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preLekára.sk / Odborné časopisy / PLOS One / 2020 - 1

Beyond the heterodimer model for mineralocorticoid and glucocorticoid receptor interactions in nuclei and at DNA

English version

Autoři: John R. Pooley aff001;  Caroline A. Rivers aff001;  Michael T. Kilcooley aff001;  Susana N. Paul aff001;  Ayse Derya Cavga aff003;  Yvonne M. Kershaw aff001;  Serena Muratcioglu aff004;  Attila Gursoy aff003;  Ozlem Keskin aff003;  Stafford L. Lightman aff001
Působiště autorů: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, United Kingdom aff001;  Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America aff002;  Department of Chemical and Biological Engineering, Koc University, Istanbul, Turkey aff003;  Department of Molecular and Cell Biology, University of California, Berkeley, California, United States of America aff004;  Howard Hughes Medical Institute, University of California, Berkeley, California, United States of America aff005
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0227520

Souhrn

Glucocorticoid (GR) and mineralocorticoid receptors (MR) are believed to classically bind DNA as homodimers or MR-GR heterodimers to influence gene regulation in response to pulsatile basal or stress-evoked glucocorticoid secretion. Pulsed corticosterone presentation reveals MR and GR co-occupy DNA only at the peaks of glucocorticoid oscillations, allowing interaction. GR DNA occupancy was pulsatile, while MR DNA occupancy was prolonged through the inter-pulse interval. In mouse mammary 3617 cells MR-GR interacted in the nucleus and at a chromatin-associated DNA binding site. Interactions occurred irrespective of ligand type and receptors formed complexes of higher order than heterodimers. We also detected MR-GR interactions ex-vivo in rat hippocampus. An expanded range of MR-GR interactions predicts structural allostery allowing a variety of transcriptional outcomes and is applicable to the multiple tissue types that co-express both receptors in the same cells whether activated by the same or different hormones.

Klíčová slova:

DNA-binding proteins – Protein interactions – Hormones – Co-immunoprecipitation – Hippocampus – Aldosterone – Dimers – Prisms

Zdroje

1. Conway-Campbell BL, Pooley JR, Hager GL, Lightman SL. Molecular dynamics of ultradian glucocorticoid receptor action. Mol Cell Endocrinol. 2012;348(2):383–93. doi: 10.1016/j.mce.2011.08.014 21872640

2. Lightman SL, Conway-Campbell BL. The crucial role of pulsatile activity of the HPA axis for continuous dynamic equilibration. Nat Rev Neurosci. 2010;11(10):710–8. doi: 10.1038/nrn2914 20842176

3. Morsink MC, Steenbergen PJ, Vos JB, Karst H, Joels M, De Kloet ER, et al. Acute activation of hippocampal glucocorticoid receptors results in different waves of gene expression throughout time. J Neuroendocrinol. 2006;18(4):239–52. doi: 10.1111/j.1365-2826.2006.01413.x 16503919

4. Stavreva DA, Wiench M, John S, Conway-Campbell BL, McKenna MA, Pooley JR, et al. Ultradian hormone stimulation induces glucocorticoid receptor-mediated pulses of gene transcription. Nat Cell Biol. 2009;11(9):1093–102. doi: 10.1038/ncb1922 19684579

5. George CL, Birnie MT, Flynn BP, Kershaw YM, Lightman SL, Conway-Campbell BL. Ultradian glucocorticoid exposure directs gene-dependent and tissue-specific mRNA expression patterns in vivo. Mol Cell Endocrinol. 2017;439:46–53. doi: 10.1016/j.mce.2016.10.019 27769714

6. Conway-Campbell BL, Sarabdjitsingh RA, McKenna MA, Pooley JR, Kershaw YM, Meijer OC, et al. Glucocorticoid ultradian rhythmicity directs cyclical gene pulsing of the clock gene period 1 in rat hippocampus. J Neuroendocrinol. 2010;22(10):1093–100. doi: 10.1111/j.1365-2826.2010.02051.x 20649850

7. Klein JF. Adverse psychiatric effects of systemic glucocorticoid therapy. Am Fam Physician. 1992;46(5):1469–74. 1442465

8. Conway-Campbell BL, McKenna MA, Wiles CC, Atkinson HC, de Kloet ER, Lightman SL. Proteasome-dependent down-regulation of activated nuclear hippocampal glucocorticoid receptors determines dynamic responses to corticosterone. Endocrinology. 2007;148(11):5470–7. doi: 10.1210/en.2007-0585 17690167

9. Mifsud KR, Reul JM. Acute stress enhances heterodimerization and binding of corticosteroid receptors at glucocorticoid target genes in the hippocampus. Proc Natl Acad Sci U S A. 2016;113(40):11336–41. doi: 10.1073/pnas.1605246113 27655894

10. Stolte EH, van Kemenade BM, Savelkoul HF, Flik G. Evolution of glucocorticoid receptors with different glucocorticoid sensitivity. J Endocrinol. 2006;190(1):17–28. doi: 10.1677/joe.1.06703 16837607

11. Griekspoor A, Zwart W, Neefjes J, Michalides R. Visualizing the action of steroid hormone receptors in living cells. Nucl Recept Signal. 2007;5:e003. doi: 10.1621/nrs.05003 17464358

12. Luisi BF, Xu WX, Otwinowski Z, Freedman LP, Yamamoto KR, Sigler PB. Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA. Nature. 1991;352(6335):497–505. doi: 10.1038/352497a0 1865905

13. Reul JM, de Kloet ER. Two receptor systems for corticosterone in rat brain: microdistribution and differential occupation. Endocrinology. 1985;117(6):2505–11. doi: 10.1210/endo-117-6-2505 2998738

14. Pearce D, Yamamoto KR. Mineralocorticoid and glucocorticoid receptor activities distinguished by nonreceptor factors at a composite response element. Science. 1993;259(5098):1161–5. doi: 10.1126/science.8382376 8382376

15. Eriksson P, Wrange O. Protein-protein contacts in the glucocorticoid receptor homodimer influence its DNA binding properties. J Biol Chem. 1990;265(6):3535–42. 2303460

16. Wrange O, Eriksson P, Perlmann T. The purified activated glucocorticoid receptor is a homodimer. J Biol Chem. 1989;264(9):5253–9. 2494184

17. Dahlman-Wright K, Siltala-Roos H, Carlstedt-Duke J, Gustafsson JA. Protein-protein interactions facilitate DNA binding by the glucocorticoid receptor DNA-binding domain. J Biol Chem. 1990;265(23):14030–5. 1974254

18. Dahlman-Wright K, Wright A, Gustafsson JA, Carlstedt-Duke J. Interaction of the glucocorticoid receptor DNA-binding domain with DNA as a dimer is mediated by a short segment of five amino acids. J Biol Chem. 1991;266(5):3107–12. 1993683

19. Drouin J, Sun YL, Tremblay S, Lavender P, Schmidt TJ, de Lean A, et al. Homodimer formation is rate-limiting for high affinity DNA binding by glucocorticoid receptor. Mol Endocrinol. 1992;6(8):1299–309. doi: 10.1210/mend.6.8.1406707 1406707

20. Fawell SE, Lees JA, White R, Parker MG. Characterization and colocalization of steroid binding and dimerization activities in the mouse estrogen receptor. Cell. 1990;60(6):953–62. doi: 10.1016/0092-8674(90)90343-d 2317866

21. Hirst MA, Hinck L, Danielsen M, Ringold GM. Discrimination of DNA response elements for thyroid hormone and estrogen is dependent on dimerization of receptor DNA binding domains. Proc Natl Acad Sci U S A. 1992;89(12):5527–31. doi: 10.1073/pnas.89.12.5527 1608965

