Restructuring Strategies for Mexican Eurobond Debt

Unless the international capital markets become widely receptive to refinancing Mexican Eurobonds, by early to mid 1996, the holders of these Eurobonds - Mexico\u27s new bondholder constituency - may find themselves at the center of a restructuring process encompassing a significant portion of the $13 billion of Eurobond debt outstanding. This article discusses strategies for restructuring

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Restructuring Strategies for Mexican Eurobond Debt

Unless the international capital markets become widely receptive to refinancing Mexican Eurobonds, by early to mid 1996, the holders of these Eurobonds - Mexico\u27s new bondholder constituency - may find themselves at the center of a restructuring process encompassing a significant portion of the $13 billion of Eurobond debt outstanding. This article discusses strategies for restructuring

The association of season and temperature with adverse pregnancy outcome in two German states, a time-series analysis.

BACKGROUND: A seasonality of low birth weight (LBW) and preterm birth (PTB) has been described for most regions and there is evidence that this pattern is caused by ambient outdoor temperature. However, the association as such, the direction of effect and the critical time of exposure remain controversial. METHODS: Logistic, time-series regression was performed on nearly 300,000 births from two German states to study the association between season and daily mean temperature and changes in daily proportions of term LBW (tLBW) or PTB. Analyses were adjusted for time-varying factors. Temperature exposures were examined during different periods of pregnancy. RESULTS: Weak evidence for an association between season of conception, season of birth or ambient outdoor temperature and tLBW or PTB was found. Results of analyses of temperature were not consistent between the two states. Different sources of bias which would have artificially led to stronger findings were detected and are described. CONCLUSIONS: No clear evidence for an association between season of conception, season of birth or temperature and tLBW or PTB was found. In the study of pregnancy outcome different sources of bias can be identified which can potentially explain heterogeneous findings of the past

Purification, Characterization, and Expression of Multiple Glutamine Synthetases from Prevotella ruminicola 23

The Prevotella ruminicola 23 genome encodes three different glutamine synthetase (GS) enzymes: glutamine synthetase I (GSI) (ORF02151), GSIII-1 (ORF01459), and GSIII-2 (ORF02034). GSI, GSIII-1, and GSIII-2 have each been heterologously expressed in and purified from Escherichia coli. The subunit molecular mass of GSI was 56 kDa, while GSIII-1 and GSIII-2 were both 83 kDa. Optimal conditions for γ-glutamyl transferase activity were found to be 35°C at pH 5.6 with 0.25 mM Mn2+ ions (GSI) or 37°C at pH 6.0 (GSIII-1 and GSIII-2) with 0.50 to 1.00 mM Mn2+ ions. GSIII biosynthetic activity was found to be optimal at 50 to 60°C and pH 6.8 to 7.0 with 10 mM Mn2+ ions, while GSI displayed no GS biosynthetic activity. Kinetic analysis revealed Km values for glutamate and ammonium as well as for hydrolysis of ATP to be 8.58, 0.48, and 1.91 mM, respectively, for GSIII-1 and 1.72, 0.43, and 2.65 mM, respectively, for GSIII-2. A quantitative reverse transcriptase PCR assay (qRT-PCR) revealed GSIII-2 to be significantly induced by high concentrations of ammonia, and this corresponded with increases in measured GS activity. Collectively, these results show that both GSIII enzymes in P. ruminicola 23 are functional and indicate that GSIII-2, flanked by GOGAT (gltB and gltD genes), plays an important role in the acquisition and metabolism of ammonia, particularly under nonlimiting ammonia growth conditions