Bacterial toxins and the immune system: show me the in vivo targets

Microorganisms that cause persistent infection often exhibit specific adaptations that allow them to avoid the adaptive immune response. Recently, several bacterial toxins have been shown in vitro to disrupt immune cell functions. However, it remains to be established whether these activities are relevant during infection and whether these toxins have specifically evolved to disrupt the adaptive immune system

The benefits are at the tail: uncovering the impact of macroprudential policy on growth-at-risk

Este estudio une los desarrollos recientes sobre la metodología de crecimiento en riesgo con la literatura sobre evaluaciones de impacto de la política macroprudencial. Para ello, extiendo el uso de regresiones cuantílicas del crecimiento del PIB con el objetivo de incluir variables macrofinancieras con propiedades de alerta temprana de riesgo sistémico y medidas macroprudenciales. Como resultado, encuentro efectos heterogéneos de la política macroprudencial sobre el crecimiento del PIB, los cuales permiten identificar beneficios importantes sobre la cola izquierda de su distribución. Este efecto positivo de la política macroprudencial en la reducción del crecimiento en riesgo es mayor que el impacto negativo sobre la mediana de la distribución, lo que sugiere un efecto neto positivo en el medio plazo. No obstante, estos efectos son heterogéneos y dependen de la posición en el ciclo financiero, la dirección de la política, el tipo de instrumento implementado y el tiempo transcurrido desde su implementación. En particular, el endurecimiento de medidas de capital durante fases expansivas del ciclo puede tardar hasta dos años en evidenciar beneficios sobre el crecimiento en riesgo, mientras que el efecto positivo de medidas de límites a los estándares crediticios se materializaría rápidamente. Esto sugiere la necesidad de implementar medidas de capital, como el colchón de capital anticíclico, con suficiente antelación respecto al desarrollo del ciclo, mientras que el endurecimiento de límites a los estándares crediticios podría implementarse en etapas más avanzadas. Por otra parte, durante episodios de crisis financieras, los beneficios de la liberación de capital son inmediatos, mientras que los de la relajación de límites a los estándares de crédito son más limitados. En general, este estudio brinda un marco de gran utilidad para la evaluación de los costes y los beneficios de la política macroprudencial en términos de crecimiento del PIB y permite identificar la estructura temporal de instrumentos específicos.This paper brings together recent developments on the growth-at-risk methodology and the literature on the impact of macroprudential policy. For this purpose, I extend the recent proposals on the use of quantile regressions of GDP growth by including macrofinancial variables with early warning properties of systemic risk, and macroprudential measures. I identify heterogeneous effects of macroprudential policy on GDP growth, uncovering important benefits on the left tail of its distribution. The positive effect of macroprudential policy on reducing the downside risk of GDP is found to be larger than the negative impact on the median, suggesting a net positive effect in the mid-term. Nonetheless, I identify heterogeneous effects depending on the position in the financial cycle, the direction of the policy, the type of instrument, and the time elapsed since its implementation. In particular, tightening capital measures during expansions may take up to two years in evidencing benefits on growth-at-risk, while the positive impact of borrower-based measures is rapidly observed. This suggests the need of implementing capital measures, such as the countercyclical capital buffer, early enough in the cycle; while borrower-based measures can be tightened in more advanced stages. Conversely, in downturns the benefits of loosening capital measures are immediate, while those of borrower-based measures are limited. Overall, this study provides a useful framework to assess costs and benefits of macroprudential policy in terms of GDP growth, and to identify the term-structure of specific types of instruments

