1,492 research outputs found

    Design and Construction of a High-Speed Match Index of Refraction Facility

    Get PDF
    The design and construction of a recirculating high speed matched index of refraction facility will aim to provide a deeper understanding of isothermal turbulent mixing at a fundamental level. The understanding of this fluid flow phenomena will allow a greater understanding of the thermal hydraulic challenges found in generation IV (Gen IV) reactors and fluid thermal systems. Particle image velocimetry combined with matching index will provide unobstructed data acquisition and increase optical access in the region of interest. Mineral oil is used, as the working fluid, in combination with two 24-inch long quartz plates to achieve index matching. The two quartz plates will be inserted in a test section which will form three channels. The test section was designed with the goal of achieving a slot channel Reynolds number of at least 10,000. A 5th order polynomial contraction was also designed with the purpose to generate a uniform velocity profile before the test section’s inlet. In conjunction with the contraction, a flow conditioner was placed three hydraulic diameters upstream of the contraction’s inlet with the goal to reduce turbulence intensity in the flow. Two expansions were also designed in order to connect different pipe sizes and geometries in the pipe system while minimizing flow separation. The pressure drop of the system was theoretically analyzed and a 20 horsepower inline centrifugal pump was selected based on the results and it is expected to operate with an efficiency between 86% and 79%. Design and construction of the facility is completed along with filling the facility with mineral oil. Leaks in the system were addressed and fixed in order to ensure a leak tight construction. After the building electrical accommodations are adjusted, experiments can be initiated

    Epidemic Leptospirosis Associated with Pulmonary Hemorrhage—Nicaragua, 1995

    Get PDF
    In October 1995, epidemic “hemorrhagic fever,” without jaundice or renal manifestations, was reported in rural Nicaragua following heavy flooding; 2259 residents were evaluated for nonmalarial febrile illnesses (cumulative incidence, 6.1%) and 15 (0.7%) died with pulmonary hemorrhage. A case-control study found that case-patients were more likely than controls to have ever walked in creeks (matched odds ratio [MOR], 15.0; 95% confidence interval [CI], 1.7–132.3), have household rodents (MOR, 10.4; 95% CI, 1.1–97.1), or own dogs with titers ≄ 400 to Leptospira species (MOR, 23.4; 95% CI, 3.6–`). Twenty-six of 51 case-patients had serologic or postmortem evidence of acute leptospirosis. Leptospira species were isolated from case-patients and potential animal reservoirs. This leptospirosis epidemic likely resulted from exposure to flood waters contaminated by urine from infected animals, particularly dogs. Leptospirosis should be included in the differential diagnosis for nonmalarial febrile illness, particularly during periods of flooding or when pulmonary hemorrhage occurs

    From Nuevo LeĂłn to the USA and Back Again: Transnational Students in Mexico

    Get PDF
    The movement of Mexicans to the United States is both longstanding and long studied and from that study we know that for many newcomers the attachment to the receiving community is fraught and tentative. The experience of immigrant children in U.S. schools is also relatively well studied and reveals challenges of intercultural communication as well as concurrent and contradictory features of welcome and unwelcome. What is less well known, in the study of migration generally and of transnational students in particular, is how students moving in a less common direction — from the U.S. to Mexico — experience that movement. Based on visits to 173 randomly selected classrooms in the state of Nuevo León Mexico, this study shares survey and interview data from 208 of the 242 students encountered who had previous experience attending school in the United States

    Un examen actualizado de la percepción de las barreras para la implementación de la farmacogenómica y la utilidad de los pares fårmaco/gen en América Latina y el Caribe

