Rare mutation of the PPOX gene in a patient with Porphyria Variegate: a case report in Peru

Introduction: Variegate porphyria (VP) is a rare disease, resulting from mutation of the protoporphyrinogen oxidase (PPOX) enzyme gene, and it is characterized by cutaneous manifestations and acute neuro-visceral symptoms. Case report: We describe the case of a 21-year-old woman from Peruvian highlands. The patient came to the emergency department for abdominal pain, quadriparesis and reddish urine. The patient also presented the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), motor neuropathy and respiratory failure. These clinical features were diagnosed as consequence of a porphyria crisis. The specific diagnosis was made with an elevated urinary porphobilinogen level (185.7 mg/24hours) and genetic analysis, which showed a rare pathogenic variant of the PPOX gene (nucleotide change: c.78C>A and protein change: p.Cys26*). The patient required intensive care until the administration of specific treatment with hemin. Conclusion: We report a case of VP with a pathogenic variant in the PPOX gene.Introducción: La porfiria variegada (PV) es una enfermedad rara, resultante de la mutación del gen de la enzima protoporfirinógeno oxidasa (PPOX), se caracteriza por manifestaciones cutáneas y síntomas neuroviscerales agudos. Reporte de caso: Describimos el caso de una mujer de 21 años de la sierra peruana. La paciente acudió al servicio de urgencias por dolor abdominal, cuadriparesia y orina rojiza. La paciente también presentó el síndrome de secreción inapropiada de hormona antidiurética (SIADH), neuropatía motora e insuficiencia respiratoria. Estas características clínicas fueron diagnosticadas como consecuencia de una crisis de porfiria. El diagnóstico específico se realizó con un nivel elevado de porfobilinógeno en orina (185,7 mg/24horas) y el análisis genético, evidenció un rara variante patogénica del gen PPOX (cambio de nucleótido: c.78C>A y consecuentemente cambio de proteína: p.Cys26*). La paciente requirió cuidados intensivos hasta la administración de un tratamiento específico con hemina. Conclusion: Reportamos un caso de VP con una rara variante mutagénica en el gen PPOX

COVID-19 in Latin America and the Caribbean: what is known about the status of school reopening?

Since December 2019, the world has been facing a rapid increase in cases and deaths from the new coronavirus (COVID-19), forcing a response from countries all over the world to stop its transmission. Thus, at the beginning of April, 172 nations closed their schools, affecting >84.8% (~1484 million) of students enrolled worldwide,1 aiming to reduce the exposure to the virus, a social measure previously used to control the H1N1 influenza pandemic.2Revisión por pare

Detection and identification of a novel 16SrXIII subgroup phytoplasma associated with strawberry red leaf disease in Argentina

Strawberry red leaf phytoplasma was found in strawberry plants from production fields in Lules (Tucumán province) and Bella Vista (Corrientes province), Argentina. Characteristic strawberry red leaf symptoms were stunting, young leaves with yellowing at the edges, mature leaves which curled and were reddish at the abaxial face, flower and fruit deformation and death. The pathogen was detected with phytoplasma-universal primer pairs P1/P7 followed by R16F2n/R16R2 as nested primers in 13 diseased plants. Based on RFLP and sequence analysis of the amplified 16S rRNA gene, the phytoplasma was related to the 16SrXIII group (Mexican periwinkle virescence). In silico the RFLP profile of all the samples analysed revealed the presence of a unique pattern, showing that the novel phytoplasma is different from all the phytoplasmas currently composing the 16SrXIII group. The phylogenetic analysis was consistent with RFLP analysis as the strawberry red leaf phytoplasma was grouped within the 16SrXIII group, but formed a particular cluster. On this basis, the Strawberry red leaf phytoplasma associated with strawberry red leaf disease was assigned to a new subgroup, 16SrXIII-F.Fil: Fernandez, Franco Daniel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; ArgentinaFil: Meneguzzi, Natalia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Famaillá; ArgentinaFil: Guzman, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; ArgentinaFil: Kirschbaum, Daniel Santiago. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Famaillá; ArgentinaFil: Conci, Vilma Cecilia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Nome Docampo, Claudia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; ArgentinaFil: Conci, Luis Rogelio. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; Argentina. Universidad Católica de Córdoba; Argentin

Cómo entender las medidas de efecto en la investigación clínica: Interpretación práctica y aplicación

