The Effect of ICT on Trade: Does Product Complexity Matter?

We use a gravity model of trade to investigate the effect of internet use on aggregate trade flows. We apply a structural gravity model using up-to-date PPML estimation techniques to a sample of bilateral exports of 120 countries over the period 2000–2014. In contrast to previous studies, we segment countries according to their degree of product complexity and estimate the model for each segment. The results show that internet use increases trade, and the segmentation by product complexity is more sensitive to internet use than segmenting by level of income. The main results also indicate that countries trade more if similar levels of ICT use are coupled with similar degrees of product complexity in the trading countries

Función de Sfrp1 (Secreted Frizzled Related Protein 1) durante el desarrollo de la corteza cerebral y estudio de su posible implicación en la Enfermedad de Alzheimer

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Bioquímica. Fecha de lectura: 26-01-2016Esta tesis tiene embargado el acceso al texto completo hasta el 26-07-2017Las proteínas Secreted Frizzled Related Proteins (Sfrps) son una familia de moléculas solubles relacionadas estructuralmente con la parte extracelular de los receptores Frizzled. Además de su papel como antagonistas de los ligandos Wnt, estas proteínas tienen otras funciones. Trabajos previos del laboratorio han demostrado que, en retina periférica, las Sfrps son requeridas para la activación de la vía de señalización Wnt/β-catenina al favorecer la difusión de los ligandos Wnt. En la retina neural central en cambio, las Sfrps modulan la actividad metaloproteinasa ADAM10, una α-secretasa responsable del procesamiento de múltiple substratos, incluidos los receptores Notch y la proteína precursora de amiloide (APP). A través de la regulación de Notch, las Sfrps por lo tanto contribuyen a una correcta neurogénesis en la retina. En esta tesis hemos analizado si esta doble función de las Sfrps ocurre únicamente en la retina o se produce también en otras regiones del Sistema Nervioso Central del ratón. Por ello, nos hemos centrado en el telencéfalo donde Sfrp1 se expresa abundantemente durante la etapa embrionaria. Nuestros datos indican que la inactivación genética de Sfrp1 implica un descenso en la señalización de la vía Wnt/β-catenina en el palio medial embrionario con una consecuente reducción del primordio hipocampal y una expansión de la futura neocorteza, defectos que se mantienen en estadios postnatales. Por otro lado, en el palio dorsal, los embriones Sfrp1-/- presentan de forma transitoria una mayor activación de la vía de señalización de Notch y una leve disminución de la expresión de Axina2, una diana de la vía β-catenina. Estos cambios moleculares se asocian a un incremento en la proliferación de los progenitores, con el resultado que el neocórtex postnatal de los ratones Sfrp1-/- es más grueso. Sfrp1 se expresa en la corteza cerebral también en la etapa adulta, y su expresión aumenta en situaciones patológicas como la Enfermedad de Alzheimer (EA). En esta tesis nos hemos preguntado si Sfrp1, regulando ADAM10, influye en el procesamiento de APP y por lo tanto en la formación de placas amiloideas. Puesto que ADAM10 corta APP dentro de la secuencia Aβ, generando un fragmento sAPPα y previniendo la formación de péptidos Aβ, una mayor actividad de ADAM10 debería aumentar los niveles de sAPPα y disminuir los de Aβ. Nuestro análisis demuestra que en ratones silvestres la inactivación genética de Sfrp1 incrementa los niveles de sAPPα. Además, en un modelo murino de EA junto a la deficiencia de Sfrp1, se observa un descenso en el número de placas amiloideas y de los daños cognitivos que normalmente caracterizan estos ratones. En su conjunto, los datos obtenidos en este trabajo revelan que Sfrp1 desempeña un papel importante en la corteza cerebral durante el desarrollo embrionario y en la homeostasis del cerebro adulto. Además, abre una importante puerta en la comprensión de las bases moleculares de enfermedades del desarrollo como el autismo así como en el diagnóstico y posible tratamiento de la EA

