bluuebunny/crossref_metadata_2025 huggingface dataset:
FoxO1 induces Ikaros splicing to promote immunoglobulin gene recombination
Authors: Alkhatib Alabbas , Werner Markus , Hug Eva , Herzog Sebastian , Eschbach Cathrin , Faraidun Hemin , Köhler Fabian , Wossning Thomas , Jumaa Hassan
Published: January 2012

Somatic rearrangement of immunoglobulin (Ig) genes is a key step during B cell development. Using pro–B cells lacking the phosphatase Pten (phosphatase and tensin homolog), which negatively regulates phosphoinositide-3-kinase (PI3K) signaling, we show that PI3K signaling inhibits Ig gene rearrangement by suppressing the expression of the transcription factor Ikaros. Further analysis revealed that the transcription factor FoxO1 is crucial for Ikaros expression and that PI3K-mediated down-regulation of FoxO1 suppresses Ikaros expression. Interestingly, FoxO1 did not influence Ikaros transcription; instead, FoxO1 is essential for proper Ikaros mRNA splicing, as FoxO1-deficient cells contain aberrantly processed Ikaros transcripts. Moreover, FoxO1-induced Ikaros expression was sufficient only for proximal VH to DJH gene rearrangement. Simultaneous expression of the transcription factor Pax5 was needed for the activation of distal VH genes; however, Pax5 did not induce any Ig gene rearrangement in the absence of Ikaros. Together, our results suggest that ordered Ig gene rearrangement is regulated by distinct activities of Ikaros, which mediates proximal VH to DJH gene rearrangement downstream of FoxO1 and cooperates with Pax5 to activate the rearrangement of distal VH genes.
IRE1α activation protects mice against acetaminophen-induced hepatotoxicity
Authors: Hur Kyu Yeon , So Jae-Seon , Ruda Vera , Frank-Kamenetsky Maria , Fitzgerald Kevin , Koteliansky Victor , Iwawaki Takao , Glimcher Laurie H. , Lee Ann-Hwee
Published: January 2012

The mammalian stress sensor IRE1α plays a central role in the unfolded protein, or endoplasmic reticulum (ER), stress response by activating its downstream transcription factor XBP1 via an unconventional splicing mechanism. IRE1α can also induce the degradation of a subset of mRNAs in a process termed regulated IRE1-dependent decay (RIDD). Although diverse mRNA species can be degraded by IRE1α in vitro, the pathophysiological functions of RIDD are only beginning to be explored. Acetaminophen (APAP) overdose is the most frequent cause of acute liver failure in young adults in the United States and is primarily caused by CYP1A2-, CYP2E1-, and CYP3A4-driven conversion of APAP into hepatotoxic metabolites. We demonstrate here that genetic ablation of XBP1 results in constitutive IRE1α activation in the liver, leading to RIDD of Cyp1a2 and Cyp2e1 mRNAs, reduced JNK activation, and protection of mice from APAP-induced hepatotoxicity. A pharmacological ER stress inducer that activated IRE1α suppressed the expression of Cyp1a2 and Cyp2e1 in WT, but not IRE1α-deficient mouse liver, indicating the essential role of IRE1α in the down-regulation of these mRNAs upon ER stress. Our study reveals an unexpected function of RIDD in drug metabolism.
Diagnosing Hypertension—Implications of the 2011 NICE Guidance
Authors: Wood Sally
Published: January 2012

The accurate diagnosis of hypertension is a difficult issue. The 2006 National Institute for Health and Clinical Excellence (NICE) guidance for the management of hypertension in adults in primary care recommended the use of clinic measurements taken on multiple occasions. However, this process was both protracted and potentially inaccurate. As a result, some patients may have been inappropriately treated with anti-hypertensive drugs causing both unnecessary side effects and excess costs to the National Health Service (NHS). Others may not have been treated at all resulting in additional cardiovascular events. Given this, NICE has recently updated its guidance in this area to include an increasing role for ‘out-of-office’ techniques, including ambulatory and home monitoring.
Blindness
Authors: El-Khayat Abdul R.
Published: January 2012

Approximately 284 million people worldwide are blind or have low vision. The majority, 90%, live in developing countries where uncorrected refractive errors and cataracts are the most common causes. In the UK, nearly 2 million people live with sight loss, the majority as a consequence of age-related macular degeneration. Visual impairment is more common among the elderly, and so with the ageing of our population, the number of people with sight loss in the UK is set to increase dramatically in the future. Blindness and low vision have a significant impact on individuals' independence, activities of daily living and finance. The GP must be familiar with blindness and partial sightedness, its registration process and be able to facilitate access to support for patients.
Preface
Authors: Johnson Alan , Reeves David
Published: January 2012

