Functional and evolutionary analysis of DXL1, a non-essential gene encoding a 1-deoxy-D-xylulose 5-phosphate synthase like protein in Arabidopsis thaliana

The synthesis of 1-deoxy-D-xylulose 5-phosphate (DXP), catalyzed by the enzyme DXP synthase (DXS), represents a key regulatory step of the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway for isoprenoid biosynthesis. In plants DXS is encoded by small multigene families that can be classified into, at least, three specialized subfamilies. Arabidopsis thaliana contains three genes encoding proteins with similarity to DXS, including the well-known DXS1/CLA1 gene, which clusters within subfamily I. The remaining proteins, initially named DXS2 and DXS3, have not yet been characterized. Here we report the expression and functional analysis of A. thaliana DXS2. Unexpectedly, the expression of DXS2 failed to rescue Escherichia coli and A. thaliana mutants defective in DXS activity. Coherently, we found that DXS activity was negligible in vitro, being renamed as DXL1 following recent nomenclature recommendation. DXL1 is targeted to plastids as DXS1, but shows a distinct expression pattern. The phenotypic analysis of a DXL1 defective mutant revealed that the function of the encoded protein is not essential for growth and development. Evolutionary analyses indicated that DXL1 emerged from DXS1 through a recent duplication apparently specific of the Brassicaceae lineage. Divergent selective constraints would have affected a significant fraction of sites after diversification of the paralogues. Furthermore, amino acids subjected to divergent selection and likely critical for functional divergence through the acquisition of a novel, although not yet known, biochemical function, were identified. Our results provide with the first evidences of functional specialization at both the regulatory and biochemical level within the plant DXS family.

CDK4 is an essential insulin effector in adipocytes.

Insulin resistance is a fundamental pathogenic factor that characterizes various metabolic disorders, including obesity and type 2 diabetes. Adipose tissue contributes to the development of obesity-related insulin resistance through increased release of fatty acids, altered adipokine secretion, and/or macrophage infiltration and cytokine release. Here, we aimed to analyze the participation of the cyclin-dependent kinase 4 (CDK4) in adipose tissue biology. We determined that white adipose tissue (WAT) from CDK4-deficient mice exhibits impaired lipogenesis and increased lipolysis. Conversely, lipolysis was decreased and lipogenesis was increased in mice expressing a mutant hyperactive form of CDK4 (CDK4R24C). A global kinome analysis of CDK4-deficient mice following insulin stimulation revealed that insulin signaling is impaired in these animals. We determined that insulin activates the CCND3-CDK4 complex, which in turn phosphorylates insulin receptor substrate 2 (IRS2) at serine 388, thereby creating a positive feedback loop that maintains adipocyte insulin signaling. Furthermore, we found that CCND3 expression and IRS2 serine 388 phosphorylation are increased in human obese subjects. Together, our results demonstrate that CDK4 is a major regulator of insulin signaling in WAT.

Multiparametric magnetic resonance imaging of the prostate: current concepts

Multiparametric MR (mpMR) imaging is rapidly evolving into the mainstay in prostate cancer (PCa) imaging. Generally, the examination consists of T2-weighted sequences, diffusion-weighted imaging (DWI), dynamic contrast-enhanced (DCE) evaluation, and less often proton MR spectroscopy imaging (MRSI). Those functional techniques are related to biological properties of the tumor, so that DWI correlates to cellularity and Gleason scores, DCE correlates to angiogenesis, and MRSI correlates to cell membrane turnover. The combined use of those techniques enhances the diagnostic confidence and allows for better characterization of PCa. The present article reviews and illustrates the technical aspects and clinical applications of each component of mpMR imaging, in a practical approach from the urological standpoint.

Learning 2.0 : concepts and experiences

E-learning arises in all educative contexts and levels with the use of information and communication technologies and massive access to internet connected computers. On the other hand, the fast development of social networking tools and web 2.0 technologies are producing an evolution of e-learning towards what is called a learning 2.0 paradigm. In this short paper weshall present the main technologies and pedagogical issues related to that new way of learning and how we can use them to improve the acquisition of competences and new knowledge.

Learning 2.0 : concepts and experiences with social networks and software

Peer-reviewed

Functional EF-hands in neuronal calcium sensor GCAP2 determine its phosphorylation state and subcellular distribution in vivo, and are essential for photoreceptor cell integrity

