Supporting Information for: A highly efficient form of the selenocysteine insertion sequence element in protozoan parasites and its use in mammalian cells

Selenoproteins are an elite group of proteins containing a rare amino acid, selenocysteine (Sec), encoded by the codon, UGA. In eukaryotes, incorporation of Sec requires a Sec insertion sequence (SECIS) element, a stem–loop structure located in the 3\u27-untranslated regions of selenoprotein mRNAs. Here we report identification of a noncanonical form of SECIS element in Toxoplasma gondii and Neospora canine, single-celled apicomplexan parasites of humans and domestic animals. This SECIS has a GGGA sequence in the SBP2-binding site in place of AUGA previously considered invariant. Using a combination of computational and molecular techniques, we show that Toxoplasma and Neospora possess both canonical and noncanonical SECIS elements. The GGGA-type SECIS element supported Sec insertion in mammalian HEK 293 and NIH 3T3 cells and did so more efficiently than the natural mammalian SECIS elements tested. In addition, mammalian type I and type II SECIS elements mutated into the GGGA forms were functional but manifested decreased Sec insertion efficiency. We carried out computational searches for both AUGA and GGGA forms of SECIS elements in Toxoplasma and detected five selenoprotein genes, including one coding for a previously undescribed selenoprotein, designated SelQ, and two containing the GGGA form of the SECIS element. In contrast, the GGGA-type SECIS elements were not detected in mammals and nematodes. As a practical outcome of the study, we developed pSelExpress1, a vector for convenient expression of selenoproteins in mammalian cells. It contains an SBP2 gene and the most efficient tested SECIS element: an AUGA mutant of the GGGA-type Toxoplasma SelT structure

Specific Excision of the Selenocysteine tRNA\u3csup\u3e [Ser]Sec\u3c/sup\u3e (\u3ci\u3eTrsp\u3c/i\u3e) Gene in Mouse Liver Demonstrates an Essential Role of Selenoproteins in Liver Function

Selenium is essential in mammalian embryonic development. However, in adults, selenoprotein levels in several organs including liver can be substantially reduced by selenium deficiency without any apparent change in phenotype. To address the role of selenoproteins in liver function, mice homozygous for a floxed allele encoding the selenocysteine (Sec) tRNA [Ser]Sec gene were crossed with transgenic mice carrying the Cre recombinase under the control of the albumin promoter that expresses the recombinase specifically in liver. Recombination was nearly complete in mice 3 weeks of age, whereas liver selenoprotein synthesis was virtually absent, which correlated with the loss of Sec tRNA [Ser]Sec and activities of major selenoproteins. Total liver selenium was dramatically decreased, whereas levels of low molecular weight selenocompounds were little affected. Plasma selenoprotein P levels were reduced by about 75%, suggesting that selenoprotein P is primarily exported from the liver. Glutathione S-transferase levels were elevated in the selenoprotein-deficient liver, suggesting a compensatory activation of this detoxification program. Mice appeared normal until about 24 h before death. Most animals died between 1 and 3 months of age. Death appeared to be due to severe hepatocellular degeneration and necrosis with concomitant necrosis of peritoneal and retroperitoneal fat. These studies revealed an essential role of selenoproteins in liver function

Bound states in the continuum and Fano resonances in the strong mode coupling regime