Macrolide antibiotics have been available for some 40 years. During that time they have proved to be invaluable for treating specific infections and have displayed, in particular, a low level of serious adverse effects. Unfortunately, in recent years there has been an accelerating rise in acquired resistance in some bacterial pathogens which has now reached a level that threatens the usefulness of existing macrolides. Newer macrolides have been introduced that have greater inherent activity and enhanced pharmacokinetic properties, but these have shown crossresistance with the older macrolides and with one another. Modification of the ring structure of erythromycin has produced a new class of antibiotics, the ketolides, which is a novel addition to the macrolidelincosamide-streptogramin group of antibiotics. These new agents show activity against strains of pathogens with acquired resistance to erythromycin, due either to erm-mediated modification of the ribosomal target site or to mef-mediated macrolide efflux. This supplement contains four reviews that give a comprehensive overview of the structure–activity relationships of members of the ketolides, and explore in detail the in vitro activity of the first member of this class to undergo clinical development, telithromycin. If the promise from its initial clinical trials is borne out, the ketolides may prove a valuable new resource, particularly for the treatment of respiratory tract infections, which remain a significant cause of morbidity and mortality around the world.
Activity of telithromycin, a new ketolide antibacterial, against atypical and intracellular respiratory tract pathogens
Authors: Hammerschlag M. R. , Roblin P. M. , Bébéar C. M.
Published: January 2012

Atypical respiratory pathogens such as Mycoplasma pneumoniae and intracellular pathogens such as Legionella spp. and Chlamydia spp. form a significant proportion of the aetiological agents underlying community-acquired pneumonia (CAP). The clinical signs or radiological features of atypical pneumonia are generally insufficient to predict accurately the pathogen involved; in addition, high costs and a considerable length of time are involved in the identification of atypical pathogens. Treatment is, therefore, most often empirical, and it is important that the activity of antibacterial agents available to treat CAP is sufficiently broad to eradicate infection with both common and atypical bacterial pathogens. Telithromycin (HMR 3647) is the first of a new family of antibacterials, the ketolides, and has been designed specifically for the treatment of community-acquired respiratory tract infections (RTIs). The excellent activity of telithromycin against the respiratory tract bacterial pathogens most commonly associated with community-acquired RTIs, including resistant strains, is well established. This review examines the considerable body of evidence showing that telithromycin also has a high level of activity against atypical and intracellular respiratory tract bacterial pathogens.
Activity of the ketolide antibacterial telithromycin against typical community-acquired respiratory pathogens
Authors: Felmingham D. , Zhanel G. , Hoban D.
Published: January 2012

Community-acquired respiratory tract infections (RTIs) are among the most prevalent infectious diseases in the developed world. They cause considerable morbidity, resulting in a major impact on public health both clinically and socioeconomically. The bacterial pathogens most commonly associated with community-acquired RTIs are Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, with Streptococcus pyogenes predominating in pharyngitis. Over the past years, each of these pathogens has developed mechanisms to evade susceptibility to antibacterials, leading to an alarming global increase in antibacterial resistance among these pathogens. There is great concern that currently available antibacterials are insufficient to treat community-acquired RTIs and there is an urgent requirement for new agents with activity against all strains of common community-acquired RTI pathogens. Telithromycin (HMR 3647) belongs to a new family of antibacterials, the ketolides, and has been specifically designed for the treatment of community-acquired RTIs. This review covers the potent in vitro activity of telithromycin against the most common community-acquired RTI pathogens compared with other currently available antimicrobial agents.
Overcoming antimicrobial resistance: profile of a new ketolide antibacterial, telithromycin
Authors: Leclercq Roland
Published: January 2012

Antimicrobial resistance amongst common respiratory pathogens has increased worldwide at an alarming rate and now threatens the clinical usefulness of a number of antibacterial agents. A major concern is the selection of resistance in the community, which tends to parallel the (often inappropriate) overuse of such agents. Such problems highlight the need for new antibacterial agents that retain activity against bacterial strains resistant to existing agents, and have a low potential to select for resistance or induce cross-resistance. Telithromycin is the first of a new family of antibacterials—the ketolides—and has been designed specifically for the treatment of community-acquired respiratory tract infections (RTIs). Numerous in vitro studies confirm the potent activity of telithromycin against pathogens commonly implicated in community-acquired RTIs, irrespective of their β-lactam, macrolide or fluoroquinolone susceptibility. Against pneumococci, for example, MICs were ≤ 1 mg/L irrespective of penicillin susceptibility, with ≥ 98% of macrolide-resistant strains inhibited at ≤ 0.5 mg/L, regardless of the underlying mechanism of resistance (including erm, mef and ribosomal L4 mutations). Against Haemophilus influenzae and Moraxella catarrhalis, including β-lactamase-positive strains, telithromycin is at least as potent as azithromycin. In addition, telithromycin has a very low potential for selection of resistant isolates or induction of cross-resistance. Importantly, and unlike existing macrolides, telithromycin does not induce MLSB resistance, a finding explained by the presence of the innovative 3-keto group in its chemical structure. Telithromycin therefore represents an important addition to the therapeutic armamentarium in an era of increasing antimicrobial resistance, with an expected low likelihood of the development of resistance in clinical use.
Pharmacokinetics and pharmacodynamics of oral β-lactam antibiotics as a two-dimensional approach to their efficacy
Authors: Auckenthaler Raymond
Published: January 2012

