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

Тенденции в изменении энергетического баланса в электроэнергетических системах будующего

Recent advances in compression molding of glass optical elements for mass production offer the potential of extending this technology to elements with micro and nano scale features. In this research, glass diffractive optical elements (DOEs) with lateral features in the order of 10 mu m and vertical height of 330 nm were fabricated using a fused silica glass mold and a special low T-g (glass transition temperature) glass material K-PG325. Molded DOEs were studied using an atomic force microscope (AFM) and scanning electron microscope (SEM) to evaluate the glass molding process capability. Optical testing of the molded DOEs was a further demonstration of the effectiveness of the molding process for high volume micro and diffractive optical component fabrication. The combination of two high-precision, high-volume processes, i.e., semiconductor batch process for optical mold making and glass molding for DOE replication, is an effective alternative manufacturing method for high-quality, low-cost optical components. The reported experiment is a detailed illustration of the glass molding process capability. With further process optimization a robust manufacturing process can be developed for mass production of diffractive and micro glass optical elements

Binding of Ribosomal Proteins to RNA Covalently Coupled to Agarose

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65486/1/j.1432-1033.1977.tb11554.x.pd

Физиологическое обоснование тренировки плечевого пояса у пловцов на этапе спортивного совершенствования

В плавании, работа плечевого пояса является достаточно актуальной темой, так как наблюдается значительное преобладание уровня физической подготовленности занимающихся которые используют тренировочную нагрузку на плечевой пояс, над теми кто мало уделяет этому внимания, что не дает по общему счету возможности совершенствоваться в данной специализации, особенно на этапах спортивного совершенствования.In swimming, the work of the shoulder girdle is quite an actual topic, since there is a significant predominance of the level of physical fitness of those engaged in that use the training load on the shoulder girdle, over those who pay little attention to it, which does not give an opportunity to improve in this specialization, Stages of sports improvement

High-Resolution 3D Structure Determination of Kaliotoxin by Solid-State NMR Spectroscopy

High-resolution solid-state NMR spectroscopy can provide structural information of proteins that cannot be studied by X-ray crystallography or solution NMR spectroscopy. Here we demonstrate that it is possible to determine a protein structure by solid-state NMR to a resolution comparable to that by solution NMR. Using an iterative assignment and structure calculation protocol, a large number of distance restraints was extracted from 1H/1H mixing experiments recorded on a single uniformly labeled sample under magic angle spinning conditions. The calculated structure has a coordinate precision of 0.6 Å and 1.3 Å for the backbone and side chain heavy atoms, respectively, and deviates from the structure observed in solution. The approach is expected to be applicable to larger systems enabling the determination of high-resolution structures of amyloid or membrane proteins

Mutagenesis of the NaChBac sodium channel discloses a functional role for a conserved S6 asparagine

Asparagine is conserved in the S6 transmembrane segments of all voltage-gated sodium, calcium, and TRP channels identified to date. A broad spectrum of channelopathies including cardiac arrhythmias, epilepsy, muscle diseases, and pain disorders is associated with its mutation. To investigate its effects on sodium channel functional properties, we mutated the simple prokaryotic sodium channel NaChBac. Electrophysiological characterization of the N225D mutant reveals that this conservative substitution shifts the voltage-dependence of inactivation by 25 mV to more hyperpolarized potentials. The mutant also displays greater thermostability, as determined by synchrotron radiation circular dichroism spectroscopy studies of purified channels. Based on our analyses of high-resolution structures of NaChBac homologues, we suggest that the side-chain amine group of asparagine 225 forms one or more hydrogen bonds with different channel elements and that these interactions are important for normal channel function. The N225D mutation eliminates these hydrogen bonds and the structural consequences involve an enhanced channel inactivation