bluuebunny/crossref_metadata_2025 huggingface dataset:
Monocytes/macrophages and/or neutrophils are the target of IL‐10 in the LPS endotoxemia model
Authors: Pils Marina C. , Pisano Fabio , Fasnacht Nicolas , Heinrich Jan‐Michael , Groebe Lothar , Schippers Angela , Rozell Björn , Jack Robert S. , Müller Werner
Published: November 2009

IL‐10 is a potent regulator of the innate and adaptive immune responses. Several cell types produce IL‐10 and its receptor chains and these may regulate different immune responses. Here we report that inactivation of the IL‐10 receptor (IL‐10R1) gene in mice leads to an increased susceptibility to chemically induced colitis as in the classical IL‐10‐deficient mutant. To identify the cells regulated by IL‐10 in immune responses, we generated several cell type specific IL‐10R1‐deficient mutants. We show that, in an IL‐10‐dependent LPS model of endotoxemia, dampening of the immune response requires expression of IL‐10R1 in monocytes/macrophages and/or neutrophils but not in T cells nor B cells. As the macrophage and/or neutrophil‐specific IL‐10‐deficient mutants also display the same phenotype, our results suggest that an autocrine loop in monocytes/macrophages is the most probable mechanism for the regulation of an LPS‐induced septic shock. In contrast, in an IL‐10‐regulated T‐cell response to Trichuris muris infection, IL‐10 acting on T cells or monocytes/macrophages/neutrophils is not critical for the control of the infection.
DC expressing transgene Foxp3 are regulatory APC
Authors: Lipscomb Michael W. , Taylor Jennifer L. , Goldbach Cristina J. , Watkins Simon C. , Wesa Amy K. , Storkus Walter J.
Published: November 2009

Tolerogenic DC and suppressive Foxp3+ Treg play important roles in preventing autoimmunity and allograft rejection. We report that (adenovirus mediated) ectopic expression of Foxp3 in human DC (i.e. DC.Foxp3) yields an APC that severely limits T‐cell proliferation and type‐1 immune responses from the naïve, but not memory, pool of responder T cells in vitro. In marked contrast, the frequencies of type‐2 and Treg responses were dramatically increased after stimulation of naïve T cells with DC.Foxp3 versus control DC. DC.Foxp3‐induced CD4+CD25+ Treg cells potently suppressed the proliferation of, and IFN‐γ production from, CD4+ and CD8+ responder T cells. Notably, the immunosuppressive biology of DC.Foxp3 was effectively normalized by addition of 1‐methyl‐tryptophan or neutralizing anti‐TGF‐β1 Ab during the period of T‐cell priming. These data suggest the potential utility of regulatory DC.Foxp3 and/or DC.Foxp3‐induced CD4+CD25+ Treg as translational agents for the amelioration or prevention of pathology in the setting of allograft transplantation and/or autoimmunity.
Hierarchy of immunosuppressive strength among myeloid‐derived suppressor cell subsets is determined by GM‐CSF
Authors: Dolcetti Luigi , Peranzoni Elisa , Ugel Stefano , Marigo Ilaria , Fernandez Gomez Audry , Mesa Circe , Geilich Markus , Winkels Gregor , Traggiai Elisabetta , Casati Anna , Grassi Fabio , Bronte Vincenzo
Published: November 2009

CD11b+/Gr‐1+ myeloid‐derived suppressor cells (MDSC) contribute to tumor immune evasion by restraining the activity of CD8+ T‐cells. Two major MDSC subsets were recently shown to play an equal role in MDSC‐induced immune dysfunctions: monocytic‐ and granulocytic‐like. We isolated three fractions of MDSC, i.e. CD11b+/Gr‐1high, CD11b+/Gr‐1int, and CD11b+/Gr‐1low populations that were characterized morphologically, phenotypically and functionally in different tumor models. In vitro assays showed that CD11b+/Gr‐1int cell subset, mainly comprising monocytes and myeloid precursors, was always capable to suppress CD8+ T‐cell activation, while CD11b+/Gr‐1high cells, mostly granulocytes, exerted appreciable suppression only in some tumor models and when present in high numbers. The CD11b+/Gr‐1int but not CD11b+/Gr‐1high cells were also immunosuppressive in vivo following adoptive transfer. CD11b+/Gr‐1low cells retained the immunosuppressive potential in most tumor models. Gene silencing experiments indicated that GM‐CSF was necessary to induce preferential expansion of both CD11b+/Gr‐1int and CD11b+/Gr‐1low subsets in the spleen of tumor‐bearing mice and mediate tumor‐induced tolerance whereas G‐CSF, which preferentially expanded CD11b+/Gr‐1high cells, did not create such immunosuppressive environment. GM‐CSF also acted on granulocyte–macrophage progenitors in the bone marrow inducing local expansion of CD11b+/Gr‐1low cells. These data unveil a hierarchy of immunoregulatory activity among MDSC subsets that is controlled by tumor‐released GM‐CSF.
Fréchet‐Type Pallado‐Dendrimers Containing Bis(pyrazolyl)methane Ligands
Authors: Sánchez‐Méndez Alberto , de Jesús Ernesto , Flores Juan C. , Gómez‐Sal Pilar
Published: November 2009