Pharmacokinetic and pharmacodynamic parameters are increasingly recognized as important determinants of the therapeutic efficacy of an antibiotic. For β-lactam antibiotics, the most important determinant of the antimicrobial efficacy, and hence predictor of therapeutic efficacy, is the length of time that serum concentrations exceed the MIC. Dosing schedules for β-lactam antibiotics should maintain serum concentrations above the MIC for the bacterial pathogen for at least 50% of the dosing interval to achieve therapeutic efficacy and prevent the development of resistance. This is a basic criterion for the clinical efficacy of β-lactams. A combination of microbiological activity and pharmacokinetic characteristics was applied to calculate the time that serum antibiotic concentrations exceed the MIC for the major respiratory tract pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes and Klebsiella pneumoniae . In contrast with some other oral β-lactam antibiotics, cefpodoxime 200 mg bd maintains serum concentrations above the MIC for each organism for at least 50% of the dosing interval and may therefore be an attractive choice for empirical therapy of community-acquired lower respiratory tract infections.
Clinical efficacy of cefpodoxime in respiratory tract infection
Authors: Cohen Robert
Published: January 2012

Acute otitis media (AOM), sinusitis and tonsillopharyngitis are respiratory tract infections frequently encountered by primary-care physicians. Increasing bacterial resistance, particularly in Streptococcus pneumoniae , which is one of the most important respiratory tract bacteria implicated in community-acquired respiratory tract infections, has led to concern about the current options for empirical antibiotic treatment and has prompted a search for effective alternative treatments. Data from in vitro studies show that cefpodoxime has good activity against the main respiratory tract pathogens, S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes . Clinical studies confirm the efficacy of cefpodoxime in AOM, sinusitis and tonsillopharyngitis. As with all broad-spectrum antibiotics, there is the risk of promotion of bacterial resistance associated with overuse. However, if used with care, cefpodoxime can be considered as an alternative for empirical treatment of bacterial respiratory tract infections encountered in general practice, particularly where penicillins and macrolides have reduced efficacy against the main bacterial pathogens.
fosB Gene Products Trigger Cell Proliferation and Morphological Alteration with an Increased Expression of a Novel Processed Form of Galectin-1 in the Rat 3Y1 Embroyo Cell Line
Authors: Nishioka Tomoko , Sakumi Kunihiko , Miura Tomofumi , Tahara Kazuki , Horie Hidenori , Kadoya Toshihiko , Nakabeppu Yusaku
Published: January 2012

In this study, we established rat 3Y1 embryo cell lines expressing FosB and AFosB as fusion proteins (ER-FosB, ER-AFosB) with the ligand-binding domain of human estrogen receptor (ER). The binding of estrogen to the fusion proteins resulted in their nuclear translocation. After estrogen administration, exponentially growing cells expressing ER-AFosB, and to a lesser extent ER-FosB, underwent morphological alteration from the flat fibroblastic shape to an extended bipolar shape, and ceased proliferating. Such morphological alteration was also induced in quiescent cells expressing ER-AFosB and ER-FosB after one round of cell division triggered by estrogen administration. The cells expressing ER-AFosB changed shape frequently, and the content of F-actin in the cytoplasm detected by binding of Alexa 488-phalloidin significantly decreased after the morphological alteration. By two-dimensional gel electrophoresis analysis of cellular proteins from the cells expressing ER-AFosB, we identified several proteins whose expression either increased or decreased after estrogen administration. Two of these proteins were identified from their amino acid sequences as novel processed form of galectin-1.
Hill-Robertson Interference is a Minor Determinant of Variations in Codon Bias Across Drosophila melanogaster and Caenorhabditis elegans Genomes
Authors: Marais Gabriel , Piganeau Gwenaël
Published: January 2012

According to population genetics models, genomic regions with lower crossing-over rates are expected to experience less effective selection because of Hill-Robertson interference (HRi). The effect of genetic linkage is thought to be particularly important for a selection of weak intensity such as selection affecting codon usage. Consistent with this model, codon bias correlates positively with recombination rate in Drosophila melanogaster and Caenorhabditis elegans. However, in these species, the G+C content of both noncoding DNA and synonymous sites correlates positively with recombination, which suggests that mutation patterns and recombination are associated. To remove this effect of mutation patterns on codon bias, we used the synonymous sites of lowly expressed genes that are expected to be effectively neutral sites. We measured the differences between codon biases of highly expressed genes and their lowly expressed neighbors. In D. melanogaster we find that HRi weakly reduces selection on codon usage of genes located in regions of very low recombination; but these genes only comprise 4% of the total. In C. elegans we do not find any evidence for the effect of recombination on selection for codon bias. Computer simulations indicate that HRi poorly enhances codon bias if the local recombination rate is greater than the mutation rate. This prediction of the model is consistent with our data and with the current estimate of the mutation rate in D. melanogaster. The case of C. elegans, which is highly self-fertilizing, is discussed. Our results suggest that HRi is a minor determinant of variations in codon bias across the genome.
Common Origin and Evolution of Glycosyltransferases Using Dol-P-monosaccharides as Donor Substrate
Authors: Oriol Rafael , Martinez-Duncker Ivan , Chantret Isabelle , Mollicone Rosella , Codogno Patrice
Published: January 2012

