The bHLH transcription factors TSAR1 and TSAR2 regulate triterpene saponin biosynthesis in Medicago truncatula

Plants respond to stresses by producing a broad spectrum of bioactive specialized metabolites. Hormonal elicitors, such as jasmonates, trigger a complex signaling circuit leading to the concerted activation of specific metabolic pathways. However, for many specialized metabolic pathways, the transcription factors involved remain unknown. Here, we report on two homologous jasmonate-inducible transcription factors of the basic helix-loop-helix family, TRITERPENE SAPONIN BIOSYNTHESIS ACTIVATING REGULATOR1 (TSAR1) and TSAR2, which direct triterpene saponin biosynthesis in Medicago truncatula. TSAR1 and TSAR2 are coregulated with and transactivate the genes encoding 3-HYDROXY-3-METHYLGLUTARYL-COENZYME A REDUCTASE1 (HMGR1) and MAKIBISHI1, the rate-limiting enzyme for triterpene biosynthesis and an E3 ubiquitin ligase that controls HMGR1 levels, respectively. Transactivation is mediated by direct binding of TSARs to the N-box in the promoter of HMGR1. In transient expression assays in tobacco (Nicotiana tabacum) protoplasts, TSAR1 and TSAR2 exhibit different patterns of transactivation of downstream triterpene saponin biosynthetic genes, hinting at distinct functionalities within the regulation of the pathway. Correspondingly, overexpression of TSAR1 or TSAR2 in M. truncatula hairy roots resulted in elevated transcript levels of known triterpene saponin biosynthetic genes and strongly increased the accumulation of triterpene saponins. TSAR2 overexpression specifically boosted hemolytic saponin biosynthesis, whereas TSAR1 overexpression primarily stimulated nonhemolytic soyasaponin biosynthesis. Both TSARs also activated all genes of the precursor mevalonate pathway but did not affect sterol biosynthetic genes, pointing to their specific role as regulators of specialized triterpene metabolism in M. truncatula

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The yeast Saccharomyces cerevisiae is sensitive to colorectal cancer routine treatment EGFR antibody Cetuximab

Cetuximab/Erbitux® (Merk Sereno), a drug used in routine treatment of colorectal cancer and other malignant pathologies, is a monoclonal antibody against the Epidermal Growth Factor Receptor (EGFR). A frequent problem affecting the clinical use of Cetuximab is the lack of effectiveness deriving from frequent mutations in K-ras (1-3). A set of mutations in K-ras gene, KRAS c.35G>A (G12D), KRAS c.38G>A (G13D) in exon 2, and KRAS c.183A>T (Q61H) in exon 3, all implicated in the development of colorectal cancer, have been recognized as impeding Cetuximab’s EGFR inhibitory action in human (1). Ras human genes have recognized counterparts in yeast, RAS1 and RAS2. The corresponding proteins belong to the PKA/cAMP MAPK pathway are involved in cell proliferation, in differentiation into hyphae and spores, in response to nitrogen starvation, and in carbon source regulation (4, 5). In opposition to Ras, yeasts do not have a recognized ortholog of EGFR. Nevertheless, yeast is sensitive to Imatinib, another drug that targets specifically EGFR in human cells (6). We generated recombinant yeast strains expressing human wild-type (wt) and mutated open reading frames (ORFs) of K-ras to use in the optimization of phenotypic tests appropriate for the assessment of cell sensitivity to Cetuximab. We observed that Saccharomyces cerevisiae, is sensitive to the treatment with this drug at identical concentration as human cell cultures. Moreover, the complementation of yeast deletions in RAS1 and/or RAS2 with wt or the above mentioned mutated forms of human K-RAS did not alter the response of the cells to the treatment. This suggests that the sensitivity of S. cerevisiae to Cetuximab is independent of the Ras/cAMP pathway. These results further indicate the existence of a paralog of EGFR protein in yeast cell surface. In view of these results, research focused on identifying the EGFR yeast counterpart, downstream effectors and target genes, and determining the correspondent Cetuximab/Erbitux® mode of action.Este trabalho é financiado por Fundos FEDER através do Programa Operacional Factores de Competitividade – COMPETE e por Fundos Nacionais através da FCT – Fundação para a Ciência e a Tecnologia no âmbito do projecto PEst-C/BIA/UI4050/201

Mathematical model with fractional order derivatives for Tuberculosis taking into account its relationship with HIV/AIDS and Diabetes

In this paper, we present a mathematical model for the study of resistance to tuberculosis treatment using fractional derivatives in the Caputo sense. This model takes into account the relationship between Tuberculosis, HIV/AIDS, and diabetes and differentiates resistance cases into MDR-TB (multidrug-resistant tuberculosis) and XDR-TB (extensively drug-resistant tuberculosis). We present the basic results associated with the model and study the behavior of the disease-free equilibrium points in the different sub-populations, TB-Only, TB-HIV/AIDS, and TB-Diabetes. We performed computational simulations for different fractional orders (α-values) using an Adams-Bashforth-Moulton type predictor-corrector PECE method. Among the results obtained, we have that the MDR-TB cases in all sub-populations decrease at the beginning of the study for the different α-values. In XDR-TB cases in the TB-Only sub-population, there is a decrease in the number of cases. XDR-TB cases in the TB-HIV/AIDS sub-population have differentiated behavior depending on α. This knowledge helps to design an effective control strategy. The XDR-TB cases in diabetics increased throughout the study period and outperformed all resistant compartments for the different α-values. We recommend special attention to the control of this compartment due to this growth

Early Cretaceous Surtseyan volcanoes of the Baño Nuevo Volcanic Complex (Aysén Basin, eastern central Patagonian Cordillera, Chile)

Tens of Surtseyan tuff cones are exposed in the Río Coichel valley, between Ñireguao and Estancia Baño Nuevo (Southern Chilean Andes). The Early Cretaceous products of the submarine eruptions rest on, or are interbedded with, shallow marine sandstones of the Hauterivian-early Aptian Apeleg Formation. The Early Cretaceous rocks typically contain large amphibole phenocrysts, clinopyroxene and plagioclase, and have compositions that range from relatively primitive basalts to andesites. The basalts are slightly enriched in LREE and incompatible trace elements. They have low Ti-contents and negative anomalies in Nb and Ta, characteristic of subduction-related magmas. Centimetre-sized amphibole megacrysts and an amphibole-bearing clinopyroxenite xenolith have been found in one of the tuff cones located near Estancia Baño Nuevo. The amphibole megacrysts are pargasite (low Si and Ti, high Mg). The xenolith has diopsidic clinopyroxene with abundant inclusions, and pargasite veins enclosing smaller clinopyroxene neoblasts. Geochemical data show that the megacrysts and the xenolith have the same origin and correspond to underplated igneous bodies crystallized at high pressure

Acoustic localization of tactile interactions for the development of novel tangible interfaces

In this paper we propose different acoustic array processing methods for the localization of tactile interactions with planar surfaces. The aim is to create a new class of tangible interfaces for musical performance that can be obtained by simply applying sensors on existing surfaces. The solutions considered in this paper are mainly based on the measurement and the analysis of the Time-Delay-Of-Arrival (TDOA) over a set of contact sensors, placed around the area of potential contact, and allows us to rapidly localize tactile interactions with reasonable accuracy