bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcription factor WRKY46 modulates the development of Arabidopsis lateral roots in osmotic/salt stress conditions via regulation of ABA signaling and auxin homeostasis
Authors: Ding Zhong Jie , Yan Jing Ying , Li Chun Xiao , Li Gui Xin , Wu Yun Rong , Zheng Shao Jian 
Published: August 2015

SummaryThe development of lateral roots (LR) is known to be severely inhibited by salt or osmotic stress. However, the molecular mechanisms underlying LR development in osmotic/salt stress conditions are poorly understood. Here we show that the gene encoding the WRKY transcription factor WRKY46 (WRKY46) is expressed throughout lateral root primordia (LRP) during early LR development and that expression is subsequently restricted to the stele of the mature LR. In osmotic/salt stress conditions, lack of WRKY46 (in loss‐of‐function wrky46 mutants) significantly reduces, while overexpression of WRKY46 enhances, LR development. We also show that exogenous auxin largely restores LR development in wrky46 mutants, and that the auxin transport inhibitor 2,3,5‐triiodobenzoic acid (TIBA) inhibits LR development in both wild‐type (WT; Col‐0) and in a line overexpressing WRKY46 (OV46). Subsequent analysis of abscisic acid (ABA)‐related mutants indicated that WRKY46 expression is down‐regulated by ABA signaling, and up‐regulated by an ABA‐independent signal induced by osmotic/salt stress. Next, we show that expression of the DR5:GUS auxin response reporter is reduced in roots of wrky46 mutants, and that both wrky46 mutants and OV46 display altered root levels of free indole‐3‐acetic acid (IAA) and IAA conjugates. Subsequent RT‐qPCR and ChIP‐qPCR experiments indicated that WRKY46 directly regulates the expression of ABI4 and of genes regulating auxin conjugation. Finally, analysis of wrky46 abi4 double mutant plants confirms that ABI4 acts downstream of WRKY46. In summary, our results demonstrate that WRKY46 contributes to the feedforward inhibition of osmotic/salt stress‐dependent LR inhibition via regulation of ABA signaling and auxin homeostasis.
Sequencing of 15 622 gene‐bearing BACs clarifies the gene‐dense regions of the barley genome
Authors: Muñoz‐Amatriaín María , Lonardi Stefano , Luo MingCheng , Madishetty Kavitha , Svensson Jan T. , Moscou Matthew J. , Wanamaker Steve , Jiang Tao , Kleinhofs Andris , Muehlbauer Gary J. , Wise Roger P. , Stein Nils , Ma Yaqin , Rodriguez Edmundo , Kudrna Dave , Bhat Prasanna R. , Chao Shiaoman , Condamine Pascal , Heinen Shane , Resnik Josh , Wing Rod , Witt Heather N. , Alpert Matthew , Beccuti Marco , Bozdag Serdar , Cordero Francesca , Mirebrahim Hamid , Ounit Rachid , Wu Yonghui , You Frank , Zheng Jie , Simková Hana , Dolezel Jaroslav , Grimwood Jane , Schmutz Jeremy , Duma Denisa , Altschmied Lothar , Blake Tom , Bregitzer Phil , Cooper Laurel , Dilbirligi Muharrem , Falk Anders , Feiz Leila , Graner Andreas , Gustafson Perry , Hayes Patrick M. , Lemaux Peggy , Mammadov Jafar , Close Timothy J. 
Published: August 2015

SummaryBarley (Hordeum vulgare L.) possesses a large and highly repetitive genome of 5.1 Gb that has hindered the development of a complete sequence. In 2012, the International Barley Sequencing Consortium released a resource integrating whole‐genome shotgun sequences with a physical and genetic framework. However, because only 6278 bacterial artificial chromosome (BACs) in the physical map were sequenced, fine structure was limited. To gain access to the gene‐containing portion of the barley genome at high resolution, we identified and sequenced 15 622 BACs representing the minimal tiling path of 72 052 physical‐mapped gene‐bearing BACs. This generated ~1.7 Gb of genomic sequence containing an estimated 2/3 of all Morex barley genes. Exploration of these sequenced BACs revealed that although distal ends of chromosomes contain most of the gene‐enriched BACs and are characterized by high recombination rates, there are also gene‐dense regions with suppressed recombination. We made use of published map‐anchored sequence data from Aegilops tauschii to develop a synteny viewer between barley and the ancestor of the wheat D‐genome. Except for some notable inversions, there is a high level of collinearity between the two species. The software HarvEST:Barley provides facile access to BAC sequences and their annotations, along with the barley–Ae. tauschii synteny viewer. These BAC sequences constitute a resource to improve the efficiency of marker development, map‐based cloning, and comparative genomics in barley and related crops. Additional knowledge about regions of the barley genome that are gene‐dense but low recombination is particularly relevant.
English in television commercials in Belgium, France, Italy, the Netherlands and Spain
Authors: RAEDTS MARIET , DUPRÉ NATALIE , HENDRICKX JEF , DEBRAUWERE SOPHIE 
Published: August 2015

