Strawberry GRN forever: insights into the transcriptional regulatory network controlling strawberry fruit ripening and quality

Ripening is a critical step for the development of flavor quality in fruits. This character has significantly declined in many fleshy fruits over recent decades. This is particularly significant in strawberry (Fragaria × ananassa), where current cultivars are derived from a narrow germplasm collection. Improving fruit quality requires two important breakthroughs: 1) a precise understanding of the fruit ripening process that will allow the targeting of relevant genes, and 2) the identification of novel alleles responsible for fruit quality traits. In our project, we aim at the identification and characterization of key transcription factors (TF) involved in fruit ripening regulation and their target genes, in order to infer the Gene Regulatory Network controlling this process. Among them, we have identified two TFs belonging to the NAC (FaRIF) and the BLH9 (FaRPL) family. Functional analyses establishing stable silencing and overexpression lines support that both TFs play a critical role in the regulation of fruit ripening and development. Furthermore, using a stage- and tissue-specific transcriptome analysis, we have identified TFs specifically expressed in the external layer of ripe receptacles of F. vesca fruits, which are involved in the regulation of wax and cuticle formation. Finally, we have implemented the use of the genome-editing tool CRISPR/Cas9 in the cultivated strawberry, which we expect to open opportunities for engineering this species to improve traits of economic importance

Pharmacokinetics of Sativex® in Dogs: Towards a Potential Cannabinoid-Based Therapy for Canine Disorders

The phytocannabinoid-based medicine Sativex® is currently marketed for the treatment of spasticity and pain in multiple sclerosis patients and is being investigated for other central and peripheral pathological conditions. It may also serve in Veterinary Medicine for the treatment of domestic animals, in particular for dogs affected by different pathologies, including human-like pathological conditions. With the purpose of assessing different dosing paradigms for using Sativex in Veterinary Medicine, we investigated its pharmacokinetics when administered to naïve dogs via sublingual delivery. In the single dose arm of the study, adult Beagle dogs were treated with 3 consecutive sprays of Sativex, and blood samples were collected at 12 intervals up to 24 h later. In the multiple dose arm of the study, Beagle dogs received 3 sprays daily for 14 days, and blood samples were collected for 24 h post final dose. Blood was used to obtain plasma samples and to determine the levels of cannabidiol (CBD), ∆9-tetrahydrocannabinol (∆9-THC) and its metabolite 11-hydroxy-∆9-THC. Maximal plasma concentrations of both ∆9-THC (Cmax = 18.5 ng/mL) and CBD (Cmax = 10.5 ng/mL) were achieved 2 h after administration in the single dose condition and at 1 h in the multiple dose treatment (∆9-THC: Cmax = 24.5 ng/mL; CBD: Cmax = 15.2 ng/mL). 11-hydroxy-∆9-THC, which is mainly formed in the liver from ∆9-THC, was almost undetected, which is consistent with the use of sublingual delivery. A potential progressive accumulation of both CBD and ∆9-THC was detected following repeated exposure, with maximum plasma concentrations for both cannabinoids being achieved following multiple dose. Neurological status, body temperature, respiratory rate and some hemodynamic parameters were also recorded in both conditions, but in general, no changes were observed. In conclusion, this study demonstrates that single or multiple dose sublingual administration of Sativex to naïve dogs results in the expected pharmacokinetic profile, with maximal levels of phytocannabinoids detected at 1–2 h and suggested progressive accumulation after the multiple dose treatment

Up-regulation of CB2 receptors in reactive astrocytes in canine degenerative myelopathy, a disease model of amyotrophic lateral sclerosis

