131 results on '"Slavov, C"'
Search Results
2. A Generalized Net Model of the Pattern of Behavior in Patients with eGFR < 20 mL/min (CKD Stage IV-V)
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Lubich, M, Shannon, A, Slavov, C, Pencheva, T, Ribagin, S, and Atanassov, K
- Abstract
In the present study a mathematical model of behavior in patients with eGFR < 20 mL/min. (Chronic kidney disease (CKD) stage IV-V) based on generalized nets (GNs) is proposed. The developed reduced GN-model allows for optimization of clinical behavior in patients with CKD stage IV-V.
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- 2022
3. Marital status and prostate cancer incidence: a pooled analysis of 12 case-control studies from the PRACTICAL consortium
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Salmon, C, Song, L, Muir, K, UKGPCS Collaborators, Pashayan, N, Dunning, AM, Batra, J, APCB BioResource (Australian Prostate Cancer BioResource), Chambers, S, Stanford, JL, Ostrander, EA, Park, JY, Lin, H-Y, Cussenot, O, Cancel-Tassin, G, Menegaux, F, Cordina-Duverger, E, Kogevinas, M, Llorca, J, Kaneva, R, Slavov, C, Razack, A, Lim, J, Gago-Dominguez, M, Castelao, JE, Kote-Jarai, Z, Eeles, RA, on behalf of the PRACTICAL Consortium, and Parent, M-É
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Male ,Marital Status ,Epidemiology ,Incidence ,Prostatic Neoplasms ,Social Support ,Single Person ,Adenocarcinoma ,Middle Aged ,1117 Public Health and Health Services ,Divorce ,Population Surveillance ,Humans ,Marriage ,Aged - Abstract
While being in a committed relationship is associated with a better prostate cancer prognosis, little is known about how marital status relates to its incidence. Social support provided by marriage/relationship could promote a healthy lifestyle and an increased healthcare seeking behavior. We investigated the association between marital status and prostate cancer risk using data from the PRACTICAL Consortium. Pooled analyses were conducted combining 12 case-control studies based on histologically-confirmed incident prostate cancers and controls with information on marital status prior to diagnosis/interview. Marital status was categorized as married/partner, separated/divorced, single, or widowed. Tumours with Gleason scores ≥ 8 defined high-grade cancers, and low-grade otherwise. NCI-SEER's summary stages (local, regional, distant) indicated the extent of the cancer. Logistic regression was used to derive odds ratios (ORs) and 95% confidence intervals (CI) for the association between marital status and prostate cancer risk, adjusting for potential confounders. Overall, 14,760 cases and 12,019 controls contributed to analyses. Compared to men who were married/with a partner, widowed men had an OR of 1.19 (95% CI 1.03-1.35) of prostate cancer, with little difference between low- and high-grade tumours. Risk estimates among widowers were 1.14 (95% CI 0.97-1.34) for local, 1.53 (95% CI 1.22-1.92) for regional, and 1.56 (95% CI 1.05-2.32) for distant stage tumours. Single men had elevated risks of high-grade cancers. Our findings highlight elevated risks of incident prostate cancer among widowers, more often characterized by tumours that had spread beyond the prostate at the time of diagnosis. Social support interventions and closer medical follow-up in this sub-population are warranted.
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- 2021
4. Temperature Dependence of the Krokinobacter rhodopsin 2 Kinetics
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Eberhardt, P., primary, Slavov, C., additional, Sörmann, J., additional, Bamann, C., additional, Braun, M., additional, and Wachtveitl, J., additional
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- 2020
- Full Text
- View/download PDF
5. Exploring the role of genes associated with familial cancer syndromes on the development of multiple primary tumors
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Mitkova, A.V., primary, Dodova, R., additional, Koleva, M., additional, Andreeva, A., additional, Tzekova-Chernopolska, M., additional, Giragosyan, S., additional, Petkova, V.Y., additional, Terziev, I., additional, Rangelov, S., additional, Slavov, C., additional, Mitev, V., additional, and Kaneva, R.P., additional
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- 2019
- Full Text
- View/download PDF
6. Germline variation at 8q24 and prostate cancer risk in men of European ancestry (vol 9, 4616, 2018)
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Matejcic, M, Saunders, EJ, Dadaev, T, Brook, MN, Wang, K, Sheng, X, Al Olama, AA, Schumacher, FR, Ingles, SA, Govindasami, K, Benlloch, S, Berndt, SI, Albanes, D, Koutros, S, Muir, K, Stevens, VL, Gapstur, SM, Tangen, CM, Batra, J, Clements, J, Gronberg, H, Pashayan, N, Schleutker, J, Wolk, A, West, C, Mucci, L, Kraft, P, Cancel-Tassin, G, Sorensen, KD, Maehle, L, Grindedal, EM, Strom, SS, Neal, DE, Hamdy, FC, Donovan, JL, Travis, RC, Hamilton, RJ, Rosenstein, B, Lu, Y-J, Giles, GG, Kibel, AS, Vega, A, Bensen, JT, Kogevinas, M, Penney, KL, Park, JY, Stanford, JL, Cybulski, C, Nordestgaard, BG, Brenner, H, Maier, C, Kim, J, Teixeira, MR, Neuhausen, SL, De Ruyck, K, Razack, A, Newcomb, LF, Lessel, D, Kaneva, R, Usmani, N, Claessens, F, Townsend, PA, Gago-Dominguez, M, Roobol, MJ, Menegaux, F, Khaw, K-T, Cannon-Albright, LA, Pandha, H, Thibodeau, SN, Schaid, DJ, Wiklund, F, Chanock, SJ, Easton, DF, Eeles, RA, Kote-Jarai, Z, Conti, DV, Haiman, CA, Henderson, BE, Stern, MC, Thwaites, A, Guy, M, Whitmore, I, Morgan, A, Fisher, C, Hazel, S, Livni, N, Cook, M, Fachal, L, Weinstein, S, Freeman, LEB, Hoover, RN, Machiela, MJ, Lophatananon, A, Carter, BD, Goodman, P, Moya, L, Srinivasan, S, Kedda, M-A, Yeadon, T, Eckert, A, Eklund, M, Cavalli-Bjoerkman, C, Dunning, AM, Sipeky, C, Hakansson, N, Elliott, R, Ranu, H, Giovannucci, E, Turman, C, Hunter, DJ, Cussenot, O, Orntoft, TF, Lane, A, Lewis, SJ, Davis, M, Key, TJ, Brown, P, Kulkarni, GS, Zlotta, AR, Fleshner, NE, Finelli, A, Mao, X, Marzec, J, MacInnis, RJ, Milne, R, Hopper, JL, Aguado, M, Bustamante, M, Castano-Vinyals, G, Gracia-Lavedan, E, Cecchini, L, Stampfer, M, Ma, J, Sellers, TA, Geybels, MS, Park, H, Zachariah, B, Kolb, S, Wokolorczyk, D, Lubinski, J, Kluzniak, W, Nielsen, SF, Weisher, M, Cuk, K, Vogel, W, Luedeke, M, Logothetis, CJ, Paulo, P, Cardoso, M, Maia, S, Silva, MP, Steele, L, Ding, YC, De Meerleer, G, De Langhe, S, Thierens, H, Lim, J, Tan, MH, Ong, AT, Lin, DW, Kachakova, D, Mitkova, A, Mitev, V, Parliament, M, Jenster, G, Bangma, C, Schroder, FH, Truong, T, Koudou, YA, Michael, A, Kierzek, A, Karlsson, A, Broms, M, Wu, H, Aukim-Hastie, C, Tillmans, L, Riska, S, McDonnell, SK, Dearnaley, D, Spurdle, A, Gardiner, R, Hayes, V, Butler, L, Taylor, R, Papargiris, M, Saunders, P, Kujala, P, Talala, K, Taari, K, Bentzen, S, Hicks, B, Vogt, A, Hutchinson, A, Cox, A, George, A, Toi, A, Evans, A, Van