bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-throughput sequencing reveals inbreeding depression in a natural population
Authors: Hoffman Joseph I. , Simpson Fraser , David Patrice , Rijks Jolianne M. , Kuiken Thijs , Thorne Michael A. S. , Lacy Robert C. , Dasmahapatra Kanchon K. 
Published: March 2014

SignificanceMany studies of wild populations reveal links between heterozygosity and fitness, with relatively heterozygous individuals carrying fewer parasites, living longer and being more attractive to mates. These patterns appear ubiquitous and are often highly significant, but heterozygosity usually accounts for very little of the total variation in fitness. However, most studies analyze only around 10 loci, representing a tiny fraction of the genome. We therefore used high-throughput DNA sequencing to estimate genome-wide heterozygosity based on over 10,000 loci and found it to accurately reflect inbreeding. Applied to wild harbor seals, genome-wide heterozygosity explained almost half of the variation in parasite infection. By implication, a greater proportion of fitness variation could be linked to genotype than previously thought.
TGF-β–inducible microRNA-183 silences tumor-associated natural killer cells
Authors: Donatelli Sarah S. , Zhou Jun-Min , Gilvary Danielle L. , Eksioglu Erika A. , Chen Xianghong , Cress W. Douglas , Haura Eric B. , Schabath Matthew B. , Coppola Domenico , Wei Sheng , Djeu Julie Y. 
Published: March 2014

Significance
Natural killer (NK) cells are potent tumor-cell killers, but exposure to transforming growth factor beta-1 (TGF-β) abrogates their effectiveness. Here, we show that this suppression is a result of TGF-β induction of microRNA (miR)-183, which binds and represses DNAX activating protein 12 kDa (DAP12), a signal adaptor for lytic function in NK cells. Because introduction of miR-183 alone or its functional blockade in the presence of TGF-β reduced or restored DAP12 levels in NK cells, we define miR-183 as a key factor in TGF-β–mediated immunosuppression. Since DAP12 is required for signaling through multiple NK cytotoxicity receptors and TGF-β is overexpressed by diverse solid malignancies, our data may have significant importance in the development of NK-based cancer immunotherapies.
Multiple cells-of-origin of mutant K-Ras–induced mouse lung adenocarcinoma
Authors: Sutherland Kate D. , Song Ji-Ying , Kwon Min Chul , Proost Natalie , Zevenhoven John , Berns Anton 
Published: March 2014

Significance
By using a series of cell-type–restricted Adeno-Cre vectors, we show that expression of mutant K-Ras in different cell types in mouse lungs can give rise to adenocarcinomas. Moreover, the cell-of-origin appears to be a determining factor in the histopathological characteristics of the resulting tumor. This is most apparent in the early stages of tumor development, whereby different routes of tumor development are taken when either Clara cells or alveolar type 2 cells serve as the initiating cell type. Both the physical site of onset and the marker expression of the early lesions are distinct. Future studies should reveal whether this affects other tumor characteristics, such as the mutation spectrum and response to treatment.
NRAS isoforms differentially affect downstream pathways, cell growth, and cell transformation
Authors: Eisfeld Ann-Kathrin , Schwind Sebastian , Hoag Kevin W. , Walker Christopher J. , Liyanarachchi Sandya , Patel Ravi , Huang Xiaomeng , Markowitz Joseph , Duan Wenrui , Otterson Gregory A. , Carson William E. , Marcucci Guido , Bloomfield Clara D. , de la Chapelle Albert 
Published: March 2014

Significance
The members of the rat sarcoma (RAS) gene family Kirsten rat sarcoma viral oncogene homolog, Harvey rat sarcoma viral oncogene homolog, and neuroblastoma RAS viral oncogene homolog (NRAS) belong to the most extensively studied oncogenes and are central players in carcinogenesis. Since their discovery approximately 30 y ago, efforts to target their aberrant activation have not led to major breakthroughs. We herein report the discovery of four so far undescribed variants of NRAS that differ in their expression patterns and, strikingly, in their downstream effects. Our results suggest that NRAS should be studied in the context of its variants. In addition, this discovery may open opportunities to develop more efficient anticancer therapies.
Article Commentary: Progress in Addiction Treatment: From One-Size-Fits-All to Medications and Treatment Matching
Authors: Woody George E. 
Published: March 2014

