119 research outputs found
Orienting Role of Terminology in Context of Its Scientific-Popular Conceptualization
The article examines the structural and functional properties of terms in popular scientific discourse. The authors aim to characterize the orientation of a term as a combination of its linguistic and functional properties, which define the concept expressed by the term, its connections with other concepts, and its place within the terminological system. The object of the study is linguistic and speech units in popular scientific texts, while the subject is the means of expressing orienting properties of terms in popular scientific discourse. The novelty of the research lies in studying the orienting properties of terms in popular scientific style based on their linguistic and speech properties, and providing a classification of these properties according to the scope and content of the expressed concepts. The relevance of the study is determined by the important role of these properties in the process of forming specialized concepts, understanding scientific, popular scientific, and educational discourses, and solving practical problems related to terminology use. The authors focus on the orienting function of a term, which is carried out through linguistic and speech means, with logical definitions, textual explanations, intercategorical connections expressed by elements of word formation and morpho-syntactic systems being the most active ones. The authors conclude that orienting properties of terms play a significant role in terminological conceptualization (formation of specialized concepts)
Coherent spin relaxation in molecular magnets
Numerical modelling of coherent spin relaxation in nanomagnets, formed by
magnetic molecules of high spins, is accomplished. Such a coherent spin
dynamics can be realized in the presence of a resonant electric circuit coupled
to the magnet. Computer simulations for a system of a large number of
interacting spins is an efficient tool for studying the microscopic properties
of such systems. Coherent spin relaxation is an ultrafast process, with the
relaxation time that can be an order shorter than the transverse spin dephasing
time. The influence of different system parameters on the relaxation process is
analysed. The role of the sample geometry on the spin relaxation is
investigated.Comment: Latex file, 22 pages, 7 figure
Quality of life of patients with different forms of hemophilia on the example of Nizhny Novgorod region
It is important for public health to monitor and improve the health indicators of the population using the system of patient's quality of life (HRQoL) assessment regardless of the nosology of the disease. The use of HRQoL assessment provides health authorities with a tool for additional analysis of the performance of health services and for making decisions about funding priorities. The definition of HRQoL is one of the decisive factors in the calculation of QALYs because it measures the effectiveness of medical treatment in terms of how much it prolongs and/or improves patients' lives. The aim of the study is to determine the QALYs of hemophilia patients in Nizhny Novgorod region by means of electronic questionnaire