der Kwast, TH, Imai, T, Saito, S, Zhao, S-C, Ren, G, Zhang, Y, Yu, Y, Wu, Y, Wu, J, Zhou, B, Pedersen, J, Lobato-Busto, R, Manuel Ruiz-Dominguez, J, Mengual, L, Alcaraz, A, Pow-Sang, J, Herkommer, K, Vlahova, A, Dikov, T, Christova, S, Carracedo, A, Tretarre, B, Rebillard, X, Mulot, C, Adolfsson, J, Stattin, P, Johansson, J-E, Martin, RM, Thompson, IM, Chambers, S, Aitken, J, Horvath, L, Haynes, A-M, Tilley, W, Risbridger, G, Aly, M, Nordstrom, T, Pharoah, P, Tammela, TLJ, Murtola, T, Auvinen, A, Burnet, N, Barnett, G, Andriole, G, Klim, A, Drake, BF, Borre, M, Kerns, S, Ostrer, H, Zhang, H-W, Cao, G, Lin, J, Ling, J, Li, M, Feng, N, Li, J, He, W, Guo, X, Sun, Z, Wang, G, Guo, J, Southey, MC, FitzGerald, LM, Marsden, G, Gomez-Caamano, A, Carballo, A, Peleteiro, P, Calvo, P, Szulkin, R, Llorca, J, Dierssen-Sotos, T, Gomez-Acebo, I, Lin, H-Y, Ostrander, EA, Bisbjerg, R, Klarskov, P, Roder, MA, Iversen, P, Holleczek, B, Stegmaier, C, Schnoeller, T, Bohnert, P, John, EM, Ost, P, Teo, S-H, Gamulin, M, Kulis, T, Kastelan, Z, Slavov, C, Popov, E, Van den Broeck, T, Joniau, S, Larkin, S, Esteban Castelao, J, Martinez, ME, Van Schaik, RHN, Xu, J, Lindstrom, S, Riboli, E, Berry, C, Siddiq, A, Canzian, F, Kolonel, LN, Le Marchand, L, Freedman, M, Cenee, S, Sanchez, M, and Commission of the European Communities
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Multidisciplinary Sciences ,Science & Technology ,MD Multidisciplinary ,Science & Technology - Other Topics ,PRACTICAL Consortium - Abstract
Correction to: Nature Communications; https://doi.org/10.1038/s41467-018-06863-1, published online 5 November 2018.
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- 2019
7. Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants
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Dadaev, T, Saunders, EJ, Newcombe, PJ, Anokian, E, Leongamornlert, DA, Brook, MN, Cieza-Borrella, C, Mijuskovic, M, Wakerell, S, Olama, AAA, Schumacher, FR, Berndt, SI, Benlloch, S, Ahmed, M, Goh, C, Sheng, X, Zhang, Z, Muir, K, Govindasami, K, Lophatananon, A, Stevens, VL, Gapstur, SM, Carter, BD, Tangen, CM, Goodman, P, Thompson, IM, Batra, J, Chambers, S, Moya, L, Clements, J, Horvath, L, Tilley, W, Risbridger, G, Gronberg, H, Aly, M, Nordström, T, Pharoah, P, Pashayan, N, Schleutker, J, Tammela, TLJ, Sipeky, C, Auvinen, A, Albanes, D, Weinstein, S, Wolk, A, Hakansson, N, West, C, Dunning, AM, Burnet, N, Mucci, L, Giovannucci, E, Andriole, G, Cussenot, O, Cancel-Tassin, G, Koutros, S, Freeman, LEB, Sorensen, KD, Orntoft, TF, Borre, M, Maehle, L, Grindedal, EM, Neal, DE, Donovan, JL, Hamdy, FC, Martin, RM, Travis, RC, Key, TJ, Hamilton, RJ, Fleshner, NE, Finelli, A, Ingles, SA, Stern, MC, Rosenstein, B, Kerns, S, Ostrer, H, Lu, Y-J, Zhang, H-W, Feng, N, Mao, X, Guo, X, Wang, G, Sun, Z, Giles, GG, Southey, MC, Macinnis, RJ, Fitzgerald, LM, Kibel, AS, Drake, BF, Vega, A, Gómez-Caamaño, A, Fachal, L, Szulkin, R, Eklund, M, Kogevinas, M, Llorca, J, Castaño-Vinyals, G, Penney, KL, Stampfer, M, Park, JY, Sellers, TA, Lin, H-Y, Stanford, JL, Cybulski, C, Wokolorczyk, D, Lubinski, J, Ostrander, EA, Geybels, MS, Nordestgaard, BG, Nielsen, SF, Weisher, M, Bisbjerg, R, Røder, MA, Iversen, P, Brenner, H, Cuk, K, Holleczek, B, Maier, C, Luedeke, M, Schnoeller, T, Kim, J, Logothetis, CJ, John, EM, Teixeira, MR, Paulo, P, Cardoso, M, Neuhausen, SL, Steele, L, Ding, YC, De Ruyck, K, De Meerleer, G, Ost, P, Razack, A, Lim, J, Teo, S-H, Lin, DW, Newcomb, LF, Lessel, D, Gamulin, M, Kulis, T, Kaneva, R, Usmani, N, Slavov, C, Mitev, V, Parliament, M, Singhal, S, Claessens, F, Joniau, S, Van Den Broeck, T, Larkin, S, Townsend, PA, Aukim-Hastie, C, Gago-Dominguez, M, Castelao, JE, Martinez, ME, Roobol, MJ, Jenster, G, Van Schaik, RHN, Menegaux, F, Truong, T, Koudou, YA, Xu, J, Khaw, K-T, Cannon-Albright, L, Pandha, H, Michael, A, Kierzek, A, Thibodeau, SN, McDonnell, SK, Schaid, DJ, Lindstrom, S, Turman, C, Ma, J, Hunter, DJ, Riboli, E, Siddiq, A, Canzian, F, Kolonel, LN, Le Marchand, L, Hoover, RN, Machiela, MJ, Kraft, P, Consortium, Practical (Prostate Cancer Association Group To Investigate Cancer-Associated Alterations In The Genome), Freedman, M, Wiklund, F, Chanock, S, Henderson, BE, Easton, DF, Haiman, CA, Eeles, RA, Conti, DV, Kote-Jarai, Z, Dadaev, Tokhir [0000-0002-8268-0438], Leongamornlert, Daniel A [0000-0002-3486-3168], Brook, Mark N [0000-0002-8969-2378], Olama, Ali Amin Al [0000-0002-7178-3431], Schumacher, Fredrick R [0000-0002-3073-7463], Muir, Kenneth [0000-0001-6429-988X], Batra, Jyotsna [0000-0003-4646-6247], Nordström, Tobias [0000-0003-4915-7546], Pharoah, Paul [0000-0001-8494-732X], Pashayan, Nora [0000-0003-0843-2468], Schleutker, Johanna [0000-0002-1863-0305], Sipeky, Csilla [0000-0002-8853-4722], Wolk, Alicja [0000-0001-7387-6845], Cancel-Tassin, Géraldine [0000-0002-9583-6382], Sorensen, Karina Dalsgaard [0000-0002-4902-5490], Kerns, Sarah [0000-0002-6503-0011], Ostrer, Harry [0000-0002-2209-5376], Fachal, Laura [0000-0002-7256-9752], Kogevinas, Manolis [0000-0002-9605-0461], Nordestgaard, Børge G [0000-0002-1954-7220], Lim, Jasmine [0000-0002-7501-1834], Truong, Thérèse [0000-0002-2943-6786], Xu, Jianfeng [0000-0002-1343-8752], Easton, Douglas F [0000-0003-2444-3247], Eeles, Rosalind A [0000-0002-3698-6241], Apollo - University of Cambridge Repository, National Institutes of Health, Urology, and Clinical Chemistry
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Male ,Risk ,Science ,GENETIC ,Quantitative Trait Loci ,Black People ,PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium ,urologic and male genital diseases ,ANNOTATION ,Polymorphism, Single Nucleotide ,Article ,White People ,REGION ,GENETIC ASSOCIATION ,SDG 3 - Good Health and Well-being ,MD Multidisciplinary ,Medicine and Health Sciences ,ELEMENTS ,Humans ,Genetic Predisposition to Disease ,GENOME-WIDE ASSOCIATION ,lcsh:Science ,Medicinsk genetik ,MODEL SELECTION ,BAYESIAN FRAMEWORK ,Cancer och onkologi ,Science & Technology ,Chromosome Mapping ,Prostatic Neoplasms ,Bayes Theorem ,Molecular Sequence Annotation ,ASSOCIATION ,JOINT ANALYSIS ,RISK LOCI ,STATISTICS ,Multidisciplinary Sciences ,Cancer and Oncology ,Multivariate Analysis ,Science & Technology - Other Topics ,lcsh:Q ,Medical Genetics ,Algorithms ,VARIABLE-SELECTION ,Genome-Wide Association Study - Abstract
Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling., Prostate cancer (PrCa) involves a large heritable genetic component. Here, the authors perform multivariate fine-mapping of known PrCa GWAS loci, identifying variants enriched for biological function, explaining more familial relative risk, and with potential application in clinical risk profiling.