22. Arnold SF, Notides AC. An antiestrogen: a phosphotyrosyl peptide that blocks dimerization of the human estrogen receptor. Proc Natl Acad Sci U S A. 1995;92(16):7475–9. doi: 10.1073/pnas.92.16.7475 7543683

23. Aumais JP, Lee HS, DeGannes C, Horsford J, White JH. Function of directly repeated half-sites as response elements for steroid hormone receptors. J Biol Chem. 1996;271(21):12568–77. doi: 10.1074/jbc.271.21.12568 8647867

24. Arriza JL, Weinberger C, Cerelli G, Glaser TM, Handelin BL, Housman DE, et al. Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor. Science. 1987;237(4812):268–75. doi: 10.1126/science.3037703 3037703

25. Liu W, Wang J, Sauter NK, Pearce D. Steroid receptor heterodimerization demonstrated in vitro and in vivo. Proc Natl Acad Sci U S A. 1995;92(26):12480–4. doi: 10.1073/pnas.92.26.12480 8618925

26. Trapp T, Rupprecht R, Castren M, Reul JM, Holsboer F. Heterodimerization between mineralocorticoid and glucocorticoid receptor: a new principle of glucocorticoid action in the CNS. Neuron. 1994;13(6):1457–62. doi: 10.1016/0896-6273(94)90431-6 7993637

27. Farman N, Rafestin-Oblin ME. Multiple aspects of mineralocorticoid selectivity. Am J Physiol Renal Physiol. 2001;280(2):F181–92. doi: 10.1152/ajprenal.2001.280.2.F181 11208593

28. Kiilerich P, Triqueneaux G, Christensen NM, Trayer V, Terrien X, Lombes M, et al. Interaction between the trout mineralocorticoid and glucocorticoid receptors in vitro. J Mol Endocrinol. 2015;55(1):55–68. doi: 10.1530/JME-15-0002 26108487

29. Ou XM, Storring JM, Kushwaha N, Albert PR. Heterodimerization of mineralocorticoid and glucocorticoid receptors at a novel negative response element of the 5-HT1A receptor gene. J Biol Chem. 2001;276(17):14299–307. doi: 10.1074/jbc.M005363200 11278286

30. Derfoul A, Robertson NM, Lingrel JB, Hall DJ, Litwack G. Regulation of the human Na/K-ATPase beta1 gene promoter by mineralocorticoid and glucocorticoid receptors. J Biol Chem. 1998;273(33):20702–11. doi: 10.1074/jbc.273.33.20702 9694812

31. Planey SL, Derfoul A, Steplewski A, Robertson NM, Litwack G. Inhibition of glucocorticoid-induced apoptosis in 697 pre-B lymphocytes by the mineralocorticoid receptor N-terminal domain. J Biol Chem. 2002;277(44):42188–96. doi: 10.1074/jbc.M205085200 12194973

32. Nishi M, Tanaka M, Matsuda K, Sunaguchi M, Kawata M. Visualization of glucocorticoid receptor and mineralocorticoid receptor interactions in living cells with GFP-based fluorescence resonance energy transfer. J Neurosci. 2004;24(21):4918–27. doi: 10.1523/JNEUROSCI.5495-03.2004 15163683

33. Savory JG, Prefontaine GG, Lamprecht C, Liao M, Walther RF, Lefebvre YA, et al. Glucocorticoid receptor homodimers and glucocorticoid-mineralocorticoid receptor heterodimers form in the cytoplasm through alternative dimerization interfaces. Mol Cell Biol. 2001;21(3):781–93. doi: 10.1128/MCB.21.3.781-793.2001 11154266

34. Smith CL, Htun H, Wolford RG, Hager GL. Differential activity of progesterone and glucocorticoid receptors on mouse mammary tumor virus templates differing in chromatin structure. J Biol Chem. 1997;272(22):14227–35. doi: 10.1074/jbc.272.22.14227 9162055

35. Bledsoe RK, Montana VG, Stanley TB, Delves CJ, Apolito CJ, McKee DD, et al. Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition. Cell. 2002;110(1):93–105. doi: 10.1016/s0092-8674(02)00817-6 12151000

36. Liu W, Wang J, Yu G, Pearce D. Steroid receptor transcriptional synergy is potentiated by disruption of the DNA-binding domain dimer interface. Mol Endocrinol. 1996;10(11):1399–406. doi: 10.1210/mend.10.11.8923466 8923466

37. Meijsing SH, Pufall MA, So AY, Bates DL, Chen L, Yamamoto KR. DNA binding site sequence directs glucocorticoid receptor structure and activity. Science. 2009;324(5925):407–10. doi: 10.1126/science.1164265 19372434

38. Kim S, Brostromer E, Xing D, Jin J, Chong S, Ge H, et al. Probing allostery through DNA. Science. 2013;339(6121):816–9. doi: 10.1126/science.1229223 23413354

39. Lefstin JA, Yamamoto KR. Allosteric effects of DNA on transcriptional regulators. Nature. 1998;392(6679):885–8. doi: 10.1038/31860 9582068

40. Han F, Ozawa H, Matsuda K, Nishi M, Kawata M. Colocalization of mineralocorticoid receptor and glucocorticoid receptor in the hippocampus and hypothalamus. Neurosci Res. 2005;51(4):371–81. doi: 10.1016/j.neures.2004.12.013 15740800

41. Beavan S, Horner A, Bord S, Ireland D, Compston J. Colocalization of glucocorticoid and mineralocorticoid receptors in human bone. J Bone Miner Res. 2001;16(8):1496–504. doi: 10.1359/jbmr.2001.16.8.1496 11499872

42. Marzolla V, Armani A, Zennaro MC, Cinti F, Mammi C, Fabbri A, et al. The role of the mineralocorticoid receptor in adipocyte biology and fat metabolism. Mol Cell Endocrinol. 2012;350(2):281–8. doi: 10.1016/j.mce.2011.09.011 21945603

43. Armanini D, Endres S, Kuhnle U, Weber PC. Parallel determination of mineralocorticoid and glucocorticoid receptors in T- and B-lymphocytes of human spleen. Acta Endocrinol (Copenh). 1988;118(4):479–82.

44. Farman N, Oblin ME, Lombes M, Delahaye F, Westphal HM, Bonvalet JP, et al. Immunolocalization of gluco- and mineralocorticoid receptors in rabbit kidney. Am J Physiol. 1991;260(2 Pt 1):C226–33. doi: 10.1152/ajpcell.1991.260.2.C226 1847584

45. Bradbury MJ, Akana SF, Dallman MF. Roles of type I and II corticosteroid receptors in regulation of basal activity in the hypothalamo-pituitary-adrenal axis during the diurnal trough and the peak: evidence for a nonadditive effect of combined receptor occupation. Endocrinology. 1994;134(3):1286–96. doi: 10.1210/endo.134.3.8119168 8119168

46. De Kloet ER, Vreugdenhil E, Oitzl MS, Joels M. Brain corticosteroid receptor balance in health and disease. Endocr Rev. 1998;19(3):269–301. doi: 10.1210/edrv.19.3.0331 9626555

47. Joels M, de Kloet ER. Mineralocorticoid and glucocorticoid receptors in the brain. Implications for ion permeability and transmitter systems. Prog Neurobiol. 1994;43(1):1–36. doi: 10.1016/0301-0082(94)90014-0 7526416

48. McNally JG, Muller WG, Walker D, Wolford R, Hager GL. The glucocorticoid receptor: rapid exchange with regulatory sites in living cells. Science. 2000;287(5456):1262–5. doi: 10.1126/science.287.5456.1262 10678832

