Phosphatidylinositol 3-kinase improves the efficiency of positive selection

We have generated transgenic mice expressing the amino-terminal fragment of the phosphatidylinositol 3-kinase (PI3K) catalytic subunit (p110(ABD)) in thymocytes. Expression of P110(ABD) results in constitutive activation of PI3K and in significant increases in the numbers of mature, single-positive thymocytes. We previously reported that the increase in mature cells was in part due to a defect in thymic emigration. In this study we identify another component to this phenotype. Expression of p110(ABD) results in an enhancement of positive selection, without alterations in thymocyte lifespan or negative selection. Since PI3K can affect activation of Btk, which in turn potentiates calcium fluxes, during B cell development, our results suggest that PI3K could play a role in the regulation of Itk kinases in T cells, and that both cell types share a common signaling network to modulate calcium responses downstream of their antigen receptor

Development of ERK Activity Sensor, an in vitro, FRET-based sensor of Extracellular Regulated Kinase activity

BACKGROUND: Study of ERK activation has thus far relied on biochemical assays that are limited to the use of phospho-specific antibodies and radioactivity in vitro, and analysis of whole cell populations in vivo. As with many systems, fluorescence resonance energy transfer (FRET) can be utilized to make highly sensitive detectors of molecular activity. Here we introduce FRET-based ERK Activity Sensors, which utilize variants of Enhanced Green Fluorescent Protein fused by an ERK-specific peptide linker to detect ERK2 activity. RESULTS: ERK Activity Sensors display varying changes in FRET upon phosphorylation by active ERK2 in vitro depending on the composition of ERK-specific peptide linker sequences derived from known in vivo ERK targets, Ets1 and Elk1. Analysis of point mutations reveals specific residues involved in ERK binding and phosphorylation of ERK Activity Sensor 3. ERK2 also shows high in vitro specificity for these sensors over two other major MAP Kinases, p38 and pSAPK/JNK. CONCLUSION: EAS's are a convenient, non-radioactive alternative to study ERK dynamics in vitro. They can be utilized to study ERK activity in real-time. This new technology can be applied to studying ERK kinetics in vitro, analysis of ERK activity in whole cell extracts, and high-throughput screening technologies

On the relevance and nature of regional inflation differentials : the case of Spain

El proposito de este trabajo es estudiar la naturaleza y relevancia de los diferenciales provinciales de inflacion en una Union Monetaria consolidada como la española. Encontramos que los diferenciales de inflacion son pequeños en magnitud (menos de medio punto porcentual por año a largo plazo), aunque las desviaciones del nivel nacional de precios para determinadas provincias pueden ser muy persistentes. Los cambios en los precios relativos responden a las caracteristicas intrinsecas de una economia muy integrada, en particular por mecanismos nacionales de fijacion de precios y salarios. Este resultado y el signo de las relaciones resultantes son los opuestos a los hallados cuando se estudian precios relativos entre paises, donde la hipotesis de Balassa- Samuelson resulta corroborada. Por lo tanto, aunque los diferenciales de inflacion en una Union Monetaria son posibles y persistentes, es probable que el diferente grado de integracion entre los paises de la UME haga que la naturaleza de estos sea distinta. (ea) (ad

Sovereign external assets and the resilience of global imbalances

Sovereign external assets (SEAs) comprise foreign exchange reserves and sovereign wealth funds (SWFs). The global stock of reserves reached 7 $trn in the second quarter of 2008, but data on SWF are rather elusive. Our estimation puts the SWFs at around 2,5$trn dollars by 2007 and in the last years they have grown at a high pace, fostered by high commodity prices. Therefore, SEAs have surpassed the 10 $trn mark (around 5$ trillion increase in 2007relative to US financing needs, this amount represents around a 135% and 50% of net and gross needs, respectively, in 2007. Reserves have in the last years contributed 80% and SWFs 20%.Looking ahead, two main conclusions can be put forward: 1) the relative importance SWFs in the financing of the US deficits and global imbalances is set to increase (also relative to reserves), but this is conditional to commodity prices remaining at high levels. On the one hand, the economic motivation of SWFs -intertemporal smoothing- is more palatable than that of reserves (exchange rate management), despite political concerns on SWFson the other hand, SWFs do not have significant internal costs, contrary to reserves, whose monetary and fiscal costs are increasing in the margin.

Debt sustainability and procyclical fiscal policies in Latin America

The computation of structural primary balances for the nine main Latin American countries and their comparison of their changes with their cyclical position during the period 1981-2004 confirms that fiscal policy is procyclical in the region. From this evidence, the paper shows strong evidence that the fiscal behaviour is closely linked to the financial vulnerability position of the economies and in particular to the perception on the sustainability of debt. The current threshold balance, defined as the primary balance which would render the debt stable under the existing economic and financial conditions, is used as our gauge for measuring debt sustainability at each point in time. The empirical analysis reveals that the fiscal stance tightens when the debt sustainability perceptions worsen, and that this effect is stronger the less sustainable debt is perceived. The results are robust to different specifications and estimation methods. [resumen de autor

Global financial integration, monetary policy and reserve accumulation : assesing the limits in emerging economies

This paper assesses whether domestic costs of reserve accumulation -and in particular monetary costs- constitute an eventual limit to the process in emerging markets. We find that sterilization is the first measure to deal with these costs. Then, we turn to study whether diminishing ability to deal with the monetary inflows through sterilization is an effective limit to the process, Indeed, when the scope for sterilization is reduced, accumulation diminishes. However, this constraint, albeit relevant in practice, has not constituted an effective limit to accumulation, hithert

International reserves and gross capital flows : dynamics during financial stress

This paper explores the role of international reserves as a stabilizer of international capital flows during periods of global financial stress. In contrast with previous contributions, aimed at explaining net capital flows, we focus on the behavior of gross capital flows. We analyze an extensive cross-country quarterly database using event analyses and standard panel regressions. We document significant heterogeneity in the response of resident investors to financial stress and relate it to a previously undocumented channel through which reserves are useful during financial stress. International reserves facilitate financial disinvestment overseas by residents, offsetting the simultaneous drop in foreign financingEste trabajo estudia el papel de las reservas internacionales como una fuerza estabilizadora de los flujos de capital internacionales durante períodos de estrés global. A diferencia de contribuciones anteriores, centradas en estudiar los flujos de capital netos, este trabajo se centra en el comportamiento de los flujos de capital brutos. Mediante el uso de técnicas de panel y análisis de eventos analizamos una base de datos trimestrales con una amplia cobertura geográfica. Nuestros resultados muestran una marcada heterogeneidad en la respuesta de los inversores residentes a períodos de estrés, y relacionan dicha heterogeneidad con un canal para el que hasta la fecha no había evidencia empírica: las reservas internacionales facilitan la repatriación del capital que los inversores residentes tienen depositado en otros países, lo cual compensa la caída en la financiación internacional que se observa durante estos evento

Los desequilibrios globales y el reequilibrio de la economía mundial

Artículo de revist

Diferenciales interregionales de inflación y sus implicaciones para la Unión Monetaria

Artículo de revistaEl objetivo del articulo es tratar de proporcionar una explicacion a la disparidad de resultados en el analisis de los diferenciales de inflacion entre provincias españolas y la que se observa entre paises. Del estudio se derivan algunas conclusiones respecto a los posibles determinantes de los diferenciales nacionales de inflacion en la UEM. (ad