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- 2018
8. Genome-wide meta-analyses of breast, ovarian, and prostate cancer association studies identify multiple new susceptibility loci shared by at least two cancer types
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Kar, SP, Beesley, J, Al Olama, AA, Michailidou, K, Tyrer, J, Kote-Jarai, ZA, Lawrenson, K, Lindstrom, S, Ramus, SJ, Thompson, DJ, Kibel, AS, Dansonka-Mieszkowska, A, Michael, A, Dieffenbach, AK, Gentry-Maharaj, A, Whittemore, AS, Wolk, A, Monteiro, A, Peixoto, A, Kierzek, A, Cox, A, Rudolph, A, Gonzalez-Neira, A, Wu, AH, Lindblom, A, Swerdlow, A, Ziogas, A, Ekici, AB, Burwinkel, B, Karlan, BY, Nordestgaard, BG, Blomqvist, C, Phelan, C, McLean, C, Pearce, CL, Vachon, C, Cybulski, C, Slavov, C, Stegmaier, C, Maier, C, Ambrosone, CB, Hogdall, CK, Teerlink, CC, Kang, D, Tessier, DC, Schaid, DJ, Stram, DO, Cramer, DW, Neal, DE, Eccles, D, Flesch-Janys, D, Velez Edwards, DR, Wokozorczyk, D, Levine, DA, Yannoukakos, D, Sawyer, EJ, Bandera, EV, Poole, EM, Goode, EL, Khusnutdinova, E, Hogdall, E, Song, F, Bruinsma, F, Heitz, F, Modugno, F, Hamdy, FC, Wiklund, F, Giles, GG, Olsson, H, Wildiers, H, and Ulmer, HU
- Abstract
© 2016 American Association for Cancer Research. Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10−8 seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/ BCL2L11; rs7937840/11q12/ INCENP; rs1469713/19p13/ GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/ SMC2; rs8037137/15q26/ RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/ NSUN4; rs9375701/6q23/ L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10−5 in the three-cancer meta-analysis. SIGNIFICANCE: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers.
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- 2016
9. Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation
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Gusev, A, Shi, H, Kichaev, G, Pomerantz, M, Li, F, Long, HW, Ingles, SA, Kittles, RA, Strom, SS, Rybicki, BA, Nemesure, B, Isaacs, WB, Zheng, W, Pettaway, CA, Yeboah, ED, Tettey, Y, Biritwum, RB, Adjei, AA, Tay, E, Truelove, A, Niwa, S, Chokkalingam, AP, John, EM, Murphy, AB, Signorello, LB, Carpten, J, Leske, MC, Wu, S-Y, Hennis, AJM, Neslund-Dudas, C, Hsing, AW, Chu, L, Goodman, PJ, Klein, EA, Witte, JS, Casey, G, Kaggwa, S, Cook, MB, Stram, DO, Blot, WJ, Eeles, RA, Easton, D, Kote-Jarai, Z, Al Olama, AA, Benlloch, S, Muir, K, Giles, GG, Southey, MC, Fitzgerald, LM, Gronberg, H, Wiklund, F, Aly, M, Henderson, BE, Schleutker, J, Wahlfors, T, Tammela, TLJ, Nordestgaard, BG, Key, TJ, Travis, RC, Neal, DE, Donovan, JL, Hamdy, FC, Pharoah, P, Pashayan, N, Khaw, K-T, Stanford, JL, Thibodeau, SN, McDonnell, SK, Schaid, DJ, Maier, C, Vogel, W, Luedeke, M, Herkommer, K, Kibel, AS, Cybulski, C, Wokolorczyk, D, Kluzniak, W, Cannon-Albright, L, Teerlink, C, Brenner, H, Dieffenbach, AK, Arndt, V, Park, JY, Sellers, TA, Lin, H-Y, Slavov, C, Kaneva, R, Mitev, V, Batra, J, Spurdle, A, Clements, JA, Teixeira, MR, Pandha, H, Michael, A, Paulo, P, Maia, S, Kierzek, A, Conti, DV, Albanes, D, Berg, C, Berndt, SI, Campa, D, Crawford, ED, Diver, WR, Gapstur, SM, Gaziano, JM, Giovannucci, E, Hoover, R, Hunter, DJ, Johansson, M, Kraft, P, Le Marchand, L, Lindstrom, S, Navarro, C, Overvad, K, Riboli, E, Siddiq, A, Stevens, VL, Trichopoulos, D, Vineis, P, Yeager, M, Trynka, G, Raychaudhuri, S, Schumacher, FR, Price, AL, Freedman, ML, Haiman, CA, Pasaniuc, B, Cook, M, Guy, M, Govindasami, K, Leongamornlert, D, Sawyer, EJ, Wilkinson, R, Saunders, EJ, Tymrakiewicz, M, Dadaev, T, Morgan, A, Fisher, C, Hazel, S, Livni, N, Lophatananon, A, Pedersen, J, Hopper, JL, Adolfson, J, Stattin, P, Johansson, J-E, Cavalli-Bjoerkman, C, Karlsson, A, Broms, M, Auvinen, A, Kujala, P, Maeaettaenen, L, Murtola, T, Taari, K, Weischer, M, Nielsen, SF, Klarskov, P, Roder, A, Iversen, P, Wallinder, H, Gustafsson, S, Cox, A, Brown, P, George, A, Marsden, G, Lane, A, Davis, M, Tillmans, L, Riska, S, Wang, L, Rinckleb, A, Lubiski, J, Stegmaier, C, Pow-Sang, J, Park, H, Radlein, S, Rincon, M, Haley, J, Zachariah, B, Kachakova, D, Popov, E, Mitkova, A, Vlahova, A, Dikov, T, Christova, S, Heathcote, P, Wood, G, Malone, G, Saunders, P, Eckert, A, Yeadon, T, Kerr, K, Collins, A, Turner, M, Srinivasan, S, Kedda, M-A, Alexander, K, Omara, T, Wu, H, Henrique, R, Pinto, P, Santos, J, Barros-Silva, J, and Consortium, PRACTICAL
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urologic and male genital diseases - Abstract
Although genome-wide association studies have identified over 100 risk loci that explain ~33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.