    Get PDF
    La farmacogenĂłmica (PGx) se considera un campo emergente en los paĂ­ses en desarrollo. La investigaciĂłn sobre PGx en la regiĂłn de AmĂ©rica Latina y el Caribe (ALC) sigue siendo escasa, con informaciĂłn limitada en algunas poblaciones. Por lo tanto, las extrapolaciones son complicadas, especialmente en poblaciones mixtas. En este trabajo, revisamos y analizamos el conocimiento farmacogenĂłmico entre la comunidad cientĂ­fica y clĂ­nica de ALC y examinamos las barreras para la aplicaciĂłn clĂ­nica. Realizamos una bĂșsqueda de publicaciones y ensayos clĂ­nicos en este campo en todo el mundo y evaluamos la contribuciĂłn de ALC. A continuaciĂłn, realizamos una encuesta regional estructurada que evaluĂł una lista de 14 barreras potenciales para la aplicaciĂłn clĂ­nica de biomarcadores en funciĂłn de su importancia. AdemĂĄs, se analizĂł una lista emparejada de 54 genes/fĂĄrmacos para determinar una asociaciĂłn entre los biomarcadores y la respuesta a la medicina genĂłmica. Esta encuesta se comparĂł con una encuesta anterior realizada en 2014 para evaluar el progreso en la regiĂłn. Los resultados de la bĂșsqueda indicaron que los paĂ­ses de AmĂ©rica Latina y el Caribe han contribuido con el 3,44% del total de publicaciones y el 2,45% de los ensayos clĂ­nicos relacionados con PGx en todo el mundo hasta el momento. Un total de 106 profesionales de 17 paĂ­ses respondieron a la encuesta. Se identificaron seis grandes grupos de obstĂĄculos. A pesar de los continuos esfuerzos de la regiĂłn en la Ășltima dĂ©cada, la principal barrera para la implementaciĂłn de PGx en ALC sigue siendo la misma, la "necesidad de directrices, procesos y protocolos para la aplicaciĂłn clĂ­nica de la farmacogenĂ©tica/farmacogenĂłmica". Las cuestiones de coste-eficacia se consideran factores crĂ­ticos en la regiĂłn. Los puntos relacionados con la reticencia de los clĂ­nicos son actualmente menos relevantes. SegĂșn los resultados de la encuesta, los pares gen/fĂĄrmaco mejor clasificados (96%-99%) y percibidos como importantes fueron CYP2D6/tamoxifeno, CYP3A5/tacrolimus, CYP2D6/opioides, DPYD/fluoropirimidinas, TMPT/tiopurinas, CYP2D6/antidepresivos tricĂ­clicos, CYP2C19/antidepresivos tricĂ­clicos, NUDT15/tiopurinas, CYP2B6/efavirenz y CYP2C19/clopidogrel. En conclusiĂłn, aunque la contribuciĂłn global de los paĂ­ses de ALC sigue siendo baja en el campo del PGx, se ha observado una mejora relevante en la regiĂłn. La percepciĂłn de la utilidad de las pruebas PGx en la comunidad biomĂ©dica ha cambiado drĂĄsticamente, aumentando la concienciaciĂłn entre los mĂ©dicos, lo que sugiere un futuro prometedor en las aplicaciones clĂ­nicas de PGx en ALC.Pharmacogenomics (PGx) is considered an emergent field in developing countries. Research on PGx in the Latin American and the Caribbean (LAC) region remains scarce, with limited information in some populations. Thus, extrapolations are complicated, especially in mixed populations. In this paper, we reviewed and analyzed pharmacogenomic knowledge among the LAC scientific and clinical community and examined barriers to clinical application. We performed a search for publications and clinical trials in the field worldwide and evaluated the contribution of LAC. Next, we conducted a regional structured survey that evaluated a list of 14 potential barriers to the clinical implementation of biomarkers based on their importance. In addition, a paired list of 54 genes/drugs was analyzed to determine an association between biomarkers and response to genomic medicine. This survey was compared to a previous survey performed in 2014 to assess progress in the region. The search results indicated that Latin American and Caribbean countries have contributed 3.44% of the total publications and 2.45% of the PGx-related clinical trials worldwide thus far. A total of 106 professionals from 17 countries answered the survey. Six major groups of barriers were identified. Despite the region’s continuous efforts in the last decade, the primary barrier to PGx implementation in LAC remains the same, the “need for guidelines, processes, and protocols for the clinical application of pharmacogenetics/pharmacogenomics”. Cost-effectiveness issues are considered critical factors in the region. Items related to the reluctance of clinicians are currently less relevant. Based on the survey results, the highest ranked (96%–99%) gene/drug pairs perceived as important were CYP2D6/tamoxifen, CYP3A5/tacrolimus, CYP2D6/opioids, DPYD/fluoropyrimidines, TMPT/thiopurines, CYP2D6/tricyclic antidepressants, CYP2C19/tricyclic antidepressants, NUDT15/thiopurines, CYP2B6/efavirenz, and CYP2C19/clopidogrel. In conclusion, although the global contribution of LAC countries remains low in the PGx field, a relevant improvement has been observed in the region. The perception of the usefulness of PGx tests in biomedical community has drastically changed, raising awareness among physicians, which suggests a promising future in the clinical applications of PGx in LAC

    Transdisciplinary studies in socio-ecosystems: Theoretical considerations and its application in Latin American contexts

