22 research outputs found

    ΠŸΡ€Π΅Π΄ΠΏΠΎΡΡ‹Π»ΠΊΠΈ ΠΈ смысловой Π³ΠΎΡ€ΠΈΠ·ΠΎΠ½Ρ‚ понятия Β«Π²ΠΎΠ²Π»Π΅Ρ‡Π΅Π½ΠΈΠ΅Β» Π² философии Π­. ΠœΡƒΠ½ΡŒΠ΅

    Get PDF
    This text describes the concept of engagement by the French philosopher E. Mounier. It examines the role of engagement in 20th century philosophy. The concept of engagement was brougtn in the personalisme by a german philosopher Landsberg. Mounier found it the key to undestarding the problem of personal engagement in history. For Mounier, personality exists to cross the engagement. The engagement according to Mounier is an intimasse act and that is why it is sacred. This character of engagement gave birth to the personality that is capable to take responsibility for humanity. By the French philosopher, the necessity of engagement was the principal vocation of her generation.Π’ философии пСрсонализма понятиС «вовлСчСния» (Β«engagementΒ») являСтся ΠΊΠ»ΡŽΡ‡Π΅Π²Ρ‹ΠΌ ΠΈ вмСстС с Ρ‚Π΅ΠΌ Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ Ρ‚Ρ€ΡƒΠ΄Π½Ρ‹ΠΌ для понимания ΠΈ историко-философской ΠΈΠ½Ρ‚Π΅Ρ€ΠΏΡ€Π΅Ρ‚Π°Ρ†ΠΈΠΈ. Как ΠΏΠΎΠ»Π°Π³Π°Π» ΠΎΠ΄ΠΈΠ½ ΠΈΠ· основатСлСй ΠΈ Π²Π΅Π΄ΡƒΡ‰ΠΈΡ… прСдставитСлСй французского пСрсонализма Π­. ΠœΡƒΠ½ΡŒΠ΅, ΠΊΠ»ΡŽΡ‡Π΅Π²Ρ‹ΠΌ для понимания Β«engagementΒ» являСтся концСпция личности. Π›ΠΈΡ‡Π½ΠΎΡΡ‚ΡŒ, ΠΏΠΎ Π΅Π³ΠΎ мнСнию, ΠΏΠΎΠ΄Π΄Π΅Ρ€ΠΆΠΈΠ²Π°Π΅Ρ‚ свою Β«ΡΡƒΠ±ΡΡ‚Π°Π½Ρ†ΠΈΡŽ Ρ‡Π΅Ρ€Π΅Π· связь с ΠΈΠ΅Ρ€Π°Ρ€Ρ…ΠΈΠ΅ΠΉ цСнностСй, свободно Π°Π΄Π°ΠΏΡ‚ΠΈΡ€ΠΎΠ²Π°Π½Π½Ρ‹Ρ…, ассимилированных ΠΈ ΠΏΠ΅Ρ€Π΅ΠΆΠΈΡ‚Ρ‹Ρ… отвСтствСнным Π²ΠΎΠ²Π»Π΅Ρ‡Π΅Π½ΠΈΠ΅ΠΌ (engagement) ΠΈ постоянным ΠΎΠ±Ρ€Π°Ρ‰Π΅Π½ΠΈΠ΅ΠΌ (conversion). Она Ρ‚Π°ΠΊΠΆΠ΅ ΠΎΠ±ΡŠΠ΅Π΄ΠΈΠ½ΡΠ΅Ρ‚ всю свою Π΄Π΅ΡΡ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΡŒ Π² свободС ΠΈ, ΠΊΡ€ΠΎΠΌΠ΅ Ρ‚ΠΎΠ³ΠΎ, Ρ€Π°Π·Π²ΠΈΠ²Π°Π΅Ρ‚ Π΅Π΄ΠΈΠ½ΠΈΡ‡Π½ΠΎΡΡ‚ΡŒ своСго призвания» [14. Π . 523]. ΠŸΠΎΡΡ‚ΠΎΠΌΡƒ Π²ΠΎΠ²Π»Π΅Ρ‡Π΅Π½ΠΈΠ΅ слСдуСт Ρ€Π°ΡΡΠΌΠ°Ρ‚Ρ€ΠΈΠ²Π°Ρ‚ΡŒ ΠΊΠ°ΠΊ условиС ΠΏΠ΅Ρ€ΡΠΎΠ½Π°Π»ΡŒΠ½ΠΎΠ³ΠΎ бытия

    The resultant on compact Riemann surfaces

    Full text link
    We introduce a notion of resultant of two meromorphic functions on a compact Riemann surface and demonstrate its usefulness in several respects. For example, we exhibit several integral formulas for the resultant, relate it to potential theory and give explicit formulas for the algebraic dependence between two meromorphic functions on a compact Riemann surface. As a particular application, the exponential transform of a quadrature domain in the complex plane is expressed in terms of the resultant of two meromorphic functions on the Schottky double of the domain.Comment: 44 page

