bluuebunny/crossref_metadata_2025 huggingface dataset:
The genetics of cow growth and body composition at first calving in two tropical beef genotypes
Authors: Wolcott M. L. , Johnston D. J. , Barwick S. A. , Corbet N. J. , Williams P. J.
Published: August 2013

The genetics of cow growth and body composition traits, measured before first calving (pre-calving: in females before calving following their first 3-month annual mating period, at an average age of 34 months) and at the start of the subsequent mating period (Mating 2: on average 109 days later), were evaluated in 1016 Brahman (BRAH) and 1094 Tropical Composite (TCOMP) cows. Measurements analysed were liveweight, ultrasound-scanned measurements of P8 and 12/13th rib fat depth and eye muscle area, body condition score and hip height. Traits describing the change in these from pre-calving to Mating 2 were also included in the analysis. The maternal genetic component of weaning weight was estimated from weaning-weight records on these cows, their steer half-sibs and their progeny generated from up to six matings (n = 12 528). Within pregnant cows at pre-calving, BRAH were significantly lighter, leaner at the P8 site and taller than their TCOMP contemporaries, and these differences were also significant at Mating 2. There was a genetic basis for variation in growth and body composition traits measured at pre-calving and Mating 2 in BRAH (h2 = 0.27–0.67) and TCOMP (h2 = 0.25–0.87). Traits describing the change from pre- calving to Mating 2 were also moderately heritable for both genotypes (h2 = 0.17–0.54), except for change in hip height (h2 = 0.00 and 0.10 for BRAH and TCOMP, respectively). Genetic correlations between measurements of the same trait at pre-calving and Mating 2 were consistently positive and strong (rg = 0.75–0.98) and similar for both genotypes. In lactating cows, genetic correlations of growth and body composition traits with their change from pre-calving to Mating 2 showed that when animals had low levels of P8 and rib fat at Mating 2, change in eye muscle area was an important descriptor of genetic body condition score (rg = 0.63). This was supported by moderate genetic relationships, which suggested that lactating cows that were genetically predisposed to lose less eye muscle area were those that ended the period with higher P8 fat (rg = 0.66), rib fat (rg = 0.72) and body condition score (rg = 0.61). Change in liveweight, body condition score and, in particular, eye muscle area was significantly related to the maternal genetic component of weaning weight (rg = from –0.40 to –0.85) in both genotypes, suggesting that cows with higher genetic milk-production potential were those with the propensity for greater loss of these traits over the period from pre-calving to Mating 2. These results showed that for tropically adapted cows, the change in eye muscle area from pre-calving to Mating 2 was a more important descriptor of body condition at Mating 2 than was change in fat depth, and that higher genetic milk-production potential, measured as maternal weaning weight, was genetically related to higher mobilisation of muscle, and therefore body condition, over this period.
Treatment with suboptimal doses of raltegravir leads to aberrant HIV-1 integrations
Authors: Varadarajan Janani , McWilliams Mary Jane , Hughes Stephen H.
Published: August 2013

Integration of the DNA copy of the HIV-1 genome into a host chromosome is required for viral replication and is thus an important target for antiviral therapy. The HIV-encoded enzyme integrase (IN) catalyzes two essential steps: 3′ processing of the viral DNA ends, followed by the strand transfer reaction, which inserts the viral DNA into host DNA. Raltegravir binds to IN and blocks the integration of the viral DNA. Using the Rous sarcoma virus-derived vector RCAS, we previously showed that mutations that cause one viral DNA end to be defective for IN-mediated integration led to abnormal integrations in which the provirus had one normal and one aberrant end, accompanied by rearrangements in the host genome. On the basis of these results, we expected that suboptimal concentrations of IN inhibitors, which could block one of the ends of viral integration, would lead to similar aberrant integrations. In contrast to the proviruses from untreated cells, which were all normal, ∼10–15% of the proviruses isolated after treatment with a suboptimal dose of raltegravir were aberrant. The aberrant integrations were similar to those seen in the RCAS experiments. Most of the aberrant proviruses had one normal end and one aberrant end and were accompanied by significant rearrangements in the host genome, including duplications, inversions, deletions and, occasionally, acquisition of sequences from other chromosomes. The rearrangements of the host DNA raise concerns that these aberrant integrations might have unintended consequences in HIV-1–infected patients who are not consistent in following a raltegravir-containing treatment regimen.
On robust regression with high-dimensional predictors
Authors: El Karoui Noureddine , Bean Derek , Bickel Peter J. , Lim Chinghway , Yu Bin
Published: August 2013

We study regression
M
-estimates in the setting where
p
, the number of covariates, and
n
, the number of observations, are both large, but

. We find an exact stochastic representation for the distribution of

at fixed
p
and
n
under various assumptions on the objective function
ρ
and our statistical model. A scalar random variable whose deterministic limit

can be studied when

plays a central role in this representation. We discover a nonlinear system of two deterministic equations that characterizes