using the SF-36 questionnaire. Methods. A validated SF-36 short form questionnaire was used in the study, which was distributed to adult patients with hemophilia A, B and Willebrand's disease of Nizhny Novgorod region together with a short form of informed voluntary consent. Twenty-eight people participated in the questionnaire. Calculation of general and final indicators of the HRQoL was carried out according to the instructions for processing data obtained with the SF-36 questionnaire. Results. The lowest score among all respondents was for GH "General Health Status" with a mean value of 61.00, and the highest score was for PF "Physical Functioning" with a mean value of 81.43. The study revealed that the majority of the surveyed patients were receiving Emicizumab (42.86 %). After comparing the ranges of values of the final indicators of physical (PH) and mental (MN') health in patients with different forms of hemophilia, the highest values of HRQoL indicators are observed in patients with hemophilia B, and the highest range of extreme values β in patients with hemophilia A. Conclusion. Patients with different forms of hemophilia are determined to have satisfactory values of HRQoL indicators, as all the results obtained in the course of the questionnaire are above the average value of the indicators. Mean HRQoL scores in patients receiving emicizumab are at a similar level compared to patients receiving other LPs, and fluctuations in HRQoL scores in these patients are less marked than in the other patients with hemophilia A
Economic analysis of the use of drugs for the treatment of hemophilia A, B and Willebrand's disease
Relevance. Therapy of hemophilia A, B and Willebrand's disease is carried out under the program of 14 VZN due to the use of federal budget funds. The use of funding is increasing in line with the growth of the total number of patients. In 2022,85.99 billion rubles were allocated, which corresponds to a 1.5βfold increase in funding compared to 2018. The aim of the study was to conduct an economic analysis of the use of drugs for the therapy of hemophilia A, B and Willebrand's disease. Methods. The materials for the analysis were the dosing regimen of LPs selected on the basis of clinical recommendations, the availability of LPs in the 14 VZN program, and the prices for LPs from the State Register of maximum selling prices for VED drugs. Costs of on demand prophylaxis and treatment regimens for hemophilia A, B and Willebrand's disease according to clinical recommendations for each INN for all trade names (TN) were assessed. Results. For hemophilia A the number of submitted drugs by INN is 7;IN β 14; of them domestic drugs were submitted β 1. The minimum cost of LPs for prophylaxis is 2 584 764,00 rubles. Coit-DVI (Grifols Therapeutics LLC, USA), and the maximum cost is RUR 9,955,517.21. Advait (Takeda Manufacturing AG, Austria). Forhemophilia B, the number of represented PL β 2 INN; INN β 6; domestic drugs β 2. The minimum cost is RUR 1,559,376.00. Innonafactor (AO Generium, Russia), maximum β 3 079 319,88 rubles for a year course of prophylaxis LP Immunin (TakedaManufacturing, Austria). To stop bleeding in patients with inhibitor form use anti-inhibitor