In clinical research, assessing the association between two variables is a critical and fundamental task. Clinical studies aim to establish the effect size of the exposure to a variable on a given outcome. To measure this effect size, various statistical measures are used, among the most common are the prevalence ratio (PR), the relative risk (RR), the odds ratio (OR), the hazard ratio (HR), the incidence rate ratio (IRR), the attributable risk (AR), the number needed to treat (NNT), the mean difference (MD), and the linear regression coefficient (β). Each of these measures has its advantages and limitations, and their choice depends on the type of study and the nature of the data being analyzed. Therefore, it is important to understand the interpretation and use of each of them to perform an appropriate analysis. In this article, our goal is to explain in a practical way how to interpret these measures and how to use their p-values and 95% confidence intervals to assess statistical inference. Understanding how to evaluate the association between two variables is crucial for the design and analysis of high-quality clinical studies. This enables evidence-based decision-making and promotes improvements in patient care.En la investigación clínica, evaluar la asociación entre dos variables es una tarea crítica y fundamental. Los estudios clínicos buscan establecer el tamaño del efecto que tiene la exposición a una variable sobre un desenlace determinado. Para medir este tamaño del efecto, se utilizan diversas medidas estadísticas, entre las más comunes se encuentran la razón de prevalencias (RP), el riesgo relativo (RR), el odds ratio (OR), el Hazard ratio (HR), la razón de tasas de incidencias (RTI), el riesgo atribuible (RA), el número necesario a tratar (NNT), la diferencia de medias (DM) y el coeficiente de regresión lineal (β). Cada una de estas medidas tiene sus ventajas y limitaciones, y su elección depende del tipo de estudio y la naturaleza de los datos que se estén analizando. Por lo tanto, es importante comprender la interpretación y uso de cada una de ellas para realizar un análisis adecuado. En este artículo, nuestro objetivo es explicar de manera práctica cómo interpretar estas medidas y cómo utilizar sus valores p e intervalos de confianza al 95% para evaluar la inferencia estadística. Entender cómo evaluar la asociación entre dos variables es crucial para el diseño y análisis de estudios clínicos de calidad. De este modo, se posibilita la toma de decisiones basadas en evidencia y se promueve la mejora en la atención de pacientes

Prevalence and factors associated with not receiving the booster dose of the COVID-19 vaccine in adults in Latin America and the Caribbean

"Background: Booster doses have been described as effective in reducing hospitalizations and deaths from the new variants. However, its coverage is heterogeneous in Latin America and the Caribbean (LAC), one of the regions most affected by the pandemic. We aimed to assess the factors associated with not receiving a coronavirus disease 2019 (COVID-19) vaccine booster dose in adults from LAC. Methods: We analyzed a secondary database compiled by the University of Maryland and Facebook assessing the global impact of COVID-19. We included Facebook users over 18 years of age who resided in LAC and responded to the survey between February 13, 2022, and March 14, 2022. We evaluated sociodemographic characteristics, comorbidities, food, and economic insecurity, mental health, and vaccination-related practices. We calculated crude (cPR) and adjusted (aPR) prevalence ratios with their respective 95% confidence intervals (95%CI). Results: The sample included 154,841 adults from 20 LAC countries. 33.7% (n = 46,459) reported not receiving the COVID-19 booster vaccine. Being under 75 years old, having a college, high school, pre-university, primary, or lower education, having no or 1 to 2 comorbidities, living in a town, having food insecurity, depressive symptoms, and having had COVID-19, were associated with a higher prevalence of not receiving the booster dose. In contrast, being female or non-binary and having anxiety symptoms were associated with a lower prevalence of not receiving the booster dose. Conclusions: Approximately three out of 10 adults surveyed in LAC reported not having received the booster vaccine. Authorities must design campaigns that promote receiving a booster dose considering the factors found.

Cursos en línea abiertos y masivos: oportunidad de aprendizaje sobre salud global en Latinoamérica

Introducción. Los cursos en línea, masivos y abiertos, brindan la oportunidad de formar profesionales e investigadores en Latinoamérica sobre salud global. Objetivos. Determinar la oferta global de los cursos en línea, masivos y abiertos, sobre salud global y conocer las características de su contenido. Materiales y métodos. Se examinaron las plataformas especializadas en cursos en línea, masivos y abiertos, para recopilar aquellos sobre salud global. La búsqueda no tuvo restricción de tiempo y se realizó por última vez en noviembre de 2021. La estrategia de búsqueda solo incluyó el descriptor “global health”. Posteriormente, se obtuvieron las características del curso, su contenido y el dominio abordado de salud global. Estos datos fueron analizados descriptivamente, y se reportaron frecuencias absolutas y relativas. Resultados. La estrategia de búsqueda identificó 4.724 cursos en línea, masivos y abiertos. De ellos, solo 92 estaban relacionados con salud global. La mayoría de estos cursos (n=44; 47,8 %) se ofrecieron mediante la plataforma Coursera. Más de la mitad de los cursos (n=50; 54,4 %) fueron realizados por instituciones de Estados Unidos y en idioma inglés (n=90; 97,8 %). La mayor parte de los cursos se centró en la “globalización de la salud y la asistencia sanitaria” (n=24; 26,1 %), seguido de los dominios “fortalecimiento de capacidades” (n=16; 17,4 %), “carga global de enfermedad” y “determinantes sociales y ambientales de la salud” (n=15; 16,3 %). Conclusiones. Se encontró una importante oferta de cursos en línea, masivos y abiertos, sobre salud global. Estos cursos abordaron las competencias de la salud global que se requieren para los profesionales sanitarios