ABSTRACTThis study investigates and compares the use of English in 1,539 prime time television commercials from five European countries: Belgium, France, Italy, Spain and the Netherlands. Our study contributes to the existing body of research by adding two methodological issues. First, we investigate whether results differ depending on which definition of the term ‘English word’ is used (i.e. a strict or a broad definition). Second, we explore which factor best predicts the occurrence and the amount of English used in European television commercials: the advertised product (i.e. culture‐free or culture‐bound) or the country where the commercial is broadcast.
Complete Genome Sequence of Bacillus megaterium Siphophage Stahl
Authors: Brizendine Ashley M. , Rousseau Simon , Hernandez Adriana C. , Kuty Everett Gabriel F. 
Published: August 2015

ABSTRACT

Stahl is a siphophage active against
Bacillus megaterium
, a Gram-positive bacterium often used as a model system in research and as a protein production strain in industrial applications. Here, we present the complete annotated genome of phage Stahl and describe its major features.
Draft Genome Sequence of Paenibacillus polymyxa Strain Mc5Re-14, an Antagonistic Root Endophyte of
Matricaria chamomilla
Authors: Köberl Martina , White Richard A. , Erschen Sabine , El-Arabi Tarek F. , Jansson Janet K. , Berg Gabriele 
Published: August 2015

ABSTRACT

Paenibacillus polymyxa
strain Mc5Re-14 was isolated from the inner root tissue of
Matricaria chamomilla
(German chamomile). Mc5Re-14 revealed promising
in vitro
antagonistic activity against plant and opportunistic human pathogens. The 6.0-Mb draft genome reveals genes putatively involved in pathogen suppression and direct and indirect plant growth promotion.
Protocol for a randomised controlled trial for Reducing Arthritis Fatigue by clinical Teams (RAFT) using cognitive–behavioural approaches
Authors: Hewlett S , Ambler N , Almeida C , Blair P S , Choy E , Dures E , Hammond A , Hollingworth W , Kirwan J , Plummer Z , Rooke C , Thorn J , Tomkinson K , Pollock J 
Published: August 2015

IntroductionRheumatoid arthritis (RA) fatigue is distressing, leading to unmanageable physical and cognitive exhaustion impacting on health, leisure and work. Group cognitive–behavioural (CB) therapy delivered by a clinical psychologist demonstrated large improvements in fatigue impact. However, few rheumatology teams include a clinical psychologist, therefore, this study aims to examine whether conventional rheumatology teams can reproduce similar results, potentially widening intervention availability.Methods and analysisThis is a multicentre, randomised, controlled trial of a group CB intervention for RA fatigue self-management, delivered by local rheumatology clinical teams. 7 centres will each recruit 4 consecutive cohorts of 10–16 patients with RA (fatigue severity ≥6/10). After consenting, patients will have baseline assessments, then usual care (fatigue self-management booklet, discussed for 5–6 min), then be randomised into control (no action) or intervention arms. The intervention, Reducing Arthritis Fatigue by clinical Teams (RAFT) will be cofacilitated by two local rheumatology clinicians (eg, nurse/occupational therapist), who will have had brief training in CB approaches, a RAFT manual and materials, and delivered an observed practice course. Groups of 5–8 patients will attend 6×2 h sessions (weeks 1–6) and a 1 hr consolidation session (week 14) addressing different self-management topics and behaviours. The primary outcome is fatigue impact (26 weeks); secondary outcomes are fatigue severity, coping and multidimensional impact, quality of life, clinical and mood status (to week 104). Statistical and health economic analyses will follow a predetermined plan to establish whether the intervention is clinically and cost-effective. Effects of teaching CB skills to clinicians will be evaluated qualitatively.Ethics and disseminationApproval was given by an NHS Research Ethics Committee, and participants will provide written informed consent. The copyrighted RAFT package will be freely available. Findings will be submitted to the National Institute for Health and Care Excellence, Clinical Commissioning Groups and all UK rheumatology departments.Trial registration numberISRCTN: 52709998; Protocol v3 09.02.2015.
Connexin 43 expression predicts poor progression-free survival in patients with non-muscle invasive urothelial bladder cancer
Authors: Poyet Cédric , Buser Lorenz , Roudnicky Filip , Detmar Michael , Hermanns Thomas , Mannhard Doris , Höhn Andrej , Rüschoff Jan , Zhong Qing , Sulser Tullio , Moch Holger , Wild Peter J 
Published: August 2015