Modelización del transporte de contaminantes en redes de saneamiento urbano

A pesar de que, en términos generales, la forma disuelta de los contaminantes suele ser más tóxica y más reactiva química y biológicamente, el impacto de la forma particulada resulta más significativo a largo plazo debido a su capacidad de acumulación y a su capacidad de actuar como una fuente secundaria de contaminantes disueltos. Por tal motivo, se ha considerado fundamental incluir la dinámica de los sólidos en suspensión puesto que la contaminación de sedimentos es considerada por varios organismos ambientales internacionales como el mayor riesgo en los ambientes acuáticos. En consecuencia, la predicción del transporte, erosión y deposición de los sedimentos es una labor de suma importancia para el entendimiento de las características de la calidad de las aguas. No obstante, debe tenerse presente que aunque la introducción de un mayor número de variables en el modelo permite realizar un análisis más preciso, requiere también de una mayor cantidad de información para alimentarlo. Las zonas de costa soportan una fuerte presión antrópica debida, principalmente, a la rápida industrialización y el aumento poblacional, lo cual, se traduce en fuentes de contaminación representadas por descargas de efluentes domésticos e industriales. Tal es el caso, por ejemplo, de la Ría de Huelva en la que, además de la presión que representa la propia actividad industrial y portuaria, los vertidos mineros y la erosión de terrenos piríticos acidifican las aguas más lejanas al mar permitiendo que los metales se mantengan en forma disuelta. El objetivo principal de este trabajo ha sido presentar un modelo simplificado para predecir la tasa de transporte de sedimentos en las tuberías de alcantarillado unitario. La distribución del tamaño de partícula y la densidad de partículas son factores muy significativos en los modelos de transporte. Varía dependiendo de la ubicación del alcantarillado y la fuente de contaminantes. En este sentido, se ha llevado a cabo un análisis de sensibilidad de la tasa de transporte y los perfiles de concentración en tuberías. El modelo que se presenta resulta de la integración de dos modelos. De un lado el Modelo de Gestión de Aguas Residuales (SWMM) de la EPA, y de otro, la incorporación a este primero del modelado del transporte de sedimentos en el interior de las conducciones del sistema de saneamiento. Esta incorporación complementa y enriquece el análisis de la red solventando la limitación del software de la EPA de no simular la propagación de contaminantes en el flujo subsuperficial, es decir, dentro de las conducciones, una vez el flujo de escorrentía entra al sistema de saneamiento.Although the dissolved form of pollutants is generally more toxic and more reactive chemically and biologically, the impact of the particulate form is more significant in the long term because of its accumulation capacity and its capacity to act as a secondary source of dissolved contaminants. For this reason, it has been considered essential to include the dynamics of suspended solids since sediment contamination is considered by several international environmental organisms as the greatest risk in aquatic environments. Consequently, prediction of sediment transport, erosion and deposition is an extremely important task in understanding the characteristics of water quality. However, it should be borne in mind that although the introduction of a greater number of variables in the model allows for a more precise analysis, it also requires a greater amount of information to feed it. The coastal zones bear strong anthropic pressure due mainly to rapid industrialization and population increase, which translates into pollution sources represented by domestic and industrial effluent discharges. This is the case, for example, of the Ria de Huelva in which, in addition to the pressure of industrial and port activity itself, mining spills and the erosion of pyritic terrains acidify the waters further away from the sea by allowing metals are maintained in dissolved form. The main aim of this work is to present a simplified model to predict the sediment transport rate in combined sewer pipe. Particle size distribution and particle density are very significant factors in transport models. It varies in function of the sewer location and pollutant source. A sensitivity analysis of the transport rate and concentration profiles in pipes has been conducted in this study. The model presented results from the integration of two models. On the one hand, the EPA's Wastewater Management Model (SWMM), and on the other, the simplified model to predict the sediment transport rate in combined sewer pipe. This integration complements and enriches the network analysis by solving the EPA's software limitation of not simulating the propagation of contaminants in the subsurface flow, i.e. within the pipelines, once the runoff flow enters the sanitation system. As well as other predictive models allow to obtain information for the analysis of the temporal and spatial distribution of the emissions to the environment, essential tool as support to the decision making to improve the control of the intermittent contamination by discharges of unitary systems. You can also obtain information on load patterns that arrive at a sewage plant or a holding tank at the start of a storm event, allowing for more rational resource planning

N-terminal palmitoylation within the appropriate amino acid environment conveys on NOS2 the ability to progress along the intracellular sorting pathways.