Neutral and cationic {bis(3,5‐dimethylpyrazol‐1‐yl)methane}palladium(II) complexes of general formula [PdClX{RCH(3,5‐Me2pz)2}] (X = Cl or Me) or [PdMe(MeCN){RCH(3,5‐Me2pz)2}][BArf4], where R is a benzyl or benzyloxycarbonyl group or a poly(aryl ether) Fréchet‐type dendron, have been synthesized and fully characterized, including by X‐ray diffraction methods in some cases. These palladium complexes have been evaluated as catalyst precursors in the Heck reaction between para‐iodotoluene and methyl acrylate. The active catalytic species formed from these precursors are apparently not coordinated to the bis(pyrazolyl)methane ligands.
Synthesis, Characterization and Hydrolysis of Osmium Tetraphosphorus Complexes
Authors: Caporali Maria , Di Vaira Massimo , Peruzzini Maurizio , Seniori Costantini Stefano , Stoppioni Piero , Zanobini Fabrizio
Published: November 2009

The reaction of [CpOs(PPh3)2Cl] (1) with one equivalent of white phosphorus in the presence of AgOTf (OTf = triflate, OSO2CF3) as chloride scavenger affords the stable metal complex [CpOs(PPh3)2(η1‐P4)]OTf (2), which contains the tetrahedral P4 η1‐bound to the CpOs(PPh3)2 metal fragment. Addition of [CpRu(PPh3)2(OTf)] to 2 yields the heterobimetallic species [{CpRu(PPh3)2}{CpOs(PPh3)2}(μ,η1:1‐P4)](OTf)2 (3), in which the tetrahedral P4 is bound to two different metal fragments through two phosphorus atoms. The compounds have been characterized by elemental analysis, IR and NMR spectroscopy, and their crystal structures have been determined by X‐ray diffraction. The coordinated P4, at variance with the free ligand, reacts with an excess amount of water in thf under mild conditions to yield several products, most of which have been characterized.
Phenolic antioxidants – radical‐scavenging and chain‐breaking activity: A comparative study
Authors: Kancheva Vessela D.
Published: November 2009

Fifty phenolic antioxidants (AH) (42 individual compounds and 8 binary mixtures of two antioxidants) were chosen for a comparative analysis of their radical‐scavenging (H‐donating) and chain‐breaking (antioxidant) activity. Correlations between experimental (antiradical and antioxidant) and predictable (theoretical) activities of 15 flavonoids, 15 hydroxy cinnamic acid derivatives, 5 hydroxy chalcones, 4 dihydroxy coumarins and 3 standard antioxidants (butylated hydroxytoluene, hydroquinone, DL‐α‐tocopherol) were summarized and discussed. The following models were applied to explain the structure‐activity relationships of phenolic antioxidants of natural origin: (a) model 1, a DPPH assay used for the determination of the radical‐scavenging capacity (AH + DPPH• → A• + DPPH‐H); (b) model 2, chemiluminescence of a model substrate RH (cumene or diphenylmethane) used for the determination of the rate constant of a reaction with model peroxyl radicals (AH + RO2• → ROOH + A•); (c) model 3, lipid autoxidation used for the determination of the chain‐breaking antioxidant efficiency and reactivity (AH + LO2• → LOOH + A•; A• + LH (+O2) → AH + LO2•); and (d) model 4, theoretical methods used for predicting the activity (predictable activity). The highest lipid oxidation stability was found for antioxidants with a catecholic structure and for their binary mixtures with DL‐α‐tocopherol, as a result of synergism between them.
Efficient and Chirally Specific Synthesis of Phenanthro‐Indolizidine Alkaloids by Parham‐Type Cycloacylation
Authors: Wang Ziwen , Li Zheng , Wang Kailiang , Wang Qingmin
Published: November 2009

A concise, efficient and modular route involving Parham‐type cycloacylation as the key step has been used to synthesize six enantiopure phenanthro‐indolizidine alkaloids 1a–c. The preparation of enantiomerically pure tylophora alkaloids and their seco analogues on a large‐scale is now feasible. The alcohol intermediates 8a–c, which are difficult to prepare by other synthetic methodologies, have been synthesized by a metallation–cyclization–reduction sequence in excellent yields.
A New Method for the Synthesis of Multisubstituted Pyrroles of Biological Interest by Double Nucleophilic Addition to α,β‐Unsaturated Imines
Authors: Takahashi Atsushi , Kawai Shiho , Hachiya Iwao , Shimizu Makoto
Published: November 2009

Double nucleophilic addition reactions of dialkoxy ketenesilyl acetals proceeded with α,β‐unsaturated imines to give 1,4‐ and 1,2‐double addition products, and their subsequent transformations afforded multisubstituted pyrroles in good yields. Application of this procedure to the synthesis of an imidazole glycerol phosphate dehydratase inhibitor (IGPDI), a physiologically active 2,3,5‐trisubstituted pyrrole, is also described.
High‐performance CE of Escherichia coli K4 cell surface polysaccharides
Authors: Restaino Odile F. , Cimini Donatella , De Rosa Mario , De Castro Cristina , Parrilli Michelangelo , Schiraldi Chiara
Published: November 2009

A high‐performance CE application for a quick, reproducible, highly precise and sensitive determination of the lipopolysaccharide produced by Escherichia coli K4 (O5:K4:H4) and of its de‐lipid A form is described. The two species were separated within 30 min on an uncoated fused‐silica capillary, in normal polarity mode at 20 kV, using an SDS buffer. Detected at 190 nm, the de‐lipid A and the LPS species showed two peaks at distinctive migration times (10.45 and 16.10 min, respectively) and were quantified with high reproducibility and linearity (the correlation factors were 0.99 and 0.98, respectively) over the ranges from 60 to 600 ng (1–10 ng/nL) for de‐lipid A lipopolysaccharide and from 150 to 600 ng (2.5–10 ng/nL) for the LPS. The described method was also employed in the contemporary analysis and the determination of the two E. coli K4 cell surface polysaccharides, the LPS and the K4, and of their defructosylated and de‐lipid A species, respectively. The four molecules were detected and precisely quantified in complex matrices as fermentation broth supernatant or in samples withdrawn throughout the purification process, thus demonstrating the possibility to apply high‐performance CE as a reliable analytical tool in biotechnological processes.
Estimating the integrity of aged DNA samples by CE
Authors: Fattorini Paolo , Marrubini Giorgio , Ricci Ugo , Gerin Fabio , Grignani Pierangela , Sorçaburu Cigliero Solange , Xamin Andrea , Edalucci Elisabetta , La Marca Giancarlo , Previderé Carlo
Published: November 2009

