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  • 1
    Online Resource
    Online Resource
    Intron-encoded cistronic transcripts for minimally invasive monitoring of coding and non-coding RNAs
    Springer Science and Business Media LLC ; 2022
    In:  Nature Cell Biology Vol. 24, No. 11 ( 2022-11), p. 1666-1676
    Details
    In: Nature Cell Biology, Springer Science and Business Media LLC, Vol. 24, No. 11 ( 2022-11), p. 1666-1676
    Abstract: Despite their fundamental role in assessing (patho)physiological cell states, conventional gene reporters can follow gene expression but leave scars on the proteins or substantially alter the mature messenger RNA. Multi-time-point measurements of non-coding RNAs are currently impossible without modifying their nucleotide sequence, which can alter their native function, half-life and localization. Thus, we developed the intron-encoded scarless programmable extranuclear cistronic transcript (INSPECT) as a minimally invasive transcriptional reporter embedded within an intron of a gene of interest. Post-transcriptional excision of INSPECT results in the mature endogenous RNA without sequence alterations and an additional engineered transcript that leaves the nucleus by hijacking the nuclear export machinery for subsequent translation into a reporter or effector protein. We showcase its use in monitoring interleukin-2 ( IL2 ) after T cell activation and tracking the transcriptional dynamics of the long non-coding RNA (lncRNA) NEAT1 during CRISPR interference-mediated perturbation. INSPECT is a method for monitoring gene transcription without altering the mature lncRNA or messenger RNA of the target of interest.
    Type of Medium: Online Resource
    ISSN: 1465-7392 , 1476-4679
    URL: Article
    DOI: 10.1038/s41556-022-00998-6
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1494945-3
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    The effects of two-week program of individually measured physical activity on insulin resistance in obese non-insulin-dependent diabetes mellitus
    National Library of Serbia ; 2003
    In:  Military Medical and Pharmaceutical Journal of Serbia Vol. 60, No. 6 ( 2003), p. 683-690
    Details
    In: Military Medical and Pharmaceutical Journal of Serbia, National Library of Serbia, Vol. 60, No. 6 ( 2003), p. 683-690
    Abstract: Poznato je da se pod uticajem redovne, individualno dozirane aerobne fizicke aktivnosti moze povecati bioloska efikasnost insulina povecanjem broja insulinskih receptora, njihove senzitivnosti i efikasnosti, povecanjem koncentracije glukoznog transportera GLUT-4 na nivou celijske membrane. Cilj istrazivanja je da se utvrdi da li se primenom programa individualno dozirane fizicke aktivnosti u periodu od 14 dana kod gojaznih insulin-nezavisnih dijabeticara (tip 2 dijabetesa) uz povecanje maksimalne potrosnje kiseonika - (VO2)max ostvaruje i smanjenje insulinske rezistencije (M/I). Kod 10 tip 2 dijabeticara zivotnog doba 47,6 ? 4,6 god. (grupa E) u periodu od 14 dana primenjen je program aerobnog treninga, 10 sesija od po 35 min hodanja na pokretnoj traci, intenziteta 60,8% (VO2)max, ucestalosti pet puta nedeljno uz dijetu od 1 600 kcal. U isto vreme drugih 10 tip 2 dijabeticara zivotnog doba 45,9 ? 5,6 god. (grupa K) bili su samo na dijeti od 1 600 kcal. Pre i nakon ovog perioda u obe grupe odredjena je: insulinska senzitivnost (M/I) metodom hiperinsulinskog euglikemijskog klampa i (VO2)max Astrandovim testom opterecenja na ergobiciklu. Za razliku od K grupe u drugom testiranju kod E grupe dobijeno je znacajno povecanje M/I (1,23 ? 0,78 prema 2,42 ? 0,95 (mg/kg/min)(mU) p〈0,001, 96,75%) i povecanje (VO2)max (26,34 ? 4,26 prema 29,16 ? 5,01 ml/kg/min p〈0,05, 10,71%). Rezultati ukazuju da je kod nasih ispitanika primenjeni dvonedeljni program aerobnog treninga znacajno uticao na povecanje aerobne sposobnosti i insulinske senzitivnosti.
