Access and utilisation of maternity care for disabled women who experience domestic abuse:a systematic review

BACKGROUND: Although disabled women are significantly more likely to experience domestic abuse during pregnancy than non-disabled women, very little is known about how maternity care access and utilisation is affected by the co-existence of disability and domestic abuse. This systematic review of the literature explored how domestic abuse impacts upon disabled women’s access to maternity services. METHODS: Eleven articles were identified through a search of six electronic databases and data were analysed to identify: the factors that facilitate or compromise access to care; the consequences of inadequate care for pregnant women’s health and wellbeing; and the effectiveness of existing strategies for improvement. RESULTS: Findings indicate that a mental health diagnosis, poor relationships with health professionals and environmental barriers can compromise women’s utilisation of maternity services. Domestic abuse can both compromise, and catalyse, access to services and social support is a positive factor when accessing care. Delayed and inadequate care has adverse effects on women’s physical and psychological health, however further research is required to fully explore the nature and extent of these consequences. Only one study identified strategies currently being used to improve access to services for disabled women experiencing abuse. CONCLUSIONS: Based upon the barriers and facilitators identified within the review, we suggest that future strategies for improvement should focus on: understanding women’s reasons for accessing care; fostering positive relationships; being women-centred; promoting environmental accessibility; and improving the strength of the evidence base

Promotion of oxygen reduction by a bio-inspired tethered iron phthalocyanine carbon nanotube-based catalyst

Electrocatalysts for oxygen reduction are a critical component that may dramatically enhance the performance of fuel cells and metal-air batteries, which may provide the power for future electric vehicles. Here we report a novel bio-inspired composite electrocatalyst, iron phthalocyanine with an axial ligand anchored on single-walled carbon nanotubes, demonstrating higher electrocatalytic activity for oxygen reduction than the state-of-the-art Pt/C catalyst as well as exceptional durability during cycling in alkaline media. Theoretical calculations suggest that the rehybridization of Fe 3d orbitals with the ligand orbitals coordinated from the axial direction results in a significant change in electronic and geometric structure, which greatly increases the rate of oxygen reduction reaction. Our results demonstrate a new strategy to rationally design inexpensive and durable electrochemical oxygen reduction catalysts for metal-air batteries and fuel cells.close34

Differences between children and adolescents in treatment response to atomoxetine and the correlation between health-related quality of life and Attention Deficit/Hyperactivity Disorder core symptoms: Meta-analysis of five atomoxetine trials

<p>Abstract</p> <p>Objectives</p> <p>To explore the influence of age on treatment responses to atomoxetine and to assess the relationship between core symptoms of attention deficit/hyperactivity disorder (ADHD) and health-related quality of life (HR-QoL) outcomes.</p> <p>Data Sources</p> <p>Data from five similar clinical trials of atomoxetine in the treatment of children and adolescents with ADHD were included in this meta-analysis.</p> <p>Study Selection</p> <p>Atomoxetine studies that used the ADHD Rating Scale (ADHD-RS) and the Child Health and Illness Profile Child Edition (CHIP-CE) as outcome measures were selected.</p> <p>Interventions</p> <p>Treatment with atomoxetine.</p> <p>Main Outcome Measures</p> <p>Treatment group differences (atomoxetine vs placebo) in terms of total score, domains, and subdomains of the CHIP-CE were compared across age groups, and correlations between ADHD-RS scores and CHIP-CE scores were calculated by age.</p> <p>Results</p> <p>Data of 794 subjects (611 children, 183 adolescents) were pooled. At baseline, adolescents showed significantly (p < 0.05) greater impairment compared with children in the Family Involvement, Satisfaction with Self, and Academic Performance subdomains of the CHIP-CE. Treatment effect of atomoxetine was significant in both age groups for the Risk Avoidance domain and its subdomains. There was a significant age-treatment interaction with greater efficacy seen in adolescents in both the Risk Avoidance domain and the Threats to Achievement subdomain. Correlations between ADHD-RS and CHIP-CE scores were generally low at baseline and moderate in change from baseline and were overall similar in adolescents and children.</p> <p>Conclusions</p> <p>Atomoxetine was effective in improving some aspects of HR-QoL in both age groups. Correlations between core symptoms of ADHD and HR-QoL were low to moderate.</p