    Efficiency of RNA Hydrolysis by Binase from Bacillus pumilus: The Impact of Substrate Structure, Metal Ions, and Low Molecular Weight Nucleotide Compounds

    No full text
    Binase is an extracellular guanyl-preferring ribonuclease from Bacillus pumilus. The main biological function of binase is RNA degradation with the formation of guanosine-2',3'-cyclic phosphate and its subsequent hydrolysis to 3'-phosphate. Extracellular RNases are believed to be key agents that affect the functional activity of the body, as they directly interact with epithelial and immune cells. The biological effects of the enzyme may consist of both direct RNA degradation, and the accumulation of 2',3'-cGMP in the human body. In this work, we have performed a comparative analysis of the cleavage efficiency of model RNA substrates, i.e., short hairpin structures that contain guanosine at various positions. It has been shown that the hydrolysis efficiency of the model RNA substrates depends on the position of guanosine. We have also demonstrated the influence of various divalent metal ions and low molecular weight nucleotide compounds on the binase-catalyzed endoribonucleolytic reaction

    Efficiency of RNA Hydrolysis by Binase from Bacillus pumilus: The Impact of Substrate Structure, Metal Ions, and Low Molecular Weight Nucleotide Compounds

    No full text
    Β© 2020, Pleiades Publishing, Inc. Abstract: Binase is an extracellular guanyl-preferring ribonuclease from Bacillus pumilus. The main biological function of binase is RNA degradation with the formation of guanosine-2',3'-cyclic phosphate and its subsequent hydrolysis to 3'-phosphate. Extracellular RNases are believed to be key agents that affect the functional activity of the body, as they directly interact with epithelial and immune cells. The biological effects of the enzyme may consist of both direct RNA degradation, and the accumulation of 2',3'-cGMP in the human body. In this work, we have performed a comparative analysis of the cleavage efficiency of model RNA substrates, i.e., short