Studying the geroprotective properties of the ATM inhibitor KU-60019 on three Drosophila species with different life span

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

The serine/threonine protein kinase ATM (ataxia-telangiectasia mutated) performs a number of functions in the cell that are interrelated with the aging process. In addition to regulating the cellular response to DNA damage, ATM phosphorylates vacuolar ATPase, leading to lysosome degradation and cellular senescence. In this work, we analysed the geroprotective potential of KU-60019, a selective ATM inhibitor, using individuals of three Drosophila species with different lifespans. KU-60019 was shown to increase the lifespan of individuals of the long-lived species D. virilis and individuals of a species with moderate lifespan D. melanogaster. However, in individuals of the short-lived species D. kikkawai, longevity is reduced after KU-60019 treatment. At the same time, KU-60019 treatment increases survival of Drosophila individuals of the three species under hyperthermia, oxidative stress and starvation, but has no effect on age-dependent changes in the level of locomotor activity. Suppression of tefu gene expression (ATM homologue) by RNA interference also causes an increase in longevity and stress tolerance of D. melanogaster individuals compared to individuals of control lines. Thus, the effect of KU-60019 on longevity varies depending on the Drosophila species, which may be related to the previously established differences of transcriptomes in the studied species and requires further experimental study.

Full Text

Restricted Access

About the authors

L. A. Koval

Komi Science Centre of the Ural Branch, Russian Academy of Sciences

Email: amoskalev@ib.komisc.ru

Institute of Biology

Russian Federation, Syktyvkar, 167982

N. V. Zemskaya

Komi Science Centre of the Ural Branch, Russian Academy of Sciences

Email: amoskalev@ib.komisc.ru

Institute of Biology

Russian Federation, Syktyvkar, 167982

N. R. Pakshina

Komi Science Centre of the Ural Branch, Russian Academy of Sciences

Email: amoskalev@ib.komisc.ru

Institute of Biology

Russian Federation, Syktyvkar, 167982

M. V. Shaposhnikov

Komi Science Centre of the Ural Branch, Russian Academy of Sciences

Email: amoskalev@ib.komisc.ru

Institute of Biology

Russian Federation, Syktyvkar, 167982

А. А. Moskalev

Komi Science Centre of the Ural Branch, Russian Academy of Sciences

Author for correspondence.
Email: amoskalev@ib.komisc.ru

Institute of Biology

Russian Federation, Syktyvkar, 167982

References

  1. Abraham R.T. (2001) Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes Dev. 15, 2177–2196.
  2. Paull T.T. (2015) Mechanisms of ATM activation. Annu. Rev. Biochem. 84, 711–738.
  3. Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R., 3rd, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. (2007) ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science. 316, 1160–1166.
  4. Shibata A., Jeggo P.A. (2021) ATM´s role in the repair of DNA double-strand breaks. Genes. 12(9),1370.
  5. Zhang X., Wan G., Berger F.G., He X., Lu X. (2011) The ATM kinase induces microRNA biogenesis in the DNA damage response. Mol. Cell. 41, 371–383.
  6. Liu J., Jin T., Ran L., Zhao Z., Zhu R., Xie G., Bi X. (2022) Profiling ATM regulated genes in Drosophila at physiological condition and after ionizing radiation. Hereditas. 159, 41.
  7. Rothblum-Oviatt C., Wright J., Lefton-Greif M.A., McGrath-Morrow S.A., Crawford T.O., Lederman H.M. (2016) Ataxia telangiectasia: a review. Orphanet. J. Rare Dis. 11, 159.
  8. Chaudhary M.W., Al-Baradie R.S. (2014) Ataxia-telangiectasia: future prospects. Appl. Clin. Genet. 7, 159–167.