Factors associated with the intention to participate in COVID-19 vaccine clinical trials: A cross-sectional study in Peru

Objective: To evaluate the factors associated with the intention to participate in COVID-19 vaccine clinical trials in the Peruvian population. Methods: Cross-sectional study and secondary analysis of a database that involved Peruvian population during September 2020. The Poisson regression model was used to estimate the associated factors. Results: Data from 3231 individuals were analyzed, 44.1% of whom intended to participate in COVID-19 vaccine clinical trials. Factors associated with the outcome were being male (RPa: 1.25; 95% CI: 1.15–1.35), being from the highlands region (RPa: 1.18; 95% CI: 1.09–1.28) or jungle (RPa: 1.30; 95% CI: 1.15–1.47), having a relative that is a healthcare professional (PRa: 1.16; 95% CI: 1.06–1.28), using a medical source of information (PRa: 1.28; 95% CI: 1.17–1.41), and trusting in the possible effectiveness of vaccines (PRa: 1.40; 95% CI: 1.29–1.51). The main reason for not participating in the trial was the possibility of developing side effects (69.80%). Conclusion: There is an urgent need to generate a perception of safety in COVID-19 vaccine clinical trials, to increase the population's intention to participate in these studies, and to provide evidence-based information about the vaccine.Revisión por pare

Producción científica en Scopus de los institutos de salud especializados públicos de Perú, 2010-2022

Objective: To evaluate the scientific production of Peruvian health institutes in Scopus, 2010-2022. Methods: We conducted a Bibliometric study in Scopus during September 2022, in 14 public specialized health institutes of Peru. We included original studies with at least one author from one of the institutes. Results: The institutes included published between 0 and 347 original articles (H-index between 0 and 51). The institutes in the city of Lima were the ones with the highest production. In the seven institutes with the highest production, the percentage of articles with a corresponding author from the institute evaluated ranged from 22.3% to 36.7%, and the percentage of studies that reported being financed by the institute ranged from 0% to 11.6%. Conclusion: The scientific production of the evaluated institutes was heterogeneous, with a predominance of those located in Lima. The institutes rarely participated in the financing of the published studies.Objetivo: Evaluar la producción científica de los institutos de salud de Perú en Scopus, 2010-2022. Métodos: Estudio bibliométrico realizado en Scopus durante septiembre del 2022, en 14 institutos de salud especializados públicos de Perú. Incluimos estudios originales que tuvieran al menos un autor de alguno de los institutos. Resultados: Los institutos incluidos publicaron entre 0 y 347 artículos originales (H-index entre 0 y 51). Los institutos de la ciudad de Lima fueron los que tuvieron mayor producción. En los siete institutos con mayor producción, el porcentaje de artículos con autor corresponsal del instituto evaluado varió entre 22.3% y 36.7%, y el porcentaje de estudios que declararon ser financiados por el instituto varió entre 0% y 11.6%. Conclusión: La producción científica de los institutos evaluados fue heterogénea, a predominio de aquellos ubicados en Lima. Los institutos raramente participaron en el financiamiento de los estudios publicados

Prevention and control practices against Sars-Cov2 infection in the peruvian population

Objetive: To describe the prevention and control practices for the infection to SARS-COV2 in the Peruvian population. Material and Methods: Observational descriptive study. We evaluated a non-probabilistic sample of adult residents in some departments of Peru. Preventive practices were evaluated in people without a history of COVID-19 and control practices in people who had suffered it. Results: We evaluated 3630 Peruvians (mean age 25.4 ± 9.5), of that 3231 don't have a history of COVID-19 and 399 who had suffered it. The prevention and control practices that were realized often or always, with more frequencies, was the use of a mask when they go out home (97.9% vs 87.7), cover their nose or mouth when they sneeze (95.4% vs 89.9%), save the distance to other people in the street (91.4% vs 74.7%), wash their hands when they came home (92.5% vs 88.7%), and disinfect the objects and personal places (82.6% vs 77.4%). The 22.1% and 83.7%, the 59.7% and 80.2, and the 8.0% and 16.8% consumed some type of medicine, medicinal plant, and chlorine dioxide to prevent and control the infection, respectively. Conclusion: In general, less than 50% of the participants performed prevention and control practices against COVID-19 often or always.Revisión por pare

Calcium-dependent oligomerization of CAR proteins at cell membrane modulates ABA signaling