. Interestingly, the system shows that

depends on
ρ
through proximal mappings of
ρ
as well as various aspects of the statistical model underlying our study. Several surprising results emerge. In particular, we show that, when

is large enough, least squares becomes preferable to least absolute deviations for double-exponential errors.
Optimal M-estimation in high-dimensional regression
Authors: Bean Derek , Bickel Peter J. , El Karoui Noureddine , Yu Bin
Published: August 2013

We consider, in the modern setting of high-dimensional statistics, the classic problem of optimizing the objective function in regression using M-estimates when the error distribution is assumed to be known. We propose an algorithm to compute this optimal objective function that takes into account the dimensionality of the problem. Although optimality is achieved under assumptions on the design matrix that will not always be satisfied, our analysis reveals generally interesting families of dimension-dependent objective functions.
Implications for the evolution of eukaryotic amino-terminal acetyltransferase (NAT) enzymes from the structure of an archaeal ortholog
Authors: Liszczak Glen , Marmorstein Ronen
Published: August 2013

Significance

There are six human amino-terminal acetyltransferases (NATs) that mediate a growing number of biological processes and are differentiated from one another on the basis of substrate specificity. Interestingly, only one more promiscuous NAT enzyme exists in archaea. The crystal structure of an archaeal NAT from
Sulfolobus solfataricus
(ssNAT), together with mutagenesis and kinetic analysis, reveal that the active site of ssNAT represents a hybrid of known eukaryotic NAT active sites. We highlight features of this protein that allow it to facilitate catalysis of distinct substrates through different catalytic strategies, which is a unique characteristic of this enzyme. The data presented here have implications for the evolution of eukaryotic NAT enzymes and substrate specificities therein.
NAF-1 and mitoNEET are central to human breast cancer proliferation by maintaining mitochondrial homeostasis and promoting tumor growth
Authors: Sohn Yang-Sung , Tamir Sagi , Song Luhua , Michaeli Dorit , Matouk Imad , Conlan Andrea R. , Harir Yael , Holt Sarah H. , Shulaev Vladimir , Paddock Mark L. , Hochberg Abraham , Cabanchick Ioav Z. , Onuchic José N. , Jennings Patricia A. , Nechushtai Rachel , Mittler Ron
Published: August 2013

Mitochondria are emerging as important players in the transformation process of cells, maintaining the biosynthetic and energetic capacities of cancer cells and serving as one of the primary sites of apoptosis and autophagy regulation. Although several avenues of cancer therapy have focused on mitochondria, progress in developing mitochondria-targeting anticancer drugs nonetheless has been slow, owing to the limited number of known mitochondrial target proteins that link metabolism with autophagy or cell death. Recent studies have demonstrated that two members of the newly discovered family of NEET proteins, NAF-1 (CISD2) and mitoNEET (mNT; CISD1), could play such a role in cancer cells. NAF-1 was shown to be a key player in regulating autophagy, and mNT was proposed to mediate iron and reactive oxygen homeostasis in mitochondria. Here we show that the protein levels of NAF-1 and mNT are elevated in human epithelial breast cancer cells, and that suppressing the level of these proteins using shRNA results in significantly reduced cell proliferation and tumor growth, decreased mitochondrial performance, uncontrolled accumulation of iron and reactive oxygen in mitochondria, and activation of autophagy. Our findings highlight NEET proteins as promising mitochondrial targets for cancer therapy.
Population-genomic insights into the evolutionary origin and fate of obligately asexualDaphnia pulex
Authors: Tucker Abraham E. , Ackerman Matthew S. , Eads Brian D. , Xu Sen , Lynch Michael
Published: August 2013

Significance

Drawing from whole-genome sequences of multiple genotypes, this study documents the molecular-genetic consequences of the loss of recombination in a microcrustacean, demonstrating that loss of heterozygosity via gene conversion-like processes is a dramatically more powerful force than accumulation of new mutations.
Língua de Preto, the Basic Variety at the root of West African Portuguese Creoles
Authors: Kihm Alain , Rouge Jean-Louis
Published: August 2013

Língua de Preto
falar Guiné

In the first part of the study (sections 1–4), we substantiate our claim that such literary representations are indeed reliable renditions of the linguistic medium African slaves in Portugal actually used in their interactions with the white population and among themselves. We propose a historical scenario to account for the ‘return’ of LdP to Africa, i.e. Senegambia, where it soon became the lingua franca of trade between Portuguese expatriates and the local populations. From this lingua franca, creoles subsequently arose.

In the second part (sections 5–11), we propose an extensive outline of LdP grammar such as we are able to retrieve from the corpus. Comparisons with present-day WAPCs are attempted.

We conclude (sections 12–13) that the availability of such historical testimonies indeed gives us the exceptional opportunity of gaining some first-hand knowledge of the transitional medium that necessarily separates a lexifier language from ‘its’ creole(s). The fact that this transitional medium, we think, looks much more like a BV than a destructured jargon lends support to the assumption that untutored L2 acquisition by adults played a crucial role in creole formation.
The transparency of creoles
Authors: Leufkens Sterre
Published: August 2013

In this article I propose that creoles are relatively transparent compared to their source languages. This means that they display more one-to-one relations between meaning and form. Transparency should be distinguished from the concepts of simplicity, ease of acquisition, and regularity. Definitions of these notions are given and it is shown how they have been mixed up in earlier literature.