  9. Barlow C., Hirotsune S., Paylor R., Liyanage M., Eckhaus M., Collins F., Shiloh Y., Crawley J.N., Ried T., Tagle D., Wynshaw-Boris A. (1996) Atm-deficient mice: a paradigm of ataxia telangiectasia. Cell. 86, 159–171.
  10. Quek H., Luff J., Cheung K., Kozlov S., Gatei M., Lee C.S., Bellingham M.C., Noakes P.G., Lim Y.C., Barnett N.L., Dingwall S., Wolvetang E., Mashimo T., Roberts T.L., Lavin M.F. (2017) A rat model of ataxia-telangiectasia: evidence for a neurodegenerative phenotype. Hum. Mol. Genet. 26, 109–123.
  11. Chen K., Wang P., Chen J., Ying Y., Chen Y., Gilson E., Lu Y., Ye J. (2022) Loss of atm in zebrafish as a model of ataxia-telangiectasia syndrome. Biomedicines. 10(2), 392.
  12. Petersen A.J., Rimkus S.A., Wassarman D.A. (2012) ATM kinase inhibition in glial cells activates the innate immune response and causes neurodegeneration in Drosophila. Proc. Natl. Acad. Sci. USA. 109, E656–664.
  13. Petersen A.J., Katzenberger R.J., Wassarman D.A. (2013) The innate immune response transcription factor relish is necessary for neurodegeneration in a Drosophila model of ataxia-telangiectasia. Genetics. 194, 133–142.
  14. Silva E., Tiong S., Pedersen M., Homola E., Royou A., Fasulo B., Siriaco G., Campbell S.D. (2004) ATM is required for telomere maintenance and chromosome stability during Drosophila development. Curr. Biol. 14, 1341–1347.
  15. Chen T., Dong B., Lu Z., Tian B., Zhang J., Zhou J., Wu H., Zhang Y., Wu J., Lin P., Zhang J., Xu H., Mo X. (2010) A functional single nucleotide polymorphism in promoter of ATM is associated with longevity. Mech. Ageing Dev. 131, 636–640.
  16. Piaceri I., Bagnoli S., Tedde A., Sorbi S., Nacmias B. (2013) Ataxia-telangiectasia mutated (ATM) genetic variant in Italian centenarians. Neurol. Sci. 34, 573–575.
  17. Fu S., Hu J., Chen X., Li B., Shun H., Deng J., Zhang Y., Yao Y., Zhao Y. (2021) Mutant single nucleotide polymorphism rs189037 in ataxia-telangiectasia mutated gene is significantly associated with ventricular wall thickness and human lifespan. Front. Cardiovasc. Med. 8, 658908.
  18. Ditch S., Paull T.T. (2012) The ATM protein kinase and cellular redox signaling: beyond the DNA damage response. Trends Biochem. Sci. 37, 15–22.
  19. Amirifar P., Ranjouri M.R., Yazdani R., Abolhassani H., Aghamohammadi A. (2019) Ataxia-telangiectasia: a review of clinical features and molecular pathology. Pediatr. Allergy Immunol. 30, 277–288.
  20. Valentin-Vega Y.A., Maclean K.H., Tait-Mulder J., Milasta S., Steeves M., Dorsey F.C., Cleveland J.L., Green D.R., Kastan M.B. (2012) Mitochondrial dysfunction in ataxia-telangiectasia. Blood. 119, 1490–1500.
  21. Hirozane T., Tohmonda T., Yoda M., Shimoda M., Kanai Y., Matsumoto M., Morioka H., Nakamura M., Horiuchi K. (2016) Conditional abrogation of Atm in osteoclasts extends osteoclast lifespan and results in reduced bone mass. Sci. Rep. 6, 34426.
  22. Weitering T.J., Takada S., Weemaes C.M.R., van Schouwenburg P.A., van der Burg M. (2021) ATM: Translating the DNA damage response to adaptive immunity. Trends Immunol. 42, 350–365.
  23. Stagni V., Cirotti C., Barilà D. (2018) Ataxia-telangiectasia mutated kinase in the control of oxidative stress, mitochondria, and autophagy in cancer: a maestro with a large orchestra. Front. Oncol. 8, 73.
  24. Stagni V., Ferri A., Cirotti C., Barilà D. (2020) ATM kinase-dependent regulation of autophagy: a key player in senescence? Front. Cell Dev. Biol. 8, 599048.
  25. Osorio F.G., Barcena C., Soria-Valles C., Ramsay A.J., de Carlos F., Cobo J., Fueyo A., Freije J.M., Lopez-Otin C. (2012) Nuclear lamina defects cause ATM-dependent NF-kappaB activation and link accelerated aging to a systemic inflammatory response. Genes Dev. 26, 2311–2324.
