bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell-specific differences in the requirements for translation quality control
Authors: Reynolds Noah M. , Ling Jiqiang , Roy Hervé , Banerjee Rajat , Repasky Sarah E. , Hamel Patrice , Ibba Michael 
Published: February 2010

Protein synthesis has an overall error rate of approximately 10
-4
for each mRNA codon translated. The fidelity of translation is mainly determined by two events: synthesis of cognate amino acid:tRNA pairs by aminoacyl-tRNA synthetases (aaRSs) and accurate selection of aminoacyl-tRNAs (aa-tRNAs) by the ribosome. To ensure faithful aa-tRNA synthesis, many aaRSs employ a proofreading (“editing”) activity, such as phenylalanyl-tRNA synthetases (PheRS) that hydrolyze mischarged Tyr-tRNA
Phe
. Eukaryotes maintain two distinct PheRS enzymes, a cytoplasmic (ctPheRS) and an organellar form. CtPheRS is similar to bacterial enzymes in that it consists of a heterotetramer in which the α-subunits contain the active site and the β-subunits harbor the editing site. In contrast, mitochondrial PheRS (mtPheRS) is an α-subunit monomer that does not edit Tyr-tRNA
Phe
, and a comparable transacting activity does not exist in organelles. Although mtPheRS does not edit, it is extremely specific as only one Tyr-tRNA
Phe
is synthesized for every ∼7,300 Phe-tRNA
Phe
, compatible with an error rate in translation of ∼10
-4
. When the error rate of mtPheRS was increased 17-fold, the corresponding strain could not grow on respiratory media and the mitochondrial genome was rapidly lost. In contrast, error-prone mtPheRS, editing-deficient ctPheRS, and their wild-type counterparts all supported cytoplasmic protein synthesis and cell growth. These striking differences reveal unexpectedly divergent requirements for quality control in different cell compartments and suggest that the limits of translational accuracy may be largely determined by cellular physiology.
An atomic-level mechanism for activation of the kinesin molecular motors
Authors: Sindelar Charles V. , Downing Kenneth H. 
Published: February 2010

Kinesin cytoskeletal motors convert the energy of ATP hydrolysis into stepping movement along microtubules. A partial model of this process has been derived from crystal structures, which show that movement of the motor domain relative to its major microtubule binding element, the switch II helix, is coupled to docking of kinesin’s neck linker element along the motor domain. This docking would displace the cargo in the direction of travel and so contribute to a step. However, the crystal structures do not reveal how ATP binding and hydrolysis govern this series of events. We used cryoelectron microscopy to derive 8–9 Å-resolution maps of four nucleotide states encompassing the microtubule-attached kinetic cycle of a kinesin motor. The exceptionally high quality of these maps allowed us to build in crystallographically determined conformations of kinesin’s key subcomponents, yielding novel arrangements of kinesin’s switch II helix and nucleotide-sensing switch loops. The resulting atomic models reveal a seesaw mechanism in which the switch loops, triggered by ATP binding, propel their side of the motor domain down and thereby elicit docking of the neck linker on the opposite side of the seesaw. Microtubules engage the seesaw mechanism by stabilizing the formation of extra turns at the N terminus of the switch II helix, which then serve as an anchor for the switch loops as they modulate the seesaw angle. These observations explain how microtubules activate kinesin’s ATP-sensing machinery to promote cargo displacement and inform the mechanism of kinesin’s ancestral relative, myosin.
pH (low) insertion peptide (pHLIP) inserts across a lipid bilayer as a helix and exits by a different path
Authors: Andreev Oleg A. , Karabadzhak Alexander G. , Weerakkody Dhammika , Andreev Gregory O. , Engelman Donald M. , Reshetnyak Yana K. 
Published: February 2010

What are the molecular events that occur when a peptide inserts across a membrane or exits from it? Using the pH-triggered insertion of the pH low insertion peptide to enable kinetic analysis, we show that insertion occurs in several steps, with rapid (0.1 sec) interfacial helix formation, followed by a much slower (100 sec) insertion pathway to give a transmembrane helix. The reverse process of unfolding and peptide exit from the bilayer core, which can be induced by a rapid rise of the pH from acidic to basic, proceeds approximately 400 times faster than folding/insertion and through different intermediate states. In the exit pathway, the helix–coil transition is initiated while the polypeptide is still inside the membrane. The peptide starts to exit when about 30% of the helix is unfolded, and continues a rapid exit as it unfolds inside the membrane. These insights may guide understanding of membrane protein folding/unfolding and the design of medically useful peptides for imaging and drug delivery.
Evaluation of Sequential Fungicide Spray Programs for Control of Soybean Rust
Authors: Sikora Edward J. , Delaney Dennis P. , Delaney Mary A. , Lawrence Kathy S. , Pegues Malcomb 
Published: February 2010