[EN] Regulation of ion transport in plants is essential for cell function. Abiotic stress unbalances cell ion homeostasis, and plants tend to readjust it, regulating membrane transporters and channels. The plant hormone abscisic acid (ABA) and the second messenger Ca2+ are central in such processes, as they are involved in the regulation of protein kinases and phosphatases that control ion transport activity in response to environmental stimuli. The identification and characterization of the molecular mechanisms underlying the effect of ABA and Ca2+ signaling pathways on membrane function are central and could provide opportunities for crop improvement. The C2-domain ABA-related (CAR) family of small proteins is involved in the Ca2+-dependent recruitment of the pyrabactin resistance 1/PYR1like (PYR/PYL) ABA receptors to the membrane. However, to fully understand CAR function, it is necessary to define a molecular mechanism that integrates Ca2+ sensing, membrane interaction, and the recognition of the PYR/PYL interacting partners. We present structural and biochemical data showing that CARs are peripheral membrane proteins that functionally cluster on the membrane and generate strong positive membrane curvature in a Ca2+-dependent manner. These features represent a mechanism for the generation, stabilization, and/or specific recognition of membrane discontinuities. Such structures may act as signaling platforms involved in the recruitment of PYR/PYL receptors and other signaling components involved in cell responses to stress.A.A. and J.A.M. thank the European Syncrotron Radiation Facility and EMBL for access to the synchrotron radiation source. This work was funded by Ministerio de Economia y Competitividad (MINECO) Grants BFU2014-59796-R (to A.A.), BFU2011-28184-C02 (to M.J.S.-B.), and BIO2014-52537-R (to P.L.R.) and Comunidad de Madrid Grant S2010/BMD-2457 (to A.A and M.M.). M.J.S.-B. is supported by Ramon y Cajal Contract RYC-2008-03449 from MINECO and M.D. by a fellowship from Senacyt-Ifarhu. Access to the High Throughput Crystallization facility at European Molecular Biology Laboratory (EMBL) Grenoble was supported by the European Community's Seventh Framework Programme through the Protein Production Platform project (P-CUBE) Grant 227764.Diaz, M.; Sanchez-Barrena, MJ.; Gonzalez Rubio, JM.; Rodríguez Solovey, LN.; Fernández, D.; Antoni-Alandes, R.; Yunta, C.... (2016). Calcium-dependent oligomerization of CAR proteins at cell membrane modulates ABA signaling. Proceedings of the National Academy of Sciences. 113(3):E396-E405. https://doi.org/10.1073/pnas.1512779113SE396E4051133Serrano, R., & Rodriguez-Navarro, A. (2001). Ion homeostasis during salt stress in plants. Current Opinion in Cell Biology, 13(4), 399-404. doi:10.1016/s0955-0674(00)00227-1Bassil, E., & Blumwald, E. (2014). The ins and outs of intracellular ion homeostasis: NHX-type cation/H + transporters. Current Opinion in Plant Biology, 22, 1-6. doi:10.1016/j.pbi.2014.08.002Batistič, O., & Kudla, J. (2012). Analysis of calcium signaling pathways in plants. Biochimica et Biophysica Acta (BBA) - General Subjects, 1820(8), 1283-1293. doi:10.1016/j.bbagen.2011.10.012Cutler, S. R., Rodriguez, P. L., Finkelstein, R. R., & Abrams, S. R. (2010). Abscisic Acid: Emergence of a Core Signaling Network. Annual Review of Plant Biology, 61(1), 651-679. doi:10.1146/annurev-arplant-042809-112122McAinsh, M. R., Brownlee, C., & Hetherington, A. M. (1990). Abscisic acid-induced elevation of guard cell cytosolic Ca2+ precedes stomatal closure. Nature, 343(6254), 186-188. doi:10.1038/343186a0Maierhofer, T., Diekmann, M., Offenborn, J. N., Lind, C., Bauer, H., Hashimoto, K., … Hedrich, R. (2014). Site- and kinase-specific phosphorylation-mediated activation of SLAC1, a guard cell anion channel stimulated by abscisic acid. Science Signaling, 7(342), ra86-ra86. doi:10.1126/scisignal.2005703Allen, G. J., Kwak, J. M., Chu, S. P., Llopis, J., Tsien, R. Y., Harper, J. F., & Schroeder, J. I. (1999). Cameleon calcium indicator reports cytoplasmic calcium dynamics in Arabidopsis guard cells. The Plant Journal, 19(6), 735-747. doi:10.1046/j.1365-313x.1999.00574.xLee, S. C., Lan, W.