This paper briefly reviews the development of treatment for substance use disorders over the last 100 years from the perspective of the author, who has participated in treatment outcome studies since the mid-1970s. It includes some personal events that contributed to the author's involvement in addiction treatment and research, and describes the gradual evolution of an approach that began with a focus on detoxification and psychosocial treatment to one that involves blending psychosocial treatments with use of Food and Drug Administration (FDA)-approved medications and adding treatments for psychiatric and medical disorders when necessary based on patient assessments. It ends with comments on the gap between what is known and the degree to which existing knowledge is applied, and how the Affordable Care Act holds promise for bridging that gap.
Wrangling Galaxy’s reference data
Authors: Blankenberg Daniel , Johnson James E. ,   The Galaxy Team, Taylor James , Nekrutenko Anton 
Published: March 2014

Abstract
Summary: The Galaxy platform has developed into a fully featured collaborative workbench, with goals of inherently capturing provenance to enable reproducible data analysis, and of making it straightforward to run one’s own server. However, many Galaxy platform tools rely on the presence of reference data, such as alignment indexes, to function efficiently. Until now, the building of this cache of data for Galaxy has been an error-prone manual process lacking reproducibility and provenance.
The Galaxy Data Manager framework is an enhancement that changes the management of Galaxy’s built-in data cache from a manual procedure to an automated graphical user interface (GUI) driven process, which contains the same openness, reproducibility and provenance that is afforded to Galaxy’s analysis tools. Data Manager tools allow the Galaxy administrator to download, create and install additional datasets for any type of reference data in real time.
Availability and implementation: The Galaxy Data Manager framework is implemented in Python and has been integrated as part of the core Galaxy platform. Individual Data Manager tools can be defined locally or installed from a ToolShed, allowing the Galaxy community to define additional Data Manager tools as needed, with full versioning and dependency support.
Contact: dan@bx.psu.edu. or anton@bx.psu.edu
Supplementary information: Supplementary data is available at Bioinformatics online.
Transcription factors controlling development and function of innate lymphoid cells
Authors: Tanriver Yakup , Diefenbach Andreas 
Published: March 2014

Abstract
Innate lymphoid cells (ILCs) are a heterogeneous group of lymphocytes, which play an important role in tissue homeostasis at epithelial surfaces. They are scarce in spleen and lymph nodes, but substantial numbers can be found in the intestinal mucosa even at steady state. There, they represent the first line of defence against invading pathogens and contribute to lymphorganogenesis, tissue repair and, when inappropriately activated, immune pathology. Lineage-specific development, function and maintenance of these cells depend on a restricted set of transcription factors that partially emerged as a result of diversification and selection during vertebrate evolution. The differential expression of transcription factors regulates unique developmental programs, which endow the different ILC subsets with specific effector functions. Despite this division of labour, ILCs are considered to share a common origin, as they all are progeny of the common lymphoid progenitor, rely on the common γ-chain (γc) used by various cytokine receptors and show a developmental requirement for the transcriptional regulator Id2 (inhibitor of DNA binding 2). Here, we review the transcriptional programs required for the development and function of ILCs and give an overview of the evolution of transcription factors and cytokines expressed by ILCs.
The Galactic Centre pulsar population
Authors: Chennamangalam Jayanth , Lorimer D. R. 
Published: March 2014

Abstract
The recent discovery of a magnetar in the Galactic Centre region has allowed Spitler et al. to characterize the interstellar scattering in that direction. They find that the temporal broadening of the pulse profile of the magnetar is substantially less than that predicted by models of the electron density of that region. This raises the question of what the plausible limits for the number of potentially observable pulsars – i.e. the number of pulsars beaming towards the Earth – in the Galactic Centre are. In this Letter, using reasonable assumptions – namely (i) the luminosity function of pulsars in the Galactic Centre region is the same as that in the field, (ii) the region has had a constant pulsar formation rate, (iii) the spin and luminosity evolution of magnetars and pulsars are similar and (iv) the scattering in the direction of the Galactic Centre magnetar is representative of the entire inner parsec – we show that the potentially observable population of pulsars in the inner parsec has a conservative upper limit of ∼200 and that it is premature to conclude that the number of pulsars in this region is small. We also show that the observational results so far are consistent with this number and make predictions for future radio pulsar surveys of the Galactic Centre.
Effect of alternating red and blue light irradiation generated by light emitting diodes on the growth of leaf lettuce
Authors: Shimokawa Akihiro , Tonooka Yuki , Matsumoto Misato , Ara Hironori , Suzuki Hiroshi , Yamauchi Naoki , Shigyo Masayoshi 
Published: March 2014

