449 research outputs found
Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ( MISEV ) guidelines for the field in 2014. We now update these MISEV2014 guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points
Theory of Generations in Russia: on the Problem of Determining the Age Boundaries of Youth
Π‘ΡΠ°ΡΡΡ ΠΏΠΎΡΠ²ΡΡΠ΅Π½Π° ΠΎΠ±Π·ΠΎΡΡ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
Π°Π²ΡΠΎΡΡΠΊΠΈΡ
ΠΏΠΎΠ΄Ρ
ΠΎΠ΄ΠΎΠ² Π² ΡΠ°ΠΌΠΊΠ°Ρ
ΠΎΡΠ΅ΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΡΠΊΠΎΠ»Ρ ΡΠ΅ΠΎΡΠΈΠΈ ΠΏΠΎΠΊΠΎΠ»Π΅Π½ΠΈΠΉ. Π ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ ΠΏΡΠ΅Π΄ΠΌΠ΅ΡΠ° ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ Π²ΡΡΡΡΠΏΠ°Π΅Ρ Π°Π½Π°Π»ΠΈΠ· ΡΠΎΡΡΠΈΠΉΡΠΊΠΈΡ
ΠΌΠΎΠ΄Π΅Π»Π΅ΠΉ ΡΠ΅ΠΎΡΠΈΠΈ ΠΏΠΎΠΊΠΎΠ»Π΅Π½ΠΈΠΉ Π² ΠΊΠΎΠ½ΡΠ΅ΠΊΡΡΠ΅ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ Π²ΠΎΠ·ΡΠ°ΡΡΠ° ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΠΎΠΉ ΠΌΠΎΠ»ΠΎΠ΄Π΅ΠΆΠΈ. ΠΠ±ΡΠ΅ΠΊΡΠΎΠΌ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΡΡΠ°Π»ΠΈ ΡΠ΅ΠΎΡΠΈΠΈ Π. Π‘. Π‘ΡΠΌΡΠΊΠΎΠΉ ΠΈ Π‘. Π. Π‘Π²Π΅ΡΠ΄Π»ΠΎΠ²Π°, Π³ΡΡΠΏΠΏΡ Π°Π²ΡΠΎΡΠΎΠ² ΡΠΎΡΡΠΈΠΉΡΠΊΠΎΠΉ ΡΠΊΠΎΠ»Ρ ΡΠ΅ΠΎΡΠΈΠΈ ΠΏΠΎΠΊΠΎΠ»Π΅Π½ΠΈΠΉ Β«RuGenerationsΒ». Π ΡΡΠ°ΡΡΠ΅ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Ρ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ Π°Π½Π°Π»ΠΈΠ·Π° ΠΎΡΠ΅ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ
ΡΠ΅ΠΎΡΠΈΠΉ. ΠΠ²ΡΠΎΡ ΡΡΠΎΡΠ½ΡΠ΅Ρ Π½Π° ΡΡΠΎΠΉ ΠΎΡΠ½ΠΎΠ²Π΅ Π²ΠΎΠ·ΡΠ°ΡΡΠ½ΡΠ΅ Π³ΡΠ°Π½ΠΈΡΡ ΡΠΈΡΡΠΎΠ²ΠΎΠΉ ΠΌΠΎΠ»ΠΎΠ΄Π΅ΠΆΠΈ.The article is devoted to the review of various authorβΊs approaches within the framework of the national school of generational theory. The subject of the study is the analysis of the Soviet and Russian models of the theory of generations in the context of determining the age of modern youth. The object of the study were the theories of Yu. Levada, A. S. Sumskaya and S. A. Sverdlov, the group of authors of the Russian 385 school of generational theory βRuGenerationsβ. The article presents the results of the analysis of domestic theories. The author clarifies on this basis the age limits of digital youth
The Experience of Studying the Media Studies of Tambov Schoolchildren