49. Chakraborti PK, Garabedian MJ, Yamamoto KR, Simons SS Jr. Creation of "super" glucocorticoid receptors by point mutations in the steroid binding domain. J Biol Chem. 1991;266(33):22075–8. 1939229

50. Droste SK, de Groote L, Atkinson HC, Lightman SL, Reul JM, Linthorst AC. Corticosterone levels in the brain show a distinct ultradian rhythm but a delayed response to forced swim stress. Endocrinology. 2008;149(7):3244–53. doi: 10.1210/en.2008-0103 18356272

51. Qian X, Droste SK, Lightman SL, Reul JM, Linthorst AC. Circadian and ultradian rhythms of free glucocorticoid hormone are highly synchronized between the blood, the subcutaneous tissue, and the brain. Endocrinology. 2012;153(9):4346–53. doi: 10.1210/en.2012-1484 22822164

52. Digman MA, Wiseman PW, Choi C, Horwitz AR, Gratton E. Stoichiometry of molecular complexes at adhesions in living cells. Proc Natl Acad Sci U S A. 2009;106(7):2170–5. doi: 10.1073/pnas.0806036106 19168634

53. Choi CK, Zareno J, Digman MA, Gratton E, Horwitz AR. Cross-correlated fluctuation analysis reveals phosphorylation-regulated paxillin-FAK complexes in nascent adhesions. Biophys J. 2011;100(3):583–92. doi: 10.1016/j.bpj.2010.12.3719 21281572

54. Zacharias DA, Violin JD, Newton AC, Tsien RY. Partitioning of lipid-modified monomeric GFPs into membrane microdomains of live cells. Science. 2002;296(5569):913–6. doi: 10.1126/science.1068539 11988576

55. Chen S, Wang J, Yu G, Liu W, Pearce D. Androgen and glucocorticoid receptor heterodimer formation. A possible mechanism for mutual inhibition of transcriptional activity. J Biol Chem. 1997;272(22):14087–92. doi: 10.1074/jbc.272.22.14087 9162033

56. Digman MA, Dalal R, Horwitz AF, Gratton E. Mapping the number of molecules and brightness in the laser scanning microscope. Biophys J. 2008;94(6):2320–32. doi: 10.1529/biophysj.107.114645 18096627

57. Fukushima R, Yamamoto J, Ishikawa H, Kinjo M. Two-detector number and brightness analysis reveals spatio-temporal oligomerization of proteins in living cells. Methods. 2018;140–141:161–71. doi: 10.1016/j.ymeth.2018.03.007 29572069

58. Presman DM, Ogara MF, Stortz M, Alvarez LD, Pooley JR, Schiltz RL, et al. Live cell imaging unveils multiple domain requirements for in vivo dimerization of the glucocorticoid receptor. PLoS Biol. 2014;12(3):e1001813. doi: 10.1371/journal.pbio.1001813 24642507

59. Tuncbag N, Gursoy A, Nussinov R, Keskin O. Predicting protein-protein interactions on a proteome scale by matching evolutionary and structural similarities at interfaces using PRISM. Nat Protoc. 2011;6(9):1341–54. doi: 10.1038/nprot.2011.367 21886100

60. Baspinar A, Cukuroglu E, Nussinov R, Keskin O, Gursoy A. PRISM: a web server and repository for prediction of protein-protein interactions and modeling their 3D complexes. Nucleic Acids Res. 2014;42(Web Server issue):W285–9. doi: 10.1093/nar/gku397 24829450

61. Presman DM, Ganguly S, Schiltz RL, Johnson TA, Karpova TS, Hager GL. DNA binding triggers tetramerization of the glucocorticoid receptor in live cells. Proc Natl Acad Sci U S A. 2016;113(29):8236–41. doi: 10.1073/pnas.1606774113 27382178

62. Stephens B, Handel TM. Chemokine receptor oligomerization and allostery. Prog Mol Biol Transl Sci. 2013;115:375–420. doi: 10.1016/B978-0-12-394587-7.00009-9 23415099

63. Jewell CM, Scoltock AB, Hamel BL, Yudt MR, Cidlowski JA. Complex human glucocorticoid receptor dim mutations define glucocorticoid induced apoptotic resistance in bone cells. Mol Endocrinol. 2012;26(2):244–56. doi: 10.1210/me.2011-1116 22174376

64. Rivers CA, Rogers MF, Stubbs FE, Conway-Campbell BL, Lightman SL, Pooley JR. Glucocorticoid Receptor-Tethered Mineralocorticoid Receptors Increase Glucocorticoid-Induced Transcriptional Responses. Endocrinology. 2019;160(5):1044–56. doi: 10.1210/en.2018-00819 30980716

65. Groeneweg FL, van Royen ME, Fenz S, Keizer VI, Geverts B, Prins J, et al. Quantitation of glucocorticoid receptor DNA-binding dynamics by single-molecule microscopy and FRAP. PLoS One. 2014;9(3):e90532. doi: 10.1371/journal.pone.0090532 24632838

66. Neumann FR, Dion V, Gehlen LR, Tsai-Pflugfelder M, Schmid R, Taddei A, et al. Targeted INO80 enhances subnuclear chromatin movement and ectopic homologous recombination. Genes Dev. 2012;26(4):369–83. doi: 10.1101/gad.176156.111 22345518

67. Edwards DP, Altmann M, DeMarzo A, Zhang Y, Weigel NL, Beck CA. Progesterone receptor and the mechanism of action of progesterone antagonists. J Steroid Biochem Mol Biol. 1995;53(1–6):449–58. doi: 10.1016/0960-0760(95)00091-d 7626494

68. Lehmann JM, Zhang XK, Graupner G, Lee MO, Hermann T, Hoffmann B, et al. Formation of retinoid X receptor homodimers leads to repression of T3 response: hormonal cross talk by ligand-induced squelching. Mol Cell Biol. 1993;13(12):7698–707. doi: 10.1128/mcb.13.12.7698 8246986

69. Miranda TB, Morris SA, Hager GL. Complex genomic interactions in the dynamic regulation of transcription by the glucocorticoid receptor. Mol Cell Endocrinol. 2013;380(1–2):16–24. doi: 10.1016/j.mce.2013.03.002 23499945

70. Voss TC, Schiltz RL, Sung MH, Yen PM, Stamatoyannopoulos JA, Biddie SC, et al. Dynamic exchange at regulatory elements during chromatin remodeling underlies assisted loading mechanism. Cell. 2011;146(4):544–54. doi: 10.1016/j.cell.2011.07.006 21835447

71. Swinstead EE, Paakinaho V, Presman DM, Hager GL. Pioneer factors and ATP-dependent chromatin remodeling factors interact dynamically: A new perspective: Multiple transcription factors can effect chromatin pioneer functions through dynamic interactions with ATP-dependent chromatin remodeling factors. Bioessays. 2016;38(11):1150–7. doi: 10.1002/bies.201600137 27633730

72. Joels M. Corticosteroid effects in the brain: U-shape it. Trends Pharmacol Sci. 2006;27(5):244–50. doi: 10.1016/j.tips.2006.03.007 16584791

73. Cairns W, Cairns C, Pongratz I, Poellinger L, Okret S. Assembly of a glucocorticoid receptor complex prior to DNA binding enhances its specific interaction with a glucocorticoid response element. J Biol Chem. 1991;266(17):11221–6. 2040629

74. Tsugita M, Iwasaki Y, Nishiyama M, Taguchi T, Shinahara M, Taniguchi Y, et al. Glucocorticoid receptor plays an indispensable role in mineralocorticoid receptor-dependent transcription in GR-deficient BE(2)C and T84 cells in vitro. Mol Cell Endocrinol. 2009;302(1):18–25. doi: 10.1016/j.mce.2008.12.008 19146914

