bluuebunny/crossref_metadata_2025_split huggingface dataset:
Site identification in high-throughput RNA–protein interaction data
Authors: Uren Philip J. , Bahrami-Samani Emad , Burns Suzanne C. , Qiao Mei , Karginov Fedor V. , Hodges Emily , Hannon Gregory J. , Sanford Jeremy R. , Penalva Luiz O. F. , Smith Andrew D. 
Published: October 2012

AbstractMotivation: Post-transcriptional and co-transcriptional regulation is a crucial link between genotype and phenotype. The central players are the RNA-binding proteins, and experimental technologies [such as cross-linking with immunoprecipitation- (CLIP-) and RIP-seq] for probing their activities have advanced rapidly over the course of the past decade. Statistically robust, flexible computational methods for binding site identification from high-throughput immunoprecipitation assays are largely lacking however.Results: We introduce a method for site identification which provides four key advantages over previous methods: (i) it can be applied on all variations of CLIP and RIP-seq technologies, (ii) it accurately models the underlying read-count distributions, (iii) it allows external covariates, such as transcript abundance (which we demonstrate is highly correlated with read count) to inform the site identification process and (iv) it allows for direct comparison of site usage across cell types or conditions.Availability and implementation: We have implemented our method in a software tool called Piranha. Source code and binaries, licensed under the GNU General Public License (version 3) are freely available for download from http://smithlab.usc.edu.Contact: andrewds@usc.eduSupplementary information: Supplementary data available at Bioinformatics online.
FeatureStack: Perl module for comparative visualization of gene features
Authors: Frech Christian , Choo Caleb , Chen Nansheng 
Published: October 2012

Abstract
Summary: FeatureStack is a Perl module for the automatic generation of multi-gene images. FeatureStack takes BioPerl-compliant gene or transcript features as input and renders them side by side using a user-defined BioPerl glyph. Output images can be generated in SVG or PNG format. FeatureStack comes with a new BioPerl glyph, decorated_gene, which can highlight protein features on top of gene models. Used in combination, FeatureStack and decorated_gene enable rapid and automated generation of annotation-rich images of stacked gene models that greatly facilitate evolutionary studies of related gene structures and gene families.
Availability and implementation: Bio-Draw-FeatureStack and Bio-Graphics-glyph-decorated_gene are freely available at the Comprehensive Perl Archive Network (CPAN) and GitHub.
Contact: chenn@sfu.ca
Supplementary information: Supplementary data are available at Bioinformatics online.
InterMine: a flexible data warehouse system for the integration and analysis of heterogeneous biological data
Authors: Smith Richard N. , Aleksic Jelena , Butano Daniela , Carr Adrian , Contrino Sergio , Hu Fengyuan , Lyne Mike , Lyne Rachel , Kalderimis Alex , Rutherford Kim , Stepan Radek , Sullivan Julie , Wakeling Matthew , Watkins Xavier , Micklem Gos 
Published: October 2012

Abstract
Summary: InterMine is an open-source data warehouse system that facilitates the building of databases with complex data integration requirements and a need for a fast customizable query facility. Using InterMine, large biological databases can be created from a range of heterogeneous data sources, and the extensible data model allows for easy integration of new data types. The analysis tools include a flexible query builder, genomic region search and a library of ‘widgets’ performing various statistical analyses. The results can be exported in many commonly used formats. InterMine is a fully extensible framework where developers can add new tools and functionality. Additionally, there is a comprehensive set of web services, for which client libraries are provided in five commonly used programming languages.
Availability: Freely available from http://www.intermine.org under the LGPL license.
Contact: g.micklem@gen.cam.ac.uk
Supplementary information: Supplementary data are available at Bioinformatics online.
Phylogenetic Estimation of Timescales Using Ancient DNA: The Effects of Temporal Sampling Scheme and Uncertainty in Sample Ages
Authors: Molak Martyna , Lorenzen Eline D. , Shapiro Beth , Ho Simon Y.W. 
Published: October 2012

