15 research outputs found
Effect of elevated temperature on critical load in stability tests of the steel plate
This paper presents the results of a study on the effect of epoxypolyester based powder coatings on the critical strength of plate specimens made of rolled steel sheets. The results show that the model using planar elements gives more accurate results than the model using three-dimensional elements. The best agreement with experiment was obtained with Ansys results using Eigenvalue bucling, less than 1%. The lowest experimental agreement was with the results obtained in Ansys using solid elements, about 70%
Improving the Russian-language Wikipedia articles on medicines using new knowledge Cochrane
To evaluate the effectiveness of the Cochrane Russia Initiative to improve the articles of the Russianlanguage Wikipedia by including information from Cochrane Systematic Reviews (CSR) to ensure the accuracy and impartiality of their content as an information basis for the quality use of medicines by doctors and the public. Methods. Wikipedia articles on selected drugs were improved by introducing evidence from Cochrane Systematic Reviews - "Cochrenized". A parallel open-label non-randomized controlled intervention study was conducted. We assigned 2 groups of drugs and Wikipedia articles about them: the intervention group ("Cochrenization") and the control group (36 articles each). Control group articles were not edited. The change in the number of visits to Wikipedia pages for the year (2018-2019) was measured, the statistical significance of the differences was assessed by using the Wilcoxon signed-rank test. Results. We edited 36 Wikipedia articles, including 13 articles on migraine treatment, 9 diabetes mellitus, 14 pain and inflammation articles. These articles constituted the intervention group. The control group consisted of articles on cardiovascular (11), gastrointestinal (14) and dermatological agents (11). We used the Cochrane Russia Initiative dashboard on Wikipedia to compare the number of article views before and after the intervention and Cochrane analytics on demand for translations of Cochrane systematic reviews summaries. After "Cochrenization", the number of Wikipedia article views (2018-2019) increased in total/average article views for treatments: migraines by 18%/47%, pain and inflammation - 16%/43%, diabetes mellitus - 18%/0%. Analysis of Cochrane reports showed an increase in the number of views of Cochrane systematic reviews summaries on the Cochrane.org website in general by 9 times and from Russian-speaking browsers by 11 times. Improvement of medicine-related articles of the Russian-language Wikipedia by the introduction of information from Cochrane systematic reviews was accompanied by an