    Get PDF
    Debido a limitaciones para abordar la complejidad de la relaciĂłn sociedad-naturaleza, los esfuerzos para solucionar los problemas ambientales han sido en general infructuosos. AquĂ­ proponemos que el enfoque holĂ­stico de “socio-ecosistema” por parte de la academia, podrĂ­a contribuir a disminuir estas limitaciones desde la adopciĂłn de cuatro cambios: i) ontolĂłgico, que presenta el concepto de “socio-ecosistemas”; ii) epistemolĂłgico, que propone a la transdisciplina como la forma de entenderlos, iii) metodolĂłgico, que sugiere intervenir en ellos de forma participativa y adaptativa y, iv) cambios institucionales que facilitarĂ­an la adopciĂłn de esta propuesta. Este planteamiento se complementa con la descripciĂłn de una experiencia transdiciplinaria en la cuenca del rĂ­o San Juan ZitĂĄcuaro, MĂ©xico, en el contexto de un curso internacional de manejo de socio-ecosistemas.Given the difficulties to approach the complex relationship bettween society and nature, efforts to solve environmental problems have generally been unsuccessful. Here we suggest that a hollistic “socio-ecosystem” approach by the sciencies could help diminish these difficulties by embracing four kinds of changes: i) ontological, which introduces the concept of “socio-ecosystem”; ii) epistemological, which proposes transdiscipline as the way to understand them, iii) metholodogical, which suggests that in intervention in them must be participatory and adaptive, iv) institutional changes that would facilitate the adoption of this approach. This is then followed by a description of a transdisciplinary work experience in the ZitĂĄcuaro river basin, in Mexico, in the context of an international course on socio-ecosystem management.Fil: Ortega Uribe, Tamara. Universidad de Chile; ChileFil: Mastrangelo, Matias Enrique. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Mar del Plata; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; ArgentinaFil: Villarroel Torrez, Daniel. Universidad de Buenos Aires. Facultad de AgronomĂ­a; Argentina. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas; ArgentinaFil: Piaz, AgustĂ­n Gabriel. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas; Argentina. Universidad Nacional de San MartĂ­n. Escuela de Humanidades. Centro de Estudios de Historia de la Ciencia y de la TĂ©cnica ; ArgentinaFil: Vallejos, MarĂ­a. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. Instituto de Investigaciones FisiolĂłgicas y EcolĂłgicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de AgronomĂ­a. Instituto de Investigaciones FisiolĂłgicas y EcolĂłgicas Vinculadas a la Agricultura; ArgentinaFil: Saenz Ceja, JesĂșs Eduardo. Universidad Nacional AutĂłnoma de MĂ©xico. Centro de Investigaciones en Ecosistemas; MĂ©xicoFil: Gallego, Federico. Universidad de la RepĂșblica. Facultad de Ciencias; UruguayFil: Franquesa Soler, Monserrat. Instituto de EcologĂ­a; MĂ©xicoFil: Calzada Peña, Leonardo. Universidad Nacional AutĂłnoma de MĂ©xico; MĂ©xicoFil: Espinosa Mellado, Noelia. Universidad de la Armada; MĂ©xicoFil: Fiestas Flores, Jerico. Instituto de Estudios Peruanos; PerĂșFil: Gill Mairhofer, Luis R.. Ministerio de la Defensa PĂșblica; ParaguayFil: GonzĂĄlez Espino, ZarahĂ­. Instituto Superior de TecnologĂ­as y Ciencias Aplicadas. Facultad de Medio Ambiente. Departamento de MeteorologĂ­a; CubaFil: Luna Salguero, BetsabĂ© Montserrat. Sociedad de Historia Natural NiparajĂĄ; MĂ©xicoFil: Martinez Peralta, Claudia MarĂ­a. ComisiĂłn de EcologĂ­a y Desarrollo Sustentable del Estado de Sonora. DirecciĂłn General de ConservaciĂłn; MĂ©xicoFil: Ochoa, Olivia. Universidad Nacional AutĂłnoma de MĂ©xico; MĂ©xicoFil: PĂ©rez Volkow,LucĂ­a. No especifica;Fil: Sala, Juan Emilio. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Centro Nacional PatagĂłnico; ArgentinaFil: SĂĄnchez Rose, Isabelle. Universidad Central de Venezuela; VenezuelaFil: Weeks, Madeline. University of Cambridge; Reino UnidoFil: Ávila GarcĂ­a, Daniela. Universidad Nacional AutĂłnoma de MĂ©xico; MĂ©xicoFil: GarcĂ­a Reyes, Isabel Bueno. Universidad Nacional AutĂłnoma de MĂ©xico. Centro de Investigaciones en Ecosistemas; MĂ©xicoFil: Carmona, Alejandra. Universidad Austral de Chile. Instituto de EconomĂ­a Agraria; ChileFil: Castro Videla, Fernando Horacio. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Mendoza; Argentina. Instituto Nacional de TecnologĂ­a Agropecuaria. Centro Regional Mendoza-San Juan; ArgentinaFil: Ferrer Gonzalez, CĂ©sar Sergio. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; ArgentinaFil: Frank Buss, MarĂ­a Elisa. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas; Argentina. Universidad Nacional de La Pampa. Facultad de AgronomĂ­a; ArgentinaFil: LĂłpez Carapia, Gabriela. Universidad Nacional AutĂłnoma de MĂ©xico; MĂ©xicoFil: NĂșñez Cruz, Martha. Universidad Nacional AutĂłnoma de MĂ©xico; MĂ©xicoFil: Taboada Hermoza, Rossi. Universidad Nacional Mayor de San Marcos; PerĂșFil: Benet, Daniel. Alternare A. C.; MĂ©xicoFil: Venegas, Ysmael. Alternare A. C.; MĂ©xicoFil: Balvanera, Patricia. Universidad Nacional AutĂłnoma de MĂ©xico. Centro de Investigaciones en Ecosistemas; MĂ©xicoFil: Mwampamba, Tuyeni H.. Universidad Nacional AutĂłnoma de MĂ©xico. Centro de Investigaciones en Ecosistemas; MĂ©xicoFil: Lazos Chavero, Elena. Universidad Nacional AutĂłnoma de MĂ©xico. Centro de Investigaciones en Ecosistemas; MĂ©xicoFil: Noellemeyer, Elke Johanna. Universidad Nacional de La Pampa. Facultad de AgronomĂ­a; Argentina. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas; ArgentinaFil: Maass, Manuel. Universidad Nacional AutĂłnoma de MĂ©xico. Centro de Investigaciones en Ecosistemas; MĂ©xic

    Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

    Get PDF
    BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

    Brain clocks capture diversity and disparities in aging and dementia across geographically diverse populations

    Get PDF
    Peer reviewe

    Rate and duration of hospitalisation for acute pulmonary embolism in the real-world clinical practice of different countries : Analysis from the RIETE registry

    Get PDF
    publishersversionPeer reviewe

    Determinants of enhanced vulnerability to coronavirus disease 2019 in UK patients with cancer: a European study