AbstractIn recent years, ancient DNA has increasingly been used for estimating molecular timescales, particularly in studies of substitution rates and demographic histories. Molecular clocks can be calibrated using temporal information from ancient DNA sequences. This information comes from the ages of the ancient samples, which can be estimated by radiocarbon dating the source material or by dating the layers in which the material was deposited. Both methods involve sources of uncertainty. The performance of Bayesian phylogenetic inference depends on the information content of the data set, which includes variation in the DNA sequences and the structure of the sample ages. Various sources of estimation error can reduce our ability to estimate rates and timescales accurately and precisely. We investigated the impact of sample-dating uncertainties on the estimation of evolutionary timescale parameters using the software BEAST. Our analyses involved 11 published data sets and focused on estimates of substitution rate and root age. We show that, provided that samples have been accurately dated and have a broad temporal span, it might be unnecessary to account for sample-dating uncertainty in Bayesian phylogenetic analyses of ancient DNA. We also investigated the sample size and temporal span of the ancient DNA sequences needed to estimate phylogenetic timescales reliably. Our results show that the range of sample ages plays a crucial role in determining the quality of the results but that accurate and precise phylogenetic estimates of timescales can be made even with only a few ancient sequences. These findings have important practical consequences for studies of molecular rates, timescales, and population dynamics.
Dissociative recombination of H
3
+
: 10 years in retrospect
Authors: Larsson Mats 
Published: October 2012

The dissociative recombination of

has been an intriguing problem for more than half a century. The early experiments on

during the first 20 years were carried out without mass analysis in decaying plasma afterglows, and thus the measured rates pertained to an uncontrolled mixture of

and impurity ions. When mass analysis was used, the rate coefficient was determined to be an uneventful value of about 10
−7
cm
3
s
−1
, a very common rate coefficient for many molecular ions. But this was not the end of the story, not even the beginning of the end; it marked only the end of the beginning. The story I will tell in this article started about 10 years ago, when the dissociative recombination of

was approaching its deepest crisis. Today, owing to an extensive experimental and theoretical effort, the state of affairs has reached a historically unique level of harmony, although there still remains many things to sort out.
To be or not to be: the early history of H
3
and H
3
+
Authors: Kragh Helge 
Published: October 2012

Triatomic hydrogen became a major research area only after 1980, but its history goes back to J. J. Thomson’s discovery in 1911. In fact, the possible existence of H
3
was suggested as early as 1895. This paper outlines the history of H
3
and

up to the mid-1930s, when chemists and physicists ceased to believe in the existence of the H
3
molecule. In the intervening years, there was a great deal of interest in ‘active hydrogen’ and also in the configuration of H
3
, which was examined by Bohr in 1919. While H
3
was abandoned,

was not. Although the properties of

were largely unknown, the existence of the ion was firmly established, and its structure studied by means of the new methods of quantum chemistry.
Aging leads to a programmed loss of brown adipocytes in murine subcutaneous white adipose tissue
Authors: Rogers Nicole H. , Landa Alejandro , Park Seongjoon , Smith Roy G. 
Published: October 2012

SummaryInsulin sensitivity deteriorates with age, but mechanisms remain unclear. Age‐related changes in the function of subcutaneous white adipose tissue (sWAT) are less characterized than those in visceral WAT. We hypothesized that metabolic alterations in sWAT, which in contrast to epididymal WAT, harbors a subpopulation of energy‐dissipating UCP1+ brown adipocytes, promote age‐dependent progression toward insulin resistance. Indeed, we show that a predominant consequence of aging in murine sWAT is loss of ‘browning’. sWAT from young mice is histologically similar to brown adipose tissue (multilocular, UCP1+), but becomes morphologically white by 12 months of age. Correspondingly, sWAT expression of ucp1 precipitously declines (~300‐fold) between 3 and 12 months. Loss continues into old age (24 months) and is inversely correlated with the development of insulin resistance. Additional age‐dependent changes in sWAT include lower expression of adbr3 and higher expression of maoa, suggesting reduced local adrenergic tone as a potential mechanism. Indeed, treatment with a β3‐adrenergic agonist to compensate for reduced tone rescues the aged sWAT phenotype. Age‐related changes in sWAT are not explained by the differences in body weight; mice subjected to 40% caloric restriction for 12 months are of body weight similar to 3‐month‐old ad lib fed mice, but display sWAT resembling that of age‐matched ad lib fed mice (devoid of brown adipose‐like morphology). Overall, findings identify the loss of ‘browning’ in sWAT as a new aging phenomenon and provide insight into the pathogenesis of age‐associated metabolic disease by revealing novel molecular changes tied to systemic metabolic dysfunction.
Estrogen Receptor α Antagonists Mediate Changes in CCL20 and CXCL1 Secretions in the Murine Female Reproductive Tract
Authors: Hickey Danica K. , Fahey John V. , Wira Charles R. 
Published: October 2012

