The Expression of width and Colour Plane in the Sur Karakul Lambs of Different Colours

The results of research into similar and distinctive features in the study of curl breadth and color consistency of karakul lambs of harsh diamond and silver coloration are presented in this article

2\u27-O-Methyl at 20-mer Guide Strand 3\u27 Termini May Negatively Affect Target Silencing Activity of Fully Chemically Modified siRNA

Small interfering RNAs (siRNAs) have the potential to treat a broad range of diseases. siRNAs need to be extensively chemically modified to improve their bioavailability, safety, and stability in vivo. However, chemical modifications variably impact target silencing for different siRNA sequences, making the activity of chemically modified siRNA difficult to predict. Here, we systematically evaluated the impact of 3\u27 terminal modifications (2\u27-O-methyl versus 2\u27-fluoro) on guide strands of different length and showed that 3\u27 terminal 2\u27-O-methyl modification negatively impacts activity for \u3e60% of siRNA sequences tested but only in the context of 20- and not 19- or 21-nt-long guide strands. These results indicate that sequence, modification pattern, and structure may cooperatively affect target silencing. Interestingly, the introduction of an extra 2\u27-fluoro modification in the seed region at guide strand position 5, but not 7, may partially compensate for the negative impact of 3\u27 terminal 2\u27-O-methyl modification. Molecular modeling analysis suggests that 2\u27-O-methyl modification may impair guide strand interactions within the PAZ domain of argonaute-2, which may affect target recognition and cleavage, specifically when guide strands are 20-nt long. Our findings emphasize the complex nature of modified RNA-protein interactions and contribute to design principles for chemically modified siRNAs

5-Vinylphosphonate improves tissue accumulation and efficacy of conjugated siRNAs in vivo

5-Vinylphosphonate modification of siRNAs protects them from phosphatases, and improves silencing activity. Here, we show that 5-vinylphosphonate confers novel properties to siRNAs. Specifically, 5-vinylphosphonate (i) increases siRNA accumulation in tissues, (ii) extends duration of silencing in multiple organs and (iii) protects siRNAs from 5-to-3 exonucleases. Delivery of conjugated siRNAs requires extensive chemical modifications to achieve stability in vivo. Because chemically modified siRNAs are poor substrates for phosphorylation by kinases, and 5-phosphate is required for loading into RNA-induced silencing complex, the synthetic addition of a 5-phosphate on a fully modified siRNA guide strand is expected to be beneficial. Here, we show that synthetic phosphorylation of fully modified cholesterol-conjugated siRNAs increases their potency and efficacy in vitro, but when delivered systemically to mice, the 5-phosphate is removed within 2 hours. The 5-phosphate mimic 5-(E)-vinylphosphonate stabilizes the 5 end of the guide strand by protecting it from phosphatases and 5-to-3 exonucleases. The improved stability increases guide strand accumulation and retention in tissues, which significantly enhances the efficacy of cholesterol-conjugated siRNAs and the duration of silencing in vivo. Moreover, we show that 5-(E)-vinylphosphonate stabilizes 5 phosphate, thereby enabling systemic delivery to and silencing in kidney and heart

Measuring the deformation of a ferrogel sphere in a homogeneous magnetic field

A sphere of a ferrogel is exposed to a homogeneous magnetic field. In accordance to theoretical predictions, it gets elongated along the field lines. The time-dependence of the elastic shear modulus causes the elongation to increase with time analogously to mechanic creep experiments, and the rapid excitation causes the sphere to vibrate. Both phenomena can be well described by a damped harmonic oscillator model. By comparing the elongation along the field with the contraction perpendicular to it, we can calculate Poisson's ratio of the gel. The magnitude of the elongation is compared with the theoretical predictions for elastic spheres in homogeneous fields.Comment: 5 pages, 8 figure

Clinical-Epidemiological Peculiarities of the Tick-Borne Borrelioses Registered in the Trans-Baikal Territory