75. van Tilborg MA, Lefstin JA, Kruiskamp M, Teuben J, Boelens R, Yamamoto KR, et al. Mutations in the glucocorticoid receptor DNA-binding domain mimic an allosteric effect of DNA. J Mol Biol. 2000;301(4):947–58. doi: 10.1006/jmbi.2000.4001 10966797

76. Watson LC, Kuchenbecker KM, Schiller BJ, Gross JD, Pufall MA, Yamamoto KR. The glucocorticoid receptor dimer interface allosterically transmits sequence-specific DNA signals. Nat Struct Mol Biol. 2013;20(7):876–83. doi: 10.1038/nsmb.2595 23728292

77. Helsen C, Claessens F. Looking at nuclear receptors from a new angle. Mol Cell Endocrinol. 2014;382(1):97–106. doi: 10.1016/j.mce.2013.09.009 24055275

78. Rogatsky I, Wang JC, Derynck MK, Nonaka DF, Khodabakhsh DB, Haqq CM, et al. Target-specific utilization of transcriptional regulatory surfaces by the glucocorticoid receptor. Proc Natl Acad Sci U S A. 2003;100(24):13845–50. doi: 10.1073/pnas.2336092100 14617768

79. Muchardt C, Yaniv M. A human homologue of Saccharomyces cerevisiae SNF2/SWI2 and Drosophila brm genes potentiates transcriptional activation by the glucocorticoid receptor. EMBO J. 1993;12(11):4279–90. 8223438

80. Hall JM, McDonnell DP, Korach KS. Allosteric regulation of estrogen receptor structure, function, and coactivator recruitment by different estrogen response elements. Mol Endocrinol. 2002;16(3):469–86. doi: 10.1210/mend.16.3.0814 11875105

81. Presman DM, Alvarez LD, Levi V, Eduardo S, Digman MA, Marti MA, et al. Insights on glucocorticoid receptor activity modulation through the binding of rigid steroids. PLoS One. 2010;5(10):e13279. doi: 10.1371/journal.pone.0013279 20949009

82. Lombes M, Binart N, Oblin ME, Joulin V, Baulieu EE. Characterization of the interaction of the human mineralocorticosteroid receptor with hormone response elements. Biochem J. 1993;292 (Pt 2):577–83.

83. Grossmann C, Ruhs S, Langenbruch L, Mildenberger S, Stratz N, Schumann K, et al. Nuclear shuttling precedes dimerization in mineralocorticoid receptor signaling. Chem Biol. 2012;19(6):742–51. doi: 10.1016/j.chembiol.2012.04.014 22726688

84. Schaaf MJ, Cidlowski JA. Molecular determinants of glucocorticoid receptor mobility in living cells: the importance of ligand affinity. Mol Cell Biol. 2003;23(6):1922–34. doi: 10.1128/MCB.23.6.1922-1934.2003 12612067

85. Chen ZP, Iyer J, Bourguet W, Held P, Mioskowski C, Lebeau L, et al. Ligand- and DNA-induced dissociation of RXR tetramers. J Mol Biol. 1998;275(1):55–65. doi: 10.1006/jmbi.1997.1413 9451439

86. Derfoul A, Robertson NM, Hall DJ, Litwack G. The N-terminal domain of the mineralocorticoid receptor modulates both mineralocorticoid receptor- and glucocorticoid receptor-mediated transactivation from Na/K ATPase beta1 target gene promoter. Endocrine. 2000;13(3):287–95. doi: 10.1385/ENDO:13:3:287 11216640

87. Rebuffat AG, Tam S, Nawrocki AR, Baker ME, Frey BM, Frey FJ, et al. The 11-ketosteroid 11-ketodexamethasone is a glucocorticoid receptor agonist. Mol Cell Endocrinol. 2004;214(1–2):27–37. doi: 10.1016/j.mce.2003.11.027 15062542

88. Medina A, Seasholtz AF, Sharma V, Burke S, Bunney W Jr., Myers RM, et al. Glucocorticoid and mineralocorticoid receptor expression in the human hippocampus in major depressive disorder. J Psychiatr Res. 2013;47(3):307–14. doi: 10.1016/j.jpsychires.2012.11.002 23219281

89. Oakley RH, Cruz-Topete D, He B, Foley JF, Myers PH, Xu X, et al. Cardiomyocyte glucocorticoid and mineralocorticoid receptors directly and antagonistically regulate heart disease in mice. Sci Signal. 2019;12(577).

90. Hoppmann J, Perwitz N, Meier B, Fasshauer M, Hadaschik D, Lehnert H, et al. The balance between gluco- and mineralo-corticoid action critically determines inflammatory adipocyte responses. J Endocrinol. 2010;204(2):153–64. doi: 10.1677/JOE-09-0292 19939912

91. Gouilleux F, Sola B, Couette B, Richard-Foy H. Cooperation between structural elements in hormono-regulated transcription from the mouse mammary tumor virus promoter. Nucleic Acids Res. 1991;19(7):1563–9. doi: 10.1093/nar/19.7.1563 1851294

92. Voss TC, Schiltz RL, Sung MH, Johnson TA, John S, Hager GL. Combinatorial probabilistic chromatin interactions produce transcriptional heterogeneity. J Cell Sci. 2009;122(Pt 3):345–56. doi: 10.1242/jcs.035865 19126674

93. Swift S, Lorens J, Achacoso P, Nolan GP. Rapid production of retroviruses for efficient gene delivery to mammalian cells using 293T cell-based systems. Curr Protoc Immunol. 2001;Chapter 10:Unit 10 7C.

94. Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, et al. Multiplex genome engineering using CRISPR/Cas systems. Science. 2013;339(6121):819–23. doi: 10.1126/science.1231143 23287718

95. van der Valk JB, Vijverberg HP. Neuroblastoma cells as possible model in the study of glutamate receptors. Amino Acids. 1991;1(1):91–5. doi: 10.1007/BF00808095 24194051

96. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, et al. The Protein Data Bank. Nucleic Acids Res. 2000;28(1):235–42. doi: 10.1093/nar/28.1.235 10592235

97. Clancy JW, Zhang Y, Sheehan C, D'Souza-Schorey C. An ARF6-Exportin-5 axis delivers pre-miRNA cargo to tumour microvesicles. Nat Cell Biol. 2019;21(7):856–66. doi: 10.1038/s41556-019-0345-y 31235936

98. Lubner CE, Jennings DP, Mulder DW, Schut GJ, Zadvornyy OA, Hoben JP, et al. Mechanistic insights into energy conservation by flavin-based electron bifurcation. Nat Chem Biol. 2017;13(6):655–9. doi: 10.1038/nchembio.2348 28394885

99. Pierce B, Weng Z. ZRANK: reranking protein docking predictions with an optimized energy function. Proteins. 2007;67(4):1078–86. doi: 10.1002/prot.21373 17373710

100. Krissinel E, Henrick K. Inference of macromolecular assemblies from crystalline state. J Mol Biol. 2007;372(3):774–97. doi: 10.1016/j.jmb.2007.05.022 17681537

101. Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, et al. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res. 2018;46(W1):W296–W303. doi: 10.1093/nar/gky427 29788355

102. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. 1990;215(3):403–10. doi: 10.1016/S0022-2836(05)80360-2 2231712

103. Bogan AA, Thorn KS. Anatomy of hot spots in protein interfaces. J Mol Biol. 1998;280(1):1–9. doi: 10.1006/jmbi.1998.1843 9653027

