CHRONIC MYELOID LEUKEMIA: EPIDEMIOLOGY AND FIFTEENTH YEARS OF THERAPY IN THE NOVOSIBIRSK REGION

The incidence of chronic myeloid leukemia from 2004 to 2018 amounted to 0.63 per 100 000 people per year. The prevalence of chronic myeloid leukemia over the past 15 years has increased from 1.88 to 7.02 case per 100 000 people. We have analyzed the therapy outcomes of chronic myeloid leukemia of patients, received imatinib treatment for more than 12 month (165 patients). Complete hematologic response is attained in 88.5 % cases (146 patients), complete cytogenetic response (CCR) (ph+<0 %) – in 72.1 % cases (119 patients), major molecular response (MMR) – in 50.3 % cases (83 patients). The primary resistance to imatinib is observed in 21.8 % cases (36 patients), secondary – in 6.1 % cases (10 patients – 7 patients have lost the complete hematologic response and CCR and 3 patients have lost the CCR and MMR). The thirteen patients of those, who have primary or secondary resistance to imatinib have been treated with second-generation tyrosine kinase inhibitors (nilotinib, dasatinib) and in 93,3 % cases (14 patients) CCR have been obtained, 10 patients (66.7 %) have attained the CCR and 9 patients (60 %) have achieved MMR. Among all those patients treated with I and II generations tyrosine kinase inhibitors, we have carried out the overall survival (OS) analysis and obtained following results: the median of OS have not been achieved, 5-year OS rate is estimated as 90 %, 10-year OS rate – more than 77 %, calculated 15-year OS – more than 60 %

The genetic history of admixture across inner Eurasia

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this record.Data Availability. Genome-wide sequence data of two Botai individuals (BAM format) are available at the European Nucleotide Archive under the accession number PRJEB31152 (ERP113669). Eigenstrat format array genotype data of 763 present-day individuals and 1240K pulldown genotype data of two ancient Botai individuals are available at the Edmond data repository of the Max Planck Society (https://edmond.mpdl.mpg.de/imeji/collection/Aoh9c69DscnxSNjm?q=).The indigenous populations of inner Eurasia, a huge geographic region covering the central Eurasian steppe and the northern Eurasian taiga and tundra, harbor tremendous diversity in their genes, cultures and languages. In this study, we report novel genome-wide data for 763 individuals from Armenia, Georgia, Kazakhstan, Moldova, Mongolia, Russia, Tajikistan, Ukraine, and Uzbekistan. We furthermore report additional damage-reduced genome-wide data of two previously published individuals from the Eneolithic Botai culture in Kazakhstan (~5,400 BP). We find that present-day inner Eurasian populations are structured into three distinct admixture clines stretching between various western and eastern Eurasian ancestries, mirroring geography. The Botai and more recent ancient genomes from Siberia show a decrease in contribution from so-called “ancient North Eurasian” ancestry over time, detectable only in the northern-most “forest-tundra” cline. The intermediate “steppe-forest” cline descends from the Late Bronze Age steppe ancestries, while the “southern steppe” cline further to the South shows a strong West/South Asian influence. Ancient genomes suggest a northward spread of the southern steppe cline in Central Asia during the first millennium BC. Finally, the genetic structure of Caucasus populations highlights a role of the Caucasus Mountains as a barrier to gene flow and suggests a post-Neolithic gene flow into North Caucasus populations from the steppe.Max Planck SocietyEuropean Research Council (ERC)Russian Foundation for Basic Research (RFBR)Russian Scientific FundNational Science FoundationU.S. National Institutes of HealthAllen Discovery CenterUniversity of OstravaCzech Ministry of EducationXiamen UniversityFundamental Research Funds for the Central UniversitiesMES R

Structural Biology by NMR: Structure, Dynamics, and Interactions

The function of bio-macromolecules is determined by both their 3D structure and conformational dynamics. These molecules are inherently flexible systems displaying a broad range of dynamics on time-scales from picoseconds to seconds. Nuclear Magnetic Resonance (NMR) spectroscopy has emerged as the method of choice for studying both protein structure and dynamics in solution. Typically, NMR experiments are sensitive both to structural features and to dynamics, and hence the measured data contain information on both. Despite major progress in both experimental approaches and computational methods, obtaining a consistent view of structure and dynamics from experimental NMR data remains a challenge. Molecular dynamics simulations have emerged as an indispensable tool in the analysis of NMR data

13C multiplet nuclear magnetic resonance relaxation-derived ring puckering and backbone dynamics in proline-containing glycine-based peptides.