ObjectivesTo evaluate the protein expression of connexin 43 (Cx43) in primary urothelial bladder cancer and test its association with the histopathological characteristics and clinical outcome.MethodsA tissue microarray containing 348 tissue samples from 174 patients with primary urothelial carcinomas of the bladder was immunohistochemically stained for Cx43. The intensity of staining was semiquantitatively evaluated (score 0, 1+, 2+), and the association with clinicopathological features was assessed. Univariable and multivariable analyses were performed to identify predictors for progression-free survival (PFS).ResultsMembranous Cx43 immunoreactivity was detected in 118 (67.8%) of 174 analysable urothelial carcinomas, of which 31 (17.8%) showed even a strong (score 2+) and mainly homogeneous staining. Strong expression levels of Cx43 (score 2+) were associated with higher tumour grade, multiplicity and increased proliferation (all p<0.05). In the subgroup of patients with stage pTa and pT1 bladder tumours (n=158), strong Cx43 expression (p<0.001), solid growth pattern (p<0.001) and increased Ki-67 proliferation fraction (p<0.05) were significantly associated with shorter PFS in an univariable Cox regression analysis. In multivariable Cox regression models, Cx43 immunoreactivity and histological growth pattern remained highly significant and adverse risk factors for PFS.ConclusionsThe expression levels of Cx43 are frequent in non-muscle invasive bladder cancer (NMIBC), with high expression levels being associated with poor prognosis. Routine assessment of Cx43 expression may improve the identification of high-risk NMIBC.
Fibulin-5 is a tumour suppressor inhibiting cell migration and invasion in ovarian cancer
Authors: Heo Jin Hyung , Song Ji-ye , Jeong Ju-yeong , Kim Gwangil , Kim Tae Heon , Kang Haeyoun , Kwon Ah-young , An Hee Jung 
Published: August 2015

AimsFibulin-5 is an extracellular matrix (ECM) glycoprotein which has a role in the organisation and stabilisation of ECM structures and regulating cell proliferation and tumourigenesis. Here, the expression of fibulin-5 and its functional effects on the migration and invasion of ovarian cancer cells were assessed.MethodsExpression of fibulin-5 was detected in 44 ovarian tumour tissues by qRT-PCR, Western blotting and immunohistochemistry. We performed cell migration and invasion assays, and cell cycle analysis in fibulin-5 transfected SKOV3 (SKOV3-FBLN5) cells and the parental SKOV3 cells. We further examined the expression of three tissue inhibitors of metalloproteinases (TIMPs) and seven matrix metalloproteinases (MMPs) by RT-PCR.ResultsmRNA and protein expression of fibulin-5 were down-regulated (0.05-fold and 0.1-fold) in ovarian carcinomas compared with control tissues (p<0.01 and p=0.022). In wound-healing and invasion assays, significantly fewer SKOV3-FBLN5 cells than SKOV3 control cells migrated and invaded (39.1%, p=0.046 and 70%, p=0.03, respectively), which was reversed by siRNA-treatment. Overexpression of fibulin-5 induced G2/M arrest and increased cyclin B1, CDC2 and CDC25C. Expression of TIMP-2 (0.56-fold), MMP-3 (0.43-fold) and MMP-13 (0.18-fold) was lower and MMP-9 expression (2.20-fold) was higher in SKOV3-FBLN5 cells than in control cells.ConclusionsFibulin-5 is significantly down-regulated in ovarian carcinoma and acts as a tumour suppressor by inhibiting the migration and invasion of ovarian cancer cells.
Heparanase Enhances Tumor Growth and Chemoresistance by Promoting Autophagy
Authors: Shteingauz Anna , Boyango Ilanit , Naroditsky Inna , Hammond Edward , Gruber Maayan , Doweck Ilana , Ilan Neta , Vlodavsky Israel 
Published: August 2015

