Interactions between the powdery mildew effector BEC1054 and barley proteins identify candidate host targets

There are over 500 candidate secreted effector proteins (CSEPs) or Blumeria effector candidates (BECs) specific to the barley powdery mildew pathogen Blumeria graminis f.sp. hordei. The CSEP/BEC proteins are expressed and predicted to be secreted by biotrophic feeding structures called haustoria. Eight BECs are required for the formation of functional haustoria. These include the RNase-like effector BEC1054 (synonym CSEP0064). In order to identify host proteins targeted by BEC1054, recombinant BEC1054 was expressed in E. coli, solubilized, and used in pull-down assays from barley protein extracts. Many putative interactors were identified by LC-MS/MS after subtraction of unspecific binders in negative controls. Therefore, a directed yeast-2-hybrid assay, developed to measure the effectiveness of the interactions in yeast, was used to validate putative interactors. We conclude that BEC1054 may target several host proteins, including a glutathione-S-transferase, a malate dehydrogenase, and a pathogen-related-5 protein isoform, indicating a possible role for BEC1054 in compromising well-known key players of defense and response to pathogens. In addition, BEC1054 interacts with an elongation factor 1 gamma. This study already suggests that BEC1054 plays a central role in barley powdery mildew virulence by acting at several levels.

Meta-analysis to integrate effect sizes within a paper: Possible misuse and Type-1 error inflation

In recent years an increasing number of papers have employed meta-analysis to integrate effect sizes of researchers’ own series of studies within a single paper (“internal meta-analysis”). Although this approach has the obvious advantage of obtaining narrower confidence intervals, we show that it could inadvertently inflate false-positive rates if researchers are motivated to use internal meta-analysis in order to obtain a significant overall effect. Specifically, if one decides whether to stop or continue a further replication experiment depending on the significance of the results in an internal meta-analysis, false-positive rates would increase beyond the nominal level. We conducted a set of Monte-Carlo simulations to demonstrate our argument, and provided a literature review to gauge awareness and prevalence of this issue. Furthermore, we made several recommendations when using internal meta-analysis to make a judgment on statistical significance.

The impact of the elderly on inflation rates in developed countries

What explains the cross-national variation in inflation rates in developed countries? Previous literature has emphasised the role of ideas and institutions, and to a lesser extent interest groups, while leaving the role of electoral politics comparatively unexplored. This paper seeks to redress this neglect by focusing on one case where electoral politics matters for inflation: the share of the population above 65 years old in a country. I argue that countries with a larger share of elderly have lower inflation because older people are both more inflation averse and politically powerful, forcing governments to pursue lower inflation. I test my argument in three steps. First, logistic regression analysis of survey data confirms older people are more inflation averse. Second, panel data regression analysis of party manifesto data reveals that European countries with more old people have more economically orthodox political parties. Third, time series cross-section regression analyses demonstrate that the share of the elderly is negatively correlated with inflation in both a sample of 21 advanced OECD economies and a larger sample of 175 countries. Ageing may therefore push governments to adopt a low inflation regime.

CMB and LSS constraints on a single-field model of inflation

A new inflationary scenario whose exponential potential V (Phi) has a quadratic dependence on the field Phi in addition to the standard linear term is confronted with the five-year observations of the Wilkinson-Microwave Anisotropy Probe and the Sloan Digital Sky Survey data. The number of e-folds (N), the ratio of tensor-to-scalar perturbations (r), the spectral scalar index of the primordial power spectrum (n(s)) and its running (dn(s)/d ln k) depend on the dimensionless parameter a multiplying the quadratic term in the potential. In the limit a. 0 all the results of the exponential potential are fully recovered. For values of alpha not equal 0, we find that the model predictions are in good agreement with the current observations of the Cosmic Microwave Background (CMB) anisotropies and Large-Scale Structure (LSS) in the Universe. Copyright (C) EPLA, 2008.