The study of resonant dielectric nanostructures with a high refractive index is a new research direction in the nanoscale optics and metamaterial-inspired nanophotonics. Because of the unique optically induced electric and magnetic Mie resonances, high-index nanoscale structures are expected to complement or even replace different plasmonic components in a range of potential applications. We study a strong coupling between modes of a single subwavelength high-index dielectric resonator and analyze the mode transformation and Fano resonances when the resonator’s aspect ratio varies. We demonstrate that strong mode coupling results in resonances with high-quality factors, which are related to the physics of bound states in the continuum when the radiative losses are almost suppressed due to the Friedrich–Wintgen scenario of destructive interference. We explain the physics of these states in terms of multipole decomposition, and show that their appearance is accompanied by a drastic change in the far-field radiation pattern. We reveal a fundamental link between the formation of the high-quality resonances and peculiarities of the Fano parameter in the scattering cross-section spectra. Our theoretical findings are confirmed by microwave experiments for the scattering of high-index cylindrical resonators with a tunable aspect ratio. The proposed mechanism of the strong mode coupling in single subwavelength high-index resonators accompanied by resonances with high-quality factors helps to extend substantially functionalities of all-dielectric nanophotonics, which opens horizons for active and passive nanoscale metadevices.The numerical calculations were performed with support from the Ministry of Education and Science of the Russian Federation (Project 3.1500.2017/4.6) and the Australian Research Council. The experimental study of the cylinder SCS in the microwave frequency range was supported by the Russian Science Foundation (17-79-20379). The analytical calculations with resonant-state expansion method were performed with support from the Russian Science Foundation (17-12-01581). A. A. B., K. L. K. and Z. F. S. acknowledge support from the Foundation for the Advancement of Theoretical Physics and Mathematics “BASIS” (Russia)

Electronic Jamming of the System of Subscriber Terminals of the Starlink Satellite Communication System

В работе поднимается проблема радиоэлектронной борьбы с системой спутниковой связи «Starlink» на фоне современной геополитической обстановки. Применение многоспутниковых группировок из малых космических аппаратов является перспективным направлением развития спутниковых систем связи. Такие системы имеют высокие показатели эффективности. Для радиоэлектронного подавления системы связи «Starlink» в работе предложено использование мобильного комплекса радиоэлектронного подавления, в котором применяется пассивный радиоотражатель, выполненный в виде сферы и вывешенный на аэростате с системой стабилизации. Приведен предварительный расчет выходной мощности передатчика помех комплекса подавления с учетом его расположения в непосредственной близости от линии соприкосновенияThe paper raises the problem of electronic warfare with the Starlink satellite communication system against the backdrop of the current geopolitical situation. The use of multi-satellite constellations of small spacecraft is a promising direction in the development of satellite communication systems. Such systems have high rates of efficiency. For electronic jamming of the Starlink communication system, the paper proposes the use of a mobile electronic jamming complex in which a passive radar reflector is used, made in the form of a sphere and hung on a balloon with a stabilization system. A preliminary calculation of the output power of the interference transmitter of the suppression complex is given, taking into account its location in the immediate vicinity of the contact lin

Multiple effects of bariatric surgery on human biochemical status

Beneficial effect of bariatric surgery is expressed not only in reducing body weight, but also in improving the functioning of the body as a whole. On the one hand, numerous studies devoted to the investigations of specific mechanisms of the influence of bariatric surgery on the general condition of an organism testify to the enormous interest of scientists in this problem. On the other hand, the range of changes is so vast that it covers almost all physiological and biochemical processes. The most noticeable response to bariatric surgery is from the digestive (including the composition of the microbiota), immune (reducing the level of systemic and local inflammation), cardiovascular (reducing the risks of atherosclerosis and other diseases) systems. Partial or complete compensation of type 2 diabetes mellitus and metabolic syndrome also occurs. Among the variety of data, there is insufficient research on only standard biomarkers: leptin, C-reactive protein, interleukin 6, etc. A detailed study of the profiles of both circulating biomarkers and local ones is necessary. At the same time, it is obligate to continue to accumulate evidence on the positive effect of bariatric surgery, since this type of surgical intervention has come into practice relatively recently. Unfortunately, at the present time in Russia bariatric surgery is not an affordable and popular treatment for morbid obesity (MO). Nevertheless, it is extremely important to change the current situation, since bariatric treatment is an optimal and effective solution to socially significant diseases such as MO or type 2 diabetes mellitus

The \u3cem\u3eChlamydomonas\u3c/em\u3e Genome Reveals the Evolution of Key Animal and Plant Functions

Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the ∼120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella

Identification of Novel Candidate Markers of Type 2 Diabetes and Obesity in Russia by Exome Sequencing with a Limited Sample Size