Abstract
Heparanase is the only enzyme in mammals capable of cleaving heparan sulfate, an activity implicated in tumor inflammation, angiogenesis, and metastasis. Heparanase is secreted as a latent enzyme that is internalized and subjected to proteolytic processing and activation in lysosomes. Its role under normal conditions has yet to be understood. Here, we provide evidence that heparanase resides within autophagosomes, where studies in heparanase-deficient or transgenic mice established its contributions to autophagy. The protumorigenic properties of heparanase were found to be mediated, in part, by its proautophagic function, as demonstrated in tumor xenograft models of human cancer and through use of inhibitors of the lysosome (chloroquine) and heparanase (PG545), both alone and in combination. Notably, heparanase-overexpressing cells were more resistant to stress and chemotherapy in a manner associated with increased autophagy, effects that were reversed by chloroquine treatment. Collectively, our results establish a role for heparanase in modulating autophagy in normal and malignant cells, thereby conferring growth advantages under stress as well as resistance to chemotherapy. Cancer Res; 75(18); 3946–57. ©2015 AACR.
Association Between Comorbidities and Outcomes in Heart Failure Patients With and Without an Implantable Cardioverter‐Defibrillator for Primary Prevention
Authors: Khazanie Prateeti , Hellkamp Anne S. , Fonarow Gregg C. , Bhatt Deepak L. , Masoudi Frederick A. , Anstrom Kevin J. , Heidenreich Paul A. , Yancy Clyde W. , Curtis Lesley H. , Hernandez Adrian F. , Peterson Eric D. , Al‐Khatib Sana M. 
Published: August 2015

Background

Implantable cardioverter‐defibrillator (
ICD
) therapy is associated with improved outcomes in patients with heart failure (
HF
), but whether this association holds among older patients with multiple comorbid illnesses and worse
HF
burden remains unclear.

Methods and Results

Using the National Cardiovascular Data Registry's
ICD
Registry and the Get With The Guidelines–Heart Failure (
GWTG
‐
HF
) registry linked with Medicare claims, we examined outcomes associated with primary‐prevention
ICD
versus no
ICD
among
HF
patients aged ≥65 years in clinical practice. We included patients with an ejection fraction ≤35% who received (
ICD
Registry) and who did not receive (
GWTG
‐
HF
) an
ICD
. Compared with patients with an
ICD
, patients in the non‐
ICD
group were older and more likely to be female and white. In matched cohorts, the 3‐year adjusted mortality rate was lower in the
ICD
group versus the non‐
ICD
group (46.7% versus 55.8%; adjusted hazard ratio [
HR
] 0.76; 95%
CI
0.69 to 0.83). There was no associated difference in all‐cause readmission (
HR
0.99; 95%
CI
0.92 to 1.08) but a lower risk of
HF
readmission (
HR
0.88; 95%
CI
0.80 to 0.97). When compared with no ICD,
ICD
s were also associated with better survival in patients with ≤3 comorbidities (
HR
0.77; 95%
CI
0.69 to 0.87) and >3 comorbidities (
HR
0.77; 95%
CI
0.64 to 0.93) and in patients with no hospitalization for
HF
(
HR
0.75; 95%
CI
0.65 to 0.86) and at least 1 prior
HF
hospitalization (
HR
0.69; 95%
CI
0.58 to 0.82). In subgroup analyses, there were no interactions between
ICD
and mortality risk for comorbidity burden (
P
=0.95) and for prior
HF
hospitalization (
P
=0.46).

Conclusion

Among older
HF
patients,
ICD
s for primary prevention were associated with lower risk of mortality even among those with high comorbid illness burden and prior
HF
hospitalization.
Remote Ischemic Conditioning Alters Methylation and Expression of Cell Cycle Genes in Aneurysmal Subarachnoid Hemorrhage
Authors: Nikkola Elina , Laiwalla Azim , Ko Arthur , Alvarez Marcus , Connolly Mark , Ooi Yinn Cher , Hsu William , Bui Alex , Pajukanta Päivi , Gonzalez Nestor R. 
Published: August 2015

Background and Purpose—
Remote ischemic conditioning (RIC) is a phenomenon in which short periods of nonfatal ischemia in 1 tissue confers protection to distant tissues. Here we performed a longitudinal human pilot study in patients with aneurysmal subarachnoid hemorrhage undergoing RIC by limb ischemia to compare changes in DNA methylation and transcriptome profiles before and after RIC.

Methods—
Thirteen patients underwent 4 RIC sessions over 2 to 12 days after rupture of an intracranial aneurysm. We analyzed whole blood transcriptomes using RNA sequencing and genome-wide DNA methylomes using reduced representation bisulfite sequencing, both before and after RIC. We tested differential expression and differential methylation using an intraindividual paired study design and then overlapped the differential expression and differential methylation results for analyses of functional categories and protein–protein interactions.

Results—

We observed 164 differential expression genes and 3493 differential methylation CpG sites after RIC, of which 204 CpG sites overlapped with 103 genes, enriched for pathways of cell cycle (
P
<3.8×10
−4
) and inflammatory responses (
P
<1.4×10
−4
). The cell cycle pathway genes form a significant protein–protein interaction network of tightly coexpressed genes (
P
<0.00001).

