RGL2 controls flower development, ovule number and fertility in Arabidopsis

[EN] DELLA proteins are a group of plant specific GRAS proteins of transcriptional regulators that have a key role in gibberellin (GA) signaling. In Arabidopsis, the DELLA family is formed by five members. The complexity of this gene family raises the question on whether single DELLA proteins have specific or overlapping functions in the control of several GA-dependent developmental processes. To better understand the roles played by RGL2, one of the DELLA proteins in Arabidopsis, two transgenic lines that express fusion proteins of Venus-RGL2 and a dominant version of RGL2, YPet-rgl2A17, were generated by recombineering strategy using a genomic clone that contained the RGL2 gene. The dominant YPet-rg12 Delta 17 protein is not degraded by GAs, and therefore it blocks the RGL2-dependent GA signaling and hence RGL2-dependent development. The RGL2 role in seed germination was further confirmed using these genetic tools, while new functions of RGL2 in plant development were uncovered. RGL2 has a clear function in the regulation of flower development, particularly stamen growth and anther dehiscence, which has a great impact in fertility. Moreover, the increased ovule number in the YPet-rg12 Delta 17 line points out the role of RGL2 in the determination of ovule number.We wish to thank Ms. J. Yun,M.A. Argomániz for technical assistance, and the IBMCP microscopy facility. Edit Syndicate (http://www.editsyndicate.com/) provided proofreading of the manuscript. This work was supported by grants from the Spanish Ministry of Economy and Competitiveness-FEDER [BI02011-26302 and BI02014-55946] and Generalitat Valenciana [ACOMP/2013/048 and ACOMP/2014/106] to M.A.P-A. and National Science Foundation [MCB-0923727] to J.M.A. MAP-A. received a fellowship of the 'Salvador de Madariaga' program from Spanish Ministry of Science and Innovation.Gómez Jiménez, MD.; Fuster Almunia, C.; Ocaña-Cuesta, J.; Alonso, J.; Perez Amador, MA. (2019). RGL2 controls flower development, ovule number and fertility in Arabidopsis. Plant Science. 281:82-92. https://doi.org/10.1016/j.plantsci.2019.01.014S829228

Secondary CoQ10 deficiency, bioenergetics unbalance in disease and aging

Coenzyme Q10 (CoQ10) deficiency is a rare disease characterized by a decreased accumulation of CoQ10 in cell membranes. Considering that CoQ10 synthesis and most of its functions are carried out in mitochondria, CoQ10 deficiency cases are usually considered a mitochondrial disease. A relevant feature of CoQ10 deficiency is that it is the only mitochondrial disease with a successful therapy available, the CoQ10 supplementation. Defects in components of the synthesis machinery caused by mutations in COQ genes generate the primary deficiency of CoQ10. Mutations in genes that are not directly related to the synthesis machinery cause secondary deficiency. Cases of CoQ10 deficiency without genetic origin are also considered a secondary deficiency. Both types of deficiency can lead to similar clinical manifestations, but the knowledge about primary deficiency is deeper than secondary. However, secondary deficiency cases may be underestimated since many of their clinical manifestations are shared with other pathologies. This review shows the current state of secondary CoQ10 deficiency, which could be even more relevant than primary deficiency for clinical activity. The analysis covers the fundamental features of CoQ10 deficiency, which are necessary to understand the biological and clinical differences between primary and secondary CoQ10 deficiencies. Further, a more in-depth analysis of CoQ10 secondary deficiency was undertaken to consider its origins, introduce a new way of classification, and include aging as a form of secondary deficiency.Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía, Grant/Award Numbers: UPO-1259581, UPO-126247, UPO-1265673; Instituto de Salud Carlos III, Grant/Award Number: PI17/01286; Ministerio de Educación, Cultura y Deporte, Grant/Award Numbers: FPU14/04873, FPU16/0326

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

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Structure-Based Modulation of the Ligand Sensitivity of a Tomato Dimeric Abscisic Acid Receptor Through a Glu to Asp Mutation in the Latch Loop