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- 2016
10. 'Super-quenching' state protects Symbiodinium from thermal stress - Implications for coral bleaching
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Slavov, C, Schrameyer, V, Reus, M, Ralph, PJ, Hill, R, Büchel, C, Larkum, AWD, and Holzwarth, AR
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Chlorophyll ,Time Factors ,Light ,Photosystem I Protein Complex ,Temperature ,Photosystem II Protein Complex ,Anthozoa ,Models, Biological ,Thylakoids ,Electron Transport ,Kinetics ,Microscopy, Electron, Transmission ,Stress, Physiological ,Luminescent Measurements ,Dinoflagellida ,Animals ,Photosynthesis ,Symbiosis ,Oxidation-Reduction ,02 Physical Sciences, 06 Biological Sciences - Abstract
The global rise in sea surface temperatures causes regular exposure of corals to high temperature and high light stress, leading to worldwide disastrous coral bleaching events (loss of symbiotic dinoflagellates (Symbiodinium) from reef-building corals). Our picosecond chlorophyll fluorescence experiments on cultured Symbiodinium clade C cells exposed to coral bleaching conditions uncovered the transformations of the alga's photosynthetic apparatus (PSA) that activate an extremely efficient non-photochemical "super-quenching" mechanism. The mechanism is associated with a transition from an initially heterogeneous photosystem II (PSII) pool to a homogeneous "spillover" pool, where nearly all excitation energy is transferred to photosystem I (PSI). There, the inherently higher stability of PSI and high quenching efficiency of P(700)(+) allow dumping of PSII excess excitation energy into heat, resulting in almost complete cessation of photosynthetic electron transport (PET). This potentially reversible "super-quenching" mechanism protects the PSA against destruction at the cost of a loss of photosynthetic activity. We suggest that the inhibition of PET and the consequent inhibition of organic carbon production (e.g. sugars) in the symbiotic Symbiodinium provide a trigger for the symbiont expulsion, i.e. bleaching.
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- 2016
11. 2029P - Exploring the role of genes associated with familial cancer syndromes on the development of multiple primary tumors
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Mitkova, A.V., Dodova, R., Koleva, M., Andreeva, A., Tzekova-Chernopolska, M., Giragosyan, S., Petkova, V.Y., Terziev, I., Rangelov, S., Slavov, C., Mitev, V., and Kaneva, R.P.
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- 2019
- Full Text
- View/download PDF
12. Targeted next generation sequencing of Bulgarian prostate cancer patients finds new somatic mutations and reflects disease heterogeneity
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Kachakova, D., primary, Vlahova, A., additional, Mihova, K., additional, Mitkova, A., additional, Popov, I., additional, Popov, E., additional, Christova, S., additional, Slavov, C., additional, Mitev, V., additional, and Kaneva, R., additional
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- 2016
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13. Photoswitchable G-quadruplex
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Thevarpadam, J., primary, Bessi, I., additional, Binas, O., additional, Goncalves, D.P.N., additional, Slavov, C., additional, Jonker, H.R.A., additional, Richter, C., additional, Wachtveitl, J., additional, Schwalbe, H., additional, and Heckel, A., additional
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- 2016
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14. Ultrafast Isomerization Dynamics of Bisazobenzenes
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Slavov, C., primary, Yang, C., additional, Schweighauser, L., additional, Boumrifak, C., additional, Dreuw, A., additional, Wegner, H., additional, and Wachtveitl, J., additional
- Published
- 2016
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15. The ultrafast reactions in the photochromic cycle of water-soluble fulgimide photoswitches
- Author
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Slavov, C., primary, Boumrifak, C., additional, Hammer, C. A., additional, Trojanowski, P., additional, Chen, X., additional, Lees, W. J., additional, Wachtveitl, J., additional, and Braun, M., additional
- Published
- 2016
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16. Ultrafast coherent oscillations reveal a reactive mode in the ring-opening reaction of fulgides
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Slavov, C., primary, Bellakbil, N., additional, Wahl, J., additional, Mayer, K., additional, Rück-Braun, K., additional, Burghardt, I., additional, Wachtveitl, J., additional, and Braun, M., additional
- Published
- 2015
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17. Malignant melanoma of glans penis and prepuce treated with organ-preserving surgical procedure
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Slavov, C., Venkov, G., Velikova, K., Christova, S., Elenko Popov, and Tsankov, N.
- Subjects
Diagnosis, Differential ,Male ,Humans ,Melanoma ,Penile Neoplasms ,malignant melanoma ,glans penis ,prepuce ,organ-preserving surgical procedure ,buccal mucosa ,Aged - Abstract
The authors present a case of malignant melanoma of glans penis and prepuce. An organ-preserving operative procedure using buccal mucosa was performed with subsequent inguino-femoral modified lymphadenectomy. There was no disease progression during the follow-up period of twelve months.
- Published
- 2009
18. 397: miR-141 and miR-375 expression in plasma samples from Bulgarian prostate cancer patients and controls
- Author
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Kachakova, D., primary, Popov, E., additional, Mitkova, A., additional, Popov, I., additional, Vlahova, A., additional, Dikov, T., additional, Christova, S., additional, Slavov, C., additional, Mitev, V., additional, and Kaneva, R., additional
- Published
- 2014
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19. Photo-physical properties of 2-(1-ethynylpyrene)-adenosine: influence of hydrogen bonding on excited state properties
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Trojanowski, P., primary, Plötner, J., additional, Grünewald, C., additional, Graupner, F. F., additional, Slavov, C., additional, Reuss, A. J., additional, Braun, M., additional, Engels, J. W., additional, and Wachtveitl, J., additional
- Published
- 2014
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- View/download PDF
20. 520 Promoter Hypermethylation of HIST1H4K and RASSF2 in Urine From Prostate Cancer Patients
- Author
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Kachakova, D., primary, Popov, E., additional, Mitkova, A., additional, Beltcheva, O., additional, Vlahova, A., additional, Dikov, T., additional, Christova, S., additional, Slavov, C., additional, Mitev, V., additional, and Kaneva, R., additional
- Published
- 2012
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- View/download PDF
21. UP-03.137 Urethroplasty with Lingual Mucosa Free Graft-Long Term Results and Operative Techniques Used
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Popov, E., primary and Slavov, C., additional
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- 2011
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22. Real-Time CEUS with SonoVue in the Diagnosis of Renal Tumors
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Djerassi, R.J., primary, Bogov, B.I., additional, Ljubomirova, M., additional, Krupev, M., additional, and Slavov, C., additional
- Published
- 2011
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- View/download PDF
23. 873 Association study of polymorphic variants in chromosome locus 8q24 linked with prostate cancer in Bulgarian patients
- Author