On the basis of the analysis of 64 glycosyltransferases from 14 species we propose that several successive duplications of a common ancestral gene, followed by divergent evolution, have generated the mannosyltransferases and the glucosyltransferases involved in asparagine-linked glycosylation (ALG) and phosphatidyl-inositol glycan anchor (PIG or GPI), which use lipid-related donor and acceptor substrates. Long and short conserved peptide motifs were found in all enzymes. Conserved and identical amino acid positions were found for the α2/6- and the α3/4-mannosyltransferases and for the α2/3-glucosyltransferases, suggesting unique ancestors for these three superfamilies. The three members of the α2-mannosyltransferase family (ALG9, PIG-B, and SMP3) and the two members of the α3-glucosyltransferase family (ALG6 and ALG8) shared 11 and 30 identical amino acid positions, respectively, suggesting that these enzymes have also originated by duplication and divergent evolution. This model predicts a common genetic origin for ALG and PIG enzymes using dolichyl-phospho-monosaccharide (Dol-P-monosaccharide) donors, which might be related to similar spatial orientation of the hydroxyl acceptors. On the basis of the multiple sequence analysis and the prediction of transmembrane topology we propose that the endoplasmic reticulum glycosyltransferases using Dol-P-monosaccharides as donor substrate have a multispan transmembrane topology with a first large luminal conserved loop containing the long motif and a small cytosolic conserved loop containing the short motif, different from the classical type II glycosyltransferases, which are anchored in the Golgi by a single transmembrane domain.
Sequence Variation and Haplotype Structure at the Putative Flowering-Time Locus COL1 of Brassica nigra
Authors: Lagercrantz Ulf , Kruskopf Osterberg Marita , Lascoux Martin
Published: January 2012

Motivated by a previous study indicating that polymorphism at an indel, Ind2, within the Brassica nigraCOL1 gene is significantly associated with flowering time, we searched for evidence of selection in a sample of 41 complete sequences of B. nigraCOL1. The within–gene population recombination rate is moderate, and all neutrality tests used in the present study failed to detect departure from the standard neutral model or evidence of selection. The haplotype structure of the 5′-half of the gene is primarily associated with the demographic history of the species and more specifically with the split between European and Ethiopian populations, whereas the structure of the 3′-half reflects the polymorphism at Ind2. This could be the result of selection or a combination of recombination and migration during the history of the sample of sequences. Without additional information on polymorphism in flanking areas, these two alternatives are difficult to tell apart. If selection acted on the gene, we suggest that if the indel itself is not the target of selection, among the polymorphic sites cosegregating with the polymorphism at Ind2, replacement polymorphisms around sites 890 and 1260 are the most likely quantitative trait nucleotides within the gene.
Testing for Differences in Rates-Across-Sites Distributions in Phylogenetic Subtrees
Authors: Susko Edward , Inagaki Yuji , Field Chris , Holder Michael E. , Roger Andrew J.
Published: January 2012

It has long been recognized that the rates of molecular evolution vary amongst sites in proteins. The usual model for rate heterogeneity assumes independent rate variation according to a rate distribution. In such models the rate at a site, although random, is assumed fixed throughout the evolutionary tree. Recent work by several groups has suggested that rates at sites often vary across subtrees of the larger tree as well as across sites. This phenomenon is not captured by most phylogenetic models but instead is more similar to the covarion model of Fitch and coworkers. In this article we present methods that can be useful in detecting whether different rates occur in two different subtrees of the larger tree and where these differences occur. Parametric bootstrapping and orthogonal regression methodologies are used to test for rate differences and to make statements about the general differences in the rates at sites. Confidence intervals based on the conditional distributions of rates at sites are then used to detect where the rate differences occur. Such methods will be helpful in studying the phylogenetic, structural, and functional bases of changes in evolutionary rates at sites, a phenomenon that has important consequences for deep phylogenetic inference.
GAI Homologues in the Hawaiian Silversword Alliance (Asteraceae-Madiinae): Molecular Evolution of Growth Regulators in a Rapidly Diversifying Plant Lineage
Authors: Remington David L. , Purugganan Michael D.
Published: January 2012

Accelerated evolution of regulatory genes has been proposed as an explanation for decoupled rates of morphological and molecular evolution. The Hawaiian silversword alliance (Asteraceae-Madiinae) has evolved drastic differences in growth form, including rosette plants, cushion plants, shrubs, and trees, since its origin ∼6 MYA. We have isolated genes in the DELLA subfamily of putative growth regulators from 13 taxa of Hawaiian and North American Madiinae. The Hawaiian taxa contain two copies of DaGAI that form separate clades within the Madiinae, consistent with an allotetraploid origin for the silversword alliance. DaGAI retains conserved features that have previously been identified in DELLA genes. Selective constraint in the Hawaiian DaGAI copies remains strong in spite of rapid growth form divergence in the silversword alliance, although the constraint was somewhat relaxed in the Hawaiian copies relative to the North American lineages. We failed to detect evidence for positive selection on individual codons. Notably, selective constraint remained especially strong in the gibberellin-responsive DELLA region for which the gene subfamily is named, which is truncated or deleted in all identified dwarf mutants in GAI homologues in different angiosperm species. In contrast with the coding region, however, ∼900 bp of the upstream flanking region shows variable rates and patterns of evolution, which might reflect positive selection on regulatory regions.
The Extent of Nucleotide Polymorphism is Highly Variable Across a 3-kb Region on Plasmodium falciparum Chromosome 2
Authors: Jongwutiwes Somchai , Putaporntip Chaturong , Friedman Robert , Hughes Austin L.
Published: January 2012

