bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of experience-dependent and -independent factors on gene expression in songbird brain
Authors: Drnevich Jenny , Replogle Kirstin L. , Lovell Peter , Hahn Thomas P. , Johnson Frank , Mast Thomas G. , Nordeen Ernest , Nordeen Kathy , Strand Christy , London Sarah E. , Mukai Motoko , Wingfield John C. , Arnold Arthur P. , Ball Gregory F. , Brenowitz Eliot A. , Wade Juli , Mello Claudio V. , Clayton David F.
Published: October 2012

Songbirds provide rich natural models for studying the relationships between brain anatomy, behavior, environmental signals, and gene expression. Under the Songbird Neurogenomics Initiative, investigators from 11 laboratories collected brain samples from six species of songbird under a range of experimental conditions, and 488 of these samples were analyzed systematically for gene expression by microarray. ANOVA was used to test 32 planned contrasts in the data, revealing the relative impact of different factors. The brain region from which tissue was taken had the greatest influence on gene expression profile, affecting the majority of signals measured by 18,848 cDNA spots on the microarray. Social and environmental manipulations had a highly variable impact, interpreted here as a manifestation of paradoxical “constitutive plasticity” (fewer inducible genes) during periods of enhanced behavioral responsiveness. Several specific genes were identified that may be important in the evolution of linkages between environmental signals and behavior. The data were also analyzed using weighted gene coexpression network analysis, followed by gene ontology analysis. This revealed modules of coexpressed genes that are also enriched for specific functional annotations, such as “ribosome” (expressed more highly in juvenile brain) and “dopamine metabolic process” (expressed more highly in striatal song control nucleus area X). These results underscore the complexity of influences on neural gene expression and provide a resource for studying how these influences are integrated during natural experience.
Putting the concept of biological embedding in historical perspective
Authors: Hertzman Clyde
Published: October 2012

This paper describes evidence that led to the concept of biological embedding and research approaches designed to elucidates its mechanisms. Biological embedding occurs when experience gets under the skin and alters human biological and developmental processes; when systematic differences in experience in different social environments in society lead to systematically different biological and developmental states; when these differences are stable and long term; and, finally, when they have the capacity to influence health, well-being, learning, or behavior over the life course. Biological embedding emerged from insights in population health on the unique characteristics of socioeconomic gradients: Ubiquity in poor and postscarcity societies alike; gradient seen regardless of whether socioeconomic status is measured by income, education, or occupation; cutting widely across health, well-being, learning, and behavior outcomes; replicating itself on new conditions entering society; and, often, showing that flatter gradients mean better overall societal outcomes. Most important, the gradient begins the life course as a gradient in developmental health, suggesting that the emergence of a multifaceted resilience/vulnerability early in life is the best place to look for evidence of biological embedding. To understand its character, the metaphor of the “archeology of biological embedding” has been used, wherein the surficial stratum of the “dig” is experience and behavior, the shallow stratum is organ system and cellular function, and the deep stratum is gene function. We are now ready to address the fundamental question of biological embedding: How do early childhood environments work together with genetic variation and epigenetic regulation to generate gradients in health and human development across the life course?
Social information changes the brain
Authors: Fernald Russell D. , Maruska Karen P.
Published: October 2012

Social animals live in complex physical and social environments requiring them to attend and rapidly respond to social and environmental information by changing their behavior. A key social influence is rank or status, a ubiquitous element in animal societies. Rank typically regulates access to reproduction and other resources, among other consequences for individuals. Because reproduction is arguably the most important event in any animals’ life, understanding how reproduction is regulated by social status and related physiological factors can instruct our understanding of evolutionary change. This article reviews evidence from a model social system in which reproduction is tightly controlled by social status. Surprisingly, changes in social status have rapid and profound effects over very short time scales and radically alter overt behavior, as well as physiological, cellular, and molecular factors that regulate reproductive capacity.
Locomotor head movements and semicircular canal morphology in primates
Authors: Malinzak Michael D. , Kay Richard F. , Hullar Timothy E.
Published: October 2012

Animal locomotion causes head rotations, which are detected by the semicircular canals of the inner ear. Morphologic features of the canals influence rotational sensitivity, and so it is hypothesized that locomotion and canal morphology are functionally related. Most prior research has compared subjective assessments of animal “agility” with a single determinant of rotational sensitivity: the mean canal radius of curvature (
R
). In fact, the paired variables of
R
and body mass are correlated with agility and have been used to infer locomotion in extinct species. To refine models of canal functional morphology and to improve locomotor inferences for extinct species, we compare 3D vector measurements of head rotation during locomotion with 3D vector measures of canal sensitivity. Contrary to the predictions of conventional models that are based upon
R
, we find that axes of rapid head rotation are not aligned with axes of either high or low sensitivity. Instead, animals with fast head rotations have similar sensitivities in all directions, which they achieve by orienting the three canals of each ear orthogonally (i.e., along planes at 90° angles to one another). The extent to which the canal configuration approaches orthogonality is correlated with rotational head speed independent of body mass and phylogeny, whereas
R
is not.
Global identification of MLL2-targeted loci reveals MLL2’s role in diverse signaling pathways
Authors: Guo Changcun , Chang Chun-Chi , Wortham Matthew , Chen Lee H. , Kernagis Dawn N. , Qin Xiaoxia , Cho Young-Wook , Chi Jen-Tsan , Grant Gerald A. , McLendon Roger E. , Yan Hai , Ge Kai , Papadopoulos Nickolas , Bigner Darell D. , He Yiping
Published: October 2012