The article presents the results of the media study related to the behavior of Tambov schoolchildren during the pandemic. The subject of the study was the values of generation Z at the age of 13 to 17 years, the object β the process of changing values under the influence of the pandemic. As research methods, we used general scientific methods-analysis and synthesis, and an empirical method of measuring the audience of representatives of generation Z using questionnaires. The results of the study allow us to predict changes in the moral priorities of young people, which will affect the media behavior of centenials in the post-pandemic period.Π ΡΡΠ°ΡΡΠ΅ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Ρ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΠΌΠ΅Π΄ΠΈΠ°ΠΏΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ ΡΠ°ΠΌΠ±ΠΎΠ²ΡΠΊΠΈΡ
ΡΠΊΠΎΠ»ΡΠ½ΠΈΠΊΠΎΠ² Π² ΠΏΠ΅ΡΠΈΠΎΠ΄ ΠΏΠ°Π½Π΄Π΅ΠΌΠΈΠΈ. ΠΡΠ΅Π΄ΠΌΠ΅ΡΠΎΠΌ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΡΡΠ°Π»ΠΈ ΡΠ΅Π½Π½ΠΎΡΡΠ½ΡΠ΅ ΡΡΡΠ°Π½ΠΎΠ²ΠΊΠΈ ΠΏΠΎΠΊΠΎΠ»Π΅Π½ΠΈΡ Z Π² Π²ΠΎΠ·ΡΠ°ΡΡΠ΅ ΠΎΡ 13 Π΄ΠΎ 17 Π»Π΅Ρ, ΠΎΠ±ΡΠ΅ΠΊΡΠΎΠΌ β ΠΏΡΠΎΡΠ΅ΡΡ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡ ΡΠ΅Π½Π½ΠΎΡΡΠ΅ΠΉ ΠΏΠΎΠ΄ Π²Π»ΠΈΡΠ½ΠΈΠ΅ΠΌ ΠΏΠ°Π½Π΄Π΅ΠΌΠΈΠΈ. Π ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π»ΠΈΡΡ ΠΎΠ±ΡΠ΅Π½Π°ΡΡΠ½ΡΠ΅ ΠΌΠ΅ΡΠΎΠ΄Ρ β Π°Π½Π°Π»ΠΈΠ· ΠΈ ΡΠΈΠ½ΡΠ΅Π·, ΠΈ ΡΠΌΠΏΠΈΡΠΈΡΠ΅ΡΠΊΠΈΠΉ ΠΌΠ΅ΡΠΎΠ΄ ΠΈΠ·ΠΌΠ΅ΡΠ΅Π½ΠΈΡ Π°ΡΠ΄ΠΈΡΠΎΡΠΈΠΈ ΠΏΡΠ΅Π΄ΡΡΠ°Π²ΠΈΡΠ΅Π»Π΅ΠΉ ΠΏΠΎΠΊΠΎΠ»Π΅Π½ΠΈΡ Z ΠΏΡΠΈ ΠΏΠΎΠΌΠΎΡΠΈ Π°Π½ΠΊΠ΅ΡΠΈΡΠΎΠ²Π°Π½ΠΈΡ. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΡΡ ΠΏΡΠΎΠ³Π½ΠΎΠ·ΠΈΡΠΎΠ²Π°ΡΡ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡ Π½ΡΠ°Π²ΡΡΠ²Π΅Π½Π½ΡΡ
ΠΏΡΠΈΠΎΡΠΈΡΠ΅ΡΠΎΠ² ΠΌΠΎΠ»ΠΎΠ΄Π΅ΠΆΠΈ, ΠΊΠΎΡΠΎΡΡΠ΅ ΠΎΡΡΠ°Π·ΡΡΡΡ Π½Π° ΠΌΠ΅Π΄ΠΈΠ°ΠΏΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠΈ ΡΠ΅Π½ΡΠ΅Π½ΠΈΠ°Π»ΠΎΠ² Π² ΠΏΠΎΡΡΠΏΠ°Π½Π΄Π΅ΠΌΠΈΡΠ΅ΡΠΊΠΈΠΉ ΠΏΠ΅ΡΠΈΠΎΠ΄
Media Texts of Modern Youth Media: the Specifics of Building the βAddressee β Addresseeβ Relationship
Π‘ΡΠ°ΡΡΡ ΠΏΠΎΡΡΡΠΏΠΈΠ»Π° Π² ΡΠ΅Π΄Π°ΠΊΡΠΈΡ 10.02.2023 Π³.Π‘ΡΠ°ΡΡΡ ΠΏΠΎΡΠ²ΡΡΠ΅Π½Π° Π°ΠΊΡΡΠ°Π»ΡΠ½ΠΎΠΉ ΠΏΡΠΎΠ±Π»Π΅ΠΌΠ΅ ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΡ Ρ ΠΌΠΎΠ»ΠΎΠ΄Π΅ΠΆΠΈ ΠΊΠΎΠΌΠΌΡΠ½ΠΈΠΊΠ°ΡΠΈΠ²Π½ΠΎΠΉ ΠΊΡΠ»ΡΡΡΡΡ. Π‘ ΡΠ΅Π»ΡΡ Π²ΡΡΠ²Π»Π΅Π½ΠΈΡ ΡΠΏΠ΅ΡΠΈΡΠΈΠΊΠΈ ΠΏΠΎΡΡΡΠΎΠ΅Π½ΠΈΡ ΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠΉ Β«Π°Π΄ΡΠ΅ΡΠ°Π½Ρ β Π°Π΄ΡΠ΅ΡΠ°ΡΒ» Π±ΡΠ» ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ Π°Π½Π°Π»ΠΈΠ· ΠΌΠ΅Π΄ΠΈΠ°ΡΠ΅ΠΊΡΡΠΎΠ², ΠΎΡΠΈΠ΅Π½ΡΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