Perspectives on supporting fathers affected by postnatal depression and a history of violence

Intimate partner violence in the perinatal period is a significant problem that remains underscreened, underdiagnosed and undertreated. The establishment of evidence-based guidelines to enable health visitors to identify couples experiencing violence and offer appropriate support has been hampered by the complex interplay between maternal and paternal mental health problems and violence. This study explored the experiences of UK fathers who voluntarily engaged with services designed to eliminate their ideation to violence. The findings indicate that the tendency to violence is increased by stresses associated with the transition to parenthood. Men felt pressured by concerns for their partner's mental health, changes in the relationship, sleep disturbances and the burden of infant care they assumed when the mother was unable to cope. Health visitors are ideally placed to assess for factors linked to the emergence of violence and put in place interventions to minimise occurrence

Priorities and strategies for improving disabled women's access to maternity services when they are affected by domestic abuse:a multi-method study using concept maps

BACKGROUND: Domestic abuse is a significant public health issue. It occurs more frequently among disabled women than those without a disability and evidence suggests that a great deal of domestic abuse begins or worsens during pregnancy. All women and their infants are entitled to equal access to high quality maternity care. However, research has shown that disabled women who experience domestic abuse face numerous barriers to accessing care. The aim of the study was to identify the priority areas for improving access to maternity services for this group of women; develop strategies for improved access and utilisation; and explore the feasibility of implementing the identified strategies. METHODS: This multi-method study was the third and final part of a larger study conducted in the UK between 2012 and 2014. The study used a modified concept mapping approach and was theoretically underpinned by Andersen’s model of healthcare use. Seven focus group interviews were conducted with a range of maternity care professionals (n = 45), incorporating quantitative and qualitative components. Participants ranked perceived barriers to women’s access and utilisation of maternity services in order of priority using a 5-point Likert scale. Quantitative data exploration used descriptive and non-parametric analyses. In the qualitative component of each focus group, participants discussed the barriers and identified potential improvement strategies (and feasibility of implementing these). Qualitative data were analysed inductively using a framework analysis approach. RESULTS: The three most highly ranked barriers to women’s access and utilisation of maternity services identified in the quantitative component were: 1) staff being unaware and not asking about domestic abuse and disability; 2) the impact of domestic abuse on women; 3) women’s fear of disclosure. The top two priority strategies were: providing information about domestic abuse to all women and promoting non-judgemental staff attitude. These were also considered very feasible. The qualitative analysis identified a range of psychosocial and environmental barriers experienced by this group of women in accessing maternity care. Congruent with the quantitative results, the main themes were lack of awareness and fear of disclosure. Key strategies were identified as demystifying disclosure and creating physical spaces to facilitate disclosure. CONCLUSIONS: The study supports findings of previous research regarding the barriers that women face in accessing and utilising maternity services, particularly regarding the issue of disclosure. But the study provides new evidence on the perceived importance and feasibility of strategies to address such barriers. This is an important step in ensuring practice-based acceptability and ease with which improvement strategies might be implemented in maternity care settings