A CE/UV method was developed to separate by a micellar system the four DNA bases and other five purinic–pyrimidinic compounds (5‐methyl‐cytosine, uracil, xanthyne, hypoxanthyne and 5‐bromo‐uracil). Selectivity, precision, accuracy and sensitivity were assessed and proved to be suitable for the analysis of the primary structure of DNA. This method was adopted to study 16 aged samples including two Egyptian mummies, formaldehyde‐fixed paraffin‐embedded tissues and other forensic specimens. Lower relative values of the four canonical unmodified DNA bases (uDNAb) and more complex pherograms were found in the aged samples when compared with the modern controls. The results of the CE analysis, together with those obtained by classical molecular methods (agarose gel electrophoresis, DNase I and RNase A assays, and UV spectrophotometry), were finally evaluated for assessing the reliability of STR typing. Since samples with low uDNAb showed no amplification or unreliable STR profiles, the uDNAb value is discussed as a further quality criterion in the evaluation of the genetic data obtained from aged samples.
Is the general conclusion justified that higher applicable field strength results in shorter analysis time with organic solvents in CE?
Authors: Téllez Adolfo , Kenndler Ernst
Published: November 2009

In this paper, a widespread opinion in CE with organic solvents for the background electrolyte is critically questioned, namely that in general a shorter analysis time can be achieved due to the higher field strength applicable compared with aqueous electrolyte systems. This view, common in the literature, is based on the supposition that the conductance in organic solvents is lower than in water. Indeed in many organic solvents with higher viscosity than water lower ion mobility is observed, and higher fields can be applied in these cases. However, in this paper the problem is sharper defined and treated two‐fold: (i) in all solvents conditions are such that either the same electric power is generated, or (ii) the same temperature increase is taken into account. It was shown that for the same electric power the field strength in the organic solvent can be changed to a less extent than the ionic mobility changes. As a result, the migration velocity of the analytes is lower and the analysis time is longer in most organic solvents compared with water; acetonitrile (MeCN) is an exception (in this solvent the mobilities are higher than in water). The more stringent treatment of the problem takes an equal temperature increase due to Joule heating into account rather than equal electric power. The temperature increase in the capillary depends on the thermal conductivity of the solvent, which is only about one‐third of that of water for organic liquids. The consequence is that in none of the organic solvent systems a shorter analysis time can be achieved compared with water (given that the experimental conditions are comparable, e.g. zero EOF). The theoretical predictions were confirmed by measurements with water, methanol, propylenecarbonate, and MeCN as solvents.
Business failure prediction using decision trees
Authors: Gepp Adrian , Kumar Kuldeep , Bhattacharya Sukanto
Published: November 2009

Accurate business failure prediction models would be extremely valuable to many industry sectors, particularly financial investment and lending. The potential value of such models is emphasised by the extremely costly failure of high‐profile companies in the recent past. Consequently, a significant interest has been generated in business failure prediction within academia as well as in the finance industry. Statistical business failure prediction models attempt to predict the failure or success of a business. Discriminant and logit analyses have traditionally been the most popular approaches, but there are also a range of promising non‐parametric techniques that can alternatively be applied. In this paper, the relatively new technique of decision trees is applied to business failure prediction. The numerical results suggest that decision trees could be superior predictors of business failure as compared to discriminant analysis. Copyright © 2009 John Wiley & Sons, Ltd.
Genetic Analysis Workshop 16: introduction to workshop summaries
Authors: MacCluer Jean W. , Amos Christopher I. , Gregersen Peter K. , Heard‐Costa Nancy , Lee Monica , Kraja Aldi T. , Borecki Ingrid B. , Cupples L. Adrienne , Almasy Laura
Published: November 2009

Genetic Analysis Workshop 16 (GAW16) was held on September 17–20, 2008 in St. Louis, Missouri. The focus of GAW16 was on methods and challenges in analysis of single‐nucleotide polymorphism data from genome‐wide scans. GAW16 attracted 221 participants from 12 countries. The 168 contributions were organized into 17 discussion groups of 6–17 papers each. Three data sets were available for analysis. Two of these were data from ongoing studies, generously provided by the investigators. The North American Rheumatoid Arthritis Consortium provided case‐control data on rheumatoid arthritis, and the Framingham Heart Study (FHS) made available information on cardiovascular risk factors for participants in three generations of pedigree data. The third data set included simulated phenotypes for participants in the FHS, using actual pedigree structures and genotypes. This volume includes a paper for each of the 17 discussion groups, summarizing their main findings. Genet. Epidemiol. 33 (Suppl. 1):S1–S7, 2009. © 2009 Wiley‐Liss, Inc.
Genome‐wide association studies for discrete traits
Authors: Thomas Duncan C.
Published: November 2009