104. Cavga AD, Karahan N, Keskin O, Gursoy A. Taming Oncogenic Signaling at Protein Interfaces: Challenges and Opportunities. Curr Top Med Chem. 2015;15(20):2005–18. doi: 10.2174/1568026615666150519101956 25986691

105. Cukuroglu E, Gursoy A, Keskin O. HotRegion: a database of predicted hot spot clusters. Nucleic Acids Res. 2012;40(Database issue):D829–33. doi: 10.1093/nar/gkr929 22080558

106. Schymkowitz J, Borg J, Stricher F, Nys R, Rousseau F, Serrano L. The FoldX web server: an online force field. Nucleic Acids Res. 2005;33(Web Server issue):W382–8. doi: 10.1093/nar/gki387 15980494

107. Van Durme J, Delgado J, Stricher F, Serrano L, Schymkowitz J, Rousseau F. A graphical interface for the FoldX forcefield. Bioinformatics. 2011;27(12):1711–2. doi: 10.1093/bioinformatics/btr254 21505037

108. Dehouck Y, Kwasigroch JM, Rooman M, Gilis D. BeAtMuSiC: Prediction of changes in protein-protein binding affinity on mutations. Nucleic Acids Res. 2013;41(Web Server issue):W333–9. doi: 10.1093/nar/gkt450 23723246

109. Pires DE, Ascher DB, Blundell TL. mCSM: predicting the effects of mutations in proteins using graph-based signatures. Bioinformatics. 2014;30(3):335–42. doi: 10.1093/bioinformatics/btt691 24281696

110. Li M, Simonetti FL, Goncearenco A, Panchenko AR. MutaBind estimates and interprets the effects of sequence variants on protein-protein interactions. Nucleic Acids Res. 2016;44(W1):W494–501. doi: 10.1093/nar/gkw374 27150810