    Type of Medium: Online Resource
    ISSN: 0042-8450 , 2406-0720
    URL: Article
    DOI: 10.2298/VSP0306683C
    Language: English
    Publisher: National Library of Serbia
    Publication Date: 2003
    detail.hit.zdb_id: 2169819-3
    SSG: 15,3
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  • 3
    Online Resource
    Online Resource
    A complete versus inducible ischemia-guided revascularization after a culprit-only primary percutaneous coronary intervention in multivessel coronary artery disease: A pilot study
    National Library of Serbia ; 2021
    In:  Srpski arhiv za celokupno lekarstvo Vol. 149, No. 3-4 ( 2021), p. 161-166
    Details
    In: Srpski arhiv za celokupno lekarstvo, National Library of Serbia, Vol. 149, No. 3-4 ( 2021), p. 161-166
    Abstract: Introduction/Objective. Revascularization in multivessel coronary artery disease (MVD) in patients with ST elevation myocardial infarction (STEMI) is a matter of debate. We sought to compare outcomes between revascularization strategies based on angiographic lesion severity or inducible ischemia. Methods. In prospective study, first ever STEMI patients with MVD, defined as 〉 70% stenosis in non-culprit vessel, treated with culprit only primary PCI were randomized to: A. Complete revascularization of all nonculprit significant lesions during initial hospitalization; B. Complete revascularization after 30 days, or C. Revascularization based on non-invasive testing for inducible ischemia. The study explored occurrence of major adverse cardio-cerebral events (MACCE) (cardiac death, repeated MI, cerebrovascular event). Results. The study enrolled 120 patients with door to balloon time within appropriate limits (A 51 ? 26 vs. B 47 ? 33 vs. C 44 ? 29 min, p = 0.604) The patients in group A underwent complete revascularization at 6 [4?7] days after primary PCI, while in the group B it was 35 [32?39] days. In group C, 16/43 (37.2%) patients underwent PCI at 82 [66?147] days after infarction (p 〈 0.001). The patients were followed for 2.7 ? 0.8 years. The events occurred less frequently in patients that underwent planned complete revascularization compared to those who underwent ischemia testing (7.8 vs. 20.9%, p = 0.040). Kaplan?Meier analysis favored complete delayed revascularization (MACCE A 8.8 vs. B 6.9 vs. C 20.9%, log rank p = 0.041). Conclusions. Planned, angiography guided, complete revascularization after initial event may be favorable strategy compared to single stress test for MVD in STEMI.
    Type of Medium: Online Resource
    ISSN: 0370-8179 , 2406-0895
    URL: Article
    DOI: 10.2298/SARH200315108I
    Language: English
    Publisher: National Library of Serbia
    Publication Date: 2021
    detail.hit.zdb_id: 2577665-4
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  • 4
    Online Resource
    Online Resource
    Non-invasive and high-throughput interrogation of exon-specific isoform expression
    Springer Science and Business Media LLC ; 2021
    In:  Nature Cell Biology Vol. 23, No. 6 ( 2021-06), p. 652-663
    Details
    In: Nature Cell Biology, Springer Science and Business Media LLC, Vol. 23, No. 6 ( 2021-06), p. 652-663
    Abstract: Expression of exon-specific isoforms from alternatively spliced mRNA is a fundamental mechanism that substantially expands the proteome of a cell. However, conventional methods to assess alternative splicing are either consumptive and work-intensive or do not quantify isoform expression longitudinally at the protein level. Here, we therefore developed an exon-specific isoform expression reporter system (EXSISERS), which non-invasively reports the translation of exon-containing isoforms of endogenous genes by scarlessly excising reporter proteins from the nascent polypeptide chain through highly efficient, intein-mediated protein splicing. We applied EXSISERS to quantify the inclusion of the disease-associated exon 10 in microtubule-associated protein tau ( MAPT ) in patient-derived induced pluripotent stem cells and screened Cas13-based RNA-targeting effectors for isoform specificity. We also coupled cell survival to the inclusion of exon 18b of FOXP1 , which is involved in maintaining pluripotency of embryonic stem cells, and confirmed that MBNL1 is a dominant factor for exon 18b exclusion. EXSISERS enables non-disruptive and multimodal monitoring of exon-specific isoform expression with high sensitivity and cellular resolution, and empowers high-throughput screening of exon-specific therapeutic interventions.