Genome‐wide association studies of discrete traits generally use simple methods of analysis based on χ2 tests for contingency tables or logistic regression, at least for an initial scan of the entire genome. Nevertheless, more power might be obtained by using various methods that analyze multiple markers in combination. Methods based on sliding windows, wavelets, Bayesian shrinkage, or penalized likelihood methods, among others, were explored by various participants of Genetic Analysis Workshop 16 Group 1 to combine information across multiple markers within a region, while others used Bayesian variable selection methods for genome‐wide multivariate analyses of all markers simultaneously. Imputation can be used to fill in missing markers on individual subjects within a study or in a meta‐analysis of studies using different panels. Although multiple imputation theoretically should give more robust tests of association, one participant contribution found little difference between results of single and multiple imputation. Careful control of population stratification is essential, and two contributions found that previously reported associations with two genes disappeared after more precise control. Other issues considered by this group included subgroup analysis, gene‐gene interactions, and the use of biomarkers. Genet. Epidemiol. 33 (Suppl. 1):S8–S12, 2009. © 2009 Wiley‐Liss, Inc.
Genome‐wide association analyses of quantitative traits: the GAW16 experience
Authors: Ghosh Saurabh
Published: November 2009

The group that formed on the theme of genome‐wide association analyses of quantitative traits (Group 2) in the Genetic Analysis Workshop 16 comprised eight sets of investigators. Three data sets were available: one on autoantibodies related to rheumatoid arthritis provided by the North American Rheumatoid Arthritis Consortium; the second on anthropometric, lipid, and biochemical measures provided by the Framingham Heart Study (FHS); and the third a simulated data set modeled after FHS. The different investigators in the group addressed a large set of statistical challenges and applied a wide spectrum of association methods in analyzing quantitative traits at the genome‐wide level. While some previously reported genes were validated, some novel chromosomal regions provided significant evidence of association in multiple contributions in the group. In this report, we discuss the different strategies explored by the different investigators with the common goal of improving the power to detect association.Genet. Epidemiol. 33 (Suppl. 1):S13–S18, 2009. © 2009 Wiley‐Liss, Inc.
Haplotype‐based analysis: a summary of GAW16 Group 4 analysis
Authors: Hauser Elizabeth , Cremer Nadine , Hein Rebecca , Deshmukh Harshal
Published: November 2009

In this summary article, we describe the contributions included in the haplotype‐based analysis group (Group 4) at the Genetic Analysis Workshop 16, which was held in September 17–20, 2008. Our group applied a large number of haplotype‐based methods in the context of genome‐wide association studies. Two general approaches were applied: a two‐stage approach that selected significant single‐nucleotide polymorphisms (SNPs) in the first stage and then created haplotypes in the second stage and genome‐wide analysis of smaller sets of SNPs selected by sliding windows or estimating haplotype blocks. Genome‐wide haplotype analyses performed in these ways were feasible. The presence of the very strong chromosome 6 association in the North American Rheumatoid Arthritis Consortium data was detected by every method, and additional analyses attempted to control for this strong result to allow detection of additional haplotype associations. Genet. Epidemiol. 33 (Suppl. 1):S24–S28, 2009. © 2009 Wiley‐Liss, Inc.
Improving the Signal‐to‐Noise ratio in genome‐wide association studies
Authors: Martin Lisa J. , Gao Guimin , Kang Guolian , Fang Yixin , Woo Jessica G.
Published: November 2009

Genome‐wide association studies employ hundreds of thousands of statistical tests to determine which regions of the genome may likely harbor disease‐causing alleles. Such large‐scale testing simultaneously requires stringent control over type I error and maintenance of sufficient power to detect true associations. These contradictory goals have led some researchers beyond Bonferroni correction of P‐values to an exploration of methods to improve the detection of a few true effects in the presence of many unassociated loci. This article reviews how Genetic Analysis Workshop 16 Group 5 investigators proposed to adjust for multiple tests while simultaneously using information about the structure of the genome to improve the detection of true positives. Genet. Epidemiol. 33 (Suppl. 1):S29–S32, 2009. © 2009 Wiley‐Liss, Inc.
Analysis of multiple phenotypes
Authors: Kent Jack W.
Published: November 2009

The complex etiology of common diseases like cardiovascular disease, diabetes, hypertension, and rheumatoid arthritis has led investigators to focus on the genetics of correlated phenotypes and risk factors. Joint analysis of multiple disease‐related phenotypes may reveal genes of pleiotropic effect and increase analytical power, but at the cost of increased analytical and computational complexity. All three data sets provided for analysis at the Genetic Analysis Workshop 16 offered multiple quantitative measures of phenotypes related to underlying disease processes as well as discrete measures of affection status. Participants in Group 6 addressed the challenges and possibilities of association analysis of these data sets on multiple levels, including phenotype definition and data reduction, multivariate approaches to gene discovery, analysis of causality and data structure, and development of predictive models. These approaches included combinations of continuous and discrete phenotypes, use of repeated measures in longitudinal data, and models that included multiple phenotypic measures and multiple single‐nucleotide polymorphism variants. Most research teams regarded the use of multiple related phenotypes as a tool for increasing analytical power, as well as for clarifying the underlying biology of complex diseases. Genet. Epidemiol. 33 (Suppl. 1):S33–S39, 2009. © 2009 Wiley‐Liss, Inc.
The challenge of detecting epistasis (G×G Interactions): Genetic Analysis Workshop 16
Authors: An Ping , Mukherjee Odity , Chanda Pritam , Yao Li , Engelman Corinne D. , Huang Chien‐Hsun , Zheng Tian , Kovac Ilija P. , Dubé Marie‐Pierre , Liang Xueying , Li Jia , de Andrade Mariza , Culverhouse Robert , Malzahn Doerthe , Manning Alisa K. , Clarke Geraldine M. , Jung Jeesun , Province Michael A.
Published: November 2009