    Get PDF
    Despite high contagiousness and rapid spread, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to heterogeneous outcomes across affected nations. Within Europe (EU), the United Kingdom (UK) is the most severely affected country, with a death toll in excess of 100,000 as of January 2021. We aimed to compare the national impact of coronavirus disease 2019 (COVID-19) on the risk of death in UK patients with cancer versus those in continental EU. Methods: We performed a retrospective analysis of the OnCovid study database, a European registry of patients with cancer consecutively diagnosed with COVID-19 in 27 centres from 27th February to 10th September 2020. We analysed case fatality rates and risk of death at 30 days and 6 months stratified by region of origin (UK versus EU). We compared patient characteristics at baseline including oncological and COVID-19-specific therapy across UK and EU cohorts and evaluated the association of these factors with the risk of adverse outcomes in multivariable Cox regression models. Findings: Compared with EU (n = 924), UK patients (n = 468) were characterised by higher case fatality rates (40.38% versus 26.5%, p < 0.0001) and higher risk of death at 30 days (hazard ratio [HR], 1.64 [95% confidence interval {CI}, 1.36-1.99]) and 6 months after COVID-19 diagnosis (47.64% versus 33.33%; p < 0.0001; HR, 1.59 [95% CI, 1.33-1.88]). UK patients were more often men, were of older age and have more comorbidities than EU counterparts (p < 0.01). Receipt of anticancer therapy was lower in UK than in EU patients (p < 0.001). Despite equal proportions of complicated COVID-19, rates of intensive care admission and use of mechanical ventilation, UK patients with cancer were less likely to receive anti-COVID-19 therapies including corticosteroids, antivirals and interleukin-6 antagonists (p < 0.0001). Multivariable analyses adjusted for imbalanced prognostic factors confirmed the UK cohort to be characterised by worse risk of death at 30 days and 6 months, independent of the patient's age, gender, tumour stage and status; number of comorbidities; COVID-19 severity and receipt of anticancer and anti-COVID-19 therapy. Rates of permanent cessation of anticancer therapy after COVID-19 were similar in the UK and EU cohorts. Interpretation: UK patients with cancer have been more severely impacted by the unfolding of the COVID-19 pandemic despite societal risk mitigation factors and rapid deferral of anticancer therapy. The increased frailty of UK patients with cancer highlights high-risk groups that should be prioritised for anti-SARS-CoV-2 vaccination. Continued evaluation of long-term outcomes is warranted

    The bHLH transcription factor SPATULA enables cytokinin signaling, and both activate auxin biosynthesis and transport genes at the medial domain of the gynoecium

