bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular plant one‐zinc‐finger protein 1/2 transcription factors regulate abiotic and biotic stress responses in Arabidopsis
Authors: Nakai Yusuke , Nakahira Yoichi , Sumida Hiroki , Takebayashi Kosuke , Nagasawa Yumiko , Yamasaki Kanako , Akiyama Masako , Ohme‐Takagi Masaru , Fujiwara Sumire , Shiina Takashi , Mitsuda Nobutaka , Fukusaki Eiichiro , Kubo Yasuyuki , Sato Masa H. 
Published: November 2012

SummaryPlants adapt to abiotic and biotic stresses by activating abscisic acid‐mediated (ABA) abiotic stress‐responsive and salicylic acid‐(SA) or jasmonic acid‐mediated (JA) biotic stress‐responsive pathways, respectively. Although the abiotic stress‐responsive pathway interacts antagonistically with the biotic stress‐responsive pathways, the mechanisms that regulate these pathways remain largely unknown. In this study, we provide insight into the function of vascular plant one‐zinc‐finger proteins (VOZs) that modulate various stress responses in Arabidopsis. The expression of many stress‐responsive genes was changed in the voz1voz2 double mutant under normal growth conditions. Consistent with altered stress‐responsive gene expression, freezing‐ and drought‐stress tolerances were increased in the voz1voz2 double mutant. In contrast, resistance to a fungal pathogen, Colletotrichum higginsianum, and to a bacterial pathogen, Pseudomonas syringae, was severely impaired. Thus, impairing VOZ function simultaneously conferred increased abiotic tolerance and biotic stress susceptibility. In a chilling stress condition, both the VOZ1 and VOZ2 mRNA expression levels and the VOZ2 protein level gradually decreased. VOZ2 degradation during cold exposure was completely inhibited by the addition of the 26S proteasome inhibitor, MG132, a finding that suggested that VOZ2 degradation is dependent on the ubiquitin/26S proteasome system. In voz1voz2, ABA‐inducible transcription factor CBF4 expression was enhanced significantly even under normal growth conditions, despite an unchanged endogenous ABA content. A finding that suggested that VOZs negatively affect CBF4 expression in an ABA‐independent manner. These results suggest that VOZs function as both negative and positive regulators of the abiotic and biotic stress‐responsive pathways, and control Arabidopsis adaptation to various stress conditions.
Seasonal variation in abiotic factors and ferulic acid toxicity in snail‐attractant pellets against the intermediate host snail Lymnaea acuminata
Authors: Agrahari P. , Singh D. K. 
Published: November 2012

SummaryLaboratory evaluation was made to access the seasonal variations in abiotic environmental factors temperature, pH, dissolved oxygen, carbon dioxide, electrical conductivity and ferulic acid toxicity in snail‐attractant pellets (SAP) against the intermediate host snail Lymnaea acuminata in each month of the years 2010 and 2011. On the basis of a 24‐h toxicity assay, it was noted that lethal concentration values of 4.03, 3.73% and 4.45% in SAP containing starch and 4.16, 4.23% and 4.29% in SAP containing proline during the months of May, June and September, respectively, were most effective in killing the snails, while SAP containing starch/proline + ferulic acid was least effective in the month of January/February (24‐h lethal concentration value was 7.67%/7.63% in SAP). There was a significant positive correlation between lethal concentration value of ferulic acid containing SAP and levels of dissolved O2/pH of water in corresponding months. On the contrary, a negative correlation was observed between lethal concentration value and dissolved CO2/temperature of test water in the same months. To ascertain that such a relationship between toxicity and abiotic factors is not co‐incidental, the nervous tissue of treated (40% and 80% of 24‐h lethal concentration value) and control group of snails was assayed for the activity of acetylcholinesterase (AChE) in each of the 12 months of the same year. There was a maximum inhibition of 58.43% of AChE, in snails exposed to 80% of the 24‐h lethal concentration value of ferulic acid + starch in the month of May. This work shows conclusively that the best time to control snail population with SAP containing ferulic acid is during the months of May, June and September.
Interaction of Lipocalin 2, Transferrin, and Siderophores Determines the Replicative Niche of Klebsiella pneumoniae during Pneumonia
Authors: Bachman Michael A. , Lenio Steven , Schmidt Lindsay , Oyler Jennifer E. , Weiser Jeffrey N. 
Published: November 2012