Interest is increasing in epistasis as a possible source of the unexplained variance missed by genome‐wide association studies. The Genetic Analysis Workshop 16 Group 9 participants evaluated a wide variety of classical and novel analytical methods for detecting epistasis, in both the statistical and machine learning paradigms, applied to both real and simulated data. Because the magnitude of epistasis is clearly relative to scale of penetrance, and therefore to some extent, to the choice of model framework, it is not surprising that strong interactions under one model might be minimized or even disappear entirely under a different modeling framework. Genet. Epidemiol. 33 (Suppl. 1):S58–S67, 2009. © 2009 Wiley‐Liss, Inc.
Detecting gene‐environment interactions in genome‐wide association data
Authors: Engelman Corinne D. , Baurley James W. , Chiu Yen‐Feng , Joubert Bonnie R. , Lewinger Juan P. , Maenner Matthew J. , Murcray Cassandra E. , Shi Gang , Gauderman W. James
Published: November 2009

Despite the importance of gene‐environment (G×E) interactions in the etiology of common diseases, little work has been done to develop methods for detecting these types of interactions in genome‐wide association study data. This was the focus of Genetic Analysis Workshop 16 Group 10 contributions, which introduced a variety of new methods for the detection of G×E interactions in both case‐control and family‐based data using both cross‐sectional and longitudinal study designs. Many of these contributions detected significant G×E interactions. Although these interactions have not yet been confirmed, the results suggest the importance of testing for interactions. Issues of sample size, quantifying the environmental exposure, longitudinal data analysis, family‐based analysis, selection of the most powerful analysis method, population stratification, and computational expense with respect to testing G×E interactions are discussed. Genet. Epidemiol. 33 (Suppl. 1):S68–S73, 2009. © 2009 Wiley‐Liss, Inc.
Combining information from linkage and association methods
Authors: Marchani Elizabeth E. , Callegaro Andrea , Daw E. Warwick , Wijsman Ellen M.
Published: November 2009

Group 12 evaluated approaches to incorporate outside information or otherwise optimize traditional linkage and association analyses. The abundance of available data allowed exploration of identity‐by‐descent (IBD) estimation, score statistics, formal combination of linkage and association testing, significance estimation, and replication. We observed that IBD estimation can be optimized with a subset of marker data while estimation of inheritance vectors can provide both IBD estimates and a measure of their uncertainty. Score statistics incorporating covariates or combining association and linkage information performed at least as well as standard approaches while requiring less computation time. The formal combination of linkage and association methods may be fruitful, although the nature of the simulated data limited our conclusions. Estimation of significance may be improved through simulation, correction for cryptic relatedness, and the inclusion of prior information. Replication using real data provided consistent results, though the same was not true of simulated data replicates. Overall, we found that increasing the amount of available data limits analyses due to computational constraints and motivates the need to improve methods for the identification of complex‐trait genes. Genet. Epidemiol. 33 (Suppl. 1):S81–S87, 2009. © 2009 Wiley‐Liss, Inc.
Population stratification and patterns of linkage disequilibrium
Authors: Hinrichs Anthony L. , Larkin Emma K. , Suarez Brian K.
Published: November 2009

Although the importance of selecting cases and controls from the same population has been recognized for decades, the recent advent of genome‐wide association studies has heightened awareness of this issue. Because these studies typically deal with large samples, small differences in allele frequencies between cases and controls can easily reach statistical significance. When, unbeknownst to a researcher, cases and controls have different substructures, the number of false‐positive findings is inflated. There have been three recent developments of purely statistical approaches to assessing the ancestral comparability of case and control samples: genomic control, structured association, and multivariate reduction analyses. The widespread use of high‐throughput technology has allowed the quick and accurate genotyping of the large number of markers required by these methods. Group 13 dealt with four population stratification issues: single‐nucleotide polymorphism marker selection, association testing, nonstandard methods, and linkage disequilibrium calculations in stratified or mixed ethnicity samples. We demonstrated that there are continuous axes of ethnic variation in both data sets of Genetic Analysis Workshop 16. Furthermore, ignoring this structure created P‐value inflation for a variety of phenotypes. Principal‐components analysis (or multidimensional scaling) can control inflation as covariates in a logistic regression. One can weigh for local ancestry estimation and allow the use of related individuals. Problems arise in the presence of extremely high association or unusually strong linkage disequilibrium (e.g., in chromosomal inversions). Our group also reported a method for performing an association test controlling for substructure, when genome‐wide markers are not available, to explicitly compute stratification Genet. Epidemiol. 33 (Suppl. 1):S88–S92, 2009. © 2009 Wiley‐Liss, Inc.
Cooperative induction of CXCL10 involves NADPH oxidase: Implications for HIV dementia
Authors: Williams Rachel , Yao Honghong , Peng Fuwang , Yang Yanjing , Bethel‐Brown Crystal , Buch Shilpa
Published: November 2009