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Kachakova, D., primary, Popov, E., additional, Mitkova, A., additional, Dodova, R., additional, Vlahova, A., additional, Dikov, T., additional, Christova, S., additional, Slavov, C., additional, Mitev, V., additional, and Kaneva, R., additional
- Published
- 2010
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- View/download PDF
24. UP-1.131: Role of Genetic Polymorphism in SRD5A2 Gene in Progression of Prostate Cancer
- Author
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Slavov, C., primary, Popov, E., additional, Mitkova, A., additional, and Kaneva, R., additional
- Published
- 2009
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- View/download PDF
25. MP-10.12: Complex Urethroplasties Using Combinations of Free Tissue Grafts
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Slavov, C., primary, Popov, E., additional, Venkov, G., additional, and Tzvetkov, M., additional
- Published
- 2009
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- View/download PDF
26. MP-10.13: Urethroplasty with Usage of Lingual Mucosa Free Graft: Single Centre Initial Experience and Early Results
- Author
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Slavov, C., primary, Popov, E., additional, Venkov, G., additional, and Tzvetkov, M., additional
- Published
- 2009
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27. PRESENCE OF BK VIRURIA IN HEART TRANSPLANT PATIENTS
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Palekar, S, primary, Slavov, C, additional, Akbar, S, additional, Mele, L, additional, and Pardi, S, additional
- Published
- 2008
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28. REDUCTION OF IMMUNOSUPPRESSION IN OHT PATIENTS WITH BK VIRURIA
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Palekar, S, primary, Slavov, C, additional, Akbar, S, additional, Mele, L, additional, and Pardi, S, additional
- Published
- 2008
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- View/download PDF
29. MORPHOMETRIC ASSESSMENT OF TISSUES IN RECONSTRUCTIVE SURGERY OF STRICTURES OF THE MALE URETHRA
- Author
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Mateev, D., primary, Sarachev, A., additional, Shishkov, D., additional, Belovejdov, V., additional, Slavov, C., additional, and Popov, E., additional
- Published
- 2008
- Full Text
- View/download PDF
30. Liquid chromatography method for simultaneous analysis of amino acids and biogenic amines in biological fluids with simultaneous gradient of pH and acetonitrile
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LOZANOV, V, primary, BENKOVA, B, additional, MATEVA, L, additional, PETROV, S, additional, POPOV, E, additional, SLAVOV, C, additional, and MITEV, V, additional
- Published
- 2007
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31. POS-03.44: Urethroplasty with combined free tissue grafts
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Slavov, C., primary, Venkov, G., additional, Popov, E., additional, and Tzvetkov, M., additional
- Published
- 2007
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- View/download PDF
32. UP-03.46
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Slavov, C., primary, Mitev, V., additional, Mateva, L., additional, Benkova, B., additional, Lozanov, V., additional, and Popov, E., additional
- Published
- 2006
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33. MP-08.19
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Slavov, C., primary, Vlahova, A., additional, Christova, S., additional, and Popov, E., additional
- Published
- 2006
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34. Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types
- Author
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Kar, S. P., Beesley, J., Amin Al Olama, A., Michailidou, K., Tyrer, J., Kote-Jarai, Z., Lawrenson, K., Lindstrom, S., Ramus, S. J., Thompson, D. J., Kibel, Adam Stuart, Dansonka-Mieszkowska, A., Michael, A., Dieffenbach, A. K., Gentry-Maharaj, A., Whittemore, A. S., Wolk, A., Monteiro, A., Peixoto, A., Kierzek, A., Cox, A., Rudolph, A., Gonzalez-Neira, A., Wu, A. H., Lindblom, A., Swerdlow, A., Ziogas, A., Ekici, A. B., Burwinkel, B., Karlan, B. Y., Nordestgaard, B. G., Blomqvist, C., Phelan, C., McLean, C., Pearce, C. L., Vachon, C., Cybulski, C., Slavov, C., Stegmaier, C., Maier, C., Ambrosone, C. B., Hogdall, C. K., Teerlink, C. C., Kang, D., Tessier, D. C., Schaid, D. J., Stram, D. O., Cramer, Daniel William, Neal, D. E., Eccles, D., Flesch-Janys, D., Edwards, D. R. V., Wokozorczyk, D., Levine, D. A., Yannoukakos, D., Sawyer, E. J., Bandera, E. V., Poole, Elizabeth M., Goode, E. L., Khusnutdinova, E., Hogdall, E., Song, F, Bruinsma, F., Heitz, F., Modugno, F., Hamdy, F. C., Wiklund, F., Giles, G. G., Olsson, H., Wildiers, H., Ulmer, H.-U., Pandha, H., Risch, H. A., Darabi, H., Salvesen, H. B., Nevanlinna, H., Gronberg, H., Brenner, H., Brauch, H., Anton-Culver, H., Song, H., Lim, H.-Y., McNeish, I., Campbell, I., Vergote, I., Gronwald, J., Lubinski, J., Stanford, J. L., Benitez, J., Doherty, J. A., Permuth, J. B., Chang-Claude, J., Donovan, J. L., Dennis, J., Schildkraut, J. M., Schleutker, J., Hopper, J. L., Kupryjanczyk, J., Park, J. Y., Figueroa, J., Clements, J. A., Knight, J. A., Peto, J., Cunningham, J. M., Pow-Sang, J., Batra, J., Czene, K., Lu, K. H., Herkommer, K., Khaw, K.-T., Matsuo, K., Muir, K., Offitt, K., Chen, K., Moysich, K. B., Aittoma ki, K., Odunsi, K., Kiemeney, L. A., Massuger, L. F. A. G., Fitzgerald, L. M., Cook, L. S., Cannon-Albright, L., Hooning, M. J., Pike, M. C., Bolla, M. K., Luedeke, M., Teixeira, M. R., Goodman, M. T., Schmidt, M. K., Riggan, M., Aly, M., Rossing, M. A., Beckmann, M. W., Moisse, M., Sanderson, M., Southey, M. C., Jones, M., Lush, M., Hildebrandt, M. A. T., Hou, M.-F., Schoemaker, M. J., Garcia-Closas, M., Bogdanova, N., Rahman, N., Le, N. D., Orr, N., Wentzensen, N., Pashayan, N., Peterlongo, P., Guenel, P., Brennan, P., Paulo, P., Webb, P. M., Broberg, P., Fasching, P. A., Devilee, P., Wang, Q., Cai, Q., Li, Q., Kaneva, R., Butzow, R., Kopperud, R. K., Schmutzler, R. K., Stephenson, R. A., MacInnis, R. J., Hoover, R. N., Winqvist, R., Ness, R., Milne, R. L., Travis, R. C., Benlloch, S., Olson, S. H., McDonnell, S. K., Tworoger, Shelley Slate, Maia, S., Berndt, S., Lee, S. C., Teo, S.-H., Thibodeau, S. N., Bojesen, S. E., Gapstur, S. M., Kjaer, S. K., Pejovic, T., Tammela, T. L. J., Do rk, T., Bru ning, T., Wahlfors, T., Key, T. J., Edwards, T. L., Menon, U., Hamann, U., Mitev, V., Kosma, V.-M., Setiawan, V. W., Kristensen, V., Arndt, V., Vogel, W., Zheng, W., Sieh, W., Blot, W. J., Kluzniak, W., Shu, X.-O., Gao, Y.-T., Schumacher, F., Freedman, M. L., Berchuck, A., Dunning, A. M., Simard, J., Haiman, C. A., Spurdle, A., Sellers, T. A., Hunter, David J., Henderson, B. E., Kraft, Peter Elias, Chanock, S. J., Couch, F. J., Hall, P., Gayther, S. A., Easton, D. F., Chenevix-Trench, G., Eeles, R., Pharoah, P. D. P., Lambrechts, D., and undefined, undefined
- Subjects
breast cancer ,ovarian cancer ,prostate cancer ,genome-wide association studies ,pleiotropy - Abstract
Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10(-8) seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10(-5) in the three-cancer meta-analysis., Other Research Unit
- Published
- 2016
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- View/download PDF
35. UP-03.46: Assessment of levels of amino acids, polyamines, metanephrines and catheholamines in serum and urine samples in patients with carcinoma of the bladder, adenocarcinoma of the prostate and BPH
- Author
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Slavov, C., Mitev, V., Mateva, L., Benkova, B., Lozanov, V., and Popov, E.
- Published
- 2006
- Full Text
- View/download PDF
36. MP-08.19: Expression of Ki67, p21, p53 in prostate biopsy tissue
- Author
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Slavov, C., Vlahova, A., Christova, S., and Popov, E.
