Nucleic acid aptamers capable of selectively recognizing their target molecules have nowadays been established as powerful and tunable tools for biospecific applications, be it therapeutics, drug ...delivery systems or biosensors. It is now generally acknowledged that in vitro selection enables one to generate aptamers to almost any target of interest. However, the success of selection and the affinity of the resulting aptamers depend to a large extent on the nature and design of an initial random nucleic acid library. In this review, we summarize and discuss the most important features of the design of nucleic acid libraries for in vitro selection such as the nature of the library (DNA, RNA or modified nucleotides), the length of a randomized region and the presence of fixed sequences. We also compare and contrast different randomization strategies and consider computer methods of library design and some other aspects.
Aim of the study is to reveal clinical and biological correlations in patients with adolescent depression and attenuated psychotic symptoms. Activity of platelet enzymes involved in glutamate-, ...glutathione- and energy metabolism was evaluated in control group and in the patients, because these systems are suspected as related to pathogenesis of psychosis. Adolescents (78 men, 16–25 years old) hospitalized with the first acute depressive state composed two groups: with prevalence of attenuated psychotic positive or negative symptoms (Gr1 and Gr2, 48 and 30 patients, respectively). Control group comprised 20 mentally healthy men of 19–25 years old. Gr1 differed significantly from Gr2 in scores by the Scale of Prodromal Symptoms (SOPS) for positive symptoms,
p
< 0.001, for disorganization symptoms,
p
< 0.003, and for total SOPS score,
p
< 0.001, before the treatment started. When patients from either Gr1 or Gr2 were compared with the control group, significantly decreased baseline activities of platelet glutamate dehydrogenase (GDH), glutathione reductase (GR) and glutathione S-transferase (GST) were found (
p
< 0.0001). Different correlations were found between baseline enzymatic activities in Gr1 and Gr2: GDH activity correlated with GR activity in Gr1 (
R
= 0.37), and with GST activity in Gr2 (
R
= 0.70). Significant correlations were found only in Gr2 between the delta of scores by SOPS negative symptoms (SOPS-N) under treatment and baseline GDH, GST, and GR activities (
R
= − 0.36,
R
= − 0.60, and
R
= 0.38, respectively). The found correlations of the baseline enzymatic activity levels with the value of the decrease (delta) in SOPS-N scores under the treatment represent interest for the prediction of the pharmacotherapy efficiency.
Bioluminescent solid-phase sandwich-type microassay was developed to detect multiple sclerosis (MS)-associated autoantibodies in human sera. The assay is based on two different 2′-F-Py RNA aptamers ...against the target autoantibodies as biospecific elements, and Ca2+-regulated photoprotein obelin as a reporter. The paper describes elaboration of the assay and its application to 91 serum samples from patients with clinically definite MS and 86 ones from individuals healthy in terms of MS. Based on the receiver-operator curve (ROC) analysis, the chosen threshold value as clinical decision limit offers sensitivity of 63.7% and specificity of 94.2%. The area under the ROC curve (AUC) value of 0.87 shows a good difference between the groups under investigation. The likelihood ratio of 10.97 proves the diagnostic value of the assay and its potential as one of the laboratory MS-tests.
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•Assay of multiple sclerosis-associated autoantibodies was developed using RNA aptamers and photoprotein obelin.•This bioluminescent assay was successfully applied to analyze 177 clinical sera samples from MS patients and healthy donors.•Its diagnostic value and potential as one of the laboratory tests for multiple sclerosis diagnosis were demonstrated.
Cellular lipid uptake (through endocytosis) is a basic physiological process. Dysregulation of this process underlies the pathogenesis of diseases such as atherosclerosis, obesity, diabetes, and ...cancer. However, to date, only some mechanisms of lipid endocytosis have been discovered. Here, we show a previously unknown mechanism of lipid cargo uptake into cells mediated by the receptor Mincle. We found that the receptor Mincle, previously shown to be a pattern recognition receptor of the innate immune system, tightly binds a range of self-lipids. Moreover, we revealed the minimal molecular motif in lipids that is sufficient for Mincle recognition. Superresolution microscopy showed that Mincle forms vesicles in cytoplasm and colocalizes with added fluorescent lipids in endothelial cells but does not colocalize with either clathrin or caveolin-1, and the added lipids were predominantly incorporated in vesicles that expressed Mincle. Using a model of ganglioside GM3 uptake in brain vessel endothelial cells, we show that the knockout of Mincle led to a dramatic decrease in lipid endocytosis. Taken together, our results have revealed a fundamental lipid endocytosis pathway, which we call Mincle-mediated endocytosis (MiME), and indicate a prospective target for the treatment of disorders of lipid metabolism, which are rapidly increasing in prevalence.
