bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasticity and innovation of regulatory mechanisms underlying seed oil content mediated by duplicated genes in the palaeopolyploid soybean
Authors: Zhang Dajian , Zhao Meixia , Li Shuai , Sun Lianjun , Wang Weidong , Cai Chunmei , Dierking Emily C. , Ma Jianxin 
Published: March 2017

SummaryMany plants have undergone whole genome duplication (WGD). However, how regulatory networks underlying a particular trait are reshaped in polyploids has not been experimentally investigated. Here we show that the regulatory pathways modulating seed oil content, which involve WRINKLED1 (WRI1), LEAFY COTYLEDON1 (LEC1), and LEC2 in Arabidopsis, have been modified in the palaeopolyploid soybean. Such modifications include functional reduction of GmWRI1b of the GmWRI1a/GmWRI1b homoeologous pair relevant to WRI1, complementary non‐allelic dosage effects of the GmLEC1a/GmLEC1b homoeologous pair relevant to LEC1, pseudogenization of the singleton GmLEC2 relevant to LEC2, and the rise of the LEC2‐like function of GmABI3b, contrasting to its homoeolog GmABI3a, which maintains the ABSCISIC ACID INSENSITIVE 3 (ABI3)‐like function in modulating seed maturation and dormancy. The function of GmABI3b in modulating seed oil biosynthesis was fulfilled by direct binding to a RY (CATGCA) cis‐regulatory element in the GmWRI1a promoter, which was absent in the GmWRI1b promoter, resulting in reduction of the GmWRI1b expression. Nevertheless, the three regulators each exhibited similar intensities of purifying selection to their respective duplicates since these pairs were formed by a WGD event that is proposed to have occurred approximately 13 million years ago (mya), suggesting that the differentiation in spatiotemporal expression between the duplicated genes is more likely to be the outcome of neutral variation in regulatory sequences. This study thus exemplifies the plasticity, dynamics, and novelty of regulatory networks mediated by WGD.
Exophthalmos due to sterile neutrophilic dermatosis in a dog
Authors: Sharpe Emily K. , Meekins Jessica M. , Bagladi‐Swanson Mary , Rankin Amy J. 
Published: March 2017

AbstractAn 8‐year‐old castrated male Bichon Frise was presented to the Kansas State University Veterinary Health Center for evaluation of unilateral right‐sided exophthalmos, suspected secondary to a retrobulbar abscess. The dog had acutely developed right‐sided periorbital swelling, exophthalmos with pain on retropulsion, as well as multiple cutaneous exudative plaques on the feet and tail base. On ophthalmic examination, the dog also exhibited mild left‐sided exophthalmos with decreased, nonpainful retropulsion. Orbital ultrasound and CT were performed to evaluate the extent of bilateral orbital disease. Incisional biopsies were obtained from the affected right periorbital tissues and skin of the feet, and histopathology revealed severe neutrophilic inflammation of the dermis with no organisms detected. Histologic changes were consistent with sterile neutrophilic dermatosis. The dog achieved clinical remission following treatment with initial immunosuppressive doses of corticosteroids and subsequent long‐term maintenance therapy using oral cyclosporine.
Biogeography of a Novel Ensifer meliloti Clade Associated with the Australian Legume Trigonella suavissima
Authors: Eardly Bertrand , Elia Patrick , Brockwell John , Golemboski Daniel , van Berkum Peter 
Published: March 2017

