктуризации предприятий; проводилась оценка финансового состояния ООО «Передвижная механизированная колона – Томь»; предложен план реструктуризации ООО «Передвижная механизированная колона – Томь» с оценкой его эффективности.The study defined economic content of the enterprise restructuring process; The mechanism of the implementation of the restructuring of enterprises; It describes the main methods for evaluating the effectiveness of the process of restructuring enterprises; evaluated the financial condition of Limited Liability Company «PMK – Tom'»; proposed restructuring plan of Limited Liability Company «PMK – Tom'» with the evaluation of its effectiveness

Динамический структурный фактор для плотной квазиклассической плазмы

Исследованы и проанализированы динамические структурные факторы для плотной квазиклассической плазмы на основе псевдопотенциала, учитывающего эффект дифракции и коллективные эффекты в широком диапазоне температур.The dynamical structure factor for dense semiclassical plasma, which takes into account the diffraction effect in a wide range of densities and temperatures was investigated