coagulant complex (Feiba, Austria), which is necessary on average 9100 units per 1 patient, and the average cost of application β 430 863,52 rubles or eptacog alpha(activated) (Coagil-VII, Russia) at multiple administration to the patient 6 times a day β maximum cost β 2 739 803,64 rubles or once a day β 293 550,35 rubles. Conclusion. In the structure of drug supply for patients with hemophilia, domestic drugs are represented by 5 names: Octofactor (JSC "Generium", Russia); Agemfil B (FGBU "NMIC Hematology" of the Ministry of Health of Russia, Russia) and Innonafactor (JSC "Generium", Russia); ArioSaven (LLC "PSK Pharma", Russia) and Coagil-VII (JSC "SG Biotech", Russia). There are no domestic drugs available for the therapy of Willebrand's disease
Morphological verification of the first missed abortion
Objective. The study aimed to compare the level of INF a2 immunoexpression in tissues obtained during medical abortion with the corresponding level of IFNa2 expression in a retained fetal egg tissues after the first missed abortion. The authors compared the anamnestic data on previous inflammatory diseases of the genital tract with the results of an extended morphological study of the material obtained during the evacuation of the contents of the uterine cavity during the first non-developing pregnancy in the first trimester.Materials and methods. The study included 15 patients with first-time missed abortions caused by a viral infection (6-8 weeks of pregnancy). All patients demonstrated either recurrent herpes simplex labialis/genitalis or PCR confirmed HSV, HPV, CMV. Exclusion criteria were recurrent miscarriage, blighted ovum, endocrinopathies, male factor infertility, and other causes of miscarriage. The comparison group included 20 women of the same age that chose to undergo a medical abortion.Results. In patients from the comparison group, the main producer of IFN a2 was syncytiotrophoblast as well as maternal decidual cells in the parietal endometrium and uteroplacental area. In the main group, manifested hematogenous infection (microabscesses, vasculitis, lymphocytic and macrophage infiltration) with dystrophy and necrosis of decidual maternal cells and secondary pathological changes in the placental villi were diagnosed, which led to a significant decrease in the IFN a2 immunoexpression in all the studied cells.Conclusion. The lack of anamnestic data on previous urogenital infections does not exclude the etiological role of the inflammatory component in the genesis of non-developing pregnancy. First-time occurred pregnancy loss requires adequate postoperative interferon therapy and a thorough examination of a couple
Synthesis and cyclization of 1,5-bis((dimethyl(oxo)-Ξ 6 - sulfanilidene)amino)-9,10- anthraquinone
In this article discusses some chemical properties of 1,5- bis((dimethyl(oxo)-Ξ» 6 -sulfaniliden)amino)-9,10-anthroquinone.Π Π΄Π°Π½Π½ΠΎΠΉ ΡΡΠ°ΡΡΠ΅ ΡΠ°ΡΡΠΌΠΎΡΡΠ΅Π½Ρ Π½Π΅ΠΊΠΎΡΠΎΡΡΠ΅ Ρ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠ²ΠΎΠΉΡΡΠ²Π° 1,5-Π±ΠΈΡ((Π΄ΠΈΠΌΠ΅ΡΠΈΠ»(ΠΎΠΊΡΠΎ)-Ξ» 6 -ΡΡΠ»ΡΡΠ°Π½ΠΈΠ»ΠΈΠ΄Π΅Π½)Π°ΠΌΠΈΠ½ΠΎ)-9,10-Π°Π½ΡΡΠ°Ρ
ΠΈΠ½ΠΎΠ½Π°