    Get PDF
    [EN] Fruits and seeds are the major food source on earth. Both derive from the gynoecium and, therefore, it is crucial to understand the mechanisms that guide the development of this organ of angiosperm species. In Arabidopsis, the gynoecium is composed of two congenitally fused carpels, where two domains: medial and lateral, can be distinguished. The medial domain includes the carpel margin meristem (CMM) that is key for the production of the internal tissues involved in fertilization, such as septum, ovules, and transmitting tract. Interestingly, the medial domain shows a high cytokinin signaling output, in contrast to the lateral domain, where it is hardly detected. While it is known that cytokinin provides meristematic properties, understanding on the mechanisms that underlie the cytokinin signaling pattern in the young gynoecium is lacking. Moreover, in other tissues, the cytokinin pathway is often connected to the auxin pathway, but we also lack knowledge about these connections in the young gynoecium. Our results reveal that cytokinin signaling, that can provide meristematic properties required for CMM activity and growth, is enabled by the transcription factor SPATULA (SPT) in the medial domain. Meanwhile, cytokinin signaling is confined to the medial domain by the cytokinin response repressor ARABIDOPSIS HISTIDINE PHOSPHOTRANSFERASE 6 (AHP6), and perhaps by ARR16 (a type-A ARR) as well, both present in the lateral domains (presumptive valves) of the developing gynoecia. Moreover, SPT and cytokinin, probably together, promote the expression of the auxin biosynthetic gene TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS 1 (TAA1) and the gene encoding the auxin efflux transporter PIN-FORMED 3 (PIN3), likely creating auxin drainage important for gynoecium growth. This study provides novel insights in the spatiotemporal determination of the cytokinin signaling pattern and its connection to the auxin pathway in the young gynoecium.IRO, VMZM, HHU and PLS were supported by the Mexican National Council of Science and Technology (CONACyT) with a PhD fellowship (210085, 210100, 243380 and 219883, respectively). Work in the SDF laboratory was financed by the CONACyT grants CB-2012-177739, FC-2015-2/1061, and INFR-2015-253504, and NMM by the CONACyT grant CB-2011-165986. SDF, CF and LC acknowledge the support of the European Union FP7-PEOPLE-2009-IRSES project EVOCODE (grant no. 247587) and H2020-MSCARISE-2015 project ExpoSEED (grant no. 691109). SDF also acknowledges the Marine Biological Laboratory (MBL) in Woods Hole for a scholarship for the Gene Regulatory Networks for Development Course 2015 (GERN2015). IE acknowledges the International European Fellowship-METMADS project and the Universita degli Studi di Milano (RTD-A; 2016). Research in the laboratory of MFY was funded by NSF (grant IOS-1121055), NIH (grant 1R01GM112976-01A1) and the Paul D. Saltman Endowed Chair in Science Education (MFY). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Reyes Olalde, J.; Zuñiga, V.; Serwatowska, J.; ChĂĄvez Montes, R.; Lozano-Sotomayor, P.; Herrera-Ubaldo, H.; Gonzalez Aguilera, K.... (2017). The bHLH transcription factor SPATULA enables cytokinin signaling, and both activate auxin biosynthesis and transport genes at the medial domain of the gynoecium. PLoS Genetics. 13(4):1-31. https://doi.org/10.1371/journal.pgen.1006726S131134Reyes-Olalde, J. I., Zuñiga-Mayo, V. M., ChĂĄvez Montes, R. A., Marsch-MartĂ­nez, N., & de Folter, S. (2013). Inside the gynoecium: at the carpel margin. Trends in Plant Science, 18(11), 644-655. doi:10.1016/j.tplants.2013.08.002Alvarez-Buylla, E. R., BenĂ­tez, M., Corvera-PoirĂ©, A., Chaos Cador, Á., de Folter, S., Gamboa de Buen, A., 
 SĂĄnchez-Corrales, Y. E. (2010). Flower Development. The Arabidopsis Book, 8, e0127. doi:10.1199/tab.0127Bowman, J. L., Baum, S. F., Eshed, Y., Putterill, J., & Alvarez, J. (1999). 4 Molecular Genetics of Gynoecium Development in Arabidopsis. Current Topics in Developmental Biology Volume 45, 155-205. doi:10.1016/s0070-2153(08)60316-6ChĂĄvez Montes, R. A., Herrera-Ubaldo, H., Serwatowska, J., & de Folter, S. (2015). Towards a comprehensive and dynamic gynoecium gene regulatory network. Current Plant Biology, 3-4, 3-12. doi:10.1016/j.cpb.2015.08.002Marsch-MartĂ­nez, N., & de Folter, S. (2016). Hormonal control of the development of the gynoecium. Current Opinion in Plant Biology, 29, 104-114. doi:10.1016/j.pbi.2015.12.006Marsch-MartĂ­nez, N., Ramos-Cruz, D., Irepan Reyes-Olalde, J., Lozano-Sotomayor, P., ZĂșñiga-Mayo, V. M., & de Folter, S. (2012). The role of cytokinin during Arabidopsis gynoecia and fruit morphogenesis and patterning. The Plant Journal, 72(2), 222-234. doi:10.1111/j.1365-313x.2012.05062.xZhao, Z., Andersen, S. U., Ljung, K., Dolezal, K., Miotk, A., Schultheiss, S. J., & Lohmann, J. U. (2010). Hormonal control of the shoot stem-cell niche. Nature, 465(7301), 1089-1092. doi:10.1038/nature09126Ashikari, M. (2005). Cytokinin Oxidase Regulates Rice Grain Production. Science, 309(5735), 741-745. doi:10.1126/science.1113373Bartrina, I., Otto, E., Strnad, M., Werner, T., & SchmĂŒlling, T. (2011). Cytokinin Regulates the Activity of Reproductive Meristems, Flower Organ Size, Ovule Formation, and Thus Seed Yield in Arabidopsis thaliana. The Plant Cell, 23(1), 69-80. doi:10.1105/tpc.110.079079Hwang, I., Sheen, J., & MĂŒller, B. (2012). Cytokinin Signaling Networks. Annual Review of Plant Biology, 63(1), 353-380. doi:10.1146/annurev-arplant-042811-105503Schaller, G. E., Bishopp, A., & Kieber, J. J. (2015). The Yin-Yang of Hormones: Cytokinin and Auxin Interactions in Plant Development. The Plant Cell, 27(1), 44-63. doi:10.1105/tpc.114.133595Kieber, J. J., & Schaller, G. E. (2010). The Perception of Cytokinin: A Story 50 Years in the Making: Figure 1. Plant Physiology, 154(2), 487-492. doi:10.1104/pp.110.161596Long, J. A., Moan, E. I., Medford, J. I., & Barton, M. K. (1996). A member of the KNOTTED class of homeodomain proteins encoded by the STM gene of Arabidopsis. Nature, 379(6560), 66-69. doi:10.1038/379066a0Jasinski, S., Piazza, P., Craft, J., Hay, A., Woolley, L., Rieu, I., 