The transparency of creoles is explained as a result of language contact. When people speaking radically different languages communicate, they tend to use maximally intelligible forms, i.e. transparent forms. The repeated selection of transparent over opaque forms will lead to the formation of a relatively transparent language. Hence, creoles are predicted to be either as transparent as or more transparent than their source languages.

An empirical study is performed to test this prediction. The transparency of four contact languages and their sub- and superstrates is measured by checking them on a list of non-transparent features. It turns out that they all exhibit opaque structures, but that there is a striking absence of so called form-based forms: linguistic elements and rules that are not motivated pragmatically or semantically. This indicates that such ‘empty’ forms are lost during intense language contact.
On the non-creole basis for Afro-Bolivian Spanish
Authors: Sessarego Sandro
Published: August 2013

This article provides a sociohistorical and linguistic account for the development of Afro-Bolivian Spanish (ABS), an Afro-Hispanic vernacular spoken in Los Yungas, Department of La Paz, Bolivia. Previous research has indicated that ABS might be the descendent of an Afro-Hispanic pidgin (Lipski 2008), which first creolized in colonial times and eventually decreolized due to contact with Spanish after the Bolivian Land Reform of 1952.

The present study argues that ABS was probably never a creole, but rather a language relatively close to Spanish from its inception. The basis on which this claim is built consists of sociodemographic and linguistic data. The findings strongly indicate that the historical conditions for a creole language to emerge were not in place in Bolivia for the period under analysis (15th–19th century).
Comportements, déguisements, rôles de fiction…
Authors: Vigier Denis
Published: August 2013

This paper focuses on a set of utterances that all contain a prepositional phrase (PP) in intrapredicative position, in the form en + NP,
and mainly denoting a behaviour, a disguise or a fictitious role. The study first proposes a brief overview of previous studies of these
uses of en since G. Guillaume (1919), before going on to examine the PPs from a syntactic and semantic point of view. Lastly, it is argued
that in all the utterances examined, the PPs denote the result of a more or less abstract transformation process.
Adjectifs d’évaluation de comportement
Authors: Paykin Katia , Tayalati Fayssal , Van de Velde Danièle
Published: August 2013

The article proposes a unified analysis of Behavior Evaluation Adjectives (BEA), like gentil ‘kind’ or prudent ‘wise’, whether the quality expressed is attributed to a human subject (Tu es vraiment gentil de nous aider ‘You are really kind to help us’) or to his/her behavior (Nous aider est vraiment gentil de ta part ‘To help us is really kind of you’). We argue that these two structures should be viewed as diathetic variants of one another, the structure with the clausal subject being the passive equivalent of the active construction with a human subject. BEAs function as part of an active complex predicate être ‘be’+A, which takes an external “agent” argument expressed by an NP+human and a direct internal argument, infinitive clause. Thus, BEAs function in all their usages as secondary predicates of “Individual level” type, providing the evaluation of a human subject as an agent.
De l’existence des prédicats d’achèvements
Authors: Haas Pauline , Jugnet Anne
Published: August 2013

The very existence of achievements (defined as instantaneous eventualities) is often questioned in the literature, which is why our first objective is to maintain that this aspectual class does exist, in the verbal as in the nominal domains. Thanks to a series of tests, we distinguish three subclasses of achievements : pure achievements (mere boundaries), right-boundary achievements (boundaries that are preceded by preparatory activity), and left-boundary achievements (boundaries that are followed by a stative interval). We use this aspectual classification as a basis to study aspectual inheritance from verbs to morphologically related (derived) nouns.
Description lexicographique du vocable breton KEUZ ‘regret’
Authors: Louis François , Milićević Jasmina
Published: August 2013

The paper proposes a lexicographic description of the polysemous word keuz ‘≈ regret’, from the Vannetais dialect of Breton. Our description is based both on written and oral usage, the latter being mostly that of the Pontivy region, in the North of the Department of Morbihan. Some of the wordsenses, not represented in the existing dictionaries of Breton, are described here for the first time.
The theoretical frame of reference adopted is the Explanatory-Combinatorial Lexicology (ECL) of the Meaning-Text theory, a cutting-edge lexicological theory applied here for the very first time to a description of Breton data. An ECL-style lexicographic description, which, on the one hand, strives to make available to speakers all linguistic means necessary for an idomatic use of lexical units and, on the other hand, obeys formal descriptive principles, is not readily accessible to a non-initiated user. Therefore, the first part of the paper is dedicated to an explanation of the notions necessary for the comprehension of the lexicographic description proper.
Contribution à l’acquisition automatique de nouveaux sens
Authors: Reutenauer Coralie , Jacquey Evelyne
Published: August 2013

This paper tackles the question of automated meaning acquisition. In several cases, meaning change can be considered as a process spreading both in time and through domains. In addition, this phenomenon relies on interactions between word meaning in discourse and dictionary definitions. We outline the main steps of a procedure to highlight the spread of a new word meaning in corpus, to extract semantic content represented by domain labels and to match corpus and dictionary information. The methodology is illustrated by experiments on several lexical units observed in a press corpus ranging from 2004 to 2010 and divided into several domains.
Task Difficulty and Response Complexity Modulate Affective Priming by Emotional Facial Expressions
Authors: Sassi Federica , Campoy Guillermo , Castillo Alejandro , Inuggi Alberto , Fuentes Luis J.
Published: August 2013