Π½Π° ΠΌΠΎΠ»ΠΎΠ΄ΡΡ
ΠΌΠ΅Π΄ΠΈΠ°ΠΏΠΎΡΡΠ΅Π±ΠΈΡΠ΅Π»Π΅ΠΉ. ΠΠ»Ρ Π΄ΠΎΡΡΠΈΠΆΠ΅Π½ΠΈΡ ΡΠ΅Π»ΠΈ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΠΏΡΠΈ ΠΏΠΎΠΌΠΎΡΠΈ ΡΠ΅ΠΊΡΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΌΠ΅ΡΠΎΠ΄Π° ΠΈΠ·ΡΡΠ°Π»ΡΡ ΠΊΠΎΠ½ΡΠ΅Π½Ρ ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΡΡ
ΠΌΠΎΠ»ΠΎΠ΄Π΅ΠΆΠ½ΡΡ
ΠΌΠ΅Π΄ΠΈΠ° Β«ΠΠ°ΡΡΡΡΒ», Β«Π―Π½Π³ΡΠΏΠ΅ΠΉΡΒ», NR. Π ΡΠ°Π±ΠΎΡΠ΅ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Ρ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ Π³Π»ΡΠ±ΠΈΠ½Π½ΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΈΠ·Π° ΡΡΡΠ°Π½ΠΈΡ Π² ΡΠΎΡΠΈΠ°Π»ΡΠ½ΡΡ
ΠΌΠ΅Π΄ΠΈΠ° ΠΏΡΠ΅Π΄ΡΡΠ°Π²ΠΈΡΠ΅Π»Π΅ΠΉ ΠΌΠΎΠ»ΠΎΠ΄Π΅ΠΆΠΈ β ΡΡΠ°ΡΡΠ½ΠΈΠΊΠΎΠ² ΠΏΡΠΎΠ΅ΠΊΡΠ° Π’Π°ΠΌΠ±ΠΎΠ²ΡΠΊΠΎΠ³ΠΎ Π³ΠΎΡΡΠ΄Π°ΡΡΡΠ²Π΅Π½Π½ΠΎΠ³ΠΎ ΡΠ½ΠΈΠ²Π΅ΡΡΠΈΡΠ΅ΡΠ° ΠΈΠΌΠ΅Π½ΠΈ Π. Π . ΠΠ΅ΡΠΆΠ°Π²ΠΈΠ½Π° Β«Π¨ΠΊΠΎΠ»Π° ΡΠ°Π·Π²ΠΈΡΠΈΡ DerzhavinskillsΒ», Π½Π°Π±Π»ΡΠ΄Π΅Π½ΠΈΠΉ ΡΡΠ΅Π΄ΠΈ ΡΡΠ΅Π½ΠΈΠΊΠΎΠ² 4β8-Ρ
ΠΊΠ»Π°ΡΡΠΎΠ² ΡΠ°ΠΌΠ±ΠΎΠ²ΡΠΊΠΎΠΉ ΡΠΊΠΎΠ»Ρ, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΈΠ½ΡΠ΅ΡΠ²ΡΡ Ρ ΡΠ°Π±ΠΎΡΠ½ΠΈΠΊΠ°ΠΌΠΈ ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΡ (ΡΠΊΠΎΠ»ΡΠ½ΡΠ΅ ΡΡΠΈΡΠ΅Π»Ρ ΠΈ ΠΏΡΠΈΡ
ΠΎΠ»ΠΎΠ³ΠΈ). Π Π·Π°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅ ΠΏΡΠΈΠ²Π΅Π΄Π΅Π½Ρ Π²ΡΠ²ΠΎΠ΄Ρ ΠΎ ΡΡΠ΅Π΄ΡΡΠ²Π°Ρ
ΠΏΠΎΡΡΡΠΎΠ΅Π½ΠΈΡ ΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠΉ Β«Π°Π΄ΡΠ΅ΡΠ°Π½Ρ β Π°Π΄ΡΠ΅ΡΠ°ΡΒ»: ΠΏΡΠ΅ΠΎΠ±Π»Π°Π΄Π°Π½ΠΈΠ΅ ΠΏΡΠΈΠ΅ΠΌΠ° Π΄ΠΈΠ°Π»ΠΎΠ³ΠΈΠ·Π°ΡΠΈΠΈ, ΡΡΠ³ΠΎΡΠ΅Π½ΠΈΠ΅ ΠΊ ΠΈΠ³ΡΠΎΡΠ΅Π°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΠΊΠ°ΠΊ ΡΠΎΡΠΌΠ΅ Π΄ΠΈΠ°Π»ΠΎΠ³Π° Ρ Π°ΡΠ΄ΠΈΡΠΎΡΠΈΠ΅ΠΉ, ΡΡΠΈΠ»Π΅Π½ΠΈΠ΅ Π²ΠΎΠ·Π΄Π΅ΠΉΡΡΠ²ΠΈΡ ΠΌΠ°Π½ΠΈΠΏΡΠ»ΡΡΠΈΠ²Π½ΡΡ
ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠΎΠ² ΠΈ Π½ΠΈΠ²Π΅Π»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΡΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π½ΠΎΡΠΌ Π² ΠΊΠΎΠ½ΡΠ΅ΠΊΡΡΠ΅ ΡΠ΅ΡΠ΅Π²ΠΎΠ³ΠΎ ΠΎΠ±ΡΠ΅Π½ΠΈΡ.The article is devoted to the actual problem of the formation of a communicative culture among young people. In order to identify the specifics of building the βaddressee β addresseeβ relationship, the study of media texts aimed at young media consumers