Ciclo financiero y ciclo económico en Uruguay : una aproximación de largo plazo (1870 - 2019)

El presente trabajo identifica y caracteriza el ciclo financiero para Uruguay, entre 1870 y 2019, e indaga sobre su relación con el ciclo real en el mismo período. El comportamiento del sector financiero es aproximado a través del crédito real interno al sector privado no financiero, mientras que el ciclo real es extraído del PIB a precios constantes. Para obtener los componentes cíclicos de cada serie, el trabajo se vale de los modelos estructurales de series temporales en su versión univariada. Las relaciones entre los ciclos son estudiadas mediante el análisis de las correlaciones cruzadas complementado por el análisis de causalidad a la Granger. Finalmente, se propone un fechado de los ciclos a partir del método de puntos de quiebre. Los resultados, en línea con la evidencia internacional, indican la existencia de un marcado componente cíclico en el crédito, con fluctuaciones de 8 años y medio y 22 años y medio, siendo las de menor frecuencia las más amplias. De forma similar, las estimaciones de los componentes inobservables del PIB arrojan ciclos de similar duración (8 años y medio y 21 años y medio, respectivamente), en línea con la evidencia documentada en la literatura local. Además, el ciclo financiero resulta más volátil y persistente que el ciclo real y presenta mínimos más profundos, lo que también está en línea con la literatura internacional. Vista por subperiodos, la mayor volatilidad del crédito se alcanza en los períodos de mayor apertura y liberalización (especialmente en la Primera Globalización), mientras que para el PIB esto sucede entre 1931 y 1973. Siguiendo las teorías que señalan el rol del sistema financiero sobre el sector real, se encuentra una relación procíclica entre el ciclo financiero y el ciclo real, especialmente en el componente cíclico de mayor duración.This work identifies and characterizes the financial cycle for Uruguay, between 1870 and 2019, and investigates its relationship with the real cycle in the same period. The behavior of financial sector is approximated through real domestic credit to non-financial private sector, while real cycle is obtained from GDP at constant prices. To get the cyclical components of each series, this work specifies univariate structural time series models. The relationship between the cycles is studied through cross-correlation analysis complemented by Granger causality analysis. Finally, dates for cycles are estimated with the turning points algorithm. Results, in line with international evidence, indicate the existence of a clear cyclical component in credit, with fluctuations of 8 and a half years and 22 and a half years, the former being the widest. Similarly, the estimates of the unobservable components of GDP show cycles of similar duration (8 and a half years and 21 and a half years, respectively), in line with evidence documented in the Uruguayan literature. Furthermore, financial cycle is more volatile and persistent than real cycle and presents deeper troughs, which also fits with the international literature. When seen by sub-periods, the greatest volatility of credit is reached in the years of greater openness and liberalization (especially in the First Globalization), while for GDP this occurs between 1931 and 1973. Following the theories that indicate the role of the financial system on the real sector, a procyclical relationship is found between financial cycles and real cycles, especially in the cyclical component of the longest duration. Evidence indicates that in the long cycle, GDP leads credit; in the short, the evidence is weak and in favor of credit leading GDP. These relationships change between 1974 and 2019, both in the short component (GDP leads credit) and in the long component (there is no comovement between cycles)

Treatment of T1D via optimized expansion of antigen-specific Tregs induced by IL-2/anti-IL-2 monoclonal antibody complexes and peptide/MHC tetramers.

Type 1 diabetes can be overcome by regulatory T cells (Treg) in NOD mice yet an efficient method to generate and maintain antigen-specific Treg is difficult to come by. Here, we devised a combination therapy of peptide/MHC tetramers and IL-2/anti-IL-2 monoclonal antibody complexes to generate antigen-specific Treg and maintain them over extended time periods. We first optimized treatment protocols conceived to obtain an improved islet-specific Treg/effector T cell ratio that led to the in vivo expansion and activation of these Treg as well as to an improved suppressor function. Optimized protocols were applied to treatment for testing diabetes prevention in NOD mice as well as in an accelerated T cell transfer model of T1D. The combined treatment led to robust protection against diabetes, and in the NOD model, to a close to complete prevention of insulitis. Treatment was accompanied with increased secretion of IL-10, detectable in total splenocytes and in Foxp3− CD4 T cells. Our data suggest that a dual protection mechanism takes place by the collaboration of Foxp3+ and Foxp3− regulatory cells. We conclude that antigen-specific Treg are an important target to improve current clinical interventions against this disease

Regulation of BMP4/Dpp retrotranslocation and signaling by deglycosylation.