  26. Lee S.S., Bohrson C., Pike A.M., Wheelan S.J., Greider C.W. (2015) ATM kinase is required for telomere elongation in mouse and human cells. Cell Rep. 13, 1623–1632.
  27. Kang H.T., Park J.T., Choi K., Kim Y., Choi H.J.C., Jung C.W., Lee Y.S., Park S.C. (2017) Chemical screening identifies ATM as a target for alleviating senescence. Nat. Chem. Biol. 13, 616–623.
  28. Kuk M.U., Kim J.W., Lee Y.S., Cho K.A., Park J.T., Park S.C. (2019) Alleviation of senescence via ATM inhibition in accelerated aging models. Mol. Cells. 42, 210–217.
  29. Hari K.L., Santerre A., Sekelsky J.J., McKim K.S., Boyd J.B., Hawley R.S. (1995) The mei-41 gene of D. melanogaster is a structural and functional homolog of the human ataxia telangiectasia gene. Cell. 82, 815–821.
  30. Bi X., Srikanta D., Fanti L., Pimpinelli S., Badugu R., Kellum R., Rong Y.S. (2005) Drosophila ATM and ATR checkpoint kinases control partially redundant pathways for telomere maintenance. Proc. Natl. Acad. Sci. USA. 102, 15167–15172.
  31. Pedersen M., Tiong S., Campbell S.D. (2010) Molecular genetic characterization of Drosophila ATM conserved functional domains. Genome. 53, 778–786.
  32. Oikemus S.R., McGinnis N., Queiroz-Machado J., Tukachinsky H., Takada S., Sunkel C.E., Brodsky M.H. (2004) Drosophila atm/telomere fusion is required for telomeric localization of HP1 and telomere position effect. Genes Dev. 18, 1850–1861.
  33. Hu Y., Comjean A., Rodiger J., Liu Y., Gao Y., Chung V., Zirin J., Perrimon N., Mohr S.E. (2021) FlyRNAi.org-the database of the Drosophila RNAi screening center and transgenic RNAi project: 2021 update. Nucl. Acids Res. 49, D908–D915.
  34. Xia B., de Belle J.S. (2016) Transgenerational programming of longevity and reproduction by post-eclosion dietary manipulation in Drosophila. Aging. 8, 1115–1134.
  35. Shaposhnikov M.V., Zemskaya N.V., Koval L.A., Schegoleva E.V., Zhavoronkov A., Moskalev A.A. (2018) Effects of N-acetyl-L-cysteine on lifespan, locomotor activity and stress-resistance of 3 Drosophila species with different lifespans. Aging. 10, 2428–2458.
  36. Moskalev A.A., Shaposhnikov M.V., Zemskaya N.V., Koval L., Schegoleva E.V., Guvatova Z.G., Krasnov G.S., Solovev I.A., Sheptyakov M.A., Zhavoronkov A., Kudryavtseva A.V. (2019) Transcriptome analysis of long-lived Drosophila melanogaster E(z) mutants sheds light on the molecular mechanisms of longevity. Sci. Rep. 9, 9151.
  37. Mantel N. (1966) Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother. Rep. 50, 163–170.
  38. Martinez R.L.M.C., Naranjo J.D. (2012) A pretest for choosing between logrank and wilcoxon tests in the two-sample problem. Metron. 68, 111–125.
  39. Wang C., Li Q., Redden D.T., Weindruch R., Allison D.B. (2004) Statistical methods for testing effects on “maximum lifespan”. Mech. Ageing Dev. 125, 629–632.
  40. Bland J.M., Altman D.G. (1995) Multiple significance tests: the Bonferroni method. BMJ. 310, 170.
  41. McHugh M.L. (2011) Multiple comparison analysis testing in ANOVA. Biochem. Med. 21, 203-209.
  42. Han S.K., Kwon H.C., Yang J.S., Kim S., Lee S.V. (2024) OASIS portable: user-friendly offline suite for secure survival analysis. Mol Cells. 47, 100011.
  43. Toledo-Sherman L., Breccia P., Cachope R., Bate J.R., Angulo-Herrera I., Wishart G., Matthews K.L., Martin S.L., Cox H.C., McAllister G., Penrose S.D., Vater H., Esmieu W., Van de Poël A., Van de Bospoort R., Strijbosch A., Lamers M., Leonard P., Jarvis R.E., Blackaby W., Barnes K., Eznarriaga M., Dowler S., Smith G.D., Fischer D.F., Lazari O., Yates D., Rose M., Jang S.W., Muñoz-Sanjuan I., Dominguez C. (2019) Optimization of potent and selective ataxia telangiectasia-mutated inhibitors suitable for a proof-of-concept study in Huntington´s disease models. J. Med. Chem. 62, 2988–3008.