increase in their demand in terms of the number of views in general by 34%, with a similar increase in control (without intervention) (p-value of the experimental group - 0.002, control - 0.000). The Wikipedia articles on medicines, which belonged to the Russian Vital and Essential Drugs List or the World Health Organization Model List of Essential Medicines, got more views. Conclusion. The role of confounding factors justifies the feasibility of developing a methodology for studying the usefulness of improving Wikipedia articles, different from controlled trial research methodology; further inclusion of Cochrane knowledge into Wikipedia is needed
IgG4-Π°ΡΡΠΎΡΠΈΠΈΡΠΎΠ²Π°Π½Π½ΡΠΉ ΡΠΊΠ»Π΅ΡΠΎΠ·ΠΈΡΡΡΡΠΈΠΉ Ρ ΠΎΠ»Π°Π½Π³ΠΈΡ β Π΄ΠΈΠ°Π³Π½ΠΎΠ·, ΠΊΠΎΡΠΎΡΡΠΉ ΠΌΠΎΠΆΠ΅Ρ ΠΈΠ·ΠΌΠ΅Π½ΠΈΡΡ Ρ ΠΎΠ΄ ΡΠΎΠ±ΡΡΠΈΠΉ (ΠΎΠ±Π·ΠΎΡ Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΡ ΠΈ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠ΅ Π½Π°Π±Π»ΡΠ΄Π΅Π½ΠΈΠ΅)
Immunoglobulin G4-associated sclerosing cholangitis (IgG4-SC) can mimic primary sclerosing cholangitis, cholangiocarcinoma, and pancreatic adenocarcinoma. Its proper diagnosis allows for an adequate therapy and an improvement of the outcomes. The article presents a short literature review with an emphasis on the challenging diagnostic and therapeutic aspects, illustrated by a clinical case. The diagnosis of IgG4-SC is based on a combination of biochemical, radiological and histological signs and symptoms, including elevated levels of serum IgG4, intra- and extrahepatic biliary strictures detected by magnetic resonance cholangiography, and multifocal IgG4-lymphoplasmic infiltrations, sclerosing fibrosis of the bile ducts, seen at morphological assessment. Glucocorticoids (GCS) are the first line agents to achieve remission in patients with IgG4-SC. Most patients respond well to the systemic GCS. However, about 20% of patients (mostly those with extensive sclerotic intra- and/or extrahepatic abnormalities and signs of advanced disease / cirrhosis) show an insufficient or no response from the beginning of the treatment. The clinical case illustrates that timely verification of the IgG4-SC diagnosis may have an important prognostic value. The case history of a 62-year old female patient confirms the difficulties of the early diagnosis of the disease: for a relatively long time, the patient had the diagnosis of primary sclerosing cholangitis. Delay with GCS prescription (the treatment was initiated only at the stage of liver cirrhosis) had led to the lack of clinical efficacy and development of complications, such as relapsing cholangitis with advanced biliary strictures. In patients with suspected primary sclerosing cholangitis, timely differential diagnosis with IgG4-SC is relevant, because early GCS administration can slow the progression of the disease.ΠΠΌΠΌΡΠ½ΠΎΠ³Π»ΠΎΠ±ΡΠ»ΠΈΠ½ G4-Π°ΡΡΠΎΡΠΈΠΈΡΠΎΠ²Π°Π½Π½ΡΠΉ ΡΠΊΠ»Π΅ΡΠΎΠ·ΠΈΡΡΡΡΠΈΠΉΒ Ρ
