ПОЯВЛЕНИЕ ЭКЗОТИЧЕСКИХ ПЕРЕНОСЧИКОВ АРБОВИРУСНЫХ ЛИХОРАДОК – НОВАЯ НЕДОСТАТОЧНО ОЦЕНИВАЕМАЯ БИОЛОГИЧЕСКАЯ УГРОЗА ЮЖНЫМ РЕГИОНАМ РОССИИ

Delivery of originators of infectious and parasitic illnesses on new territories can pass by means of mosquitoes which in modern conditions extend quickly. Getting on new territories they take roots and provide transfer of this or that originator. Or they provide initial case rate, and then viruses start to circulate among mosquitoes – natural representatives of local fauna. As it was with virus Denge delivered to Greece with mosquitoes Aedes aegypti. This kind of a mosquito by 1950 has been destroyed at the Black Sea coast of Caucasus. In the beginning of 21 centuries this kind again began to be found out in earlier free territories. Occurrence after 50-years absence of an effective carrier in the south of Russia is serious biological threat to epidemic well-being of the country in case of delivery of originators arbovirus infections.Завоз возбудителей инфекционных и паразитарных болезней на новые территории может проходить с помощью комаров, которые в современных условиях распространяются быстро. Попадая на новые территории, они укореняются и обеспечивают передачу того или иного возбудителя, либо они обеспечивают начальную заболеваемость, а затем вирусы начинают циркулировать среди комаров – естественных представителей местной фауны. Так было с вирусом Денге, завезенным в Грецию с комарами Aedes aegypti. Этот вид комара к 1950 г. был уничтожен на черноморском побережье Кавказа. В начале XXI в. этот вид вновь стал обнаруживаться на ранее свободных территориях. Появление после 50-летнего отсутствия эффективного переносчика на юге России является серьезной биологической угрозой эпидемическому благополучию страны в случае завоза возбудителей арбовирусных инфекций

Гипотеза о внеафриканском происхождении вируса иммунодефицита человека 1-го типа (ВИЧ -1)

Longitudinal co-evolution of human beings and pathogens resulted in polymorphism of Homo sapiens. CCR5Δ32 HIV-resistance allele is the exception to the rules. Recent origin of HIV-1 in Africa contradicted with the appearance of CCR5Δ32 allele in Northern Europe in previous ages.The author proposed non-contradictory theory of primary appearance of ancient HIV-1 in the Northern Europe 5-7 thousand years ago. The primary epidemics of HIV-infection had been stopped by the appearance of CCR5Δ32 mutation among the affected population. Re-emergence of HIV-1 nowadays resulted by the penetration of hibernated HIV-1 into population of drug addicts and homosexual men.Длительная ко-эволюция человека и возбудителей инфекционных болезней привела к полиморфизму человека и появлению генетической резистентности к ряду патогенов. Единственным исключением является вирус иммунодефицита человека 1-го типа (ВИЧ-1). Аллель CCR5Δ32 обеспечивает 99,9% невосприимчивость к заражению ВИЧ-1. Согласно принятой гипотезе, ВИЧ-1 появился только в середине ХХ в. в Африке. Столь короткий период циркуляции патогена в человеческой популяции недостаточен для выработки генетического механизма невосприимчивости. Эпицентром распространения мутации, обеспечивающей генетическую защиту от ВИЧ-1, является север Европы. Частота встречаемости CCR5Δ32 убывает по направлению с севера на юго-восток. Эта мутация не встречается среди африканцев, что противоречит гипотезе об африканском происхождении ВИЧ-1. Автор обосновывает гипотезу о первичном происхождении ВИЧ-1 на севере Европы 5–7 тысяч лет назад. Настоящая эпидемическая ситуация является не первой волной распространения ВИЧ-инфекции. Распространение ВИЧ-инфекции во 2-й половине ХХ в. связано с попаданием резерватного варианта ВИЧ-1 в популяцию иммунокомпрометированных наркоманов и гомосексуалов

Cholera and the Death of the Ancient Indus Civilization

The paper presents a hypothesis that the most probable cause of death of the ancient world Indus (Harappa) civilization was the epidemic of Asiatic cholera. A brief description of the Indus civilization that existed for two millennia (3300–1300 BC) is given. It is shown that the previously described factors for the decline of the thriving Indus civilization (climate change, shallowing of the Indus river and reduction in floods, catastrophic floods, drought, economic crisis, etc.) do not provide a consistent and comprehensive explanation of the causes of its death. Meanwhile, the natural environment and peculiarities of agriculture of the Indus civilization (annual floods affecting not only fields, but also sewage systems) created ideal conditions for the spread of water-borne cholera. The evolution of the Asiatic cholera agent is discussed. The results of paleogenomics study of this pathogen and their significance for the reconstruction of evolutionary events are briefly reviewed. The stages of evolution of Vibrio cholerae of the classical biovar are described, and possible mechanisms for the preservation of the pathogen during inter-epidemic period are considered. It is demonstrated that aside from cholera, other catastrophic, destructive epidemics are recorded in the history of mankind