-Z., Kim, B.-G., Li, L., Cheong, Y. H., Pandey, G. K., … Luan, S. (2007). A protein phosphorylation/dephosphorylation network regulates a plant potassium channel. Proceedings of the National Academy of Sciences, 104(40), 15959-15964. doi:10.1073/pnas.0707912104Sánchez-Barrena, M., Martínez-Ripoll, M., & Albert, A. (2013). Structural Biology of a Major Signaling Network that Regulates Plant Abiotic Stress: The CBL-CIPK Mediated Pathway. International Journal of Molecular Sciences, 14(3), 5734-5749. doi:10.3390/ijms14035734Quan, R., Lin, H., Mendoza, I., Zhang, Y., Cao, W., Yang, Y., … Guo, Y. (2007). SCABP8/CBL10, a Putative Calcium Sensor, Interacts with the Protein Kinase SOS2 to Protect Arabidopsis Shoots from Salt Stress. The Plant Cell, 19(4), 1415-1431. doi:10.1105/tpc.106.042291Ma, Y., Szostkiewicz, I., Korte, A., Moes, D., Yang, Y., Christmann, A., & Grill, E. (2009). Regulators of PP2C Phosphatase Activity Function as Abscisic Acid Sensors. Science. doi:10.1126/science.1172408Park, S.-Y., Fung, P., Nishimura, N., Jensen, D. R., Fujii, H., Zhao, Y., … Cutler, S. R. (2009). Abscisic Acid Inhibits Type 2C Protein Phosphatases via the PYR/PYL Family of START Proteins. Science. doi:10.1126/science.1173041Santiago, J., Rodrigues, A., Saez, A., Rubio, S., Antoni, R., Dupeux, F., … Rodriguez, P. L. (2009). Modulation of drought resistance by the abscisic acid receptor PYL5 through inhibition of clade A PP2Cs. The Plant Journal, 60(4), 575-588. doi:10.1111/j.1365-313x.2009.03981.xNishimura, N., Sarkeshik, A., Nito, K., Park, S.-Y., Wang, A., Carvalho, P. C., … Schroeder, J. I. (2009). PYR/PYL/RCAR family members are major in-vivo ABI1 protein phosphatase 2C-interacting proteins in Arabidopsis. The Plant Journal, 61(2), 290-299. doi:10.1111/j.1365-313x.2009.04054.xWang, P., Xue, L., Batelli, G., Lee, S., Hou, Y.-J., Van Oosten, M. J., … Zhu, J.-K. (2013). Quantitative phosphoproteomics identifies SnRK2 protein kinase substrates and reveals the effectors of abscisic acid action. Proceedings of the National Academy of Sciences, 110(27), 11205-11210. doi:10.1073/pnas.1308974110Umezawa, T., Sugiyama, N., Takahashi, F., Anderson, J. C., Ishihama, Y., Peck, S. C., & Shinozaki, K. (2013). Genetics and Phosphoproteomics Reveal a Protein Phosphorylation Network in the Abscisic Acid Signaling Pathway in Arabidopsis thaliana. Science Signaling, 6(270), rs8-rs8. doi:10.1126/scisignal.2003509Kollist, H., Nuhkat, M., & Roelfsema, M. R. G. (2014). Closing gaps: linking elements that control stomatal movement. New Phytologist, 203(1), 44-62. doi:10.1111/nph.12832Lind, C., Dreyer, I., López-Sanjurjo, E. J., von Meyer, K., Ishizaki, K., Kohchi, T., … Hedrich, R. (2015). Stomatal Guard Cells Co-opted an Ancient ABA-Dependent Desiccation Survival System to Regulate Stomatal Closure. Current Biology, 25(7), 928-935. doi:10.1016/j.cub.2015.01.067Geiger, D., Scherzer, S., Mumm, P., Stange, A., Marten, I., Bauer, H., … Hedrich, R. (2009). Activity of guard cell anion channel SLAC1 is controlled by drought-stress signaling kinase-phosphatase pair. Proceedings of the National Academy of Sciences, 106(50), 21425-21430. doi:10.1073/pnas.0912021106Imes, D., Mumm, P., Böhm, J., Al-Rasheid, K. A. S., Marten, I., Geiger, D., & Hedrich, R. (2013). Open stomata 1 (OST1) kinase controls R-type anion channel QUAC1 in Arabidopsis guard cells. The Plant Journal, 74(3), 372-382. doi:10.1111/tpj.12133Ishitani, M., Liu, J., Halfter, U., Kim, C.-S., Shi, W., & Zhu, J.-K. (2000). SOS3 Function in Plant Salt Tolerance Requires N-Myristoylation and Calcium Binding. The Plant Cell, 12(9), 1667-1677. doi:10.1105/tpc.12.9.1667Grefen, C., & Blatt, M. R. (2012). Do Calcineurin B-Like Proteins Interact Independently of the Serine Threonine Kinase CIPK23 with the K+ Channel AKT1? Lessons Learned from a Ménage à Trois. Plant Physiology, 159(3), 915-919. doi:10.1104/pp.112.198051Qiu, Q.