With the increasing prevalence of HIV‐associated neurocognititve disorders (HAND), understanding the mechanisms by which HIV‐1 induces neuro‐inflammation and subsequent neuronal damage is important. The hallmark features of HIV‐encephalitis, the pathological correlate of HIV‐associated Dementia (HAD), are gliosis, oxidative stress, chemokine dysregulation, and neuronal damage/death. Since neurons are not infected by HIV‐1, the current thinking is that these cells are damaged indirectly by pro‐inflammatory chemokines released by activated glial cells. CXCL10 is a neurotoxic chemokine that is upregulated in astroglia activated by HIV‐1 Tat, IFN‐γ, and TNF‐α. In this study we have demonstrated that HIV‐1 Tat increases CXCL10 expression in IFN‐γ and TNF‐α stimulated human astrocytes via NADPH oxidase. We have shown that the treatment of astrocytes with a mixture of Tat and cytokines leads to a respiratory burst that is abrogated by apocynin, an NADPH oxidase inhibitor. Pretreatment of Tat, IFN‐γ, and TNF‐α stimulated astrocytes with apocynin also resulted in concomitant inhibition of CXCL10 expression. Additionally, apocynin was also able to reduce Tat and cytokine‐mediated activation of the corresponding signaling molecules Erk1/2, Jnk, and Akt with a decrease in activation and nuclear translocation of NF‐κB, important regulators of CXCL10 induction. Understanding the mechanisms involved in reducing both oxidative stress and the release of pro‐inflammatory agents could lead to the development of therapeutics aimed at decreasing neuro‐inflammation in patients suffering from HAD. © 2009 Wiley‐Liss, Inc.
The short‐term impacts of a schooling conditional cash transfer program on the sexual behavior of young women
Authors: Baird Sarah , Chirwa Ephraim , McIntosh Craig , Özler Berk
Published: November 2009

Recent evidence suggests that conditional cash transfer (CCT) programs for schooling are effective in raising school enrolment and attendance. However, there is also reason to believe that such programs can affect other outcomes, such as the sexual behavior of their young beneficiaries. Zomba Cash Transfer Program is a randomized ongoing CCT intervention targeting young women in Malawi that provides incentives (in the form of school fees and cash transfers) to current schoolgirls and recent dropouts to stay in or return to school. An average offer of US$10/month conditional on satisfactory school attendance – plus direct payment of secondary school fees – led to significant declines in early marriage, teenage pregnancy, and self‐reported sexual activity among program beneficiaries after just one year of program implementation. For program beneficiaries who were out of school at baseline, the probability of getting married and becoming pregnant declined by more than 40 and 30%, respectively. In addition, the incidence of the onset of sexual activity was 38% lower among all program beneficiaries than the control group. Overall, these results suggest that CCT programs not only serve as useful tools for improving school attendance but may also reduce sexual activity, teen pregnancy, and early marriage. Copyright © 2009 John Wiley & Sons, Ltd.
Metabolic characteristics and importance of the universal methionine salvage pathway recycling methionine from 5′‐methylthioadenosine
Authors: Albers Eva
Published: November 2009

The methionine salvage pathway, also called the 5′‐methylthioadenosine (MTA) cycle, recycles the sulfur of MTA, which is a by‐product in the biosyntheses of polyamine and the plant hormone ethylene. MTA is first converted to 5′‐methylthioribose‐1‐phosphate either by MTA phosphorylase or the combined action of MTA nucleosidase and 5′‐methylthioribose kinase. Subsequently, five additional enzymatic steps, catalyzed by four or five proteins, will form 4‐methylthio‐2‐oxobutyrate, the deaminated form of methionine. The final transamination is achieved by transaminases active in the amino acid biosynthesis. This pathway is present with some variations in all types of organisms and seems to be designed for a quick removal of MTA achieved by high affinities of the first enzymes. During evolution some enzymes have attained additional functions, like a proposed role in nuclear mRNA processing by the aci‐reductone dioxygenase. For others the function seems to be lost due to conditions in specific ecological niches, such as, presence of sulfur and/or absence of oxygen resulting in that, for example, Escherichia coli is lacking a functional pathway. The pathway is regulated as response to sulfur availability and take part in the regulation of polyamine synthesis. Some of the enzymes in the pathway show separate specificities in different organisms and some others are unique for groups of bacteria and parasites. Thus, promising targets for antimicrobial agents have been identified. Other medical topics to which this pathway has connections are cancer, apoptosis, and inflammatory response. © 2009 IUBMB IUBMB Life, 61: 1132–1142, 2009
Oxidative damage induced in A549 cells by physically and chemically characterized air particulate matter (PM2.5) collected in Abidjan, Côte d'Ivoire
Authors: Kouassi Kouakou S. , Billet Sylvain , Garçon Guillaume , Verdin Anthony , Diouf Amadou , Cazier Fabrice , Djaman Joseph , Courcot Dominique , Shirali Pirouz
Published: November 2009

Exposure to high levels of air pollution particulate matter (PM) is strongly associated with increased pulmonary morbidity and mortality. However, the underlying mechanisms of action whereby PM cause adverse health effects are still unclear. In developing countries, like in the sub‐Saharian region of Africa, people are often exposed to high PM levels. Hence, three PM2.5 samples were collected in the District of Abidjan (Côte d'Ivoire), under rural, urban or industrial influences. Their most toxicologically relevant physical and chemical characteristics were determined – thereby showing that most of them were equal or smaller than 2.5 µm – and the influence of both natural (Ca, Na, Mg, Ti, etc.) and anthropic (Al, Fe, Mn, Cr, Pb, Zn, Cu, Ni, benzene and its derivatives, paraffins, etc.) emission sources. The toxicity induced by the three PM samples was studied through 5‐bromodeoxyuridine incorporation to DNA, mitochondrial dehydrogenase activity and extracellular lactate dehydrogenase activity. Hence, effect concentrations at 10 and 50% (EC10 and EC50, respectively) were as follows: (i) rural PM – EC10 = 5.91 µg cm−2 and EC50 = 29.55 µg cm−2; (ii) urban PM – EC10 = 5.45 µg cm−2 and EC50 = 27.23 µg cm−2; and (iii) industrial PM – EC10 = 6.86 µg cm−2 and EC50 = 34.29 µg cm−2. Moreover, PM‐induced oxidative damage in A549 cells was observed through the induction of lipid peroxidation, the alteration of superoxide dismutase activity, and the disruption of glutathione status. Both the transition metals and the organic chemicals within the three collected PM samples under study might be involved in the oxidative damage and, therefore, the toxicity they induced in A549 cells. Copyright © 2009 John Wiley & Sons, Ltd.
An examination of applicant characteristics of successfully matched interns: Is the Glass Half Full or Half Empty and Leaking Miserably?
Authors: Callahan Jennifer L. , Collins Frank L. , Klonoff Elizabeth A.
Published: November 2009

