bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploration of sequence space as the basis of viral RNA genome segmentation
Authors: Moreno Elena , Ojosnegros Samuel , García-Arriaza Juan , Escarmís Cristina , Domingo Esteban , Perales Celia 
Published: April 2014

Significance
The molecular basis of a drastic evolutionary change, akin to RNA genome segmentation, previously observed with foot-and-mouth disease virus was unknown. Here we report that point mutations that accumulated in the genome during replication permitted the transition toward genome segmentation. This effect of mutations has been shown by placing the deletions in the sequence context of the parental and evolved RNAs and quantifying protein expression and infectious progeny production. The results document that an extensive exploration of sequence space was required prior to this multifactorial evolutionary transition. An unsegmented viral genome can reach a point in sequence space at which a different genomic organization is favored. The observation underlines the value of quasi-species dynamics as a factor in the emergence of viral genomes.
Expression of a codon-optimized Aspergillus niger pectin methylesterase gene in the methylotrophic yeast Candida boidinii
Authors: Kawaguchi Kosuke , Yurimoto Hiroya , Sakai Yasuyoshi 
Published: April 2014

Abstract
A codon-optimized Aspergillus niger pectin methylesterase (PME) gene was expressed in the methylotrophic yeast Canidia boidinii. The PME-producing strains showed better growth on pectin than the wild-type strains, suggesting that the PME-producing strains could efficiently utilize methyl ester moieties of pectin. On the other hand, overproduction of PME negatively affected the proliferation of C. boidinii on leaves of Arabidopsis thaliana.
Downhill walking to improve lower limb strength in healthy young adults
Authors: Rodio Angelo , Fattorini Luigi 
Published: April 2014

AbstractWalking is the most natural physical activity to maintain and improve fitness and health. Walking downhill is usefully adopted to plan training programmes to improve the strength, particularly in older adults. The present research was aimed to evaluate the influence of downhill walking on leg strength in young adult. A total of 32 females (age 26 ± 4 years; height 1.64 ± 0.05 m; body mass 57.6 ± 5.6 kg) were divided into four groups and they carried out an exercise intervention consisting of three sessions per week for 6 weeks, each lasting 30 minutes. Groups were defined at several workloads characterised by treadmill inclination (%) and walking speed (m·s−1): Level Walking at treadmill inclination 0% and walking speed 1.0; Uphill Walking at +20%, 0.75; Downhill Walking (DW) at −20%, 1.36; and Mixed Walking at +20%, 0.75 and −20%, 1.36 each lasting 15 minutes. Maximum voluntary contraction (MVC) developed by the Quadriceps Femoris and Endurance Time at 60% MVC were evaluated before and after experimental period. At the end of each session, Borg's scale and Visual Analogue Scale (VAS) were adopted in order to evaluate perception of rate exertion and pain. Statistical analysis showed significant only in MVC for DW in both right and left legs. Borg's scale and VAS described light activity free of pain. Present findings showed how an eccentric exercise, short lasting and at a low workload, can be useful in inducing improvements in leg strength.
GNAS Gene Variants Affect β-blocker–related Survival after Coronary Artery Bypass Grafting
Authors: Frey Ulrich H. , Muehlschlegel Jochen D. , Ochterbeck Christoph , Fox Amanda A. , Shernan Stanton K. , Collard Charles D. , Lichtner Peter , Peters Jürgen , Body Simon 
Published: April 2014

Abstract

Background:
Cardiac overexpression of the β-adrenoreceptor (βAR)–coupled stimulatory G-protein subunit Gαs enhances inotropic responses to adrenergic stimulation and improves survival in mice under βAR blockade. The authors recently identified three common haplotypes in the GNAS gene encoding Gαs, with the greatest Gαs protein expression and signal transduction in haplotype *3 carriers and less in haplotype *2 and *1 carriers. The authors tested the hypothesis that these GNAS variants result in altered mortality in patients after coronary artery bypass graft surgery, particularly in those receiving βAR blockade.

Methods:
This prospective analysis included 1,627 European ancestry patients undergoing primary coronary artery bypass graft surgery. Patients were genotyped for two GNAS haplotype tagging single-nucleotide polymorphisms defining three major haplotypes. Up to 5-yr all-cause mortality was estimated using a Cox proportional hazard model; hazard ratios and 95% CIs were calculated while adjusting for demographics, clinical covariates, and the new EuroSCORE II.

