María de Lourdes Girard Cuesy

Biología de Sistemas y Biología Sintética Investigador

Inv. Tit. B T.C. Definitivo

Semblanza

La Dra. María de Lourdes Girard Cuesy es Bióloga Experimental por la Universidad Autónoma Metropolitana-Iztapalapa. Se graduó de Maestría y Doctorado en Investigación Biomédica Básica en la UNAM.
Desde hace 20 años es investigadora de la UNAM. Su labor de investigación se ha centrado en el campo de la genética molecular bacteriana, enfocándose principalmente en las bacterias fijadoras de nitrógeno conocidas como Rhizobia, que establecen simbiosis con plantas leguminosas. El establecimiento del mapa físico del plásmido simbiótico de R. etli CFN42 así como el análisis de su actividad transcripcional son trabajos pioneros en el campo de la Rhizobiología en cuanto a la caracterización estructural y funcional de un replicón completo antes de la era genómica. Sus principales contribuciones se enmarcan en la regulación transcripcional y el análisis de las redes funcionales esenciales para el control de la fijación de nitrógeno en respuesta a estímulos ambientales como el oxígeno y los estreses abióticos. Empleando diferentes enfoques experimentales tanto de genética y biología molecular como de genómica, ha elucidado las complejas redes regulatorias caracterizando sus distintos componentes principalmente en la bacteria R. etli (simbionte del frijol) , contribuyendo a entender lo que la hace particular y diferente de otras bacterias de su género. Recientemente, ha extendido sus intereses al estudio global de la expresión transcripcional, tanto bacteriana como vegetal, utilizando cepas de R. etli que le confieren ventajas a la simbiosis Rhizobium-frijol.
El grupo de la Dra. Girard mantiene exitosas colaboraciones académicas con la mayoría de los grupos de investigación del CCG y con otras entidades nacionales y extranjeras. Su trabajo ha sido apoyado a través de diferentes donativos nacionales de investigación (DGAPA-PAPIIT y CONACYT), así como por convenios de intercambio académico con el extranjero. Es tutora de estudiantes Tesistas de Licenciatura y de Posgrado y asesora a posdoctorales internacionales.

Ligas

OrcID
Scopus

Teléfono: (777) 3291686
Correo: girard@ccg.unam.mx

Publicaciones

AñoPublicaciónPMID
2019Hidalgo-Garcia, A, Torres, M, Sales, A, Bedmar, E, Girard, L, Delgado, M. (2019). "Rhizobium etli Produces Nitrous Oxide by Coupling the Assimilatory and Denitrification Pathways". Frontiers in Microbiology. 10():980-980. [doi:10.3389/fmicb.2019.00980]31134023
2019Bañuelos-Vazquez, L, Torres Tejerizo, G, Cervantes-De La Luz, L, Girard, L, Romero, D, Brom, S. (2019). "Conjugative transfer between Rhizobium etli endosymbionts inside the root nodule". Environmental Microbiology. ():-. [doi:10.1111/1462-2920.14645]
2018Isidra-Arellano, M, Reyero-Saavedra, M, Sánchez-Correa, M, Pingault, L, Sen, S, Joshi, T, Girard, L, Castro-Guerrero, N, Mendoza-Cozatl, D, Libault, M, Valdés-López, O. (2018). "Phosphate deficiency negatively affects early steps of the symbiosis between common bean and Rhizobia". Genes. 9(10):498-. [doi:10.3390/genes9100498]30326664
2018Aguilar A, Mora Y, Dávalos A, Girard L, Mora J, Peralta H. (2018). "Analysis of genome sequence and symbiotic ability of rhizobial strains isolated from seeds of common bean (Phaseolus vulgaris).". Bmc Genomics. 19(1):645-645. [doi:10.1186/s12864-018-5023-0]30165827
2018Chiozzotto, R, Ramirez, M, Talbi, C, Cominelli, E, Girard, L, Sparvoli, F, Hernandez, G. (2018). "Characterization of the symbiotic nitrogen-fixing common bean Low Phytic Acid (lpa1) mutant response to water stress". Genes. 9(2):99-. [doi:10.3390/genes9020099]29462877