During endoplasmic reticulum-associated degradation (ERAD), the cytoplasmic enzyme N-glycanase 1 (NGLY1) is proposed to remove N-glycans from misfolded N-glycoproteins after their retrotranslocation from the ER to the cytosol. We previously reported that NGLY1 regulates Drosophila BMP signaling in a tissue-specific manner (Galeone et al., 2017). Here, we establish the Drosophila Dpp and its mouse ortholog BMP4 as biologically relevant targets of NGLY1 and find, unexpectedly, that NGLY1-mediated deglycosylation of misfolded BMP4 is required for its retrotranslocation. Accumulation of misfolded BMP4 in the ER results in ER stress and prompts the ER recruitment of NGLY1. The ER-associated NGLY1 then deglycosylates misfolded BMP4 molecules to promote their retrotranslocation and proteasomal degradation, thereby allowing properly-folded BMP4 molecules to proceed through the secretory pathway and activate signaling in other cells. Our study redefines the role of NGLY1 during ERAD and suggests that impaired BMP4 signaling might underlie some of the NGLY1 deficiency patient phenotypes

A locus on mouse chromosome 13 inversely regulates CD1d expression and the development of invariant natural killer T-cells.

Invariant natural killer T (iNKT)-cell development is controlled by many polymorphic genes present in commonly used mouse inbred strains. Development of type 1 diabetes (T1D) in NOD mice partly results from their production of fewer iNKT-cells compared with non-autoimmune-prone control strains, including ICR. We previously identified several iNKT-cell quantitative trait genetic loci co-localized with known mouse and human T1D regions in a (NOD × ICR)F2 cross. To further dissect the mechanisms underlying the impaired iNKT-cell compartment in NOD mice, we carried out a series of bone marrow transplantation as well as additional genetic mapping studies. We found that impaired iNKT-cell development in NOD mice was mainly due to the inability of their double-positive (DP) thymocytes to efficiently select this T-cell population. Interestingly, we observed higher levels of CD1d expression by NOD than by ICR DP thymocytes. The genetic control of the inverse relationship between the CD1d expression level on DP thymocytes and the frequency of thymic iNKT-cells was further mapped to a region on chromosome 13 between 60.12 and 70.59 Mb. The NOD allele was found to promote CD1d expression and suppress iNKT-cell development. Our results indicate that genetically controlled physiological variation of CD1d expression levels modulates iNKT-cell development. Genes Immun 2015 Apr; 16(3):221-30

Nfkbid Overexpression in Nonobese Diabetic Mice Elicits Complete Type 1 Diabetes Resistance in Part Associated with Enhanced Thymic Deletion of Pathogenic CD8 T Cells and Increased Numbers and Activity of Regulatory T Cells.

Type 1 diabetes (T1D) in both humans and NOD mice is caused by T cell-mediated autoimmune destruction of pancreatic β cells. Increased frequency or activity of autoreactive T cells and failures of regulatory T cells (Tregs) to control these pathogenic effectors have both been implicated in T1D etiology. Due to the expression of MHC class I molecules on β cells, CD8 T cells represent the ultimate effector population mediating T1D. Developing autoreactive CD8 T cells normally undergo extensive thymic negative selection, but this process is impaired in NOD mice and also likely T1D patients. Previous studies identified an allelic variant o

Treatment of T1D via optimized expansion of antigen-specific Tregs induced by IL-2/anti-IL-2 monoclonal antibody complexes and peptide/MHC tetramers.

Type 1 diabetes can be overcome by regulatory T cells (Treg) in NOD mice yet an efficient method to generate and maintain antigen-specific Treg is difficult to come by. Here, we devised a combination therapy of peptide/MHC tetramers and IL-2/anti-IL-2 monoclonal antibody complexes to generate antigen-specific Treg and maintain them over extended time periods. We first optimized treatment protocols conceived to obtain an improved islet-specific Treg/effector T cell ratio that led to the in vivo expansion and activation of these Treg as well as to an improved suppressor function. Optimized protocols were applied to treatment for testing diabetes prevention in NOD mice as well as in an accelerated T cell transfer model of T1D. The combined treatment led to robust protection against diabetes, and in the NOD model, to a close to complete prevention of insulitis. Treatment was accompanied with increased secretion of IL-10, detectable in total splenocytes and in Foxp3− CD4 T cells. Our data suggest that a dual protection mechanism takes place by the collaboration of Foxp3+ and Foxp3− regulatory cells. We conclude that antigen-specific Treg are an important target to improve current clinical interventions against this disease