Myeloid/lymphoid
or
mixed-lineage leukemia
(
MLL
)-family genes encode histone lysine methyltransferases that play important roles in epigenetic regulation of gene transcription.
MLL
genes are frequently mutated in human cancers. Unlike MLL1, MLL2 (also known as ALR/MLL4) and its homolog MLL3 are not well-understood. Specifically, little is known regarding the extent of global MLL2 involvement in the regulation of gene expression and the mechanism underlying its alterations in driving tumorigenesis. Here we profile the global loci targeted by MLL2. A combinatorial analysis of the MLL2 binding profile and gene expression in
MLL2
wild-type versus
MLL2
-null isogenic cell lines identified direct transcriptional target genes and revealed the connection of MLL2 to multiple cellular signaling pathways, including the p53 pathway, cAMP-mediated signaling, and cholestasis signaling. In particular, we demonstrate that MLL2 participates in retinoic acid receptor signaling by promoting retinoic acid-responsive gene transcription. Our results present a genome-wide integrative analysis of the MLL2 target loci and suggest potential mechanisms underlying tumorigenesis driven by MLL2 alterations.
Phase of atmospheric secondary organic material affects its reactivity
Authors: Kuwata Mikinori , Martin Scot T.
Published: October 2012

The interconversion of atmospheric organic particles among solid, semisolid, and liquid phases is of keen current scientific interest, especially for particles of secondary organic material (SOM). Herein, the influence of phase on ammonia uptake and subsequent particle-phase reactions was investigated for aerosol particles of adipic acid and α-pinene ozonolysis SOM. The nitrogen content of the particles was monitored by online mass spectrometry for increasing ammonia exposure. Solid and semisolid adipic acid particles were inert to the ammonia uptake for low RH (< 5%). For the solid particles, ammonia exposure at high relative humidity (RH; > 94%) induced a first-order deliquescence phase transition into aqueous particles. Solid particles exposed to supersaturated (RH > 100%) conditions and cycled back to high RH (> 94%), thereby becoming acidic metastable particles, underwent a gradual second-order transition upon ammonia exposure to form aqueous, partially neutralized particles. For α-pinene SOM, ammonia exposure at low RH increased the particle-phase ammonium content by a small amount. Mass spectrometric observations suggest a mechanism of neutralization and co-condensation of acidic gas-phase species, consistent with a highly viscous semisolid upon which adsorption occurs. At high RH the ammonium content increased greatly, indicative of rapid diffusion and absorption in a liquid environment. The mass spectra indicated the production of organonitrogen compounds, possibly by particle-phase reactive chemistry. The present results demonstrate that phase can be a key regulator of the reactivity of atmospheric SOM particles.
Trisomy 21-associated defects in human primitive hematopoiesis revealed through induced pluripotent stem cells
Authors: Chou Stella T. , Byrska-Bishop Marta , Tober Joanna M. , Yao Yu , VanDorn Daniel , Opalinska Joanna B. , Mills Jason A. , Choi John Kim , Speck Nancy A. , Gadue Paul , Hardison Ross C. , Nemiroff Richard L. , French Deborah L. , Weiss Mitchell J.
Published: October 2012

Patients with Down syndrome (trisomy 21, T21) have hematologic abnormalities throughout life. Newborns frequently exhibit abnormal blood counts and a clonal preleukemia. Human T21 fetal livers contain expanded erythro-megakaryocytic precursors with enhanced proliferative capacity. The impact of T21 on the earliest stages of embryonic hematopoiesis is unknown and nearly impossible to examine in human subjects. We modeled T21 yolk sac hematopoiesis using human induced pluripotent stem cells (iPSCs). Blood progenitor populations generated from T21 iPSCs were present at normal frequency and proliferated normally. However, their developmental potential was altered with enhanced erythropoiesis and reduced myelopoiesis, but normal megakaryocyte production. These abnormalities overlap with those of T21 fetal livers, but also reflect important differences. Our studies show that T21 confers distinct developmental stage- and species-specific hematopoietic defects. More generally, we illustrate how iPSCs can provide insight into early stages of normal and pathological human development.
Localization of Usher 1 proteins to the photoreceptor calyceal processes, which are absent from mice
Authors: Sahly Iman , Dufour Eric , Schietroma Cataldo , Michel Vincent , Bahloul Amel , Perfettini Isabelle , Pepermans Elise , Estivalet Amrit , Carette Diane , Aghaie Asadollah , Ebermann Inga , Lelli Andrea , Iribarne Maria , Hardelin Jean-Pierre , Weil Dominique , Sahel José-Alain , El-Amraoui Aziz , Petit Christine
Published: October 2012