Silicon particles as trojan horses for potential cancer therapy

[EN] Background: Porous silicon particles (PSiPs) have been used extensively as drug delivery systems, loaded with chemical species for disease treatment. It is well known from silicon producers that silicon is characterized by a low reduction potential, which in the case of PSiPs promotes explosive oxidation reactions with energy yields exceeding that of trinitrotoluene (TNT). The functionalization of the silica layer with sugars prevents its solubilization, while further functionalization with an appropriate antibody enables increased bioaccumulation inside selected cells. Results: We present here an immunotherapy approach for potential cancer treatment. Our platform comprises the use of engineered silicon particles conjugated with a selective antibody. The conceptual advantage of our system is that after reaction, the particles are degraded into soluble and excretable biocomponents. Conclusions: In our study, we demonstrate in particular, specific targeting and destruction of cancer cells in vitro. The fact that the LD50 value of PSiPs-HER-2 for tumor cells was 15-fold lower than the LD50 value for control cells demonstrates very high in vitro specificity. This is the first important step on a long road towards the design and development of novel chemotherapeutic agents against cancer in general, and breast cancer in particular.The authors acknowledge financial support from the following projects FIS2009-07812, MAT2012-35040, PROMETEO/2010/043, CTQ2011-23167, CrossSERS, FP7 MC-IEF 329131, and HSFP (project RGP0052/2012) and Medcom Tech SA. Xiang Yu acknowledges support by the Chinese government (CSC, Nr. 2010691036).Fenollosa Esteve, R.; Garcia-Rico, E.; Alvarez, S.; Alvarez, R.; Yu, X.; Rodriguez, I.; Carregal-Romero, S.... (2014). Silicon particles as trojan horses for potential cancer therapy. Journal of Nanobiotechnology. 12:1-10. https://doi.org/10.1186/s12951-014-0035-7S11012Prasad PN: Introduction to Nanomedicine and Nanobioengineering. Wiley, New York, 2012.Randall CL, Leong TG, Bassik N, Gracias DH: 3D lithographically fabricated nanoliter containers for drug delivery. Adv Drug Del Rev. 2007, 59: 1547-1561. 10.1016/j.addr.2007.08.024.Reibetanz U, Chen MHA, Mutukumaraswamy S, Liaw ZY, Oh BHL, Venkatraman S, Donath E, Neu BR: Colloidal DNA carriers for direct localization in cell compartments by pH sensoring. Biogeosciences. 2010, 11: 1779-1784.Tasciotti E, Liu X, Bhavane R, Plant K, Leonard AD, Price BK, Cheng MM-C, Decuzzi P, Tour JM, Robertson F, Ferrari M: Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications. Nat Nano. 2008, 3: 151-157. 10.1038/nnano.2008.34.Park J-H, Gu L, von Maltzahn G, Ruoslahti E, Bhatia SN, Sailor MJ: Biodegradable luminescent porous silicon nanoparticles for in vivo applications. Nat Mater. 2009, 8: 331-336. 10.1038/nmat2398.Hong C, Lee J, Son M, Hong SS, Lee C: In-vivo cancer cell destruction using porous silicon nanoparticles. Anti-Cancer Drugs. 2011, 22: 971-977. 910.1097/CAD.1090b1013e32834b32859cCanham LT: Device Comprising Resorbable Silicon for Boron Capture Neutron Therapy. UK Patent Nr. 0302283.7. Book Device Comprising Resorbable Silicon for Boron Capture Neutron Therapy. UK Patent Nr. 0302283.7 (Editor ed.^eds.). 2003, UK Patent Nr. 0302283.7, CityXiao L, Gu L, Howell SB, Sailor MJ: Porous silicon nanoparticle photosensitizers for singlet oxygen and their phototoxicity against cancer cells. ACS Nano. 2011, 5: 3651-3659. 