Complex analysis of the data on epidemiology and clinical picture of the tick-borne borrelioses in the territory of the Trans-Baikal Region over the last decade since 2003 to 2012 has demonstrated that there is a distinct upward tendency as concerns its morbidity rates. Spotted have been the potentially hazardous, as regards the infection, areas. Highest incidence rates are registered between May-July among adult men, and erythema form of the disease prevails. Based on the results of molecular-genetic investigation of Ixodidae ticks, for the first time ever in the territory of the Dul’durginsk Region identified has been circulation of Borrelia garinii , and B. afzelii , pathogenic for humans bacterial species of Borrelia genus

Epidemiological Situation on Tick-Borne Viral Encephalitis in the Russian Federation in 2011–2021 and Short-Term Forecast of its Development

The aim of the work was to analyze the epidemiological situation on tick-borne viral encephalitis in the endemic territories of the Russian Federation in 2021 in comparison with the dynamics over 2011–2020 and its shortterm forecast for 2022. In Russia, 48 constituent entities belonging to seven federal districts are endemic for tick-borne viral encephalitis (TBVE). There is a statistically significant downward trend in the incidence of TBVE in the Siberian Federal District (which is characterized by the maximum incidence rate in the country), the Volga and Far Eastern Federal Districts. In the Ural Federal District (the second in terms of TBVE incidence), the decline in the incidence has stalled since 2021. The average long-term incidence of TBVE in the constituent entities of the Russian Federation varies from sporadic (Republic of Crimea)  up to 12.5 per 100 thousand of the population (0/0000) (Krasnoyarsk Territory). In 2021, TBVE cases were detected in 42 endemic regions and in one non-endemic region – Stavropol Territory. At the same time, 1015 cases of TBVE were in the country (0.69 0/0000). In all Federal Districts, the incidence of TBVE is below the long-term average values. Using the Quantum GIS program, the incidence of TBVE in 917 administrative territories of the country has been ranked and grouped according to the level of epidemiological risk. This made it possible to establish that 65 % of the territories form a zone of low epidemiological risk. High and very high epidemiological risk is observed in 13% of the analyzed districts. The structure of TBVE clinical manifestations in 2021 was dominated by febrile (59.7 %) and meningeal (24.3 %) forms. 14 lethal outcomes were reported. In 2021, 2 889 515 people were vaccinated (including 1 433 850 children), of which 14 fell ill. Specific immunoglobulin was used to prevent the overt development of infection in 100 704 individuals, which accounts for 22.6 % of the persons affected by tick bites (30.6 % among children). Acaricidic treatments were carried out on an operational area of 233 125 hectares of territories of socially significant objects. The scope of all TBVE prevention measures in 2021 increased as compared to 2020. In 2022, a decline in the incidence of TBVE in endemic Federal Districts and in the country on the whole is forecasted to (0,64±0,192) 0/0000

The influence of the LED lighting on structural-functional parameters of lettuce plants

Comparative studies were conducted on morphofunctional parameters of lettuce (Lactuca sativa) plants cultivated with the use of supplementary lighting from different light sources - LED lamps, high-pressure mercury arc lamp (HPM) and high-pressure sodium arc lamp (HPS). The work showed that morphofunctional parameters of lettuce were significantly higher with LED lighting, in comparison to plants cultivated with HPM illumination, and main parameters of leaves grown under LED were barely discernible from the samples grown under HPS lighting. We observed accelerated transfer into reproductive period during HPM lighting, what can lead to quality degradation of the product. Considering the approximate values of leaf character range in experiments with HPS and LED lighting and greater energy efficiency of LED, light emitting diodes are obviously more promising for supplementary illumination in protected ground conditions

Diversity of Protein and mRNA Forms of Mammalian Methionine Sulfoxide Reductase B1 Due to Intronization and Protein Processing