- Published
- 2006
- Full Text
- View/download PDF
37. A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer
- Author
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Aa, Al Olama, Kote-Jarai Z, Si, Berndt, Dv, Conti, Schumacher F, Han Y, Benlloch S, Dj, Hazelett, Wang Z, Saunders E, Leongamornlert D, Lindstrom S, Jugurnauth-Little S, Dadaev T, Tymrakiewicz M, Do, Stram, Rand K, Wan P, Stram A, Sheng X, Lc, Pooler, Park K, Xia L, Tyrer J, Ln, Kolonel, Le Marchand L, Rn, Hoover, Mj, Machiela, Yeager M, Burdette L, Cc, Chung, Hutchinson A, Yu K, Goh C, Ahmed M, Govindasami K, Guy M, Tl, Tammela, Auvinen A, Wahlfors T, Schleutker J, Visakorpi T, Ka, Leinonen, Xu J, Aly M, Donovan J, Rc, Travis, Tj, Key, Siddiq A, Canzian F, Kt, Khaw, Takahashi A, Kubo M, Pharoah P, Pashayan N, Weischer M, Bg, Nordestgaard, Sf, Nielsen, Klarskov P, Ma, Røder, Iversen P, Sn, Thibodeau, Sk, Mcdonnell, Dj, Schaid, Jl, Stanford, Kolb S, Holt S, Knudsen B, Ah, Coll, Sm, Gapstur, Wr, Diver, Vl, Stevens, Maier C, Luedeke M, Herkommer K, Ae, Rinckleb, Ss, Strom, Pettaway C, Ed, Yeboah, Tettey Y, Rb, Biritwum, Aa, Adjei, Tay E, Truelove A, Niwa S, Ap, Chokkalingam, Cannon-Albright L, Cybulski C, Wokołorczyk D, Kluźniak W, Park J, Sellers T, Hy, Lin, Wb, Isaacs, Aw, Partin, Brenner H, Ak, Dieffenbach, Stegmaier C, Chen C, El, Giovannucci, Ma J, Stampfer M, Kl, Penney, Mucci L, Em, John, Sa, Ingles, Ra, Kittles, Ab, Murphy, Pandha H, Michael A, Am, Kierzek, Blot W, Lb, Signorello, Zheng W, Albanes D, Virtamo J, Weinstein S, Nemesure B, Carpten J, Leske C, Sy, Wu, Hennis A, As, Kibel, Ba, Rybicki, Neslund-Dudas C, Aw, Hsing, Chu L, Pj, Goodman, Ea, Klein, Sl, Zheng, Batra J, Clements J, Spurdle A, Teixeira MR, Maia S, Slavov C, Kaneva R, Mitev V, Js, Witte, Casey G, Em, Gillanders, Seminara D, Riboli E, Fc, Hamdy, Ga, Coetzee, Li Q, Ml, Freedman, Dj, Hunter, Muir K, Gronberg H, Neal DE, Southey M, Gg, Giles, Severi G, Mb, Cook, Nakagawa H, Wiklund F, Kraft P, Sj, Chanock, Be, Henderson, Df, Easton, Ra, Eeles, and Ca, Haiman
38. Evaluation of the clinical value of the newly identified urine biomarker HIST1H4K for diagnosis and prognosis of prostate cancer in Bulgarian patients
- Author
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Kachakova, D., Mitkova, A., Popov, E., Beltcheva, O., Aleksandrina Vlahova, Dikov, T., Hristova, S., Mitev, V., Slavov, C., and Kaneva, R.
- Subjects
Adult ,Aged, 80 and over ,Male ,Adolescent ,Prostatic Hyperplasia ,Prostatic Neoplasms ,DNA Methylation ,Middle Aged ,Prostate-Specific Antigen ,Prognosis ,Real-Time Polymerase Chain Reaction ,Histones ,Young Adult ,Case-Control Studies ,Biomarkers, Tumor ,Humans ,Neoplasm Grading ,Neoplasm Metastasis ,Promoter Regions, Genetic ,Aged ,Follow-Up Studies ,Neoplasm Staging - Abstract
Searching for diagnostic and prognostic biomarkers for prostate cancer (PC) is main public health priority. DNA methylation in body fluids is a stable, easily detectable and promising PC biomarker. The major advantages of urine-based assays are their noninvasive nature and the ability to monitor PC with heterogeneous foci. The aim of this study was to determine the diagnostic value of the recently identified candidate PC biomarker HIST1H4K.We investigated DNA methylation of HIST1H4K in urine samples from 57 PC patients, 29 controls with benign prostatic hyperplasia (BPH) and 50 young asymptomatic men (YAM) by MethyLight real-time PCR.The frequency of HIST1H4K promoter hypermethylation significantly discriminated PC patients from YAM (AUC =0.763; 95% CI 0.672-0.839; p0.0001), but did not show any statistical difference between PC patients and BPH controls (AUC=0.513, 95% CI 0.402-0.622; p=0.8255). HIST1H4K could not outperform the prostatic specific antigen (PSA) in our sample (AUC=0.785; 95% CI 0.679-0.870; p0.0001). Methylation of HIST1H4K showed significant correlation with aging (r=0.5418; p0.0001), but with no other clinicopathological characteristics.The results suggest that the promoter hypermethylation of HIST1H4K is rather due to aging than related to prostate carcinogenesis. To elucidate this observation analysis of larger samples is needed.
39. 154 - Targeted next generation sequencing of Bulgarian prostate cancer patients finds new somatic mutations and reflects disease heterogeneity.
- Author
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Kachakova, D., Vlahova, A., Mihova, K., Mitkova, A., Popov, I., Popov, E., Christova, S., Slavov, C., Mitev, V., and Kaneva, R.
- Subjects
- *
GENETIC mutation , *SEQUENCE analysis , *BULGARIANS , *CANCER patients , *PROSTATE tumors - Published
- 2016
- Full Text
- View/download PDF
40. 176 MORPHOMETRIC ASSESSMENT OF TISSUES IN RECONSTRUCTIVE SURGERY OF STRICTURES OF THE MALE URETHRA
- Author
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Mateev, D., Sarachev, A., Shishkov, D., Belovejdov, V., Slavov, C., and Popov, E.
- Published
- 2008
- Full Text
- View/download PDF
41. Contemporary Molecular Markers for Predicting Systemic Treatment Response in Urothelial Bladder Cancer: A Narrative Review.
- Author
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Dimitrov G, Mangaldzhiev R, Slavov C, and Popov E
- Abstract
The search for dependable molecular biomarkers to enhance routine clinical practice is a compelling challenge across all oncology fields. Urothelial bladder carcinoma, known for its significant heterogeneity, presents difficulties in predicting responses to systemic therapies and outcomes post-radical cystectomy. Recent advancements in molecular cancer biology offer promising avenues to understand the disease's biology and identify emerging predictive biomarkers. Stratifying patients based on their recurrence risk post-curative treatment or predicting the efficacy of conventional and targeted therapies could catalyze personalized treatment selection and disease surveillance. Despite progress, reliable molecular biomarkers to forecast responses to systemic agents, in neoadjuvant, adjuvant, or palliative treatment settings, are still lacking, underscoring an urgent unmet need. This review aims to delve into the utilization of current and emerging molecular signatures across various stages of urothelial bladder carcinoma to predict responses to systemic therapy.
- Published
- 2024
- Full Text
- View/download PDF
42. Wavelength Selective Photocontrol of Hybrid Azobenzene-Spiropyran Photoswitches with Overlapping Chromophores.
- Author
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Saßmannshausen T, Kunz A, Oberhof N, Schneider F, Slavov C, Dreuw A, Wachtveitl J, and Wegner HA
- Abstract
Compounds with multiple photoswitching units are appealing for complex photochemical control of molecular materials and nanostructures. Herein, we synthesized novel meta- and para- connected (related to the nitrogen of the indoline) azobenzene-spiropyran dyads, in which the central benzene unit is shared by both switches. We investigated their photochemistry using static and time-resolved transient absorption spectroscopy as well as quantum chemical calculations. In the meta-compound, the individual components are photochemically decoupled due to the meta-pattern. In the para-compound the spiro-connectivity leads to a bifunctional photoswitchable system with a red-shifted absorption. The azobenzene and the spiropyran can thus be addressed and switched independently by light of appropriate wavelength. Through the different connectivity patterns two different orthogonally photoswitchable systems have been obtained which are promising candidates for complex applications of light control., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
- Published
- 2024
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43. Precision Medicine in Castration-Resistant Prostate Cancer: Advances, Challenges, and the Landscape of PARPi Therapy-A Narrative Review.
