Gene loss rather than gene gain is associated with a host jump from monocots to dicots in the smut fungus Melanopsichium pennsylvanicum
- Smut fungi are well-suited to investigate the ecology and evolution of plant pathogens, as they are strictly biotrophic, yet cultivable on media. Here we report the genome sequence of Melanopsichium pennsylvanicum, closely related to Ustilago maydis and other Poaceae-infecting smuts, but parasitic to a dicot plant. To explore the evolutionary patterns resulting from host adaptation after this huge host jump, the genome of M. pennsylvanicum was sequenced and compared to the genomes of Ustilago maydis, Sporisorium reilianum, and Ustilago hordei. While all four genomes had a similar completeness in CEGMA analyses, gene absence was highest in M. pennsylvanicum, and most pronounced in putative secreted proteins, which are often considered as effector candidates. In contrast, the amount of private genes was similar among the species, highlighting that gene loss rather than gene gain is the hallmark of adaptation after the host jump to the dicot host. Our analyses revealed a trend of putative effectors to be next to another putative effector, but the majority of these are not in clusters and thus the focus on pathogenicity clusters might not be appropriate for all smut genomes. Positive selection studies revealed that M. pennsylvanicum has the highest number and proportion of genes under positive selection. In general, putative effectors showed a higher proportion of positively selected genes than non-effector candidates. The 248 putative secreted effectors found in all four smut genomes might constitute a core set needed for pathogenicity, while those 92 that are found in all grass-parasitic smuts, but have no ortholog in M. pennsylvanicum might constitute a set of effectors important for successful colonization of grass hosts.
Obesity and associated lifestyle in a large sample of multi-morbid german primary care attendees
Juliana J. Petersen
Hendrik van den Bussche
Steffi G. Riedel-Heller
- Background: Obesity and the accompanying increased morbidity and mortality risk is highly prevalent among older adults. As obese elderly might benefit from intentional weight reduction, it is necessary to determine associated and potentially modifiable factors on senior obesity. This cross-sectional study focuses on multi-morbid patients which make up the majority in primary care. It reports on the prevalence of senior obesity and its associations with lifestyle behaviors.
Methods: A total of 3,189 non-demented, multi-morbid participants aged 65–85 years were recruited in primary care within the German MultiCare-study. Physical activity, smoking, alcohol consumption and quantity and quality of nutritional intake were classified as relevant lifestyle factors. Body Mass Index (BMI, general obesity) and waist circumference (WC, abdominal obesity) were used as outcome measures and regression analyses were conducted.
Results: About one third of all patients were classified as obese according to BMI. The prevalence of abdominal obesity was 73.5%. Adjusted for socio-demographic variables and objective and subjective disease burden, participants with low physical activity had a 1.6 kg/m2 higher BMI as well as a higher WC (4.9 cm, p<0.001). Current smoking and high alcohol consumption were associated with a lower BMI and WC. In multivariate logistic regression, using elevated WC and BMI as categorical outcomes, the same pattern in lifestyle factors was observed. Only for WC, not current but former smoking was associated with a higher probability for elevated WC. Dietary intake in quantity and quality was not associated with BMI or WC in either model.
Conclusions: Further research is needed to clarify if the huge prevalence discrepancy between BMI and WC also reflects a difference in obesity-related morbidity and mortality. Yet, age-specific thresholds for the BMI are needed likewise. Encouraging and promoting physical activity in older adults might a starting point for weight reduction efforts.
Prevalence, Determinants and Patterns of Multimorbidity in Primary Care: A Systematic Review of Observational Studies
Jose M. Valderas
- Introduction: Multimorbidity is a major concern in primary care. Nevertheless, evidence of prevalence and patterns of multimorbidity, and their determinants, are scarce. The aim of this study is to systematically review studies of the prevalence, patterns and determinants of multimorbidity in primary care.
Methods: Systematic review of literature published between 1961 and 2013 and indexed in Ovid (CINAHL, PsychINFO, Medline and Embase) and Web of Knowledge. Studies were selected according to eligibility criteria of addressing prevalence, determinants, and patterns of multimorbidity and using a pretested proforma in primary care. The quality and risk of bias were assessed using STROBE criteria. Two researchers assessed the eligibility of studies for inclusion (Kappa = 0.86).