ΠΎΠ»Π°Π½Π³ΠΈΡ (IgG4-Π‘Π₯) ΠΌΠΎΠΆΠ΅Ρ ΠΈΠΌΠΈΡΠΈΡΠΎΠ²Π°ΡΡ ΠΏΠ΅ΡΠ²ΠΈΡΠ½ΡΠΉ ΡΠΊΠ»Π΅ΡΠΎΠ·ΠΈΡΡΡΡΠΈΠΉ Ρ
ΠΎΠ»Π°Π½Π³ΠΈΡ, Ρ
ΠΎΠ»Π°Π½Π³ΠΈΠΎΠΊΠ°ΡΡΠΈΠ½ΠΎΠΌΡ, Π°Π΄Π΅Π½ΠΎΠΊΠ°ΡΡΠΈΠ½ΠΎΠΌΡ ΠΏΠΎΠ΄ΠΆΠ΅Π»ΡΠ΄ΠΎΡΠ½ΠΎΠΉΒ ΠΆΠ΅Π»Π΅Π·Ρ. Π‘Π²ΠΎΠ΅Π²ΡΠ΅ΠΌΠ΅Π½Π½Π°Ρ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠ° ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅ΡΒ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΡΡΒ Π°Π΄Π΅ΠΊΠ²Π°ΡΠ½ΡΡΒ ΡΠ΅ΡΠ°ΠΏΠΈΡ ΠΈ ΡΠ»ΡΡΡΠ°ΡΡ ΠΏΡΠΎΠ³Π½ΠΎΠ· Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ. Π Π½Π°ΡΡΠΎΡΡΠ΅ΠΉ ΡΡΠ°ΡΡΠ΅Β ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Β Β ΠΊΡΠ°ΡΠΊΠΈΠΉΒ ΠΎΠ±Π·ΠΎΡΒ Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΡΒ Ρ Π°ΠΊΡΠ΅Π½ΡΠΎΠΌΒ Π½Π°Β Π°ΡΠΏΠ΅ΠΊΡΠ°Ρ
, Π²ΡΠ·ΡΠ²Π°ΡΡΠΈΡ
Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΡΠ΅ΡΠΊΠΈΠ΅Β Β Β ΠΈΒ Β Β ΡΠ΅ΡΠ°ΠΏΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅Β Β Β ΡΡΡΠ΄Π½ΠΎΡΡΠΈ, ΠΏΡΠΎΠΈΠ»Π»ΡΡΡΡΠΈΡΠΎΠ²Π°Π½Π½ΡΠ΅ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΌ ΠΏΡΠΈΠΌΠ΅ΡΠΎΠΌ. ΠΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠ°Β IgG4-Π‘Π₯ ΠΎΡΠ½ΠΎΠ²Π°Π½Π°Β Π½Π° ΡΠΎΡΠ΅ΡΠ°Π½ΠΈΠΈΒ Β Π±ΠΈΠΎΡ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΡ
,Β Β ΡΠ°Π΄ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΒ Β Π³ΠΈΡΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
Β Β ΠΏΡΠΈΠ·Π½Π°ΠΊΠΎΠ²,Β Β ΡΡΠ΅Π΄ΠΈΒ Β ΠΊΠΎΡΠΎΡΡΡ
β ΠΏΠΎΠ²ΡΡΠ΅Π½Π½ΡΠΉ ΡΡΠΎΠ²Π΅Π½ΡΒ IgG4 Π² ΡΡΠ²ΠΎΡΠΎΡΠΊΠ΅ ΠΊΡΠΎΠ²ΠΈ, Π²Π½ΡΡΡΠΈΠΏΠ΅ΡΠ΅Π½ΠΎΡΠ½ΡΠ΅ ΠΈ Π²Π½Π΅ΠΏΠ΅ΡΠ΅Π½ΠΎΡΠ½ΡΠ΅ Π±ΠΈΠ»ΠΈΠ°ΡΠ½ΡΠ΅ ΡΡΡΠΈΠΊΡΡΡΡ, Π²ΡΡΠ²Π»ΡΠ΅ΠΌΡΠ΅ ΠΏΡΠΈ ΠΌΠ°Π³Π½ΠΈΡΠ½ΠΎ-ΡΠ΅Π·ΠΎΠ½Π°Π½ΡΠ½ΠΎΠΉ Ρ
ΠΎΠ»Π°Π½Π³ΠΈΠΎΠ³ΡΠ°ΡΠΈΠΈ, ΠΈ ΠΌΡΠ»ΡΡΠΈΡΠΎΠΊΠ°Π»ΡΠ½ΡΠ΅ IgG4-Π»ΠΈΠΌΡΠΎΠΏΠ»Π°Π·ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΈΠ½ΡΠΈΠ»ΡΡΡΠ°ΡΠΈΠΈ, ΡΠΊΠ»Π΅ΡΠΎΠ·ΠΈΡΡΡΡΠΈΠΉ ΡΠΈΠ±ΡΠΎΠ· ΠΆΠ΅Π»ΡΠ½ΡΡ
ΠΏΡΠΎΡΠΎΠΊΠΎΠ², ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΠ΅ΠΌΡΠ΅ ΠΌΠΎΡΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈ. ΠΠ»ΡΠΊΠΎΠΊΠΎΡΡΠΈΠΊΠΎΡΡΠ΅ΡΠΎΠΈΠ΄Ρ (ΠΠΠ‘) β ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΡΒ ΠΏΠ΅ΡΠ²ΠΎΠΉΒ Π»ΠΈΠ½ΠΈΠΈ Π΄Π»Ρ Π΄ΠΎΡΡΠΈΠΆΠ΅Π½ΠΈΡΒ ΡΠ΅ΠΌΠΈΡΡΠΈΠΈΒ Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ²Β Ρ IgG4-Π‘Π₯. ΠΠΎΠ»ΡΡΠΈΠ½ΡΡΠ²ΠΎΒ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ²Β Ρ
ΠΎΡΠΎΡΠΎ ΡΠ΅Π°Π³ΠΈΡΡΡΡ Π½Π° ΡΠ΅ΡΠ°ΠΏΠΈΡ ΡΠΈΡΡΠ΅ΠΌΠ½ΡΠΌΠΈ ΠΠΠ‘. ΠΠ΄Π½Π°ΠΊΠΎ ΠΎΠΊΠΎΠ»ΠΎ 20% Π±ΠΎΠ»ΡΠ½ΡΡ
