Nitric oxide molecular targets: reprogramming plant development upon stress

[EN] Plants are sessile organisms that need to complete their life cycle by the integration of different abiotic and biotic environmental signals, tailoring developmental cues and defense concomitantly. Commonly, stress responses are detrimental to plant growth and, despite the fact that intensive efforts have been made to understand both plant development and defense separately, most of the molecular basis of this trade-off remains elusive. To cope with such a diverse range of processes, plants have developed several strategies including the precise balance of key plant growth and stress regulators [i.e. phytohormones, reactive nitrogen species (RNS), and reactive oxygen species (ROS)]. Among RNS, nitric oxide (NO) is a ubiquitous gasotransmitter involved in redox homeostasis that regulates specific checkpoints to control the switch between development and stress, mainly by post-translational protein modifications comprising S-nitrosation of cysteine residues and metals, and nitration of tyrosine residues. In this review, we have sought to compile those known NO molecular targets able to balance the crossroads between plant development and stress, with special emphasis on the metabolism, perception, and signaling of the phytohormones abscisic acid and salicylic acid during abiotic and biotic stress responses

IL-1β inhibition in cardiovascular complications associated to diabetes mellitus

Diabetes mellitus (DM) is a chronic disease that affects nowadays millions of people worldwide. In adults, type 2 diabetes mellitus (T2DM) accounts for the majority of all diagnosed cases of diabetes. The course of the T2DM is characterized by insulin resistance and a progressive loss of β-cell mass. DM is associated with a number of related complications, among which cardiovascular complications and atherosclerosis are the main cause of morbidity and mortality in patients suffering from the disease. DM is acknowledged as a low-grade chronic inflammatory state characterized by the over-secretion of pro-inflammatory cytokines, including interleukin (IL)-1β, which reinforce inflammatory signals thus contributing to the development of complications. In this context, the pharmacological approaches to treat diabetes should not only correct hyperglycaemia, but also attenuate inflammation and prevent the development of metabolic and cardiovascular complications. Over the last years, novel biological drugs have been developed to antagonize the pathophysiological actions of IL-1β. The drugs currently used in clinical practice are anakinra, a recombinant form of the naturally occurring IL-1 receptor antagonist, the soluble decoy receptor rilonacept and the monoclonal antibodies canakinumab and gevokizumab. This review will summarize the main experimental and clinical findings obtained with pharmacological IL-1β inhibitors in the context of the cardiovascular complications of DM, and discuss the perspectives of IL-1β inhibitors as novel therapeutic tools for treating these patients.This work was supported by grants from Ministerio de Economía y Competitividad (SAF2014-52762-R) and Banco de Santander-Universidad Autónoma de Madrid (CEAL-AL/2015-17