Results:
Univariate analysis revealed haplotype-dependent 5-yr mortality rates (*1/*1: 18.9%, *2/*1: 13.7%, *2/*2: 9.3%, *3/*1: 10.6%, *3/*2: 9.1%, and *3/*3: 9.6%; P = 0.0006). After adjustment for other predictors of death, homozygote haplotype *1 carriers showed a doubled risk for death (hazard ratio, 2.2; 95% CI, 1.2 to 3.8; P = 0.006). Considering only patients receiving βAR blockers (n = 1,267), the adjusted risk of death even tripled (hazard ratio, 3.0; 95% CI, 1.5 to 6.1; P = 0.002).

Conclusions:

GNAS haplotypes independently associate with an increased risk of death after primary coronary artery bypass graft surgery. These results are most pronounced in patients receiving βAR blockers, strengthening the rationale for personalized treatment, to decrease medication side effects and improve outcomes.
Predicting Risk of Postoperative Lung Injury in High-risk Surgical Patients
Authors: Kor Daryl J. , Lingineni Ravi K. , Gajic Ognjen , Park Pauline K. , Blum James M. , Hou Peter C. , Hoth J. Jason , Anderson Harry L. , Bajwa Ednan K. , Bartz Raquel R. , Adesanya Adebola , Festic Emir , Gong Michelle N. , Carter Rickey E. , Talmor Daniel S. 
Published: April 2014

Abstract

Background:
Acute respiratory distress syndrome (ARDS) remains a serious postoperative complication. Although ARDS prevention is a priority, the inability to identify patients at risk for ARDS remains a barrier to progress. The authors tested and refined the previously reported surgical lung injury prediction (SLIP) model in a multicenter cohort of at-risk surgical patients.

Methods:
This is a secondary analysis of a multicenter, prospective cohort investigation evaluating high-risk patients undergoing surgery. Preoperative ARDS risk factors and risk modifiers were evaluated for inclusion in a parsimonious risk-prediction model. Multiple imputation and domain analysis were used to facilitate development of a refined model, designated SLIP-2. Area under the receiver operating characteristic curve and the Hosmer–Lemeshow goodness-of-fit test were used to assess model performance.

Results:
Among 1,562 at-risk patients, ARDS developed in 117 (7.5%). Nine independent predictors of ARDS were identified: sepsis, high-risk aortic vascular surgery, high-risk cardiac surgery, emergency surgery, cirrhosis, admission location other than home, increased respiratory rate (20 to 29 and ≥30 breaths/min), Fio
2 greater than 35%, and Spo
2 less than 95%. The original SLIP score performed poorly in this heterogeneous cohort with baseline risk factors for ARDS (area under the receiver operating characteristic curve [95% CI], 0.56 [0.50 to 0.62]). In contrast, SLIP-2 score performed well (area under the receiver operating characteristic curve [95% CI], 0.84 [0.81 to 0.88]). Internal validation indicated similar discrimination, with an area under the receiver operating characteristic curve of 0.84.

Conclusions:
In this multicenter cohort of patients at risk for ARDS, the SLIP-2 score outperformed the original SLIP score. If validated in an independent sample, this tool may help identify surgical patients at high risk for ARDS.
Comparison of Three Techniques for Ultrasound-guided Femoral Nerve Catheter Insertion
Authors: Farag Ehab , Atim Abdulkadir , Ghosh Raktim , Bauer Maria , Sreenivasalu Thilak , Kot Michael , Kurz Andrea , Dalton Jarrod E. , Mascha Edward J. , Mounir-Soliman Loran , Zaky Sherif , Ali Sakr Esa Wael , Udeh Belinda L. , Barsoum Wael , Sessler Daniel I. 
Published: April 2014

Abstract

Background:
Ultrasound guidance for continuous femoral perineural catheters may be supplemented by electrical stimulation through a needle or through a stimulating catheter. The authors tested the primary hypothesis that ultrasound guidance alone is noninferior on both postoperative pain scores and opioid requirement and superior on at least one of the two. Second, the authors compared all interventions on insertion time and incremental cost.

Methods:
Patients having knee arthroplasty with femoral nerve catheters were randomly assigned to catheter insertion guided by: (1) ultrasound alone (n = 147); (2) ultrasound and electrical stimulation through the needle (n = 152); or (3) ultrasound and electrical stimulation through both the needle and catheter (n = 138). Noninferiority between any two interventions was defined for pain as not more than 0.5 points worse on a 0 to 10 verbal response scale and for opioid consumption as not more than 25% greater than the mean.