ABSTRACT

Pathogenic bacteria require iron for replication within their host.
Klebsiella pneumoniae
and other Gram-negative pathogens produce the prototypical siderophore enterobactin (Ent) to scavenge iron
in vivo
. In response, mucosal surfaces secrete lipocalin 2 (Lcn2), an innate immune protein that binds Ent to disrupt bacterial iron acquisition and promote acute inflammation during colonization. A subset of
K. pneumoniae
isolates attempt to evade Lcn2 by producing glycosylated Ent (Gly-Ent, salmochelin) or the alternative siderophore yersiniabactin (Ybt). However, these siderophores are not functionally equivalent and differ in their abilities to promote growth in the upper respiratory tract, lungs, and serum. To understand how Lcn2 exploits functional differences between siderophores, isogenic mutants of an Ent
+
Gly-Ent
+
Ybt
+
K. pneumoniae
strain were inoculated into
Lcn2
+/+
and
Lcn2
−/−
mice, and the pattern of pneumonia was examined. Lcn2 effectively protected against the
iroA ybtS
mutant (Ent
+
Gly-Ent
−
Ybt
−
).
Lcn2
+/+
mice had small foci of pneumonia, whereas
Lcn2
−/−
mice had many bacteria in the perivascular space. The
entB
mutant (Ent
−
Ybt
+
Gly-Ent
−
) caused moderate bronchopneumonia but did not invade the transferrin-containing perivascular space. Accordingly, transferrin blocked Ybt-dependent growth
in vitro
. The wild type and the
iroA
mutant, which both produce Ent and Ybt, had a mixed phenotype, causing a moderate bronchopneumonia in
Lcn2
+/+
mice and perivascular overgrowth in
Lcn2
−/−
mice. Together, these data indicate that Lcn2, in combination with transferrin, confines
K. pneumoniae
to the airways and prevents invasion into tissue containing the pulmonary vasculature.

IMPORTANCE
Gram-negative bacteria are a common cause of severe hospital-acquired infections. To cause disease, they must obtain iron and secrete the small molecule enterobactin to do so. Animal models of pneumonia using
Klebsiella pneumoniae
indicate that enterobactin promotes severe disease. Accordingly, the host defense protein lipocalin 2 exploits this common target by binding enterobactin and disrupting its function. However, pathogenic bacteria often make additional siderophores that lipocalin 2 cannot bind, such as yersiniabactin, which could make this host defense ineffective. This work compares the pattern and severity of pneumonia caused by
K. pneumoniae
based on which siderophores it produces. The results indicate that enterobactin promotes growth around blood vessels that are rich in the iron-binding protein transferrin, but yersiniabactin does not. Together, transferrin and lipocalin 2 protect this space against all types of
K. pneumoniae
tested. Therefore, the ability to acquire iron determines where bacteria can grow in the lung.
Concurrent sexual partnerships among female sex workers and their non-commercial male partners in Tijuana and Ciudad Juárez, Mexico
Authors: Robertson Angela Marie , Syvertsen Jennifer L , Rangel M Gudelia , Staines Hugo S , Morris Martina , Patterson Thomas L , Ulibarri Monica D , Strathdee Steffanie A 
Published: November 2012