The mechanisms underlying retinal dystrophy in Usher syndrome type I (USH1) remain unknown because mutant mice lacking any of the USH1 proteins—myosin VIIa, harmonin, cadherin-23, protocadherin-15, sans—do not display retinal degeneration. We found here that, in macaque photoreceptor cells, all USH1 proteins colocalized at membrane interfaces (i) between the inner and outer segments in rods and (ii) between the microvillus-like calyceal processes and the outer segment basolateral region in rods and cones. This pattern, conserved in humans and frogs, was mediated by the formation of an USH1 protein network, which was associated with the calyceal processes from the early embryonic stages of outer segment growth onwards. By contrast, mouse photoreceptors lacked calyceal processes and had no USH1 proteins at the inner–outer segment interface. We suggest that USH1 proteins form an adhesion belt around the basolateral region of the photoreceptor outer segment in humans, and that defects in this structure cause the retinal degeneration in USH1 patients.
Cdk1 and Plk1 mediate a CLASP2 phospho-switch that stabilizes kinetochore–microtubule attachments
Authors: Maia Ana R.R. , Garcia Zaira , Kabeche Lilian , Barisic Marin , Maffini Stefano , Macedo-Ribeiro Sandra , Cheeseman Iain M. , Compton Duane A. , Kaverina Irina , Maiato Helder
Published: October 2012

Accurate chromosome segregation during mitosis relies on a dynamic kinetochore (KT)–microtubule (MT) interface that switches from a labile to a stable condition in response to correct MT attachments. This transition is essential to satisfy the spindle-assembly checkpoint (SAC) and couple MT-generated force with chromosome movements, but the underlying regulatory mechanism remains unclear. In this study, we show that during mitosis the MT- and KT-associated protein CLASP2 is progressively and distinctively phosphorylated by Cdk1 and Plk1 kinases, concomitant with the establishment of KT–MT attachments. CLASP2 S1234 was phosphorylated by Cdk1, which primed CLASP2 for association with Plk1. Plk1 recruitment to KTs was enhanced by CLASP2 phosphorylation on S1234. This was specifically required to stabilize KT–MT attachments important for chromosome alignment and to coordinate KT and non-KT MT dynamics necessary to maintain spindle bipolarity. CLASP2 C-terminal phosphorylation by Plk1 was also required for chromosome alignment and timely satisfaction of the SAC. We propose that Cdk1 and Plk1 mediate a fine CLASP2 “phospho-switch” that temporally regulates KT–MT attachment stability.
Early redox, Src family kinase, and calcium signaling integrate wound responses and tissue regeneration in zebrafish
Authors: Yoo Sa Kan , Freisinger Christina M. , LeBert Danny C. , Huttenlocher Anna
Published: October 2012

Tissue injury can lead to scar formation or tissue regeneration. How regenerative animals sense initial tissue injury and transform wound signals into regenerative growth is an unresolved question. Previously, we found that the Src family kinase (SFK) Lyn functions as a redox sensor in leukocytes that detects H2O2 at wounds in zebrafish larvae. In this paper, using zebrafish larval tail fins as a model, we find that wounding rapidly activated SFK and calcium signaling in epithelia. The immediate SFK and calcium signaling in epithelia was important for late epimorphic regeneration of amputated fins. Wound-induced activation of SFKs in epithelia was dependent on injury-generated H2O2. A SFK member, Fynb, was responsible for fin regeneration. This work provides a new link between early wound responses and late regeneration and suggests that redox, SFK, and calcium signaling are immediate “wound signals” that integrate early wound responses and late epimorphic regeneration.
Neuropilin 1 deficiency on CD4+Foxp3+ regulatory T cells impairs mouse melanoma growth
Authors: Hansen Wiebke , Hutzler Marina , Abel Simone , Alter Christina , Stockmann Christian , Kliche Stefanie , Albert Juliane , Sparwasser Tim , Sakaguchi Shimon , Westendorf Astrid M. , Schadendorf Dirk , Buer Jan , Helfrich Iris
Published: October 2012