hairpin structures that contain guanosine at various positions. It has been shown that the hydrolysis efficiency of the model RNA substrates depends on the position of guanosine. We have also demonstrated the influence of various divalent metal ions and low molecular weight nucleotide compounds on the binase-catalyzed endoribonucleolytic reaction

    Роль Π°Π΄Ρ€Π΅Π½ΠΎΡ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€ΠΎΠ² Π² Ρ€Π΅Π°Π»ΠΈΠ·Π°Ρ†ΠΈΠΈ стимуляторного дСйствия сСротонина Π½Π° ΠΌΠΎΡ‚ΠΎΡ€ΠΈΠΊΡƒ ΠΆΠ΅Π»ΡƒΠ΄ΠΊΠ°

    No full text
    Purpose of the study - study of the role of adrenoreceptors in the development of the stimulatory action of serotonin on the gastric motor activity. Materials and methods. The experiments were performed on rats (27) of the Wistar line in the surgical stage of anesthesia. Electromyogram and hydrostatic pressure in the stomach cavity were recorded using a BioAmp ML132 amplifier (Adinstruments, Australia), an Maclab 8e analog-to-digital converter (Adinstruments, Australia), a Macintosh Performa 6400/180 computer, and Chart 4.2.3. program. Serotonin injected into the body to intact animals and against the background of separate and joint blockade of Ξ±- and Ξ²-adrenoreceptors. The results of the study. In experiments on rats established that the preliminary simultaneous blockade of Ξ±- and Ξ²- adrenoreceptors leads to an increase in the stimulatory effect of the stomach with the introduction of serotonin by 58%, blockade of Ξ±-adrenoreceptors only - by 62%, Ξ²-adrenoreceptor blockade - by 89%. In intact animals, the stimulatory effect of serotonin is only + 26%. Simultaneous blockade of Ξ±- and Ξ²-adrenoreceptors and blockade of Ξ±-adrenoreceptors only (without serotonin administration) did not affect the gastric motor activity of intact animals. Blockade only Ξ²-adrenoreceptors will lead to an increase in gastric contractions by 34%. Conclusion. Intact Ξ±- and Ξ²-adrenoreceptors inhibit the stimulatory effect of serotonin on gastric motor activity.