ObjectivesTo investigate the prevalence and correlates of concurrent (overlapping) sexual partnerships among female sex workers (FSWs) and their non-commercial male partners in two Mexico–US border cities.MethodsA cross-sectional survey of FSWs and their non-commercial male partners was conducted in Tijuana and Ciudad Juárez, Mexico (2010–2011). Eligible FSWs and verified non-commercial partners were aged ≥18 years; FSWs had ever used hard drugs (lifetime) and recently exchanged sex for money, drugs or other goods (past month). Participants underwent baseline questionnaires obtaining dates of sex and condom use with ≤5 other recurring partners, including FSWs’ regular clients. These dates were compared with dates of sex with enrolled study partners to determine overlap (ie, ‘recurring’ concurrency). Bivariate probit regression identified recurring concurrency correlates.ResultsAmong 428 individuals (214 couples), past-year recurring concurrency prevalence was 16% and was higher among women than their non-commercial male partners (26% vs 6%). In 10 couples (5%), both partners reported recurring concurrency. The majority of couples (64%) always had unprotected sex, and most of the individuals (70%) with recurring concurrency ‘sometimes’ or ‘never’ used condoms with their concurrent partners. Recurring concurrency was positively associated with FSWs’ income, men's caballerismo (a form of traditional masculinity) and men's belief that their FSW partners had sexually transmitted infections (STIs).ConclusionsRecurring concurrency, representing sustained periods of overlapping partnerships in which unprotected sex was common, should be addressed by couple-based STI prevention interventions.
Engineering Approaches for Investigating Tumor Angiogenesis: Exploiting the Role of the Extracellular Matrix
Authors: Hielscher Abigail C. , Gerecht Sharon 
Published: November 2012

Abstract
A major paradigm shift in cancer research is the emergence of multidisciplinary approaches to investigate complex cell behaviors, to elucidate regulatory mechanisms and to identify therapeutic targets. Recently, efforts are focused on the engineering of complex in vitro models, which more accurately recapitulate the growth and progression of cancer. These strategies have proven vital for investigating and targeting the events that control tumor angiogenesis. In this review, we explore how the emerging engineering approaches are being used to unlock the complex mechanisms regulating tumor angiogenesis. Emphasis is placed on models using natural and synthetic biomaterials to generate scaffolds mimicking the extracellular matrix, which is known to play a critical role in angiogenesis. While the models presented in this review are revolutionary, improvements are still necessary and concepts for advancing and perfecting engineering approaches for modeling tumor angiogenesis are proposed. Overall, the marriage between disparate scientific fields is expected to yield significant improvements in our understanding and treatment of cancer. Cancer Res; 72(23); 6089–96. ©2012 AACR.
Predictive Impact of Circulating Vascular Endothelial Growth Factor in Four Phase III Trials Evaluating Bevacizumab
Authors: Hegde Priti S. , Jubb Adrian M. , Chen Dafeng , Li Nicole F. , Meng Y. Gloria , Bernaards Coen , Elliott Rebecca , Scherer Stefan J. , Chen Daniel S. 
Published: November 2012

Abstract
Purpose: We evaluated the prognostic and predictive use of circulating VEGF-A levels in phase III trials of bevacizumab in colorectal cancer, lung cancer, and renal cell carcinoma.
Methods: Baseline plasma samples from 1,816 patients were analyzed for VEGF-A using an ELISA, which recognizes the major isoforms with equivalent sensitivity. HR and 95% confidence intervals (CI) for study end points were estimated using Cox regression analysis. A subset of matched archival tumor samples was analyzed for VEGF-A expression using in situ hybridization.
Results: Higher VEGF-A levels showed trends toward adverse prognostic significance in the control arms of multiple trials, reaching statistical significance for overall survival (OS) in AVF2107 (highest vs. lowest 50%: HR = 1.76; 95% CI, 1.28–2.41), AVAiL (HR = 1.52; 95% CI, 1.16–2.00), and AVOREN (HR = 1.67; 95% CI, 1.18–2.36). In predictive analyses, the HRs for progression-free survival were similar across low and high VEGF-A subgroups and favored bevacizumab-containing treatment. In the low VEGF-A subgroups, HRs (95% CIs) were 0.61 (0.43–0.87) in AVF2107, 0.71 (0.43–1.16) in E4599, 0.74 (0.59–0.94) in AVAiL (low-dose), 0.89 (0.70–1.13) in AVAiL (high-dose), and 0.56 (0.40–0.78) in AVOREN. Analyses of OS data have shown similar results. No correlation between primary tumor VEGF-A expression and plasma VEGF-A levels was observed.
Conclusions: In this comprehensive evaluation, pretreatment total circulating VEGF-A was prognostic for outcome in metastatic colorectal, lung, and renal cell cancers, but it was not predictive for bevacizumab-based treatment benefit. Clin Cancer Res; 19(4); 929–37. ©2012 AACR.
Durable Cancer Regression Off-Treatment and Effective Reinduction Therapy with an Anti-PD-1 Antibody
Authors: Lipson Evan J. , Sharfman William H. , Drake Charles G. , Wollner Ira , Taube Janis M. , Anders Robert A. , Xu Haiying , Yao Sheng , Pons Alice , Chen Lieping , Pardoll Drew M. , Brahmer Julie R. , Topalian Suzanne L. 
Published: November 2012