ABSTRACTHere, we describe a novel clade withinEnsifer melilotiand consider how geographic and ecological isolation contributed to the limited distribution of this group. Members of the genusEnsiferare best known for their ability to form nitrogen-fixing symbioses with forage legumes of three related genera,MedicagoL.,MelilotusMill., andTrigonellaL., which are members of the tribe Trifolieae. These legumes have a natural distribution extending from the Mediterranean Basin through western Asia, where there is an unsurpassed number of species belonging to these genera.Trigonella suavissimaL. is unusual in that it is the only species in the tribe Trifolieae that is native to Australia. We compared the genetic diversity and taxonomic placement of rhizobia nodulatingT. suavissimawith those of members of anEnsiferreference collection. Our goal was to determine if theT. suavissimarhizobial strains, like their plant host, are naturally limited to the Australian continent. We used multilocus sequence analysis to estimate the genetic relatedness of 56T. suavissimasymbionts to 28Ensiferreference strains. Sequence data were partitioned according to the replicons in which the loci are located. The results were used to construct replicon-specific phylogenetic trees. In both the chromosomal and chromid trees, the Australian strains formed a distinct clade withinE. meliloti. The strains also shared few alleles withEnsiferreference strains from other continents. Carbon source utilization assays revealed that the strains are also unusual in their ability to utilize 2-oxoglutarate as a sole carbon source. A strategy was outlined for locating similar strains elsewhere.IMPORTANCEIn this study, we employed a biogeographical approach to investigate the origins of a symbiotic relationship between an Australian legume and its nitrogen-fixing rhizobia. The question of the ancestral origins of these symbionts is based on the observation that the legume host is not closely related to other native Australian legumes. Previous research has shown that the legume hostTrigonella suavissimais instead closely related to legumes native to the Mediterranean Basin and western Asia, suggesting that it may have been introduced in Australia from those regions. This led to the question of whether its rhizobia may have been introduced as well. In this study, we were unable to find persuasive evidence supporting this hypothesis. Instead, our results suggest either that theT. suavissimarhizobia are native to Australia or that our methods for locating their close relatives elsewhere are inadequate. A strategy to investigate the latter alternative is proposed.
Obesity paradox and mortality in adults with and without incident type 2 diabetes: a matched population-level cohort study
Authors: Badrick Ellena , Sperrin Matthew , Buchan Iain E , Renehan Andrew G 
Published: March 2017

ObjectiveAmong adults with type 2 diabetes (T2D), several (but not all) studies show that being overweight (body mass index (BMI): 25.0–29.9 kg/m2) or obese I (BMI: 30.0–34.9 kg/m2) near the time of diagnosis, is unexpectedly associated with reduced all-cause mortality compared with normal weight—the obesity paradox. We addressed whether this observation is causal (eg, a true protective effect); due to confounding (including effect modification); or due to selection (‘collider’) bias.Research design and methodsWe performed a matched population-level cohort study using primary care records from Salford, UK (1995–2012) in 10 464 patients with incident T2D paired (1:3) with 31 020 individuals who never developed T2D. We estimated HRs for associations of BMI with all-cause mortality using Cox models, stratified by smoking status.ResultsMedian follow-up was 8.7 years. For never smokers, the hazard of all-cause mortality increased from 25 kg/m2, in a linear manner, with increasing BMI in the T2D cohort (HR per 5 kg/m2: 1.23, ptrend<0.001) and in the non-diabetes cohort (HR per 5 kg/m2: 1.34, ptrend<0.001). In contrast, among ever smokers, BMI-mortality relationships were U-shaped in the T2D and non-diabetes cohorts. Evidence of the obesity paradox in ever smokers, with and without T2D, argued against a selection bias, but supported a contribution of effect modification by smoking (pinteraction=0.009). Results were stable to various sensitivity analyses.ConclusionsIn this cohort, the obesity paradox is mainly explained by smoking as an effect modifier. These findings indicate that the obesity paradox does not challenge standard weight management recommendations among T2D patients.
Optimizing Therapeutic Effect of Aurora B Inhibition in Acute Myeloid Leukemia with AZD2811 Nanoparticles
Authors: Floc'h Nicolas , Ashton Susan , Taylor Paula , Trueman Dawn , Harris Emily , Odedra Rajesh , Maratea Kim , Derbyshire Nicola , Caddy Jacqueline , Jacobs Vivien N. , Hattersley Maureen , Wen Shenghua , Curtis Nicola J. , Pilling James E. , Pease Elizabeth J. , Barry Simon T. 
Published: March 2017