- Author
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Dimitrov G, Mangaldzhiev R, Slavov C, and Popov E
- Subjects
- Male, Female, Humans, Poly(ADP-ribose) Polymerase Inhibitors pharmacology, Poly(ADP-ribose) Polymerase Inhibitors therapeutic use, Precision Medicine, BRCA2 Protein genetics, Poly(ADP-ribose) Polymerases, BRCA1 Protein genetics, Prostatic Neoplasms, Castration-Resistant drug therapy, Prostatic Neoplasms, Castration-Resistant genetics, Prostatic Neoplasms, Castration-Resistant pathology
- Abstract
After recent approvals, poly-adenosine diphosphate [ADP]-ribose polymerase inhibitors (PARPis) have emerged as a frontline treatment for metastatic castration-resistant prostate cancer (mCRPC). Unlike their restricted use in breast or ovarian cancers, where approval is limited to those with BRCA1/2 alterations, PARPis in mCRPC are applied across a broader spectrum of genetic aberrations. Key findings from the phase III PROPEL trial suggest that PARPis' accessibility may broaden, even without mandatory testing. An increasing body of evidence underscores the importance of distinct alterations in homologous recombination repair (HRR) genes, revealing unique sensitivities to PARPis. Nonetheless, despite the initial effectiveness of PARPis in treating BRCA-mutated tumors, resistance to therapy is frequently encountered. This review aims to discuss patient stratification based on biomarkers and genetic signatures, offering insights into the nuances of first-line PARPis' efficacy in the intricate landscape of mCRPC.
- Published
- 2024
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- View/download PDF
44. Enhancing the Potential of Fused Heterocycle-Based Triarylhydrazone Photoswitches.
- Author
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Hegedüsová L, Blaise N, Pašteka LF, Budzák Š, Medved' M, Filo J, Mravec B, Slavov C, Wachtveitl J, Grabarz AM, and Cigáň M
- Abstract
Invited for the cover of this issue are Marek Cigáň, Anna M. Grabarz and co-workers. The image depicts how a non-expert might imagine a "molecular photoswitch". Read the full text of the article at 10.1002/chem.202303509., (© 2024 Wiley-VCH GmbH.)
- Published
- 2024
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45. Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants.
- Author
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Wang A, Shen J, Rodriguez AA, Saunders EJ, Chen F, Janivara R, Darst BF, Sheng X, Xu Y, Chou AJ, Benlloch S, Dadaev T, Brook MN, Plym A, Sahimi A, Hoffman TJ, Takahashi A, Matsuda K, Momozawa Y, Fujita M, Laisk T, Figuerêdo J, Muir K, Ito S, Liu X, Uchio Y, Kubo M, Kamatani Y, Lophatananon A, Wan P, Andrews C, Lori A, Choudhury PP, Schleutker J, Tammela TLJ, Sipeky C, Auvinen A, Giles GG, Southey MC, MacInnis RJ, Cybulski C, Wokolorczyk D, Lubinski J, Rentsch CT, Cho K, Mcmahon BH, Neal DE, Donovan JL, Hamdy FC, Martin RM, Nordestgaard BG, Nielsen SF, Weischer M, Bojesen SE, Røder A, Stroomberg HV, Batra J, Chambers S, Horvath L, Clements JA, Tilly W, Risbridger GP, Gronberg H, Aly M, Szulkin R, Eklund M, Nordstrom T, Pashayan N, Dunning AM, Ghoussaini M, Travis RC, Key TJ, Riboli E, Park JY, Sellers TA, Lin HY, Albanes D, Weinstein S, Cook MB, Mucci LA, Giovannucci E, Lindstrom S, Kraft P, Hunter DJ, Penney KL, Turman C, Tangen CM, Goodman PJ, Thompson IM Jr, Hamilton RJ, Fleshner NE, Finelli A, Parent MÉ, Stanford JL, Ostrander EA, Koutros S, Beane Freeman LE, Stampfer M, Wolk A, Håkansson N, Andriole GL, Hoover RN, Machiela MJ, Sørensen KD, Borre M, Blot WJ, Zheng W, Yeboah ED, Mensah JE, Lu YJ, Zhang HW, Feng N, Mao X, Wu Y, Zhao SC, Sun Z, Thibodeau SN, McDonnell SK, Schaid DJ, West CML, Barnett G, Maier C, Schnoeller T, Luedeke M, Kibel AS, Drake BF, Cussenot O, Cancel-Tassin G, Menegaux F, Truong T, Koudou YA, John EM, Grindedal EM, Maehle L, Khaw KT, Ingles SA, Stern MC, Vega A, Gómez-Caamaño A, Fachal L, Rosenstein BS, Kerns SL, Ostrer H, Teixeira MR, Paulo P, Brandão A, Watya S, Lubwama A, Bensen JT, Butler EN, Mohler JL, Taylor JA, Kogevinas M, Dierssen-Sotos T, Castaño-Vinyals G, Cannon-Albright L, Teerlink CC, Huff CD, Pilie P, Yu Y, Bohlender RJ, Gu J, Strom SS, Multigner L, Blanchet P, Brureau L, Kaneva R, Slavov C, Mitev V, Leach RJ, Brenner H, Chen X, Holleczek B, Schöttker B, Klein EA, Hsing AW, Kittles RA, Murphy AB, Logothetis CJ, Kim J, Neuhausen SL, Steele L, Ding YC, Isaacs WB, Nemesure B, Hennis AJM, Carpten J, Pandha H, Michael A, De Ruyck K, De Meerleer G, Ost P, Xu J, Razack A, Lim J, Teo SH, Newcomb LF, Lin DW, Fowke JH, Neslund-Dudas CM, Rybicki BA, Gamulin M, Lessel D, Kulis T, Usmani N, Abraham A, Singhal S, Parliament M, Claessens F, Joniau S, Van den Broeck T, Gago-Dominguez M, Castelao JE, Martinez ME, Larkin S, Townsend PA, Aukim-Hastie C, Bush WS, Aldrich MC, Crawford DC, Srivastava S, Cullen J, Petrovics G, Casey G, Wang Y, Tettey Y, Lachance J, Tang W, Biritwum RB, Adjei AA, Tay E, Truelove A, Niwa S, Yamoah K, Govindasami K, Chokkalingam AP, Keaton JM, Hellwege JN, Clark PE, Jalloh M, Gueye SM, Niang L, Ogunbiyi O, Shittu O, Amodu O, Adebiyi AO, Aisuodionoe-Shadrach OI, Ajibola HO, Jamda MA, Oluwole OP, Nwegbu M, Adusei B, Mante S, Darkwa-Abrahams A, Diop H, Gundell SM, Roobol MJ, Jenster G, van Schaik RHN, Hu JJ, Sanderson M, Kachuri L, Varma R, McKean-Cowdin R, Torres M, Preuss MH, Loos RJF, Zawistowski M, Zöllner S, Lu Z, Van Den Eeden SK, Easton DF, Ambs S, Edwards TL, Mägi R, Rebbeck TR, Fritsche L, Chanock SJ, Berndt SI, Wiklund F, Nakagawa H, Witte JS, Gaziano JM, Justice AC, Mancuso N, Terao C, Eeles RA, Kote-Jarai Z, Madduri RK, Conti DV, and Haiman CA
- Subjects
- Humans, Male, Black People genetics, Genome-Wide Association Study, Hispanic or Latino genetics, Polymorphism, Single Nucleotide, Risk Factors, White People genetics, Asian People genetics, Genetic Predisposition to Disease, Prostatic Neoplasms genetics
- Abstract
The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Published
- 2023
- Full Text
- View/download PDF
46. Conserved tyrosine in phytochromes controls the photodynamics through steric demand and hydrogen bonding capabilities.