is carried out. To achieve the research goal, the content of modern youth media βMarusyaβ, βYangspaceβ, NR was studied based on the textual method. The paper presents the results of an inβdepth analysis of the social media pages of youth representatives participating in the Tambov State University named after G. R. Derzhavin School of Development Derzhavinskills, the results of observation among students of grades 4β8 of the Tambov school and interviews with educators (school teachers and psychologists). In conclusion, the conclusions about the means of building the βaddressee β addresseeβ relationship are presented: the predominance of the method of dialogization, the attraction to game realization as a form of dialogue with the audience, the strengthening of the impact of manipulative mechanisms and the leveling of ethical norms in the context of speech communication
Diverse lipid conjugates for functional extra-hepatic siRNA delivery in vivo
Small interfering RNA (siRNA)-based therapies are proving to be efficient for treating liver-associated disorders. However, extra-hepatic delivery remains challenging, limiting therapeutic siRNA utility. We synthesized a panel of fifteen lipid-conjugated siRNAs and systematically evaluated the impact of conjugate on siRNA tissue distribution and efficacy. Generally, conjugate hydrophobicity defines the degree of clearance and the liver-to-kidney distribution profile. In addition to primary clearance tissues, several conjugates achieve significant siRNA accumulation in muscle, lung, heart, adrenal glands and fat. Oligonucleotide distribution to extra-hepatic tissues with some conjugates was significantly higher than with cholesterol, a well studied conjugate, suggesting that altering conjugate structure can enhance extra-hepatic delivery. These conjugated siRNAs enable functional gene silencing in lung, muscle, fat, heart and adrenal gland. Required levels for productive silencing vary (5-200 mug/g) per tissue, suggesting that the chemical nature of conjugates impacts tissue-dependent cellular/intracellular trafficking mechanisms. The collection of conjugated siRNA described here enables functional gene modulation in vivo in several extra-hepatic tissues opening these tissues for gene expression modulation. A systemic evaluation of a panel of conjugated siRNA, as reported here, has not previously been investigated and shows that chemical engineering of lipid siRNAs is essential to advance the RNA therapeutic field