We have analysed the mechanism by which palmitoylation permits the progression of nitric oxide synthase 2 (NOS2) along the ER-Golgi-TGN pathway. Introduction of an additional myristoylation site at the N-terminus of NOS2 resulted in a chimera that displayed an enhanced association with the particulate fraction and with the plasma membrane but did not display increased enzymatic activity. In the absence of palmitoylation, introduction of a surrogate myristoylation site resulted in a mutant NOS2 with only 25% activity compared with the wild-type enzyme. Hence, the novel surrogate myristoyl moiety not only failed to increase NOS2 activity when introduced in a wild-type sequence environment, but was also unable to rescue the inactive phenotype of the Cys3Ser mutant. Introduction of an additional palmitoylatable Cys at position 2 of the wild-type sequence resulted in a chimera that associated to a larger degree with membranes and displayed decreased activity. Our data indicate that palmitoylation of inducible NOS at position 3 exquisitely determines its transit along the secretory pathway following a route that cannot be mimicked by a surrogate myristoylation or by a palmitate at position 2. In addition, the exit of NOS2 from the TGN and the accumulation in the cellular plasma membrane per se did not correlate with increased .NO synthesis.S

Autophagic flux is required for the synthesis of triacylglycerols and ribosomal protein turnover in Chlamydomonas

Autophagy is an intracellular catabolic process that allows cells to recycle unneeded or damaged material to maintain cellular homeostasis. This highly dynamic process is characterized by the formation of double-membrane vesicles called autophagosomes, which engulf and deliver the cargo to the vacuole. Flow of material through the autophagy pathway and its degradation in the vacuole is known as autophagic flux, and reflects the autophagic degradation activity. A number of assays have been developed to determine autophagic flux in yeasts, mammals, and plants, but it has not been examined yet in algae. Here we analyzed autophagic flux in the model green alga Chlamydomonas reinhardtii. By monitoring specific autophagy markers such as ATG8 lipidation and using immunofluorescence and electron microscopy techniques, we show that concanamycin A, a vacuolar ATPase inhibitor, blocks autophagic flux in Chlamydomonas. Our results revealed that vacuolar lytic function is needed for the synthesis of triacylglycerols and the formation of lipid bodies in nitrogen- or phosphate-starved cells. Moreover, we found that concanamycin A treatment prevented the degradation of ribosomal proteins RPS6 and RPL37 under nitrogen or phosphate deprivation. These results indicate that autophagy might play an important role in the regulation of lipid metabolism and the recycling of ribosomal proteins under nutrient limitation in ChlamydomonasEspaña, MINECO BFU2015-68216-PEspaña, Junta de Andalucía CVI-7336 (to JLC), BIO2015-74432-JIN (to MEPP

The impact of peer attachment on prosocial behavior, emotional difficulties and conduct problems in adolescence: The mediating role of empathy.

Attachment theories postulate that during adolescence, peer relationships become more important as a predictor of positive social, emotional and behavioral outcomes. Adolescents develop the ability to empathize with others, which is related to healthy functioning and positive peer relationships. Empathy has been studied as a potential mechanism that may help to explain how strong and healthy emotional bonds are associated with less emotional disorders and conduct problems in youth. The main purpose of this study was to examine the relationship between peer attachment and strengths and difficulties during adolescence, considering empathy as a potential mediator of this association. A total of 800 Spanish adolescents (56.65% girls), aged between 12 and 15 years (M= 14.02, SD= 1.21), completed measures of peer attachment, empathy, conduct problems, emotional difficulties and prosocial behavior. Structural equation models indicated that peer attachment was negatively associated with conduct problems and emotional difficulties but positively related to prosocial behavior. In general, empathy mediated the link between peer attachment and both emotional and behavioral outcomes, without significant group differences between boys and girls. The discussion focuses on the importance of healthy peer relationships as a powerful predictor of emotional well-being and psychological problems in adolescence

The TOR Signaling Network in the Model Unicellular Green Alga Chlamydomonas reinhardtii

Cell growth is tightly coupled to nutrient availability. The target of rapamycin (TOR) kinase transmits nutritional and environmental cues to the cellular growth machinery. TOR functions in two distinct multiprotein complexes, termed TOR complex 1 (TORC1) and TOR complex 2 (TORC2). While the structure and functions of TORC1 are highly conserved in all eukaryotes, including algae and plants, TORC2 core proteins seem to be missing in photosynthetic organisms. TORC1 controls cell growth by promoting anabolic processes, including protein synthesis and ribosome biogenesis, and inhibiting catabolic processes such as autophagy. Recent studies identified rapamycin-sensitive TORC1 signaling regulating cell growth, autophagy, lipid metabolism, and central metabolic pathways in the model unicellular green alga Chlamydomonas reinhardtii. The central role that microalgae play in global biomass production, together with the high biotechnological potential of these organisms in biofuel production, has drawn attention to the study of proteins that regulate cell growth such as the TOR kinase. In this review we discuss the recent progress on TOR signaling in algae.España, MINECO BFU2015-68216-

Investigating the effect of target of rapamycin kinase inhibition on the Chlamydomonas reinhardtii phosphoproteome: from known homologs to new targets