ЦСль исслСдования - ΠΈΠ·ΡƒΡ‡Π΅Π½ΠΈΠ΅ Ρ€ΠΎΠ»ΠΈ Π°Π΄Ρ€Π΅Π½ΠΎΡ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€ΠΎΠ² Π² Ρ€Π°Π·Π²ΠΈΡ‚ΠΈΠΈ стимуляторного дСйствия сСротонина Π½Π° ΠΌΠΎΡ‚ΠΎΡ€ΠΈΠΊΡƒ ΠΆΠ΅Π»ΡƒΠ΄ΠΊΠ°. ΠœΠ°Ρ‚Π΅Ρ€ΠΈΠ°Π»Ρ‹ ΠΈ ΠΌΠ΅Ρ‚ΠΎΠ΄Ρ‹. ЭкспСримСнты Π²Ρ‹ΠΏΠΎΠ»Π½Π΅Π½Ρ‹ Π½Π° крысах (27) Π»ΠΈΠ½ΠΈΠΈ Вистар Π² условиях хирургичСской стадии Π½Π°Ρ€ΠΊΠΎΠ·Π°. РСгистрировали элСктромиограмму ΠΈ гидростатичСскоС Π΄Π°Π²Π»Π΅Π½ΠΈΠ΅ Π² полости ΠΆΠ΅Π»ΡƒΠ΄ΠΊΠ° с ΠΏΠΎΠΌΠΎΡ‰ΡŒΡŽ усилитСля BioAmp ML132 (Adinstruments, Австралия), Π°Π½Π°Π»ΠΎΠ³ΠΎ-Ρ†ΠΈΡ„Ρ€ΠΎΠ²ΠΎΠ³ΠΎ прСобразоватСля Maclab 8e (Adinstruments, Австралия), ΠΊΠΎΠΌΠΏΡŒΡŽΡ‚Π΅Ρ€Π° Масintosh Performa 6400/180 ΠΈ ΠΏΡ€ΠΎΠ³Ρ€Π°ΠΌΠΌΡ‹ Chart 4.2.3. Π‘Π΅Ρ€ΠΎΡ‚ΠΎΠ½ΠΈΠ½ Π²Π²ΠΎΠ΄ΠΈΠ»ΠΈ Π² ΠΎΡ€Π³Π°Π½ΠΈΠ·ΠΌ ΠΈΠ½Ρ‚Π°ΠΊΡ‚Π½Ρ‹ΠΌ ΠΆΠΈΠ²ΠΎΡ‚Π½Ρ‹ΠΌ ΠΈ Π½Π° Ρ„ΠΎΠ½Π΅ Ρ€Π°Π·Π΄Π΅Π»ΡŒΠ½ΠΎΠΉ ΠΈ совмСстной Π±Π»ΠΎΠΊΠ°Π΄Ρ‹ Ξ±- ΠΈ Ξ²-Π°Π΄Ρ€Π΅Π½ΠΎΡ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€ΠΎΠ². Π Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Ρ‹ исслСдования. Π’ экспСримСнтах Π½Π° крысах установили, Ρ‡Ρ‚ΠΎ ΠΏΡ€Π΅Π΄Π²Π°Ρ€ΠΈΡ‚Π΅Π»ΡŒΠ½Π°Ρ одноврСмСнная Π±Π»ΠΎΠΊΠ°Π΄Π° Ξ±-ΠΈ Ξ²- Π°Π΄Ρ€Π΅Π½ΠΎΡ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€ΠΎΠ² Π²Π΅Π΄Π΅Ρ‚ ΠΊ ΡƒΠ²Π΅Π»ΠΈΡ‡Π΅Π½ΠΈΡŽ стимуляторного эффСкта ΠΆΠ΅Π»ΡƒΠ΄ΠΊΠ° ΠΏΡ€ΠΈ Π²Π²Π΅Π΄Π΅Π½ΠΈΠΈ сСротонина Π½Π° 58%, Π±Π»ΠΎΠΊΠ°Π΄Π° Ρ‚ΠΎΠ»ΡŒΠΊΠΎ Ξ±-Π°Π΄Ρ€Π΅Π½ΠΎΡ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€ΠΎΠ²-Π½Π° 62%, Π±Π»ΠΎΠΊΠ°Π΄Π° Ξ²- Π°Π΄Ρ€Π΅Π½ΠΎΡ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€ΠΎΠ²-Π½Π° 89%. Π£ ΠΈΠ½Ρ‚Π°ΠΊΡ‚Π½Ρ‹Ρ… ΠΆΠΈΠ²ΠΎΡ‚Π½Ρ‹Ρ… стимуляторный эффСкт сСротонина составляСт лишь + 26%. ΠžΠ΄Π½ΠΎΠ²Ρ€Π΅ΠΌΠ΅Π½Π½Π°Ρ Π±Π»ΠΎΠΊΠ°Π΄Π° Ξ±- ΠΈ Ξ²- Π°Π΄Ρ€Π΅Π½ΠΎΡ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€ΠΎΠ² ΠΈ Π±Π»ΠΎΠΊΠ°Π΄Π° Ρ‚ΠΎΠ»ΡŒΠΊΠΎ Ξ±-Π°Π΄Ρ€Π΅Π½ΠΎΡ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€ΠΎΠ² (Π±Π΅Π· ввСдСния сСротонина) Π½Π΅ влияли Π½Π° ΠΌΠΎΡ‚ΠΎΡ€ΠΈΠΊΡƒ ΠΆΠ΅Π»ΡƒΠ΄ΠΊΠ° ΠΈΠ½Ρ‚Π°ΠΊΡ‚Π½Ρ‹Ρ… ΠΆΠΈΠ²ΠΎΡ‚Π½Ρ‹Ρ…. Π‘Π»ΠΎΠΊΠ°Π΄Π° ΠΆΠ΅ Ρ‚ΠΎΠ»ΡŒΠΊΠΎ Ξ²- Π°Π΄Ρ€Π΅Π½ΠΎΡ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€ΠΎΠ² Π²Π΅Π΄Π΅Ρ‚ ΠΊ ΡƒΡΠΈΠ»Π΅Π½ΠΈΡŽ сокращСний ΠΆΠ΅Π»ΡƒΠ΄ΠΊΠ° Π½Π° 34%. Π’Ρ‹Π²ΠΎΠ΄. Π˜Π½Ρ‚Π°ΠΊΡ‚Π½Ρ‹Π΅ a- ΠΈ b- Π°Π΄Ρ€Π΅Π½ΠΎΡ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€Ρ‹ ΠΏΡ€Π΅ΠΏΡΡ‚ΡΡ‚Π²ΡƒΡŽΡ‚ стимуляторному Π΄Π΅ΠΉΡΡ‚Π²ΠΈΡŽ сСротонина Π½Π° ΠΌΠΎΡ‚ΠΎΡ€ΠΈΠΊΡƒ ΠΆΠ΅Π»ΡƒΠ΄ΠΊΠ°

    ΠšΡ€ΠΈΡ‚Π΅Ρ€ΠΈΠΈ диагностики Π»ΠΈΠΌΡ„ΠΎΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ‚ΠΈΠ²Π½Ρ‹Ρ… Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ ΠΏΠΎ пСрифСричСской ΠΊΡ€ΠΎΠ²ΠΈ ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚ΠΎΠ² ΠΏΡ€ΠΈ ΠΏΠΎΠΌΠΎΡ‰ΠΈ ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠ³ΠΎ Π±ΠΈΠΎΡ‡ΠΈΠΏΠ°