 Tsiantis, M. (2005). KNOX Action in Arabidopsis Is Mediated by Coordinate Regulation of Cytokinin and Gibberellin Activities. Current Biology, 15(17), 1560-1565. doi:10.1016/j.cub.2005.07.023Yanai, O., Shani, E., Dolezal, K., Tarkowski, P., Sablowski, R., Sandberg, G., 
 Ori, N. (2005). Arabidopsis KNOXI Proteins Activate Cytokinin Biosynthesis. Current Biology, 15(17), 1566-1571. doi:10.1016/j.cub.2005.07.060Scofield, S., Dewitte, W., Nieuwland, J., & Murray, J. A. H. (2013). The Arabidopsis homeobox gene SHOOT MERISTEMLESS has cellular and meristem-organisational roles with differential requirements for cytokinin and CYCD3 activity. The Plant Journal, 75(1), 53-66. doi:10.1111/tpj.12198Gordon, S. P., Chickarmane, V. S., Ohno, C., & Meyerowitz, E. M. (2009). Multiple feedback loops through cytokinin signaling control stem cell number within the Arabidopsis shoot meristem. Proceedings of the National Academy of Sciences, 106(38), 16529-16534. doi:10.1073/pnas.0908122106Chickarmane, V. S., Gordon, S. P., Tarr, P. T., Heisler, M. G., & Meyerowitz, E. M. (2012). Cytokinin signaling as a positional cue for patterning the apical-basal axis of the growing Arabidopsis shoot meristem. Proceedings of the National Academy of Sciences, 109(10), 4002-4007. doi:10.1073/pnas.1200636109Leibfried, A., To, J. P. C., Busch, W., Stehling, S., Kehle, A., Demar, M., 
 Lohmann, J. U. (2005). WUSCHEL controls meristem function by direct regulation of cytokinin-inducible response regulators. Nature, 438(7071), 1172-1175. doi:10.1038/nature04270Werner, T., Motyka, V., Laucou, V., Smets, R., Van Onckelen, H., & SchmĂŒlling, T. (2003). Cytokinin-Deficient Transgenic Arabidopsis Plants Show Multiple Developmental Alterations Indicating Opposite Functions of Cytokinins in the Regulation of Shoot and Root Meristem Activity. The Plant Cell, 15(11), 2532-2550. doi:10.1105/tpc.014928Larsson, E., Franks, R. G., & Sundberg, E. (2013). Auxin and the Arabidopsis thaliana gynoecium. Journal of Experimental Botany, 64(9), 2619-2627. doi:10.1093/jxb/ert099Weijers, D., & Wagner, D. (2016). Transcriptional Responses to the Auxin Hormone. Annual Review of Plant Biology, 67(1), 539-574. doi:10.1146/annurev-arplant-043015-112122Robert, H. S., Crhak Khaitova, L., Mroue, S., & BenkovĂĄ, E. (2015). The importance of localized auxin production for morphogenesis of reproductive organs and embryos inArabidopsis. Journal of Experimental Botany, 66(16), 5029-5042. doi:10.1093/jxb/erv256Kuusk, S., Sohlberg, J. J., Magnus Eklund, D., & Sundberg, E. (2006). Functionally redundantSHIfamily genes regulate Arabidopsis gynoecium development in a dose-dependent manner. The Plant Journal, 47(1), 99-111. doi:10.1111/j.1365-313x.2006.02774.xSohlberg, J. J., MyrenĂ„s, M., Kuusk, S., Lagercrantz, U., Kowalczyk, M., Sandberg, G., & Sundberg, E. (2006). STY1regulates auxin homeostasis and affects apical-basal patterning of the Arabidopsis gynoecium. The Plant Journal, 47(1), 112-123. doi:10.1111/j.1365-313x.2006.02775.xStĂ„ldal, V., Sohlberg, J. J., Eklund, D. M., Ljung, K., & Sundberg, E. (2008). Auxin can act independently ofCRC,LUG,SEU,SPTandSTY1in style development but not apical-basal patterning of theArabidopsisgynoecium. New Phytologist, 180(4), 798-808. doi:10.1111/j.1469-8137.2008.02625.xVan Gelderen, K., van Rongen, M., Liu, A., Otten, A., & Offringa, R. (2016). An INDEHISCENT-Controlled Auxin Response Specifies the Separation Layer in Early Arabidopsis Fruit. Molecular Plant, 9(6), 857-869. doi:10.1016/j.molp.2016.03.005JosĂ© Ripoll, J., Bailey, L. J., Mai, Q.-A., Wu, S. L., Hon, C. T., Chapman, E. J., 
 Yanofsky, M. F. (2015). microRNA regulation of fruit growth. Nature Plants, 1(4). doi:10.1038/nplants.2015.36Larsson, E., Roberts, C. J., Claes, A. R., Franks, R. G., & Sundberg, E. (2014). Polar Auxin Transport Is Essential for Medial versus Lateral Tissue Specification and Vascular-Mediated Valve Outgrowth in Arabidopsis Gynoecia. Plant Physiology, 166(4), 1998-2012. doi:10.1104/pp.114.245951Nole-Wilson, S., Azhakanandam, S., & Franks, R. G. (2010). Polar auxin transport together with AINTEGUMENTA and REVOLUTA coordinate early Arabidopsis gynoecium development. Developmental Biology, 346(2), 181-195. doi:10.1016/j.ydbio.2010.07.016De Folter, S. (2016). Auxin Is Required for Valve Margin Patterning in Arabidopsis After All. Molecular Plant, 9(6), 768-770. doi:10.1016/j.molp.2016.05.005Moubayidin, L., & Østergaard, L. (2014). Dynamic Control of Auxin Distribution Imposes a Bilateral-to-Radial Symmetry Switch during Gynoecium Development. Current Biology, 24(22), 2743-2748. doi:10.1016/j.cub.2014.09.080Girin, T., Paicu, T., Stephenson, P., Fuentes, S., Körner, E., O’Brien, M., 