Loss of huntingtin function slows synaptic vesicle endocytosis in striatal neurons from the htt(Q140/Q140) mouse model of Huntington\u27s disease
Huntington\u27s disease (HD) is caused by CAG repeat expansion within the HTT gene, with the dysfunction and eventual loss of striatal medium spiny neurons a notable feature. Since medium spiny neurons receive high amounts of synaptic input, we hypothesised that this vulnerability originates from an inability to sustain presynaptic performance during intense neuronal activity. To test this hypothesis, primary cultures of either hippocampal or striatal neurons were prepared from either wild-type mice or a knock-in HD mouse model which contains 140 poly-glutamine repeats in the huntingtin protein (htt(Q140/Q140)). We identified a striatum-specific defect in synaptic vesicle (SV) endocytosis in htt(Q140/Q140) neurons that was only revealed during high frequency stimulation. This dysfunction was also present in neurons that were heterozygous for the mutant HTT allele. Depletion of endogenous huntingtin using hydrophobically-modified siRNA recapitulated this activity-dependent defect in wild-type neurons, whereas depletion of mutant huntingtin did not rescue the effect in htt(Q140/Q140) neurons. Importantly, this SV endocytosis defect was corrected by overexpression of wild-type huntingtin in homozygous htt(Q140/Q140) neurons. Therefore, we have identified an activity-dependent and striatum-specific signature of presynaptic dysfunction in neurons derived from pre-symptomatic HD mice, which is due to loss of wild-type huntingtin function. This presynaptic defect may render this specific neuronal subtype unable to operate efficiently during high frequency activity patterns, potentially resulting in dysfunctional neurotransmission, synapse failure and ultimately degeneration
The Practice of Media Consumption of Β«Digital YouthΒ» in Social Media