    No full text
    Background: At present, the diagnosis of lymphoproliferative disorders is based on the combination of blood or bone marrow smear morphology and immunophenotyping by flow cytometry. Immunophenotypic testing by flow cytometry technique is available only in big medical centers, which is not always convenient for a Β patient. Therefore, development of an available method for preliminary diagnosis of lymphoproliferative diseases not requiring special equipment seems relevant.Materials and methods: Peripheral blood mononuclear cells from 17 Β patients admitted to the hospital with suspicion of a Β lymphoproliferative disorder, and 17 Β healthy donors were studied on a cell biochip for determination of proportions of cells positive for various surface CD antigens. The diagnosis was verified by flow cytometry.Results: Compared to healthy controls and patients with T-cell lymphoproliferative disorders (TCLPD), the patients with B-cell lymphoproliferative disorders (BCLPD) had significantly lower proportion of CD7+ cells (medians, 7% and 73% respectively, p=2Γ—10-6 for comparison with healthy controls; median Β 7% and 93% for comparison with TCLPD, p=0.032). In addition, the patients with BCLPD had higher proportion of peripheral Π‘D19+ mononuclear cells, compared to that in the patients with TCLPD and healthy donors (medians 84% and 13% for comparison between BCLPD and healthy control, p=2Γ—10-5; 84% and 3% for comparison of BCLPD and TCLPD, p=0.033). The patients with B-cell chronic lymphocytic leukemia had significantly higher CD5+ cells in the cell biochip compared to the patients with other BCLPD (medians 72% and 9%, p=0.024). The patients with TCLPD had significantly lower proportion of CD19+ cells than the healthy controls (medians, 3% and 13%, respectively, Ρ€=0.042).Conclusion: The study has demonstrated the potential to use the previously developed cell biochip for diagnosis of lymphoproliferative diseases. The biochip makes it possible to sort out white blood cells according to their surface differentiation antigen for their further morphological analysis. The cell biochip allows for the differential diagnosis between BCLPD and TCLPD and determination the lymphocyte clones based on the expression of immunoglobulin light chains.