Infiltration of Foxp3+ regulatory T (T reg) cells is considered to be a critical step during tumor development and progression. T reg cells supposedly suppress locally an effective anti-tumor immune response within tumor tissues, although the precise mechanism by which T reg cells infiltrate the tumor is still unclear. We provide evidence that Neuropilin 1 (Nrp-1), highly expressed by Foxp3+ T reg cells, regulates the immunological anti-tumor control by guiding T reg cells into the tumor in response to tumor-derived vascular endothelial growth factor (VEGF). We demonstrate for the first time that T cell–specific ablation of Nrp-1 expression results in a significant breakdown in tumor immune escape in various transplantation models and in a spontaneous, endogenously driven melanoma model associated with strongly reduced tumor growth and prolonged tumor-free survival. Strikingly, numbers of tumor-infiltrating Foxp3+ T reg cells were significantly reduced accompanied by enhanced activation of CD8+ T cells within tumors of T cell–specific Nrp-1–deficient mice. This phenotype can be reversed by adoptive transfer of Nrp-1+ T reg cells from wild-type mice. Thus, our data strongly suggest that Nrp-1 acts as a key mediator of Foxp3+ T reg cell infiltration into the tumor site resulting in a dampened anti-tumor immune response and enhanced tumor progression.
Characterization of novel genomic alterations and therapeutic approaches using acute megakaryoblastic leukemia xenograft models
Authors: Thiollier Clarisse , Lopez Cécile K. , Gerby Bastien , Ignacimouttou Cathy , Poglio Sandrine , Duffourd Yannis , Guégan Justine , Rivera-Munoz Paola , Bluteau Olivier , Mabialah Vinciane , Diop M’Boyba , Wen Qiang , Petit Arnaud , Bauchet Anne-Laure , Reinhardt Dirk , Bornhauser Beat , Gautheret Daniel , Lecluse Yann , Landman-Parker Judith , Radford Isabelle , Vainchenker William , Dastugue Nicole , de Botton Stéphane , Dessen Philippe , Bourquin Jean-Pierre , Crispino John D. , Ballerini Paola , Bernard Olivier A. , Pflumio Françoise , Mercher Thomas
Published: October 2012

Acute megakaryoblastic leukemia (AMKL) is a heterogeneous disease generally associated with poor prognosis. Gene expression profiles indicate the existence of distinct molecular subgroups, and several genetic alterations have been characterized in the past years, including the t(1;22)(p13;q13) and the trisomy 21 associated with GATA1 mutations. However, the majority of patients do not present with known mutations, and the limited access to primary patient leukemic cells impedes the efficient development of novel therapeutic strategies. In this study, using a xenotransplantation approach, we have modeled human pediatric AMKL in immunodeficient mice. Analysis of high-throughput RNA sequencing identified recurrent fusion genes defining new molecular subgroups. One subgroup of patients presented with MLL or NUP98 fusion genes leading to up-regulation of the HOX A cluster genes. A novel CBFA2T3-GLIS2 fusion gene resulting from a cryptic inversion of chromosome 16 was identified in another subgroup of 31% of non–Down syndrome AMKL and strongly associated with a gene expression signature of Hedgehog pathway activation. These molecular data provide useful markers for the diagnosis and follow up of patients. Finally, we show that AMKL xenograft models constitute a relevant in vivo preclinical screening platform to validate the efficacy of novel therapies such as Aurora A kinase inhibitors.
Magnetization studies of first-order magnetostructural phase transition in polycrystalline FeRh thin films
Authors: Lu Wei , Huang Ping , Chen Zhe , He Chenchong , Wang Yuxin , Yan Biao
Published: October 2012

The nucleation and growth of the transformed phase in the matrix of the original phase played an important role in the progress of magnetic transition. In spite of extensive investigations in B2 ordered FeRh alloy systems, until now few studies have been conducted for clarifying the nucleation and growth mechanism of the antiferromagnetic–ferromagnetic phase transition in FeRh alloys. In this work, B2 ordered polycrystalline FeRh thin films were fabricated on glass substrates by a sputtering technique and subsequent heat treatment. The as-deposited film shows a nonmagnetic property because of its face centred cubic structure. After annealing, the polycrystalline FeRh thin films show a clear first-order magnetostructural phase transition. The FeRh thin film shows an overall activation energy of about 228.6 kJ mol−1 for the entire first-order magnetostructural phase transition process. Results suggest that the first-order magnetostructural phase transition in ordered FeRh thin films follows the Johnson–Mehl–Avrami model with characteristic exponent n in the range 1–4, indicating that the phase transition process is a multi-step process characterized by different nucleation and growth mechanisms of the new ferromagnetic phase. The results obtained in this study will shed light on the underlying physics of the first-order magnetostructural phase transition of ordered FeRh alloys. The applicability of the concepts used in this study to the FeRh system shows universality and can be applied to other material systems where there is a first-order magnetostructural phase transition such as in manganites.
A novel missense-mutation-related feature extraction scheme for ‘driver’ mutation identification
Authors: Tan Hua , Bao Jiguang , Zhou Xiaobo
Published: October 2012

Motivation: It becomes widely accepted that human cancer is a disease involving dynamic changes in the genome and that the missense mutations constitute the bulk of human genetic variations. A multitude of computational algorithms, especially the machine learning-based ones, has consequently been proposed to distinguish missense changes that contribute to the cancer progression (‘driver’ mutation) from those that do not (‘passenger’ mutation). However, the existing methods have multifaceted shortcomings, in the sense that they either adopt incomplete feature space or depend on protein structural databases which are usually far from integrated.

Results: In this article, we investigated multiple aspects of a missense mutation and identified a novel feature space that well distinguishes cancer-associated driver mutations from passenger ones. An index (DX score) was proposed to evaluate the discriminating capability of each feature, and a subset of these features which ranks top was selected to build the SVM classifier. Cross-validation showed that the classifier trained on our selected features significantly outperforms the existing ones both in precision and robustness. We applied our method to several datasets of missense mutations culled from published database and literature and obtained more reasonable results than previous studies.