Type 2 diabetes (T2D) and obesity are common chronic disorders with multifactorial etiology. In our study, we performed an exome sequencing analysis of 110 patients of Russian ethnicity together with a multi-perspective approach based on biologically meaningful filtering criteria to detect novel candidate variants and loci for T2D and obesity. We have identified several known single nucleotide polymorphisms (SNPs) as markers for obesity (rs11960429), T2D (rs9379084, rs1126930), and body mass index (BMI) (rs11553746, rs1956549 and rs7195386) (p < 0.05). We show that a method based on scoring of case-specific variants together with selection of protein-altering variants can allow for the interrogation of novel and known candidate markers of T2D and obesity in small samples. Using this method, we identified rs328 in LPL (p = 0.023), rs11863726 in HBQ1 (p = 8 × 10−5), rs112984085 in VAV3 (p = 4.8 × 10−4) for T2D and obesity, rs6271 in DBH (p = 0.043), rs62618693 in QSER1 (p = 0.021), rs61758785 in RAD51B (p = 1.7 × 10−4), rs34042554 in PCDHA1 (p = 1 × 10−4), and rs144183813 in PLEKHA5 (p = 1.7 × 10−4) for obesity; and rs9379084 in RREB1 (p = 0.042), rs2233984 in C6orf15 (p = 0.030), rs61737764 in ITGB6 (p = 0.035), rs17801742 in COL2A1 (p = 8.5 × 10−5), and rs685523 in ADAMTS13 (p = 1 × 10−6) for T2D as important susceptibility loci in Russian population. Our results demonstrate the effectiveness of whole exome sequencing (WES) technologies for searching for novel markers of multifactorial diseases in cohorts of limited size in poorly studied populations

ARDD 2020: from aging mechanisms to interventions

Aging is emerging as a druggable target with growing interest from academia, industry and investors. New technologies such as artificial intelligence and advanced screening techniques, as well as a strong influence from the industry sector may lead to novel discoveries to treat age-related diseases. The present review summarizes presentations from the 7th Annual Aging Research and Drug Discovery (ARDD) meeting, held online on the 1st to 4th of September 2020. The meeting covered topics related to new methodologies to study aging, knowledge about basic mechanisms of longevity, latest interventional strategies to target the aging process as well as discussions about the impact of aging research on society and economy. More than 2000 participants and 65 speakers joined the meeting and we already look forward to an even larger meeting next year. Please mark your calendars for the 8th ARDD meeting that is scheduled for the 31st of August to 3rd of September, 2021, at Columbia University, USA

THE MORPHOGENESIS OF THE TISSUE REACTIONS IN THE LYMPHOID ORGANS, LEVER AND ENTERIC WALL OF THE MACAQUE RHESUS MONKEY WITH PERORAL INFECTIONS BY THE TICK-BORNE ENCEPHALITIS WITH THE DIFFERENT BIOLOGICAL ACTIVITY

45 macaque-rhesus monkeys have been examined. The purpose of the work: the development of the morphological justification of the immunogenicity of the weakened virus of the tick-borne encephalitis strain of Elantsev, clone 15x20/3. For the first time, a comparative morphological study of the immune system organs tissue reaction has been performed with the peroral infection of monkeys with the tick-borne encephalitis strains of Elantsev. The obtained results indicate of the immunogecity of the tick-borne encephalitis vircs strain to be studied, which may be used for its further study creating the living vaccine against the tick-borne encephalitis on its base. The result can be used in the scientific investigations in the field of virusology. The results of the investigations have been introduced in the laboratory of the arbovirus infections of the Tumensky SRI of the krai infection pathology in studying the attenuated strains of the tick-borne encephalitis virus. The field of application: the study process in medical Higher Schools, section Pathological Anatomy; the scientific investigations in the field of morphology and virusologyAvailable from VNTIC / VNTIC - Scientific & Technical Information Centre of RussiaSIGLERURussian Federatio