(ΡΠ°ΡΠ΅ ΡΡΠΎ ΠΏΠ°ΡΠΈΠ΅Π½ΡΡ Ρ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΡΠΌΠΈΒ ΡΠΊΠ»Π΅ΡΠΎΠ·ΠΈΡΡΡΡΠΈΠΌΠΈΒ Π²Π½ΡΡΡΠΈΠΏΠ΅ΡΠ΅Π½ΠΎΡΠ½ΡΠΌΠΈΒ ΠΈ/ΠΈΠ»ΠΈ Π²Π½Π΅ΠΏΠ΅ΡΠ΅Π½ΠΎΡΠ½ΡΠΌΠΈ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡΠΌΠΈ ΠΈ ΠΏΡΠΈΠ·Π½Π°ΠΊΠ°ΠΌΠΈΒ ΠΏΡΠΎΠ΄Π²ΠΈΠ½ΡΡΠΎΠ³ΠΎΒ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ Π½Π° ΡΡΠ°Π΄ΠΈΠΈ ΡΠΈΡΡΠΎΠ·Π°Β ΠΏΠ΅ΡΠ΅Π½ΠΈ) ΠΈΠΌΠ΅ΡΡ Π½Π΅ΠΏΠΎΠ»Π½ΡΠΉ ΠΎΡΠ²Π΅ΡΒ ΠΈΠ»ΠΈΒ ΠΈΠ·Π½Π°ΡΠ°Π»ΡΠ½ΠΎΒ Β Π½Π΅Β ΠΎΡΠ²Π΅ΡΠ°ΡΡΒ Π½Π°Β Π»Π΅ΡΠ΅Π½ΠΈΠ΅. ΠΡΠΈΠ²Π΅Π΄Π΅Π½Π½ΠΎΠ΅Β ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠ΅ Π½Π°Π±Π»ΡΠ΄Π΅Π½ΠΈΠ΅ Π½Π°Π³Π»ΡΠ΄Π½ΠΎΒ Π΄Π΅ΠΌΠΎΠ½ΡΡΡΠΈΡΡΠ΅Ρ,Β ΡΡΠΎΒ ΡΠ²ΠΎΠ΅Π²ΡΠ΅ΠΌΠ΅Π½Π½Π°Ρ Π²Π΅ΡΠΈΡΠΈΠΊΠ°ΡΠΈΡΒ Π΄ΠΈΠ°Π³Π½ΠΎΠ·Π° IgG4-Π‘Π₯ ΠΌΠΎΠΆΠ΅Ρ ΠΈΠΌΠ΅ΡΡ Π²Π°ΠΆΠ½ΠΎΠ΅ ΠΏΡΠΎΠ³Π½ΠΎΡΡΠΈΡΠ΅ΡΠΊΠΎΠ΅Β Π·Π½Π°ΡΠ΅Π½ΠΈΠ΅. ΠΡΡΠΎΡΠΈΡ Π±ΠΎΠ»Π΅Π·Π½ΠΈΒ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΊΠΈ 62 Π»Π΅Ρ ΠΏΠΎΠ΄ΡΠ²Π΅ΡΠΆΠ΄Π°Π΅ΡΒ ΡΡΡΠ΄Π½ΠΎΡΡΠΈ ΡΠ°Π½Π½Π΅ΠΉ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ: Π΄ΠΎΡΡΠ°ΡΠΎΡΠ½ΠΎ Π΄Π»ΠΈΡΠ΅Π»ΡΠ½ΠΎΠ΅Β Π²ΡΠ΅ΠΌΡ Π΄ΠΈΠ°Π³Π½ΠΎΠ·ΠΎΠΌ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΊΠΈ Π±ΡΠ» ΠΏΠ΅ΡΠ²ΠΈΡΠ½ΡΠΉ ΡΠΊΠ»Π΅ΡΠΎΠ·ΠΈΡΡΡΡΠΈΠΉ Ρ
ΠΎΠ»Π°Π½Π³ΠΈΡ. ΠΠ΅ΡΠ²ΠΎΠ΅Π²ΡΠ΅ΠΌΠ΅Π½Π½ΠΎΠ΅ Π½Π°Π·Π½Π°ΡΠ΅Π½ΠΈΠ΅Β ΠΠΠ‘Β (ΡΠ΅ΡΠ°ΠΏΠΈΡ Π±ΡΠ»Π° Π½Π°Π·Π½Π°ΡΠ΅Π½Π° ΡΠΆΠ΅ Π½Π° ΡΡΠ°Π΄ΠΈΠΈ ΡΠΈΡΡΠΎΠ·Π°Β ΠΏΠ΅ΡΠ΅Π½ΠΈ) ΠΏΡΠΈΠ²Π΅Π»ΠΎΒ ΠΊ ΠΎΡΡΡΡΡΡΠ²ΠΈΡ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉΒ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΈ ΡΠ°Π·Π²ΠΈΡΠΈΡΒ ΠΎΡΠ»ΠΎΠΆΠ½Π΅Π½ΠΈΠΉΒ β ΡΠ΅ΡΠΈΠ΄ΠΈΠ²ΠΈΡΡΡΡΠ΅ΠΌΡ Ρ
ΠΎΠ»Π°Π½Π³ΠΈΡΡ Π½Π° ΡΠΎΠ½Π΅Β Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΡΡ
Β Π±ΠΈΠ»ΠΈΠ°ΡΠ½ΡΡ
ΡΡΡΠΈΠΊΡΡΡ. ΠΠ°ΡΠΈΠ΅Π½ΡΠ°ΠΌ Ρ ΠΏΠΎΠ΄ΠΎΠ·ΡΠ΅Π½ΠΈΠ΅ΠΌ Π½Π° ΠΏΠ΅ΡΠ²ΠΈΡΠ½ΡΠΉΒ ΡΠΊΠ»Π΅ΡΠΎΠ·ΠΈΡΡΡΡΠΈΠΉΒ Ρ
ΠΎΠ»Π°Π½Π³ΠΈΡ ΡΠ΅Π»Π΅ΡΠΎΠΎΠ±ΡΠ°Π·Π½ΠΎΒ ΡΠ²ΠΎΠ΅Π²ΡΠ΅ΠΌΠ΅Π½Π½ΠΎ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΡΡΒ Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΡΠΉ Π΄ΠΈΠ°Π³Π½ΠΎΠ· Ρ IgG4-Π‘Π₯, ΠΏΠΎΡΠΊΠΎΠ»ΡΠΊΡ ΡΠ°Π½Π½Π΅Π΅ Π½Π°Π·Π½Π°ΡΠ΅Π½ΠΈΠ΅Β ΠΠΠ‘ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅ΡΒ Π·Π°ΠΌΠ΅Π΄Π»ΠΈΡΡΒ ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ.
Clinical case of special legal liability which is the result of a doctor when combination of specialties
We analyzed a forensic case related to an unfavorable outcome of medical care by a pediatrician. One of the reasons for the unfavorable outcome of medical care was the combination of pediatric and pediatric neurology specialties by the doctor, which, according to experts, contributed to an incorrect assessment of the severity of the child's condition and incorrect assessment of general cerebral symptoms and neurological disorders, without proper differentiation. As a result, the diagnostic was not fully provided, and more serious diseases at the time were not excluded. We determined the objective and subjective aspects of liability for combination several specialties. A medical-legal and forensic assessment of a specific unfavorable outcome of medical practice is given. It is concluded that any combination of different specialties by a doctor not only requires additional professional duties but, at the same time, creates additional legal risks in term of criminal law, which should be taken into account by each specialist who has assumed additional obligations