Availability: The software is available online at http://www.methodisthealth.com/software and https://sites.google.com/site/drivermutationidentification/.

Contact: xzhou@tmhs.org

Supplementary information: Supplementary data are available at Bioinformatics online.
Gene set analysis for self-contained tests: complex null and specific alternative hypotheses
Authors: Rahmatallah Y. , Emmert-Streib F. , Glazko G.
Published: October 2012

Motivation: The analysis of differentially expressed gene sets became a routine in the analyses of gene expression data. There is a multitude of tests available, ranging from aggregation tests that summarize gene-level statistics for a gene set to true multivariate tests, accounting for intergene correlations. Most of them detect complex departures from the null hypothesis but when the null hypothesis is rejected, the specific alternative leading to the rejection is not easily identifiable.

Results: In this article we compare the power and Type I error rates of minimum-spanning tree (MST)-based non-parametric multivariate tests with several multivariate and aggregation tests, which are frequently used for pathway analyses. In our simulation study, we demonstrate that MST-based tests have power that is for many settings comparable with the power of conventional approaches, but outperform them in specific regions of the parameter space corresponding to biologically relevant configurations. Further, we find for simulated and for gene expression data that MST-based tests discriminate well against shift and scale alternatives. As a general result, we suggest a two-step practical analysis strategy that may increase the interpretability of experimental data: first, apply the most powerful multivariate test to find the subset of pathways for which the null hypothesis is rejected and second, apply MST-based tests to these pathways to select those that support specific alternative hypotheses.

Contact:  gvglazko@uams.edu or yrahmatallah@uams.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Pathway-based visualization of cross-platform microarray datasets
Authors: Wrzodek Clemens , Eichner Johannes , Zell Andreas
Published: October 2012

Motivation: Traditionally, microarrays were almost exclusively used for the genome-wide analysis of differential gene expression. But nowadays, their scope of application has been extended to various genomic features, such as microRNAs (miRNAs), proteins and DNA methylation (DNAm). Most available methods for the visualization of these datasets are focused on individual platforms and are not capable of integratively visualizing multiple microarray datasets from cross-platform studies. Above all, there is a demand for methods that can visualize genomic features that are not directly linked to protein-coding genes, such as regulatory RNAs (e.g. miRNAs) and epigenetic alterations (e.g. DNAm), in a pathway-centred manner.

Results: We present a novel pathway-based visualization method that is especially suitable for the visualization of high-throughput datasets from multiple different microarray platforms that were used for the analysis of diverse genomic features in the same set of biological samples. The proposed methodology includes concepts for linking DNAm and miRNA expression datasets to canonical signalling and metabolic pathways. We further point out strategies for displaying data from multiple proteins and protein modifications corresponding to the same gene. Ultimately, we show how data from four distinct platform types (messenger RNA, miRNA, protein and DNAm arrays) can be integratively visualized in the context of canonical pathways.

Availability: The described method is implemented as part of the InCroMAP application that is freely available at www.cogsys.cs.uni-tuebingen.de/software/InCroMAP.

Contact:  clemens.wrzodek@uni-tuebingen.de or andreas.zell@uni-tuebingen.de
KGBassembler: a karyotype-based genome assembler for Brassicaceae species
Authors: Ma Chuang , Chen Hao , Xin Mingming , Yang Ruolin , Wang Xiangfeng
Published: October 2012

Motivation: The Brassicaceae family includes the most important plant model Arabidopsis thaliana and many cruciferous vegetable crops. A number of close relatives of Arabidopsis and economically important Brassica species are being sequenced with whole-genome shotgun sequencing technologies. However, de novo assembly of full chromosomes is difficult, since many non-model Brassicaceae species are lacking genetic and/or physical maps. As a unique feature for Brassicaceae, the genome of each member is composed of 24 conserved chromosomal blocks, and the arrangement of the 24 blocks can be obtained from karyotype analysis via comparative chromosome painting experiments. Taking this advantage, we developed a bioinformatic tool named KGBassembler to automatically finalize assembly of full chromosomes from contigs and/or scaffolds based on available karyotypes of Brassicaceae species.

Availability: KGBassembler was implemented in C++ with a graphical user interface. It is freely available to academic users at http://www.cmbb.arizona.edu/KGBassembler/.

Contact:  xwang1@cals.arizona.edu
SemMedDB: a PubMed-scale repository of biomedical semantic predications
Authors: Kilicoglu Halil , Shin Dongwook , Fiszman Marcelo , Rosemblat Graciela , Rindflesch Thomas C.
Published: October 2012

Summary: Effective access to the vast biomedical knowledge present in the scientific literature is challenging. Semantic relations are increasingly used in knowledge management applications supporting biomedical research to help address this challenge. We describe SemMedDB, a repository of semantic predications (subject–predicate–object triples) extracted from the entire set of PubMed citations. We propose the repository as a knowledge resource that can assist in hypothesis generation and literature-based discovery in biomedicine as well as in clinical decision-making support.