Soybean rust (SBR), caused by the fungus Phakopsora pachyrhiza, has been a recurring problem for soybean growers in the southern United States. In some cases, growers in this region have followed a fungicide spray program consisting of two fungicide applications to protect their crop from the disease. Our study was conducted to determine how various sequential fungicide spray programs perform under the relatively high SBR pressure found in Alabama. Results from this study suggest that there are significant differences in the relative effectiveness of a program based on products used and the sequence in which they are applied. Factors such as recent weather conditions, proximity to sources of SBR, cost of available products, and an estimate of a crops yield potential should be considered when choosing a fungicide program. Accepted for publication 10 February 2009. Published 2 April 2009.
First Report of Dicyma pulvinata on Epichloë typhina and Its Potential for Control of E. typhina
Authors: Alderman Stephen C. , Rao Sujaya , Martin Ruth 
Published: February 2010

The hyperparasite Dicyma pulvinata is reported for the first time on Epichloë typhina, which causes choke disease in orchardgrass seed production fields in the Willamette Valley, OR. In an orchardgrass field near Corvallis, OR, D. pulvinata was found on 7% of E. typhina stromata. Infected stromata had fewer perithecia and appeared shrunken, desiccated, and pale gray to grayish-white, in contrast to the orange colored noninfected stromata with mature perithecia. In greenhouse inoculations, D. pulvinata significantly (P < 0.05) reduced perithecial formation on E. typhina. However, under field conditions, a significant (P < 0.05) reduction in perithecial development occurred in one trial initiated in mid-May, but not in a second trial initiated in early June, although D. pulvinata sporulated on 92% of the inoculated stromata from each trial within 72 h after their incubation in moist chambers. Under field conditions, D. pulvinata may have potential as a biocontrol agent of E. typhina if applied when stromata start to emerge during mid late April to early May when rain and high humidity conditions are typical. However, development of D. pulvinata would likely be limited by low humidity conditions that often occur during mid- to late June in the Willamette Valley. There are currently no effective chemical or cultural controls for choke in orchardgrass. Accepted for publication 3 November 2009. Published 16 February 2010.
First Report of Two Curtoviruses in Spinach and Common Beet in Arizona
Authors: Nischwitz Claudia , Olsen Mary W. 
Published: February 2010

Curtoviruses can cause severe financial losses for growers of leafy greens such as spinach and common beets. Research is currently underway to determine if these viruses are established in weeds and problematic in leafy greens crops throughout Arizona. To our knowledge this is the first report of curtoviruses in common beet and in spinach in Arizona. Accepted for publication 18 November 2009. Published 16 February 2010.
Mild Endotoxemia during Mechanical Ventilation Produces Spatially Heterogeneous Pulmonary Neutrophilic Inflammation in Sheep
Authors: Costa Eduardo L. V. , Musch Guido , Winkler Tilo , Schroeder Tobias , Harris R. Scott , Jones Hazel A. , Venegas Jose G. , Vidal Melo Marcos F. 
Published: February 2010

Background
There is limited information on the regional inflammatory effects of mechanical ventilation and endotoxemia on the production of acute lung injury. Measurement of F-fluorodeoxyglucose (F-FDG) uptake with positron emission tomography allows for the regional, in vivo and noninvasive, assessment of neutrophilic inflammation. The authors tested whether mild endotoxemia combined with large tidal volume mechanical ventilation bounded by pressures within clinically acceptable limits could yield measurable and anatomically localized neutrophilic inflammation.

Methods
Sheep were mechanically ventilated with plateau pressures = 30-32 cm H2O and positive end-expiratory pressure = 0 for 2 h. Six sheep received intravenous endotoxin (10 ng x kg x min), whereas six did not (controls), in sequentially performed studies. The authors imaged with positron emission tomography the intrapulmonary kinetics of infused N-nitrogen and F-FDG to compute regional perfusion and F-FDG uptake. Transmission scans were used to assess aeration.