2017Vargas-Lagunas, C, Mora, Y, Diaz, R, Martinez-Batallar, G, Girard, L, Encarnacion, S, Peralta, H, Mora, J. (2017). "Overproduction of Sinorhizobium meliloti argC (N-acetyl-gamma-glutamyl phosphate reductase) promotes growth delay and inefficient nodules". Fems Microbiology Letters. 364(23):fnx233-. [doi:10.1093/femsle/fnx233]29121239
2016Aguilar A, Peralta H, Mora Y, Díaz R, Vargas-Lagunas C, Girard L, Mora J. (2016). "Genomic comparison of Agrobacterium Pusense strains isolated from bean nodules". Frontiers in Microbiology. 7(OCT):1720-1720. [doi:10.3389/fmicb.2016.01720]27833604
2016Peralta H, Aguilar A, Díaz R, Mora Y, Martínez-Batallar G, Salazar E, Vargas-Lagunas C, Martínez E, Encarnación S, Girard L, Mora J. (2016). "Genomic studies of nitrogen-fixing rhizobial strains from Phaseolus vulgaris seeds and nodules". Bmc Genomics. 17(1):1-1. [doi:10.1186/s12864-016-3053-z]27601031
2016Reyes-Gonzalez, A, Talbi, C, Rodriguez, S, Rivera, P, Zamorano-Sanchez, D, Girard, L. (2016). "Expanding the regulatory network that controls nitrogen fixation in Sinorhizobium meliloti: elucidating the role of the two-component system hFixL-FxkR". MICROBIOLOGY-UK. 162(6):979-988. [doi:10.1099/mic.0.000284]27010660
2015Hernandez, V, Girard, L, Hernandez-Lucas, I, Vazquez, A, Ortiz-Ortiz, C, Diaz, R, Dunn, M. (2015). "Genetic and biochemical characterization of arginine biosynthesis in Sinorhizobium meliloti 1021". MICROBIOLOGY-UK. 161(8):1671-1682. [doi:10.1099/mic.0.000122]26271664
2015Girard Cuesy, M, Zamorano Sánchez, D. (2015). "Fnr - like proteins in Rhizobia: past and future". Biological Nitrogen Fixation. 1():155-166. [doi:10.1002/9781119053095]
2015Nova-Franco B, Íñiguez LP, Valdés-López O, Alvarado-Affantranger X, Leija A, Fuentes SI, Ramírez M, Paul S, Reyes JL, Girard L, Hernández G. (2015). "The Micro-RNA172c-APETALA2-1 Node as a Key Regulator of the Common Bean-Rhizobium etli Nitrogen Fixation Symbiosis". Plant Physiology. 168(1):273-502. [doi:10.1104/pp.114.255547]25739700
2015Zamorano-Sanchez, D, Girard, L. (2015). "Fnr-Like Proteins in Rhizobia: Past and Future". Biological Nitrogen Fixation, Vols 1 And 2. ():155-165.
2014Mora, Y, Diaz, R, Vargas-Lagunas, C, Peralta, H, Guerrero, G, Aguilar, A, Encarnacion, S, Girard, L, Mora, J. (2014). "Nitrogen-fixing rhizobial strains isolated from common bean seeds: Phylogeny, physiology, and genome analysis". Applied And Environmental Microbiology. 80(18):5644-5654. [doi:10.1128/AEM.01491-14]25002426
2014Garcia-Garcia, J, Girard Cuesy, M, Hernández Delgado, G, Saavedra, E, Pardo, J, Rodríguez-Zavala, J, Encalada, R, Reyes-Prieto, A, Mendoza-Cozatl, D, Moreno-Sánchez, R. (2014). "Zn-bis-glutathionate is the best co-substrate of the monomeric phytochelatin synthase from the photosynthetic heavy metal-hyperaccumulator Euglena Gracilis". Metallomics. 6(3):604-616. [doi:10.1039/c3mt00313b]24464102
2013Ramírez Yáñez, M, Guillén, G, Fuentes Membreño, S, Iñiguez Rabago, L, Aparicio Fabre, R, Zamorano Sánchez, D, Encarnación Guevara, S, Panzeri, D, Castiglioni, B, Cremonesi, P, Strozzi, F, Stella, A, Girard Cuesy, M, Sparvoli, F, Hernández Delgado, G. (2013). "Transcript profiling of common bean nodules subjected to oxidative stress". Physiologia Plantarum. 149(3):389-407. [doi:10.1111/ppl.12040]23432573
2013Reyes González, A, Zamorano Sánchez, D, Rivera Rosas, P, Girard Cuesy, M. (2013). "hFixL-FxkR are the key regulators for fixKf-related gene expression". Mexican Journal of Scientific Research. ():-.