Availability and implementation: The SemMedDB repository is available as a MySQL database for non-commercial use at http://skr3.nlm.nih.gov/SemMedDB. An UMLS Metathesaurus license is required.

Contact:  kilicogluh@mail.nih.gov
De novo detection of copy number variation by co-assembly
Authors: Nijkamp Jurgen F. , van den Broek Marcel A. , Geertman Jan-Maarten A. , Reinders Marcel J. T. , Daran Jean-Marc G. , de Ridder Dick
Published: October 2012

Motivation: Comparing genomes of individual organisms using next-generation sequencing data is, until now, mostly performed using a reference genome. This is challenging when the reference is distant and introduces bias towards the exact sequence present in the reference. Recent improvements in both sequencing read length and efficiency of assembly algorithms have brought direct comparison of individual genomes by de novo assembly, rather than through a reference genome, within reach.

Results: Here, we develop and test an algorithm, named Magnolya, that uses a Poisson mixture model for copy number estimation of contigs assembled from sequencing data. We combine this with co-assembly to allow de novo detection of copy number variation (CNV) between two individual genomes, without mapping reads to a reference genome. In co-assembly, multiple sequencing samples are combined, generating a single contig graph with different traversal counts for the nodes and edges between the samples. In the resulting ‘coloured’ graph, the contigs have integer copy numbers; this negates the need to segment genomic regions based on depth of coverage, as required for mapping-based detection methods. Magnolya is then used to assign integer copy numbers to contigs, after which CNV probabilities are easily inferred. The copy number estimator and CNV detector perform well on simulated data. Application of the algorithms to hybrid yeast genomes showed allotriploid content from different origin in the wine yeast Y12, and extensive CNV in aneuploid brewing yeast genomes. Integer CNV was also accurately detected in a short-term laboratory-evolved yeast strain.

Availability: Magnolya is implemented in Python and available at: http://bioinformatics.tudelft.nl/

Contact:  d.deridder@tudelft.nl

Supplementary information: Supplementary data are available at Bioinformatics online.
Wages and Human Capital in the U.S. Finance Industry: 1909–2006*
Authors: Philippon Thomas , Reshef Ariell
Published: October 2012

We study the allocation and compensation of human capital in the U.S. finance industry over the past century. Across time, space, and subsectors, we find that financial deregulation is associated with skill intensity, job complexity, and high wages for finance employees. All three measures are high before 1940 and after 1985, but not in the interim period. Workers in finance earn the same education-adjusted wages as other workers until 1990, but by 2006 the premium is 50% on average. Top executive compensation in finance follows the same pattern and timing, where the premium reaches 250%. Similar results hold for other top earners in finance. Changes in earnings risk can explain about one half of the increase in the average premium; changes in the size distribution of firms can explain about one fifth of the premium for executives.
Pattern and process of biotic homogenization in the New Pangaea
Authors: Baiser Benjamin , Olden Julian D. , Record Sydne , Lockwood Julie L. , McKinney Michael L.
Published: October 2012

Human activities have reorganized the earth's biota resulting in spatially disparate locales becoming more or less similar in species composition over time through the processes of biotic homogenization and biotic differentiation, respectively. Despite mounting evidence suggesting that this process may be widespread in both aquatic and terrestrial systems, past studies have predominantly focused on single taxonomic groups at a single spatial scale. Furthermore, change in pairwise similarity is itself dependent on two distinct processes, spatial turnover in species composition and changes in gradients of species richness. Most past research has failed to disentangle the effect of these two mechanisms on homogenization patterns. Here, we use recent statistical advances and collate a global database of homogenization studies (20 studies, 50 datasets) to provide the first global investigation of the homogenization process across major faunal and floral groups and elucidate the relative role of changes in species richness and turnover. We found evidence of homogenization (change in similarity ranging from −0.02 to 0.09) across nearly all taxonomic groups, spatial extent and grain sizes. Partitioning of change in pairwise similarity shows that overall change in community similarity is driven by changes in species richness. Our results show that biotic homogenization is truly a global phenomenon and put into question many of the ecological mechanisms invoked in previous studies to explain patterns of homogenization.
Mouth asymmetry in the textbook example of scale-eating cichlid fish is not a discrete dimorphism after all
Authors: Kusche Henrik , Lee Hyuk Je , Meyer Axel
Published: October 2012