Π€Π°ΡΠΌΠ°ΠΊΠΎΡΠΏΠΈΠ΄Π΅ΠΌΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠΉ Π°Π½Π°Π»ΠΈΠ· ΠΈ Π°Π½Π°Π»ΠΈΠ· ΠΌΠ΅ΠΆΠ»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠΉ Π² ΡΠ΅ΡΠ°ΠΏΠΈΠΈ Ρ ΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΏΠΎΡΠ΅ΡΠ½ΠΎΠΉ ΠΈ ΠΏΠ΅ΡΠ΅Π½ΠΎΡΠ½ΠΎΠΉ Π½Π΅Π΄ΠΎΡΡΠ°ΡΠΎΡΠ½ΠΎΡΡΠΈ
Objective: to perform pharmacoepidemiological and drug interaction analysis of pharmacotherapy for liver/kidney transplantation.Material and methods. The study was conducted on the basis of multidisciplinary hospital in Nizhny Novgorod, which provides both therapeutic and high-tech surgical care. The object of the study was medical records of 34 patients who had undergone pharmacotherapy for liver/kidney transplantation. We evaluated the particularly dangerous moderate interactions that pose the greatest risk to patient health using Drugs.com electronic resource. Pharmacoepidemiologic assessment was performed using the ATC/DDD methodology (anatomical therapeutic chemical (ATC) classification system β defined daily dose (DDD)) recommended by the World Health Organization. The βaverage bed occupancy per yearβ was calculated using DDD per 100 bed-days. ABC analysis was used to estimate the costs of drug groups in therapy for liver/kidney transplantation. Results. In most cases, the third generation cephalosporins were used in the therapy of liver/kidney transplant patients (55.56% of all prescriptions). Antimicrobial drugs were mostly prescribed as monotherapy (61.9%). There were 111 potential major (14.41%) and moderate (72.07%) interactions detected. The largest number of moderate type risks was associated with changes in blood pressure levels (in 23.75% of cases β possible decrease, in 10% β increase), 7.5% of cases were accompanied by headaches, 6.25% β by reduction of drug effectiveness. In antimicrobial therapy, two main interactions were found: moxifloxacin β tacrolimus (arrhythmia), and metipred β moxifloxacin (tendon dystrophy), which is 12.5% of all main interactions for 21 case histories. In the ABC analysis, immunosuppressants were in group A (cost share 85.8%). Tacrolimus accounted for the largest amount of consumption: number of defined daily doses (NDDD) per year was 532.27 mg, NDDD per 100 bed days reached 432.18 (the highest among all drugs).Conclusion. Pharmacoepidemiologic analysis allows us to systematize data on medication use. The choice of drugs in order to ensure safe and effective use of the registered drug interactions is facilitated by electronic databases.Π¦Π΅Π»Ρ: ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠ΅ ΡΠ°ΡΠΌΠ°ΠΊΠΎΡΠΏΠΈΠ΄Π΅ΠΌΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΈΠ·Π° ΠΈ Π°Π½Π°Π»ΠΈΠ·Π° ΠΌΠ΅ΠΆΠ»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ
Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠΉ ΠΏΡΠΈ ΡΠ°ΡΠΌΠ°ΠΊΠΎΡΠ΅ΡΠ°ΠΏΠΈΠΈ, ΡΠΎΠΏΡΠΎΠ²ΠΎΠΆΠ΄Π°ΡΡΠ΅ΠΉ ΡΡΠ°Π½ΡΠΏΠ»Π°Π½ΡΠ°ΡΠΈΡ ΠΏΠ΅ΡΠ΅Π½ΠΈ/ΠΏΠΎΡΠ΅ΠΊ.ΠΠ°ΡΠ΅ΡΠΈΠ°Π» ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ Π²ΡΠΏΠΎΠ»Π½Π΅Π½ΠΎ Π½Π° Π±Π°Π·Π΅ ΠΌΠ½ΠΎΠ³ΠΎΠΏΡΠΎΡΠΈΠ»ΡΠ½ΠΎΠ³ΠΎ ΡΡΠ°ΡΠΈΠΎΠ½Π°ΡΠ° Π³. ΠΠΈΠΆΠ½Π΅Π³ΠΎ ΠΠΎΠ²Π³ΠΎΡΠΎΠ΄Π°, ΠΎΠΊΠ°Π·ΡΠ²Π°ΡΡΠ΅Π³ΠΎ ΠΊΠ°ΠΊ ΡΠ΅ΡΠ°ΠΏΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΡΡ, ΡΠ°ΠΊ ΠΈ Π²ΡΡΠΎΠΊΠΎΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΡΠ½ΡΡ Ρ