Abstract
Barasertib (AZD1152), a highly potent and selective aurora kinase B inhibitor, gave promising clinical activity in elderly acute myeloid leukemia (AML) patients. However, clinical utility was limited by the requirement for a 7-day infusion. Here we assessed the potential of a nanoparticle formulation of the selective Aurora kinase B inhibitor AZD2811 (formerly known as AZD1152-hQPA) in preclinical models of AML. When administered to HL-60 tumor xenografts at a single dose between 25 and 98.7 mg/kg, AZD2811 nanoparticle treatment delivered profound inhibition of tumor growth, exceeding the activity of AZD1152. The improved antitumor activity was associated with increased phospho-histone H3 inhibition, polyploidy, and tumor cell apoptosis. Moreover, AZD2811 nanoparticles increased antitumor activity when combined with cytosine arabinoside. By modifying dose of AZD2811 nanoparticle, therapeutic benefit in a range of preclinical models was further optimized. At high-dose, antitumor activity was seen in a range of models including the MOLM-13 disseminated model. At these higher doses, a transient reduction in bone marrow cellularity was observed demonstrating the potential for the formulation to target residual disease in the bone marrow, a key consideration when treating AML. Collectively, these data establish that AZD2811 nanoparticles have activity in preclinical models of AML. Targeting Aurora B kinase with AZD2811 nanoparticles is a novel approach to deliver a cell-cycle inhibitor in AML, and have potential to improve on the clinical activity seen with cell-cycle agents in this disease. Mol Cancer Ther; 16(6); 1031–40. ©2017 AACR.
Direct Comparison of 4 Very Early Rule-Out Strategies for Acute Myocardial Infarction Using High-Sensitivity Cardiac Troponin I
Authors: Boeddinghaus Jasper , Nestelberger Thomas , Twerenbold Raphael , Wildi Karin , Badertscher Patrick , Cupa Janosch , Bürge Tobias , Mächler Patrick , Corbière Sydney , Grimm Karin , Giménez Maria Rubini , Puelacher Christian , Shrestha Samyut , Flores Widmer Dayana , Fuhrmann Jakob , Hillinger Petra , Sabti Zaid , Honegger Ursina , Schaerli Nicolas , Kozhuharov Nikola , Rentsch Katharina , Miró Òscar , López Beatriz , Martin-Sanchez F. Javier , Rodriguez-Adrada Esther , Morawiec Beata , Kawecki Damian , Ganovská Eva , Parenica Jiri , Lohrmann Jens , Kloos Wanda , Buser Andreas , Geigy Nicolas , Keller Dagmar I. , Osswald Stefan , Reichlin Tobias , Mueller Christian 
Published: March 2017

Background:
Four strategies for very early rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I (hs-cTnI) have been identified. It remains unclear which strategy is most attractive for clinical application.

Methods:
We prospectively enrolled unselected patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction. The final diagnosis was adjudicated by 2 independent cardiologists. Hs-cTnI levels were measured at presentation and after 1 hour in a blinded fashion. We directly compared all 4 hs-cTnI–based rule-out strategies: limit of detection (LOD, hs-cTnI<2 ng/L), single cutoff (hs-cTnI<5 ng/L), 1-hour algorithm (hs-cTnI<5 ng/L and 1-hour change<2 ng/L), and the 0/1-hour algorithm recommended in the European Society of Cardiology guideline combining LOD and 1-hour algorithm.

Results:

Among 2828 enrolled patients, acute myocardial infarction was the final diagnosis in 451 (16%) patients. The LOD approach ruled out 453 patients (16%) with a sensitivity of 100% (95% confidence interval [CI], 99.2%–100%), the single cutoff 1516 patients (54%) with a sensitivity of 97.1% (95% CI, 95.1%–98.3%), the 1-hour algorithm 1459 patients (52%) with a sensitivity of 98.4% (95% CI, 96.8%–99.2%), and the 0/1-hour algorithm 1463 patients (52%) with a sensitivity of 98.4% (95% CI, 96.8%–99.2%). Predefined subgroup analysis in early presenters (≤2 hours) revealed significantly lower sensitivity (94.2%, interaction
P
=0.03) of the single cutoff, but not the other strategies. Two-year survival was 100% with LOD and 98.1% with the other strategies (
P
<0.01 for LOD versus each of the other strategies).

Conclusions:
All 4 rule-out strategies balance effectiveness and safety equally well. The single cutoff should not be applied in early presenters, whereas the 3 other strategies seem to perform well in this challenging subgroup.

Clinical Trial Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00470587.
Robust Generation of Quiescent Porcine Valvular Interstitial Cell Cultures
Authors: Porras Ana M. , van Engeland Nicole C. A. , Marchbanks Evelyn , McCormack Ann , Bouten Carlijn V. C. , Yacoub Magdi H. , Latif Najma , Masters Kristyn S. 
Published: March 2017

Background

Valvular interstitial cells (
VIC
s) in the healthy aortic valve leaflet exhibit a quiescent phenotype, with <5% of
VIC
s exhibiting an activated phenotype. Yet, in vitro culture of
VIC
s on tissue culture polystyrene surfaces in standard growth medium results in rapid transformation to an activated phenotype in >90% of cells. The inability to preserve a healthy
VIC
phenotype during in vitro studies has hampered the elucidation of mechanisms involved in calcific aortic valve disease. This study describes the generation of quiescent populations of porcine
VIC
s in 2‐dimensional in vitro culture and their utility in studying valve pathobiology.