    Type of Medium: Online Resource
    ISSN: 1465-7392 , 1476-4679
    URL: Article
    DOI: 10.1038/s41556-021-00678-x
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 1494945-3
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Exonuclease-enhanced prime editors
    Springer Science and Business Media LLC ; 2024
    In:  Nature Methods Vol. 21, No. 3 ( 2024-03), p. 455-464
    Details
    In: Nature Methods, Springer Science and Business Media LLC, Vol. 21, No. 3 ( 2024-03), p. 455-464
    Abstract: Prime editing (PE) is a powerful gene-editing technique based on targeted gRNA-templated reverse transcription and integration of the de novo synthesized single-stranded DNA. To circumvent one of the main bottlenecks of the method, the competition of the reverse-transcribed 3′ flap with the original 5′ flap DNA, we generated an enhanced fluorescence-activated cell sorting reporter cell line to develop an exonuclease-enhanced PE strategy (‘Exo-PE’) composed of an improved PE complex and an aptamer-recruited DNA-exonuclease to remove the 5′ original DNA flap. Exo-PE achieved better overall editing efficacy than the reference PE2 strategy for insertions ≥30 base pairs in several endogenous loci and cell lines while maintaining the high editing precision of PE2. By enabling the precise incorporation of larger insertions, Exo-PE complements the growing palette of different PE tools and spurs additional refinements of the PE machinery.
    Type of Medium: Online Resource
    ISSN: 1548-7091 , 1548-7105
    URL: Article
    DOI: 10.1038/s41592-023-02162-w
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2024
    detail.hit.zdb_id: 2163081-1
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Current State of Cold Atmospheric Plasma and Cancer‐Immunity Cycle: Therapeutic Relevance and Overcoming Clinical Limitations Using Hydrogels
    Wiley ; 2023
    In:  Advanced Science Vol. 10, No. 8 ( 2023-03)
    Details
    In: Advanced Science, Wiley, Vol. 10, No. 8 ( 2023-03)
    Abstract: Cold atmospheric plasma (CAP) is a partially ionized gas that gains attention as a well‐tolerated cancer treatment that can enhance anti‐tumor immune responses, which are important for durable therapeutic effects. This review offers a comprehensive and critical summary on the current understanding of mechanisms in which CAP can assist anti‐tumor immunity: induction of immunogenic cell death, oxidative post‐translational modifications of the tumor and its microenvironment, epigenetic regulation of aberrant gene expression, and enhancement of immune cell functions. This should provide a rationale for the effective and meaningful clinical implementation of CAP. As discussed here, despite its potential, CAP faces different clinical limitations associated with the current CAP treatment modalities: direct exposure of cancerous cells to plasma, and indirect treatment through injection of plasma‐treated liquids in the tumor. To this end, a novel modality is proposed: plasma‐treated hydrogels (PTHs) that can not only help overcome some of the clinical limitations but also offer a convenient platform for combining CAP with existing drugs to improve therapeutic responses and contribute to the clinical translation of CAP. Finally, by integrating expertise in biomaterials and plasma medicine, practical considerations and prospective for the development of PTHs are offered.
    Type of Medium: Online Resource
    ISSN: 2198-3844 , 2198-3844
    URL: Issue
    URL: Article
    DOI: 10.1002/advs.v10.8
    DOI: 10.1002/advs.202205803
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2808093-2
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