Transformation of 2-methyl-1-phenylethynyl-1,2,3,4-tetrahydroisoquinoline by the action of activated alkynes
[Figure not available: see fulltext.] Transformations of 2-methyl-1-phenylethynyl-1,2,3,4-tetrahydroisoquinoline resulting from the action of activated alkynes in trifluoroethanol and hexafluoroisopropanol were studied. In reactions with dimethyl acetylenedicarboxylate, 6-phenylethynyl-substituted benzazocines were prepared, while methyl 4-benzyl-5-(2-ethenylphenyl)-1-methyl-1H-pyrrole-3-carboxylate and benzo[d][3]-azacyclodeca[4,6,7]triene with the allene fragment, respectively, were isolated in reactions with methyl propiolate and acetylacetylene in addition to the corresponding benzazocines. As a rule, in hexafluoroisopropanol, the yields of azocines are higher. In reaction with acetylacetylene in dichloromethane, 1-(2-acetylvinyl)-1-phenylethynyltetrahydroisoquinoline is formed in high yield. Β© 2018, Springer Science+Business Media, LLC, part of Springer Nature
Transformation of 2-methyl-1-phenylethynyl-1,2,3,4-tetrahydroisoquinoline by the action of activated alkynes
[Figure not available: see fulltext.] Transformations of 2-methyl-1-phenylethynyl-1,2,3,4-tetrahydroisoquinoline resulting from the action of activated alkynes in trifluoroethanol and hexafluoroisopropanol were studied. In reactions with dimethyl acetylenedicarboxylate, 6-phenylethynyl-substituted benzazocines were prepared, while methyl 4-benzyl-5-(2-ethenylphenyl)-1-methyl-1H-pyrrole-3-carboxylate and benzo[d][3]-azacyclodeca[4,6,7]triene with the allene fragment, respectively, were isolated in reactions with methyl propiolate and acetylacetylene in addition to the corresponding benzazocines. As a rule, in hexafluoroisopropanol, the yields of azocines are higher. In reaction with acetylacetylene in dichloromethane, 1-(2-acetylvinyl)-1-phenylethynyltetrahydroisoquinoline is formed in high yield. Β© 2018, Springer Science+Business Media, LLC, part of Springer Nature
Alternative splicing of telomerase catalytic subunit hTERT generated by apoptotic endonuclease EndoG induces human CD4+ T cell death
Telomerase activity is regulated by alternative splicing of its catalytic subunit human Telomerase Reverse Transcriptase (hTERT) mRNA. Induction of a non-active spliced hTERT leads to inhibition of telomerase activity. However, very little is known about the mechanism of hTERT mRNA alternative splicing. The aim of this study was to determine the role of the apoptotic endonuclease EndoG in alternative splicing of hTERT and telomerase activity. A strong correlation was identified between EndoG