Individuals of the scale-eating cichlid fish,Perissodus microlepis, from Lake Tanganyika tend to have remarkably asymmetric heads that are either left-bending or right-bending. The ‘left’ morph opens its mouth markedly towards the left and preferentially feeds on the scales from the right-hand side of its victim fish, and the ‘right’ morph bites scales from the victims’ left-hand side. This striking dimorphism made these fish a textbook example of their astonishing degree of ecological specialization and as one of the few known incidences of negative frequency-dependent selection acting on an asymmetric morphological trait, where left and right forms are equally frequent within a species. We investigated the degree and the shape of the frequency distribution of head asymmetry inP. microlepisto test whether the variation conforms to a discrete dimorphism, as generally assumed. In both adult and juvenile fish, mouth asymmetry appeared to be continuously and unimodally distributed with no clear evidence for a discrete dimorphism. Mixture analyses did not reveal evidence of a discrete or even strong dimorphism. These results raise doubts about previous claims, as reported in textbooks, that head variation inP. microlepisrepresents a discrete dimorphism of left- and right-bending forms. Based on extensive field sampling that excluded ambiguous (i.e. symmetric or weakly asymmetric) individual adults, we found that left and right morphs occur in equal abundance in five populations. Moreover, mate pairing for 51 wild-caught pairs was random with regard to head laterality, calling into question reports that this laterality is maintained through disassortative mating.
Striking Natural Diversity in Glandular Trichome Acylsugar Composition Is Shaped by Variation at the Acyltransferase2 Locus in the Wild Tomato Solanum habrochaites
Authors: Kim Jeongwoon , Kang Kiyoon , Gonzales-Vigil Eliana , Shi Feng , Jones A. Daniel , Barry Cornelius S. , Last Robert L.
Published: October 2012

Acylsugars are polyesters of short- to medium-length acyl chains on sucrose or glucose backbones that are produced in secretory glandular trichomes of many solanaceous plants, including cultivated tomato (Solanum lycopersicum). Despite their roles in biotic stress adaptation and their wide taxonomic distribution, there is relatively little information about the diversity of these compounds and the genes responsible for their biosynthesis. In this study, acylsugar diversity was assessed for 80 accessions of the wild tomato species Solanum habrochaites from throughout the Andes Mountains. Trichome metabolites were analyzed by liquid chromatography-time of flight-mass spectrometry, revealing the presence of at least 34 structurally diverse acylsucroses and two acylglucoses. Distinct phenotypic classes were discovered that varied based on the presence of glucose or sucrose, the numbers and lengths of acyl chains, and the relative total amounts of acylsugars. The presence or absence of an acetyl chain on the acylsucrose hexose ring caused clustering of the accessions into two main groups. Analysis of the Acyltransferase2 gene (the apparent ortholog of Solyc01g105580) revealed differences in enzyme activity and gene expression correlated with polymorphism in S. habrochaites accessions that varied in acylsucrose acetylation. These results are consistent with the hypothesis that glandular trichome acylsugar acetylation is under selective pressure in some populations of S. habrochaites and that the gene mutates to inactivity in the absence of selection.
Anbar Abstracts Issue
Authors: Fojt Martin
Published: October 2012

This special “Anbar Abstracts” issue of the Journal of Management in Medicine is split into seven sections covering abstracts under the following headings: General Management; Personnel and Training; Quality in Health Care; Health Care Marketing; Financial Management; Information Technology; Leadership, management styles and
decision making.
Strategic issues for training
Authors: Fojt Martin
Published: October 2012

The trend now in many organizations is to decentralize operations, giving greater responsibility to employees in the form of empowerment. Getting rid of a whole layer of
management may sound wonderful to the company accountant and also to many employees, but where does this leave the majority of aspiring young workers who expect to have a career ahead of them? By eradicating middle management, the chain to the highest echelons of the company are dramatically reduced. This can of course be a very good policy in that people have quicker and better contact with the decision‐making people, but this can also leave a vacuum of promotional uncertainty owing to the flattening in the hierarchical chain. Many people like the extra responsibility that empowerment brings, but they must also be able to see that they also have a future within the organization.
Service receivers' negative emotions in airline and hospital service settings
Authors: Petzer Daniel J. , De Meyer Christine F. , Svari Sander , Svensson Göran
Published: October 2012

Purpose

The purpose of this paper is to examine service receivers' negative emotions in two different service settings, namely at an airport and in a hospital.

Design/methodology/approach

A descriptive, convenience sampling survey method was used to collect data in South Africa consisting of a sample of 294 respondents at an airport and 288 respondents in a hospital. Data analysis included an exploratory factor analysis, and the results reported in this paper are based on the critical incident technique.

Findings

The findings indicate both similarities and differences in service receivers' negative emotions between the two service settings. Furthermore, the results were found to be valid and reliable.

Research limitations/implications

The results obtained pertaining to the negative emotions that service receivers experience in two service settings in South Africa may provide the foundation for further research and replication in other countries. Furthermore, the results can aid in refining and extending service providers' efforts of managing critical incidents in different service settings in airline and hospital service settings.

Practical implications

Three main aspects of negative incidences in service encounters should be considered in strategies to manage critical incidents, namely those that are caused by: the service receiver; the service provider; or the service encounter context.

Originality/value

This study complements and reinforces existing theory pertaining to the negative emotions service receivers' experience in negative service encounters.
The effects of exercise education intervention on the exercise behaviour, depression, and fatigue status of chronic kidney disease patients
Authors: Kao Yu‐Hsiu , Huang Yi‐Ching , Chen Pei‐Ying , Wang Kuo‐Ming
Published: October 2012

Purpose

The purpose of this paper is to investigate the effects of an exercise education intervention on exercise behavior, depression and fatigue status of chronic kidney disease (CKD) patients.