ΠΠΊΡ‚ΡƒΠ°Π»ΡŒΠ½ΠΎΡΡ‚ΡŒ. Π’  настоящСС врСмя диагностика Π»ΠΈΠΌΡ„ΠΎΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ‚ΠΈΠ²Π½Ρ‹Ρ… Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ базируСтся Π½Π° сочСтании морфологичСского исслСдования ΠΌΠ°Π·ΠΊΠΎΠ² ΠΊΡ€ΠΎΠ²ΠΈ ΠΈΠ»ΠΈ костного ΠΌΠΎΠ·Π³Π° с Β ΠΈΠΌΠΌΡƒΠ½ΠΎΡ„Π΅Π½ΠΎΡ‚ΠΈΠΏΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΎΠΌ ΠΏΡ€ΠΎΡ‚ΠΎΡ‡Π½ΠΎΠΉ Ρ†ΠΈΡ‚ΠΎΠΌΠ΅Ρ‚Ρ€ΠΈΠΈ. ΠŸΡ€ΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠ΅ иммунофСнотипичСского исслСдования ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΎΠΌ ΠΏΡ€ΠΎΡ‚ΠΎΡ‡Π½ΠΎΠΉ Ρ†ΠΈΡ‚ΠΎΠΌΠ΅Ρ‚Ρ€ΠΈΠΈ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎ Ρ‚ΠΎΠ»ΡŒΠΊΠΎ Π² Β ΠΊΡ€ΡƒΠΏΠ½Ρ‹Ρ… мСдицинских Ρ†Π΅Π½Ρ‚Ρ€Π°Ρ…, Ρ‡Ρ‚ΠΎ Π½Π΅ всСгда ΡƒΠ΄ΠΎΠ±Π½ΠΎ для ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚Π°. Π’  этой связи созданиС доступного ΠΌΠ΅Ρ‚ΠΎΠ΄Π° ΠΏΡ€Π΅Π΄Π²Π°Ρ€ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎΠΉ диагностики Π»ΠΈΠΌΡ„ΠΎΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ‚ΠΈΠ²Π½Ρ‹Ρ… Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ, ΠΊΠΎΡ‚ΠΎΡ€Ρ‹ΠΉ Π½Π΅ Ρ‚Ρ€Π΅Π±ΡƒΠ΅Ρ‚ ΡΠΏΠ΅Ρ†ΠΈΠ°Π»ΡŒΠ½ΠΎΠ³ΠΎ оборудования, прСдставляСтся Π°ΠΊΡ‚ΡƒΠ°Π»ΡŒΠ½ΠΎΠΉ Π·Π°Π΄Π°Ρ‡Π΅ΠΉ.ΠœΠ°Ρ‚Π΅Ρ€ΠΈΠ°Π» ΠΈ ΠΌΠ΅Ρ‚ΠΎΠ΄Ρ‹. ΠœΠΎΠ½ΠΎΠ½ΡƒΠΊΠ»Π΅Π°Ρ€Ρ‹ пСрифСричСской ΠΊΡ€ΠΎΠ²ΠΈ 17 Β ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚ΠΎΠ², ΠΏΠΎΡΡ‚ΡƒΠΏΠΈΠ²ΡˆΠΈΡ… Π²  стационар с Β ΠΏΠΎΠ΄ΠΎΠ·Ρ€Π΅Π½ΠΈΠ΅ΠΌ Π½Π° Π»ΠΈΠΌΡ„ΠΎΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ‚ΠΈΠ²Π½ΠΎΠ΅ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠ΅, ΠΈ 17 Π·Π΄ΠΎΡ€ΠΎΠ²Ρ‹Ρ… Π΄ΠΎΠ½ΠΎΡ€ΠΎΠ² исслСдовались Π½Π° ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠΌ Π±ΠΈΠΎΡ‡ΠΈΠΏΠ΅ для опрСдСлСния Π΄ΠΎΠ»ΠΈ ΠΊΠ»Π΅Ρ‚ΠΎΠΊ, ΠΏΠΎΠ»ΠΎΠΆΠΈΡ‚Π΅Π»ΡŒΠ½Ρ‹Ρ… ΠΏΠΎ Ρ€Π°Π·Π»ΠΈΡ‡Π½Ρ‹ΠΌ повСрхностным CD-Π°Π½Ρ‚ΠΈΠ³Π΅Π½Π°ΠΌ. Для Π²Π΅Ρ€ΠΈΡ„ΠΈΠΊΠ°Ρ†ΠΈΠΈ Π΄ΠΈΠ°Π³Π½ΠΎΠ·Π° использовали ΠΏΡ€ΠΎΡ‚ΠΎΡ‡Π½ΡƒΡŽ Ρ†ΠΈΡ‚ΠΎΠΌΠ΅Ρ‚Ρ€ΠΈΡŽ.Π Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Ρ‹. ΠŸΠ°Ρ†ΠΈΠ΅Π½Ρ‚Ρ‹ с Β Π’-ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½Ρ‹ΠΌΠΈ Π»ΠΈΠΌΡ„ΠΎΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ‚ΠΈΠ²Π½Ρ‹ΠΌΠΈ заболСваниями (Π’-Π›ΠŸΠ—) статистичСски Π·Π½Π°Ρ‡ΠΈΠΌΠΎ ΠΎΡ‚Π»ΠΈΡ‡Π°Π»ΠΈΡΡŒ ΠΎΡ‚ Π·Π΄ΠΎΡ€ΠΎΠ²Ρ‹Ρ… Π΄ΠΎΠ½ΠΎΡ€ΠΎΠ² Π±ΠΎΠ»Π΅Π΅ Π½ΠΈΠ·ΠΊΠΎΠΉ Π΄ΠΎΠ»Π΅ΠΉ CD7+ (ΠΌΠ΅Π΄ΠΈΠ°Π½Ρ‹ Β 7 ΠΈ Β 73% ΠΏΡ€ΠΈ сравнСнии Π’-Π›ΠŸΠ— ΠΈ  контроля, p=2Γ—10-6; ΠΌΠ΅Π΄ΠΈΠ°Π½Ρ‹ 93 ΠΈ 7% ΠΏΡ€ΠΈ сравнСнии ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚ΠΎΠ² с Β T-ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½Ρ‹ΠΌΠΈ Π»ΠΈΠΌΡ„ΠΎΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ‚ΠΈΠ²Π½Ρ‹ΠΌΠΈ заболСваниями (Π’-Π›ΠŸΠ—) ΠΈ Π’-Π›ΠŸΠ—, p=0,032) ΠΈ Π±ΠΎΠ»Π΅Π΅ высокой Π΄ΠΎΠ»Π΅ΠΉ Π‘D19+ ΠΌΠΎΠ½ΠΎΠ½ΡƒΠΊΠ»Π΅Π°Ρ€Π½Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΠΊ пСрифСричСской ΠΊΡ€ΠΎΠ²ΠΈ ΠΏΠΎ ΡΡ€Π°Π²Π½Π΅Π½ΠΈΡŽ с Β ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚Π°ΠΌΠΈ с Β Π’-Π›ΠŸΠ— ΠΈ Β Π·Π΄ΠΎΡ€ΠΎΠ²Ρ‹ΠΌΠΈ Π΄ΠΎΠ½ΠΎΡ€Π°ΠΌΠΈ (ΠΌΠ΅Π΄ΠΈΠ°Π½Ρ‹ Β 84 ΠΈ Β 13% ΠΏΡ€ΠΈ сравнСнии ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚ΠΎΠ² с Β Π’-Π›ΠŸΠ— ΠΈ  контроля, p=2Γ—10-5; 84 ΠΈ Β 3% ΠΏΡ€ΠΈ сравнСнии ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚ΠΎΠ² с B-Π›ΠŸΠ— ΠΈ T-Π›ΠŸΠ—, p=0,033). ΠŸΠ°Ρ†ΠΈΠ΅Π½Ρ‚Ρ‹ с Β Π’-ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½Ρ‹ΠΌ хроничСским Π»ΠΈΠΌΡ„ΠΎΠ»Π΅ΠΉΠΊΠΎΠ·ΠΎΠΌ (Π’-Π₯Π›Π›) статистичСски Π·Π½Π°Ρ‡ΠΈΠΌΠΎ ΠΎΡ‚Π»ΠΈΡ‡Π°Π»ΠΈΡΡŒ ΠΎΡ‚ ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚ΠΎΠ² с Π΄Ρ€ΡƒΠ³ΠΈΠΌΠΈ Π’-Π›ΠŸΠ— Π±ΠΎΠ»Π΅Π΅ высокой Π΄ΠΎΠ»Π΅ΠΉ Π‘D5+ ΠΊΠ»Π΅Ρ‚ΠΎΠΊ Π½Π° ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠΌ Π±ΠΈΠΎΡ‡ΠΈΠΏΠ΅ (ΠΌΠ΅Π΄ΠΈΠ°Π½Ρ‹ Β 72 ΠΈ Β 9% ΠΏΡ€ΠΈ сравнСнии ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚ΠΎΠ² с Π’-Π₯Π›Π› ΠΈ Π’-Π›ΠŸΠ—, p=0,024). ΠŸΠ°Ρ†ΠΈΠ΅Π½Ρ‚Ρ‹ с Π’-Π›ΠŸΠ— статистичСски Π·Π½Π°Ρ‡ΠΈΠΌΠΎ ΠΎΡ‚Π»ΠΈΡ‡Π°Π»ΠΈΡΡŒ ΠΎΡ‚ Π·Π΄ΠΎΡ€ΠΎΠ²Ρ‹Ρ… Π΄ΠΎΠ½ΠΎΡ€ΠΎΠ² Π±ΠΎΠ»Π΅Π΅ Π½ΠΈΠ·ΠΊΠΎΠΉ Π΄ΠΎΠ»Π΅ΠΉ Π‘D19+ ΠΊΠ»Π΅Ρ‚ΠΎΠΊ (ΠΌΠ΅Π΄ΠΈΠ°Π½Ρ‹ 3 ΠΈ 13% ΠΏΡ€ΠΈ сравнСнии ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚ΠΎΠ² с Π’-Π›ΠŸΠ— ΠΈ контроля, Ρ€=0,042).Π—Π°ΠΊΠ»ΡŽΡ‡Π΅Π½ΠΈΠ΅. Показана Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡ‚ΡŒ диагностики Π»ΠΈΠΌΡ„ΠΎΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ‚ΠΈΠ²Π½Ρ‹Ρ… Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ с  использованиСм Ρ€Π°Π·Ρ€Π°Π±ΠΎΡ‚Π°Π½Π½ΠΎΠ³ΠΎ Ρ€Π°Π½Π΅Π΅ ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠ³ΠΎ Π±ΠΈΠΎΡ‡ΠΈΠΏΠ°. Π‘ Β Π΅Π³ΠΎ ΠΏΠΎΠΌΠΎΡ‰ΡŒΡŽ ΠΌΠΎΠΆΠ½ΠΎ Ρ€Π°ΡΡΠΎΡ€Ρ‚ΠΈΡ€ΠΎΠ²Π°Ρ‚ΡŒ Π»Π΅ΠΉΠΊΠΎΡ†ΠΈΡ‚Ρ‹ Π²  пространствС ΠΏΠΎ ΠΈΡ… повСрхностным Π΄ΠΈΡ„Ρ„Π΅Ρ€Π΅Π½Ρ†ΠΈΡ€ΠΎΠ²ΠΎΡ‡Π½Ρ‹ΠΌ Π°Π½Ρ‚ΠΈΠ³Π΅Π½Π°ΠΌ для дальнСйшСго морфологичСского Π°Π½Π°Π»ΠΈΠ·Π°. ΠšΠ»Π΅Ρ‚ΠΎΡ‡Π½Ρ‹ΠΉ Π±ΠΈΠΎΡ‡ΠΈΠΏ позволяСт ΠΏΡ€ΠΎΠ²ΠΎΠ΄ΠΈΡ‚ΡŒ Π΄ΠΈΡ„Ρ„Π΅Ρ€Π΅Π½Ρ†ΠΈΠ°Π»ΡŒΠ½ΡƒΡŽ диагностику ΠΌΠ΅ΠΆΠ΄Ρƒ Π’- ΠΈ Β Π’-Π›ΠŸΠ— ΠΈ Β ΠΎΠΏΡ€Π΅Π΄Π΅Π»ΡΡ‚ΡŒ ΠΊΠ»ΠΎΠ½Π°Π»ΡŒΠ½ΠΎΡΡ‚ΡŒ Π’-Π»ΠΈΠΌΡ„ΠΎΡ†ΠΈΡ‚ΠΎΠ² Π½Π° основС экспрСссии Π»Π΅Π³ΠΊΠΈΡ… Ρ†Π΅ΠΏΠ΅ΠΉ ΠΈΠΌΠΌΡƒΠ½ΠΎΠ³Π»ΠΎΠ±ΡƒΠ»ΠΈΠ½ΠΎΠ²