Although the “balance” between the number of potential interns and the number of internship slots needs be addressed, it is imperative that more attention be devoted to examining applicant and program characteristics that result in a successful match. To that end, the current study included pre‐ and post‐match data provided by 330 applicants of the 2009 Association of Psychology Postdoctoral and Internship Centers Match system. In this sample, we found very little evidence that applicant characteristics are related to match outcome. Suggestions to applicants and directors of training are provided and understudied variables and needed analyses are identified. Policy considerations are discussed in terms of not only resolving the supply and demand imbalance but also improving the application process and clearinghouse system. © 2009 Wiley Periodicals, Inc. J Clin Psychol 66: 1–16, 2010.
Cell growth and Trametes versicolor laccase production in transformed Pichia pastoris cultured by solid‐state or submerged fermentations
Authors: López Marcos , Loera Octavio , Guerrero‐Olazarán Martha , Viader‐Salvadó José M. , Gallegos‐López Juan A. , Fernández Francisco J. , Favela‐Torres Ernesto , Viniegra‐González Gustavo
Published: November 2009

BACKGROUND: Growth kinetics of Pichia pastoris and heterologous expression of Trametes versicolor laccase were compared. This is the first study of its kind between solid‐state yeast cultures done on polyurethane foam (PUF) and submerged liquid fermentations (SmF).

RESULTS: The maximum values of biomass were similar for SSF (solid‐state fermentation) and SmF experiments when the BOD (biochemical oxygen demand) was lower than 100 g L−1. For higher BOD levels, the maximum values of biomass were 55 g L−1 (SSF) and 35 g L−1 (SmF). Micrographs of PUF preparations showed yeast growing within liquid lamellae, thinner than 100 µm, forming large horizontal aggregates. Yeast aggregates were much smaller in SmF than in SSF experiments; however, laccase expression was lower in PUF than in SmF, unless the methanol concentration was increased to 63 g L−1, which was inhibitory only to the SmF system.

CONCLUSION: The results show that oxygen mass transfer is more efficient in SSF, which is related to the higher area/volume ratio compared with SmF. Induction differences may also be due to hindered diffusion of methanol within large yeast aggregates. Copyright © 2009 Society of Chemical Industry
Electro‐mediated gene transfer and expression are controlled by the life‐time of DNA/membrane complex formation
Authors: Faurie Cécile , Rebersek Matej , Golzio Muriel , Kanduser Masa , Escoffre Jean‐Michel , Pavlin Mojca , Teissie Justin , Miklavcic Damijan , Rols Marie‐Pierre
Published: November 2009

Background

Electroporation is a physical method used to transfer molecules into cells and tissues. Clinical applications have been developed for antitumor drug delivery. Clinical trials of gene electrotransfer are under investigation. However, knowledge about how DNA enters cells is not complete. By contrast to small molecules that have direct access to the cytoplasm, DNA forms a long lived complex with the plasma membrane and is transferred into the cytoplasm with a considerable delay.

Methods

To increase our understanding of the key step of DNA/membrane complex formation, we investigated the dependence of DNA/membrane interaction and gene expression on electric pulse polarity and repetition frequency.

Results

We observed that both are affected by reversing the polarity and by increasing the repetition frequency of pulses. The results obtained in the present study reveal the existence of two classes of DNA/membrane interaction: (i) a metastable DNA/membrane complex from which DNA can leave and return to external medium and (ii) a stable DNA/membrane complex, where DNA cannot be removed, even by applying electric pulses of reversed polarity. Only DNA belonging to the second class leads to effective gene expression.

Conclusions

The life‐time of DNA/membrane complex formation is of the order of 1 s and has to be taken into account to improve protocols of electro‐mediated gene delivery. Copyright © 2009 John Wiley & Sons, Ltd.
The role of olfaction throughout juvenile development: Functional adaptations in elasmobranchs
Authors: Schluessel Vera , Bennett Michael B. , Bleckmann Horst , Collin Shaun P.
Published: November 2009

Seven elasmobranch species, a group known for their highly‐developed sense of smell, were examined for developmental changes in the number of olfactory lamellae, the size of the surface area of the sensory olfactory epithelium and the mass of both the olfactory rosettes (primary input to the CNS), and the olfactory bulbs. Within each species, juveniles possessed miniature versions of the adult olfactory organs, visually not distinguishable from these and without any obvious structural differences (e.g., with respect to the number of lamellae and the extent of secondary folding) between differently sized individuals. The size of the olfactory organs was positively correlated with body length and body mass, although few species showed proportional size scaling. In Aetobatus narinari and Aptychotrema rostrata, olfactory structures increased in proportion to body size. With respect to the growth of the olfactory bulb, all species showed allometric but not proportional growth. Olfaction may be of particular importance to juveniles in general, which are often subjected to heavy predation rates and fierce inter/intraspecific competition. Accordingly, it would be advantageous to possess a fully functional olfactory system early on in development. Slow growth rates of olfactory structures could then be attributed to a greater reliance on other sensory systems with increasing age or simply be regarded as maintaining an already optimized olfactory system. J. Morphol., 2010. © 2009 Wiley‐Liss, Inc.
Middle ear structure and bone conduction in Spalax, Eospalax, and Tachyoryctes mole‐rats (Rodentia: Spalacidae)
Authors: Mason Matthew J. , Lai Flora W.S. , Li Jin‐Gang , Nevo Eviatar
Published: November 2009