Článek Disparate effects of antibiotic-induced microbiome change and enhanced fitness in Daphnia magna
Článek Deliver on Your Own: Disrespectful Maternity Care in rural Kenya
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Článek Practical considerations in the use of a porcine model (Sus scrofa domesticus) to assess prevention of postoperative peritubal adhesions
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Článek Cauda Equina Syndrome Core Outcome Set (CESCOS): An international patient and healthcare professional consensus for research studies
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Článek Development and validation of a prognostic model predicting symptomatic hemorrhagic transformation in acute ischemic stroke at scale in the OHDSI network
Článek Complex patterns of cell growth in the placenta in normal pregnancy and as adaptations to maternal diet restriction
Článek Tofu intake is inversely associated with risk of breast cancer: A meta-analysis of observational studies
Článek Influence of light on the infection of Aureococcus anophagefferens CCMP 1984 by a “giant virus”
Článek Temporal ordering of input modulates connectivity formation in a developmental neuronal network model of the cortex
Článek From organ to cell: Multi-level telomere length assessment in patients with idiopathic pulmonary fibrosis
Článek How do critical care staff respond to organisational challenge? A qualitative exploration into personality types and cognitive processing in critical care
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Článek Community-Based Health Planning and Services Plus programme in Ghana: A qualitative study with stakeholders in two Systems Learning Districts on improving the implementation of primary health care
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Článek Comparison of gridded precipitation datasets for rainfall-runoff and inundation modeling in the Mekong River Basin
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Článek The effects of dual-task cognitive interference on gait and turning in Huntington’s disease
Článek Novel imaging biomarkers for mapping the impact of mild mitochondrial uncoupling in the outer retina in vivo
Článek Hyperkalemia treatment modalities: A descriptive observational study focused on medication and healthcare resource utilization
Článek Long term impact of PositiveLinks: Clinic-deployed mobile technology to improve engagement with HIV care
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Článek A definition-by-example approach and visual language for activity patterns in engineering disciplines
Článek A network analysis revealed the essential and common downstream proteins related to inguinal hernia
Článek Use of conventional cardiac troponin assay for diagnosis of non-ST-elevation myocardial infarction: ‘The Ottawa Troponin Pathway’
Článek Identification and characterization of miRNAs involved in cold acclimation of zebrafish ZF4 cells
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Článek Detailed analysis of the transverse arch of hallux valgus feet with and without pain using weightbearing ultrasound imaging and precise force sensors
Článek Surrogate R-spondins for tissue-specific potentiation of Wnt Signaling
Článek Apolipoprotein-AI mimetic peptides D-4F and L-5F decrease hepatic inflammation and increase insulin sensitivity in C57BL/6 mice
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Článek Efficient processing of raster and vector data
Článek Therapeutic hypothermia after out of hospital cardiac arrest improve 1-year survival rate for selective patients
Článek Carotid plaques and neurological impairment in patients with acute cerebral infarction
Článek Deep learning based image reconstruction algorithm for limited-angle translational computed tomography
Článek Association between coffee drinking and telomere length in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
Článek Hyperbaric oxygen preconditioning and the role of NADPH oxidase inhibition in postischemic acute kidney injury induced in spontaneously hypertensive rats
Článek Rad51 paralogs and the risk of unselected breast cancer: A case-control study
Článek Diagnostic differences in respiratory breathing patterns and work of breathing indices in children with Duchenne muscular dystrophy
Článek The role of narrative in collaborative reasoning and intelligence analysis: A case study
Článek Proportions of CD4 test results indicating advanced HIV disease remain consistently high at primary health care facilities across four high HIV burden countries
Článek Modelling of amino acid turnover in the horse during training and racing: A basis for developing a novel supplementation strategy
Článek Single-modal and multi-modal false arrhythmia alarm reduction using attention-based convolutional and recurrent neural networks
Článek Eye-gaze information input based on pupillary response to visual stimulus with luminance modulation
Článek Trends of litter decomposition and soil organic matter stocks across forested swamp environments of the southeastern US
Článek Post mortem evaluation of inflammation, oxidative stress, and PPARγ activation in a nonhuman primate model of cardiac sympathetic neurodegeneration
Článek Were ancient foxes far more carnivorous than recent ones?—Carnassial morphological evidence
Článek Disruption in daily eating-fasting and activity-rest cycles in Indian adolescents attending school
Článek Plasma proteome profiling of freshwater and seawater life stages of rainbow trout (Oncorhynchus mykiss)
Článek Percent amplitude of fluctuation: A simple measure for resting-state fMRI signal at single voxel level
Článek Antimicrobial activity of Asteraceae species against bacterial pathogens isolated from postmenopausal women
Článek Are changes in depressive symptoms, general health and residential area socio-economic status associated with trajectories of waist circumference and body mass index?
Článek Extracellular vesicles of U937 macrophage cell line infected with DENV-2 induce activation in endothelial cells EA.hy926
Článek Link-centric analysis of variation by demographics in mobile phone communication patterns
Článek Tobacco smoking and health-related quality of life among university students: Mediating effect of depression
Článek Incidence of hospital-acquired pressure ulcers in patients with "minimal risk" according to the "Norton-MI" scale
Článek Lipoprotein(a) plasma levels are not associated with survival after acute coronary syndromes: An observational cohort study
Článek Use of Nanotrap particles for the capture and enrichment of Zika, chikungunya and dengue viruses in urine
Článek Biochemical characterization of Ty1 retrotransposon protease
Článek Lateral pressure equalisation as a principle for designing support surfaces to prevent deep tissue pressure ulcers
Článek The validation of the Beijing version of the Montreal Cognitive Assessment in Chinese patients undergoing hemodialysis
Článek Inflammasome expression is higher in ovarian tumors than in normal ovary
Článek HCV genotype profile in Brazil of mono-infected and HIV co-infected individuals: A survey representative of an entire country
Článek Engaging with change: Information and communication technology professionals’ perspectives on change at the mid-point in the UK/EU Brexit process
Článek Adherence to iron-folic acid supplement and associated factors among antenatal care attending pregnant mothers in governmental health institutions of Adwa town, Tigray, Ethiopia: Cross-sectional study
Článek Flower, seed, and fruit development in three Tunisian species of Polygonum: Implications for their taxonomy and evolution of distyly in Polygonaceae
Článek Development of a risk score for prediction of poor treatment outcomes among patients with multidrug-resistant tuberculosis
Článek Preclinical evaluation of AT-527, a novel guanosine nucleotide prodrug with potent, pan-genotypic activity against hepatitis C virus
Článek Aqueous extract from Mangifera indica Linn. (Anacardiaceae) leaves exerts long-term hypoglycemic effect, increases insulin sensitivity and plasma insulin levels on diabetic Wistar rats
Článek Discovery of Jogalong virus, a novel hepacivirus identified in a Culex annulirostris (Skuse) mosquito from the Kimberley region of Western Australia
Článek Clinical, cytogenetic and molecular genetic characterization of a tandem fusion translocation in a male Holstein cattle with congenital hypospadias and a ventricular septal defect
Článek Detection of Torque Teno Virus (TTV) and TTV-Like Minivirus in patients with presumed infectious endophthalmitis in India
Článek CD4 rate of increase is preferred to CD4 threshold for predicting outcomes among virologically suppressed HIV-infected adults on antiretroviral therapy
Článek Estimating the basic reproduction number of a pathogen in a single host when only a single founder successfully infects
Článek What drugs modify the risk of iatrogenic impulse-control disorders in Parkinson’s disease? A preliminary pharmacoepidemiologic study
Článek Evaluating emotional distress and health-related quality of life in patients with heart failure and their family caregivers: Testing dyadic dynamics using the Actor-Partner Interdependence Model
Článek Catchment-scale export of antibiotic resistance genes and bacteria from an agricultural watershed in central Iowa
Článek Characterization of a universal screening approach for congenital CMV infection based on a highly-sensitive, quantitative, multiplex real-time PCR assay
Článek Proof-of-concept for a non-invasive, portable, and wireless device for cardiovascular monitoring in pediatric patients
Článek On PTV definition for glioblastoma based on fiber tracking of diffusion tensor imaging data
Článek Genes associated with body weight gain and feed intake identified by meta-analysis of the mesenteric fat from crossbred beef steers
Článek Intraoperative computed tomography imaging for dose calculation in intraoperative electron radiation therapy: Initial clinical observations
Článek Human lung epithelial BEAS-2B cells exhibit characteristics of mesenchymal stem cells
Článek Evaluation of a bioengineered ACL matrix’s osteointegration with BMP-2 supplementation
Článek Psychosocial profiles of physical activity fluctuation in office employees: A latent profile analysis
Článek Soluble AXL as a marker of disease progression and survival in melanoma
Článek Gender differences influence over insomnia in Korean population: A cross-sectional study
Článek Impact of scion/rootstock reciprocal effects on metabolomics of fruit juice and phloem sap in grafted Citrus reticulata
Článek Adapting cognitive diagnosis computerized adaptive testing item selection rules to traditional item response theory
Článek Autumn shifts in cold tolerance metabolites in overwintering adult mountain pine beetles
Článek Umbilical cord separation time, predictors and healing complications in newborns with dry care
