'Pandora’s box': A textile tool set from a Scythian burial in Ukraine

Textile tools made of perishable materials such as wood are extremely rare in the archaeological contexts of ancient Mediterranean, but numerous complete and fragmentary boxes containing textile tools and other materials have been found in Scythian burials of the 5th-4th centuries BC in southern Ukraine. The boxes are found exclusively in female burials and are clearly of Hellenic craftsmanship. The paper presents preliminary observations about a 4th century BC female burial 2 from Kurgan 5 at Bulgakovo, which was accompanied by a wooden box containing three wooden distaffs, a spindle whorl made of an amphora fragment, a wooden comb and two smaller wooden boxes, one of which stored a set of at least 19 wooden weaving tablets with four holes each, an iron needle and some yarn

Topical issues of vaccination and epidemiological surveillance over measles and rubella in Ukraine.

The analysis of measles and rubella morbidity, the state of their vaccination in Ukraine was carried out. Despite decades of preventive vaccination, there is a 5-6 years’ cyclicity of measles epidemic process at present time. Measles morbidity increased 46.8 times in 2017 in comparison with 2016. Elevated rates of rubella epidemic morbidity were registered in 2004 and 2011. There was decrease of routine measles and rubella immunization coverage in the period from 2009 to 2016. Critically low rates were noted in 2016 – 45.5% (vaccination) and 30.2% (revaccination). In spite of progress in the measles and rubella vaccination in 2017 (93.3% – vaccination and 90.7% – revaccination), Ukraine has not achieved the immunization coverage (≥95.0%) necessary to interrupt these pathogens circulation. The national laboratory and a network of regional ones, in-system of the Global Measles and Rubella Laboratory Network, were established in Ukraine to ensure high-quality performance of epidemiological surveillance. Genotyping of the clinical samples from Ukrainian measles and rubella patients is carried out in the WHO Regional Reference Laboratory (Luxembourg). Different genetic lines of the measles virus with prevalence of D8 genotype were indicated to circulate in Ukraine. The genotype B3 was also identified and the genotype D9 was isolated for the first time. In the furtherance of the goal of rubella and measles elimination in Ukraine, standard international approaches to clinical, laboratory and epide­miological diagnosis of cases, investigation of viruses transmission chains and detection of endemicity cases are in the course of implementation. Quality of the executing activities is assessed according to relevant standard indicators

Problematics of proving the fact of occupational TB in health care workers.

The incidence of tuberculosis in medical per­sonnel in the Dnipropetrovsk region, incl. TB facilities, was analyzed for the period from 2008 to 2017. Occupational TB is an important indicator of infection control efficacy in health care facilities. Despite reducing trend of incidence in entire population and medical workers, their morbidity rates exceeded Ukrainian average ones by 25.0% and 2.5 times, respectively. There is about one and a half thousand employees in TB facilities of Dnipropetrovsk region. Their TB incidence rate was almost 5 times (p≤0.05) higher than in employees of other health care institutions and 6.6 times (p≤0.05) exceeded incidence of tuberculosis in community. In TB facilities, the highest incidence was registered among nurses – 506.8 per 100000. Non-medical workers have the second rank of incidence (409.4 per 100000). They did not contact TB patients directly, but inhaled air containing Mycobacterium tuberculosis. The incidence of TB in doctors and hospital attendants was lower – 384.6 and 357.1 per 100000, respectively. Nurses prevailed among TB-ill medical personnel of TB facilities – 41±3,4%. Hospital attendants had morbidity of 24±5,4%, non-medical stuff – 22±5,2%, doctors – 13±4,%. The confirmation of healthcare workers’ occupational TB cases is complicated. Taking info account that this infection is widely spread in community it is necessary to reveal active and latent tuberculosis infection with the quantiferon test and other modern methods, as well as to carry out genotyping of mycobacterium tuberculosis for finding epidemiological links in nosocomial TB transmission. To reduce the risks of occupational disease, it is important to carry out trainings on TB infection control for medical personnel and support staff

FAD binding, cobinamide binding and active site communication in the corrin reductase (CobR)