NMR assignments of the WBSCR27 protein related to Williams-Beuren syndrome

© 2018, Springer Science+Business Media B.V., part of Springer Nature. Williams-Beuren syndrome is a genetic disorder characterized by physiological and mental abnormalities, and is caused by hemizygous deletion of several genes in chromosome 7. One of the removed genes encodes the WBSCR27 protein. Bioinformatic analysis of the sequence of WBSCR27 indicates that it belongs to the family of SAM-dependent methyltransferases. However, exact cellular functions of this protein or phenotypic consequences of its deficiency are still unknown. Here we report nearly complete 1H, 15N, and 13C chemical shifts assignments of the 26 kDa WBSCR27 protein from Mus musculus in complex with the cofactor S-adenosyl-l-methionine (SAM). Analysis of the assigned chemical shifts allowed us to characterize the protein’s secondary structure and backbone dynamics. The topology of the protein’s fold confirms the assumption that the WBSCR27 protein belongs to the family of class I methyltransferases

Cleavage of the sarcin–ricin loop of 23S rRNA differentially affects EF-G and EF-Tu binding

Ribotoxins are potent inhibitors of protein biosynthesis and inactivate ribosomes from a variety of organisms. The ribotoxin α-sarcin cleaves the large 23S ribosomal RNA (rRNA) at the universally conserved sarcin–ricin loop (SRL) leading to complete inactivation of the ribosome and cellular death. The SRL interacts with translation factors that hydrolyze GTP, and it is important for their binding to the ribosome, but its precise role is not yet understood. We studied the effect of α-sarcin on defined steps of translation by the bacterial ribosome. α-Sarcin-treated ribosomes showed no defects in mRNA and tRNA binding, peptide-bond formation and sparsomycin-dependent translocation. Cleavage of SRL slightly affected binding of elongation factor Tu ternary complex (EF-Tu•GTP•tRNA) to the ribosome. In contrast, the activity of elongation factor G (EF-G) was strongly impaired in α-sarcin-treated ribosomes. Importantly, cleavage of SRL inhibited EF-G binding, and consequently GTP hydrolysis and mRNA–tRNA translocation. These results suggest that the SRL is more critical in EF-G than ternary complex binding to the ribosome implicating different requirements in this region of the ribosome during protein elongation

Molecular dynamics of ribosomal elongation factors G and Tu

Translation on the ribosome is controlled by external factors. During polypeptide lengthening, elongation factors EF-Tu and EF-G consecutively interact with the bacterial ribosome. EF-Tu binds and delivers an aminoacyl-tRNA to the ribosomal A site and EF-G helps translocate the tRNAs between their binding sites after the peptide bond is formed. These processes occur at the expense of GTP. EF-Tu:tRNA and EF-G are of similar shape, share a common binding site, and undergo large conformational changes on interaction with the ribosome. To characterize the internal motion of these two elongation factors, we used 25 ns long all-atom molecular dynamics simulations. We observed enhanced mobility of EF-G domains III, IV, and V and of tRNA in the EF-Tu:tRNA complex. EF-Tu:GDP complex acquired a configuration different from that found in the crystal structure of EF-Tu with a GTP analogue, showing conformational changes in the switch I and II regions. The calculated electrostatic properties of elongation factors showed no global similarity even though matching electrostatic surface patches were found around the domain I that contacts the ribosome, and in the GDP/GTP binding region

E. coli metabolic protein aldehydealcohol dehydrogenase-E binds to the ribosome: a unique moonlighting action revealed

It is becoming increasingly evident that a high degree of regulation is involved in the protein synthesis machinery entailing more interacting regulatory factors. A multitude of proteins have been identified recently which show regulatory function upon binding to the ribosome. Here, we identify tight association of a metabolic protein aldehyde-alcohol dehydrogenase E (AdhE) with the E. coli 70S ribosome isolated from cell extract under low salt wash conditions. Cryo-EM reconstruction of the ribosome sample allows us to localize its position on the head of the small subunit, near the mRNA entrance. Our study demonstrates substantial RNA unwinding activity of AdhE which can account for the ability of ribosome to translate through downstream of at least certain mRNA helices. Thus far, in E. coli, no ribosome-associated factor has been identified that shows downstream mRNA helicase activity. Additionally, the cryo-EM map reveals interaction of another extracellular protein, outer membrane protein C (OmpC), with the ribosome at the peripheral solvent side of the 50S subunit. Our result also provides important insight into plausible functional role of OmpC upon ribosome binding. Visualization of the ribosome purified directly from the cell lysate unveils for the first time interactions of additional regulatory proteins with the ribosom