Článek Analysis of attitudinal components towards statistics among students from different academic degrees
Článek Effects of fatigue induced by repeated-sprint on kicking accuracy and velocity in female soccer players
Článek A pre-clinical validation plan to evaluate analytical sensitivities of molecular diagnostics such as BD MAX MDR-TB, Xpert MTB/Rif Ultra and FluoroType MTB
Článek Leadership for success in transforming medical abortion policy in Canada
Článek Clinical correlates associated with the long-term response of bipolar disorder patients to lithium, valproate or lamotrigine: A retrospective study
Článek Forecasting stock prices with long-short term memory neural network based on attention mechanism
Článek On the genus Crossaster (Echinodermata: Asteroidea) and its distribution
Článek Intracellular and in vivo evaluation of imidazo[2,1-b]thiazole-5-carboxamide anti-tuberculosis compounds
Článek An integrated vitamin E-coated polymer hybrid nanoplatform: A lucrative option for an enhanced in vitro macrophage retention for an anti-hepatitis B therapeutic prospect
Článek The effect of strontium and silicon substituted hydroxyapatite electrochemical coatings on bone ingrowth and osseointegration of selective laser sintered porous metal implants
Článek Molecular prevalence of Bartonella, Babesia, and hemotropic Mycoplasma species in dogs with hemangiosarcoma from across the United States
Článek Color discrimination and gas chromatography-mass spectrometry fingerprint based on chemometrics analysis for the quality evaluation of Schizonepetae Spica
Článek Comparisons of recurrence-free survival and overall survival between microwave versus radiofrequency ablation treatment for hepatocellular carcinoma: A multiple centers retrospective cohort study with propensity score matching
Článek Dynamic Extreme Aneuploidy (DEA) in the vegetable pathogen Phytophthora capsici and the potential for rapid asexual evolution
Článek Assertive, trainable and older dogs are perceived as more dominant in multi-dog households
Článek Prediction of Uropathogens by Flow Cytometry and Dip-stick Test Results of Urine Through Multivariable Logistic Regression Analysis
Článek Interleukin 6 is increased in preclinical HNSCC models of acquired cetuximab resistance, but is not required for maintenance of resistance
Článek Impact of viral disease hypophagia on pig jejunal function and integrity
Článek Molecular evidence for horizontal transmission of chelonid alphaherpesvirus 5 at green turtle (Chelonia mydas) foraging grounds in Queensland, Australia
Článek Evaluation and validation of 2D biomechanical models of the knee for radiograph-based preoperative planning in total knee arthroplasty
Článek Soil-Transmitted Helminth infections reduction in Bhutan: A report of 29 years of deworming
Článek Fast quantitative time lapse displacement imaging of endothelial cell invasion
Článek Two novel mutations in MSX1 causing oligodontia
Článek Dome-shaped macula in children and adolescents
Článek Targeted transcriptomic study of the implication of central metabolic pathways in mannosylerythritol lipids biosynthesis in Pseudozyma antarctica T-34
Článek Preliminary evidences of the presence of extracellular DNA single stranded forms in soil
Článek A comparison of quality of life between patients treated with different dialysis modalities in Taiwan
Článek Transcriptome analysis of Actinidia chinensis in response to Botryosphaeria dothidea infection
Článek Comparative study on skin protection activity of polyphenol-rich extract and polysaccharide-rich extract from Sargassum vachellianum
Článek Real-world data about emotional stress, disability and need for social care in a German IBD patient cohort
Článek The regenerative compatibility: A synergy between healthy ecosystems, environmental attitudes, and restorative experiences
Článek Perceptions of risk and influences of choice in pregnant women with obesity. An evidence synthesis of qualitative research
Článek Sexual risk classes among youth experiencing homelessness: Relation to childhood adversities, current mental symptoms, substance use, and HIV testing
Článek Effects of CK2β subunit down-regulation on Akt signalling in HK-2 renal cells
Článek Novel broad-spectrum activity-based probes to profile malarial cysteine proteases
Článek Association between opioid analgesic therapy and initiation of buprenorphine management: An analysis of prescription drug monitoring program data
Článek Improvement project in higher education institutions: A BPEP-based model
Článek An updated evaluation of serum sHER2, CA15.3, and CEA levels as biomarkers for the response of patients with metastatic breast cancer to trastuzumab-based therapies
Článek Genome-wide association study of metabolic syndrome in Korean populations
Článek Drug therapy problems and treatment satisfaction among ambulatory patients with epilepsy in a specialized hospital in Ethiopia
Článek Occurrence and distribution of anthropogenic persistent organic pollutants in coastal sediments and mud shrimps from the wetland of central Taiwan
Článek Intensified visual clutter induces increased sympathetic signalling, poorer postural control, and faster torsional eye movements during visual rotation
Článek Gut microbiota composition alterations are associated with the onset of diabetes in kidney transplant recipients
Článek Shock index and TIMI risk index as valuable prognostic tools in patients with acute coronary syndrome complicated by cardiogenic shock
Článek Merit overrules theory of mind when young children share resources with others
Článek Metabolic analysis of amino acids and vitamin B6 pathways in lymphoma survivors with cancer related chronic fatigue
Článek Immunopathogenesis of canine chronic ulcerative stomatitis
Článek Generalizing findings from a randomized controlled trial to a real-world study of the iLookOut, an online education program to improve early childhood care and education providers’ knowledge and attitudes about reporting child maltreatment
Článek When and what to test for: A cost-effectiveness analysis of febrile illness test-and-treat strategies in the era of responsible antibiotic use
Článek Comparison of effects and safety in providing controlled hypotension during surgery between dexmedetomidine and magnesium sulphate: A meta-analysis of randomized controlled trials
Článek The gene encoding the ketogenic enzyme HMGCS2 displays a unique expression during gonad development in mice
Článek Efficacy of a mitochondrion-targeting agent for reducing the level of urinary protein in rats with puromycin aminonucleoside-induced minimal-change nephrotic syndrome
Článek Association of endothelial nitric oxide synthase (NOS3) gene polymorphisms with primary open-angle glaucoma in a Saudi cohort
Článek Antitrust analysis with upward pricing pressure and cost efficiencies
Článek Natural selection contributes to food web stability
Článek Pyramiding QTLs controlling tolerance against drought, salinity, and submergence in rice through marker assisted breeding
Článek Diversity and plant growth-promoting functions of diazotrophic/N-scavenging bacteria isolated from the soils and rhizospheres of two species of Solanum
Článek Sofosbuvir-based regimen for genotype 2 HCV infected patients in Taiwan: A real world experience
Článek The virulence domain of Shigella IcsA contains a subregion with specific host cell adhesion function
Článek Sequencing artifacts derived from a library preparation method using enzymatic fragmentation
Článek Quantitative analysis of adsorption and desorption of volatile organic compounds on reusable zeolite filters using gas chromatography
Článek Quo vadis Pantanal? Expected precipitation extremes and drought dynamics from changing sea surface temperature
Článek Cloud-computing and machine learning in support of country-level land cover and ecosystem extent mapping in Liberia and Gabon
Článek The Brief Measure of Emotional Preoperative Stress (B-MEPS) as a new predictive tool for postoperative pain: A prospective observational cohort study
Článek The impact of diabetes mellitus medication on the incidence of endogenous endophthalmitis
Článek Clinical and pathological features of thrombotic microangiopathy influencing long-term kidney transplant outcomes
Článek Occupational exposure to particulate matter from air pollution in the outdoor workplaces in Almaty during the cold season
Článek Morphological adjustment in free-living Steinernema feltiae infective juveniles to increasing concentration of Nemafric-BL phytonematicide
Článek Key necroptotic proteins are required for Smac mimetic-mediated sensitization of cholangiocarcinoma cells to TNF-α and chemotherapeutic gemcitabine-induced necroptosis
Článek Concurrent lipidomics and proteomics on malignant plasma cells from multiple myeloma patients: Probing the lipid metabolome
Článek Retraction: SDR9C7 Promotes Lymph Node Metastases in Patients with Esophageal Squamous Cell Carcinoma
Článek Association between tuberculosis and depression on negative outcomes of tuberculosis treatment: A systematic review and meta-analysis
Článek Bioluminescent imaging of Arabidopsis thaliana using an enhanced Nano-lantern luminescence reporter system
Článek Biosynthetic pathway of indole-3-acetic acid in ectomycorrhizal fungi collected from northern Thailand
Článek Sex-specific and opposite modulatory aspects revealed by PPI network and pathway analysis of ischemic stroke in humans
Článek Control of the microsporidian parasite Nosema ceranae in honey bees (Apis mellifera) using nutraceutical and immuno-stimulatory compounds
Článek Role of donor genotype in RT-QuIC seeding activity of chronic wasting disease prions using human and bank vole substrates
Článek Oral magnesium supplementation for leg cramps in pregnancy—An observational controlled trial
Článek Health care professionals’ knowledge of commonly used sedative, analgesic and neuromuscular drugs: A single center (Rambam Health Care Campus), prospective, observational survey
Článek Campylobacter portucalensis sp. nov., a new species of Campylobacter isolated from the preputial mucosa of bulls
Článek Transgenic interleukin 11 expression causes cross-tissue fibro-inflammation and an inflammatory bowel phenotype in mice
Článek Sleep quality and sex modify the relationships between trait energy and fatigue on state energy and fatigue
Článek The role of peer, parental, and school norms in predicting adolescents’ attitudes and behaviours of majority and different minority ethnic groups in Croatia
Článek Availability, prices and affordability of selected antibiotics and medicines against non-communicable diseases in western Cameroon and northeast DR Congo
Článek The effect of mutations derived from mouse-adapted H3N2 seasonal influenza A virus to pathogenicity and host adaptation
Článek Detection of posttraumatic pneumothorax using electrical impedance tomography—An observer-blinded study in pigs with blunt chest trauma
Článek Educators’ perceptions of organisational readiness for implementation of a pre-adolescent transdisciplinary school health intervention for inter-generational outcomes