ΠΡΠ΅Π΄ΠΌΠ΅ΡΠΎΠΌ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ Π΄Π°Π½Π½ΠΎΠΉ ΡΠ°Π±ΠΎΡΡ ΡΠ²Π»ΡΠ΅ΡΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Β«ΡΠΈΡΡΠΎΠ²ΠΎΠΉ ΠΌΠΎΠ»ΠΎΠ΄Π΅ΠΆΠΈΒ» Π² ΡΠΎΡΠΈΠ°Π»ΡΠ½ΡΡ
ΠΌΠ΅Π΄ΠΈΠ°. ΠΠ±ΡΠ΅ΠΊΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ β ΠΌΠ΅Π΄ΠΈΠ°ΠΏΠΎΡΡΠ΅Π±Π»Π΅Π½ΠΈΠ΅ ΠΌΠΎΠ»ΠΎΠ΄Π΅ΠΆΠ½ΠΎΠΉ Π°ΡΠ΄ΠΈΡΠΎΡΠΈΠΈ Π² ΡΠΎΡΠΈΠ°Π»ΡΠ½ΡΡ
ΡΠ΅ΡΡΡ
ΠΈ ΠΌΠ΅ΡΡΠ΅Π½Π΄ΠΆΠ΅ΡΠ°Ρ
. Π ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ Π³Π»ΡΠ±ΠΈΠ½Π½ΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΈΠ·Π° ΠΌΠ΅Π΄ΠΈΠ°ΠΊΠΎΠ½ΡΠ΅Π½ΡΠ° ΠΌΠΎΠ»ΠΎΠ΄Π΅ΠΆΠΈ ΠΏΡΠΈΠ²Π»Π΅ΡΠ΅Π½Π° Π³ΡΡΠΏΠΏΠ° ΡΡΡΠ΄Π΅Π½ΡΠΎΠ² ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΡΠΏΠ΅ΡΠΈΠ°Π»ΡΠ½ΠΎΡΡΠ΅ΠΉ, ΠΏΡΠΎΡ
ΠΎΠ΄ΡΡΠΈΡ
ΠΎΠ±ΡΡΠ΅Π½ΠΈΠ΅ Π² ΠΏΡΠΎΠ΅ΠΊΡΠ΅ Β«DerzhavinskillsΒ» Π’Π°ΠΌΠ±ΠΎΠ²ΡΠΊΠΎΠ³ΠΎ Π³ΠΎΡΡΠ΄Π°ΡΡΡΠ²Π΅Π½Π½ΠΎΠ³ΠΎ ΡΠ½ΠΈΠ²Π΅ΡΡΠΈΡΠ΅ΡΠ° ΠΈΠΌΠ΅Π½ΠΈ Π. Π . ΠΠ΅ΡΠΆΠ°Π²ΠΈΠ½Π°. Π ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ Π°Π²ΡΠΎΡΡ ΡΡΠ°ΡΡΠΈ ΡΠΎΡΠΌΡΠ»ΠΈΡΡΡΡ Π²ΡΠ²ΠΎΠ΄Ρ ΠΎ ΡΡΠ½ΠΊΡΠΈΠΎΠ½Π°Π»Π΅ ΠΈ ΡΡΠ΅ΠΏΠ΅Π½ΠΈ Π΄ΠΎΠ²Π΅ΡΠΈΡ Β«ΡΠΈΡΡΠΎΠ²ΠΎΠΉ ΠΌΠΎΠ»ΠΎΠ΄Π΅ΠΆΠΈΒ» ΠΏΠΎΠΏΡΠ»ΡΡΠ½ΡΠΌ ΡΠΎΡΠΈΠ°Π»ΡΠ½ΡΠΌ ΠΌΠ΅Π΄ΠΈΠ°. ΠΡΠΌΠ΅ΡΠ°Π΅ΡΡΡ ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΠ΅ Π² ΠΌΠ΅Π΄ΠΈΠ°ΠΏΠΎΡΡΠ΅Π±Π»Π΅Π½ΠΈΠΈ ΠΏΡΠ°ΠΊΡΠΈΠΊΠΈ Β«Digital detoxΒ», ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΡΡΠ΅ΠΉ ΠΎΠ± Β«ΡΡΡΠ°Π»ΠΎΡΡΠΈ ΠΎΡ ΠΏΡΠ±Π»ΠΈΡΠ½ΠΎΡΡΠΈΒ» ΠΈ ΡΡΡΠ΅ΠΌΠ»Π΅Π½ΠΈΠΈ Β«ΡΠΈΡΡΠΎΠ²ΠΎΠΉ ΠΌΠΎΠ»ΠΎΠ΄Π΅ΠΆΠΈΒ» ΠΊ Π°ΡΡΠΈΠΌΠΈΠ»ΡΡΠΈΠΈ Π² Π½Π΅Π±ΠΎΠ»ΡΡΠΈΠ΅ Π³ΡΡΠΏΠΏΡ.The subject of this work is the activity of βdigital youthβ in social media. The object of the study is the media consumption of the youth audience in social networks and instant messengers. A group of students of various specialties studying in the Derzhavinskills project of Derzhavin Tambov State University. As a result of the study, the authors of the article formulate conclusions about the functionality and degree of trust of βdigital youthβ in popular social media. There are manifestations in media consumption of the practice of βDigital detoxβ, indicating βpublicity fatigueβ and the desire of βdigital youthβ to assimilate into small groups
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
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
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