Conclusions—
Gene expression and DNA methylation changes in aneurysmal subarachnoid hemorrhage patients undergoing RIC are involved in coordinated cell cycle and inflammatory responses.
Do Patient Characteristics Explain the Differences in Outcome Between Medically Treated Patients in SAMMPRIS and WASID?
Authors: Chaturvedi Seemant , Turan Tanya N. , Lynn Michael J. , Derdeyn Colin P. , Fiorella David , Janis L. Scott , Chimowitz Marc I. 
Published: August 2015

Background and Purpose—
The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) medical group had a much lower primary end point rate than predicted from the preceding Warfarin Aspirin Symptomatic Intracranial Disease (WASID) trial. This result has been attributed to the aggressive medical therapy used in SAMMPRIS, but an alternative hypothesis is that SAMMPRIS patients were at lower risk. We undertook analyses to evaluate these competing hypotheses.

Methods—
Using proportional hazards regression, we compared the SAMMPRIS primary end point between SAMMPRIS medical patients and WASID patients meeting the same qualifying criteria adjusted for confounding baseline characteristics.

Results—

The unadjusted comparison of the SAMMPRIS primary end point showed a significantly higher risk for WASID patients (
P
=0.009, logrank test) with 12 month Kaplan–Meier estimates of 21.9% in WASID and 12.6% in SAMMPRIS and hazard ratio 1.9 (95% confidence interval =1.2–3.0). The analyses identified the following confounding factors that varied between the studies and that conferred a higher risk: lack of statin use at enrollment (hazard ratio =1.8, 95% confidence interval =1.1–2.9,
P
=0.027) that was more prevalent among WASID patients (39% versus 14%,
P
<0.0001) and prior infarcts in the territory of the symptomatic vessel (hazard ratio =1.8, 95% confidence interval =1.1–2.9,
P
=0.023) that was more prevalent among SAMMPRIS patients (34% versus 22%,
P
=0.015).The hazard ratio for WASID versus SAMMPRIS adjusted for these 2 characteristics was 1.9 (95% confidence interval =1.1–3.2).

Conclusions—
After adjustment for confounding baseline characteristics, WASID patients had an almost 2-fold higher risk of the SAMMPRIS primary end point, which supports the hypothesis that the lower rate of the primary end point in the medical arm of SAMMPRIS compared with WASID patients was as a result of the aggressive medical management used in SAMMPRIS.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00576693.
Patients With Ischemic Stroke and Incident Atrial Fibrillation
Authors: Fauchier Laurent , Clementy Nicolas , Pelade Christele , Collignon Cecile , Nicolle Emmanuelle , Lip Gregory Y.H. 
Published: August 2015

Background and Purpose—
A substantial part of ischemic strokes is attributed to atrial fibrillation (AF). We hypothesized that patients with ischemic stroke without prior diagnosed AF were at higher risk of having a subsequent diagnosis of AF, and this was associated with multiple risk factors.

Methods—
This French longitudinal cohort study was based on the national database covering hospital care from 2008 to 2012 for the entire population.

Results—

Of 65 807 patients with ischemic stroke in 2009, 48 992 did not have AF at baseline. A total of 4828 of these patients were diagnosed as having AF during a follow-up of 15±15 months (incidence rate 7.9 per 100 person-years). By comparison, the yearly rate of new-onset AF for the 826 416 patients with a cardiac hospitalization was 5.9%. CHADS
2
(congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack) and CHA
2
DS
2
-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack [doubled], vascular disease, age 65–75 years, and sex category [female]) scores were both associated with the risk of new-onset AF during follow-up (CHADS
2
: hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.66–1.75; CHA
2
DS
2
-VASc: HR 1.45, 95% CI 1.42–1.48). The c statistics were 0.700 (95% CI 0.696–0.706) for CHADS
2
and 0.706 (95% CI 0.702–0.710) with CHA
2
DS
2
-VASc (
P
=0.003 for comparison of the 2 scores). Independent predictors of subsequent diagnosis of AF were age 65 to 74 years (HR 2.29, 95% CI 2.06–2.54), age ≥75 years (HR 3.31, 95% CI 3.02–3.64), hypertension (HR 1.22, 95% CI 1.13–1.32), heart failure (HR 2.56, 95% CI 2.41–2.72), and vascular disease (HR 1.10, 95% CI 1.04–1.17).

Conclusions—

Ischemic stroke was associated with a substantially increased risk of incident AF, particularly among individuals with higher CHADS
2
or CHA
2
DS
2
-VASc scores. These risk scores seem to be simple tools for identifying patients at higher risk of incident AF after ischemic stroke.