Results:
The stimulating needle group was significantly noninferior to the stimulating catheter group (difference [95% CI] in mean verbal response scale pain score [stimulating needle vs. stimulating catheter] of −0.16 [−0.61 to 0.29], P < 0.001; percentage difference in mean IV morphine equivalent dose of −5% [−25 to 21%], P = 0.002) and to ultrasound-only group (difference in mean verbal response scale pain score of −0.28 [−0.72 to 0.16], P < 0.001; percentage difference in mean IV morphine equivalent dose of −2% [−22 to 25%], P = 0.006). In addition, the use of ultrasound alone for femoral nerve catheter insertion was faster and cheaper than the other two methods.

Conclusion:
Ultrasound guidance alone without adding either stimulating needle or needle/catheter combination thus seems to be the best approach to femoral perineural catheters.
Isoflurane Impairs Learning and Hippocampal Long-term Potentiation via the Saturation of Synaptic Plasticity
Authors: Uchimoto Kazuhiro , Miyazaki Tomoyuki , Kamiya Yoshinori , Mihara Takahiro , Koyama Yukihide , Taguri Masataka , Inagawa Gaku , Takahashi Takuya , Goto Takahisa 
Published: April 2014

Abstract

Background:
General anesthesia induces long-lasting cognitive and learning deficits. However, the underlying mechanism remains unknown. The GluA1 subunit of AMPAR is a key molecule for learning and synaptic plasticity, which requires trafficking of GluA1-containing AMPARs into the synapse.

Methods:
Adult male rats were exposed to 1.8% isoflurane for 2 h and subjected to an inhibitory avoidance task, which is a hippocampus-dependent contextual fear learning paradigm (n = 16 to 39). The in vitro extracellular field potential of hippocampal synapses between the Schaffer collateral and the CA1 was evaluated using a multielectrode recorder (n = 6 per group). GluA1 expression in the synaptoneurosome was assessed using Western blotting (n = 5 to 8). The ubiquitination level of GluA1 was evaluated using immunoprecipitation and Western blotting (n = 7 per group).

Results:
Seven days after exposure to 1.8% isoflurane for 2 h (Iso1.8), the inhibitory avoidance learning (control vs. Iso1.8; 294 ± 34 vs. 138 ± 28, the mean ± SEM [%]; P = 0.002) and long-term potentiation (125.7 ± 6.1 vs. 105.7 ± 3.3; P < 0.001) were impaired. Iso1.8 also temporarily increased GluA1 in the synaptoneurosomes (100 ± 9.7 vs. 138.9 ± 8.9; P = 0.012) and reduced the GluA1 ubiquitination, a main degradation pathway of GluA1 (100 ± 8.7 vs. 71.1 ± 6.1; P = 0.014).

Conclusions:
Isoflurane impairs hippocampal learning and modulates synaptic plasticity in the postanesthetic period. Increased GluA1 may reduce synaptic capacity for additional GluA1-containing AMPARs trafficking.
A 16-Year Experience in Minimally Invasive Aortic Valve Replacement
Authors: Gosev Igor , Kaneko Tsuyoshi , McGurk Siobhan , McClure Scott R. , Maloney Ann , Cohn Lawrence H. 
Published: April 2014

Objective The aim of this study was to evaluate short- and long-term morbidity and mortality in patients with aortic valve disease who had minimally invasive aortic valve replacement (AVR) through upper hemisternotomy. Methods From July 1996 to June 2012, a total of 1639 patients underwent minimally invasive aortic valve surgery (AVR). Patient data were extracted from hospital electronic records after institutional review board approval. Outcomes of interest included postoperative complication rates, perioperative mortality, and long-term survival. Results The mean age was 67 years (SD, 14 years; range, 22–95 years). Of the total cohort, 211 (13%) underwent reoperative AVR. Postoperatively, 2.3% (37/1639) had reoperations to correct bleeding, 2.7% (44/1639) had strokes, 20.4% (334/1639) had new-onset atrial fibrillation, and 1.5% (24/1639) required permanent pacemakers. Only 34% (571/1639) of the patients received packed red blood cells. The median discharge was on day 6 (5–8), and 72.2% of the patients (1184/1639) were discharged home. Operative mortality was 2.9% (48/1639), and long-term survival at 1, 5, 10, and 15 years was 96%, 93%, 92%, and 92%, respectively. Operative mortality was 5.7% (12/208) for the reoperative patients. Conclusions The upper hemisternotomy approach for AVR is safe and reliable, especially for patients undergoing reoperations and those older than 80 years.
Six-Month Healing of the Nonocclusive Coronary Anastomotic Connector in an Off-Pump Porcine Bypass Model
Authors: Stecher David , Agostoni Pierfrancesco , Pasterkamp Gerard , Hoefer Imo E. , van Herwerden Lex A. , Buijsrogge Marc P. 
Published: April 2014