2013Ramírez Yáñez, M, Flores-Pacheco, G, Reyes, J, Álvarez, A, Drevon, J, Girard Cuesy, M, Hernández Delgado, G. (2013). "Two Common Bean Genotypes with Contrasting Response to Phosphorus Deficiency Show Variations in the microRNA 399-Mediated PvPHO2 Regulation within the PvPHR1 Signaling Pathway". International Journal Of Molecular Sciences. 14(4):8328-8344. [doi:10.3390/ijms14048328]23591845
2013Aparicio Fabre, R, Guillén, G, Loredo, M, Arellano García, J, Valdes López, O, Ramírez Yáñez, M, Iñiguez Rabago, L, Panzeri, D, Castiglioni, B, Cremonesi, P, Strozzi, F, Stella, A, Girard Cuesy, M, Sparvoli, F, Hernández Delgado, G. (2013). "Common bean (Phaseolus vulgaris L.) PvTIFY orchestrates global changes in transcript profile response to jasmonate and phosphorus deficiency". Bmc Plant Biology. 13():26-26. [doi:10.1186/1471-2229-13-26]23402340
2012Zamorano Sánchez, D, Reyes-González, A, Gómez Hernández, N, Rivera, P, Georgellis, D, Girard Cuesy, M. (2012). "FxkR Provides the Missing Link in the fixL-fixK Signal Transduction Cascade in Rhizobium etli CFN42". Molecular Plant-Microbe Interactions. 25(11):1506-1517. [doi:10.1094/MPMI-05-12-0136-R]22809273
2012García-García, J, Olin-Sandoval, V, Saavedra, E, Girard Cuesy, M, Hernández Delgado, G, Moreno-Sánchez, R. (2012). "Sulfate uptake in photosynthetic Euglena Gracilis. Mechanisms of regulation and contribution to cysteine homeostasis". Biochimica Et Biophysica Acta-General Subjects. 1820(10):1567-1575. [doi:10.1016/j.bbagen.2012.05.002]22609877
2012Talbi, C, Sánchez, C, Hidalgo-García, A, González, E, Arrese-Igor, C, Girard Cuesy, M, Bedmar, E, Delgado, M. (2012). "Enhanced expression of Rhizobium etli cbb(3) oxidase improves drought tolerance of common bean symbiotic nitrogen fixation". Journal Of Experimental Botany. 63(14):5035-5043. [doi:10.1093/jxb/ers101]22511804
2011Cervantes de la Luz, L, Bustos Arcos, V, Girard Cuesy, M, Santamaria Gutiérrez, R, Dávila Ramos, J, Vinuesa Fleischmann, P, Romero Camarena, D, Brom Klanner, S. (2011). "The conjugative plasmid of a bean-nodulating Sinorhizobium fredii strain is assembled from sequences of two Rhizobium plasmids and the chromosome of a Sinorhizobium strain". Bmc Microbiology. 11(1):1-11. [doi:10.1186/1471-2180-11-149]21702991
2011Gómez Hernández, N, Reyes González, A, Sanchez, C, Pérez-Tejada Domínguez, Y, Delgado, M, Girard Cuesy, M. (2011). "Regulation and Symbiotic Role of nirK and norC Expression in Rhizobium etli". Molecular Plant-Microbe Interactions. 24(2):233-245. [doi:10.1094/MPMI-07-10-0173]21043576
2011Díaz Mendez, R, Vargas Lagunas, M, Villalobos López, M, Peralta Díaz, H, Pérez-Tejada Domínguez, Y, Encarnación Guevara, S, Girard Cuesy, M, Mora Celis, J. (2011). "argC orthologs from Rhizobiales show diverse profiles of transcriptional efficiency and functionality in Sinorhizobium meliloti". Journal Of Bacteriology. 193(2):460-472. [doi:10.1128/JB.01010-10]21075924
2010Talbi, C, Delgado, M, Girard, L, Ramirez-Trujillo, A, Caballero-Mellado, J, Bedmar, E. (2010). "Burkholderia Phymatum Strains Capable of Nodulating Phaseolus vulgaris Are Present in Moroccan Soils". Applied And Environmental Microbiology. 76(13):4587-4591. [doi:10.1128/AEM.02886-09]20472732
2010Sanchez, C, Gates, A, Meakin, G, Uchiumi, T, Girard, L, Richardson, D, Bedmar, E, Delgado, M. (2010). "Production of Nitric Oxide and Nitrosylleghemoglobin Complexes in Soybean Nodules in Response to Flooding". Molecular Plant-Microbe Interactions. 23(5):702-711. [doi:10.1094/MPMI-23-5-0702]20367476
2010Talbi, C, Sánchez, C, Girard Cuesy, M, Bedmar, E, Delgado, M. (2010). "La sobreexpresión de la oxidasa cbb3 de Rhizobium etli incrementa la tolerancia de Phaseolus vulgaris a la sequía". Avances en el metabolismo del Nitrógeno. ():223-228.