ProblemEstradiol regulates chemokine secretion from uterine epithelial cells, but little is known about estradiol regulation in vivo or the role of estrogen receptors (ERs).MethodCCL20 and CXCL1 present in reproductive washes following treatment with selective estrogen receptor modulators (SERMs) were compared with that during estrous and following estradiol‐treated ovariectomized BALB/c mice. Cellular regulation was determined using isolated vaginal and uterine epithelial/stromal cells in vitro.ResultsUterine and vaginal chemokine secretion is cyclically regulated with CCL20 at low levels but CXCL1 at high levels during high estradiol, generally mimicking estradiol effect in vivo. ERα but not ERβ regulated CCL20/CXCL1 secretion by uterine epithelial cells in vitro and vaginal CCL20 in vivo. Estradiol/SERMs failed to alter uterine CCL20 secretion in ovariectomized mice. Diminished uterine epithelial ERα staining following ovariectomy corresponded with estradiol unresponsiveness of uterine tissue.ConclusionEstrogen receptors α regulates CCL20/CXCL1 secretion in the female reproductive tract, and ERα antagonists directly oppose the regulation by estradiol. Understanding ER‐mediated antimicrobial chemokine expression is important to elucidate cyclic susceptibility to sexually transmitted pathogens.
Cigarette smoking and impulsivity in bipolar disorder
Authors: Heffner Jaimee L , Fleck David E , DelBello Melissa P , Adler Caleb M , Strakowski Stephen M 
Published: October 2012

Heffner JL, Fleck DE, DelBello MP, Adler CM, Strakowski SM. Cigarette smoking and impulsivity in bipolar disorder. Bipolar Disord 2012: 14: 735–742. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S.Objectives:  There is a high prevalence of smoking among individuals with bipolar disorder, yet there have been few efforts to identify potential contributing factors as a means of improving prevention and treatment approaches. The goal of this study was to examine the association between impulsivity and the initiation or maintenance of smoking in bipolar disorder.Methods:  Participants comprised 97 adolescents and adults, ages 16–50, with bipolar I disorder who were experiencing a mixed or manic episode at the time of study enrollment. Participants completed the Barratt Impulsiveness Scale‐11 (BIS‐11) as a self‐report indicator of trait impulsivity, and the Logan Stop‐Signal Task (SST), Delayed Reward Task (DRT), and Degraded Stimulus Continuous Performance Task (DSCPT) as behavioral measures of impulsivity.Results:  Current smokers (34%) and former smokers (23%) generally reported higher trait impulsivity on the BIS‐11 than never smokers (43%), with minimal evidence for differences among the two ever‐smoking groups. No differences in impulsivity by smoking status emerged on the behavioral measures.Conclusions:  Trait impulsivity is associated with the initiation, but not necessarily the maintenance, of cigarette smoking in adolescents and adults with bipolar disorder. Our findings provide no evidence that smoking is associated with impulsive responding on cognitive tasks during a symptomatic period during which impulsivity is elevated.
Phase I trial of OTS11101, an anti‐angiogenic vaccine targeting vascular endothelial growth factor receptor 1 in solid tumor
Authors: Hayashi Hidetoshi , Kurata Takayasu , Fujisaka Yasuhito , Kawakami Hisato , Tanaka Kaoru , Okabe Takafumi , Takeda Masayuki , Satoh Taroh , Yoshida Koji , Tsunoda Takuya , Arao Tokuzo , Nishio Kazuto , Nakagawa Kazuhiko 
Published: October 2012