13CH2-multiplet nuclear magnetic resonance relaxation studies on proline (P)-containing glycine (G)-based peptides, GP, PG, GPG, PGG, and GPGG, provided numerous dipolar auto- and cross-correlation times for various motional model analyses of backbone and proline-ring bond rotations. Molecular dynamics simulations and bond rotation energy profiles were calculated to assess which motions could contribute most to observed relaxation phenomena. Results indicate that proline restricts backbone psi 1, psi 2, and phi 2 motions by 50% relative to those found for a polyglycine control peptide. psi 1 rotations are more restricted in the trans-proline isomer state than in the cis form. A two-state jump model best approximates proline ring puckering which in water could occur either by the C gamma endo-exo or by the C2 interconversion mechanism. The temperature dependence (5 degrees to 75 degrees C) of C beta, and C gamma, and C delta angular changes is rather flat, suggesting a near zero enthalpic contribution to the ring puckering process. In lower dielectric solvents, dimethylsulfoxide and methanol, which may mimic the hydrophobic environment within a protein, the endo-exo mechanism is preferred

Магнітометрія скіфського курганного могильника Катеринівка у Нижньому Подніпров’ї

The magnetometry of the Katerinovka burial ground (Nikopol district, Dnipropet-rovsk region, Ukraine) conducted on the area of 3.65 hectares showed three times more kurgans than they were visually detected or deciphered from satellite images. Archaeological excavations performed throughout the whole territory of geomagnetic survey area showed that most of the kurgans (24) belong to the Scythian epoch (IV century BC). There were also four burial mounds of the Golden Horde time (XIII—XIV centuries) and one — of the Bronze Age (beginning of the III millennium BC). Anomalies of magnetic induction (Bа) on the burial ground were mainly caused by objects deepened into the loess parent rock with magnetic susceptibility k = (0,3 ¸ 0,4) × 10–3 SI units and puddled with dark humus soil with k = (0.7 ¸ 0.9) × 10–3 SI units. The structural elements of the kurgans — pits, catacombs, ditches, and near-kurgan grooves — create weak (2—10 nT) anomalies of geomagnetic induction, which are reliably recorded using cesium magnetometers even under conditions of intense manmade interference from a heavy machinery in a quarry nearby. The fact of the existence of the near-kurgan grooves, from where the soil was taken to pour the Scythian mounds, was discovered for the first time from magnetometry results. The Bronze Age kurgan was identified by the semiring Bа anomaly from the groove 15—20 m wide. Among 10 burials, only two, the deepest ones, have created Bа anomalies with an intensity of 1.5—5.4 nT. Golden Horde kurgans were defined on the Bа map by weak ring anomalies from the ditches, as well as from the burnt bricks heaps covering some burials. The results of geomagnetic survey and archaeological excavations on the anomalies proved the inter-kurgan space of the visible mounds to be full of smaller sized and worse preserved kurgans. It has been shown that there is an urgent need to use high-resolution magnetometry at registering and studying the kurgan monuments of Ukraine, especially in areas of intensive industrial and agricultural land use.Магнитометрия могильника Катериновка (Никопольский р-н, Днепропетровская обл., Украина) на площади 3,65 га показала наличие втрое большего количества курганов, чем обнаружено визуально и дешифрировано по космоснимкам. Согласно археологическим исследованиям, проведенным на всей площади геомагнитной съемки, большинство курганов (24) относится к скифской эпохе (IV в. до н. э.), также на могильнике расположены четыре кургана золотоордынского времени (XIII-XIV вв.) и один - эпохи бронзы (начало III тыс. до н. э.). Аномалии магнитной индукции (Bа) на могильнике связаны преимущественно с объектами, углубленными в лессовую материковую породу с магнитной восприимчивостью k = (0,3 ё 0,4) Ч 10–3 ед. СИ, которые имеют затечное заполнение темным гумусированным грунтом с k = (0,7 ё 0,9) ґ ґ 10–3 ед. СИ. Структурные элементы скифских курганов - ямы, катакомбы, рвы и