Measuring credit-to-GDP gaps : the Hodrick-Prescott filter revisited

La brecha crédito-PIB calculada con la metodología recomendada por el Comité de Supervisión Bancaria de Basilea (BCBS, por sus siglas en inglés) presenta importantes limitaciones, debido principalmente a la alta inercia de la tendencia de largo plazo estimada, que no permite capturar de manera apropiada cambios estructurales o rápidos en la tendencia. Como resultado, la brecha estimada presenta actualmente en muchos países valores muy negativos, que no reflejan de un modo adecuado el entorno de riesgo cíclico ni su posición en el ciclo financiero. Esto ha llevado a que la gran mayoría de los países que han activado recientemente el Colchón de Capital Anticíclico (CCA) no estén siguiendo las señales derivadas de este indicador. La principal razón de estas discrepancias entre las señales del indicador y la actual posición en el ciclo financiero de muchos países puede estar relacionada no solo con las propiedades de los métodos de filtrado estadístico, sino también con la adaptación específica del filtro de Hodrick-Prescott (HP) recomendada por el BCBS para el cálculo de la brecha. En particular, el parámetro de suavización del filtro HP propuesto asume una duración del ciclo de crédito mucho mayor que la evidenciada empíricamente en la mayoría de los países, lo que lleva a que la tendencia de largo plazo estimada tenga una memoria muy larga. Este estudio evalúa si una relajación de este supuesto mejora la capacidad predictiva del indicador y su utilidad para identificar señales de riesgo sistémico cíclico que permitan informar adecuadamente sobre decisiones de política macroprudencial en los próximos añosLos resultados sugieren que adaptaciones del filtro HP que asumen una menor duración del ciclo de crédito, más coherente con la evidencia empírica, mejoran la capacidad predictiva del indicador y corrigen el sesgo negativo tras los eventos de crisis, en comparación con la brecha calculada con la metodología propuesta por el BCBS. Esto se evidencia no solo en el caso de España, sino también en otros países de la Unión Europea. Finalmente, se encuentra que los resultados obtenidos con las diferentes adaptaciones del filtro HP presentan una capacidad predictiva superior a la de otros métodos de filtrado estadístico y comparable con la obtenida con modelos econométricosThe credit-to-GDP gap computed under the methodology recommended by Basel Committee for Banking Supervision (BCBS) suffers of important limitations mainly regarding the great inertia of the estimated long-run trend, which does not allow capturing properly structural changes or sudden changes in the trend. As a result, the estimated gap currently yields large negative values which do not reflect properly the position in the financial cycle and the cyclical risk environment in many countries. Certainly, most countries that have activated the Countercyclical Capital Buffer (CCyB) in recent years appear not to be following the signals provided by this indicator. The main underlying reason for this might not be only related to the properties of statistical filtering methods, but to the particular adaptation made by the BCBS for the computation of the gap. In particular, the proposed one-sided Hodrick-Prescott filter (HP) only accounts for past observations and the value of the smoothing parameter assumes a much longer length of the credit cycle that those empirically evidenced in most countries, leading the trend to have very long memory. This study assesses whether relaxing this assumption improves the performance of the filter and would still allow this statistical method to be useful in providing accurate signals of cyclical systemic risk and thereby inform macroprudential policy decisionsFindings suggest that adaptations of the filter that assume a lower length of the credit cycle, more consistent with empirical evidence, help improve the early warning performance and correct the downward bias compared to the original gap proposed by the BCBS. This is not only evidenced in the case of Spain but also in several other EU countries. Finally, the results of the proposed adaptations of the HP filter are also found to perform fairly well when compared to other statistical filters and model-based indicator

Heterogeneous effects of risk-taking on bank efficiency : a stochastic frontier model with random coefficients

We estimate a stochastic frontier model with random inefficiency parameters, which allows us not only to identify the role of bank risk-taking on driving cost and profit inefficiency, but also to recognize heterogeneous effects of risk exposure on banks with different characteristics. We account for an integral group of risk exposure covariates including credit, liquidity, capital and market risk, as well as bank-specific characteristics of size and affiliation. The model is estimated for the Colombian banking sector during the period 2002-2012. Results suggest that risk-taking drives inefficiency and its omission leads to over (under) estimate cost (profit) efficiency. Risk-taking is also found to have different effects on efficiency of banks with different size and affiliation, and those involved in mergers and acquisitions. In particular, greater exposures to credit and market risk are found to be key profit efficiency drivers.Likewise, lower liquidity risk and capital risk lead to higher efficiency in both costs and profits. Large, foreign and merged banks benefit more when assuming credit risk, while small, domestic and non-merged banks institutions take advantage of assuming higher market riskJorge E. Galán acknowledges financial support from the Spanish Ministry of Education and Science, research project ECO2012-340

Taking control : Hijacking of Rab GTPases by intracellular bacterial pathogens

Work in the Spanò laboratory is supported by the Wellcome Trust (grant no. 109680/Z/15/Z), the Royal Society (grant no. RG150386), and the BBSRC (grant no. BB/N017854/1). Work in the Galán laboratory is supported by the National Institute of Allergy and Infectious Diseases (grants AI055472 and AI079022 to J.E.G.).Peer reviewedPostprin

Campylobacter jejuni Survives within Epithelial Cells by Avoiding Delivery to Lysosomes

Campylobacter jejuni is one of the major causes of infectious diarrhea world-wide, although relatively little is know about its mechanisms of pathogenicity. This bacterium can gain entry into intestinal epithelial cells, which is thought to be important for its ability to persistently infect and cause disease. We found that C. jejuni is able to survive within intestinal epithelial cells. However, recovery of intracellular bacteria required pre-culturing under oxygen-limiting conditions, suggesting that C. jejuni undergoes significant physiological changes within the intracellular environment. We also found that in epithelial cells the C. jejuni–containing vacuole deviates from the canonical endocytic pathway immediately after a unique caveolae-dependent entry pathway, thus avoiding delivery into lysosomes. In contrast, in macrophages, C. jejuni is delivered to lysosomes and consequently is rapidly killed. Taken together, these studies indicate that C. jejuni has evolved specific adaptations to survive within host cells

Delivery of a Salmonella Typhi Exotoxin from a Host Intracellular Compartment

SummarySalmonella Typhi, an exclusive human pathogen and the cause of typhoid fever, expresses a functional cytolethal distending toxin for which only the active subunit, CdtB, has been identified. Here, we show that PltA and PltB, which are encoded in the same pathogenicity islet as cdtB, associate with CdtB to form a multipartite toxin. PltA and PltB are homologs of components of the pertussis toxin, including its ADP-ribosyl transferase subunit. We also show that PltA and PltB are required for the delivery of CdtB from an intracellular compartment to target cells via autocrine and paracrine pathways. We hypothesize that this toxin, which we have named “typhoid toxin,” and its delivery mechanism may contribute to S. Typhi's unique virulence properties