Methods and Results

Within 4 days of isolation from fresh porcine hearts,
VIC
s cultured in standard growth conditions were predominantly myofibroblastic (activated
VIC
s). This myofibroblastic phenotype was partially reversed within 4 days, and fully reversed within 9 days, following application of a combination of a fibroblast media formulation with culture on collagen coatings. Specifically, culture in this combination significantly reduced several markers of
VIC
activation, including proliferation, apoptosis, α‐smooth muscle actin expression, and matrix production, relative to standard growth conditions. Moreover,
VIC
s raised in a fibroblast media formulation with culture on collagen coatings exhibited dramatically increased sensitivity to treatment with transforming growth factor β1, a known pathological stimulus, compared with
VIC
s raised in either standard culture or medium with a fibroblast media formulation.

Conclusions

The approach using a fibroblast media formulation with culture on collagen coatings generates quiescent
VIC
s that more accurately mimic a healthy
VIC
population and thus has the potential to transform the study of the mechanisms of
VIC
activation and dysfunction involved in the early stages of calcific aortic valve disease.
Edmund Husserl’s Internal Time Consciousness and Modern Times, a Socio-historical Interpretation
Authors: Martineau Jonathan 
Published: March 2017

Abstract
This article revisits Edmund Husserl’s philosophy of time in light of the modern standardisation of time. After assessing Husserl’s innovative analysis of the experience of time and raising key issues pertaining to his derivation of objective time from an originary ‘absolute flux of consciousness’, the article addresses potential relationships between this conception of time and the historically unique experience of time based in the rise of modern clock-time. Drawing on insights from the literature within the sociology of time, the article concludes that Husserl’s conception of time both reproduces and rejects certain features of modern time relations.
The Kurdish Adpositional System: New Perspectives
Authors: Saeed Sameerah Tawfeeq 
Published: March 2017

In this paper I present a basic descriptive overview of the adpositional system in Kurdish supported by illustrative examples from the Sorani dialect. Based on this, two classes are identified: simple and compound. Their morphological, syntactic and semantic properties are discussed in detail, highlighting the distinctions among them. The classification is further supported by the application of an extended P projection as proposed in Saeed (2015) which shares the basic ideas of Svenonius’ (2010) model of spatial P projection providing a new perspective of the role of spatial adpositions. I also examine the categorial status of several bound morphemes which attach to complements of some adpositions and argue that they are clitics associated with specific locative meanings. I propose the existence of PLACE head as a solution to the syntactic status of the locative clitics. I also show that postulating PLACE in the P projection does not clash with the existence of AxPart as they are two distinct elements syntactically and semantically.
Polyurethane coatings used in twentieth century outdoor painted sculptures. Part I: comparative study of various systems by means of ATR-FTIR spectroscopy
Authors: Defeyt Catherine , Langenbacher Julia , Rivenc Rachel 
Published: March 2017

Abstract
Like acrylics and alkyds, polyurethanes (PUs) represent an important class of industrial paints adopted by 20th and 21st artists; primarily by those creating outdoor painted sculptures (OPS). Because PU coatings offer a compromise between aesthetic and performance expectations, unachievable with other types of paints, they are commonly recognized as the most appropriate option for painted artworks intended for an outdoor setting. However, the PU class includes various systems and subgroups possessing very different properties. Through the FTIR-ATR study of 137 PU coating references from the Getty Conservation Institute (GCI) reference collection, this paper outlines the differences and the similarities existing, in terms of the composition, of two package solvent-borne, two package water-borne, one package water-borne and fluoropolymer polyurethanes. The comparison of the obtained FTIR-ATR results allowed determining markers helpful to discriminate specific PU subgroups by means of ATR-FTIR spectroscopy. The goals of this paper are to provide to the conservation professionals a better understanding of the versatility and diversity of PU coatings and to facilitate the identification of the various types initially used by the artists.
The mazy case of Notch and immunoregulatory cells
Authors: Grazioli Paola , Felli Maria Pia , Screpanti Isabella , Campese Antonio Francesco 
Published: March 2017