The neuronal calcium sensor proteins GCAPs (guanylate cyclase activating proteins) switch between Ca2+-free and Ca2+-bound conformational states and confer calcium sensitivity to guanylate cyclase at retinal photoreceptor cells. They play a fundamental role in light adaptation by coupling the rate of cGMP synthesis to the intracellular concentration of calcium. Mutations in GCAPs lead to blindness. The importance of functional EF-hands in GCAP1 for photoreceptor cell integrity has been well established. Mutations in GCAP1 that diminish its Ca2+ binding affinity lead to cell damage by causing unabated cGMP synthesis and accumulation of toxic levels of free cGMP and Ca2+. We here investigate the relevance of GCAP2 functional EF-hands for photoreceptor cell integrity. By characterizing transgenic mice expressing a mutant form of GCAP2 with all EF-hands inactivated (EF(-)GCAP2), we show that GCAP2 locked in its Ca2+-free conformation leads to a rapid retinal degeneration that is not due to unabated cGMP synthesis. We unveil that when locked in its Ca2+-free conformation in vivo, GCAP2 is phosphorylated at Ser201 and results in phospho-dependent binding to the chaperone 14-3-3 and retention at the inner segment and proximal cell compartments. Accumulation of phosphorylated EF(-)GCAP2 at the inner segment results in severe toxicity. We show that in wildtype mice under physiological conditions, 50% of GCAP2 is phosphorylated correlating with the 50% of the protein being retained at the inner segment. Raising mice under constant light exposure, however, drastically increases the retention of GCAP2 in its Ca2+-free form at the inner segment. This study identifies a new mechanism governing GCAP2 subcellular distribution in vivo, closely related to disease. It also identifies a pathway by which a sustained reduction in intracellular free Ca2+ could result in photoreceptor damage, relevant for light damage and for those genetic disorders resulting in 'equivalent-light'' scenarios.

Social media marketing strategy: concepts and steps to form connections

The emergence of social media has led many companies to adopt them as marketing channels. Yet these media are novel enough that many marketers are still unsure as to how to plan an effective social media marketing strategy, actually oriented towards engaging prospects. In this article, we discuss how to shape a social media strategy. To do so, we show the key concepts and steps involved in the planning process of this type of digital marketing strategy, and how to measure their impact immediately.

Concepts and Reference. Defending a Dual Theory of Natural Kind Concepts

In this thesis I argue that the psychological study of concepts and categorisation, and the philosophical study of reference are deeply intertwined. I propose that semantic intuitions are a variety of categorisation judgements, determined by concepts, and that because of this, concepts determine reference. I defend a dual theory of natural kind concepts, according to which natural kind concepts have distinct semantic cores and non-semantic identification procedures. Drawing on psychological essentialism, I suggest that the cores consist of externalistic placeholder essence beliefs. The identification procedures, in turn, consist of prototypes, sets of exemplars, or possibly also theory-structured beliefs. I argue that the dual theory is motivated both by experimental data and theoretical considerations. The thesis consists of three interrelated articles. Article I examines philosophical causal and description theories of natural kind term reference, and argues that they involve, or need to involve, certain psychological elements. I propose a unified theory of natural kind term reference, built on the psychology of concepts. Article II presents two semantic adaptations of psychological essentialism, one of which is a strict externalistic Kripkean-Putnamian theory, while the other is a hybrid account, according to which natural kind terms are ambiguous between internalistic and externalistic senses. We present two experiments, the results of which support the strict externalistic theory. Article III examines Fodor’s influential atomistic theory of concepts, according to which no psychological capacities associated with concepts constitute them, or are necessary for reference. I argue, contra Fodor, that the psychological mechanisms are necessary for reference.

Design concepts for the Cherenkov Telescope Array CTA: an advanced facility for ground-based high-energy gamma-ray astronomy

Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.

Design concepts for the Cherenkov Telescope Array CTA: an advanced facility for ground-based high-energy gamma-ray astronomy

Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.

Design concepts for the Cherenkov Telescope Array CTA: an advanced facility for ground-based high-energy gamma-ray astronomy

Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.

Pensamiento geográfico versus teoría de la comunicación. Hacia un modelo de análisis comunicativo del paisaje

The study of the communicative implications related to landscapes opens a wide range of possibilities concerning the treatment of the communication and landscape relationship. Issues such as the effects of the landscape on the processes of human communication (intrapersonal and interpersonal communication), the follow-up of the communicative processes by means of which the landscape becomes an object of trade (mass communication), the construction of individual and collective imaginaries arising from the citizenship and landscape exchange and, recently, the construction of territorial identities through the production of a brand image of a city or country (i. e., tourist promotion, city marketing and branding). All of them have important implications in the contemporary societies. For that reason, it appears almost essential to progress towards a communicative landscape model, a target which becomes possible if we interrelate geography and communication studies, two fields apparently unrelated one another concerning their origins and practice, although they are very close if we look at the recent evolution of their paradigms and the approach to certain concepts, such as space and landscape.

Composition and antifungal activity of essential oils from Piper aduncum, Piper arboreum and Piper tuberculatum

The composition of essential oils from leaves, stems and fruits of Piper aduncum, P. arboreum and P. tuberculatum was examined by means of GC-MS and antifungal assay. There was a predominance of monoterpenes in P. aduncum and P. tuberculatum and of sesquiterpenes in P. arboreum. P. aduncum showed the richest essential oil composition, including linalool. The essential oils from fruits of P. aduncum and P. tuberculatum showed the highest antifungal activity with the MIC of 10 µg as determined against Cladosporium cladosporioides and C. sphaerospermum, respectively. This is the first report of the composition of essential oils from P. tuberculatum.