In this study we used an affective priming task to address the issue of whether the processing of emotional facial expressions occurs automatically independent of attention or attentional resources. Participants had to attend to the emotion expression of the prime face, or to a nonemotional feature of the prime face, the glasses. When participants attended to glasses (emotion unattended), they had to report whether the face wore glasses or not (the glasses easy condition) or whether the glasses were rounded or squared (the shape difficult condition). Affective priming, measured on valence decisions on target words, was mainly defined as interference from incongruent rather than facilitation from congruent trials. Significant priming effects were observed just in the emotion and glasses tasks but not in the shape task. When the key–response mapping increased in complexity, taxing working memory load, affective priming effects were reduced equally for the three types of tasks. Thus, attentional load and working memory load affected additively to the observed reduction in affective priming. These results cast some doubts on the automaticity of processing emotional facial expressions.
IL-25 simultaneously elicits distinct populations of innate lymphoid cells and multipotent progenitor type 2 (MPPtype2) cells
Authors: Saenz Steven A. , Siracusa Mark C. , Monticelli Laurel A. , Ziegler Carly G.K. , Kim Brian S. , Brestoff Jonathan R. , Peterson Lance W. , Wherry E. John , Goldrath Ananda W. , Bhandoola Avinash , Artis David
Published: August 2013

The predominantly epithelial cell–derived cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) can promote CD4+ Th2 cell–dependent immunity, inflammation, and tissue repair at barrier surfaces through the induction of multiple innate immune cell populations. IL-25 and IL-33 were previously shown to elicit four innate cell populations, named natural helper cells, nuocytes, innate type 2 helper cells, and multipotent progenitor type 2 (MPPtype2) cells, now collectively termed group 2 innate lymphoid cells (ILC2). In contrast to other types of ILC2, MPPtype2 cells exhibit multipotent potential and do not express T1/ST2 or IL-7Rα, suggesting that MPPtype2 cells may be a distinct population. Here, we show that IL-33 elicits robust ILC2 responses, whereas IL-25 predominantly promotes MPPtype2 cell responses at multiple tissue sites with limited effects on ILC2 responses. MPPtype2 cells were distinguished from ILC2 by their differential developmental requirements for specific transcription factors, distinct genome-wide transcriptional profile, and functional potential. Furthermore, IL-25–induced MPPtype2 cells promoted Th2 cytokine–associated inflammation after depletion of ILC2. These findings indicate that IL-25 simultaneously elicits phenotypically and functionally distinct innate lymphoid– and nonlymphoid-associated cell populations and implicate IL-25–elicited MPPtype2 cells and extramedullary hematopoiesis in the promotion of Th2 cytokine responses at mucosal surfaces.
Vulnerability of Primary Care Organizations to the National Health Service Reform in England
Authors: Iparraguirre José , Gentry Tom , Peña Diego
Published: August 2013

We study how ready or vulnerable each Primary Care Organization (PCO) in England was in 2010 to the National Health Service reforms announced in the Government white paper Equity and Excellence: Liberating the NHS, later enacted by the Health and Social Care Act 2012. We define vulnerability as a combination of latent variables and present a novel methodological approach to measuring organizational and wider impacts of health policy reforms. Areas with higher concentrations of older people were not correlated with vulnerability except where there was also deprivation. This contrasts with wide‐spread qualitative and quantitative evidence of sub‐optimal care of older people within the health service. This suggests there may be an over‐reliance on using activity, which was proportionately higher in the least vulnerable areas, to determine funding and quality markers rather than outcomes. A risk of the reform process could be a negative impact on deprived areas which appear to be financially less secure and more likely to have long‐established health inequalities.
A Turing test for artificial expression data
Authors: Maier Robert , Zimmer Ralf , Küffner Robert
Published: August 2013

Motivation: The lack of reliable, comprehensive gold standards complicates the development of many bioinformatics tools, particularly for the analysis of expression data and biological networks. Simulation approaches can provide provisional gold standards, such as regulatory networks, for the assessment of network inference methods. However, this just defers the problem, as it is difficult to assess how closely simulators emulate the properties of real data.

Results: In analogy to Turing’s test discriminating humans and computers based on responses to questions, we systematically compare real and artificial systems based on their gene expression output. Different expression data analysis techniques such as clustering are applied to both types of datasets. We define and extract distributions of properties from the results, for instance, distributions of cluster quality measures or transcription factor activity patterns. Distributions of properties are represented as histograms to enable the comparison of artificial and real datasets. We examine three frequently used simulators that generate expression data from parameterized regulatory networks. We identify features distinguishing real from artificial datasets that suggest how simulators could be adapted to better emulate real datasets and, thus, become more suitable for the evaluation of data analysis tools.