-S., Guo, Y., Dietrich, M. A., Schumaker, K. S., & Zhu, J.-K. (2002). Regulation of SOS1, a plasma membrane Na+/H+ exchanger in Arabidopsis thaliana, by SOS2 and SOS3. Proceedings of the National Academy of Sciences, 99(12), 8436-8441. doi:10.1073/pnas.122224699Quintero, F. J., Martinez-Atienza, J., Villalta, I., Jiang, X., Kim, W.-Y., Ali, Z., … Pardo, J. M. (2011). Activation of the plasma membrane Na/H antiporter Salt-Overly-Sensitive 1 (SOS1) by phosphorylation of an auto-inhibitory C-terminal domain. Proceedings of the National Academy of Sciences, 108(6), 2611-2616. doi:10.1073/pnas.1018921108Núñez-Ramírez, R., Sánchez-Barrena, M. J., Villalta, I., Vega, J. F., Pardo, J. M., Quintero, F. J., … Albert, A. (2012). Structural Insights on the Plant Salt-Overly-Sensitive 1 (SOS1) Na+/H+ Antiporter. Journal of Molecular Biology, 424(5), 283-294. doi:10.1016/j.jmb.2012.09.015Ohta, M., Guo, Y., Halfter, U., & Zhu, J.-K. (2003). A novel domain in the protein kinase SOS2 mediates interaction with the protein phosphatase 2C ABI2. Proceedings of the National Academy of Sciences, 100(20), 11771-11776. doi:10.1073/pnas.2034853100Xu, J., Li, H.-D., Chen, L.-Q., Wang, Y., Liu, L.-L., He, L., & Wu, W.-H. (2006). A Protein Kinase, Interacting with Two Calcineurin B-like Proteins, Regulates K+ Transporter AKT1 in Arabidopsis. Cell, 125(7), 1347-1360. doi:10.1016/j.cell.2006.06.011Geiger, D., Scherzer, S., Mumm, P., Marten, I., Ache, P., Matschi, S., … Hedrich, R. (2010). Guard cell anion channel SLAC1 is regulated by CDPK protein kinases with distinct Ca2+affinities. Proceedings of the National Academy of Sciences, 107(17), 8023-8028. doi:10.1073/pnas.0912030107Brandt, B., Brodsky, D. E., Xue, S., Negi, J., Iba, K., Kangasjarvi, J., … Schroeder, J. I. (2012). Reconstitution of abscisic acid activation of SLAC1 anion channel by CPK6 and OST1 kinases and branched ABI1 PP2C phosphatase action. Proceedings of the National Academy of Sciences, 109(26), 10593-10598. doi:10.1073/pnas.1116590109Rodriguez, L., Gonzalez-Guzman, M., Diaz, M., Rodrigues, A., Izquierdo-Garcia, A. C., Peirats-Llobet, M., … Rodriguez, P. L. (2014). C2-Domain Abscisic Acid-Related Proteins Mediate the Interaction of PYR/PYL/RCAR Abscisic Acid Receptors with the Plasma Membrane and Regulate Abscisic Acid Sensitivity in Arabidopsis. The Plant Cell, 26(12), 4802-4820. doi:10.1105/tpc.114.129973Martens, S., & McMahon, H. T. (2008). Mechanisms of membrane fusion: disparate players and common principles. Nature Reviews Molecular Cell Biology, 9(7), 543-556. doi:10.1038/nrm2417Martens, S., Kozlov, M. M., & McMahon, H. T. (2007). How Synaptotagmin Promotes Membrane Fusion. Science, 316(5828), 1205-1208. doi:10.1126/science.1142614Jahn, R., Lang, T., & Südhof, T. C. (2003). Membrane Fusion. Cell, 112(4), 519-533. doi:10.1016/s0092-8674(03)00112-0Sutter, J.-U., Sieben, C., Hartel, A., Eisenach, C., Thiel, G., & Blatt, M. R. (2007). Abscisic Acid Triggers the Endocytosis of the Arabidopsis KAT1 K+ Channel and Its Recycling to the Plasma Membrane. Current Biology, 17(16), 1396-1402. doi:10.1016/j.cub.2007.07.020Bueso, E., Rodriguez, L., Lorenzo-Orts, L., Gonzalez-Guzman, M., Sayas, E., Muñoz-Bertomeu, J., … Rodriguez, P. L. (2014). The single-subunit RING-type E3 ubiquitin ligase RSL1 targets PYL4 and PYR1 ABA receptors in plasma membrane to modulate abscisic acid signaling. The Plant Journal, 80(6), 1057-1071. doi:10.1111/tpj.12708Larsen, J. B., Jensen, M. B., Bhatia, V. K., Pedersen, S. L., Bjørnholm, T., Iversen, L., … Stamou, D. (2015). Membrane curvature enables N-Ras lipid anchor sorting to liquid-ordered membrane phases. Nature Chemical Biology, 11(3), 192-194. doi:10.1038/nchembio.1733Demir, F., Horntrich, C., Blachutzik, J. O., Scherzer, S., Reinders, Y., Kierszniowska, S., … Kreuzer, I. (2013). Arabidopsis nanodomain-delimited ABA signaling pathway regulates the anion channel SLAH3. Proceedings of the National Academy of Sciences, 110(20), 