Design/methodology/approach

This was a pilot study using an exercise education program as an intervention for CKD patients. The authors used the transtheoretical model (TTM) to design the exercise education programs. A total of 94 subjects diagnosed with CKD at a medical center in Taiwan participated in this quasi‐experimental study. Subjects were randomly divided into the experimental group (n=45) and the control group (n=49). The education program included written materials and teaching activities designed to encourage participants to initiate and continue regular exercise. Both groups took the pre‐test and post‐test containing a depression inventory, a fatigue scale and an exercise behavior inventory.

Findings

The findings indicated that changes in the exercise behavior, depression and fatigue status of the experimental group were statistically significant after the exercise education intervention compared with the control group.

Originality/value

The paper demonstrates that exercise education intervention can be administered by nursing staff, or a health educator, to encourage patients to exercise in order to enhance their quality of care.
Healthy eating and physical activity in schools in Europe
Authors: Simovska Venka , Dadaczynski Kevin , Woynarowska Barbara
Published: October 2012

Purpose

The purpose of this paper is to introduce the HEPS project (Healthy Eating and Physical Activity in Schools) and discuss initial steps of the project implementation within EU countries. On the basis of the Health Promoting School approach as a conceptual foundation for the project, HEPS aimed at developing and implementing an effective tool for supporting the development of national policies on healthy eating and physical activity in schools across Europe. For this purpose, a package of publications (HEPS Toolkit) was produced and disseminated within the Schools for Health in Europe (SHE) network.

Design/methodology/approach

An initial implementation survey was carried out with national coordinators of the SHE network (n=24).

Findings

Results indicate that more than half of the respondents were familiar with and disseminated the HEPS Toolkit to relevant stakeholders at national, regional and local levels. However a number of problems and barriers in the implementation were encountered, such as lack of support and resources, existence of competing programmes, and frequent education and health reforms.

Practical implications

The findings are discussed against two models of implementation and a few recommendations are suggested for optimizing the further implementation of this, and other similar projects.

Originality/value

THE HEPS toolkit is the first attempt to support all EU member states in the development and implementation of a national policy on healthy eating and physical activity in schools. The involvement of the national coordinators of a well established European network of school health can be seen as an innovative way to implement and disseminate the project outcomes.
Health promotion in pre‐service teacher education
Authors: Byrne Jenny , Speller Viv , Dewhirst Sue , Roderick Paul , Almond Palo , Grace Marcus , Memon Anjum
Published: October 2012

Purpose

The purpose of this paper is to discuss a curriculum change in the provision of health promotion in pre‐service teacher education in a one‐year postgraduate certificate in education (PGCE) secondary course in one Higher Education Institution (HEI) in England.

Design/methodology/approach

The paper describes the iterative development process, from an initial survey and mapping of the existing pre‐service teacher training programme, which provided an evidence base for the piloting of a new health promotion component in the curriculum, and its subsequent evaluation. Changes to the health promotion element of the curriculum reflect the programme philosophy which balances the requirements of a competency based curriculum with a more liberal approach to education and training in which pre‐service teachers are expected to critically reflect on, and evaluate their practice. This work adopts a socio‐constructivist approach to teacher education, in which teachers develop their knowledge, skills and attitudes by interacting with others through dialogue, and learning from more knowledgeable others in a cooperative and scaffolded manner.

Findings

The paper presents the results of these changes and discusses implications for their sustainability. The changes made to the health promotion component of the programme and their implementation would not have been possible without the inter‐professional collaboration that took place over three years.

Originality/value

To the authors’ knowledge similar work involving a multi‐disciplinary collaborative approach to the development of a health education component of a pre‐service teacher education curriculum has not been employed or reported.
Relationships between occupational self efficacy, human resource development climate, and work engagement
Authors: Chaudhary Richa , Rangnekar Santosh , Barua Mukesh Kumar
Published: October 2012

Purpose

Improving work engagement can have significant implications for performance at individual, team and organisational level. The purpose of this paper is to investigate the effects of occupational self efficacy and human resource development (HRD) climate on work engagement among business executives of select business organisations in India. In addition, it aims to attempt to examine the mediating effect of HRD climate on self efficacy and work engagement relationship.

Design/methodology/approach

The sample consisted of 150 business executives from both public and private sector manufacturing and service organisations in India. Data were collected through both personal visits and online questionnaires. Correlation and regression analyses were used to test the research hypotheses. Specifically, Baron and Kenny's method was used for testing the hypotheses of mediation.

Findings

A significant relationship was found between all variables in the study. All the study hypotheses were supported. HRD climate was found to partially mediate the relationship between occupational self‐efficacy and work engagement. Interestingly, both HRD climate and self‐efficacy affect work engagement both directly and indirectly through influencing the other.

Practical implications

Work engagement requires the workforce that is endorsed with self‐efficacy as dispositional trait. In addition, improving the HRD climate can have significant implications for enhancing the work engagement among Indian business executives.

Originality/value

By investigating the relationship between self‐efficacy, HRD climate and work engagement the present study made an effort to fulfil the gap in academic literature where there is a significant dearth of academic literature on work engagement from developing economies.