10.1021/nn1035262.Gil PR, Parak WJ: Composite nanoparticles take Aim at cancer. ACS Nano. 2008, 2: 2200-2205. 10.1021/nn800716j.Gomella LG: Is interstitial hyperthermia a safe and efficacious adjunct to radiotherapy for localized prostate cancer?. Nat Clin Pract Urol. 2004, 1: 72-73. 10.1038/ncpuro0041.Maier-Hauff K, Ulrich F, Nestler D, Niehoff H, Wust P, Thiesen B, Orawa H, Budach V, Jordan A: Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme. J Neuro-Oncol. 2011, 103: 317-324. 10.1007/s11060-010-0389-0.Lal S, Clare SE, Halas NJ: Nanoshell-enabled photothermal cancer therapy: Impending clinical impact. Acc Chem Res. 2008, 41: 1842-1851. 10.1021/ar800150g.Lee C, Kim H, Hong C, Kim M, Hong SS, Lee DH, Lee WI: Porous silicon as an agent for cancer thermotherapy based on near-infrared light irradiation. J Mater Chem. 2008, 18: 4790-4795. 10.1039/b808500e.Osminkina LA, Gongalsky MB, Motuzuk AV, Timoshenko VY, Kudryavtsev AA: Silicon nanocrystals as photo- and sono-sensitizers for biomedical applications. Appl Phys B. 2011, 105: 665-668. 10.1007/s00340-011-4562-8.Jain PK, Huang X, El-Sayed IH, El-Sayed MA: Noble metals on the nanoscale: optical and photothermal properties and some applications in imaging, sensing, biology, and medicine. Acc Chem Res. 2008, 41: 1578-1586. 10.1021/ar7002804.Serda RE, Godin B, Blanco E, Chiappini C, Ferrari M: Multi-stage delivery nano-particle systems for therapeutic applications. Biochim Biophys Acta. 1810, 2011: 317-329.Xu R, Huang Y, Mai J, Zhang G, Guo X, Xia X, Koay EJ, Qin G, Erm DR, Li Q, Liu X, Ferrari M, Shen H: Multistage vectored siRNA targeting ataxia-telangiectasia mutated for breast cancer therapy. Small. 2013, 9: 1799-1808. 10.1002/smll.201201510.Park JS, Kinsella JM, Jandial DD, Howell SB, Sailor MJ: Cisplatin-loaded porous Si microparticles capped by electroless deposition of platinum. Small. 2011, 7: 2061-2069. 10.1002/smll.201100438.Xue M, Zhong X, Shaposhnik Z, Qu Y, Tamanoi F, Duan X, Zink JI: pH-operated mechanized porous silicon nanoparticles. J Am Chem Soc. 2011, 133: 8798-8801. 10.1021/ja201252e.Canham LT: Bioactive silicon structure fabrication through nanoetching techniques. Adv Mater. 1995, 7: 1033-1037. 10.1002/adma.19950071215.Popplewell JF, King SJ, Day JP, Ackrill P, Fifield LK, Cresswell RG, Di Tada ML, Liu K: Kinetics of uptake and elimination of silicic acid by a human subject: a novel application of 32Si and accelerator mass spectrometry. J Inorganic Biochem. 1998, 69: 177-180. 10.1016/S0162-0134(97)10016-2.Shabir Q, Pokale A, Loni A, Johnson DR, Canham LT, Fenollosa R, Tymczenko M, Rodr guez I, Meseguer F, Cros A, Cantarero A: Medically biodegradable hydrogenated amorphous silicon microspheres. Silicon. 2011, 3: 173-176. 10.1007/s12633-011-9097-4.Chen Y, Wan Y, Wang Y, Zhang H, Jiao Z: Anticancer efficacy enhancement and attenuation of side effects of doxorubicin with titanium dioxide nanoparticles. Int J Nanomed. 2011, 6: 2321-2326.Mackowiak SA, Schmidt A, Weiss V, Argyo C, von Schirnding C, Bein T, Bräuchle C: Targeted drug delivery in cancer cells with Red-light photoactivated mesoporous silica nanoparticles. Nano Lett. 2013, 13: 2576-2583. 10.1021/nl400681f.Li Z, Barnes JC, Bosoy A, Stoddart JF, Zink JI: Mesoporous silica nanoparticles in biomedical applications. Chem Soc Rev. 2012, 41: 2590-2605. 10.1039/c1cs15246g.O Mara WC, Herring B, Hunt P: Handbook of Semiconductor Silicon Technology. Noyes Publication, New Jersey, 1990.Mikulec FV, Kirtland JD, Sailor MJ: Explosive nanocrystalline porous silicon and its Use in atomic emission spectroscopy. Adv Mater. 