Aims and objectives/purpose/research questions:
The primary goal of this study was to investigate the knowledge of Russian gender in young heritage speakers through different agreement constructions.
...Design/methodology/approach:
Participants were 30 Russian–Spanish–Catalan multilinguals from Spain aged 7–11 years, divided into two proficiency groups, and a baseline group of 24 age-matched Russian monolinguals residing in Russia. All participants completed four experiments using an oral elicited production task addressing different linguistic conditions.
Data and analysis:
The accuracy scores were compared between the two proficiency groups and between the heritage and monolingual speakers to document any changes as a function of the type of agreement construction, gender value, noun form transparency, and crosslinguistic congruency.
Findings/conclusions:
The results demonstrated a hierarchy of gender values; masculine being the easiest gender value, neuter the most difficult, and feminine in between the two. The crosslinguistic influence was yelled under vulnerable conditions: when (1) the proficiency in heritage language is low, (2) in opaque and (or) incongruent nouns, and (3) in agreement construction which is absent in Spanish and Catalan. The results also suggest that the heritage language from the high-proficiency group can attain monolingual-like gender agreement knowledge.
Originality:
We documented gender agreement production in trilingual speakers, which is an under-explored topic. The study employs a new method of analysing gender in several constructions, including adjectival and verbal agreement at Noun Phrase and sentence levels.
Significance/implications:
The study provides insights into heritage language development during the early years of exposure to the two majority languages. The results may offer a greater understanding of the characteristics of heritage language/L2 development in trilingual children.
Satirical cinemagazine Fitil (The Fuse), one of the final products of the Thaw, the time of liberalization in both foreign and domestic policy of the Soviet Union, appeared in 1962 and was produced ...under the supervision of Sergei Mikhalkov, a prominent public and literary figure in the USSR. Vivid and engaging, the cinemagazine starred many famous theatre and cinema actors and soon became an important part of mainstream satire, which was aimed at reinforcing the Soviet regime by criticizing some of its flaws. The significance attached to Fitil by Soviet authorities can be illustrated by the fact that its episodes were shown before films in cinemas, that is, it was officially promoted and was seen by the mass public across the Union. Fitil was expected not only to relieve social tension, but also marked the boundaries of the permissible in public criticism and satire. The agenda of Fitil was heterogeneous and dynamic: apart from a number of permanent themes, such as bureaucracy and red tape, bad management, poor service in retail and catering, alcohol abuse, morals, and manners, there were variations in the choice of themes and subjects of satire in different periods. The changes also affected the degree of generalization, the scale of the problems discussed and characteristics of the comic itself. This article analyzes Fitil issues of 1962-1991 and outlines the cinemagazine’s agenda and its changes in time. It is shown that Fitil was a part of mainstream satire, determined by the state policy in the sphere of humour and comedy.
Nowadays there are great quantities of academic courses in which political discourse is being studied. The present paper analyzes the teaching of American political discourse in Russian academic ...areas as an actualization of the most important aspects of both the cultural features and the historical background of the USA influencing not only vocabulary but semantics as well. We have selected 5 speeches of the former and current presidents of the USA to analyze their way of speaking from the linguistic point of view. We confirmed the hypothesis that language cannot be learnt without country’ background, history and culture. Hence, we have implemented some exercises developing oral, writing, listening and reading skills. We have reckoned the individual features of our students as well as the field of their interests using a communicative approach. The following exercises are integrated in courses of English for political purposes in RUDN University.
In this Perspective, we sketch out a vision of fast charging and self-healable energy systems that are primarily organic, feature only abundant elements, and operate with ions other than lithium. ...Using conductive oligomers as highly configurable building blocks, it is possible to create intrinsically adaptable conductive polymeric networks that can be rejuvenated and recycled using simple and safe chemical treatments. Using the versatile organic chemistry toolbox, these oligomers can be further functionalized, for example, with redox-active side chains for high charge storage capacity and ligands capable of complexing metal centers. Cross-linking with metal ions converts the soluble oligomers into insoluble supramolecular networks to yield high-performing electrode materials. The oligomer-based approach can thus provide an exceptional level of control to the design of organic-based battery materials.
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