Availability: See http://www2.bio.ifi.lmu.de/∼kueffner/attfad/ and the supplement for precomputed analyses; other compendia can be analyzed via the CRAN package attfad. The full datasets can be obtained from http://www2.bio.ifi.lmu.de/∼kueffner/attfad/data.tar.gz.

Contact:  robert.kueffner@bio.ifi.lmu.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Incorporating prior knowledge into Gene Network Study
Authors: Wang Zixing , Xu Wenlong , San Lucas F. Anthony , Liu Yin
Published: August 2013

Motivation: A major goal in genomic research is to identify genes that may jointly influence a biological response. From many years of intensive biomedical research, a large body of biological knowledge, or pathway information, has accumulated in available databases. There is a strong interest in leveraging these pathways to improve the statistical power and interpretability in studying gene networks associated with complex phenotypes. This prior information is a valuable complement to large-scale genomic data such as gene expression data generated from microarrays. However, it is a non-trivial task to effectively integrate available biological knowledge into gene expression data when reconstructing gene networks.

Results: In this article, we developed and applied a Lasso method from a Bayesian perspective, a method we call prior Lasso (pLasso), for the reconstruction of gene networks. In this method, we partition edges between genes into two subsets: one subset of edges is present in known pathways, whereas the other has no prior information associated. Our method assigns different prior distributions to each subset according to a modified Bayesian information criterion that incorporates prior knowledge on both the network structure and the pathway information. Simulation studies have indicated that the method is more effective in recovering the underlying network than a traditional Lasso method that does not use the prior information. We applied pLasso to microarray gene expression datasets, where we used information from the Pathway Commons (PC) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) as prior information for the network reconstruction, and successfully identified network hub genes associated with clinical outcome in cancer patients.

Availability: The source code is available at http://nba.uth.tmc.edu/homepage/liu/pLasso.

Contact:  Yin.Liu@uth.tmc.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Oncofuse: a computational framework for the prediction of the oncogenic potential of gene fusions
Authors: Shugay Mikhail , Ortiz de Mendíbil Iñigo , Vizmanos José L. , Novo Francisco J.
Published: August 2013

Motivation: Gene fusions resulting from chromosomal aberrations are an important cause of cancer. The complexity of genomic changes in certain cancer types has hampered the identification of gene fusions by molecular cytogenetic methods, especially in carcinomas. This is changing with the advent of next-generation sequencing, which is detecting a substantial number of new fusion transcripts in individual cancer genomes. However, this poses the challenge of identifying those fusions with greater oncogenic potential amid a background of ‘passenger’ fusion sequences.

Results: In the present work, we have used some recently identified genomic hallmarks of oncogenic fusion genes to develop a pipeline for the classification of fusion sequences, namely, Oncofuse. The pipeline predicts the oncogenic potential of novel fusion genes, calculating the probability that a fusion sequence behaves as ‘driver’ of the oncogenic process based on features present in known oncogenic fusions. Cross-validation and extensive validation tests on independent datasets suggest a robust behavior with good precision and recall rates. We believe that Oncofuse could become a useful tool to guide experimental validation studies of novel fusion sequences found during next-generation sequencing analysis of cancer transcriptomes.

Availability and implementation: Oncofuse is a naive Bayes Network Classifier trained and tested using Weka machine learning package. The pipeline is executed by running a Java/Groovy script, available for download at www.unav.es/genetica/oncofuse.html.

Contact:  fnovo@unav.es

Supplementary information:  Supplementary data are available at Bioinformatics online.
SPOCS: software for predicting and visualizing orthology/paralogy relationships among genomes
Authors: Curtis Darren S. , Phillips Aaron R. , Callister Stephen J. , Conlan Sean , McCue Lee Ann
Published: August 2013

Summary: At the rate that prokaryotic genomes can now be generated, comparative genomics studies require a flexible method for quickly and accurately predicting orthologs among the rapidly changing set of genomes available. SPOCS implements a graph-based ortholog prediction method to generate a simple tab-delimited table of orthologs and in addition, html files that provide a visualization of the predicted ortholog/paralog relationships to which gene/protein expression metadata may be overlaid.

Availability and Implementation: A SPOCS web application is freely available at http://cbb.pnnl.gov/portal/tools/spocs.html. Source code for Linux systems is also freely available under an open source license at http://cbb.pnnl.gov/portal/software/spocs.html; the Boost C++ libraries and BLAST are required.

Contact:  leeann.mccue@pnnl.gov
Imputation of coding variants in African Americans: better performance using data from the exome sequencing project
Authors: Duan Qing , Liu Eric Yi , Auer Paul L. , Zhang Guosheng , Lange Ethan M. , Jun Goo , Bizon Chris , Jiao Shuo , Buyske Steven , Franceschini Nora , Carlson Chris S. , Hsu Li , Reiner Alex P. , Peters Ulrike , Haessler Jeffrey , Curtis Keith , Wassel Christina L. , Robinson Jennifer G. , Martin Lisa W. , Haiman Christopher A. , Le Marchand Loic , Matise Tara C. , Hindorff Lucia A. , Crawford Dana C. , Assimes Themistocles L. , Kang Hyun Min , Heiss Gerardo , Jackson Rebecca D. , Kooperberg Charles , Wilson James G. , Abecasis Gonçalo R. , North Kari E. , Nickerson Deborah A. , Lange Leslie A. , Li Yun
Published: August 2013