Background: Methionine sulfoxide reductases (Msrs) are repair enzymes that protect proteins from oxidative stress by catalyzing stereospecific reduction of oxidized methionine residues. MsrB1 is a selenocysteine-containing cytosolic/nuclear Msr with high expression in liver and kidney. Principal Findings: Here, we identified differences in MsrB1 gene structure among mammals. Human MsrB1 gene consists of four, whereas the corresponding mouse gene of five exons, due to occurrence of an additional intron that flanks the stop signal and covers a large part of the 3′-UTR. This intron evolved in a subset of rodents through intronization of exonic sequences, whereas the human gene structure represents the ancestral form. In mice, both splice forms were detected in liver, kidney, brain and heart with the five-exon form being the major form. We found that both mRNA forms were translated and supported efficient selenocysteine insertion into MsrB1. In addition, MsrB1 occurs in two protein forms that migrate as 14 and 5 kDa proteins. We found that each mRNA splice form generated both protein forms. The abundance of the 5 kDa form was not influenced by protease inhibitors, replacement of selenocysteine in the active site or mutation of amino acids in the cleavage site. However, mutation of cysteines that coordinate a structural zinc decreased the levels of 5 and 14 kDa forms, suggesting importance of protein structure for biosynthesis and/stability of these forms. Conclusions: This study characterized unexpected diversity of protein and mRNA forms of mammalian selenoprotein MsrB1

Codon Size Reduction as the Origin of the Triplet Genetic Code

The genetic code appears to be optimized in its robustness to missense errors and frameshift errors. In addition, the genetic code is near-optimal in terms of its ability to carry information in addition to the sequences of encoded proteins. As evolution has no foresight, optimality of the modern genetic code suggests that it evolved from less optimal code variants. The length of codons in the genetic code is also optimal, as three is the minimal nucleotide combination that can encode the twenty standard amino acids. The apparent impossibility of transitions between codon sizes in a discontinuous manner during evolution has resulted in an unbending view that the genetic code was always triplet. Yet, recent experimental evidence on quadruplet decoding, as well as the discovery of organisms with ambiguous and dual decoding, suggest that the possibility of the evolution of triplet decoding from living systems with non-triplet decoding merits reconsideration and further exploration. To explore this possibility we designed a mathematical model of the evolution of primitive digital coding systems which can decode nucleotide sequences into protein sequences. These coding systems can evolve their nucleotide sequences via genetic events of Darwinian evolution, such as point-mutations. The replication rates of such coding systems depend on the accuracy of the generated protein sequences. Computer simulations based on our model show that decoding systems with codons of length greater than three spontaneously evolve into predominantly triplet decoding systems. Our findings suggest a plausible scenario for the evolution of the triplet genetic code in a continuous manner. This scenario suggests an explanation of how protein synthesis could be accomplished by means of long RNA-RNA interactions prior to the emergence of the complex decoding machinery, such as the ribosome, that is required for stabilization and discrimination of otherwise weak triplet codon-anticodon interactions

The Role of Thioredoxin Reductases in Brain Development

The thioredoxin-dependent system is an essential regulator of cellular redox balance. Since oxidative stress has been linked with neurodegenerative disease, we studied the roles of thioredoxin reductases in brain using mice with nervous system (NS)-specific deletion of cytosolic (Txnrd1) and mitochondrial (Txnrd2) thioredoxin reductase. While NS-specific Txnrd2 null mice develop normally, mice lacking Txnrd1 in the NS were significantly smaller and displayed ataxia and tremor. A striking patterned cerebellar hypoplasia was observed. Proliferation of the external granular layer (EGL) was strongly reduced and fissure formation and laminar organisation of the cerebellar cortex was impaired in the rostral portion of the cerebellum. Purkinje cells were ectopically located and their dendrites stunted. The Bergmann glial network was disorganized and showed a pronounced reduction in fiber strength. Cerebellar hypoplasia did not result from increased apoptosis, but from decreased proliferation of granule cell precursors within the EGL. Of note, neuron-specific inactivation of Txnrd1 did not result in cerebellar hypoplasia, suggesting a vital role for Txnrd1 in Bergmann glia or neuronal precursor cells