ΠΈΡΡΡΠ³ΠΈΡΠ΅ΡΠΊΡΡ ΠΏΠΎΠΌΠΎΡΡ. ΠΠ±ΡΠ΅ΠΊΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ β ΠΌΠ΅Π΄ΠΈΡΠΈΠ½ΡΠΊΠΈΠ΅ ΠΊΠ°ΡΡΡ 34 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ², ΠΏΡΠΎΡ
ΠΎΠ΄ΠΈΠ²ΡΠΈΡ
ΡΠ°ΡΠΌΠ°ΠΊΠΎΡΠ΅ΡΠ°ΠΏΠΈΡ ΠΏΡΠΈ ΡΡΠ°Π½ΡΠΏΠ»Π°Π½ΡΠ°ΡΠΈΠΈ ΠΏΠ΅ΡΠ΅Π½ΠΈ/ΠΏΠΎΡΠ΅ΠΊ. ΠΡΠ΅Π½ΠΈΠ²Π°Π»ΠΈ ΠΎΡΠΎΠ±ΠΎ ΠΎΠΏΠ°ΡΠ½ΡΠ΅ ΡΠΌΠ΅ΡΠ΅Π½Π½ΡΠ΅ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² (ΠΠ), ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΡΡΠΈΠ΅ Π½Π°ΠΈΠ±ΠΎΠ»ΡΡΠΈΠΉ ΡΠΈΡΠΊ Π΄Π»Ρ Π·Π΄ΠΎΡΠΎΠ²ΡΡ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠ°, Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΡΠ»Π΅ΠΊΡΡΠΎΠ½Π½ΠΎΠ³ΠΎ ΡΠ΅ΡΡΡΡΠ° Drugs.com. Π€Π°ΡΠΌΠ°ΠΊΠΎΡΠΏΠΈΠ΄Π΅ΠΌΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠΉ Π°Π½Π°Π»ΠΈΠ· ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΈ Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΡΠ΅ΠΊΠΎΠΌΠ΅Π½Π΄ΡΠ΅ΠΌΠΎΠΉ ΠΡΠ΅ΠΌΠΈΡΠ½ΠΎΠΉ ΠΎΡΠ³Π°Π½ΠΈΠ·Π°ΡΠΈΠ΅ΠΉ Π·Π΄ΡΠ°Π²ΠΎΠΎΡ
ΡΠ°Π½Π΅Π½ΠΈΡ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ»ΠΎΠ³ΠΈΠΈ ATC/DDD (Π°Π½Π³Π». anatomical therapeutic chemical (ATC) classification system β Π°Π½Π°ΡΠΎΠΌΠΎ-ΡΠ΅ΡΠ°ΠΏΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΎ-Ρ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠ°Ρ ΠΊΠ»Π°ΡΡΠΈΡΠΈΠΊΠ°ΡΠΈΡ, defined daily dose (DDD) β ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½Π½Π°Ρ ΡΡΡΠΎΡΠ½Π°Ρ Π΄ΠΎΠ·Π°) ΠΏΠΎ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Ρ DDD Π·Π° 100 ΠΊΠΎΠΉΠΊΠΎ-Π΄Π½Π΅ΠΉ, ΡΠ°ΡΡΡΠΈΡΡΠ²Π°Π»ΠΈ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Ρ Β«ΡΡΠ΅Π΄Π½ΡΡ Π·Π°Π½ΡΡΠΎΡΡΡ ΠΊΠΎΠΉΠΊΠΈ Π² Π³ΠΎΠ΄ΡΒ». Π‘ ΠΏΠΎΠΌΠΎΡΡΡ ABC-Π°Π½Π°Π»ΠΈΠ·Π° ΠΎΡΠ΅Π½ΠΈΠ»ΠΈ Π·Π°ΡΡΠ°ΡΡ Π½Π° Π³ΡΡΠΏΠΏΡ ΠΠ Π² ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΠΏΡΠΈ ΡΡΠ°Π½ΡΠΏΠ»Π°Π½ΡΠ°ΡΠΈΠΈ ΠΏΠΎΡΠ΅ΠΊ ΠΈΠ»ΠΈ ΠΏΠ΅ΡΠ΅Π½ΠΈ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. Π Π±ΠΎΠ»ΡΡΠΈΠ½ΡΡΠ²Π΅ ΡΠ»ΡΡΠ°Π΅Π² Π² ΡΠ΅ΡΠ°ΠΏΠΈΠΈ Π±ΠΎΠ»ΡΠ½ΡΡ
ΠΏΡΠΈ ΡΡΠ°Π½ΡΠΏΠ»Π°Π½ΡΠ°ΡΠΈΠΈ ΠΏΠ΅ΡΠ΅Π½ΠΈ/ΠΏΠΎΡΠ΅ΠΊ ΠΏΡΠΈΠΌΠ΅Π½ΡΠ»ΠΈΡΡ ΡΠ΅ΡΠ°Π»ΠΎΡΠΏΠΎΡΠΈΠ½Ρ ΡΡΠ΅ΡΡΠ΅Π³ΠΎ ΠΏΠΎΠΊΠΎΠ»Π΅Π½ΠΈΡ (55,56% ΡΡΠ΅Π΄ΠΈ Π²ΡΠ΅Ρ
Π½Π°Π·Π½Π°ΡΠ΅Π½ΠΈΠΉ). ΠΠ½ΡΠΈΠΌΠΈΠΊΡΠΎΠ±Π½ΡΠ΅ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π»ΠΈ ΠΏΡΠ΅ΠΈΠΌΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎ Π² ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ ΠΌΠΎΠ½ΠΎΡΠ΅ΡΠ°ΠΏΠΈΠΈ (61,9%). ΠΡΠ΅Π³ΠΎ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½ΠΎ 111 ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΡΡ
Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠΉ, ΡΡΠ΅Π΄ΠΈ ΠΊΠΎΡΠΎΡΡΡ
ΠΎΡΠ½ΠΎΠ²Π½ΡΠ΅ (major) ΡΠΎΡΡΠ°Π²ΠΈΠ»ΠΈ 14,41%, ΡΠΌΠ΅ΡΠ΅Π½Π½ΡΠ΅ (moderate) β 72,07%. ΠΠ°ΠΈΠ±ΠΎΠ»ΡΡΠ΅Π΅ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²ΠΎ ΡΠΈΡΠΊΠΎΠ² ΡΠΌΠ΅ΡΠ΅Π½Π½ΠΎΠ³ΠΎ ΡΠΈΠΏΠ° ΡΠ²ΡΠ·Π°Π½ΠΎ Ρ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ΠΌ ΡΡΠΎΠ²Π½Ρ Π΄Π°Π²Π»Π΅Π½ΠΈΡ (Π² 23,75% Π½Π°Π·Π½Π°ΡΠ΅Π½ΠΈΠΉ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΠ΅, Π² 10% β ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΠ΅), 7,5% ΡΠ»ΡΡΠ°Π΅Π² ΡΠΎΠΏΡΠΎΠ²ΠΎΠΆΠ΄Π°ΡΡΡΡ Π³ΠΎΠ»ΠΎΠ²Π½ΡΠΌΠΈ Π±ΠΎΠ»ΡΠΌΠΈ, 6,25% β ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΠ΅ΠΌ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΠ. ΠΡΠΈ Π°Π½ΡΠΈΠΌΠΈΠΊΡΠΎΠ±Π½ΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½ΠΎ Π΄Π²Π° ΠΎΡΠ½ΠΎΠ²Π½ΡΡ
Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡ: ΠΌΠΎΠΊΡΠΈΡΠ»ΠΎΠΊΡΠ°ΡΠΈΠ½ β ΡΠ°ΠΊΡΠΎΠ»ΠΈΠΌΡΡ (Π°ΡΠΈΡΠΌΠΈΡ) ΠΈ ΠΌΠ΅ΡΠΈΠΏΡΠ΅Π΄ β ΠΌΠΎΠΊΡΠΈΡΠ»ΠΎΠΊΡΠ°ΡΠΈΠ½ (Π΄ΠΈΡΡΡΠΎΡΠΈΡ ΡΡΡ