2009Onofre-Lemus, J, Hernandez-Lucas, I, Girard, L, Caballero-Mellado, J. (2009). "ACC (1-Aminocyclopropane-1-Carboxylate) Deaminase Activity, a Widespread Trait in Burkholderia Species, and Its Growth-Promoting Effect on Tomato Plants". Applied And Environmental Microbiology. 75(20):6581-6590. [doi:10.1128/AEM.01240-09]19700546
2008Valdes-Lopez, O, Arenas-Huertero, C, Ramirez, M, Girard, L, Sanchez, F, Vance, C, Reyes, J, Hernandez, G. (2008). "Essential role of MYB transcription factor: PvPHR1 and microRNA: PvmiR399 in phosphorus-deficiency signalling in common bean roots". Plant Cell And Environment. 31(12):1834-1843. [doi:10.1111/j.1365-3040.2008.01883.x]18771575
2008Vargas, M, Villalobos, M, Diaz, R, Flores, M, Contreras, S, Encarnacion, S, Mora, Y, Dunn, M, Girard, L, Mora, J. (2008). "COMPARATIVE ANALYSIS OF argC PROTEIN EXPRESSION IN Rhizobium SPECIES". Biological Nitrogen Fixation: Towards Poverty Alleviation Through Sustainable Agriculture. 42():239-240.
2007Granados Baeza, M, Gómez Hernández, N, Mora, Y, Delgado, M, Romero Camarena, D, Girard Cuesy, M. (2007). "Novel reiterated Fnr-type proteins control the production of the symbiotic terminal oxidase cbb3 in Rhizobium etli CFN42". Molecular Plant-Microbe Interactions. 20(10):1241-1249. [doi:10.1094/MPMI-20-10-1241]17918626
2007Flores López, M, Morales Reyes, L, Gonzaga Jáuregui, C, Domínguez Vidaña, R, Zepeda Mendoza, C, Yáñez Cuna, J, Gutiérrez Arcelus, M, Lemus Vergara, T, Valle García, D, Ávila Arcos, M, Blanco Melo, D, Medina Ruiz, S, Meza Sosa, K, Ayala Ortega, E, García Alonso, D, Bustos Arcos, V, González Zúñiga, V, Girard Cuesy, M, Tusie-Luna, T, Dávila Ramos, J, Palacios de la Lama, R. (2007). "Recurrent DNA inversion rearrangements in the human genome". PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 104(15):6099-6106. [doi:10.1073/pnas.0701631104]17389356
2005Bueno, E, Gomez-Hernandez, N, Girard, L, Bedmar, E, Delgado, M. (2005). "Function of the Rhizobium etli CFN42 nirK gene in nitrite metabolism". BIOCHEMICAL SOCIETY TRANSACTIONS. 33(1):162-163. [doi:10.1042/BST0330162]15667294
2005Vargas Lagunas, M, Encarnación Guevara, S, Girard Cuesy, M, Reyes Pérez, A, Pérez-Tejada Domínguez, Y, Mora Celis, J. (2005). "Characterization of the alternative protection programs against oxidative-stress in free life and simbiosis from Rhizobium etli". Current Plant Science and Biotechnology. Agriculture Biological Nitrogen Fixation, Sustainable Agriculture and the Environment. 41():331-.