8296-8301. doi:10.1073/pnas.1211667110Guerrero-Valero, M., Ferrer-Orta, C., Querol-Audi, J., Marin-Vicente, C., Fita, I., Gomez-Fernandez, J. C., … Corbalan-Garcia, S. (2009). Structural and mechanistic insights into the association of PKC -C2 domain to PtdIns(4,5)P2. Proceedings of the National Academy of Sciences, 106(16), 6603-6607. doi:10.1073/pnas.0813099106Guillen, J., Ferrer-Orta, C., Buxaderas, M., Perez-Sanchez, D., Guerrero-Valero, M., Luengo-Gil, G., … Corbalan-Garcia, S. (2013). Structural insights into the Ca2+ and PI(4,5)P2 binding modes of the C2 domains of rabphilin 3A and synaptotagmin 1. Proceedings of the National Academy of Sciences, 110(51), 20503-20508. doi:10.1073/pnas.1316179110Corbalan-Garcia, S., & Gómez-Fernández, J. C. (2014). Signaling through C2 domains: More than one lipid target. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1838(6), 1536-1547. doi:10.1016/j.bbamem.2014.01.008CHO, W., & STAHELIN, R. (2006). Membrane binding and subcellular targeting of C2 domains. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1761(8), 838-849. doi:10.1016/j.bbalip.2006.06.014Verdaguer, N., Corbalan-Garcia, S., Ochoa, W. F., Fita, I., & Gómez-Fernández, J. C. (1999). Ca2+ bridges the C2 membrane-binding domain of protein kinase Cα directly to phosphatidylserine. The EMBO Journal, 18(22), 6329-6338. doi:10.1093/emboj/18.22.6329Honigmann, A., van den Bogaart, G., Iraheta, E., Risselada, H. J., Milovanovic, D., Mueller, V., … Jahn, R. (2013). Phosphatidylinositol 4,5-bisphosphate clusters act as molecular beacons for vesicle recruitment. Nature Structural & Molecular Biology, 20(6), 679-686. doi:10.1038/nsmb.2570Ausili, A., Corbalán-García, S., Gómez-Fernández, J. C., & Marsh, D. (2011). Membrane docking of the C2 domain from protein kinase Cα as seen by polarized ATR-IR. The role of PIP2. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1808(3), 684-695. doi:10.1016/j.bbamem.2010.11.035Hermoso, J. A., Lagartera, L., González, A., Stelter, M., García, P., Martínez-Ripoll, M., … Menéndez, M. (2005). Insights into pneumococcal pathogenesis from the crystal structure of the modular teichoic acid phosphorylcholine esterase Pce. Nature Structural & Molecular Biology, 12(6), 533-538. doi:10.1038/nsmb940Thompson, D., Pepys, M. B., & Wood, S. P. (1999). The physiological structure of human C-reactive protein and its complex with phosphocholine. Structure, 7(2), 169-177. doi:10.1016/s0969-2126(99)80023-9Ochoa, W. F., Garcia-Garcia, J., Fita, I., Corbalan-Garcia, S., Verdaguer, N., & Gomez-Fernandez, J. C. (2001). Structure of the C2 domain from novel protein kinase Cϵ. A membrane binding model for Ca2+-independent C2 domains. Journal of Molecular Biology, 311(4), 837-849. doi:10.1006/jmbi.2001.4910Fuson, K., Rice, A., Mahling, R., Snow, A., Nayak, K., Shanbhogue, P., … Sutton, R. B. (2014). Alternate Splicing of Dysferlin C2A Confers Ca2+-Dependent and Ca2+-Independent Binding for Membrane Repair. Structure, 22(1), 104-115. doi:10.1016/j.str.2013.10.001Radhakrishnan, A., Stein, A., Jahn, R., & Fasshauer, D. (2009). The Ca2+Affinity of Synaptotagmin 1 Is Markedly Increased by a Specific Interaction of Its C2B Domain with Phosphatidylinositol 4,5-Bisphosphate. Journal of Biological Chemistry, 284(38), 25749-25760. doi:10.1074/jbc.m109.042499Schapire, A. L., Voigt, B., Jasik, J., Rosado, A., Lopez-Cobollo, R., Menzel, D., … Botella, M. A. (2008). Arabidopsis Synaptotagmin 1 Is Required for the Maintenance of Plasma Membrane Integrity and Cell Viability. The Plant Cell, 20(12), 3374-3388. doi:10.1105/tpc.108.063859Wang, J., Bello, O., Auclair, S. M., Wang, J., Coleman, J., Pincet, F., … Rothman, J. E. (2014). Calcium sensitive ring-like oligomers formed by synaptotagmin. Proceedings of the National Academy of Sciences, 111(38), 13966-13971. doi:10.1073/pnas.1415849111Jaenicke, R., & Rudolph, R. (1986). [12]Refolding and association of oligomeric proteins. Enzyme Structure Part L, 