AbstractBecause global climate change has made agricultural supply unstable, plant factories are expected to be a safe and stable means of food production. As the light source of a plant factory or controlled greenhouse, the light emitting diode (LED) is expected to solve cost problems and promote plant growth efficiently. In this study, we examined the light condition created by using monochromatic red and blue LEDs, to provide both simultaneous and alternating irradiation to leaf lettuce. The result was that simultaneous red and blue irradiation promoted plant growth more effectively than monochromatic and fluorescent light irradiation. Moreover, alternating red and blue light accelerated plant growth significantly even when the total light intensity per day was the same as with simultaneous irradiation. The fresh weight in altering irradiation was almost two times higher than with fluorescent light and about 1.6 times higher than with simultaneous irradiation. The growth-promoting effect of alternating irradiation of red and blue light was observed in different cultivars. From the results of experiments, we offer a novel plant growth method named "Shigyo Method", the core concept of which is the alternating irradiation of red and blue light.
Genomic Repeat Element Analyzer for Mammals (GREAM)
Authors: Chandrashekar Darshan S , Dey Poulami , Acharya Kshitish K 
Published: March 2014

AbstractBackground: Understanding the mechanism behind the transcriptional regulation of genes is still a challenge. Recent findings indicate that the genomic repeat elements (such as LINES, SINES and LTRs) could play an important role in the transcription control. Hence, it is important to further explore the role of genomic repeat elements in the gene expression regulation, and perhaps in other molecular processes. Although many computational tools exists for repeat element analysis, almost all of them simply identify and/or classifying the genomic repeat elements within query sequence(s); none of them facilitate identification of repeat elements that are likely to have a functional significance, particularly in the context of transcriptional regulation.Result: We developed the ‘Genomic Repeat Element Analyzer for Mammals’ (GREAM) to allow gene-centric analysis of genomic repeat elements in 17 mammalian species, and validated it by comparing with some of the existing experimental data. The output provides a categorized list of the specific type of transposons, retro-transposons and other genome-wide repeat elements that are statistically over-represented across specific neighborhood regions of query genes. The position and frequency of these elements, within the specified regions, are displayed as well. The tool also offers queries for position-specific distribution of repeat elements within chromosomes. In addition, GREAM facilitates the analysis of repeat element distribution across the neighborhood of orthologous genes.Conclusion: GREAM allows researchers to short-list the potentially important repeat elements, from the genomic neighborhood of genes, for further experimental analysis. GREAM is free and available for all athttp://resource.ibab.ac.in/GREAM/
High Bacterial Load Predicts Poor Outcomes in Patients with Idiopathic Pulmonary Fibrosis
Authors: Molyneaux P L , Cox M J , Willis-Owen S A G , Russell K E , Mallia P , Russell A M , Johnston S L , Wells A U , Cookson W O C , Maher T M , Moffatt M F 
Published: March 2014

AbstractBackgroundRepetitive alveolar damage and aberrant repair may be important in the development of the fatal condition Idiopathic Pulmonary Fibrosis (IPF). The role played by microorganisms in this cycle is unknown.MethodsWe consecutively enrolled patients diagnosed with IPF according to international criteria together with healthy smokers, non-smokers and subjects with moderate Chronic Obstructive Pulmonary Disease (COPD) as controls. Subjects underwent bronchoalveolar lavage (BAL) from which genomic DNA was isolated. The V3-V5 region of the bacterial 16S rRNA gene was amplified, allowing quantification of bacterial load and identification of communities by 16S rRNA qPCR and pyrosequencing.ResultsOur 65 IPF patients had 3.9×109copies of the 16S rRNA gene per ml of BAL, two-fold more than the 1.8×109copies in 44 sex- and smoking-matched controls (P<0.0001). Baseline BAL bacterial burden predicted Forced Vital Capacity (FVC) decline (P=0.02). Patients in the highest tertile of bacterial burden were at a higher risk of mortality compared to subjects in the lowest tertile (hazard ratio 4.59 (95% CI, 1.05-20);P=0.04).Sequencing yielded 912,883 high quality reads from all subjects. Operational Taxonomic Units (OTUs) representingHaemophilus, Streptococcus, NeisseriaandVeillonellawere 1.5 to 3.5 fold more abundant in cases than controls (P<0.05). Regression analyses indicated that these specific OTUs as well as bacterial burden associated independently with IPF.ConclusionsIPF is characterised by an increased bacterial burden in BAL that predicts decline in lung function and death. Clinical trials of antimicrobial therapy may determine if microbial burden is causal or not in IPF progression.
Ultraviolet-B-Induced Stomatal Closure in Arabidopsis Is Regulated by the UV RESISTANCE LOCUS8 Photoreceptor in a Nitric Oxide-Dependent Mechanism
Authors: Tossi Vanesa , Lamattina Lorenzo , Jenkins Gareth I. , Cassia Raúl O. 
Published: March 2014