2002, 14: 38-41. 10.1002/1521-4095(20020104)14:13.0.CO;2-Z.Clement D, Diener J, Gross E, Kunzner N, Timoshenko VY, Kovalev D: Highly explosive nanosilicon-based composite materials. Phys Stat Sol A. 2005, 202: 1357-1359. 10.1002/pssa.200461102.Canham LT: Silicon quantum wire array fabrication by electrochemical and chemical dissolution of wafers. Appl Phys Lett. 1990, 57: 1046-1049. 10.1063/1.103561.Canham LT: Properties of Porous Silicon. INSPEC, United Kindom, 1997.Heinrich JL, Curtis CL, Credo GM, Sailor MJ, Kavanagh KL: Luminescent colloidal silicon suspensions from porous silicon. Science. 1992, 255: 66-68. 10.1126/science.255.5040.66.Littau KA, Szajowski PJ, Muller AJ, Kortan AR, Brus LE: A luminescent silicon nanocrystal colloid via a high-temperature aerosol reaction. J Phys Chem. 1993, 97: 1224-1230. 10.1021/j100108a019.Menz WJ, Shekar S, Brownbridge GPE, Mosbach S, Kōrmer R, Peukert W, Kraft M: Synthesis of silicon nanoparticles with a narrow size distribution: a theoretical study. J Aerosol Sci. 2012, 44: 46-61. 10.1016/j.jaerosci.2011.10.005.Swihart MT, Girshick SL: Thermochemistry and kinetics of silicon hydride cluster formation during thermal decomposition of silane. J Phys Chem B. 1998, 103: 64-76. 10.1021/jp983358e.Fenollosa R, Ramiro-Manzano F, Tymczenko M, Meseguer F: Porous silicon microspheres: synthesis, characterization and application to photonic microcavities. J Mater Chem. 2010, 20: 5210-5214. 10.1039/c0jm00079e.Ramiro-Manzano F, Fenollosa R, Xifré-Pérez E, Garín M, Meseguer F: Porous silicon microcavities based photonic barcodes. Adv Mater. 2011, 23: 3022-3025. 10.1002/adma.201100986.Kastl L, Sasse D, Wulf V, Hartmann R, Mircheski J, Ranke C, Carregal-Romero S, Martínez-López JA, Fernández-Chacón R, Parak WJ, Elsasser HP, Rivera-Gil P: Multiple internalization pathways of polyelectrolyte multilayer capsules into mammalian cells. ACS Nano. 2013, 7: 6605-6618. 10.1021/nn306032k.Schweiger C, Hartmann R, Zhang F, Parak W, Kissel T, Rivera_Gil P: Quantification of the internalization patterns of superparamagnetic iron oxide nanoparticles with opposite charge. J Nanobiotech. 2012, 10: 28-10.1186/1477-3155-10-28.Sanles-Sobrido M, Exner W, Rodr guez-Lorenzo L, Rodríguez-Gonzílez B, Correa-Duarte MA, Álvarez-Puebla RA, Liz-Marzán LM: Design of SERS-encoded, submicron, hollow particles through confined growth of encapsulated metal nanoparticles. J Am Chem Soc. 2009, 131: 2699-2705. 10.1021/ja8088444.Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J: Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011, 365: 1273-1283. 10.1056/NEJMoa0910383.Agus DB, Gordon MS, Taylor C, Natale RB, Karlan B, Mendelson DS, Press MF, Allison DE, Sliwkowski MX, Lieberman G, Kelsey SM, Fyfe G: Phase I clinical study of pertuzumab, a novel HER dimerization inhibitor, in patients with advanced cancer. J Clin Oncol. 2005, 23: 2534-2543. 10.1200/JCO.2005.03.184.Colombo M, Mazzucchelli S, Montenegro JM, Galbiati E, Corsi F, Parak WJ, Prosperi D: Protein oriented ligation on nanoparticles exploiting O6-alkylguanine-DNA transferase (SNAP) genetically encoded fusion. Small. 2012, 8: 1492-1497. 10.1002/smll.201102284.Franklin MC, Carey KD, Vajdos FF, Leahy DJ, de Vos AM, Sliwkowski MX: Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell. 2004, 5: 317-328. 