Targeting of the CB2 receptor results in neuroprotection in the SOD1G93A mutant mouse model of amyotrophic lateral sclerosis (ALS). The neuroprotective effects of CB2 receptors are facilitated by their upregulation in the spinal cord of the mutant mice. Here, we investigated whether similar CB2 receptor upregulation, as well as parallel changes in other endocannabinoid elements, is evident in the spinal cord of dogs with degenerative myelopathy (DM), caused by mutations in the superoxide dismutase 1 gene (SOD1). We used well-characterized post-mortem spinal cords from unaffected and DM-affected dogs. Tissues were used first to confirm the loss of motor neurons using Nissl staining, which was accompanied by glial reactivity (elevated GFAP and Iba-1 immunoreactivity). Next, we investigated possible differences in the expression of endocannabinoid genes measured by qPCR between DM-affected and control dogs. We found no changes in expression of the CB1 receptor (confirmed with CB1 receptor immunostaining) or NAPE-PLD, DAGL, FAAH and MAGL enzymes. In contrast, CB2 receptor levels were significantly elevated in DM-affected dogs determined by qPCR and western blotting, which was confirmed in the grey matter using CB2 receptor immunostaining. Using double-labelling immunofluorescence, CB2 receptor immunolabelling colocalized with GFAP but not Iba-1, indicating upregulation of CB2 receptors on astrocytes in DM-affected dogs. Our results demonstrate a marked upregulation of CB2 receptors in the spinal cord in canine DM, which is concentrated in activated astrocytes. Such receptors could be used as a potential target to enhance the neuroprotective effects exerted by these glial cells.Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)Ministerio Economia y competitividadGW PharmaceuticalsDepto. de Bioquímica y Biología MolecularFac. de MedicinaTRUEpu

Nuestra biblioteca viaja en la red : hacia una biblioteca 2.0

El trabajo obtuvo un premio de la Modalidad B de los Premios Tomás García Verdejo a las buenas prácticas educativas en la Comunidad Autónoma de Extremadura para el curso 2011En el curso 2004/2005 comenzó la organización y dinamización de la biblioteca del IES Miguel Durán (Azuaga, Badajoz), obteniendo en 2008/2009 el Tercer Premio Nacional de Buenas Prácticas en Bibliotecas Escolares de centros de secundaria. Se describen las actuaciones llevadas a cabo para promover el uso de la biblioteca y la animación a la lectura: clubes de lectura, recitales de poesía, encuentros con autores, concursos de escritura, rutas literarias, visita a la Biblioteca Nacional, etc.ExtremaduraES

El teatro áureo en la pantalla: estrategias de cinematización del monólogo (I)

The purpose of this essay is to propose, through some significant examples, a model of study of film rewriting strategies of Spanish Golden Age drama, starting with monologues modalities of adaptation. After a methodological introduction, the study will focus on appropriation tactics of two famous female monologues, taken from Lope de Vega’s Fuente Ovejuna and Calderón de la Barca’s El alcalde de Zalame

Thorough assessment of the effectiveness of belimumab in a large Spanish multicenter cohort of systemic lupus erythematosus patients

To provide an overview on the current use of belimumab (BLM) in SLE patients in clinical practice and to examine its efficacy in terms of standardized outcomes, drug survival, as well as patient and safety profiles.Funding was received from GlaxoSimthKline to support the statistical analysis of this work. Disclosure statement: I.A-G.: received payments for educa- tional talks from: GSK, AstraZeneca. J.M.P-R.: member of speakers’ bureau: Advisory boards for GSK, Otsuka, Astrazeneca, Gebro. Received grants/research support: Investigator Sponsorized Study Grant from GSK. Research support from Pfizer International (Competitive International Grants for Learning and Change). T.C.S-M.: received payments for educational talks and consulting activities from: GSK, Otzuka, Vifor. Received grants/research support: Investigator Sponsorized Study Grant from GSK. J.A.G-P.: received payments for educational talks from Abbvie, Astra Zeneca, GSK, Janssen, Lilly, Pfizer, Gala´ pagos and Otsuka. B.F-S.: received payments for educational talks from Abbvie, Astrazeneca, MSD and BMS for presentations. I.J.R-F.: received honoraria as speaker in GSK scientific meetings and as a member of advisory boards.Medicin