Abstract
UV RESISTANCE LOCUS8 (UVR8) signaling involves CONSTITUTIVELY PHOTOMORPHOGENIC1, the ELONGATED HYPOCOTYL5 (HY5) transcription factor, and the closely related HY5 HOMOLOG. Some UV-B responses mediated by UVR8 are also regulated by nitric oxide (NO), a bioactive molecule that orchestrates a wide range of processes in plants. In this study, we investigated the participation of the UVR8 pathway and its interaction with NO in UV-B-induced stomatal movements in Arabidopsis (Arabidopsis thaliana). Stomata in abaxial epidermal strips of Arabidopsis ecotype Landsberg erecta closed in response to increasing UV-B fluence rates, with maximal closure after 3-h exposure to 5.46 μmol m–2 s–1 UV-B. Both hydrogen peroxide (H2O2) and NO increased in response to UV-B, and stomatal closure was maintained by NO up to 24 h after the beginning of exposure. Stomata of plants expressing bacterial NO dioxygenase, which prevents NO accumulation, did not close in response to UV-B, although H2O2 still increased. When the uvr8-1 null mutant was exposed to UV-B, stomata remained open, irrespective of the fluence rate. Neither NO nor H2O2 increased in stomata of the uvr8-1 mutant. However, the NO donor S-nitrosoglutathione induced closure of uvr8-1 stomata to the same extent as in the wild type. Experiments with mutants in UVR8 signaling components implicated CONSTITUTIVELY PHOTOMORPHOGENIC1, HY5, and HY5 HOMOLOG in UV-B-induced stomatal closure. This research provides evidence that the UVR8 pathway regulates stomatal closure by a mechanism involving both H2O2 and NO generation in response to UV-B exposure.
Arabidopsis WRKY45 Transcription Factor Activates PHOSPHATE TRANSPORTER1;1 Expression in Response to Phosphate Starvation
Authors: Wang Hui , Xu Qian , Kong You-Han , Chen Yun , Duan Jun-Ye , Wu Wei-Hua , Chen Yi-Fang 
Published: March 2014

Abstract
The WRKY transcription factor family has more than 70 members in the Arabidopsis (Arabidopsis thaliana) genome, and some of them are involved in plant responses to biotic and abiotic stresses. This study evaluated the role of WRKY45 in regulating phosphate (Pi) uptake in Arabidopsis. WRKY45 was localized in the nucleus and mainly expressed in roots. During Pi starvation, WRKY45 expression was markedly induced, typically in roots. WRKY45 overexpression in Arabidopsis increased Pi content and uptake, while RNA interference suppression of WRKY45 decreased Pi content and uptake. Furthermore, the WRKY45-overexpressing lines were more sensitive to arsenate, the analog of Pi, compared with wild-type seedlings. These results indicate that WRKY45 positively regulates Arabidopsis Pi uptake. Quantitative real-time polymerase chain reaction and β-glucuronidase staining assays showed that PHOSPHATE TRANSPORTER1;1 (PHT1;1) expression was enhanced in the WRKY45-overexpressing lines and slightly repressed in the WRKY45 RNA interference line. Chromatin immunoprecipitation and eclectrophoretic mobility shift assay results indicated that WRKY45 can bind to two W-boxes within the PHT1;1 promoter, confirming the role of WRKY45 in directly up-regulating PHT1;1 expression. The pht1;1 mutant showed decreased Pi content and uptake, and overexpression of PHT1;1 resulted in enhanced Pi content and uptake. Furthermore, the PHT1;1-overexpressing line was much more sensitive to arsenate than WRKY45-overexpressing and wild-type seedlings, indicating that PHT1;1 overexpression can enhance Arabidopsis Pi uptake. Moreover, the enhanced Pi uptake and the increased arsenate sensitivity of the WRKY45-overexpressing line was impaired by pht1;1 (35S:WRKY45-18::pht1;1), demonstrating an epistatic genetic regulation between WRKY45 and PHT1;1. Together, our results demonstrate that WRKY45 is involved in Arabidopsis response to Pi starvation by direct up-regulation of PHT1;1 expression.
Diagnostic challenges in patients with bleeding phenotype and von Willebrand exon 28 polymorphism p.D1472H
Authors: Francis J. C. , Hui S.‐K. , Mahoney D. , Dietrich J. E. , Friedman K. D. , Soundar E. , Srivaths L. V. 
Published: March 2014

