Cointegration and Asymmetric Adjustment between Output and Unemployment: an Application to the U.S. Economy

This paper focuses on the properties of the adjustment between the real output and the unemployment rate for the U.S. economy in the period from 1975 to 2006. It starts by checking the order of integration of the two series and then tests for the presence of asymmetry in the Okun’s law relationship through a cyclical equation, a first differences equation and an ADL(p,q). Using the threshold cointegration approach this study also accounts for the possible existence of a long-run equilibrium relationship and it is ability to test for the asymmetric adjustment hypothesis. It is found that Okun’s coefficient ranges between -0.41 and -0.59, being the latter estimated by the cointegrating equation. Furthermore, the unemployment rate behaves differently along the business cycle and increases faster in recessions than it recovers in expansions. A long-run equilibrium relationship is established where adjustment is made asymmetrically. Positive deviations away from equilibrium are corrected slightly faster than negative ones. Our explanation concerns the higher speed of flows within the labor market during a recession than during an expansion which may also be related to the existence of nominal rigidities in the US economy that causes imperfectly flexible prices.Okun’s Law, Threshold Cointegration, Asymmetric Adjustment, Monte Carlo Simulations, U.S. Economy

A Contribution to the Empirics of Convergence: the Case of the European State Members

This study aims to examine the absolute and conditional convergence across the 27 EU Member States. To examine the absolute β convergence was used Baumol model (1986) estimated by OLS and Panel Data, and to examine the absolute σ convergence the Quah model (1993) by graphical analysis. Subsequently, we analyzed the conditional convergence, also estimated by OLS regressions and Panel Data. Finally, we performed a cluster analysis with the aim to understand the differences between different schools of economic growth thought. With this work we conclude that there is absolute β convergence in general, but the absolute convergence σ occurs only in the 12 most recent member states. The conditional convergence is verified in general and with a top speed of convergence β absolute. Finally we conclude that the neoclassical school, since 1980, proves to be important for economic growth and convergence of the EU as the school Neo Schumpeterian just proves to be important since 1991

A Contribution to the Empirics of Convergence: the Case of the European State Members

This study aims to examine the absolute and conditional convergence across the 27 EU Member States. To examine the absolute β convergence was used Baumol model (1986) estimated by OLS and Panel Data, and to examine the absolute σ convergence the Quah model (1993) by graphical analysis. Subsequently, we analyzed the conditional convergence, also estimated by OLS regressions and Panel Data. Finally, we performed a cluster analysis with the aim to understand the differences between different schools of economic growth thought. With this work we conclude that there is absolute β convergence in general, but the absolute convergence σ occurs only in the 12 most recent member states. The conditional convergence is verified in general and with a top speed of convergence β absolute. Finally we conclude that the neoclassical school, since 1980, proves to be important for economic growth and convergence of the EU as the school Neo Schumpeterian just proves to be important since 1991

Corporate Bankruptcy of Portuguese Firms

Over the time has been increasing the interest in understanding the subjects of insolvency and bankruptcy due to its consequences for the country’s economic performance, and, actually, to its importance in the actual economic European context. The present work studies the evolution of bankruptcy of Portuguese fi rms in the last two decades, and obtains a set of macroeconomic factors which can explain this occurrence. It was considered the period 1990-2009, and the methodology used was a regression model including variables considerate in several empirical studies sustained in the literature review. The obtained results pointed to the relevance of macroeconomic variables as most signifi cant explanatory variables for the Portuguese case

MSH3 polymorphisms and protein levels affect CAG repeat instability in huntington's disease mice

Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD) (CAG)~100 transgene, when present in a congenic C57BL/6J (B6) background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy) background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with polymorphisms of DNA repair genes may have prognostic implications for various repeat-associated diseases

Objectively measured patterns of sedentary time and physical activity in young adults of the Raine study cohort

Background: To provide a detailed description of young adults' sedentary time and physical activity. Methods: 384 young women and 389 young men aged 22.1±0.6 years, all participants in the 22 year old follow-up of the Raine Study pregnancy cohort, wore Actigraph GT3X+ monitors on the hip for 24 h/day over a one-week period for at least one 'valid' day (=10 h of waking wear time). Each minute epoch was classified as sedentary, light, moderate or vigorous intensity using 100 count and Freedson cut-points. Mixed models assessed hourly and daily variation; t-tests assessed gender differences. Results: The average (mean±SD) waking wear time was 15.0±1.6 h/day, of which 61.4±10.1 % was spent sedentary, 34.6±9.1 % in light-, 3.7±5.3 % in moderate- and, 0.3±0.6 % in vigorous-intensity activity. Average time spent in moderate to vigorous activity (MVPA) was 36.2±27.5 min/day. Relative to men, women had higher sedentary time, but also higher vigorous activity time. The 'usual' bout duration of sedentary time was 11.8±4.5 min in women and 11.7±5.2 min in men. By contrast, other activities were accumulated in shorter bout durations. There was large variation by hour of the day and by day of the week in both sedentary time and MVPA. Evenings and Sundays through Wednesdays tended to be particularly sedentary and/or inactive. Conclusion: For these young adults, much of the waking day was spent sedentary and many participants were physically inactive (low levels of MVPA). We provide novel evidence on the time for which activities were performed and on the time periods when young adults were more sedentary and/or less active. With high sedentary time and low MVPA, young adults may be at risk for the life-course sequelae of these behaviours

Elucidating the clinical and molecular spectrum of SMARCC2-associated NDD in a cohort of 65 affected individuals