La arquitectura geográfica manchega : recurso y compromiso educativo

En La Mancha, donde la llanura entra en contacto con los Montes de Toledo y el vulcanismo del Campo de Calatrava, allí, donde no ha mucho tiempo, el Guadiana nacía en los enigmáticos Ojos, y junto con el Gigüela se desbordaban ambos formando un amplio humedal de tablas, aparece una expresión cultural, formal, espacial y temporal que es síntesis de un paisaje, de un tiempo y de una forma de vida: la arquitectura geográfica manchega. Esta arquitectura popular, en gran parte deteriorada, olvidada y abandonada, presenta una gran diversidad de formas, como resultado de la interacción de diversos factores, bióticos y abióticos, como: el clima, el sustrato, los materiales disponibles, la herencia histórica, las actividades rurales, las creencias populares, etc. La confluencia de estos factores, originó diversos modelos arquitectónicos, resultado del cual es un amplio muestrario tipológico, que incluye manifestaciones como la quintería, el molino de agua y de viento, el bombo, el silo, la bodega, el caserío, etc. En este artículo, presentamos una aproximación al estudio geográfico de la arquitectura popular de La Mancha, un objeto que responde a un espacio, a un tiempo y a una forma, de manera que a partir del conocimiento de las influencias del medio sobre estas construcciones (espacio), de la huella histórica y la actividad humana (tiempo, técnica y función) y de las ideas, creencias y valores estéticos (forma), presentamos una tipología que, aun habiendo perdido actualmente en gran parte su significado funcional primigenio, creemos que cuenta con una serie de valores patrimoniales y didácticos cuya transmisión pretende contribuir a la sensibilización ciudadana, a su conocimiento, valoración y conservación.In La Mancha, where the plain enters contact with the Montes de Toledo and the volcanism of the Campo de Calatrava, there, where there is not a lot of time, the Guadiana was born in the enigmatic Ojos, and along with the Gigüela both overflowed forming an extensive one overflow, a temporary, spatial, formal, and cultural expression appears that is synthesis of a landscape, of a time and of a form life: the geographical architecture of La Mancha. This popular architecture, to a large extent deteriorated, forgot and abandoned, presente a great diversity morphological, as a consequence of the interaction of diverse factors, biotic and abiotic, as: the climate, the substrate, the available materials, the historie inheritance, the rural activities, the popular beliefs, etc. The confluence of these, originated diverse architectural models, result of which is an extensivo one typoligy that includes demonstrations as the farmhouse, the mili of water and of wind, the bass drum, the silo, the wine cellar, the settiement, etc. In this article, we present an approximation to geographical study of the popular architecture of La Mancha, an object that responds to a space, at the same time and to a form, so that from the knowledge of the influences of the middie on these constructions (space), of the historie track and the human activity (time, technical and function) and of the ideas, beliefs and esthetic values (form), we present a typology that, even having lost to a large extent its original functional meaning, we believe that counts on a series of didactic and hereditary values whose broadcast intends to contribute to the contributing to the civic sensibility, to its knowledge, appraisal and conservation

DPP4 and ACE2 in diabetes and COVID-19: Therapeutic targets for cardiovascular complications?

COVID-19 outbreak, caused by severe acute respiratory syndrome (SARS)-CoV-2 coronavirus has become an urgent health and economic challenge. Diabetes is a risk factor for severity and mortality of COVID-19. Recent studies support that COVID-19 has effects beyond the respiratory tract, with vascular complications arising as relevant factors worsening its prognosis, then making patients with previous vascular disease more prone to severity or fatal outcome. Angiotensin-II converting enzime-2 (ACE2) has been proposed as preferred receptor for SARS-CoV-2 host infection, yet specific proteins participating in the virus entry are not fully known. SARS-CoV-2 might use other co-receptor or auxiliary proteins allowing virus infection. In silico experiments proposed that SARS-CoV-2 might bind dipeptidyl peptidase 4 (DPP4/CD26), which was established previously as receptor for MERS-CoV. The renin–angiotensin–aldosterone system (RAAS) component ACE2 and DPP4 are proteins dysregulated in diabetes. Imbalance of the RAAS and direct effect of soluble DPP4 exert deleterious vascular effects. We hypothesize that diabetic patients might be more affected by COVID-19 due to increased presence ACE2 and DPP4 mediating infection and contributing to a compromised vasculature. Here, we discuss the role of ACE2 and DPP4 as relevant factors linking the risk of SARS-CoV-2 infection and severity of COVID-19 in diabetic patients and present an outlook on therapeutic potential of current drugs targeted against RAAS and DPP4 to treat or prevent COVID-19-derived vascular complications. Diabetes affects more than 400 million people worldwide, thus better understanding of how they are affected by COVID-19 holds an important benefit to fight against this disease with pandemic proportionsIV is the recipient of a FPU fellowship (FPU16/02612). TR and JE are supported by KomIT-Center of Competence for Innovative Diabetes Therapy- funded by EFRE-NRW. CP and CS-F are supported by a grant from Plan Nacional de I+D (SAF2017-84776-R