OTS11101 is a novel peptide vaccine that acts as an angiogenesis inhibitor by inducing cytotoxic T lymphocyte (CTL) cells that specifically target vascular endothelial cells expressing vascular endothelial growth factor (VEGF) receptor 1. We conducted a phase I study to evaluate the safety, tolerability, maximum tolerated dose, and pharmacodynamic biomarker status of this vaccine. Nine patients with advanced solid tumors received 1.0, 2.0, or 3.0 mg of OTS11101 subcutaneously, once a week in a 28‐day cycle. Three patients experienced grade 1 injection site reactions, which were the most frequent adverse events. Grade 2 proteinuria and hypertension each occurred in one patient. As other toxicities were generally mild, the maximum tolerated dose was not reached. Furthermore, we explored the induction of specific activated CTLs, and biomarkers related to angiogenesis. A pharmacodynamics study revealed that induction of specific CTLs was observed for a dose of 2.0 and 3.0 mg. The serum concentrations of soluble VEGF receptor 1 and 2 after vaccination increased significantly compared with baseline. A microarray was performed to give a comprehensive analysis of gene expression, suggesting that OTS11101 vaccination resulted in T cell activation in a clinical setting. In conclusion, OTS11101 was well tolerated in patients up to 3.0 mg once weekly and our biomarker analysis suggested that this anti‐angiogenesis vaccine is biologically active. (Cancer Sci 2013; 104: 98–104)
Segmental allergen challenge enhances chitinase activity and levels of CCL18 in mild atopic asthma
Authors: Gavala M. L. , Kelly E. A. B. , Esnault S. , Kukreja S. , Evans M. D. , Bertics P. J. , Chupp G. L. , Jarjour N. N. 
Published: October 2012

SummaryBackgroundAllergic airway inflammation contributes to the airway remodelling that has been linked to increased obstruction and morbidity in asthma. However, the mechanisms by which allergens contribute to airway remodelling in humans are not fully established. CCL18, chitotriosidase (CHIT1) and YKL‐40 are readily detectable in the lungs and contribute to remodelling in other fibrotic diseases, but their involvement in allergic asthma is unclear.ObjectiveWe hypothesized that CCL18, YKL‐40 and CHIT1 bioactivity are enhanced in allergic asthma subjects after segmental allergen challenge and are related to increased pro‐fibrotic and Th2‐associated mediators in the lungs.MethodsLevels of CCL18 and YKL‐40 protein and chitotriosidase (CHIT1) bioactivity in bronchoalveolar lavage (BAL) fluid, as well as CCL18, YKL‐40 and CHIT1 mRNA levels in BAL cells were evaluated in patients with asthma at baseline and 48 h after segmental allergen challenge. We also examined the correlation between CCL18 and YKL‐40 levels and CHIT1 activity with the levels of other pro‐fibrotic factors and chemokines previously shown to be up‐regulated after allergen challenge.ResultsChitotriosidase activity and YKL‐40 and CCL18 levels were elevated after segmental allergen challenge and these levels correlated with those of other pro‐fibrotic factors, T cell chemokines, and inflammatory cells after allergen challenge. CCL18 and YKL‐40 mRNA levels also increased in BAL cells after allergen challenge.Conclusions and Clinical RelevanceOur results suggest that CCL18 and YKL‐40 levels and CHIT1 activity are enhanced in allergic airway inflammation and thus may contribute to airway remodelling in asthma.
Population structure of Chrysoporthe austroafricana in southern Africa determined using Vegetative Compatibility Groups (VCGs)
Authors: Vermeulen M. , Gryzenhout M. , Wingfield M. J. , Roux J. 
Published: October 2012

SummaryChrysoporthe austroafricana is one of the most damaging pathogens of Eucalyptus trees in southern Africa. It also occurs on non‐native Tibouchina granulosa trees and native Syzygium species. Additional isolates of the pathogen from previously unstudied countries in the region have become available from survey studies. The aim of this study was to use VCGs to consider the diversity in populations of isolates collected in various countries in southern Africa (Malawi, Mozambique, Namibia, South Africa and Zambia) and from different hosts. We also wanted to determine whether there are shared VCGs among these countries and hosts in southern Africa and establish a VCG tester strain database. Results showed a high diversity amongst isolates from different countries and hosts, but suggested little movement of VCGs among countries or hosts based on the available isolates. A total of 108 VCG tester strains were identified for southern Africa.
Plant diversity controls arthropod biomass and temporal stability
Authors: Borer Elizabeth T. , Seabloom Eric W. , Tilman David 
Published: October 2012