 Østergaard, L. (2011). INDEHISCENT and SPATULA Interact to Specify Carpel and Valve Margin Tissue and Thus Promote Seed Dispersal in Arabidopsis. The Plant Cell, 23(10), 3641-3653. doi:10.1105/tpc.111.090944Ioio, R. D., Nakamura, K., Moubayidin, L., Perilli, S., Taniguchi, M., Morita, M. T., 
 Sabatini, S. (2008). A Genetic Framework for the Control of Cell Division and Differentiation in the Root Meristem. Science, 322(5906), 1380-1384. doi:10.1126/science.1164147Bishopp, A., Help, H., El-Showk, S., Weijers, D., Scheres, B., Friml, J., 
 Helariutta, Y. (2011). A Mutually Inhibitory Interaction between Auxin and Cytokinin Specifies Vascular Pattern in Roots. Current Biology, 21(11), 917-926. doi:10.1016/j.cub.2011.04.017De Rybel, B., Adibi, M., Breda, A. S., Wendrich, J. R., Smit, M. E., NovĂĄk, O., 
 Weijers, D. (2014). Integration of growth and patterning during vascular tissue formation in Arabidopsis. Science, 345(6197), 1255215. doi:10.1126/science.1255215Pernisova, M., Klima, P., Horak, J., Valkova, M., Malbeck, J., Soucek, P., 
 Hejatko, J. (2009). Cytokinins modulate auxin-induced organogenesis in plants via regulation of the auxin efflux. Proceedings of the National Academy of Sciences, 106(9), 3609-3614. doi:10.1073/pnas.0811539106Cheng, Z. J., Wang, L., Sun, W., Zhang, Y., Zhou, C., Su, Y. H., 
 Zhang, X. S. (2012). Pattern of Auxin and Cytokinin Responses for Shoot Meristem Induction Results from the Regulation of Cytokinin Biosynthesis by AUXIN RESPONSE FACTOR3. Plant Physiology, 161(1), 240-251. doi:10.1104/pp.112.203166Alvarez, J., & Smyth, D. R. (2002). CRABS CLAWandSPATULAGenes Regulate Growth and Pattern Formation during Gynoecium Development inArabidopsis thaliana. International Journal of Plant Sciences, 163(1), 17-41. doi:10.1086/324178Groszmann, M., Bylstra, Y., Lampugnani, E. R., & Smyth, D. R. (2010). Regulation of tissue-specific expression of SPATULA, a bHLH gene involved in carpel development, seedling germination, and lateral organ growth in Arabidopsis. Journal of Experimental Botany, 61(5), 1495-1508. doi:10.1093/jxb/erq015Smyth, D. R., Bowman, J. L., & Meyerowitz, E. M. (1990). Early flower development in Arabidopsis. The Plant Cell, 2(8), 755-767. doi:10.1105/tpc.2.8.755MĂŒller, B., & Sheen, J. (2008). Cytokinin and auxin interaction in root stem-cell specification during early embryogenesis. Nature, 453(7198), 1094-1097. doi:10.1038/nature06943Argyros, R. D., Mathews, D. E., Chiang, Y.-H., Palmer, C. M., Thibault, D. M., Etheridge, N., 
 Schaller, G. E. (2008). Type B Response Regulators of Arabidopsis Play Key Roles in Cytokinin Signaling and Plant Development. The Plant Cell, 20(8), 2102-2116. doi:10.1105/tpc.108.059584Mason, M. G., Mathews, D. E., Argyros, D. A., Maxwell, B. B., Kieber, J. J., Alonso, J. M., 
 Schaller, G. E. (2005). Multiple Type-B Response Regulators Mediate Cytokinin Signal Transduction in Arabidopsis. The Plant Cell, 17(11), 3007-3018. doi:10.1105/tpc.105.035451Ishida, K., Yamashino, T., Yokoyama, A., & Mizuno, T. (2008). Three Type-B Response Regulators, ARR1, ARR10 and ARR12, Play Essential but Redundant Roles in Cytokinin Signal Transduction Throughout the Life Cycle of Arabidopsis thaliana. Plant and Cell Physiology, 49(1), 47-57. doi:10.1093/pcp/pcm165Yokoyama, A., Yamashino, T., Amano, Y.-I., Tajima, Y., Imamura, A., Sakakibara, H., & Mizuno, T. (2006). Type-B ARR Transcription Factors, ARR10 and ARR12, are Implicated in Cytokinin-Mediated Regulation of Protoxylem Differentiation in Roots of Arabidopsis thaliana. Plant and Cell Physiology, 48(1), 84-96. doi:10.1093/pcp/pcl040Schuster, C., Gaillochet, C., & Lohmann, J. U. (2015). Arabidopsis HECATE genes function in phytohormone control during gynoecium development. Development, 142(19), 3343-3350. doi:10.1242/dev.120444Toledo-Ortiz, G., Huq, E., & Quail, P. H. (2003). The Arabidopsis Basic/Helix-Loop-Helix Transcription Factor Family. The Plant Cell, 15(8), 1749-1770. doi:10.1105/tpc.013839Reymond, M. C., Brunoud, G., Chauvet, A., MartĂ­nez-Garcia, J. F., Martin-Magniette, M.-L., MonĂ©ger, F., & Scutt, C. P. (2012). A Light-Regulated Genetic Module Was Recruited to Carpel Development in Arabidopsis following a Structural Change to SPATULA. The Plant Cell, 24(7), 2812-2825. doi:10.1105/tpc.112.097915Ballester, P., Navarrete-GĂłmez, M., Carbonero, P., Oñate-SĂĄnchez, L., & FerrĂĄndiz, C. (2015). Leaf expansion in Arabidopsis is controlled by a TCP-NGA regulatory module likely conserved in distantly related species. Physiologia Plantarum, 155(1), 21-32. doi:10.1111/ppl.12327Hellens, R., Allan, A., Friel, E., Bolitho, K., Grafton, K., Templeton, M., 
 Laing, W. (2005). Plant Methods, 1(1), 13. doi:10.1186/1746-4811-1-13Makkena, S., & Lamb, R. S. (2013). The bHLH transcription factor SPATULA regulates root growth by controlling the size of the root meristem. BMC Plant Biology, 13(1), 1. doi:10.1186/1471-2229-13-1Stepanova, A. N., Robertson-Hoyt, J., Yun, J., Benavente, L. M., Xie, D.-Y., DoleĆŸal, K., 
 Alonso, J. M. (2008). TAA1-Mediated Auxin Biosynthesis Is Essential for Hormone Crosstalk and Plant Development. Cell, 133(1), 177-191. doi:10.1016/j.cell.2008.01.047Bhargava, A., Clabaugh, I., To, J. P., Maxwell, B. B., Chiang, Y.-H., Schaller, G. E., 