Results: We identified 39 eligible publications describing studies that included a total of 70,057,611 patients in 12 countries. The number of health conditions analysed per study ranged from 5 to 335, with multimorbidity prevalence ranging from 12.9% to 95.1%. All studies observed a significant positive association between multimorbidity and age (odds ratio [OR], 1.26 to 227.46), and lower socioeconomic status (OR, 1.20 to 1.91). Positive associations with female gender and mental disorders were also observed. The most frequent patterns of multimorbidity included osteoarthritis together with cardiovascular and/or metabolic conditions.
Conclusions: Well-established determinants of multimorbidity include age, lower socioeconomic status and gender. The most prevalent conditions shape the patterns of multimorbidity. However, the limitations of the current evidence base means that further and better designed studies are needed to inform policy, research and clinical practice, with the goal of improving health-related quality of life for patients with multimorbidity. Standardization of the definition and assessment of multimorbidity is essential in order to better understand this phenomenon, and is a necessary immediate step.
Humanized mice as preclinical model for HIV infections
Sarah Manon Büchner
- HIV vaccine preclinical testing is difficult because HIV’s only relevant hosts are humans and no correlates of protection are known. To this end, we are working on the humanization of different mouse strains with human peripheral blood mononuclear cells (PBMCs) as well as human hematopoietic stem cells (HSC) to generate a useful small animal model.
We generated immune deficient mice (NOD Scid IL2gc -/- /NOD Rag1-/- IL2gc -/-) expressing human MHC class II (HLA-DQ8) on a mouse class II deficient background (Ab-/-). Here, the human HLA-DQ8 should interact with the matching T cell receptors of transferred matching human PBMCs and therefore could support the functionality of the transferred human CD4+ cells in the mice.
Mice that were adoptively transferred with human HLA-DQ8 PBMCs only showed engraftment of CD3+ T cells. Surprisingly, the presence of HLA class II did not significantly change the repopulation rates in the mice. Also, the presence of HLA class II did not advance B cell engraftment, such that humoral immune responses were undetectable. However, the overall survival of DQ8-expressing mice was significantly prolonged, compared to mice expressing mouse MHC class II molecules, and correlated with an increased time span until onset of GvHD.
To avoid GVHD and to increase and maintain the level of human cell reconstitution over a long period of time, the same mouse strains were reconstituted with human HSC. Compared to PBMC-repopulated mice, HSC-reconstituted mice develop almost all subpopulations of the human immune system detectable at week 12 after HSC transfer. These mice developed adaptive immune responses after Tetanus Toxoide (TT) immunizations. In addition, we are testing the susceptibility of these humanized mice to different HIV strains with a detailed look at immune responses.
Everything you always wanted to know about systemic importance (but were afraid to ask)
- We develop a methodology to identify and rank “systemically important financial institutions” (SIFIs). Our approach is consistent with that followed by the Financial Stability Board (FSB) but, unlike the latter, it is free of judgment and it is based entirely on publicly available data, thus filling the gap between the official views of the regulator and those that market participants can form with their own information set. We apply the methodology to annual data on three samples of banks (global, EU and euro area) for the years 2007-2012. We examine the evolution of the SIFIs over time and document the shifs in the relative weights of the major geographic areas. We also discuss the implication of the 2013 update of the identification methodology proposed by the FSB.
Credit default swaps and corporate cash holdings : [Version 27 Mai 2014]
Marti G. Subrahmanyam
Dragon Yongjun Tang
Sarah Qian Wang
- We examine the effects of credit default swaps (CDS), a major type of over-the-counter derivative, on the corporate liquidity management of the reference firms. CDS help firms to access the credit market since the lenders can hedge their credit risk more easily using these contracts. However, CDS-protected creditors can be tougher in debt renegotiations and less willing to support distressed borrowers, causing some firms to become more cautious. Consequently, we find that firms hold significantly more cash after the inception of CDS trading on their debt. The increase in cash holdings by CDS firms is more pronounced for financially constrained firms and firms facing higher refinancing risk. Moreover, bank relationships and outstanding credit facilities intensify the CDS effect on cash holding. Finally, firms with greater financial expertise hold more cash when their debt is referenced by CDS. These findings suggest that CDS, which are primarily a risk management tool for lenders, induce firms to adopt more conservative liquidity policies.