Objective This pilot study evaluates the anastomotic healing of the Excimer Laser Assisted Nonocclusive Anastomosis coronary connector at 6 months in a porcine off-pump coronary artery bypass (OPCAB) model. Methods Left internal thoracic artery to left anterior descending coronary artery bypass in two animals and left internal thoracic artery to left anterior descending coronary artery and right internal thoracic artery to right coronary artery bypasses in one animal were evaluated intraoperatively and at 6 months. The anastomoses (n = 4) were examined by angiography, intravascular ultrasound, optical coherence tomography, scanning electron microscopy, and histology. Results At follow-up, all anastomoses (n = 4) were fully patent (FitzGibbon grade A). Scanning electron microscopy demonstrated complete endothelial coverage of the anastomotic surface, and histology showed minimal streamlining intimal hyperplasia. The in vivo intravascular ultrasound and optical coherence tomography acquisitions confirmed histologic findings. Optical coherence tomography demonstrated 0.06-mm intimal coverage of the intraluminal part of the connector along the full circumference of the anastomosis. Conclusions In this pilot study, the Excimer Laser Assisted Non-occlusive Anastomosis coronary connector showed an excellent healing response on the long-term in the porcine OPCAB model. Hence, this new concept might be a potential alternative to hand-sutured anastomosis in (minimally invasive) OPCAB surgery.
Aortic Valve Replacement via Right Minithoracotomy versus Median Sternotomy
Authors: Glower Donald D. , Desai Bhargavi S. , Hughes G. Chad , Milano Carmelo A. , Gaca Jeffrey G. 
Published: April 2014

Objective The aim of this study was to define the relative role of a right minithoracotomy (RT) versus standard median sternotomy (ST) for open aortic valve replacement (AVR). Methods A retrospective analysis was performed of all 1348 patients undergoing isolated, open AVR at a single institution during a 14-year period. Because relatively few patients were technically suitable for redo AVR with the RT approach (n = 20), all redo patients (n = 209) were excluded, leaving 1139 patients available for analysis. Patients converting from RT to ST approach (n = 15) were analyzed separately. Results Relative to ST (n = 672), the RT patients (n = 452) were older with more stenosis but with more recent operation year, lower rate of congestive heart failure, higher ejection fraction, lower rate of endocarditis, and lower rate of renal disease than the ST AVR patients (all P < 0.0001). Right minithoracotomy AVR was associated with longer cardiopulmonary bypass times [157 (25) vs 131 (38), P = 0.0004] and clamp times [103 (20) vs 85 (27), P < 0.0001] but less transfusion (1.4 vs 3.4 U, P = 0.0003), less chest tube output (405 vs 950 mL, P < 0.0001), fewer reoperations for bleeding (0.4% vs 4%, P < 0.0001), shorter length of stay (6 vs 8 days, P = 0.03), and lower rate of atrial fibrillation (15% vs 20%, P = 0.03). Stroke, operative mortality, and survival were not significantly different between the groups. Conclusions Given the biases of retrospective propensity-adjusted analysis, these data suggest that RT AVR is a safe alternative to ST AVR in selected patients, with advantages of avoiding sternotomy with associated bleeding, transfusion, and delayed wound healing, at the expense of longer pump and clamp times.
Contrasting Roles of the Apoplastic Aspartyl Protease APOPLASTIC, ENHANCED DISEASE SUSCEPTIBILITY1-DEPENDENT1 and LEGUME LECTIN-LIKE PROTEIN1 in Arabidopsis Systemic Acquired Resistance
,
Authors: Breitenbach Heiko H. , Wenig Marion , Wittek Finni , Jordá Lucia , Maldonado-Alconada Ana M. , Sarioglu Hakan , Colby Thomas , Knappe Claudia , Bichlmeier Marlies , Pabst Elisabeth , Mackey David , Parker Jane E. , Vlot A. Corina 
Published: April 2014