There is evidence that spalacine, tachyoryctine, and myospalacine mole‐rats all communicate with conspecifics through a form of seismic signaling, but the route for the detection of these signals is disputed. It has been proposed that two unusual anatomical adaptations in Spalax allow jaw vibrations to pass to the inner ear via the incus and stapes: a pseudoglenoid (=postglenoid) fossa which accomodates the condylar process of the mandible, and a bony cup, supported by a periotic lamina, through which the incus articulates with the skull. In this study, a combination of dissection and computed tomography was used to examine the ear region in more detail in both Spalax and its subterranean relatives Tachyoryctes and Eospalax, about which much less is known. Tachyoryctes was found to lack a pseudoglenoid fossa, while Eospalax lacks a periotic lamina and bony cup. This shows that these structures need not simultaneously be present for the detection of ground vibrations in mole‐rats. Based on the observed anatomy, three hypothetical modes of bone conduction are argued to represent more likely mechanisms through which mole‐rats can detect ground vibrations: ossicular inertial bone conduction, a pathway involving sound radiation into the external auditory meatus, and a newly‐described fluid pathway between pseudoglenoid fossa and cranial cavity. The caudolateral extension of the tympanic cavity and the presence of a bony cup might represent synapomorphies uniting Spalax and Tachyoryctes, while the loss of the tensor tympani muscle in Spalax and Eospalax may be convergently derived. J. Morphol., 2010. © 2009 Wiley‐Liss, Inc.
Functional morphology of the female reproductive apparatus of Stephanitis pyrioides (Heteroptera, Tingidae): A novel role for the pseudospermathecae
Authors: Marchini Daniela , Bene Giovanna Del , Dallai Romano
Published: November 2009

At mating, female insects generally receive and store sperm in specific organs of their reproductive tract called spermathecae. Some Heteroptera, such as Cimicomorpha, lack a true spermatheca; some have receptacles of novel formation where sperm cells can transit or be stored. In Tingidae, there are two sac‐like diverticula, the “pseudospermathecae,” each at the base of a lateral oviduct, which previously were considered to function as spermathecae. However, this role has never been documented, either by ultrastructural studies or by observations of sperm transit in the female reproductive tract. In this article, we investigate the morphology and the ultrastructure of the female reproductive apparatus in the economically important tingid species Stephanitis pyrioides, focusing our attention on the functional role of the pseudospermathecae in an evolutionary perspective. Each ovary consists of seven telotrophic meroistic ovarioles, the long pedicels of which enlarge into a bulb‐like structure near the terminal oocyte. The ovarioles flow into two long lateral oviducts, which join to form a very short common oviduct. Basally, each lateral oviduct is connected through a short duct to one of two pseudospermathecae. The ultrastructure of the ectodermal epithelium of the pseudospermathecae is dramatically different in sexually immature or mated females. In virgin females, cells delimit a very irregular lumen, filled with a moderately electron‐dense granular material. The large nucleus adapts to their irregular shape, which can have long projections in some regions and be flattened in others. After mating, epithelial cells generally elongate and display an apical layer of microvilli extending beneath the cuticle, often containing mitochondria. In the lumen of the pseudospermathecae there is a dense brownish secretion. No sperm cells were ever found inside this organ. After mating, sperm move upward along the lateral oviducts and the ovarioles, accumulating in the bulb‐like structure of the pedicels, and proceeding into the distal region between the follicle cells surrounding the oocyte and the ovariole wall. The egg, most likely fertilized in the bulb‐like region of the ovariole, moves through the lateral oviduct, entirely enters the pseudospermatheca and is smeared with its secretion just before oviposition. We exclude a function of sperm storage for the pseudospermathecae, and instead suggest a novel role for these organs as reproductive accessory glands. J. Morphol., 2010. © 2009 Wiley‐Liss, Inc.
A new human catalytic antibody Se‐scFv‐2D8 and its selenium‐containing single domains with high GPX activity
Authors: Xu Junjie , Song Jian , Su Jiaming , Wei Jingyan , Yu Yang , Lv Shaowu , Li Wei , Nie Guangjun
Published: November 2009

Glutathione peroxidase (GPX) is a well‐known antioxidant selenoenzyme, which can catalyze the reduction of a variety of hydroperoxides and consequently protect cells and other biological tissues against oxidative damage. Many attempts have been made to mimic its function, and a human catalytic antibody Se‐scFv‐B3 with GPX activity has been prepared in our previous study. This time, a new clone 2D8 that bound specifically to the glutathione analog GSH‐S‐DNPBu was selected again by using the technology of phage display antibody library, and then scFv‐2D8 was successfully expressed in soluble form and purified using Ni2+‐immobilized metal affinity chromatography. After being converted into selenium‐containing scFv by chemically modification, it showed higher GPX activity than previous abzyme Se‐scFv‐B3. The heavy chain variable fragment of scFv‐2D8 was also prepared and converted into selenium‐containing protein using the same method. This selenium‐containing single‐domain antibody showed some GPX activity and, to the best of our knowledge, is the first human single‐domain abzyme with GPX activity, which lays a foundation for preparing GPX abzyme with human origin, lower molecular weight and higher activity. Copyright © 2009 John Wiley & Sons, Ltd.