  44. Moskalev A., Chernyagina E., Kudryavtseva A., Shaposhnikov M. (2017) Geroprotectors: a unified concept and screening approaches. Aging Dis. 8, 354–363.
  45. Земская Н.В., Шапошников М.В., Москалев А.А. (2017) Взаимосвязь продолжительности жизни с характеристиками жизненного цикла и стрессоустойчивостью у 12 видов рода Drosophila. Успехи геронтологии. 30, 192–199.
  46. Maslov D.L., Zemskaya N.V., Trifonova O.P., Lichtenberg S., Balashova E.E., Lisitsa A.V., Moskalev A.A., Lokhov P.G. (2021) Comparative metabolomic study of Drosophila species with different lifespans. Int. J. Mol. Sci. 22, 12873.
  47. Ma S., Avanesov A.S., Porter E., Lee B.C., Mariotti M., Zemskaya N., Guigo R., Moskalev A.A., Gladyshev V.N. (2018) Comparative transcriptomics across 14 Drosophila species reveals signatures of longevity. Aging Cell. 17, e12740.
  48. Lushchak O., Strilbytska O., Storey K.B. (2023) Gender-specific effects of pro-longevity interventions in Drosophila. Mech. Ageing Dev. 209, 111754.
  49. Zhu Y., Mao C., Wu J., Li S., Ma R., Cao H., Ji M., Jing C., Tang J. (2014) Improved ataxia telangiectasia mutated kinase inhibitor KU60019 provides a promising treatment strategy for non-invasive breast cancer. Oncol. Lett. 8, 2043–2048.
  50. Cao W., Shen R., Richard S., Liu Y., Jalalirad M., Cleary M.P., D´Assoro A.B., Gradilone S.A., Yang D.Q. (2022) Inhibition of triple-negative breast cancer proliferation and motility by reactivating p53 and inhibiting overactivated Akt. Oncol. Rep. 47(2), 41.
  51. Qian M., Liu Z., Peng L., Tang X., Meng F., Ao Y., Zhou M., Wang M., Cao X., Qin B., Wang Z., Zhou Z., Wang G., Gao Z., Xu J., Liu B. (2018) Boosting ATM activity alleviates aging and extends lifespan in a mouse model of progeria. eLife. 7, e34836.
  52. Lee J.H., Guo Z., Myler L.R., Zheng S., Paull T.T. (2014) Direct activation of ATM by resveratrol under oxidizing conditions. PLoS One. 9, e97969.
  53. Qi Y., Qiu Q., Gu X., Tian Y., Zhang Y. (2016) ATM mediates spermidine-induced mitophagy via PINK1 and Parkin regulation in human fibroblasts. Sci. Rep. 6, 24700.
  54. Kang H.T., Park J.T., Choi K., Kim Y., Choi H.J.C., Jung C.W., Lee Y.S., Park S.C. (2017) Chemical screening identifies ATM as a target for alleviating senescence. Nat. Chem. Biol. 13, 616–623.
  55. Cheng A., Tse K.H., Chow H.M., Gan Y., Song X., Ma F., Qian Y.X.Y., She W., Herrup K. (2021) ATM loss disrupts the autophagy-lysosomal pathway. Autophagy. 17, 1998–2010.
  56. Boya P., Kroemer G. (2008) Lysosomal membrane permeabilization in cell death. Oncogene. 27, 6434–6451.
  57. Гусакова Е.А., Городецкая И.В. (2012) Стресс и протеолитические ферменты лизосом. Вестник ВГМУ. 11, 15–25.
  58. Kurz T., Terman A., Gustafsson B., Brunk U.T. (2008) Lysosomes and oxidative stress in aging and apoptosis. Biochim. Biophys. Acta. 1780, 1291–1303.
  59. Pivtoraiko V.N., Stone S.L., Roth K.A., Shacka J.J. (2009) Oxidative stress and autophagy in the regulation of lysosome-dependent neuron death. Antioxid. Redox Signal. 11, 481–496.
  60. Nishikawa H., Miyazaki T., Nakayama H., Minematsu A., Yamauchi S., Yamashita K., Takazono T., Shimamura S., Nakamura S., Izumikawa K., Yanagihara K., Kohno S., Mukae H. (2016) Roles of vacuolar H+-ATPase in the oxidative stress response of Candida glabrata. FEMS Yeast Res. 16(5), fow054.
  61. Lee C., Lamech L., Johns E., Overholtzer M. (2020) Selective lysosome membrane turnover is induced by nutrient starvation. Dev. Cell. 55, 289–297 e284.