    The formation of catalytically competent enzyme–substrate complex is not a bottleneck in lesion excision by human alkyladenine DNA glycosylase

    No full text
    <p>Human alkyladenine DNA glycosylase (AAG) protects DNA from alkylated and deaminated purine lesions. AAG flips out the damaged nucleotide from the double helix of DNA and catalyzes the hydrolysis of the N-glycosidic bond to release the damaged base. To understand better, how the step of nucleotide eversion influences the overall catalytic process, we performed a pre-steady-state kinetic analysis of AAG interaction with specific DNA-substrates, 13-base pair duplexes containing in the 7th position 1-N6-ethenoadenine (Ξ΅A), hypoxanthine (Hx), and the stable product analogue tetrahydrofuran (F). The combination of the fluorescence of tryptophan, 2-aminopurine, and 1-N6-ethenoadenine was used to record conformational changes of the enzyme and DNA during the processes of DNA lesion recognition, damaged base eversion, excision of the N-glycosidic bond, and product release. The thermal stability of the duplexes characterized by the temperature of melting, <i>T</i><sub>m</sub>, and the rates of spontaneous opening of individual nucleotide base pairs were determined by NMR spectroscopy. The data show that the relative thermal stability of duplexes containing a particular base pair in position 7, (<i>T</i><sub>m</sub>(F/T) < <i>T</i><sub>m</sub>(Ξ΅A/T) < <i>T</i><sub>m</sub>(Hx/T) < <i>T</i><sub>m</sub>(A/T)) correlates with the rate of reversible spontaneous opening of the base pair. However, in contrast to that, the catalytic lesion excision rate is two orders of magnitude higher for Hx-containing substrates than for substrates containing Ξ΅A, proving that catalytic activity is not correlated with the stability of the damaged base pair. Our study reveals that the formation of the catalytically competent enzyme–substrate complex is not the bottleneck controlling the catalytic activity of AAG.</p
    corecore