Článek The effects of sport expertise and shot results on basketball players’ action anticipation
Článek Framework and algorithms for identifying honest blocks in blockchain
Článek Exploring the impact of terminology differences in blood and organ donor decision making
Článek Platelet indices significantly correlate with liver fibrosis in HCV-infected patients
Článek The nitrate content of fresh and cooked vegetables and their health-related risks
Článek Multiplex real-time PCR for the detection of Clavibacter michiganensis subsp. michiganensis, Pseudomonas syringae pv. tomato and pathogenic Xanthomonas species on tomato plants
Článek The 24-hour urinary cortisol in post-traumatic stress disorder: A meta-analysis
Článek “I like the way I am, but I feel like I could get a little bit bigger”: Perceptions of body image among adolescents and youth living with HIV in Durban, South Africa
Článek Nanoparticle-based ‘turn-on’ scattering and post-sample fluorescence for ultrasensitive detection of water pollution in wider window
Článek Insights into the strategy of micro-environmental adaptation: Transcriptomic analysis of two alvinocaridid shrimps at a hydrothermal vent
Článek Thirty-day readmission after medical-surgical hospitalization for people who experience imprisonment in Ontario, Canada: A retrospective cohort study
Článek Hyper-spectral response and estimation model of soil degradation in Kenli County, the Yellow River Delta
Článek Construction of a high-density genetic map and fine mapping of a candidate gene locus for a novel branched-spike mutant in barley
Článek Natural hybridization between Phyllagathis and Sporoxeia species produces a hybrid without reproductive organs
Článek Diagnostic performance of serum interferon gamma, matrix metalloproteinases, and periostin measurements for pulmonary tuberculosis in Japanese patients with pneumonia
Článek Characterization of black patina from the Tiber River embankments using Next-Generation Sequencing
Článek Validity of cerebrovascular ICD-9-CM codes in healthcare administrative databases. The Umbria Data-Value Project
Článek Torque teno virus viral load is related to age, CMV infection and HLA type but not to Alzheimer's disease
Článek Associations of cigarette smoking and burden of thoracic aortic calcification in asymptomatic individuals: A dose-response relationship
Článek Transforming assessment of speech in children with cleft palate via online crowdsourcing
Článek Assessment of peritoneal microbial features and tumor marker levels as potential diagnostic tools for ovarian cancer
Článek Deficiency syndromes in top predators associated with large-scale changes in the Baltic Sea ecosystem
Článek Perceived relative social status and cognitive load influence acceptance of unfair offers in the Ultimatum Game
Článek Hepatitis B and C virus infection among HIV patients within the public and private healthcare systems in Chile: A cross-sectional serosurvey
Článek Retraction: Oncogenic Fibulin-5 Promotes Nasopharyngeal Carcinoma Cell Metastasis through the FLJ10540/AKT Pathway and Correlates with Poor Prognosis
Článek From seed to flour: Sowing sustainability in the use of cantaloupe melon residue (Cucumis melo L. var. reticulatus)
Článek Core Scientific Dataset Model: A lightweight and portable model and file format for multi-dimensional scientific data
Článek Accounting for measurement error to assess the effect of air pollution on omic signals
Článek Leucine zipper transcription factor-like 1 binds adaptor protein complex-1 and 2 and participates in trafficking of transferrin receptor 1
Článek Barriers for tuberculosis case finding in Southwest Ethiopia: A qualitative study
Článek Genetic predisposition to celiac disease in Kazakhstan: Potential impact on the clinical practice in Central Asia
Článek A lower psoas muscle volume was associated with a higher rate of recurrence in male clear cell renal cell carcinoma
Článek Two angles of overqualification-the deviant behavior and creative performance: The role of career and survival job
Článek Cost-utility analysis of de-escalating biological disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis
Článek Efficient estimation of stereo thresholds: What slope should be assumed for the psychometric function?
Článek Learning efficient haptic shape exploration with a rigid tactile sensor array
Článek Effects of dietary supplementation with a microalga (Schizochytrium sp.) on the hemato-immunological, and intestinal histological parameters and gut microbiota of Nile tilapia in net cages
Článek Regional versus local wind speed and direction at a narrow beach with a high and steep foredune
Článek Fragmented QRS complex in patients with systemic lupus erythematosus at the time of diagnosis and its relationship with disease activity
Článek Severe thiamine deficiency in eastern Baltic cod (Gadus morhua)
Článek Transfer entropy as a variable selection methodology of cryptocurrencies in the framework of a high dimensional predictive model
Článek Psychometric validation of Czech version of the Sport Motivation Scale
Článek Correction: Multiple innate antibacterial immune defense elements are correlated in diverse ungulate species
Článek Recognition of personality disorder and anxiety disorder comorbidity in patients treated for depression in secondary psychiatric care
Článek Correction: Strategies for achieving high sequencing accuracy for low diversity samples and avoiding sample bleeding using illumina platform
Článek ETAPOD: A forecast model for prediction of black pod disease outbreak in Nigeria
Článek Number of days required to estimate physical activity constructs objectively measured in different age groups: Findings from three Brazilian (Pelotas) population-based birth cohorts
Článek Exploring the mechanism of olfactory recognition in the initial stage by modeling the emission spectrum of electron transfer
Článek The impact of a wireless audio system on communication in robotic-assisted laparoscopic surgery: A prospective controlled trial
Článek Dense carbon-nanotube coating scaffolds stimulate osteogenic differentiation of mesenchymal stem cells
Článek Physicians’ perspectives regarding non-medical switching of prescription medications: Results of an internet e-survey
Článek Potential socioeconomic impacts from ocean acidification and climate change effects on Atlantic Canadian fisheries
Článek Modeling aggressive market order placements with Hawkes factor models
Článek Healthy lifestyle index and its association with hypertension among community adults in Sri Lanka: A cross-sectional study
Článek Effects of Allium hookeri on gut microbiome related to growth performance in young broiler chickens
Článek The Shapley value for a fair division of group discounts for coordinating cooling loads
Článek Pancreatic secretory trypsin inhibitor reduces multi-organ injury caused by gut ischemia/reperfusion in mice
Článek Community- and trophic-level responses of soil nematodes to removal of a non-native tree at different stages of invasion
Článek Association of ECG parameters with late gadolinium enhancement and outcome in patients with clinical suspicion of acute or subacute myocarditis referred for CMR imaging
Článek Impact of multi-drug resistant bacteria on economic and clinical outcomes of healthcare-associated infections in adults: Systematic review and meta-analysis
Článek Simple non-mydriatic retinal photography is feasible and demonstrates retinal microvascular dilation in Chronic Obstructive Pulmonary Disease (COPD)
Článek Maternal depressive symptoms and children’s cognitive development: Does early childcare and child’s sex matter?
Článek Prevalence and characteristics of Livestock-Associated Methicillin-Resistant Staphylococcus aureus (LA-MRSA) isolated from chicken meat in the province of Quebec, Canada
Článek Using machine learning methods to determine a typology of patients with HIV-HCV infection to be treated with antivirals
Článek Oral misoprostol, low dose vaginal misoprostol, and vaginal dinoprostone for labor induction: Randomized controlled trial
Článek The association between dietary patterns before and in early pregnancy and the risk of gestational diabetes mellitus (GDM): Data from the Malaysian SECOST cohort
Článek cagA gene EPIYA motif genetic characterization from Colombian Helicobacter pylori isolates: Standardization of a molecular test for rapid clinical laboratory detection
Článek Spectral characteristics of urine from patients with end-stage kidney disease analyzed using Raman Chemometric Urinalysis (Rametrix)
Článek Comparison of Monocyte Distribution Width (MDW) and Procalcitonin for early recognition of sepsis
Článek Morphological association between the muscles and bones in the craniofacial region
Článek Antenatal depression and its association with adverse birth outcomes in low and middle-income countries: A systematic review and meta-analysis
Článek The role of refugee and migrant migration status on medication adherence: Mediation through illness perceptions
Článek Effect of a community-based approach of iron and folic acid supplementation on compliance by pregnant women in Kiambu County, Kenya: A quasi-experimental study
Článek Plasma kynurenines and prognosis in patients with heart failure
Článek Correction: Chl1 DNA helicase and Scc2 function in chromosome condensation through cohesin deposition
Článek Bioreactor for mobilization of mesenchymal stem/stromal cells into scaffolds under mechanical stimulation: Preliminary results
Článek Non-gradient and genotype-dependent patterns of RSV gene expression
Článek Drug-eluting versus bare-metal stents for first myocardial infarction in patients with atrial fibrillation: A nationwide population-based cohort study
Článek Health-related quality of life among patients with type 2 diabetes mellitus in Eastern Province, Saudi Arabia: A cross-sectional study
Článek The association of telomere length and telomerase activity with adverse outcomes in older patients with non-ST-elevation acute coronary syndrome
Článek Alterations of aqueous humor Aβ levels in Aβ-infused and transgenic mouse models of Alzheimer disease
Článek The impact of peer attachment on prosocial behavior, emotional difficulties and conduct problems in adolescence: The mediating role of empathy
Článek Problem gambling, associations with comorbid health conditions, substance use, and behavioural addictions: Opportunities for pathways to treatment
Článek Nanosheet wrapping-assisted coverslip-free imaging for looking deeper into a tissue at high resolution
Článek Human-raptor conflict in rural settlements of Colombia
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PLOS One

2020 Číslo 1
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Aktuální možnosti diagnostiky a léčby litiáz
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Autori: MUDr. Tomáš Ürge, PhD.
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