Purpose: Coffin-Siris and Nicolaides-Baraitser syndromes are recognizable neurodevelopmental disorders caused by germline variants in BAF complex subunits. The SMARCC2 BAFopathy was recently reported. Herein, we present clinical and molecular data on a large cohort. Methods: Clinical symptoms for 41 novel and 24 previously published affected individuals were analyzed using the Human Phenotype Ontology. For genotype-phenotype correlations, molecular data were standardized and grouped into non-truncating and likely gene-disrupting (LGD) variants. Missense variant protein expression and BAF-subunit interactions were examined using 3D protein modeling, co-immunoprecipitation, and proximity-ligation assays. Results: Neurodevelopmental delay with intellectual disability, muscular hypotonia, and behavioral disorders were the major manifestations. Clinical hallmarks of BAFopathies were rare. Clinical presentation differed significantly, with LGD variants being predominantly inherited and associated with mildly reduced or normal cognitive development, whereas non-truncating variants were mostly de novo and presented with severe developmental delay. These distinct manifestations and non-truncating variant clustering in functional domains suggest different pathomechanisms. In vitro testing showed decreased protein expression for N-terminal missense variants similar to LGD. Conclusion: This study improved SMARCC2 variant classification and identified discernible SMARCC2-associated phenotypes for LGD and non-truncating variants, which were distinct from other BAFopathies. The pathomechanism of most non-truncating variants has yet to be investigated.</p

Integrated MicroRNA-mRNA-Analysis of Human Monocyte Derived Macrophages upon Mycobacterium avium subsp. hominissuis Infection

Many efforts have been made to understand basal mechanisms of mycobacterial infections. Macrophages are the first line of host immune defence to encounter and eradicate mycobacteria. Pathogenic species have evolved different mechanisms to evade host response, e.g. by influencing macrophage apoptotic pathways. However, the underlying molecular regulation is not fully understood. A new layer of eukaryotic regulation of gene expression is constituted by microRNAs. Therefore, we present a comprehensive study for identification of these key regulators and their targets in the context of host macrophage response to mycobacterial infections.We performed microRNA as well as mRNA expression analysis of human monocyte derived macrophages infected with several Mycobacterium avium hominissuis strains by means of microarrays as well as quantitative reverse transcription PCR (qRT-PCR). The data revealed the ability of all strains to inhibit apoptosis by transcriptional regulation of BCL2 family members. Accordingly, at 48 h after infection macrophages infected with all M. avium strains showed significantly decreased caspase 3 and 7 activities compared to the controls. Expression of let-7e, miR-29a and miR-886-5p were increased in response to mycobacterial infection at 48 h. The integrated analysis of microRNA and mRNA expression as well as target prediction pointed out regulative networks identifying caspase 3 and 7 as potential targets of let-7e and miR-29a, respectively. Consecutive reporter assays verified the regulation of caspase 3 and 7 by these microRNAs.We show for the first time that mycobacterial infection of human macrophages causes a specific microRNA response. We furthermore outlined a regulatory network of potential interactions between microRNAs and mRNAs. This study provides a theoretical concept for unveiling how distinct mycobacteria could manipulate host cell response. In addition, functional relevance was confirmed by uncovering the control of major caspases 3 and 7 by let-7e and miR-29a, respectively

Elucidating the clinical and molecular spectrum of SMARCC2-associated NDD in a cohort of 65 affected individuals

Purpose: Coffin-Siris and Nicolaides-Baraitser syndromes are recognizable neurodevelopmental disorders caused by germline variants in BAF complex subunits. The SMARCC2 BAFopathy was recently reported. Herein, we present clinical and molecular data on a large cohort. Methods: Clinical symptoms for 41 novel and 24 previously published affected individuals were analyzed using the Human Phenotype Ontology. For genotype-phenotype correlations, molecular data were standardized and grouped into non-truncating and likely gene-disrupting (LGD) variants. Missense variant protein expression and BAF-subunit interactions were examined using 3D protein modeling, co-immunoprecipitation, and proximity-ligation assays. Results: Neurodevelopmental delay with intellectual disability, muscular hypotonia, and behavioral disorders were the major manifestations. Clinical hallmarks of BAFopathies were rare. Clinical presentation differed significantly, with LGD variants being predominantly inherited and associated with mildly reduced or normal cognitive development, whereas non-truncating variants were mostly de novo and presented with severe developmental delay. These distinct manifestations and non-truncating variant clustering in functional domains suggest different pathomechanisms. In vitro testing showed decreased protein expression for N-terminal missense variants similar to LGD. Conclusion: This study improved SMARCC2 variant classification and identified discernible SMARCC2-associated phenotypes for LGD and non-truncating variants, which were distinct from other BAFopathies. The pathomechanism of most non-truncating variants has yet to be investigated.</p

Continuous and Periodic Expansion of CAG Repeats in Huntington's Disease R6/1 Mice

Huntington's disease (HD) is one of several neurodegenerative disorders caused by expansion of CAG repeats in a coding gene. Somatic CAG expansion rates in HD vary between organs, and the greatest instability is observed in the brain, correlating with neuropathology. The fundamental mechanisms of somatic CAG repeat instability are poorly understood, but locally formed secondary DNA structures generated during replication and/or repair are believed to underlie triplet repeat expansion. Recent studies in HD mice have demonstrated that mismatch repair (MMR) and base excision repair (BER) proteins are expansion inducing components in brain tissues. This study was designed to simultaneously investigate the rates and modes of expansion in different tissues of HD R6/1 mice in order to further understand the expansion mechanisms in vivo. We demonstrate continuous small expansions in most somatic tissues (exemplified by tail), which bear the signature of many short, probably single-repeat expansions and contractions occurring over time. In contrast, striatum and cortex display a dramatic—and apparently irreversible—periodic expansion. Expansion profiles displaying this kind of periodicity in the expansion process have not previously been reported. These in vivo findings imply that mechanistically distinct expansion processes occur in different tissues