12 pags., 6 figs. -- This article is part of the Research Topic: Structural Bioinformatics and Biophysical Approaches for Understanding the Plant Responses to Biotic and Abiotic StressThe binding of the plant phytohormone Abscisic acid (ABA) to the family of ABA receptors (PYR/PYL/RCAR) triggers plant responses to abiotic stress. Thus, the implementation of genetic or chemical strategies to modulate PYR/PYL activity might be biotechnologically relevant. We have employed the available structural information on the PYR/PYL receptors to design SlPYL1, a tomato receptor, harboring a single point mutation that displays enhanced ABA dependent and independent activity. Interestingly, crystallographic studies show that this mutation is not directly involved in ABA recognition or in the downstream phosphatase (PP2C) inhibitory interaction, rather, molecular dynamic based ensemble refinement restrained by crystallographic data indicates that it enhances the conformational variability required for receptor activation and it is involved in the stabilization of an active form of the receptor. Moreover, structural studies on this receptor have led to the identification of niacin as an ABA antagonist molecule in vivo. We have found that niacin blocks the ABA binding site by mimicking ABA receptor interactions, and the niacin interaction inhibits the biochemical activity of the receptor.The authors are funded by the Agencia Estatal de Investigación of the Spanish Ministry of Science and Innovation with grant number PID2020-119805RB-I00 to AA and grant PID2020-113100RB-I00 to PR funded by MCIN/AEI/10.13039/501100011033, and PRE2018-083280 to MD-M

The mitochondrial phosphatase PPTC7 orchestrates mitochondrial metabolism regulating coenzyme Q10 biosynthesis

Coenzyme Q10 (CoQ10) is a redox molecule critical for the proper function of energy metabolism and antioxidant defenses. Despite its essential role in cellular metabolism, the regulation of CoQ10 biosynthesis in humans remains mostly unknown. Herein, we determined that PPTC7 is a regulatory protein of CoQ10 biosynthesis required for human cell survival. We demonstrated by in vitro approaches that PPTC7 is a bona fide protein phosphatase that dephosphorylates the human COQ7. Expression modulation experiments determined that human PPTC7 dictates cellular CoQ10 content. Using two different approaches (PPTC7 over-expression and caloric restriction), we demonstrated that PPTC7 facilitates and improves the human cell adaptation to respiratory conditions. Moreover, we determined that the physiological role of PPTC7 takes place in the adaptation to starvation and pro-oxidant conditions, facilitating the induction of mitochondrial metabolism while preventing the accumulation of ROS. Here we unveil the first post-translational mechanism regulating CoQ10 biosynthesis in humans and propose targeting the induction of PPTC7 activity/expression for the treatment of CoQ10-related mitochondrial diseases.The research group is funded by the Andalusian Government as the BIO177 group through FEDER funds (European Commission), by the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III (FIS PI14/01962 and FIS PI17/01286)

Evaluación de estenosis carotídea en pacientes subsidiarios de revascularización miocárdica

Introducción. La estenosis carotídea (EC) crítica es frecuente en pacientes pendientes de revascularización miocárdica (RM), aumenta el riesgo de ictus durante la cirugía y su diagnóstico es importante, aunque el tratamiento sea controvertido cuando coexisten ambas patologías. Objetivos. Estudiar la lesión carotídea en pacientes pendientes de RM y los factores asociados. Determinar la morbimortalidad de la cirugía combinada carotídea y la RM frente a cirugías separadas. Pacientes y métodos. Estudio prospectivo, observacional y consecutivo durante 16 meses; se realiza dúplex carotídeo en 140 candidatos a RM, y consideramos la EC crítica: lesión carotídea = 70%, con un 72,9% varones y una edad media de 69,8 años. Realizamos análisis estadístico con SPSS 10.1, chi al cuadrado y test exacto de Fisher: p £ 0,05 es significativamente estadística. Resultados. Prevalencia de lesión carotídea: 16,5% EC = 50%, 10% EC = 70%, pero sólo 7,1% quirúrgicas, ya que cuatro casos fueron oclusión carotídea. 42,6% angor inestable, 5% fracción de eyección del ventrículo izquierdo < 30%. Encontramos asociación significativa entre EC crítica en este tipo de pacientes con las siguientes variables: enfermedad cerebrovascular en el 37,5% de los casos (p = 0,009); lesión de tronco coronario izquierdo (TCI) = 50% en el 22,2% (p = 0,002) y no padecer diabetes (p = 0,028). Practicamos cinco cirugías secuenciales: endarterectomía carotídea (EAC) seguida de RM cuatro cirugías combinadas y una RM emergente sin EAC. La morbimortalidad de la RM en pacientes con EC < 70% fue: 0,61% mortalidad, 0,69% morbilidad ¿seis infartos agudos de miocardio (IAM) y tres ictus¿. En EC quirúrgicas hubo un exitus, un IAM. Conclusiones. Consideramos indicación primaria el estudio con dúplex carotídeo en estos pacientes; es especialmente importante cuando existe lesión del TCI significativa (= 50%) y enfermedad cerebrovascular. Proponemos cirugía combinada en pacientes cardiológicamente inestables y es recomendable en lesión del TCI ³ 50%, aunque sean necesarios ensayos clínicos que mejoren la indicación