Results
Mean gas fraction and perfusion distribution were similar between groups. In contrast, a significant increase in F-FDG uptake was observed in all lung regions of the endotoxin group. In this group, F-FDG uptake in the middle and dorsal regions was significantly larger than that in the ventral regions. Multivariate analysis showed that the F-FDG uptake was associated with regional aeration (P < 0.01) and perfusion (P < 0.01).

Conclusions
Mild short-term endotoxemia in the presence of heterogeneous lung aeration and mechanical ventilation with pressures within clinically acceptable limits produces marked spatially heterogeneous increases in pulmonary neutrophilic inflammation. The dependence of inflammation on aeration and perfusion suggests a multifactorial basis for that finding. F-FDG uptake may be a sensitive marker of pulmonary neutrophilic inflammation in the studied conditions.
An Analysis of Patient Variables That Influence Intravenous Patient-controlled Analgesic Use of Morphine with Quantile Regression
Authors: Yen Chia-Rong , Tsou Mei-Yung , Mandell Mercedes Susan , Chan Chia-Tai , Chan Kwok-Hon , Chen Tony Hsiu-Hsi , Chang Kuang-Yi 
Published: February 2010

Background
Previous studies using linear regression analysis have shown that age, weight, gender, and the site of operation affect intravenous patient-controlled analgesia (IVPCA) narcotic use. However, there are inconsistent observations in the literature. The authors postulate that patient variables could have different effects at various doses of narcotics. To test this hypothesis, the authors analyzed the effect of patient variables on increasing doses of IVPCA narcotic with quantile regression.

Methods
The authors collected retrospective data from 1,782 patients who received IVPCA for a minimum of 3 days after surgery. The authors used stepwise linear regression model to identify variables that significantly affected the total IVPCA requirements. Quantile regression model was further applied to assess the effects of selected variables on the ascending percentile of IVPCA narcotic use.

Results
Gender, age, body weight, cancer, and surgical site were identified as significant predictors for IVPCA demand. Body weight had the most and cancer had the least significant effects on total IVPCA demands. The results of quantile regression model revealed that the determinants under consideration varied with different percentiles of IVPCA demand. The patient variables correlated with IVPCA narcotic use differently when the dose exceeded the seventieth to eightieth percentiles compared with other percentiles of narcotic use.

Conclusions
The authors' findings highlight the heterogeneous postoperative pain requirements among patients and the consequent complex process of efficiently managing postoperative pain.
Competitive Inhibition at the Glycine Site of the N -Methyl-d-Aspartate Receptor Mediates Xenon Neuroprotection against Hypoxia–Ischemia
Authors: Banks Paul , Franks Nicholas P. , Dickinson Robert 
Published: February 2010

Background
The general anesthetic gas xenon is neuroprotective and is undergoing clinical trials as a treatment for ischemic brain injury. A small number of molecular targets for xenon have been identified, the N-methyl-D-aspartate (NMDA) receptor, the two-pore-domain potassium channel TREK-1, and the adenosine triphosphate-sensitive potassium channel (KATP). However, which of these targets are relevant to acute xenon neuroprotection is not known. Xenon inhibits NMDA receptors by competing with glycine at the glycine-binding site. We test the hypothesis that inhibition of the NMDA receptor at the glycine site underlies xenon neuroprotection against hypoxia-ischemia.

Methods
We use an in vitro model of hypoxia-ischemia to investigate the mechanism of xenon neuroprotection. Organotypic hippocampal brain slices from mice are subjected to oxygen-glucose deprivation, and injury is quantified by propidium iodide fluorescence.

Results
We show that 50% atm xenon is neuroprotective against hypoxia-ischemia when applied immediately after injury or after a delay of 3 h after injury. To validate our method, we show that neuroprotection by gavestinel is abolished when glycine is added, confirming that NMDA receptor glycine site antagonism underlies gavestinel neuroprotection. We then show that adding glycine abolishes the neuroprotective effect of xenon, consistent with competitive inhibition at the NMDA receptor glycine site mediating xenon neuroprotection.

Conclusions
We show that xenon neuroprotection against hypoxia- ischemia can be reversed by increasing the glycine concentration. This is consistent with competitive inhibition by xenon at the NMDA receptor glycine site, playing a significant role in xenon neuroprotection. This finding may have important implications for xenon's clinical use as an anesthetic and neuroprotectant.
Preoperative C-reactive Protein Predicts Long-term Mortality and Hospital Length of Stay after Primary, Nonemergent Coronary Artery Bypass Grafting
Authors: Perry Tjörvi E. , Muehlschlegel Jochen D. , Liu Kuang-Yu , Fox Amanda A. , Collard Charles D. , Body Simon C. , Shernan Stanton K. 
Published: February 2010

Background
Preoperative C-reactive protein (CRP) levels more than 10 mg/l have been shown to be associated with increased morbidity and mortality after cardiac surgery. We examine the value of preoperative CRP levels less than 10 mg/l for predicting long-term, all-cause mortality and hospital length of stay in surgical patients undergoing primary, nonemergent coronary artery bypass graft-only surgery.