SummaryExon 28 polymorphism p.D1472H is associated with significantly lower von Willebrand Ristocetin cofactor activity (VWF:RCoF) to von Willebrand antigen (VWF:Ag) ratio compared to normal, but has been reported as not conferring haemorrhagic risk. The impact of this polymorphism while assessing symptomatic patients for von Willebrand disease (VWD) has not been previously analysed. We retrospectively reviewed charts of children with clinically significant bleeding and abnormal VW panel who underwent VW exon 28 analysis. Twenty‐three of 63 patients studied had p.D1472H. Of these 23 patients, 6 with borderline low VWF:RCo were given provisional diagnosis of VWD type 1 by treating physicians, which could be alternatively explained as due to the effect of p.D1472H. None of the patients with low VWF:RCo, decreased VWF:RCo/VWF:Ag ratio and p.D1472H had VWD type 2M mutations identified. This study illustrates the challenge in diagnosing VWD using ristocetin‐based VW assay in symptomatic patients with p.D1472H.
A dosimetric characterization of a novel linear accelerator collimator
Authors: Thompson C. M. , Weston S. J. , Cosgrove V. C. , Thwaites D. I. 
Published: March 2014

Purpose:The aim of this work is to characterize a new linear accelerator collimator which contains a single pair of sculpted diaphragms mounted orthogonally to a 160 leaf multileaf collimator (MLC). The diaphragms have “thick” regions providing full attenuation and “thin” regions where attenuation is provided by both the leaves and the diaphragm. The leaves are mounted on a dynamic leaf guide allowing rapid leaf motion and leaf travel over 350 mm.Methods:Dosimetric characterization, including assessment of leaf transmission, leaf tip transmission, penumbral width, was performed in a plotting tank. Head scatter factor was measured using a mini‐phantom and the effect of leaf guide position on output was assessed using a water phantom. The tongue and groove effect was assessed using multiple exposures on radiochromic film. Leaf reproducibility was assessed from portal images of multiple abutting fields.Results:The maximum transmission through the multileaf collimator is 0.44% at 6 MV and 0.52% at 10 MV. This reduced to 0.22% and 0.27%, respectively, when the beam passes through the dynamic leaf guide in addition to the MLC. The maximum transmission through the thick part of the diaphragm is 0.32% and 0.36% at 6 and 10 MV. The combination of leaf and diaphragm transmission ranges from 0.08% to 0.010% at 6 MV and 0.10% to 0.14% depending on whether the shielding is through the thick or thin part of the diaphragm. The off‐axis intertip transmission for a zero leaf gap is 2.2% at 6 and 10 MV. The leaf tip penumbra for a 100 × 100 mm field ranges from 5.4 to 4.3 mm at 6 and 10 MV across the full range of leaf motion when measured in the AB direction, which reduces to 4.0–3.4 mm at 6 MV and 4.5–3.8 mm at 10 MV when measured in the GT direction. For a 50 × 50 mm field, the diaphragm penumbra ranges from 4.3 to 3.7 mm at 6 MV and 4.5 to 4.1 mm at 10 MV in the AB direction and 3.7 to 3.2 mm at 6 MV and 4.2 to 3.7 mm when measured in the GT direction. The tongue and groove effect observed from exposure of a radiochromic film to two abutting fields is an underdose of 25%. The head scatter factor at both 6 and 10 MV is similar to that from the MLCi2 collimator to within 0.8%. The uncertainty in the leaf position reproducibility is 0.05 mm (2σ).Conclusions:The Agility collimator is a low leakage, high definition collimator where both the MLC and the sculpted diaphragm have been optimized for dynamic treatments.