Abstract
Purpose: Results from the first-in-human phase I trial of the anti–programmed death-1 (PD-1) antibody BMS-936558 in patients with treatment-refractory solid tumors, including safety, tolerability, pharmacodynamics, and immunologic correlates, have been previously reported. Here, we provide long-term follow-up on three patients from that trial who sustained objective tumor regressions off therapy, and test the hypothesis that reinduction therapy for late tumor recurrence can be effective.
Experimental Design: Three patients with colorectal cancer, renal cell cancer, and melanoma achieved objective responses on an intermittent dosing regimen of BMS-936558. Following cessation of therapy, patients were followed for more than 3 years. A patient with melanoma who experienced a prolonged partial regression followed by tumor recurrence received reinduction therapy.
Results: A patient with colorectal cancer experienced a complete response, which is ongoing after 3 years. A patient with renal cell cancer experienced a partial response lasting 3 years off therapy, which converted to a complete response, which is ongoing at 12 months. A patient with melanoma achieved a partial response that was stable for 16 months off therapy; recurrent disease was successfully treated with reinduction anti-PD-1 therapy.
Conclusion: These data represent the most prolonged observation to date of patients with solid tumors responding to anti-PD-1 immunotherapy and the first report of successful reinduction therapy following delayed tumor progression. They underscore the potential for immune checkpoint blockade with anti-PD-1 to reset the equilibrium between tumor and the host immune system. Clin Cancer Res; 19(2); 462–8. ©2012 AACR.
Glucose 6-Phosphate Dehydrogenase Deficiency Increases Redox Stress and Moderately Accelerates the Development of Heart Failure
Authors: Hecker Peter A. , Lionetti Vincenzo , Ribeiro Rogerio F. , Rastogi Sharad , Brown Bethany H. , O’Connell Kelly A. , Cox James W. , Shekar Kadambari C. , Gamble Dionna M. , Sabbah Hani N. , Leopold Jane A. , Gupte Sachin A. , Recchia Fabio A. , Stanley William C. 
Published: November 2012

Background—
Glucose 6-phosphate dehydrogenase (G6PD) is the most common deficient enzyme in the world. In failing hearts, G6PD is upregulated and generates reduced nicotinamide adenine dinucleotide phosphate (NADPH) that is used by the glutathione pathway to remove reactive oxygen species but also as a substrate by reactive oxygen species-generating enzymes. Therefore, G6PD deficiency might prevent heart failure by decreasing NADPH and reactive oxygen species production.