Cuaderno de prácticas virtual de Fitopatología Molecular de Plantas

Memoria ID12-0167. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2012-2013

IL-1β Inhibition in Cardiovascular Complications Associated to Diabetes Mellitus

Diabetes mellitus (DM) is a chronic disease that affects nowadays millions of people worldwide. In adults, type 2 diabetes mellitus (T2DM) accounts for the majority of all diagnosed cases of diabetes. The course of the T2DM is characterized by insulin resistance and a progressive loss of β-cell mass. DM is associated with a number of related complications, among which cardiovascular complications and atherosclerosis are the main cause of morbidity and mortality in patients suffering from the disease. DM is acknowledged as a low-grade chronic inflammatory state characterized by the over-secretion of pro-inflammatory cytokines, including interleukin (IL)-1β, which reinforce inflammatory signals thus contributing to the development of complications. In this context, the pharmacological approaches to treat diabetes should not only correct hyperglycaemia, but also attenuate inflammation and prevent the development of metabolic and cardiovascular complications. Over the last years, novel biological drugs have been developed to antagonize the pathophysiological actions of IL-1β. The drugs currently used in clinical practice are anakinra, a recombinant form of the naturally occurring IL-1 receptor antagonist, the soluble decoy receptor rilonacept and the monoclonal antibodies canakinumab and gevokizumab. This review will summarize the main experimental and clinical findings obtained with pharmacological IL-1β inhibitors in the context of the cardiovascular complications of DM, and discuss the perspectives of IL-1β inhibitors as novel therapeutic tools for treating these patients

Singlet oxygen triggers chloroplast rupture and cell death in the zeaxanthin epoxidase defective mutant aba1 of Arabidopsis thaliana under high light stress

[EN] The two Arabidopsis thaliana mutants, aba1 and max4, were previously identified as sharing a number of coregulated genes with both the flu mutant and Arabidopsis cell suspension cultures exposed to high light (HL). On this basis, we investigated whether aba1 and max4 were generating high amounts of singlet oxygen (1O2) and activating 1O2-mediated cell death. Thylakoids of aba1 produced twice as much 1O2 as thylakoids of max4 and wild type (WT) plants when illuminated with strong red light. 1O2 was measured using the spin probe 2,2,6,6-tetramethyl-4-piperidone hydrochloride. 77-K chlorophyll fluorescence emission spectra of thylakoids revealed lower aggregation of the light harvesting complex II in aba1. This was rationalized as a loss of connectivity between photosystem II (PSII) units and as the main cause for the high yield of 1O2 generation in aba1. Upregulation of the 1O2 responsive gene AAA-ATPase was only observed with statistical significant in aba1 under HL. Two early jasmonate (JA)-responsive genes, JAZ1 and JAZ5, encoding for two repressor proteins involved in the negative feedback regulation of JA signalling, were not up-regulated to the WT plant levels. Chloroplast aggregation followed by chloroplast rupture and eventual cell death was observed by confocal imaging of the fluorescence emission of leaf cells of transgenic aba1 plants expressing the chimeric fusion protein SSU-GFP. Cell death was not associated with direct 1O2 cytotoxicity in aba1, but rather with a delayed stress response. In contrast, max4 did not show evidence of 1O2-mediated cell death. In conclusion, aba1 may serve as an alternative model to other 1O2-overproducing mutants of Arabidopsis for investigating 1O2-mediated cell death

A protein phosphatase 2A from Fagus sylvatica is regulated by GA3 and okadaic acid in seeds and related to the transition from dormancy to germination

Several gibberellic acid (GA3)-induced cDNA fragments encoding putative serine/threonine protein phosphatase (PP) 2A catalytic subunits were obtained by means of differential reverse transcriptase-PCR approach. The full-length clone, named FsPP2A1, isolated from a beechnut cDNA library, exhibited all the features of and homology to members of the PP2A family. By transient expression of FsPP2A1 in tobacco and Arabidopsis cells as a green fluorescent fusion protein, we have obtained evidence supporting the subcellular localization of this protein in both the cytosol and the nucleus. Analysis of FsPP2A1 expression during seed stratification shows that these transcripts increase in the presence of GA3, a treatment proved to be efficient in breaking the dormancy of Fagus sylvatica seeds, but they are almost undetectable in dormant seeds or when dormancy is maintained after treatment with either abscisic acid or the gibberellin biosynthesis inhibitor paclobutrazol. The PP inhibitor okadaic acid (OKA) has a clear effect in decreasing both seed germination and FsPP2A1 expression. Furthermore, FsPP2A1 is specifically expressed in seed tissues, not being detected in other vegetative tissues examined. These results show the regulation of this PP by GA3 and OKA in these seeds. Its relationship with the processes taking place during the transition from dormancy to germination is also discussed