Genomic nucleotide polymorphism in the virulent human malarial parasite Plasmodium falciparum was surveyed by sequencing a 3-kb region of chromosome 2 from 21 isolates, including the MSP4 and MSP5 genes. Extensive sequence polymorphism was observed in the coding regions of these genes and in the region downstream to MSP5, and the average pairwise divergence time of haplotypes in this region was estimated to be at least about 200,000 years. But nucleotide polymorphism was not found in the introns and was much reduced in the intergenic region. Over the entire region, nucleotide diversity was negatively correlated with a nucleotide content skewed toward thymine. Together with the previous evidence of limited nucleotide polymorphism in introns of P. falciparum, these data suggest the existence of a mechanism suppressing single-nucleotide polymorphism in regions of the P. falciparum genome with highly skewed nucleotide content.
Bayesian Phylogenetics Using an RNA Substitution Model Applied to Early Mammalian Evolution
Authors: Jow H. , Hudelot C. , Rattray M. , Higgs P. G.
Published: January 2012

We study the phylogeny of the placental mammals using molecular data from all mitochondrial tRNAs and rRNAs of 54 species. We use probabilistic substitution models specific to evolution in base paired regions of RNA. A number of these models have been implemented in a new phylogenetic inference software package for carrying out maximum likelihood and Bayesian phylogenetic inferences. We describe our Bayesian phylogenetic method which uses a Markov chain Monte Carlo algorithm to provide samples from the posterior distribution of tree topologies. Our results show support for four primary mammalian clades, in agreement with recent studies of much larger data sets mainly comprising nuclear DNA. We discuss some issues arising when using Bayesian techniques on RNA sequence data.
Methodological Artifacts in Measures of Political Efficacy and Trust: A Multiple Correspondence Analysis
Authors: Blasius Jörg , Thiessen Victor
Published: January 2012

Many authors report a positive relationship of education and political interest with political efficacy and trust, but it is well known that both of the former are associated with response styles, such as a tendency to “strongly agree.” Since they are related to both a substantive concept (political efficacy and trust), and to methodological effects (agreement bias and a tendency to give non-substantive responses) it is important to assess whether the substantive relationship is due to methodological artifacts. Applying multiple correspondence analysis to the 1984 Canadian National Election Study, we will discuss a method which allows to test a set of items for measurement effects such as ordinality and response sets. In the given example, ordinality of the political efficacy and trust items could be confirmed only for politically interested respondents. For respondents with low political interest, there is clear evidence of a response set resulting in a tendency to “strongly agree” regardless of the direction of the items. Taken together, these findings call into question the substantive relationships reported in the literature.
Do Surveys Provide Representative or Whimsical Assessments of the Economy?
Authors: Palmer Harvey D. , Duch Raymond M.
Published: January 2012

We argue that survey responses to economic evaluation questions exhibit instability and can be affected by fairly trivial changes in questionnaire wording. Our analyses make three empirical contributions to this area of survey research. First, we demonstrate that within the course of the interview there is considerable instability in economic evaluations. Second, one source of this instability is cues regarding economic performance, such as those provided by the media. We find that respondents can be persuaded to change their economic evaluations if they receive contradictory cues. Finally, we demonstrate that question placement can affect economic evaluations. More specifically, we demonstrate that proximity to political questions can contaminate economic evaluations. If economic evaluations closely follow political preference questions, respondents have a tendency to give economic responses that are “consistent” with their political responses. Our empirical analysis is based on economic evaluations of respondents to the Hungarian Markets and Democracy Survey administered during December 1997.
A Linear Poisson Autoregressive Model: The Poisson AR(p) Model
Authors: Brandt Patrick T. , Williams John T.
Published: January 2012

Time series of event counts are common in political science and other social science applications. Presently, there are few satisfactory methods for identifying the dynamics in such data and accounting for the dynamic processes in event counts regression. We address this issue by building on earlier work for persistent event counts in the Poisson exponentially weighted moving-average model (PEWMA) of Brandt et al. (American Journal of Political Science44(4):823–843, 2000). We develop an alternative model for stationary mean reverting data, the Poisson autoregressive model of orderp, or PAR(p) model. Issues of identification and model selection are also considered. We then evaluate the properties of this model and present both Monte Carlo evidence and applications to illustrate.
Classification by Opinion-Changing Behavior: A Mixture Model Approach
Authors: Hill Jennifer L. , Kriesi Hanspeter
Published: January 2012