Adenosylcobalamin, the coenzyme form of vitamin B12, is one Nature's most complex coenzyme whose de novo biogenesis proceeds along either an anaerobic or aerobic metabolic pathway. The aerobic synthesis involves reduction of the centrally chelated cobalt metal ion of the corrin ring from Co(II) to Co(I) before adenosylation can take place. A corrin reductase (CobR) enzyme has been identified as the likely agent to catalyse this reduction of the metal ion. Herein, we reveal how Brucella melitensis CobR binds its coenzyme FAD (flavin dinucleotide) and we also show that the enzyme can bind a corrin substrate consistent with its role in reduction of the cobalt of the corrin ring. Stopped-flow kinetics and EPR reveal a mechanistic asymmetry in CobR dimer that provides a potential link between the two electron reduction by NADH to the single electron reduction of Co(II) to Co(I)

Cholera in Azov area

The purpose of research is analysis of clinical course and treatment results of patients with cholera in the Azov area. Materials and methods. During the period from 29.05.2011 to 19.08.2011 33 cases of cholera (32 adults and 1 child) and 25 vibrio carriers (22 adults and 3 children), which were caused by toxigenic strains of Vibrio cholera El Tor serogroup O1 Ogawa. Results. Likely factors of disease transmission in Mariupol are sea and river water, and the fish that were caught in the waters of the city. Typical and watery diarrhoea, vomiting, abdominal pain and lack of normal body temperature, dehydration syndrome, characterized clinical cholera for adults in most cases. The mean duration of diarrhoea was 6,6 days. At 46.9% observed atypical symptoms in 10 (31,3%) – abdominal pain (1 patient cramping in 7 cases, localized in the epigastria region, at 2-over stomach). In 5 patients (15,6%) had an increase in body temperature to 37,2–37,7 degrees Celsius. In 15 (46,9%) patients had severe nausea accompanied by vomiting. Easy for cholera was observed in 1 (3.1%), moderate – in 14 (43,8%), heavy – in 17 (53,1%) patients. Dehydration I level is set at 4 (12,5%), II – from 6 (18,7%), III – in 18 (56,3%), IV – 4 (12,5%) patients. Cholera outbreak was characterized by a predominance of severe disease and severe dehydration (III and IV), which was observed in 68.8% of patients. The decisive factor in the treatment of cholera patients was initiated in a timely manner rehydration therapy, in particular the introduction of the solution «Trisol». Against the background of rehydration therapy hyperkalaemia was observed in 9,4% of cases, vascular rehydration at 9,4%, the cell rehydration in 3,1% of patients. Fatal accidents cholera outbreaks have not been observed. Conclusion. Clinical diagnosis of cholera and the provision of medical care in the prehospital phase were poor, indicating the need for systematic conducting training seminars among experts of ambulance, as well as doctors of primary medical network. Cholera hospitals (or base hospitals) must be equipped with a mobile diagnostics (ultrasound, X-rays) and modern laboratory equipment. The required list of drug supply cholera hospitals should be expanded in view of possible complications and comorbidities

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

NMR Studies on Structure and Dynamics of the Monomeric Derivative of BS-RNase: New Insights for 3D Domain Swapping

Three-dimensional domain swapping is a common phenomenon in pancreatic-like ribonucleases. In the aggregated state, these proteins acquire new biological functions, including selective cytotoxicity against tumour cells. RNase A is able to dislocate both N- and C-termini, but usually this process requires denaturing conditions. In contrast, bovine seminal ribonuclease (BS-RNase), which is a homo-dimeric protein sharing 80% of sequence identity with RNase A, occurs natively as a mixture of swapped and unswapped isoforms. The presence of two disulfides bridging the subunits, indeed, ensures a dimeric structure also to the unswapped molecule. In vitro, the two BS-RNase isoforms interconvert under physiological conditions. Since the tendency to swap is often related to the instability of the monomeric proteins, in these paper we have analysed in detail the stability in solution of the monomeric derivative of BS-RNase (mBS) by a combination of NMR studies and Molecular Dynamics Simulations. The refinement of NMR structure and relaxation data indicate a close similarity with RNase A, without any evidence of aggregation or partial opening. The high compactness of mBS structure is confirmed also by H/D exchange, urea denaturation, and TEMPOL mapping of the protein surface. The present extensive structural and dynamic investigation of (monomeric) mBS did not show any experimental evidence that could explain the known differences in swapping between BS-RNase and RNase A. Hence, we conclude that the swapping in BS-RNase must be influenced by the distinct features of the dimers, suggesting a prominent role for the interchain disulfide bridges