Methods and Results—
This hypothesis was evaluated in a mouse model of human G6PD deficiency (G6PDX mice, ≈40% normal activity). Myocardial infarction with 3 months follow-up resulted in left ventricular dilation and dysfunction in both wild-type and G6PDX mice but significantly greater end diastolic volume and wall thinning in G6PDX mice. Similarly, pressure overload induced by transverse aortic constriction (TAC) for 6 weeks caused greater left ventricular dilation in G6PDX mice than wild-type mice. We further stressed transverse aortic constriction mice by feeding a high fructose diet to increase flux through G6PD and reactive oxygen species production and again observed worse left ventricular remodeling and a lower ejection fraction in G6PDX than wild-type mice. Tissue content of lipid peroxidation products was increased in G6PDX mice in response to infarction and aconitase activity was decreased with transverse aortic constriction, suggesting that G6PD deficiency increases myocardial oxidative stress and subsequent damage.

Conclusions—
Contrary to our hypothesis, G6PD deficiency increased redox stress in response to infarction or pressure overload. However, we found only a modest acceleration of left ventricular remodeling, suggesting that, in individuals with G6PD deficiency and concurrent hypertension or myocardial infarction, the risk for developing heart failure is higher but limited by compensatory mechanisms.
High-Risk Plaque for Carotid Artery Stenting Evaluated With 3-Dimensional T1-Weighted Gradient Echo Sequence
Authors: Tanemura Hiroshi , Maeda Masayuki , Ichikawa Naoki , Miura Yoichi , Umeda Yasuyuki , Hatazaki Seiji , Toma Naoki , Asakura Fumio , Suzuki Hidenori , Sakaida Hiroshi , Matsushima Satoshi , Taki Waro 
Published: November 2012

Background and Purpose—
Preventing cerebral embolisms is a major concern with carotid artery stenting (CAS). This study evaluated 3-dimensional T1-weighted gradient echo (3D T1GRE) sequence to predict cerebral embolism related to CAS.

Methods—
We performed quantitative analyses of the characteristics of 47 carotid plaques before CAS by measuring the signal intensity ratio (SIR) and plaque volume using 3D T1GRE images. We used T1-weighted turbo field echo sequence to obtain 3D T1GRE images. We also evaluated diffusion-weighted images (DWI) of the brain before and after CAS to detect ischemic lesions (DWI lesions) from cerebral emboli.

Results—

SIR (2.17 [interquartile range 1.50–3.07] versus 1.35 [interquartile range 1.08–1.97];
P
=0.010) and plaque volume (456 mm
3
[interquartile range 256–696] versus 301 mm
3
[interquartile range 126–433];
P
=0.008) were significantly higher in the group of patients positive for DWI lesions (P-group: n=26) than DWI lesion-negative patients (N-group: n=21). In multivariate logistic regression analysis, SIR (
P
=0.007) and plaque volume (
P
=0.042) were independent predictors of DWI lesions with CAS. Furthermore, SIR (
r
s=0.42,
P
=0.005) and plaque volume (
r
s=0.36,
P
=0.012) were positively correlated with the number of DWI lesions. From analysis of a receiver-operating characteristic curve, the most reliable cutoff values of SIR and plaque volume to predict DWI lesions related to CAS were 1.80 and 373 mm
3
, respectively.

Conclusions—
Quantitative evaluation of carotid plaques using 3D T1GRE images may be useful in predicting cerebral embolism related to CAS.
Atrial Fibrillation in Ischemic Stroke
Authors: Saposnik Gustavo , Gladstone David , Raptis Roula , Zhou Limei , Hart Robert G. 
Published: November 2012

Background and Purpose—
Atrial fibrillation (AF) increases the risk of stroke and is associated with poor stroke outcomes. Limited tools are available to evaluate clinical outcomes and response to thrombolysis in stroke patients with AF.

Methods—

We applied the iScore (
http://www.sorcan.ca/iscore
), a validated risk score, to consecutive patients with an acute ischemic stroke admitted to stroke centers in the Registry of the Canadian Stroke Network. The main outcome considered was a favorable outcome (defined as a modified Rankin scale 0–2) at discharge after thrombolysis. Secondary outcomes included intracerebral hemorrhage, death at 30 days, and at 1 year stratified by terciles of the iScore.