- Author
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Fischer T, Köhler L, Engel PD, Song C, Gärtner W, Wachtveitl J, and Slavov C
- Subjects
- Tyrosine, Hydrogen Bonding, Spectrum Analysis, Phytochrome genetics, Phytochrome metabolism, Biochemical Phenomena
- Abstract
Using ultrafast spectroscopy and site-specific mutagenesis, we demonstrate the central role of a conserved tyrosine within the chromophore binding pocket in the forward (P
r → Pfr ) photoconversion of phytochromes. Taking GAF1 of the knotless phytochrome All2699g1 from Nostoc as representative member of phytochromes, it was found that the mutations have no influence on the early (<30 ps) dynamics associated with conformational changes of the chromophore in the excited state. Conversely, they drastically impact the extended protein-controlled excited state decay (>100 ps). Thus, the steric demand, position and H-bonding capabilities of the identified tyrosine control the chromophore photoisomerization while leaving the excited state chromophore dynamics unaffected. In effect, this residue operates as an isomerization-steric-gate that tunes the excited state lifetime and the photoreaction efficiency by modulating the available space of the chromophore and by stabilizing the primary intermediate Lumi-R. Understanding the role of such a conserved structural element sheds light on a key aspect of phytochrome functionality and provides a basis for rational design of optimized photoreceptors for biotechnological applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)- Published
- 2023
- Full Text
- View/download PDF
47. Watching the release of a photopharmacological drug from tubulin using time-resolved serial crystallography.
- Author
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Wranik M, Weinert T, Slavov C, Masini T, Furrer A, Gaillard N, Gioia D, Ferrarotti M, James D, Glover H, Carrillo M, Kekilli D, Stipp R, Skopintsev P, Brünle S, Mühlethaler T, Beale J, Gashi D, Nass K, Ozerov D, Johnson PJM, Cirelli C, Bacellar C, Braun M, Wang M, Dworkowski F, Milne C, Cavalli A, Wachtveitl J, Steinmetz MO, and Standfuss J
- Subjects
- Crystallography, Ligands, Crystallography, X-Ray, Tubulin metabolism, Microtubules metabolism
- Abstract
The binding and release of ligands from their protein targets is central to fundamental biological processes as well as to drug discovery. Photopharmacology introduces chemical triggers that allow the changing of ligand affinities and thus biological activity by light. Insight into the molecular mechanisms of photopharmacology is largely missing because the relevant transitions during the light-triggered reaction cannot be resolved by conventional structural biology. Using time-resolved serial crystallography at a synchrotron and X-ray free-electron laser, we capture the release of the anti-cancer compound azo-combretastatin A4 and the resulting conformational changes in tubulin. Nine structural snapshots from 1 ns to 100 ms complemented by simulations show how cis-to-trans isomerization of the azobenzene bond leads to a switch in ligand affinity, opening of an exit channel, and collapse of the binding pocket upon ligand release. The resulting global backbone rearrangements are related to the action mechanism of microtubule-destabilizing drugs., (© 2023. The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
48. Influence of the PHY domain on the ms-photoconversion dynamics of a knotless phytochrome.
- Author
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Fischer T, Köhler L, Ott T, Song C, Wachtveitl J, and Slavov C
- Subjects
- Bacterial Proteins chemistry, Protein Binding, Nostoc metabolism, Phytochrome chemistry
- Abstract
The ability of some knotless phytochromes to photoconvert without the PHY domain allows evaluation of the distinct effect of the PHY domain on their photodynamics. Here, we compare the ms dynamics of the single GAF domain (g1) and the GAF-PHY (g1g2) construct of the knotless phytochrome All2699 from cyanobacterium Nostoc punctiforme. While the spectral signatures and occurrence of the intermediates are mostly unchanged by the domain composition, the presence of the PHY domain slows down the early forward and reverse dynamics involving chromophore and protein binding pocket relaxation. We assign this effect to a more restricted binding pocket imprinted by the PHY domain. The photoproduct formation is also slowed down by the presence of the PHY domain but to a lesser extent than the early dynamics. This indicates a rate limiting step within the GAF and not the PHY domain. We further identify a pH dependence of the biphasic photoproduct formation hinting towards a pKa dependent tuning mechanism. Our findings add to the understanding of the role of the individual domains in the photocycle dynamics and provide a basis for engineering of phytochromes towards biotechnological applications., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
49. The Voltage Dependent Sidedness of the Reprotonation of the Retinal Schiff Base Determines the Unique Inward Pumping of Xenorhodopsin.
- Author
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Weissbecker J, Boumrifak C, Breyer M, Wießalla T, Shevchenko V, Mager T, Slavov C, Alekseev A, Kovalev K, Gordeliy V, Bamberg E, and Wachtveitl J
- Subjects
- Electric Conductivity, Hydrogen-Ion Concentration, Kinetics, Light, Optogenetics, Proton Pumps chemistry, Protons, Rhodopsins, Microbial chemistry, Spectrophotometry, Temperature, Proton Pumps metabolism, Rhodopsins, Microbial metabolism, Schiff Bases chemistry
- Abstract
The new class of microbial rhodopsins, called xenorhodopsins (XeRs),
[1] extends the versatility of this family by inward H+ pumps.[2-4] These pumps are an alternative optogenetic tool to the light-gated ion channels (e.g. ChR1,2), because the activation of electrically excitable cells by XeRs is independent from the surrounding physiological conditions. In this work we functionally and spectroscopically characterized XeR from Nanosalina (NsXeR).[1] The photodynamic behavior of NsXeR was investigated on the ps to s time scale elucidating the formation of the J and K and a previously unknown long-lived intermediate. The pH dependent kinetics reveal that alkalization of the surrounding medium accelerates the photocycle and the pump turnover. In patch-clamp experiments the blue-light illumination of NsXeR in the M state shows a potential-dependent vectoriality of the photocurrent transients, suggesting a variable accessibility of reprotonation of the retinal Schiff base. Insights on the kinetically independent switching mechanism could furthermore be obtained by mutational studies on the putative intracellular H+ acceptor D220., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)- Published
- 2021
- Full Text
- View/download PDF
50. Ultrafast Photoconversion Dynamics of the Knotless Phytochrome Syn Cph2.
- Author
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Fischer T, van Wilderen LJGW, Gnau P, Bredenbeck J, Essen LO, Wachtveitl J, and Slavov C
- Subjects
- Kinetics, Light, Models, Molecular, Photoreceptors, Microbial chemistry, Photoreceptors, Microbial metabolism, Protein Conformation, Spectrum Analysis, Structure-Activity Relationship, Photochemical Processes, Phytochrome chemistry, Phytochrome metabolism
- Abstract
The family of phytochrome photoreceptors contains proteins with different domain architectures and spectral properties. Knotless phytochromes are one of the three main subgroups classified by their distinct lack of the PAS domain in their photosensory core module, which is in contrast to the canonical PAS-GAF-PHY array. Despite intensive research on the ultrafast photodynamics of phytochromes, little is known about the primary kinetics in knotless phytochromes. Here, we present the ultrafast P
r ⇆ Pfr photodynamics of Syn Cph2, the best-known knotless phytochrome. Our results show that the excited state lifetime of Pr * (~200 ps) is similar to bacteriophytochromes, but much longer than in most canonical phytochromes. We assign the slow Pr * kinetics to relaxation processes of the chromophore-binding pocket that controls the bilin chromophore's isomerization step. The Pfr photoconversion dynamics starts with a faster excited state relaxation than in canonical phytochromes, but, despite the differences in the respective domain architectures, proceeds via similar ground state intermediate steps up to Meta-F. Based on our observations, we propose that the kinetic features and overall dynamics of the ultrafast photoreaction are determined to a great extent by the geometrical context (i.e., available space and flexibility) within the binding pocket, while the general reaction steps following the photoexcitation are most likely conserved among the red/far-red phytochromes.- Published
- 2021
- Full Text
- View/download PDF
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