To disclose or not to disclose: transparency and liquidity in the structured product market : [Version 5 Mai 2014]
Marti G. Subrahmanyam
- We use a unique data set from the Trade Reporting and Compliance Engine (TRACE) to study liquidity effects in the US structured product market. Our main contribution is the analysis of the relation between the accuracy in measuring liquidity and the potential degree of disclosure. Having access to all relevant trading information, we provide evidence that transaction cost measures that use dealer specific information such as trader identity and trade direction can be efficiently proxied by measures that use less detailed information. This finding is important for all market participants in the context of OTC markets, as it fosters our understanding of the information contained in transaction data. Thus, our results provide guidance for improving transparency while maintaining trader confidentiality. In addition, we analyze liquidity in the structured product market in general and show that securities that are mainly institutionally traded, guaranteed by a federal authority, or have low credit risk, tend to be more liquid.
Spectral densities of the τ lepton in a global U(2)L × U(2)R linear sigma model with electroweak interaction
- This work is dedicated to the study of the vector and axial vector spectral functions of the τ lepton within the framework of a U(2)L × U(2)R Linear Sigma Model with electroweak interaction. As an effective field theory the Linear Sigma Model describes hadronic degrees of freedom based on the symmetries of the Standard Model. Therefore, the following section aims at giving a very general and concise introduction to the Standard Model and the meaning of symmetries for contemporary elementary particle physics. In the next section the SU(3)C symmetry group will be discussed in short, followed by an introduction to chiral symmetry SU(2)L × SU(2)R. In the last section of this chapter the Glashow-Weinberg-Salam theory of the local group SU(2)L × U(1)Y is presented. Important concepts of the theoretical framework of the Standard Model, such as the Noether Theorem, the Gauge Principle, Spontaneous Symmetry Breaking, and the Higgs Mechanism will be introduced in the context of these three symmetry groups. In Chapter 2 it will be first shown how the symmetries of the Standard Model are realised within the global U(2)L × U(2)R Linear Sigma Model and how electroweak interactions can be introduced to the model on the basis of local SU(2)L × U(1)Y symmetry transformations of the hadronic degrees of freedom. The vertices that are relevant for the vector and axial vector decay channels in weak τ decay are extracted from the Lagrangian with electroweak interaction in Chapter 3. This is followed by a short introduction to the Källen-Lehmann Representation of spectral functions and how these can be parametrised within the framework of this model (Chapter 4). The results of the vector and axial vector spectral functions are presented in Chapter 5 and 6.
Evaluating point and density forecasts of DSGE models : [Version 23 Januar 2012]
Maik Hendrik Wolters
- This paper investigates the accuracy of point and density forecasts of four DSGE models for inflation, output growth and the federal funds rate. Model parameters are estimated and forecasts are derived successively from historical U.S. data vintages synchronized with the Fed’s Greenbook projections. Point forecasts of some models are of similar accuracy as the forecasts of nonstructural large dataset methods. Despite their common underlying New Keynesian modeling philosophy, forecasts of different DSGE models turn out to be quite distinct. Weighted forecasts are more precise than forecasts from individual models. The accuracy of a simple average of DSGE model forecasts is comparable to Greenbook projections for medium term horizons. Comparing density forecasts of DSGE models with the actual distribution of observations shows that the models overestimate uncertainty around point forecasts.
Evaluating point and density forecasts of DSGE models : [Version 4 September 2012]
Maik Hendrik Wolters
- This paper investigates the accuracy of forecasts from four DSGE models for inflation, output growth and the federal funds rate using a real-time dataset synchronized with the Fed’s Greenbook projections. Conditioning the model forecasts on the Greenbook nowcasts leads to forecasts that are as accurate as the Greenbook projections for output growth and the federal funds rate. Only for inflation the model forecasts are dominated by the Greenbook projections. A comparison with forecasts from Bayesian VARs shows that the economic structure of the DSGE models which is useful for the interpretation of forecasts does not lower the accuracy of forecasts. Combining forecasts of several DSGE models increases precision in comparison to individual model forecasts. Comparing density forecasts with the actual distribution of observations shows that DSGE models overestimate uncertainty around point forecasts.