Beyond the LTV ratio: new macroprudential lessons from Spain

Incrementos excesivos de los precios de la vivienda han estado históricamente correlacionados con el deterioro de los estándares crediticios de las hipotecas. No obstante, la evidencia en España muestra que la ratio préstamo-valor (LTV, por sus siglas en inglés) no refleja apropiadamente estos estándares. Utilizando dos extensas bases de datos que incluyen información de más de cinco millones de operaciones hipotecarias en España durante un período que cubre el pasado ciclo financiero, encontramos evidencia de que el indicador LTV presenta importantes limitaciones para el análisis de vulnerabilidades. Hallamos que la identificación de los riesgos mejora cuando se incluyen otros indicadores. En particular, reconocemos que la ratio préstamo-precio de transmisión (LTP, por sus siglas en inglés), así como ratios que incorporan el ingreso de los prestatarios, son determinantes muy relevantes de los impagos de hipotecas. Adicionalmente, identificamos importantes efectos no lineales de los estándares de crédito sobre el riesgo de impago. Por último, encontramos que la relación entre los estándares de crédito y la probabilidad de impago es dinámica y cambia a lo largo del ciclo financiero. En general, nuestros resultados proporcionan un mejor entendimiento de los efectos que puede tener la implementación de medidas macroprudenciales.Booming house prices have been historically correlated with the loosening of banks’ lending standards. Nonetheless, the evidence in Spain shows that the deterioration of lending policies may not be fully captured by the popular loan-to-value (LTV) ratio. Drawing on two large datasets comprising more than five million mortgage operations that cover the last financial cycle, we show that the LTV indicator may exhibit a misleading picture of actual mortgage credit imbalances and risk. In turn, risk identification improves when other metrics are considered. In particular, we show that loan-to-price (LTP) as well as ratios that consider the income of borrowers are major determinants of mortgage defaults. Moreover, we identify relevant non-linear effects of lending standards on default risk. Finally, we document that the relationship between lending standards and default rates changes over the cycle. Overall, the findings provide useful insights for the design of the macroprudential policy mix and, in particular, for the implementation of borrower-based measures

Modulation of Rab GTPase function by a protein phosphocholine transferase.

The intracellular pathogen Legionella pneumophila modulates the activity of host GTPases to direct the transport and assembly of the membrane-bound compartment in which it resides. In vitro studies have indicated that the Legionella protein DrrA post-translationally modifies the GTPase Rab1 by a process called AMPylation. Here we used mass spectrometry to investigate post-translational modifications to Rab1 that occur during infection of host cells by Legionella. Consistent with in vitro studies, DrrA-mediated AMPylation of a conserved tyrosine residue in the switch II region of Rab1 was detected during infection. In addition, a modification to an adjacent serine residue in Rab1 was discovered, which was independent of DrrA. The Legionella effector protein AnkX was required for this modification. Biochemical studies determined that AnkX directly mediates the covalent attachment of a phosphocholine moiety to Rab1. This phosphocholine transferase activity used CDP-choline as a substrate and required a conserved histidine residue located in the FIC domain of the AnkX protein. During infection, AnkX modified both Rab1 and Rab35, which explains how this protein modulates membrane transport through both the endocytic and exocytic pathways of the host cell. Thus, phosphocholination of Rab GTPases represents a mechanism by which bacterial FIC-domain-containing proteins can alter host-cell functions

Drivers of productivity in the Spanish banking sector : recent evidence

Este estudio analiza los determinantes de la productividad total de los factores de los bancos españoles desde el año 2000 hasta el período poscrisis. En particular, analizamos los cambios en la productividad derivados del proceso de reestructuración que ha experimentado el sector bancario español después de la crisis. Encontramos que, tras un período de continuo crecimiento, la productividad se ha reducido desde el comienzo de la crisis, aunque los bancos más grandes se han visto menos afectados. También identificamos que el riesgo, los niveles de capital, la competencia y los precios de los inputs han sido determinantes muy importantes que explican las diferencias en los cambios de productividad entre bancos. Finalmente, nuestros resultados sugieren que, al final de la muestra, existe margen para mejoras adicionales en la productividad, principalmente a través del aprovechamiento de economías de escala y de incrementos de la eficiencia en costes. Identificamos que estas oportunidades son, en general, mayores para los bancos pequeños en nuestra muestraWe analyse the drivers of total factor productivity of Spanish banks from early 2000, including the last financial crisis and the post-crisis period. This allows us to study changes in productivity following a major restructuring process in the banking sector such as the one experienced in Spain. Overall, we find that following a period of continued growth, productivity declined after the height of the crisis, though large banks were less affected. We also find that risk, capital levels, competition and input prices were important drivers of the differences in productivity change between banks. Finally, our results suggest that, by the end of our sample period, there was still some room for potential improvements in productivity via exploiting scale economies and enhancing cost efficiency. These opportunities appear to be generally greater for the smaller banks in our sampl