218-250. doi:10.1016/0076-6879(86)31043-7Goni, G. M., Epifano, C., Boskovic, J., Camacho-Artacho, M., Zhou, J., Bronowska, A., … Lietha, D. (2014). Phosphatidylinositol 4,5-bisphosphate triggers activation of focal adhesion kinase by inducing clustering and conformational changes. Proceedings of the National Academy of Sciences, 111(31), E3177-E3186. doi:10.1073/pnas.1317022111Wilkie, A. O. (1994). The molecular basis of genetic dominance. Journal of Medical Genetics, 31(2), 89-98. doi:10.1136/jmg.31.2.89Saez, A., Apostolova, N., Gonzalez-Guzman, M., Gonzalez-Garcia, M. P., Nicolas, C., Lorenzo, O., & Rodriguez, P. L. (2003). Gain-of-function and loss-of-function phenotypes of the protein phosphatase 2CHAB1reveal its role as a negative regulator of abscisic acid signalling. The Plant Journal, 37(3), 354-369. doi:10.1046/j.1365-313x.2003.01966.xSimons, K., & Gerl, M. J. (2010). Revitalizing membrane rafts: new tools and insights. Nature Reviews Molecular Cell Biology, 11(10), 688-699. doi:10.1038/nrm2977McMahon, H. T., & Boucrot, E. (2015). Membrane curvature at a glance. Journal of Cell Science, 128(6), 1065-1070. doi:10.1242/jcs.114454Tapken, W., & Murphy, A. S. (2015). Membrane nanodomains in plants: capturing form, function, and movement. Journal of Experimental Botany, 66(6), 1573-1586. doi:10.1093/jxb/erv054Lingwood, D., & Simons, K. (2007). Detergent resistance as a tool in membrane research. Nature Protocols, 2(9), 2159-2165. doi:10.1038/nprot.2007.294Schuck, P. (2000). Size-Distribution Analysis of Macromolecules by Sedimentation Velocity Ultracentrifugation and Lamm Equation Modeling. Biophysical Journal, 78(3), 1606-1619. doi:10.1016/s0006-3495(00)76713-0Bensmihen, S., To, A., Lambert, G., Kroj, T., Giraudat, J., & Parcy, F. (2004). Analysis of an activated ABI5 allele using a new selection method for transgenic Arabidopsis seeds. FEBS Letters, 561(1-3), 127-131. doi:10.1016/s0014-5793(04)00148-6Deblaere, R., Bytebier, B., De Greve, H., Deboeck, F., Schell, J., Van Montagu, M., & Leemans, J. (1985). Efficient octopine Ti plasmid-derived vectors forAgrobacterium-mediated gene transfer to plants. Nucleic Acids Research, 13(13), 4777-4788. doi:10.1093/nar/13.13.4777Clough, S. J., & Bent, A. F. (1998). Floral dip: a simplified method forAgrobacterium-mediated transformation ofArabidopsis thaliana. The Plant Journal, 16(6), 735-743. doi:10.1046/j.1365-313x.1998.00343.xHua, J. (2001). Plant growth homeostasis is controlled by the Arabidopsis BON1 and BAP1 genes. Genes & Development, 15(17), 2263-2272. doi:10.1101/gad.918101Kabsch, W. (2010). XDS. Acta Crystallographica Section D Biological Crystallography, 66(2), 125-132. doi:10.1107/s0907444909047337Winn, M. D., Ballard, C. C., Cowtan, K. D., Dodson, E. J., Emsley, P., Evans, P. R., … Wilson, K. S. (2011). Overview of theCCP4 suite and current developments. Acta Crystallographica Section D Biological Crystallography, 67(4), 235-242. doi:10.1107/s0907444910045749Adams, P. D., Afonine, P. V., Bunkóczi, G., Chen, V. B., Davis, I. W., Echols, N., … Zwart, P. H. (2010). PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallographica Section D Biological Crystallography, 66(2), 213-221. doi:10.1107/s0907444909052925Emsley, P., & Cowtan, K. (2004). Coot: model-building tools for molecular graphics. Acta Crystallographica Section D Biological Crystallography, 60(12), 2126-2132. doi:10.1107/s0907444904019158Dimasi, N., Flot, D., Dupeux, F., & Márquez, J. A. (2007). Expression, crystallization and X-ray data collection from microcrystals of the extracellular domain of the human inhibitory receptor expressed on myeloid cells IREM-1. Acta Crystallographica Section F Structural Biology and Crystallization Communications, 63(3), 204-208. doi:10.1107/s1744309107004903Emsley, P., Lohkamp, B., Scott, W. G., & Cowtan, K. (2010). Features and development ofCoot. Acta Crystallographica Section D Biological Crystallography, 66(4), 486-501. doi:10.1107/s0907444910007493DeLano (2002) The PyMOL Molecular Graphics System, 1.5.0.4 (DeLano Scientific, San Carlos, CA