Summary: Although the 1000 Genomes haplotypes are the most commonly used reference panel for imputation, medical sequencing projects are generating large alternate sets of sequenced samples. Imputation in African Americans using 3384 haplotypes from the Exome Sequencing Project, compared with 2184 haplotypes from 1000 Genomes Project, increased effective sample size by 8.3–11.4% for coding variants with minor allele frequency <1%. No loss of imputation quality was observed using a panel built from phenotypic extremes. We recommend using haplotypes from Exome Sequencing Project alone or concatenation of the two panels over quality score-based post-imputation selection or IMPUTE2’s two-panel combination.

Contact:  yunli@med.unc.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Acoustic surveys for juvenile anchovy in the Bay of Biscay: abundance estimate as an indicator of the next year's recruitment and spatial distribution patterns
Authors: Boyra G. , Martínez U. , Cotano U. , Santos M. , Irigoien X. , Uriarte A.
Published: August 2013

Boyra, G., Martínez, U., Cotano, U., Santos, M., Irigoien, X., and Uriarte, A. 2013. Acoustic surveys for juvenile anchovy in the Bay of Biscay: abundance estimate as an indicator of the next year's recruitment and spatial distribution patterns. – ICES Journal of Marine Science, 70: . A series of acoustic surveys (JUVENA) began in 2003 targeting juvenile anchovy (Engraulis encrasicolus) in the Bay of Biscay. A specific methodology was designed for mapping and estimating juvenile abundance annually, four months after the spawning season. After eight years of the survey, a consistent picture of the spatial pattern of the juvenile anchovy has emerged. Juveniles show a vertical and horizontal distribution pattern that depends on size. The younger individuals are found isolated from other species in waters closer to the surface, mainly off the shelf within the mid-southern region of the bay. The largest juveniles are usually found deeper and closer to the shore in the company of adult anchovy and other pelagic species. In these eight years, the survey has covered a wide range of juvenile abundances, and the estimates show a significant positive relationship between the juvenile biomasses and the one-year-old recruits of the following year. This demonstrates that the JUVENA index provides an early indication of the strength of next year's recruitment to the fishery and can therefore be used to improve the management advice for the fishery of this short-lived species.
Modelling prey consumption and switching by UK grey seals
Authors: Smout Sophie , Rindorf Anna , Hammond Philip S. , Harwood John , Matthiopoulos Jason
Published: August 2013

Smout, S., Rindorf, A., Hammond, P. S., Harwood, J., and Matthiopoulos, J. Modelling prey consumption and switching by UK grey seals. – ICES Journal of Marine Science, 71: . Grey seals (Halichoerus grypus) are adaptable generalist predators whose diet includes commercial fish species such as cod. Consumption by the seals may reduce the size of some fish stocks or have an adverse effect on stock recovery programmes, especially because predation may trap sparse prey populations in a “predator pit”. To assess the likely impact of such effects, it is important to know how consumption and consequent predation mortality respond to the changing availability of prey. We present a model of grey seal consumption as a function of the availability of multiple prey types [a Multi-Species Functional Response (MSFR)]. We fit this MSFR to data on seal diet and prey availability (based on the overlap between the distributions of predators and prey). Bayesian methodology was employed to account for uncertainties in both dependent and independent variables, improve estimation convergence by the use of informative priors, and allow the estimation of missing data on prey availability. Both hyperbolic (Type 2) and sigmoidal (Type 3) functional response models were fitted to the data and the Type 3 model was clearly favoured during model selection, supporting the conclusion that seal–prey encounter rates change with prey abundance (sometimes referred to as “switching”). This suggests that some prey species may be vulnerable to predator pit effects. The fitted model reproduced contrasts in diet observed between different regions/years and, importantly, added information to the prior distributions of prey abundance in areas where the availability of some prey species (such as sandeels) was not known. This suggests that the diet of predators such as seals could provide information about the abundance and distribution of prey in areas that are not covered by fisheries and research surveys.
Deep-sea sponge grounds enhance diversity and abundance of epibenthic megafauna in the Northwest Atlantic
Authors: Beazley Lindsay I. , Kenchington Ellen L. , Murillo Francisco Javier , Sacau María del Mar
Published: August 2013