10.1016/S1535-6108(04)00083-2.Paris L, Cecchetti S, Spadaro F, Abalsamo L, Lugini L, Pisanu ME, Lorio E, Natali PG, Ramoni C, Podo F: Inhibition of phosphatidylcholine-specific phospholipase C downregulates HER2 overexpression on plasma membrane of breast cancer cells. Breast Cancer Res. 2010, 12: R27-10.1186/bcr2575.Fenollosa R, Meseguer F, Tymczenko M: Silicon colloids: from microcavities to photonic sponges. Adv Mater. 2008, 20: 95-98. 10.1002/adma.200701589.Jasinski JM, Gates SM: Silicon chemical vapor deposition one step at a time: fundamental studies of silicon hydride chemistry. Acc Chem Res. 1991, 24: 9-15. 10.1021/ar00001a002.Xiao Q, Liu Y, Qiu Y, Zhou G, Mao C, Li Z, Yao Z-J, Jiang S: Potent antitumor mimetics of annonaceous acetogenins embedded with an aromatic moiety in the left hydrocarbon chain part. J Med Chem. 2010, 54: 525-533. 10.1021/jm101053k.Allman SA, Jensen HH, Vijayakrishnan B, Garnett JA, Leon E, Liu Y, Anthony DC, Sibson NR, Feizi T, Matthews S, Davis BG: Potent fluoro-oligosaccharide probes of adhesion in toxoplasmosis. ChemBioChem. 2009, 10: 2522-2529. 10.1002/cbic.200900425.Chambers DJ, Evans GR, Fairbanks AJ: Elimination reactions of glycosyl selenoxides. Tetrahedron. 2004, 60: 8411-8419. 10.1016/j.tet.2004.07.005.Tomabechi Y, Suzuki R, Haneda K, Inazu T: Chemo-enzymatic synthesis of glycosylated insulin using a GlcNAc tag. Bioorg Med Chem. 2010, 18: 1259-1264. 10.1016/j.bmc.2009.12.031.Pastoriza-Santos I, Gomez D, Perez-Juste J, Liz-Marzan LM, Mulvaney P: Optical properties of metal nanoparticle coated silica spheres: a simple effective medium approach. Phys Chem Chem Phys. 2004, 6: 5056-5060. 10.1039/b405157b

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

[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.; Chávez 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., Chávez Montes, R. A., Marsch-Martínez, 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., Benítez, M., Corvera-Poiré, A., Chaos Cador, Á., de Folter, S., Gamboa de Buen, A., … Sánchez-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)60316-6Chávez 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-Martínez, 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-Martínez, N., Ramos-Cruz, D., Irepan Reyes-Olalde, J., Lozano-Sotomayor, P., Zúñiga-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., & Schmülling, 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., & Müller, 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., & Schmülling, 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., & Benková, 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., Myrenås, 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.xStåldal, 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.2016.03.005José 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., Novák, 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.2.8.755Müller, 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., Martínez-Garcia, J. F., Martin-Magniette, M.-L., Monéger, 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-Gómez, M., Carbonero, P., Oñate-Sánchez, L., & Ferrándiz, 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., Doležal, 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.2013.06.025Benková, E., Michniewicz, M., Sauer, M., Teichmann, T., Seifertová, D., Jürgens, 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-Martínez, N., Reyes-Olalde, J. I., Ramos-Cruz, D., Lozano-Sotomayor, P., Zúñiga-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., Szécsi, 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