We illustrate the use of a class of statistical models, finite mixture models, that can be used to allow for differences in model parameterizations across groups, even in the absence of group labels. We also introduce a methodology for fitting these models, data augmentation. Neither finite mixture models nor data augmentation is routine in the world of political science methodology, but both are quite standard in the statistical literature. The techniques are applied to an investigation of the empirical support for a theory (developed fully by Hill and Kriesi 2001) that extends Converse's (1964) “black-and-white” model of response stability. Our model formulation enables us (1) to provide reliable estimates of the size of the two groups of individuals originally distinguished in this model, opinion holders and unstable opinion changers; (2) to examine the evidence for Converse's basic claim that these unstable changers truly exhibit nonattitudes; and (3) to estimate the size of a newly defined group, durable changers, whose members exhibit more stable opinion change. Our application uses survey data collected at four time points over nearly 2 years which track Swiss citizens' readiness to support pollution-reduction policies. The results, combined with flexible model checks, provide support for portions of Converse and Zaller's (1992) theories on response instability and appear to weaken the measurement-error arguments of Achen (1975) and others. This paper concentrates on modeling issues and serves as a companion paper to Hill and Kriesi (2001), which uses the same data set and model but focuses more on the details of the opinion-changing behavior debate.
Maximum Likelihood Estimation of Models with Beta-Distributed Dependent Variables
Authors: Paolino Philip
Published: January 2012

Research in political science is often concerned with modeling dependent variables that are proportions. Proportions are relevant in a wide variety of substantive areas, including elections, the bureaucracy, and interest groups. Yet because most researchers rely upon an approach, OLS, that does not recognize key aspects of proportions, the conclusions we reach from normal models may not provide the best understanding of phenomena of interest in these areas. In this paper, I use Monte Carlo simulations to show that maximum likelihood estimation of these data using the beta distribution may provide more accurate and more precise results. I then present empirical analyses illustrating some of these differences.
Computing Nash Equilibria in Probabilistic, Multiparty Spatial Models with Nonpolicy Components
Authors: Merrill Samuel , Adams James
Published: January 2012

Although there exist extensive results concerning equilibria in spatial models of two-party elections with probabilistic voting, we know far less about equilibria in multiparty elections—i.e., under what conditions will equilibria exist, and what are the characteristics of equilibrium configurations? We derive conditions that guarantee the existence of a unique Nash equilibrium and develop an algorithm to compute that equilibrium inmultiparty elections with probabilistic voting, in which voters choose according to the behaviorists' fully specified multivariate vote model. Previously, such computations could only be approximated by laborious search methods. The algorithm, which assumes a conditional logit choice function, can be applied to spatial competition for a variety of party objectives including vote-maximization and margin-maximization, and can also encompass alternative voter policy metrics such as quadratic and linear loss functions. We show that our conditions for an equilibrium are plausible given the empirically-estimated parameters that behaviorists report for voting behavior in historical elections. We also show that parties' equilibrium positions depend not only on the distribution of voters' policy preferences but also on their nonpolicy-related attributes such as partisanship and sociodemographic variables. Empirical applications to data from a recent French election illustrate the use of the algorithm and suggest that a unique Nash equilibrium existed in that election.
Confronting Political—Economic Theories of Voting with Evidence
Authors: Grafstein Robert , Moser Ann
Published: January 2012

This paper illustrates one strategy for testing a theory of economic influences on voting. We use a competitive equilibrium model of the economy to determine the impact of an individual's economic position on his or her economic interests and, ultimately, political interests. We then test whether this impact is observed in voting behavior, addressing the resulting specification and estimation problems in the context of U.S. presidential election data. Our empirical results suggest that, despite these formidable problems, we can usefully connect political-economic models and discrete-choice (probit) models of voting.
Surgery and Brain Atrophy in Cognitively Normal Elderly Subjects and Subjects Diagnosed with Mild Cognitive Impairment
Authors: Kline Richard P. , Pirraglia Elizabeth , Cheng Hao , De Santi Susan , Li Yi , Haile Michael , de Leon Mony J. , Bekker Alex
Published: January 2012

Background

Structural magnetic resonance imaging is used to longitudinally monitor the progression of Alzheimer disease from its presymptomatic to symptomatic phases. Using magnetic resonance imaging data from the Alzheimer's Disease Neuroimaging Initiative, we tested the hypothesis that surgery would impact brain parameters associated with progression of dementia.

Methods

Brain images from the neuroimaging initiative database were used to study normal volunteer subjects and patients with mild cognitive impairment for the age group 55 to 90 inclusive. We compared changes in regional brain anatomy for three visits that defined two intervisit intervals for a surgical cohort (n = 41) and a propensity matched nonsurgical control cohort (n = 123). The first interval for the surgical cohort contained the surgical date. Regional brain volumes were determined with Freesurfer and quantitatively described with J-image software (University of California at San Francisco, San Francisco, California). Statistical analysis used Repeated Measures ANCOVA (SPSS, v.18.0; Chicago, IL).