Results—

Among 12 686 patients with an acute ischemic stroke, 2185 (17.2%) had AF. Overall, AF patients had higher risk of death at 30 days (22.3% versus 10.2%;
P
<0.0001), 1 year (37.1% versus 19.5%;
P
<0.0001) and death or disability at discharge (69.7% versus 54.7%;
P
<0.0001) compared with non-AF patients. After adjustment, thrombolysis was associated with a favorable outcome for patients without AF (relative risk, 1.18; 95% CI, 1.10–1.27), but no benefit was observed for patients with AF (relative risk, 0.91; 95% CI, 0.71–1.17). There was a modestly increased risk of intracranial hemorrhage (any type) (16.5% versus 11.6%; relative risk, 1.42; 95% CI, 1.05–1.91) after thrombolysis among AF compared with non-AF patients. In the logistic regression analysis, there was an interaction between tPA and iScore for a favorable outcome (
P
-value interaction <0.001). The interaction also was significant (
P
<0.0012) among patients without AF, but did not reach significance (
P
=0.17) in patients with AF.

Conclusions—
Stroke patients with AF have higher mortality, greater risk of intracerebral hemorrhage, and a similar response trend to thrombolysis compared with non-AF patients.
Formation Mechanism of Dust Devil–Like Vortices in Idealized Convective Mixed Layers
Authors: Ito Junshi , Niino Hiroshi , Nakanishi Mikio 
Published: November 2012

AbstractDust devils are small-scale vertical vortices often observed over deserts or bare land during the daytime under fair weather conditions. Previous numerical studies have demonstrated that dust devil–like vertical vortices can be simulated in idealized convective mixed layers in the absence of background winds or environmental shear. Their formation mechanism, however, has not been completely clarified. In this paper, the authors attempt to clarify the vorticity source of a dust devil–like vortex by means of a large-eddy simulation, in which a material surface initially placed in the vortex is tracked backward and the circulation on the material surface is examined. The material surface is found to originate from downdrafts, which already have sufficient circulation. As the material surface converges toward the vortex, the vorticity is increased because of conservation of circulation. It is shown that a convective mixed layer is inherently accompanied by circulation, which is scaled by a product of the convective velocity scale and the depth of the convective mixed layer. This circulation is considered to be originally generated by tilting of baroclinically generated horizontal vorticity principally at middepths of the convective mixed layer.
Diagnosing Northern Hemisphere Jet Portrayal in 17 CMIP3 Global Climate Models: Twenty-First-Century Projections
Authors: Delcambre Sharon C. , Lorenz David J. , Vimont Daniel J. , Martin Jonathan E. 
Published: November 2012

Abstract
The anthropogenic climate change impacts on the eddy–jet system include an intensified midlatitude jet stream and an elevated tropopause, as well as a poleward-shifted jet. While both responses are evident in phase 3 of the Coupled Model Intercomparison Project (CMIP3) ensemble mean twenty-first-century projections, uncertainty in the poleward shift response is large enough that even the sign of the shift is not consistent among all models, especially in the Northern Hemisphere. The present analysis finds that twenty-first-century projections of the ensemble mean zonal wind change at 300 hPa predict a weakening and poleward expansion of the Pacific jet and an overall expansion of the Atlantic jet. In contrast with the direct zonal mean climate change signal of increasing midlatitude upper-level winds, zonal winds are projected to decrease in the core of the Pacific and Atlantic jets, with increasing zonal winds located primarily in the jet exit regions and the meridional flanks of the jets. Uncertainties in SST changes from the twentieth century to the twenty-first century between models are shown to impact modeled Northern Hemisphere jet stream changes. In particular, El Niño–Southern Oscillation–like mean winter SST changes explain 30% of intermodel variance of midlatitude zonal wind compared to the 8% explained by the domain-averaged warming SST signal. This suggests that a reduction of uncertainty in the tropical Pacific SST response to global warming will significantly reduce uncertainty in the Northern Hemisphere zonal wind response to climate change.