Novel inhibitors of the calcineurin/NFATc hub - alternatives to CsA and FK506?

The drugs cyclosporine A (CsA) and tacrolimus (FK506) revolutionized organ transplantation. Both compounds are still widely used in the clinic as well as for basic research, even though they have dramatic side effects and modulate other pathways than calcineurin-NFATc, too. To answer the major open question - whether the adverse side effects are secondary to the actions of the drugs on the calcineurin-NFATc pathway - alternative inhibitors were developed. Ideal inhibitors should discriminate between the inhibition of (i) calcineurin and peptidyl-prolyl cis-trans isomerases (PPIases; the matchmaker proteins of CsA and FK506), (ii) calcineurin and the other Ser/Thr protein phosphatases, and (iii) NFATc and other transcription factors. In this review we summarize the current knowledge about novel inhibitors, synthesized or identified in the last decades, and focus on their mode of action, specificity, and biological effects

Carrot floral development and reproductive biology

The defining characteristic of the botanical family of Apiaceae (former Umbelliferae) is the inflorescence. The flowers aggregate in terminal umbels that may be commonly compound, often umbelliform cymes. Likewise, flowers of the carrot are clustered in flat, dense umbels, partially with zygomorphic petals at the edges. Carrot producers and consumers mainly consider the vegetative phase namely the storage root as vegetable. Nevertheless, the reproductive phase is an important topic for genetic research, for breeding new cultivars and seed production. Hence, an improved knowledge on the genetic control mechanisms of reproduction such as flowering time, flower development and architecture, pollen fertility and male sterility as well as seed set are of essential importance. The chapter reviews key steps on carrot floral development and reproductive biology especially under consideration of the comprehensive genomic data set recently obtained from carrot.Fil: Linke, Betina. Humboldt-Universität zu Berlin; AlemaniaFil: Alessandro, Maria Soledad. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Mendoza-San Juan. Estación Experimental Agropecuaria La Consulta; ArgentinaFil: Galmarini, Claudio Romulo. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Mendoza-San Juan. Estación Experimental Agropecuaria La Consulta; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias; ArgentinaFil: Nothnagel, Thomas. Institute for Breeding Research on Horticultural Crops; Alemani