Results

We found that surgical patients, during the first follow-up interval (5-9 months), but not subsequently, had increased rates of atrophy for cortical gray matter and hippocampus, and lateral ventricle enlargement, as compared with nonsurgical controls. A composite score of five cognitive tests during this interval showed reduced performance for surgical patients with mild cognitive impairment.

Conclusions

Elderly subjects after surgery experienced an increased rate of brain atrophy during the initial evaluation interval, a time associated with enhanced risk for postoperative cognitive dysfunction. Although there was no difference in atrophy rate by diagnosis, subjects with mild cognitive impairment suffered greater subsequent cognitive effects.
Pluripotency of a polyploid H1 (ES) cell system without leukaemia inhibitory factor
Authors: Fujikawa‐Yamamoto K. , Ota T. , Miyagoshi M. , Yamagishi H.
Published: January 2012

Objectives:  Tetraploid cells are strictly biologically inhibited from composition of embryos; by the same token, only diploid cells compose embryos. However, the distinction between diploid and tetraploid cells in development has not been well explained. To examine pluripotency of polyploid ES cells, a polyploid embryonic stem (ES)‐cell system was prepared.

Materials and methods:  Diploid, tetraploid, pentaploid, hexaploid, octaploid and decaploid H1 (ES) cells (2H1, 4H1, 5H1, 6H1, 8H1 and 10H1 cells, respectively) were cultured for about 460 days in L15F10 medium without leukaemia inhibitory factor (LIF). The cells cultured under LIF‐free conditions were denoted as 2H1(−), 4H1(−), 5H1(−), 6H1(−), 8H1(−) and 10H1(−) cells, respectively. Pluripotency and gene expression were examined.

Results:  Ploidy alteration of H1(−) cells was similar to that of H1 cells. The polyploid H1(−) cells showed positive activity of alkaline phosphatase, suggesting that they maintained pluripotency in vitro without LIF. The polyploid H1(−) cells formed teratocarcinomas in mouse abdomen, suggesting they could differentiate in mouse abdomen in vivo. 2H1, 4H1 and polyploid H1(−) cells expressed nanog, oct3/4 and sox2 genes, suggesting that they fulfilled the criteria of ES cells. Nanog gene was significantly over‐expressed in 4H1 and polyploid H1(−) cells, suggesting that overexpression of nanog gene was a characteristic of polyploid H1 cells.

Conclusion:  Polyploid H1 (ES) cells retained pluripotency in vitro, without LIF with nanog over‐expression.
Photoconversion of DAPI following UV or violet excitation can cause DAPI to fluoresce with blue or cyan excitation
Authors: PITERBURG M. , PANET H. , WEISS A.
Published: January 2012

4’‐6‐Diamidino‐2‐phenylindole is a fluorescent dye commonly used to visualize deoxyribonucleic acid or cell nuclei in fixed cell preparations, and is often used together with fluorescein or green fluorescent protein, which can be excited without exciting 4’‐6‐Diamidino‐2‐phenylindole. It is assumed that when using typical fluorescein or green fluorescent protein filter cubes, 4’‐6‐Diamidino‐2‐phenylindole will not be observed. In this paper, we show that following observation of 4’‐6‐Diamidino‐2‐phenylindole using UV or violet excitation, it may become sensitive to the blue/cyan excitation used in fluorescein/green fluorescent protein filter cubes. This has serious implications for the use of 4’‐6‐Diamidino‐2‐phenylindole together with widely used green fluorophores in double labelling experiments.
Putative members of the Arabidopsis Nup107‐160 nuclear pore sub‐complex contribute to pathogen defense
Authors: Wiermer Marcel , Cheng Yu Ti , Imkampe Julia , Li Meilan , Wang Dongmei , Lipka Volker , Li Xin
Published: January 2012

In eukaryotic cells, transduction of external stimuli into the nucleus to induce transcription and export of mRNAs for translation in the cytoplasm is mediated by nuclear pore complexes (NPCs) composed of nucleoporin proteins (Nups). We previously reported that ArabidopsisMOS3, encoding the homolog of vertebrate Nup96, is required for plant immunity and constitutive resistance mediated by the de‐regulated Toll interleukin 1 receptor/nucleotide‐binding/leucine‐rich repeat (TNL)‐typeRgenesnc1. In vertebrates, Nup96 is a component of the conserved Nup107‐160 nuclear pore sub‐complex, and implicated in immunity‐related mRNA export. Here, we used a reverse genetics approach to examine the requirement for additional subunits of the predicted Arabidopsis Nup107‐160 complex in plant immunity. We show that, among eight putative complex members, beside MOS3, only plants with defects inNup160orSeh1are impaired in basal resistance. Constitutive resistance in thesnc1mutant and immunity mediated by TNL‐typeR genes also depend on functionalNup160and have a partial requirement forSeh1. Conversely, resistance conferred by coiled coil‐type immune receptors operates largely independently of both genes, demonstrating specific contributions to plant defense signaling. Our functional analysis further revealed that defects innup160andseh1result in nuclear accumulation of poly(A) mRNA, and, in the case ofnup160, considerable depletion of EDS1, a key positive regulator of basal and TNL‐triggered resistance. These findings suggest thatNup160is required for nuclear mRNA export and full expression of EDS1‐conditioned resistance pathways in Arabidopsis.
Relationship Between Condition, Aggression, Signaling, Courtship, and Egg Laying in the Field Cricket, Gryllus assimilis
Authors: Bertram Susan M. , Rook Vanessa
Published: January 2012