Beazley, L. I., Kenchington E. L., Murillo, F. J., and Sacau, M. 2013. Deep-sea sponge grounds enhance diversity and abundance of epibenthic megafauna in the Northwest Atlantic. – ICES Journal of Marine Science, 70: . The influence of structure-forming deep-water sponge grounds on the composition, diversity, and abundance of the local epibenthic megafaunal community of the Flemish Pass area, Northwest Atlantic was statistically assessed. These habitats are considered vulnerable marine ecosystems and, therefore, warrant conservation measures to protect them from bottom fishing activities. The epibenthic megafauna were quantified from four photographic transects, three of which were located on the western slope of the Flemish Cap with an overall depth range of 444–940 m, and the fourth in the southern Flemish Pass between 1328 and 1411 m. We observed a diverse megafaunal community dominated by large numbers of ophiuroids and sponges. On the slope of the Flemish Cap, sponge grounds were dominated by axinellid and polymastid sponges, while the deeper sponge ground in the southern Flemish Pass was formed mainly by geodiids and Asconema sp. The presence of structure-forming sponges was associated with a higher biodiversity and abundance of associated megafauna compared with non-sponge habitat. The composition of megafauna significantly differed between sponge grounds and non-sponge grounds and also between different sponge morphologies. Surface chlorophyll a and near-bottom salinity were important environmental determinants in generalized linear models of megafaunal species richness and abundance.
Effect of region on the food-related benefits to age-0 walleye pollock (Theragra chalcogramma) in association with midwater habitat characteristics in the Gulf of Alaska
Authors: Wilson Matthew T. , Mier Kathryn L. , Jump Christina M.
Published: August 2013

Wilson, M. T., Mier, K. L., and Jump, C. M. 2013. Effect of region on the food-related benefits to age-0 walleye pollock (Theragra chalcogramma) in association with midwater habitat characteristics in the Gulf of Alaska – ICES Journal of Marine Science, 70: . In the western Gulf of Alaska (GOA), we compared age-0 juvenile walleye pollock body weight, food habits, and expected growth rates between two regions during 3 years. The benefit to rearing off Kodiak Island vs. in the Semidi Islands vicinity increased among years with body length because larger fish consumed more euphausiids, and euphausiids were apparently more available in the Kodiak region. This explains previously observed regional variation in body size, condition, and growth rates within the GOA population and points to potential importance of the Kodiak region as a walleye pollock nursery. During September 2005, 2007, and 2009, Kodiak midwater was cooler and saltier than Semidi midwater, presumably due to a relatively narrow continental shelf and greater oceanic influence. Zooplankton composition differed between regions with the greater euphausiid population density off Kodiak being most relevant to walleye pollock food habits. As found historically, age-0 walleye pollock abundance was lower in the Kodiak region than in the Semidi region. However, the Kodiak fish were larger in both length and length-specific weight, and had fuller stomachs than Semidi fish, although differences were not significant in all years. Regional differences were most pronounced during the relatively warm year 2005 when fish were particularly large. Fish dietary mass was dominated by euphausiids, especially for Kodiak fish ≥55 mm standard length. Bioenergetics model output suggests that the greater euphausiid dietary proportion translates into faster growth of the Kodiak fish. The midwater habitat off Kodiak Island might therefore support above-average production of recruits to the GOA adult population due to better condition and likely survival of walleye pollock juveniles, especially when fish are large and thus able to more fully exploit euphausiids, but confirmation of above-average production of recruits depends on our ability to determine spatial structure in juvenile-adult population connectivity.
CYP1A1 and Cnr nitroreductase bioactivated niclosamide in vitro
Authors: Beristain-Castillo Evelyn , Martínez-Vázquez Mariano , Camacho-Carranza Rafael , Espinosa-Aguirre Javier J.
Published: August 2013

Niclosamide produces genotoxic effects, such as point mutations in Salmonella sp., sperm-head abnormalities in mice and clastogenic effects in human lymphocytes in vitro and in vivo. As cytochrome P450 could be involved in the bioactivation of niclosamide, we investigated which subfamily was involved. We used liver microsomal fractions from rats treated with phenobarbital/β-naphthoflavone (PB/β-NF), benzo[a]pyrene (BaP) or cyclohexanol, which are known to induce different cytochrome P450 subfamilies, such as CYP2B, CYP1A1, CYP1A2 and CYP2E1. We also inhibited CYP1A and CYP2E using α-NF and diethyldithiocarbamate to identify the cytochrome P450 involved. Liver-S9 fractions obtained from PB/β-NF- and BaP-treated rats significantly increased the number of revertants induced by niclosamide, while the CYP1A1 inhibitor α-NF decreased the number of revertants. The incubation of niclosamide with CYP1A1 Supersomes™ increased the number of revertants, suggesting that CYP1A1 is responsible for the bioactivation of niclosamide. Nitroreduction is also involved in niclosamide bioactivation, as the nitroreductase-deficient strain YG7132 did not respond to the niclosamide treatment. Our findings indicated that a metabolite, derived from the action of CYP1A1 and a nitroreduction-reaction process, has a key role in the bioactivation of niclosamide.
Increasing the complexity of chromatin: functionally distinct roles for replication-dependent histone H2A isoforms in cell proliferation and carcinogenesis
Authors: Singh Rajbir , Mortazavi Amir , Telu Kelly H. , Nagarajan Prabakaran , Lucas David M. , Thomas-Ahner Jennifer M. , Clinton Steven K. , Byrd John C. , Freitas Michael A. , Parthun Mark R.
Published: August 2013