 Kieber, J. J. (2013). Identification of Cytokinin-Responsive Genes Using Microarray Meta-Analysis and RNA-Seq in Arabidopsis. Plant Physiology, 162(1), 272-294. doi:10.1104/pp.113.217026Sakai, H., Aoyama, T., & Oka, A. (2000). Arabidopsis ARR1 and ARR2 response regulators operate as transcriptional activators. The Plant Journal, 24(6), 703-711. doi:10.1046/j.1365-313x.2000.00909.xSakai, H. (2001). ARR1, a Transcription Factor for Genes Immediately Responsive to Cytokinins. Science, 294(5546), 1519-1521. doi:10.1126/science.1065201Moubayidin, L., Di Mambro, R., Sozzani, R., Pacifici, E., Salvi, E., Terpstra, I., 
 Sabatini, S. (2013). Spatial Coordination between Stem Cell Activity and Cell Differentiation in the Root Meristem. Developmental Cell, 26(4), 405-415. doi:10.1016/j.devcel.2013.06.025BenkovĂĄ, E., Michniewicz, M., Sauer, M., Teichmann, T., SeifertovĂĄ, D., JĂŒrgens, G., & Friml, J. (2003). Local, Efflux-Dependent Auxin Gradients as a Common Module for Plant Organ Formation. Cell, 115(5), 591-602. doi:10.1016/s0092-8674(03)00924-3Okada, K., Ueda, J., Komaki, M. K., Bell, C. J., & Shimura, Y. (1991). Requirement of the Auxin Polar Transport System in Early Stages of Arabidopsis Floral Bud Formation. The Plant Cell, 677-684. doi:10.1105/tpc.3.7.677Blilou, I., Xu, J., Wildwater, M., Willemsen, V., Paponov, I., Friml, J., 
 Scheres, B. (2005). The PIN auxin efflux facilitator network controls growth and patterning in Arabidopsis roots. Nature, 433(7021), 39-44. doi:10.1038/nature03184Mahonen, A. P. (2006). Cytokinin Signaling and Its Inhibitor AHP6 Regulate Cell Fate During Vascular Development. Science, 311(5757), 94-98. doi:10.1126/science.1118875Besnard, F., Refahi, Y., Morin, V., Marteaux, B., Brunoud, G., Chambrier, P., 
 Vernoux, T. (2013). Cytokinin signalling inhibitory fields provide robustness to phyllotaxis. Nature, 505(7483), 417-421. doi:10.1038/nature12791Longabaugh, W. J. R., Davidson, E. H., & Bolouri, H. (2005). Computational representation of developmental genetic regulatory networks. Developmental Biology, 283(1), 1-16. doi:10.1016/j.ydbio.2005.04.023Faure, E., Peter, I. S., & Davidson, E. H. (2013). A New Software Package for Predictive Gene Regulatory Network Modeling and Redesign. Journal of Computational Biology, 20(6), 419-423. doi:10.1089/cmb.2012.0297Mangan, S., & Alon, U. (2003). Structure and function of the feed-forward loop network motif. Proceedings of the National Academy of Sciences, 100(21), 11980-11985. doi:10.1073/pnas.2133841100Chen, Q., Liu, Y., Maere, S., Lee, E., Van Isterdael, G., Xie, Z., 
 Vanneste, S. (2015). A coherent transcriptional feed-forward motif model for mediating auxin-sensitive PIN3 expression during lateral root development. Nature Communications, 6(1). doi:10.1038/ncomms9821Qiu, K., Li, Z., Yang, Z., Chen, J., Wu, S., Zhu, X., 
 Zhou, X. (2015). EIN3 and ORE1 Accelerate Degreening during Ethylene-Mediated Leaf Senescence by Directly Activating Chlorophyll Catabolic Genes in Arabidopsis. PLOS Genetics, 11(7), e1005399. doi:10.1371/journal.pgen.1005399Seaton, D. D., Smith, R. W., Song, Y. H., MacGregor, D. R., Stewart, K., Steel, G., 
 Halliday, K. J. (2015). Linked circadian outputs control elongation growth and flowering in response to photoperiod and temperature. Molecular Systems Biology, 11(1), 776. doi:10.15252/msb.20145766Roeder, A. H. K., & Yanofsky, M. F. (2006). Fruit Development in Arabidopsis. The Arabidopsis Book, 4, e0075. doi:10.1199/tab.0075Marsch-MartĂ­nez, N., Reyes-Olalde, J. I., Ramos-Cruz, D., Lozano-Sotomayor, P., ZĂșñiga-Mayo, V. M., & de Folter, S. (2012). Hormones talking. Plant Signaling & Behavior, 7(12), 1698-1701. doi:10.4161/psb.22422Balanza, V., Navarrete, M., Trigueros, M., & Ferrandiz, C. (2006). Patterning the female side of Arabidopsis: the importance of hormones. Journal of Experimental Botany, 57(13), 3457-3469. doi:10.1093/jxb/erl188Kamiuchi, Y., Yamamoto, K., Furutani, M., Tasaka, M., & Aida, M. (2014). The CUC1 and CUC2 genes promote carpel margin meristem formation during Arabidopsis gynoecium development. Frontiers in Plant Science, 5. doi:10.3389/fpls.2014.00165Scofield, S., Dewitte, W., & Murray, J. A. H. (2007). The KNOX gene SHOOT MERISTEMLESS is required for the development of reproductive meristematic tissues in Arabidopsis. The Plant Journal, 50(5), 767-781. doi:10.1111/j.1365-313x.2007.03095.xLi, K., Yu, R., Fan, L.-M., Wei, N., Chen, H., & Deng, X. W. (2016). DELLA-mediated PIF degradation contributes to coordination of light and gibberellin signalling in Arabidopsis. Nature Communications, 7(1). doi:10.1038/ncomms11868Oh, E., Zhu, J.-Y., & Wang, Z.-Y. (2012). Interaction between BZR1 and PIF4 integrates brassinosteroid and environmental responses. Nature Cell Biology, 14(8), 802-809. doi:10.1038/ncb2545Sharma, N., Xin, R., Kim, D.-H., Sung, S., Lange, T., & Huq, E. (2016). NO FLOWERING IN SHORT DAY (NFL) is a bHLH transcription factor that promotes flowering specifically under short-day conditions inArabidopsis. Development, 143(4), 682-690. doi:10.1242/dev.128595Varaud, E., Brioudes, F., SzĂ©csi, J., Leroux, J., Brown, S., Perrot-Rechenmann, C., & Bendahmane, M. (2011). AUXIN RESPONSE FACTOR8 Regulates Arabidopsis Petal Growth by Interacting with the bHLH Transcription Factor BIGPETALp. The Plant Cell, 23(3), 973-983. doi:10.1105/tpc.110.081653Savaldi-Goldstein, S., & Chory, J. (2008). Growth coordination and the shoot epidermis. Current Opinion in Plant Biology, 11(1), 42-48. doi:10.1016/j.pbi.2007.10.009Schuster, C., Gaillochet, C., Medzihradszky, A., Busch, W., Daum, G., Krebs, M., 
 Lohmann, J. U. (2014). A Regulatory Framework for Shoot Stem Cell Co
    • 

    corecore