Sexual selection theory suggests males in good condition should be more successful than males in poor condition when competing with rivals for territories and mates. Understanding how condition influences the interplay between aggression, mate attraction, and courtship displays could help explain why variation is maintained in traits that confer fitness. Using laboratory‐reared Jamaican field crickets, Gryllus assimilis, we found that fine‐scale temporal components of mate attraction signals were positively correlated with body condition (residual body mass) and body size; signaling effort was positively correlated with both body condition and fine‐scale temporal signaling components; aggression was positively correlated with signaling effort; number of eggs laid was positively correlated with female body size, male body condition and aggression. Together our correlative study suggests that variation in body condition and size may drive some of the variation in cricket mate attraction signaling and aggression. Given condition and body size are influenced by foraging ability, nutrient availability and the organism’s ability to uptake and retain these essential nutrients could explain some of the persistent variation in fitness conferring traits.
HISTORY, INSTITUTIONS, AND CITIES: A VIEW FROM THE AMERICAS*
Authors: Kim Sukkoo , Law Marc T.
Published: January 2012

ABSTRACT Every nation, formally or informally, defines and establishes the lines of political and fiscal authority among its national, regional, and local governments. Historically, centralized governments tend to restrict the power and autonomy of provincial and local governments. In this paper, we exploit the quasi‐experimental distribution of political institutions in the Americas caused by variation in European colonial experience to examine the impact of institutions on urban and local development, specifically on the degree of urban primacy, the size distribution of cities, the number and density of local government units, and the fragmentation of metropolitan areas. We argue that centralization of political power at the national level, as experienced in many countries in Latin America, contributes to urban primacy and a size distribution of cities favoring large cities. Additionally, even in more politically decentralized countries such as Canada and the U.S., variance in political centralization at the provincial (state) level over local governments led to significant divergences in urban primacy, the distribution of city sizes, as well as the form, number, and density of local governments. While we cannot rule out the importance of other factors, our findings suggest that political centralization affects spatial economic development.
THE SOURCES OF URBAN DEVELOPMENT: WAGES, HOUSING, AND AMENITY GAPS ACROSS AMERICAN CITIES*
Authors: Kemeny Thomas , Storper Michael
Published: January 2012

ABSTRACT This paper asks whether worker utility levels—composed of wages, rents, and amenities—are being equalized among American cities. Using microdata on U.S. urban workers in 1980 and 2000, little evidence of equalization is found. Comparable workers earn higher real wages in large cities, where amenities are also concentrated. Moreover, population growth between 1980 and 2000 has not been significantly different in low‐ and high‐utility cities, suggesting that other forces are at work shaping the sorting processes that match workers and firms. We outline an alternative view of the drivers of change in the American urban system, and urban development more generally, by applying theory from economic geography.
A Simple Panel‐CADF Test for Unit Roots*
Authors: Costantini Mauro , Lupi Claudio
Published: January 2012

In this paper, we propose a simple extension to the panel case of the covariate‐augmented Dickey–Fuller (CADF) test for unit roots developed in Hansen (1995). The panel test we propose is based on a P values combination approach that takes into account cross‐section dependence. We show that the test has good size properties and gives power gains with respect to other popular panel approaches. An empirical application is carried out for illustration purposes on international data to test the purchasing power parity (PPP) hypothesis.
Meningoencephaloradiculomyelitis after tick‐borne encephalitis virus infection: a case series
Authors: Ponfick M. , Hacker S. , Gdynia H‐J. , Linden R. , Gränz M. , Nowak D. A.
Published: January 2012

Background:  Tick‐borne encephalitis (TBE) is caused by a RNA‐virus and is in about 50% of cases characterized by a biphasic clinical course in adults. Different clinical syndromes have been described, including meningitis, meningoencephalitis, meningoencephalomyelitis and meningoencephaloradiculomyelitis. The latter seems to be the most disabling and severe form of TBE virus infection.

Methods:  Here we report five cases with meningoencephaloradiculomyelitis. Only in three patients a tick prick was remembered.

Results:  Only two patients could be weaned successfully from assisted ventilation; only one patient was able to return to self‐dependent life without nursing support. The youngest patient in this case series showed the most favourable outcome.

Conclusions:  Polyradiculopathy and/or myelopathy as verified by electrophysiological examination within 4 weeks from symptom onset were indicative of a more severe disease course and a greater likelihood of moderate to serious sequelae even after long‐term rehabilitation. Older age at symptom onset seems to be associated with a less favourable outcome. Because of frequent long‐term hospitalization with immobilization and invasive ventilation, secondary complications, such as ventilation associated pulmonary infections and decubiti, must be avoided.