Abstract
Systemic acquired resistance (SAR) is an inducible immune response that depends on ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1). Here, we show that Arabidopsis (Arabidopsis thaliana) EDS1 is required for both SAR signal generation in primary infected leaves and SAR signal perception in systemic uninfected tissues. In contrast to SAR signal generation, local resistance remains intact in eds1 mutant plants in response to Pseudomonas syringae delivering the effector protein AvrRpm1. We utilized the SAR-specific phenotype of the eds1 mutant to identify new SAR regulatory proteins in plants conditionally expressing AvrRpm1. Comparative proteomic analysis of apoplast-enriched extracts from AvrRpm1-expressing wild-type and eds1 mutant plants led to the identification of 12 APOPLASTIC, EDS1-DEPENDENT (AED) proteins. The genes encoding AED1, a predicted aspartyl protease, and another AED, LEGUME LECTIN-LIKE PROTEIN1 (LLP1), were induced locally and systemically during SAR signaling and locally by salicylic acid (SA) or its functional analog, benzo 1,2,3-thiadiazole-7-carbothioic acid S-methyl ester. Because conditional overaccumulation of AED1-hemagglutinin inhibited SA-induced resistance and SAR but not local resistance, the data suggest that AED1 is part of a homeostatic feedback mechanism regulating systemic immunity. In llp1 mutant plants, SAR was compromised, whereas the local resistance that is normally associated with EDS1 and SA as well as responses to exogenous SA appeared largely unaffected. Together, these data indicate that LLP1 promotes systemic rather than local immunity, possibly in parallel with SA. Our analysis reveals new positive and negative components of SAR and reinforces the notion that SAR represents a distinct phase of plant immunity beyond local resistance.
Clathrin and Membrane Microdomains Cooperatively Regulate RbohD Dynamics and Activity in Arabidopsis
Authors: Hao Huaiqing , Fan Lusheng , Chen Tong , Li Ruili , Li Xiaojuan , He Qihua , Botella Miguel A. , Lin Jinxing 
Published: April 2014

Abstract
Arabidopsis thaliana respiratory burst oxidase homolog D (RbohD) functions as an essential regulator of reactive oxygen species (ROS). However, our understanding of the regulation of RbohD remains limited. By variable-angle total internal reflection fluorescence microscopy, we demonstrate that green fluorescent protein (GFP)-RbohD organizes into dynamic spots at the plasma membrane. These RbohD spots have heterogeneous diffusion coefficients and oligomerization states, as measured by photobleaching techniques. Stimulation with ionomycin and calyculin A, which activate the ROS-producing enzymatic activity of RbohD, increases the diffusion and oligomerization of RbohD. Abscisic acid and flg22 treatments also increase the diffusion coefficient and clustering of GFP-RbohD. Single-particle analysis in clathrin heavy chain2 mutants and a Flotillin1 artificial microRNA line demonstrated that clathrin- and microdomain-dependent endocytic pathways cooperatively regulate RbohD dynamics. Under salt stress, GFP-RbohD assembles into clusters and then internalizes into the cytoplasm. Dual-color fluorescence cross-correlation spectroscopy analysis further showed that salt stress stimulates RbohD endocytosis via membrane microdomains. We demonstrate that microdomain-associated RbohD spots diffuse at the membrane with high heterogeneity, and these dynamics closely relate to RbohD activity. Our results provide insight into the regulation of RbohD activity by clustering and endocytosis, which facilitate the activation of redox signaling pathways.
The Rice Basic Helix-Loop-Helix Transcription Factor TDR INTERACTING PROTEIN2 Is a Central Switch in Early Anther Development
Authors: Fu Zhenzhen , Yu Jing , Cheng Xiaowei , Zong Xu , Xu Jie , Chen Mingjiao , Li Zongyun , Zhang Dabing , Liang Wanqi 
Published: April 2014

Abstract
In male reproductive development in plants, meristemoid precursor cells possessing transient, stem cell–like features undergo cell divisions and differentiation to produce the anther, the male reproductive organ. The anther contains centrally positioned microsporocytes surrounded by four distinct layers of wall: the epidermis, endothecium, middle layer, and tapetum. Here, we report that the rice (Oryza sativa) basic helix-loop-helix (bHLH) protein TDR INTERACTING PROTEIN2 (TIP2) functions as a crucial switch in the meristemoid transition and differentiation during early anther development. The tip2 mutants display undifferentiated inner three anther wall layers and abort tapetal programmed cell death, causing complete male sterility. TIP2 has two paralogs in rice, TDR and EAT1, which are key regulators of tapetal programmed cell death. We revealed that TIP2 acts upstream of TDR and EAT1 and directly regulates the expression of TDR and EAT1. In addition, TIP2 can interact with TDR, indicating a role of TIP2 in later anther development. Our findings suggest that the bHLH proteins TIP2, TDR, and EAT1 play a central role in regulating differentiation, morphogenesis, and degradation of anther somatic cell layers, highlighting the role of paralogous bHLH proteins in regulating distinct steps of plant cell–type determination.