  62. Bandyopadhyay U., Todorova P., Pavlova N.N., Tada Y., Thompson C.B., Finley L.W.S., Overholtzer M. (2022) Leucine retention in lysosomes is regulated by starvation. Proc. Natl. Acad. Sci. USA. 119(6), e2114912119.
  63. Ingemann L., Kirkegaard T. (2014) Lysosomal storage diseases and the heat shock response: convergences and therapeutic opportunities. J. Lipid. Res. 55, 2198–2210.
  64. Nylandsted J., Gyrd-Hansen M., Danielewicz A., Fehrenbacher N., Lademann U., Hoyer-Hansen M., Weber E., Multhoff G., Rohde M., Jaattela M. (2004) Heat shock protein 70 promotes cell survival by inhibiting lysosomal membrane permeabilization. J. Exp. Med. 200, 425–435.
  65. Milanović Z., Pantelić S., Trajković N., Sporiš G., Kostić R., James N. (2013) Age-related decrease in physical activity and functional fitness among elderly men and women. Clin. Interv. Aging. 8, 549–556.
  66. Buchman A.S., Wilson R.S., Yu L., James B.D., Boyle P.A., Bennett D.A. (2014) Total daily activity declines more rapidly with increasing age in older adults. Arch. Gerontol. Geriatr. 58, 74–79.
  67. Iliadi K.G., Boulianne G.L. (2010) Age-related behavioral changes in Drosophila. Ann. N.Y. Acad. Sci. 1197, 9–18.
  68. Jones M.A., Grotewiel M. (2011) Drosophila as a model for age-related impairment in locomotor and other behaviors. Exp. Gerontol. 46, 320–325.
  69. Tower J. (2023) Markers and mechanisms of death in Drosophila. Front Aging. 4, 1292040.
  70. Lints F.A., Le Bourg E., Lints C.V. (1984) Spontaneous locomotor activity and life span. A test of the rate of living theory in Drosophila melanogaster. Gerontology. 30, 376–387.
  71. Le Bourg E. (1987) The rate of living theory. Spontaneous locomotor activity, aging and longevity in Drosophila melanogaster. Exp. Gerontol. 22, 359–369.
  72. Shaposhnikov M.V., Guvatova Z.G., Zemskaya N.V., Koval L.A., Schegoleva E.V., Gorbunova A.A., Golubev D.A., Pakshina N.R., Ulyasheva N.S., Solovev I.A., Bobrovskikh M.A., Gruntenko N.E., Menshanov P.N., Krasnov G.S., Kudryavseva A.V., Moskalev A.A. (2022) Molecular mechanisms of exceptional lifespan increase of Drosophila melanogaster with different genotypes after combinations of pro-longevity interventions. Commun. Biol. 5, 566.
  73. Mueller J.M., Zhang N., Carlson J.M., Simpson J.H. (2021) Variation and variability in Drosophila grooming behavior. Front. Behav. Neurosci. 15, 769372.
  74. Bi X., Wei S.C., Rong Y.S. (2004) Telomere protection without a telomerase; the role of ATM and Mre11 in Drosophila telomere maintenance. Curr. Biol. 14, 1348–1353.
  75. Bi X., Gong M., Srikanta D., Rong Y.S. (2005) Drosophila ATM and Mre11 are essential for the G2/M checkpoint induced by low-dose irradiation. Genetics. 171, 845–847.
  76. Ciapponi L., Cenci G., Gatti M. (2006) The Drosophila Nbs protein functions in multiple pathways for the maintenance of genome stability. Genetics. 173, 1447–1454.
  77. Scoles D.R., Gandelman M., Paul S., Dexheimer T., Dansithong W., Figueroa K.P., Pflieger L.T., Redlin S., Kales S.C., Sun H., Maloney D., Damoiseaux R., Henderson M.J., Simeonov A., Jadhav A., Pulst S.M. (2022) A quantitative high-throughput screen identifies compounds that lower expression of the SCA2-and ALS-associated gene ATXN2. J. Biol. Chem. 298, 102228.
  78. Patel P.R., Sun H., Li S.Q., Shen M., Khan J., Thomas C.J., Davis M.I. (2013) Identification of potent Yes1 kinase inhibitors using a library screening approach. Bioorg. Med. Chem. Lett. 23, 4398–4403.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Effect of the ATM inhibitor KU-60019 at concentrations of 1 and 100 μM on the lifespan of males (а, в, д) and females (б, г, е) of the genus Drosophila: D. melanogaster (CS), D. kikkawai, D. virilis. ** – p < 0.001, log-rank test with Bonferroni correction.