AbstractUnderstanding the linkages among species diversity, biomass production and stability underlies effective predictions for conservation, agriculture and fisheries. Although these relationships have been well studied for plants and, to a lesser extent, consumers, relationships among plant and consumer diversity, productivity, and temporal stability remain relatively unexplored. We used structural equation models to examine these relationships in a long‐term experiment manipulating plant diversity and enumerating the arthropod community response. We found remarkably similar strength and direction of interrelationships among diversity, productivity and temporal stability of consumers and plants. Further, our results suggest that the frequently observed relationships between plant and consumer diversity occur primarily via changes in plant production leading to changed consumer production rather than via plant diversity directly controlling consumer diversity. Our results demonstrate that extinction or invasion of plant species can resonate via biomass and energy flux to control diversity, production and stability of both plant and consumer communities.
Human melanoma cells in the rhombencephalon of the chick embryo: a novel model for brain metastasis
Authors: Busch Christian , Krochmann Jelena , Drews Ulrich 
Published: October 2012

AbstractMalignant melanoma has the highest propensity to metastasize to the brain of all primary neoplasms in adults. Here, we describe invasive growth and the development of melanoma metastases from suspensions of human melanoma cells in the brain of the chick embryo. Patient‐derived melanoma cells and established melanoma cell lines were injected into the rhombencephalic brain vesicle of the two‐day‐chick embryo. After 48 and 96 h, tumor formation was studied in serial paraffin sections with melanoma‐specific HMB45 and human‐specific MIB1 proliferation markers. The majority of the cells injected into the embryonic liquor cavity perished. Only melanoma cells in newly formed aggregates or when attached to the dorsal roof plate escaped apoptosis. Local invasion occurred not in the ventral differentiating neural epithelium but only in the roof plate. Although after 48 h melanoma cells invaded the rhombencephalic roof plate profusely at both sides, after 96 h typically one large tumor developed in the midline between roof plate and the dorsal surface epithelium. From the tumor, single cells invaded the mesenchyme and blood vessels. Cell lines with different invasive properties retained their graded invasive behaviour. Maximally invasive cells formed continuous tracks via vessels and along nerve fibres. The central tumor in the roof plate of the chick embryo rhombencephalon resembles a metastatic nodule in the patients with melanoma. Penetration of the roof plate epithelium, tumor formation and invasion of surrounding tissues by single cells can reliably be reproduced. The chick embryo model can be used for molecular studies of early phases of melanoma brain metastasis.
Climate‐driven range retraction of an Arctic freshwater crustacean
Authors: LINDHOLM MARKUS , STORDAL FRODE , MOE S. JANNICKE , HESSEN DAG O. , AASS PER 
Published: October 2012

Summary1. Species responses to global warming are predicted to be manifest as poleward and upward extension of species ranges, whereas cold‐adapted species experience range retractions. We report on recent range retraction of a freshwater crustacean, the Arctic fairy shrimp Branchinecta paludosa (Branchiopoda, Anostraca) from alpine ponds of southern Norway, a southernmost extension of its otherwise arctic range.2. The species was mapped during two separate surveys, in 1970 and 2011. In 1970, it occurred in numerous ponds from the tree line at 900 m altitude to high alpine sites at 1500 m. Re‐sampling of the same ponds 41 years later revealed extinction of populations from ponds along the lowest 200 m of its altitudinal range.3. Reconstruction of summer temperatures for the periods 1965–70 and 2005–10 revealed a thermal increase for the period, corresponding to a c. 200‐m upward shift of the local isotherms. More specifically, the number of warm summer days had doubled in the lowest 200 m of the region, which might be particularly detrimental for the species.4. The extinctions at lower altitudes were not compensated for by corresponding upward colonisations. The range retraction of B. paludosa is possibly associated with oxygen stress and hypoxia, induced by increased water temperatures.