Abstract
The Notch pathway represents a conserved signal transduction machinery that is straightforward and based on a few elements (ligands, receptors, transducers). However, the existence of multiple control levels of the Notch signaling final outcome makes it strictly context dependent and dose dependent. The function of Notch as a regulator of cell development and differentiation, as well as the aberrant consequences of its modulation, either positive or negative, is well established. In this review, we will discuss our current knowledge about Notch-dependent regulation of generation and function of 2 subsets of the immunoregulatory system, namely regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Then, we will focus on an unforeseen mechanism that may unveil an additional way of Notch to govern the surrounding environment in cancer.
IL-18-dependent NKG2D ligand upregulation on accessory cells is mediated by the PI3K/GSK-3 pathway
Authors: Brandstadter Joshua D , Chen Huiyao , Jiang Songfu , Huang Xiaopei , Yang Yiping 
Published: March 2017

Abstract
NK cells are critical for the control of viral infections. Studies have shown that efficient NK cell activation in response to infection with VV in vivo requires multiple pathways, including the NKG2D pathway. We have recently shown that IL-18 is necessary for the activation of NK cells through upregulation of the NKG2D ligand Rae-1 on DCs upon VV infection. However, how IL-18R signaling on the accessory cells contributes to Rae-1 up-regulation remains to be defined. In this study, we found IL-18-mediated Rae-1 up-regulation in accessory cells, including macrophages and DCs, to be dependent on the MyD88-PI3K pathway. We further found that IL-18 signaling through PI3K led to inhibition of GSK-3, which we found to be a negative regulator of Rae-1. Finally, we demonstrated that in vivo inhibition of GSK-3 could restore Rae-1 up-regulation on IL18R−/− DCs and partially rescue NK-cell activation against VV, leading to improved viral control in IL-18R−/− mice. Our results showed that IL18-dependent Rae-1 up-regulation on accessory cells is mediated by the MyD88-PI3K-GSK3 pathway. These observations may provide important insights into the design of effective NK cell-based immunotherapies.
Blake Schwarzenbach and the anxieties of American punk rock: 1991–present
Authors: Keeble Arin 
Published: March 2017

Abstract
This article argues that Blake Schwarzenbach was a pivotal figure in the evolution of American punk from the early 1990s. Schwarzenbach’s journey as a punk figure has exemplified some of the interconnected ‘anxieties’ of this period relating to punk aesthetics and philosophies, authenticity and ‘selling out’, and the roles of literary cultures. Schwarzenbach’s music, particularly with his first major band Jawbreaker, has also consistently artistically engaged with these anxieties. I argue that Schwarzenbach’s life and work has much to say generally about the radical potential and limitations of American punk, and that it ultimately, and perhaps conversely, embodies the enduring value and appeal of punk as an idea – despite its various iterations, countless sub-genres, and the ever-shifting landscapes of its scenes.
An experimental evaluation of simrank-based similarity search algorithms
Authors: Zhang Zhipeng , Shao Yingxia , Cui Bin , Zhang Ce 
Published: March 2017

Given a graph, SimRank is one of the most popular measures of the similarity between two vertices. We focus on efficiently calculating SimRank, which has been studied intensively over the last decade. This has led to many algorithms that efficiently calculate or approximate SimRank being proposed by researchers. Despite these abundant research efforts, there is no systematic comparison of these algorithms. In this paper, we conduct a study to compare these algorithms to understand their pros and cons.
We first introduce a taxonomy for different algorithms that calculate SimRank and classify each algorithm into one of the following three classes, namely, iterative-, non-iterative-, and random walk-based method. We implement ten algorithms published from 2002 to 2015, and compare them using synthetic and real-world graphs. To ensure the fairness of our study, our implementations use the same data structure and execution framework, and we try our best to optimize each of these algorithms. Our study reveals that none of these algorithms dominates the others: algorithms based on iterative method often have higher accuracy while algorithms based on random walk can be more scalable. One noniterative algorithm has good effectiveness and efficiency on graphs with medium size. Thus, depending on the requirements of different applications, the optimal choice of algorithms differs. This paper provides an empirical guideline for making such choices.