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