Download (272KB)
Indexing metadata
3. Fig. 2. Effect of the ATM inhibitor KU-60019 at concentrations of 1 and 100 μM on stress resistance of males (а, в, д) and females (б, г, е) of D. melanogaster. * – p < 0.05, *** – p < 0.001, log-rank test with Bonferroni correction.

Download (273KB)
Indexing metadata
4. Fig. 3. Effect of the ATM inhibitor KU-60019 at concentrations of 1 and 100 μM on stress resistance of males (а, в, д) and females (б, г, е) of D. kikkawai. elements: ** – p < 0.01, *** – p < 0.001, log-rank test with Bonferroni correction.

Download (283KB)
Indexing metadata
5. Fig. 4. Effect of the ATM inhibitor KU-60019 at concentrations of 1 and 100 μM on stress resistance of males (а, в, д) and females (б, г, е) of D. virilis. *** – p < 0.001, log-rank test with Bonferroni correction.

Download (282KB)
Indexing metadata
6. Fig. 5. Effect of the ATM inhibitor KU-60019 at concentrations of 1 and 100 μM on spontaneous locomotor activity of male (а, в, д) and female (б, г, е) D. melanogaster (а, б), D. kikkawai (в, г), and D. virilis (д, е). *p < 0.024, Tukey's post hoc test. Error bars indicate standard error of the mean.

Download (375KB)
Indexing metadata
7. Fig. 6. The role of the tefu gene in the effect of the ATM inhibitor KU-60019 at concentrations of 1 and 100 μM on the lifespan of males (а, в, д) and females (б, г, е) of D. melanogaster. ** – p < 0.01, *** – p < 0.0001 – log-rank test with Bonferroni correction.

Download (292KB)
Indexing metadata
8. Fig. 7. Effect of the ATM inhibitor KU-60019 at concentrations of 1 and 100 μM on stress resistance of D. melanogaster males with suppressed tefu gene expression. * – p < 0.001, ** and ## – p < 0.0001 relative to the parental line da-GAL4 (а, в, д) and UAS-RNAi-tefu (б, г, е), respectively, log-rank test.

Download (425KB)
Indexing metadata
9. Fig. 8. Effect of the ATM inhibitor KU-60019 at concentrations of 1 and 100 μM on stress resistance of D. melanogaster females with RNA interference of the tefu gene. ** and ## – p < 0.0001 relative to the parental line da-GAL4 (а, в, д) and UAS-RNAi-tefu (б, г, е), respectively, log-rank test.

Download (407KB)
Indexing metadata
10. Fig. 9. Effect of the ATM inhibitor KU-60019 at concentrations of 1 and 100 μM on spontaneous motional activity of male (а, б) and female (в, г) D. melanogaster with RNA interference of the tefu gene. # – p < 0.003 relative to the parental line da-GAL4 (а, в) and UAS-RNAi-tefu (б, г), Tukey post-hoc test. Error bars indicate the standard error of the mean.

Download (360KB)
Indexing metadata

Copyright (c) 2024 Russian Academy of Sciences

Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».