прикурганные выемки, создают слабые (2-10 нТл) аномалии Bа, которые надежно регистрируются с помощью цезиевых магнитометров даже в условиях интенсивных техногенных помех от тяжелой техники в близрасположенном карьере. Факт наличия выемок, откуда брали грунт для отсыпки скифских курганов, обнаружен впервые благодаря магнитометрии. Курган эпохи бронзы идентифицирован по полукольцевой аномалии Bа от выемки шириной 15-20 м. Из 10 захоронений только 2 наиболее глубоких создали аномалии Bа интенсивностью 1,5-5,4 нТл. Золотоордынские курганы определены на карте Bа по слабым кольцевым аномалиям от рвов, а также от завалов из обожженного кирпича над некоторыми захоронениями. Результаты геомагнитной съемки и археологических исследований аномалий доказывают,что межкурганное пространство видимых курганов насыщено курганами меньшего размера и худшей степени сохранности. Показана настоятельная необходимость применения высокоточной магнитометрии для учета и исследования курганных памятников Украины, особенно на участках интенсивного промышленного и сельскохозяйственного землепользования.Магнітометрія могильника Катеринівка (Нікопольський р-н, Дніпропетровська обл., Україна) на площі 3,65 га показала наявність втричі більшої кількості курганів, ніж виявлено візуально і розшифрувати по космознімків. Згідно з археологічними дослідженнями, проведеними на всій площі геомагнітної зйомки, більшість курганів (24) відноситься до скіфської епохи (IV ст. До н. Е.), Також на могильнику розташовані чотири кургани золотоординського часу (XIII-XIV ст.) І один - епохи бронзи (початок III тис. до н. е.). Аномалії магнітної індукції (Bа) на могильнику пов'язані переважно з об'єктами, поглибленими в лесових материкову породу з магнітною сприйнятливістю k = (0,3 е 0,4) Ч 10-3 од. СІ, які мають затечное заповнення темним гумусірованние грунтом з k = (0,7 е 0,9) ґ ґ 10-3 од. СІ. Структурні елементи скіфських курганів - ями, катакомби, рови і прікурганние виїмки, створюють слабкі (2-10 нТл) аномалії Bа, які надійно реєструються за допомогою цезієвого магнітометрів навіть в умовах інтенсивних техногенних перешкод від важкої техніки в блізрасположенних кар'єрі. Факт наявності виїмок, звідки брали грунт для відсипки скіфських курганів, виявлений вперше завдяки магнітометри. Курган епохи бронзи ідентифікований по напівкільцевий аномалії Bа від виїмки шириною 15-20 м. З 10 поховань тільки 2 найбільш глибоких створили аномалії Bа інтенсивністю 1,5-5,4 нТл. Золотоординські кургани визначені на карті Bа по слабких кільцевих аномалій від ровів, а також від завалів з обпаленої цегли над деякими похованнями. Результати геомагнітної зйомки і археологічних досліджень аномалій доводять, що межкурганное простір видимих курганів насичене курганами меншого розміру і гіршою ступеня збереження. Показана нагальна необхідність застосування високоточної магнітометри для обліку і дослідження курганних пам'яток України, особливо на ділянках інтенсивного промислового і сільськогосподарського землекористування

Specific binding of ethanol to cholesterol in organic solvents.

Although ethanol has been reported to affect cholesterol homeostasis in biological membranes, the molecular mechanism of action is unknown. Here, nuclear magnetic resonance (NMR) spectroscopic techniques have been used to investigate possible direct interactions between ethanol and cholesterol in various low dielectric solvents (acetone, methanol, isopropanol, DMF, DMSO, chloroform, and CCl(4)). Measurement of (13)C chemical shifts, spin-lattice and multiplet relaxation times, as well as self-diffusion coefficients, indicates that ethanol interacts weakly, yet specifically, with the HC-OH moiety and the two flanking methylenes in the cyclohexanol ring of cholesterol. This interaction is most strong in the least polar-solvent carbon tetrachloride where the ethanol-cholesterol equilibrium dissociation constant is estimated to be 2 x 10(-3) M. (13)C-NMR spin-lattice relaxation studies allow insight into the geometry of this complex, which is best modeled with the methyl group of ethanol sandwiched between the two methylenes in the cyclohexanol ring and the hydroxyl group of ethanol hydrogen bonded to the hydroxyl group of cholesterol