expression levels and hTERT splice variants in human CD4+ and CD8+ T lymphocytes. Overexpression of EndoG in CD4+ T cells down-regulated the expression of the active full-length hTERT variant and up-regulated expression of the non-active spliced variant. A reduction in full-length hTERT transcripts down-regulated telomerase activity. Long-term in vitro cultivation of EndoG-overexpressing CD4+ T cells led to dramatically shortened telomeres, conversion of cells into a replicative senescence state, and activation of the BCL2/BAX-associated apoptotic pathway finally leading to cell death. These data indicated the participation of EndoG in alternative mRNA splicing of the telomerase catalytic subunit hTERT, regulation of telomerase activity and determination of cell fate. Β© 2017 Elsevier Gmb
Synthesis of 1-(para-methoxyphenyl)tetrazolyl-Substituted 1,2,3,4-Tetrahydroisoquinolines and Their Transformations Involving Activated Alkynes
1-(p-Methoxyphenyl)tetrazolyl-substituted 6,7-dimethoxy(6,7-methylenedioxy)-1,2,3,4-tetrahydroisoquinolines formed tetrazolyl-substituted azocines in high yields by using activated alkynes. Unsubstituted at 6,7,8-aromatic fragment 1-tetrazolylisoquinoline interacted in several pathways forming tetrazolyl-substituted azocines, 1-tetrazolyl-1-R-vinylisoquinolines and 3-azaspiro[5.5]undeca-1,7,9-triene
Alternative splicing of telomerase catalytic subunit hTERT generated by apoptotic endonuclease EndoG induces human CD4+ T cell death
Telomerase activity is regulated by alternative splicing of its catalytic subunit human Telomerase Reverse Transcriptase (hTERT) mRNA. Induction of a non-active spliced hTERT leads to inhibition of telomerase activity. However, very little is known about the mechanism of hTERT mRNA alternative splicing. The aim of this study was to determine the role of the apoptotic endonuclease EndoG in alternative splicing of hTERT and telomerase activity. A strong correlation was identified between EndoG expression levels and hTERT splice variants in human CD4+ and CD8+ T lymphocytes. Overexpression of EndoG in CD4+ T cells down-regulated the expression of the active full-length hTERT variant and up-regulated expression of the non-active spliced variant. A reduction in full-length hTERT transcripts down-regulated telomerase activity. Long-term in vitro cultivation of EndoG-overexpressing CD4+ T cells led to dramatically shortened telomeres, conversion of cells into a replicative senescence state, and activation of the BCL2/BAX-associated apoptotic pathway finally leading to cell death. These data indicated the participation of EndoG in alternative mRNA splicing of the telomerase catalytic subunit hTERT, regulation of telomerase activity and determination of cell fate. Β© 2017 Elsevier Gmb