Replication-dependent histones are encoded by multigene families found in several large clusters in the human genome and are thought to be functionally redundant. However, the abundance of specific replication-dependent isoforms of histone H2A is altered in patients with chronic lymphocytic leukemia. Similar changes in the abundance of H2A isoforms are also associated with the proliferation and tumorigenicity of bladder cancer cells. To determine whether these H2A isoforms can perform distinct functions, expression of several H2A isoforms was reduced by siRNA knockdown. Reduced expression of the HIST1H2AC locus leads to increased rates of cell proliferation and tumorigenicity. We also observe that regulation of replication-dependent histone H2A expression can occur on a gene-specific level. Specific replication-dependent histone H2A genes are either up- or downregulated in chronic lymphocytic leukemia tumor tissue samples. In addition, discreet elements are identified in the 5′ untranslated region of the HIST1H2AC locus that confer translational repression. Taken together, these results indicate that replication-dependent histone isoforms can possess distinct cellular functions and that regulation of these isoforms may play a role in carcinogenesis.
Population Pharmacokinetic Modeling of Hydromorphone in Cardiac Surgery Patients during Postoperative Pain Therapy
Authors: Jeleazcov Christian , Saari Teijo I. , Ihmsen Harald , Mell Jan , Fröhlich Katharina , Krajinovic Ljubica , Fechner Jörg , Schüttler Jürgen
Published: August 2013

Background:

Hydromorphone is a µ-selective opioid agonist used in postoperative pain therapy. This study aimed to evaluate the pharmacokinetics of hydromorphone in cardiac surgery patients during postoperative analgesia with target-controlled infusion and patient-controlled analgesia.

Methods:

In this study, 50 adult patients were enrolled to receive intravenous hydromorphone during postoperative pain therapy. Arterial plasma samples were collected for measurements of drug concentration. Population pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling. Results were validated and simulations were carried out to evaluate results.

Results:

Data from 49 patients (age range, 40–81 yr) were analyzed. The pharmacokinetics of hydromorphone were best described by a three-compartment model. Age was incorporated as a significant covariate for elimination clearance and central volume of distribution. Scaling all parameters with body weight improved the model significantly. The final estimates of the model parameters for the typical adult patient (67 yr old, weighing 70 kg) undergoing cardiac surgery were as follows: CL1 = 1.01 l/min, V1 = 3.35 l, CL2 = 1.47 l/min, V2 = 13.9 l, CL3 = 1.41 l/min, and V3 = 145 l. The elimination clearance decreased by 43% between the age of 40 and 80 yr, and simulations demonstrated that context-sensitive half-time increased from 26 to 84 min in 40- and 80-yr-old subjects, respectively.

Conclusions:

The final pharmacokinetic model gave a robust representation of hydromorphone pharmacokinetics. Inclusion of age and body weight to the model demonstrated a significant influence of these covariates on hydromorphone pharmacokinetics. The application of this patient-derived population model in individualized pain therapy should improve the dosing of hydromorphone in patients undergoing cardiac surgery.
An odd-number limitation of extended time-delayed feedback control in autonomous systems
Authors: Amann Andreas , Hooton Edward W.
Published: August 2013

We propose a necessary condition for the successful stabilization of a periodic orbit, using the extended version of time-delayed feedback control. This condition depends on the number of real Floquet multipliers larger than unity and is therefore related to the well-known odd-number limitation in non-autonomous systems. We show that the period of the orbit that is induced by mismatching the delay time of the control scheme and the period of the uncontrolled orbit plays an important role in the formulation of the odd-number limitation in the autonomous case.
Human papillomavirus 16-encoded E7 protein inhibits IFN-γ-mediated MHC class I antigen presentation and CTL-induced lysis by blocking IRF-1 expression in mouse keratinocytes
Authors: Zhou Fang , Chen JieZhong , Zhao Kong-Nan
Published: August 2013

Human papillomavirus 16 (HPV16) infection causes 50 % or more of cervical cancers in women. The HPV16 E7 oncogene is continuously expressed in infected epithelium with its oncogenicity linked to cervical cancer. The E7 protein is an ideal target in control of HPV infection through T-cell-mediated immunity. Using HPV16 E7-transgenic mouse keratinocytes (KCs–E7) to investigate T-cell-mediated immune responses, we have shown previously that HPV16-encoded E7 protein inhibits IFN-γ-mediated enhancement of MHC class I antigen processing and T-cell-induced target cell lysis. In this study, we found that HPV16 E7 suppresses IFN-γ-induced phosphorylation of STAT1(Tyr701), leading to the blockade of interferon regulatory factor-1 (IRF-1) and transporter associated antigen processing subunit 1 (TAP-1) expression in KCs–E7. The results of a51Cr release assay demonstrated that IFN-γ-treated KCs–E7 escaped from CTL recognition because HPV16 E7 downregulated MHC class I antigen presentation on KCs. Restoration of IRF-1 expression in KCs–E7 overcame the inhibitory effect of E7 protein on IFN-γ-mediated CTL lysis and MHC class I antigen presentation on KCs. Our results suggest that HPV16 E7 interferes with the IFN-γ-mediated JAK1/JAK2/STAT1/IRF-1 signal transduction pathway and reduces the efficiency of peptide loading and MHC class I antigen presentation on KCs–E7. These results may reveal a new mechanism whereby HPV16 escapes from immune surveillancein vivo.