Recuperado de: https://www.biorxiv.org/content/10.1101/310102v1Target of rapamycin (TOR) kinase is a conserved regulator of cell growth whose activity is modulated in response to nutrients, energy and stress. Key proteins involved in the pathway are conserved in the model photosynthetic microalga Chlamydomonas reinhardtii, but the substrates of TOR kinase and downstream signaling network have not been elucidated. Our study provides a new resource for investigating the phosphorylation networks governed by the TOR kinase pathway in Chlamydomonas. We used quantitative phosphoproteomics to investigate the effects of inhibiting Chlamydomonas TOR kinase on dynamic protein phosphorylation. Wild-type and AZD-insensitive Chlamydomonas strains were treated with TOR-specific chemical inhibitors (rapamycin, AZD8055 and Torin1), after which differentially affected phosphosites were identified. Our quantitative phosphoproteomic dataset comprised 2547 unique phosphosites from 1432 different proteins. Inhibition of TOR kinase caused significant quantitative changes in phosphorylation at 258 phosphosites, from 219 unique phosphopeptides. Our results include Chlamydomonas homologs of TOR signaling-related proteins, including a site on RPS6 with a decrease in phosphorylation. Additionally, phosphosites on proteins involved in translation and carotenoid biosynthesis were identified. Follow-up experiments guided by these phosphoproteomic findings in lycopene beta/epsilon cyclase showed that carotenoid levels are affected by TORC1 inhibition and carotenoid production is under TOR control in algae.National Science Foundation CAREER MCB-155252

Distance-dependent cellular palmitoylation of de-novo-designed sequences and their translocation to plasma membrane subdomains.

Using recursive PCR, we created an artificial protein sequence that consists of a consensus myristoylation motif (MGCTLS) followed by the triplet AGS repeated nine times and fused to the GFP reporter. This linker-GFP sequence was utilized as a base to produce multiple mutants that were used to transfect COS-7 cells. Constructs where a 'palmitoylable' cysteine residue was progressively moved apart from the myristoylation site to positions 3, 9, 15 and 21 of the protein sequence were made, and these mutants were used to investigate the effect of protein myristoylation on subsequent palmitoylation, subcellular localization, membrane association and caveolin-1 colocalization. In all cases, dual acylation of the GFP chimeras correlated with translocation to Triton X-100-insoluble cholesterol/sphingomyelin-enriched subdomains. Whereas a strong Golgi labeling was observed in all the myristoylated chimeras, association with the plasma membrane was only observed in the dually acylated constructs. Taking into account the conflicting data regarding the existence and specificity of cellular palmitoyl-transferases, our results provide evidence that de-novo-designed sequences can be efficiently S-acylated with palmitic acid in vivo, strongly supporting the hypothesis that non-enzymatic protein palmitoylation can occur within mammalian cells. Additionally, this palmitoylation results in the translocation of the recombinant construct to low-fluidity domains in a myristate-palmitate distance-dependent manner.S

Phosphorus Availability Regulates TORC1 Signaling via LST8 in Chlamydomonas

Target of rapamycin complex 1 (TORC1) is a central regulator of cell growth. It balances anabolic and catabolic processes in response to nutrients, growth factors, and energy availability. Nitrogen- and carbon-containing metabolites have been shown to activate TORC1 in yeast, animals, and plants. Here, we show that phosphorus (P) regulates TORC1 signaling in the model green alga Chlamydomonas (Chlamydomonas reinhardtii) via LST8, a conserved TORC1 subunit that interacts with the kinase domain of TOR. P starvation results in a sharp decrease in LST8 abundance and downregulation of TORC1 activity. A hypomorphic lst8 mutation resulted in decreased LST8 abundance, and it both reduced TORC1 signaling and altered the cellular response to P starvation. Additionally, we found that LST8 levels and TORC1 activity were not properly regulated in a mutant defective in the transcription factor PSR1, which is the major mediator of P deprivation responses in Chlamydomonas. Unlike wild-type cells, the psr1 mutant failed to downregulate LST8 abundance and TORC1 activity when under P limitation. These results identify PSR1 as an upstream regulator of TORC1 and demonstrate that TORC1 is a key component in P signaling in Chlamydomonas.España Ministerio de Economía y Competitividad (grants BFU2015-68216-P and PGC2018-099048- B-100 to J.L.C. and grant BIO2015-74432-JIN to M.E.P.-P.)National Science Foundation (CAREER award MCB-1552522 to L.M.H. and grant MCB-1616820 to J.G.U.)European Commission (grant number 750996