2005Vargas, M, Encarnacion, S, Girard, M, Reyes, A, Mora, Y, Mora, J. (2005). "Characterization of the alternative protection programs against oxidative-stress in free life and symbiosis from Rhizobium etli". Biological Nitrogen Fixation, Sustainable Agriculture And The Environment. 41():331-331.
2004Brom Klanner, S, Girard Cuesy, M, Tun Garrido, C, García de los Santos, A, Bustos Arcos, V, González Zúñiga, V, Romero Camarena, D. (2004). "Transfer of the symbiotic plasmid of Rhizobium etli CFN42 requires cointegration with p42a, which may be mediated by site-specific recombination". Journal Of Bacteriology. 186(22):7538-7548. [doi:10.1128/JB.186.22.7538-7548.2004]15516565
2004Vargas, M, Encarnacin, S, Girard, M, Reyes, A, Mora, Y, Mora, J. (2004). "Physiological and proteome characterizations of oxidative-stress response in Rhizobium etli during free life and symbiosis with Phaseolus vulgaris.". MOLECULAR & CELLULAR PROTEOMICS. 3(10, S):160-160.
2003González Zúñiga, V, Bustos Arcos, V, Ramírez Romero, M, Medrano Soto, L, Salgado Osorio, H, Hernández González, I, Hernández Celis, J, Quintero Hernández, V, Moreno Hagelsieb, G, Girard Cuesy, M, Rodríguez Sánchez, O, Flores López, M, Cevallos Gaos, M, Collado Vides, P, Romero Camarena, D, Dávila Ramos, J. (2003). "The mosaic structure of the symbiotic plasmid of Rhizobium etli CFN42 and its relation to other symbiotic genome compartments.". Genome Biology. 4(6):R36-. [doi:10.1186/gb-2003-4-6-r36]12801410
2002Brom Klanner, S, Girard Cuesy, M, García de los Santos, A, Sanjuan-Pinilla, J, Olivares, J, Sanjuan, J. (2002). "Conservation of plasmid-encoded traits among bean-nodulating Rhizobium species". Applied And Environmental Microbiology. 68(5):2555-2561. [doi:10.1128/AEM.68.5.2555-2561.2002]11976134
2001López, O, Morera, C, Miranda-Ríos, J, Girard Cuesy, M, Romero Camarena, D, Soberón Chávez, M. (2001). "Regulation of gene expression in response to oxygen in Rhizobium etli: Role of FnrN in fixNOQP expression and in symbiotic nitrogen fixation". Journal Of Bacteriology. 183(24):6999-7006. [doi:10.1128/JB.183.24.6999-7006.2001]11717256
2000Girard Cuesy, M, Brom Klanner, S, Dávalos Rodríguez, A, López, O, Soberón Chávez, M, Romero Camarena, D. (2000). "Differential regulation of fixN-reiterated genes in Rhizobium etli by a novel fixL-fixK cascade". Molecular Plant-Microbe Interactions. 13(12):1283-1292. [doi:10.1094/MPMI.2000.13.12.1283]11106020
2000Reyes, J, Tabche, M, Morera, C, Girard Cuesy, M, Romero Camarena, D, Krol, E, Miranda, J, Soberón Chávez, M. (2000). "Expression pattern of Rhizobium etli ccmIEFH genes involved in c-type cytochrome maturation". Gene. 250(1-2):149-157. [doi:10.1016/S0378-1119(00)00176-1]10854788
1999Soberon, M, Lopez, O, Morera, C, Girard, M, Tabche, M, Miranda, J. (1999). "Enhanced nitrogen fixation in a Rhizobium etli ntrC mutant that overproduces the Bradyrhizobium japonicum symbiotic terminal oxidase cbb(3)". Applied And Environmental Microbiology. 65(5):2015-2019. 10223993
1998Flores, M, Mavingui, P, Girard, L, Perret, X, Broughton, W, Martinez-Romero, E, Davila, G, Palacios, R. (1998). "Three replicons of Rhizobium sp. strain NGR234 harbor symbiotic gene sequences". Journal Of Bacteriology. 180(22):6052-6053. 9811668