ΠΎΠΆΠΈΠ»ΠΈΠΉ), ΡΡΠΎ ΡΠΎΡΡΠ°Π²Π»ΡΠ΅Ρ 12,5% ΠΎΡ Π²ΡΠ΅Ρ
ΠΎΡΠ½ΠΎΠ²Π½ΡΡ
Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠΉ ΠΏΠΎ 21 ΠΈΡΡΠΎΡΠΈΠΈ Π±ΠΎΠ»Π΅Π·Π½ΠΈ. ΠΡΠΈ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠΈ ΠΠΠ‘-Π°Π½Π°Π»ΠΈΠ·Π° Π² Π³ΡΡΠΏΠΏΡ Π Π²Ρ
ΠΎΠ΄ΡΡ ΠΈΠΌΠΌΡΠ½ΠΎΠ΄Π΅ΠΏΡΠ΅ΡΡΠ°Π½ΡΡ (Π΄ΠΎΠ»Ρ Π·Π°ΡΡΠ°Ρ 85,8%). ΠΠ°ΠΈΠ±ΠΎΠ»ΡΡΠ΅Π΅ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²ΠΎ ΠΏΠΎΡΡΠ΅Π±Π»Π΅Π½ΠΈΡ ΠΏΡΠΈΡ
ΠΎΠ΄ΠΈΠ»ΠΎΡΡ Π½Π° ΡΠ°ΠΊΡΠΎΠ»ΠΈΠΌΡΡ: ΡΠΈΡΠ»ΠΎ ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½Π½ΡΡ
ΡΡΡΠΎΡΠ½ΡΡ
Π΄ΠΎΠ· (Π°Π½Π³Π». number of defined daily doses, NDDD) Π² Π³ΠΎΠ΄ ΡΠΎΡΡΠ°Π²ΠΈΠ»ΠΎ 532,27 ΠΌΠ³, Π° NDDD Π·Π° 100 ΠΊΠΎΠΉΠΊΠΎ-Π΄Π½Π΅ΠΉ β 432,18 ΠΌΠ³, ΡΡΠΎ ΡΠ²Π»ΡΠ΅ΡΡΡ ΡΠ°ΠΌΡΠΌ Π²ΡΡΠΎΠΊΠΈΠΌ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Π΅ΠΌ ΡΡΠ΅Π΄ΠΈ Π²ΡΠ΅Ρ
ΠΠ.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. Π€Π°ΡΠΌΠ°ΠΊΠΎΡΠΏΠΈΠ΄Π΅ΠΌΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠΉ Π°Π½Π°Π»ΠΈΠ· ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ ΡΠΈΡΡΠ΅ΠΌΠ°ΡΠΈΠ·ΠΈΡΠΎΠ²Π°ΡΡ Π΄Π°Π½Π½ΡΠ΅ ΠΎΠ± ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠΈ ΠΠ. ΠΡΠ±ΠΎΡ ΠΠ Ρ ΡΠ΅Π»ΡΡ ΠΎΠ±Π΅ΡΠΏΠ΅ΡΠ΅Π½ΠΈΡ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΠ³ΠΎ ΠΈ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠ³ΠΎ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ Π·Π°ΡΠ΅Π³ΠΈΡΡΡΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΠΌΠ΅ΠΆΠ»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ
Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠΉ ΡΠΏΡΠΎΡΠ°Π΅ΡΡΡ ΠΏΡΠΈ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠΈ ΡΠ»Π΅ΠΊΡΡΠΎΠ½Π½ΡΡ
Π±Π°Π· Π΄Π°Π½Π½ΡΡ
Mechanism of Disruption of the Amt-GlnK Complex by PII-Mediated Sensing of 2-Oxoglutarate
GlnK proteins regulate the active uptake of ammonium by Amt transport proteins by inserting their regulatory T-loops into the transport channels of the Amt trimer and physically blocking substrate passage. They sense the cellular nitrogen status through 2-oxoglutarate, and the energy level of the cell by binding both ATP and ADP with different affinities. The hyperthermophilic euryarchaeon Archaeoglobus fulgidus possesses three Amt proteins, each encoded in an operon with a GlnK ortholog. One of these proteins, GlnK2 was recently found to be incapable of binding 2-OG, and in order to understand the implications of this finding we conducted a detailed structural and functional analysis of a second GlnK protein from A. fulgidus, GlnK3. Contrary to Af-GlnK2 this protein was able to bind both ATP/2-OG and ADP to yield inactive and functional states, respectively. Due to the thermostable nature of the protein we could observe the exact positioning of the notoriously flexible T-loops and explain the binding behavior of GlnK proteins to their interaction partner, the Amt proteins. A thermodynamic analysis of these binding events using microcalorimetry evaluated by microstate modeling revealed significant differences in binding cooperativity compared to other characterized PII proteins, underlining the diversity and adaptability of this class of regulatory signaling proteins
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