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 %

Холера в Приазовье

The purpose of research is analysis of clinical course and treatment results of patients with cholera in the Azov area. Materials and methods. During the period from 29.05.2011 to 19.08.2011 33 cases of cholera (32 adults and 1 child) and 25 vibrio carriers (22 adults and 3 children), which were caused by toxigenic strains of Vibrio cholera El Tor serogroup O1 Ogawa. Results. Likely factors of disease transmission in Mariupol are sea and river water, and the fish that were caught in the waters of the city. Typical and watery diarrhoea, vomiting, abdominal pain and lack of normal body temperature, dehydration syndrome, characterized clinical cholera for adults in most cases. The mean duration of diarrhoea was 6,6 days. At 46.9% observed atypical symptoms in 10 (31,3%) – abdominal pain (1 patient cramping in 7 cases, localized in the epigastria region, at 2-over stomach). In 5 patients (15,6%) had an increase in body temperature to 37,2–37,7 degrees Celsius. In 15 (46,9%) patients had severe nausea accompanied by vomiting. Easy for cholera was observed in 1 (3.1%), moderate – in 14 (43,8%), heavy – in 17 (53,1%) patients. Dehydration I level is set at 4 (12,5%), II – from 6 (18,7%), III – in 18 (56,3%), IV – 4 (12,5%) patients. Cholera outbreak was characterized by a predominance of severe disease and severe dehydration (III and IV), which was observed in 68.8% of patients. The decisive factor in the treatment of cholera patients was initiated in a timely manner rehydration therapy, in particular the introduction of the solution «Trisol». Against the background of rehydration therapy hyperkalaemia was observed in 9,4% of cases, vascular rehydration at 9,4%, the cell rehydration in 3,1% of patients. Fatal accidents cholera outbreaks have not been observed. Conclusion. Clinical diagnosis of cholera and the provision of medical care in the prehospital phase were poor, indicating the need for systematic conducting training seminars among experts of ambulance, as well as doctors of primary medical network. Cholera hospitals (or base hospitals) must be equipped with a mobile diagnostics (ultrasound, X-rays) and modern laboratory equipment. The required list of drug supply cholera hospitals should be expanded in view of possible complications and comorbidities.Цель исследования – анализ клинического течения и результатов лечения больных холерой в Приазовье. Материалы и методы. За период с 29.05.2011 г. по 19.08.2011 г. зарегистрировано 33 случая заболевания холерой (32 взрослых и 1 ребенок) и 25 вибрионосителей (22 взрослых и 3 детей), которые были вызваны токсигенными штаммами холерного вибриона Эль-Тор серогруппы O1 Огава. Результаты. Вероятными факторами передачи заболевания в г. Мариуполе являлись морская и речная вода, а также рыба, которая была выловлена в акватории города. Клиническое течение холеры у взрослых в большинстве случаев было типичным и характеризовалось водянистой диареей, рвотой, отсутствием болей в животе, нормальной температурой тела, синдромом обезвоживания. Средняя продолжительность диареи составила 6,6 суток. У 46,9% наблюдались нетипичные симптомы: у 10 (31,3%) – боль в животе (у 1 больного схваткообразная, в 7 случаях локализовалась в эпигастральной области, у 2 – по всему животу). У 5 пациентов (15,6%) отмечено повышение температуры тела до 37,2–37,7 °С. У 15 (46,9%) пациентов рвота сопровождалась выраженной тошнотой. Легкое течение холеры отмечено у 1 (3,1%), средней тяжести – у 14 (43,8%), тяжелое – у 17 (53,1%) больных. Дегидратация I степени установлена у 4 (12,5%), II – у 6 (18,7%), III – у 18 (56,3%), IV – у 4 (12,5%) пациентов. Вспышка холеры характеризовалась преобладанием тяжелых форм болезни и выраженной дегидратацией (III и IV степени), которая отмечена у 68,8% больных. Решающим фактором в терапии больных холерой была своевременно начатая регидратационная терапия, в частности, введение раствора «Трисоль». На фоне регидратационной терапии наблюдали гиперкалиемию в 9,4% случаев, сосудистую гипергидратацию у 9,4%, клеточную гипергидратацию у 3,1% больных. Летальные случаи на вспышке холеры не наблюдались. Заключение. Клиническая диагностика холеры и оказание лечебной помощи на догоспитальном этапе были неудовлетворительными, что свидетельствует о необходимости систематического проведения учебно-зачетных семинаров среди специалистов СМП, а также врачей первичной врачебной сети. Холерные госпитали (или базовые лечебные учреждения) должны быть оснащены передвижной диагностической (УЗИ, рентген) и современной лабораторной аппаратурой. Необходимый перечень лекарственного обеспечения холерных госпиталей следует расширить с учетом возможных осложнений и сопутствующих заболеваний. 

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