1997RamirezRomero, M, Bustos, P, Girard, L, Rodriguez, O, Cevallos, M, Davila, G. (1997). "Sequence, localization and characteristics of the replicator region of the symbiotic plasmid of Rhizobium etli". MICROBIOLOGY-UK. 143(8):2825-2831. [doi:10.1099/00221287-143-8-2825]9274036
1996Girard, L, Valderrama, B, Palacios, R, Romero, D, Davila, G. (1996). "Transcriptional activity of the symbiotic plasmid of Rhizobium etli is affected by different environmental conditions". MICROBIOLOGY-UK. 142(10):2847-2856. [doi:10.1099/13500872-142-10-2847]
1996Valderrama, B, Davalos, A, Girard, L, Morett, E, Mora, J. (1996). "Regulatory proteins and CIS-acting elements involved in the transcriptional control of Rhizobium etli reiterated nifH genes". Journal Of Bacteriology. 178(11):3119-3126. [doi:10.1128/jb.178.11.3119-3126.1996]8655489
1995ROMERO, D, MARTINEZSALAZAR, J, GIRARD, L, BROM, S, DAVILA, G, PALACIOS, R, FLORES, M, RODRIGUEZ, C. (1995). "Discrete amplifiable regions (amplicons) in the symbiotic plasmid of Rhizobium etli CFN42". Journal Of Bacteriology. 177(4):973-980. [doi:10.1128/jb.177.4.973-980.1995]7860608
1993Flores López, M, Brom Klanner, S, Stepkowsky, T, Girard Cuesy, M, Dávila Ramos, J, Romero Camarena, D, Palacios de la Lama, R. (1993). "Gene amplification in Rhizobium: Identification and in vivo cloning of discrete amplifiable DNA regions (amplicons) from Rhizobium leguminosarum biovar phaseoli". PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 90(11):4932-4936. [doi:10.1073/pnas.90.11.4932]8506337
1991GIRARD, M, FLORES, M, BROM, S, ROMERO, D, PALACIOS, R, DAVILA, G. (1991). "Structural complexity of the symbiotic plasmid of Rhizobium leguminosarum bv. phaseoli". Journal Of Bacteriology. 173(8):2411-2419. [doi:10.1128/jb.173.8.2411-2419.1991]2013564
1991MARTINEZSALAZAR, J, ROMERO, D, GIRARD, M, DAVILA, G. (1991). "Molecular cloning and characterization of the recA gene of Rhizobium phaseoli and construction of recA mutants". Journal Of Bacteriology. 173(10):3035-3040. [doi:10.1128/jb.173.10.3035-3040.1991]2022610
1991ROMERO, D, BROM, S, MARTINEZSALAZAR, J, GIRARD, M, PALACIOS, R, DAVILA, G. (1991). "Amplification and deletion of a nod-nif region in the symbiotic plasmid of Rhizobium phaseoli". Journal Of Bacteriology. 173(8):2435-2441. [doi:10.1128/jb.173.8.2435-2441.1991]2013567
1991BROM, S, DELOSSANTOS, A, DELOURDESGIRARD, M, DAVILA, G, PALACIOS, R, ROMERO, D. (1991). "High-frequency rearrangements in Rhizobium leguminosarum bv. phaseoli plasmids". Journal Of Bacteriology. 173(3):1344-1346. [doi:10.1128/jb.173.3.1344-1346.1991]1991727
1991ROMERO, D, BROM, S, MARTINEZSALAZAR, J, GIRARD, M, FLORES, M, DURAN, L, DELOSSANTOS, A, PALACIOS, R, DAVILA, G. (1991). "GEONOMIC INSTABILITY IN Rhizobium - FRIEND OR FOE". Advances In Molecular Genetics Of Plant-Microbe Interactions, Vol 1. 10():211-214.
1985Quinto, C, de la Vega, H, Flores López, M, Leemans, J, Cevallos Gaos, M, Pardo Galván, M, Azpiroz, R, Girard Cuesy, M, Calva Mercado, E, Palacios de la Lama, R. (1985). "NITROGENASE REDUCTASE - A FUNCTIONAL MULTIGENE FAMILY IN Rhizobium-phaseoli". PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 82(4):1170-1174. [doi:10.1073/pnas.82.4.1170]16593543