Leptin Targets in the Mouse Brain

The central actions of leptin are essential for homeostatic control of adipose tissue mass, glucose metabolism, and many autonomic and neuroendocrine systems. In the brain, leptin acts on numerous different cell types via the long-form leptin receptor (LepRb) to elicit its effects. The precise identification of leptin`s cellular targets is fundamental to understanding the mechanism of its pleiotropic central actions. We have systematically characterized LepRb distribution in the mouse brain using in situ hybridization in wildtype mice as well as by EYFP immunoreactivity in a novel LepRb-IRES-Cre EYFP reporter mouse line showing high levels of LepRb mRNA/EYFP coexpression. We found substantial LepRb mRNA and EYFP expression in hypothalamic and extrahypothalamic sites described before, including the dorsomedial nucleus of the hypothalamus, ventral premammillary nucleus, ventral tegmental area, parabrachial nucleus, and the dorsal vagal complex. Expression in insular cortex, lateral septal nucleus, medial preoptic area, rostral linear nucleus, and in the Edinger-Westphal nucleus was also observed and had been previously unreported. The LepRb-IRES-Cre reporter line was used to chemically characterize a population of leptin receptor-expressing neurons in the midbrain. Tyrosine hydroxylase and Cre reporter were found to be coexpressed in the ventral tegmental area and in other midbrain dopaminergic neurons. Lastly, the LepRbI-RES-Cre reporter line was used to map the extent of peripheral leptin sensing by central nervous system (CNS) LepRb neurons. Thus, we provide data supporting the use of the LepRb-IRES-Cre line for the assessment of the anatomic and functional characteristics of neurons expressing leptin receptor. J. Comp. Neurol. 514:518-532, 2009. (C) 2009 Wiley-Liss, Inc.

Evidence for the thalamic targets of the medial hypothalamic defensive system mediating emotional memory to predatory threats

Previous studies from our laboratory have documented that the medial hypothalamic defensive system is critically involved in processing actual and contextual predatory threats, and that the dorsal premammillary nucleus (PMd) represents the hypothalamic site most responsive to predatory threats. Anatomical findings suggest that the PMd is in a position to modulate memory processing through a projecting branch to specific thalamic nuclei, i.e., the nucleus reuniens (RE) and the ventral part of the anteromedial nucleus (AMv). In the present study, we investigated the role of these thalamic targets in both unconditioned (i.e., fear responses to predatory threat) and conditioned (i.e., contextual responses to predator-related cues) defensive behaviors. During cat exposure, all experimental groups exhibited intense defensive responses with the animals spending most of the time in the home cage displaying freezing behavior. However, during exposure to the environment previously associated with a cat, the animals with combined RE + AMv lesions, and to a lesser degree, animals with single AMv unilateral lesions, but not animals with single RE lesions, presented a reduction of contextual conditioned defensive responses. Overall, the present results provide clear evidence suggesting that the PMd`s main thalamic targets (i.e., the nucleus reuniens and the AMv) seem to be critically involved in the emotional memory processing related to predator cues. (C) 2010 Elsevier Inc. All rights reserved.

Differential Antitumor Effects of IgG and IgM Monoclonal Antibodies and Their Synthetic Complementarity-Determining Regions Directed to New Targets of B16F10-Nex2 Melanoma Cells

Malignant melanoma has increased incidence worldwide and causes most skin cancer-related deaths. A few cell surface antigens that can be targets of antitumor immunotherapy have been characterized in melanoma. This is an expanding field because of the ineffectiveness of conventional cancer therapy for the metastatic form of melanoma. In the present work, antimelanoma monoclonal antibodies (mAbs) were raised against B16F10 cells (subclone Nex4, grown in murine serum), with novel specificities and antitumor effects in vitro and in vivo. MAb A4 (IgG2ak) recognizes a surface antigen on B16F10-Nex2 cells identified as protocadherin beta(13). It is cytotoxic in vitro and in vivo to B16F10-Nex2 cells as well as in vitro to human melanoma cell lines. MAb A4M (IgM) strongly reacted with nuclei of permeabilized murine tumor cells, recognizing histone 1. Although it is not cytotoxic in vitro, similarly with mAb A4, mAb A4M significantly reduced the number of lung nodules in mice challenged intravenously with B16F10-Nex2 cells. The V(H) CDR3 peptide from mAb A4 and V(L) CDR1 and CDR2 from mAb A4M showed significant cytotoxic activities in vitro, leading tumor cells to apoptosis. A cyclic peptide representing A4 CDR H3 competed with mAb A4 for binding to melanoma cells. MAb A4M CDRs L1 and L2 in addition to the antitumor effect also inhibited angiogenesis of human umbilical vein endothelial cells in vitro. As shown in the present work, mAbs A4 and A4M and selected CDR peptides are strong candidates to be developed as drugs for antitumor therapy for invasive melanoma.