Analysis of NOMA-Based Retransmission Schemes for Factory Automation Applications

New use cases and applications in factory automation scenarios impose demanding requirements for traditional industrial communications. In particular, latency and reliability are considered as some of the most representative Key Performance Indicators (KPI) that limit the technological choices addressing wireless communications. Indeed, there is a considerable research effort ongoing in the area of wireless systems, not only from academia, but also from companies, towards novel solutions that fit Industry 4.0 KPIs. A major limitation for traditional wireless architectures is related to the harsh nature of the industrial propagation channel. Accordingly, this paper addresses these challenges by studying the reliability and latency performance of the joint use of different retransmission schemes in combination with Non-Orthogonal Multiple Access (NOMA) techniques. Two general retransmission schemes have been tested: time-based and spatial diversity-based retransmissions. An adaptive injection level NOMA solution has been combined with the retransmission schemes to improve the reliability of critical information. In all cases, a particular set of simulations has been carried out varying the main parameters, such as modulation, code rate and the injection level. Moreover, the impact of the number of transmitters in relation to the communication reliability has been analyzed. Results show that spatial diversity-based retransmissions overcome considerably the reliability obtained with time-domain retransmissions while maintaining assumable latency ratesThis work was supported in part by the Basque Government under Grant IT1234-19, in part by the PREDOC under Grant PRE_2020_2_0105, and in part by the Spanish Government through project PHANTOM (MCIU/AEI/FEDER, UE) under Grant RTI2018-099162-B-I0

Negative Regulation of Abscisic Acid Signaling by the Fagus sylvatica FsPP2C1 Plays A Role in Seed Dormancy Regulation and Promotion of Seed Germination

FsPP2C1 was previously isolated from beech (Fagus sylvatica) seeds as a functional protein phosphatase type-2C (PP2C) with all the conserved features of these enzymes and high homology to ABI1, ABI2, and PP2CA, PP2Cs identified as negative regulators of ABA signaling. The expression of FsPP2C1 was induced upon abscisic acid (ABA) treatment and was also up-regulated during early weeks of stratification. Furthermore, this gene was specifically expressed in ABA-treated seeds and was hardly detectable in vegetative tissues. In this report, to provide genetic evidence on FsPP2C1 function in seed dormancy and germination, we used an overexpression approach in Arabidopsis because transgenic work is not feasible in beech. Constitutive expression of FsPP2C1 under the cauliflower mosaic virus 35S promoter confers ABA insensitivity in Arabidopsis seeds and, consequently, a reduced degree of seed dormancy. Additionally, transgenic 35S:FsPP2C1 plants are able to germinate under unfavorable conditions, as inhibitory concentrations of mannitol, NaCl, or paclobutrazol. In vegetative tissues, Arabidopsis FsPP2C1 transgenic plants show ABA-resistant early root growth and diminished induction of the ABA-response genes RAB18 and KIN2, but no effect on stomatal closure regulation. Seed and vegetative phenotypes of Arabidopsis 35S:FsPP2C1 plants suggest that FsPP2C1 negatively regulates ABA signaling. The ABA inducibility of FsPP2C1 expression, together with the transcript accumulation mainly in seeds, suggest that it could play an important role modulating ABA signaling in beechnuts through a negative feedback loop. Finally, we suggest that negative regulation of ABA signaling by FsPP2C1 is a factor contributing to promote the transition from seed dormancy to germination during early weeks of stratification