Cysteine proteases of Trypanosoma (Megatrypanum) theileri: Cathepsin L-like gene sequences as targets for phylogenetic analysis, genotyping diagnosis

Although Trypanosoma theileri and allied trypanosomes are the most widespread trypanosomes in bovids little is known about proteolytic enzymes in these species. We have characterized genes encoding for cathepsin L-like (CATL) cysteine proteases from isolates of cattle, water buffalo and deer that largely diverged from homologues of other trypanosome species. Analysis of 78 CATL catalytic domain sequences from 22 T. theileri trypanosomes disclosed 6 genotypes tightly clustered together into the T. theileri clade. The CATL genes in these trypanosomes are organized in tandem arrays of similar to 1.7 kb located in 2 chromosomal bands of 600-720 kb. A diagnostic PCR assay targeting CATL sequences detected T. theileri of all genotypes from cattle, buffaloes and cervids and also from tabanid vectors. Expression of T. theileri cysteine proteases was demonstrated by proteolytic activity in gelatin gels and hydrolysis of Z-Phe-Arg-AMC substrate. Results from this work agree with previous data using ribosomal and spliced leader genes demonstrating that CATL gene sequences are useful for diagnosis, population genotyping and evolutionary studies of T. theileri trypanosomes. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

CLUSTER MODEL FOR REACTIONS INDUCED BY WEAKLY BOUND AND/OR EXOTIC HALO NUCLEI WITH MEDIUM-MASS TARGETS

An experimental overview of reactions induced by the stable, but weakly-bound nuclei (6)Li, (7)Li and (9)Be, and by the exotic, halo nuclei (6)He, (8)B, (11)Be and (17)F On medium-mass targets, such as (58)Ni, (59)Co or (64)Zn, is presented. Existing data on elastic scattering, total reaction cross sections, fusion, breakup and transfer channels are discussed in the framework of a CDCC approach taking into account the breakup degree of freedom.

Reaction mechanisms for weakly-bound, stable nuclei and unstable, halo nuclei on medium-mass targets

An experimental overview of reactions induced by the stable, but weakly-bound nuclei (6)Li, (7)Li and (9)Be, and by the exotic, halo nuclei (6)He, (8)B, (11)Be and (17)F on medium-mass targets, such as (58)Ni, (59)Co or (64)Zn, is presented. Existing data on elastic scattering, total reaction cross sections, fusion processes, breakup and transfer channels are discussed in the framework of a CDCC approach taking into account the breakup degree of freedom.

MODELLING AND FORECASTING INFLATION RATES IN GHANA: AN APPLICATION OF SARIMA MODELS

Ghana faces a macroeconomic problem of inflation for a long period of time. The problem in somehow slows the economic growth in this country. As we all know, inflation is one of the major economic challenges facing most countries in the world especially those in African including Ghana. Therefore, forecasting inflation rates in Ghana becomes very important for its government to design economic strategies or effective monetary policies to combat any unexpected high inflation in this country. This paper studies seasonal autoregressive integrated moving average model to forecast inflation rates in Ghana. Using monthly inflation data from July 1991 to December 2009, we find that ARIMA (1,1,1)(0,0,1)12 can represent the data behavior of inflation rate in Ghana well. Based on the selected model, we forecast seven (7) months inflation rates of Ghana outside the sample period (i.e. from January 2010 to July 2010). The observed inflation rate from January to April which was published by Ghana Statistical Service Department fall within the 95% confidence interval obtained from the designed model. The forecasted results show a decreasing pattern and a turning point of Ghana inflation in the month of July.

Are central bank independence reforms necessary for achieving low and stable inflation?

Using data on the occurence of central bank independence (CBI) reforms in 131 countries during 1980-2005, we test whether they were important in reducing inflation and maintaining price stability. CBI reforms are found to have reduced inflation on average 3.31% when countries with historically high inflation rates are included. But countries with lower inflation have reduced it without institutional reforms granting central banks more independence, undermining the theoretical time-inconsistency case for CBI. There is furthermore no evidence that CBI reforms have helped reduce inflation variability.

Effects of central bank independence reforms on inflation in different parts of the world

The purpose of this study is to analyze the effect of CBI-reforms on inflation in different parts of the world from a theoretical and empirical perspective. Compared to previous studies, this study focuses on whether CBI-reforms have different effects on reducing inflation in different parts of the world. The study is based on a 132 country data-set from 1980 to 2005 compiled by Daunfeldt et al. (2008). The result indicates that the reduction in inflation due to the CBI-reforms varies between 2.2 and 12.32 percentage points in Asia, Europe, South America and Oceania, supporting the claim that implementing CBI-reforms can be successful in reducing inflation in most of the parts of the world.