Methods
We examined the association between preoperative CRP levels stratified into four categories (< 1, 1-3, 3-10, and > 10 mg/l), and 7-yr all-cause mortality and hospital length of stay in 914 prospectively enrolled primary, nonemergent coronary artery bypass graft-only surgical patients using a proportional hazards regression model.

Results
Eighty-seven patients (9.5%) died during a mean follow-up period of 4.8 +/- 1.5 yr. After proportional hazards adjustment, the 3-10 and > 10 mg/l preoperative CRP groups were associated with long-term, all-cause mortality (hazards ratios [95% CI]: 2.50 [1.22-5.16], P = 0.01 and 2.66 [1.21-5.80], P = 0.02, respectively) and extended hospital length of stay (1.32 [1.07-1.63], P < 0.001 and 1.27 [1.02-1.62], P = 0.001, respectively).

Conclusion
We demonstrate that preoperative CRP levels as low as 3 mg/l are associated with increased long-term mortality and extended hospital length of stay in relatively lower-acuity patients undergoing primary, nonemergent coronary artery bypass graft-only surgery. These important findings may allow for more objective risk stratification of patients who present for uncomplicated surgical coronary revascularization.
Lung Ventilation and Perfusion in Prone and Supine Postures with Reference to Anesthetized and Mechanically Ventilated Healthy Volunteers
Authors: Nyrén Sven , Radell Peter , Lindahl Sten G. E. , Mure Margareta , Petersson Johan , Larsson Stig A. , Jacobsson Hans , Sánchez-Crespo Alejandro 
Published: February 2010

Background
The literature on ventilation (V) and lung perfusion (Q) distributions during general anesthesia and controlled mechanical ventilation in supine and prone position is contradictory. The authors aimed to investigate whether V, Q, and ventilation to perfusion ratio (V/Q ratio) matching in anesthetized and mechanically ventilated volunteers are gravity dependent irrespective of posture.

Methods
Seven healthy volunteers were studied at two different occasions during general anesthesia and controlled mechanical ventilation. One occasion studied ventral to dorsal V and Q distributions in the supine posture and the other in the prone posture. Imaging was performed in supine posture at both occasions. A dual radiotracer technique and single photon emission computed tomography were used. V and Q were simultaneously tagged with Tc-Technegas (Tetley Manufacturing Ltd., Sydney, Australia) and In-labeled macroaggregates of human albumin (TechneScan LyoMAA, Mallinckrodt Medica, Petten, The Netherlands), respectively.

Results
No differences in V between postures were observed. Q differed between postures, being more uniform over different lung regions in prone posture and dependent in supine posture. The contribution of the vertical direction to the total V/Q ratio heterogeneity was larger in supine (31.4%) than in prone (16.4%) (P = 0.0639, two-tailed, paired t test) posture.

Conclusions
During mechanical ventilation, prone posture favors a more evenly distributed Q between lung regions. V distribution is independent of posture. This results in a tendency toward lower V/Q gradients in the ventral to dorsal direction in prone compared with supine posture.
Carboetomidate
Authors: Cotten Joseph F. , Forman Stuart A. , Laha Joydev K. , Cuny Gregory D. , Husain S. Shaukat , Miller Keith W. , Nguyen Hieu H. , Kelly Elizabeth W. , Stewart Deirdre , Liu Aiping , Raines Douglas E. 
Published: February 2010

Background
Etomidate is a sedative hypnotic that is often used in critically ill patients because it provides superior hemodynamic stability. However, it also binds with high affinity to 11beta-hydroxylase, potently suppressing the synthesis of steroids by the adrenal gland that are necessary for survival. The authors report the results of studies to define the pharmacology of (R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (carboetomidate), a pyrrole analog of etomidate specifically designed not to bind with high affinity to 11beta-hydroxylase.

Methods
The hypnotic potency of carboetomidate was defined in tadpoles and rats using loss of righting reflex assays. Its ability to enhance wild-type alpha1beta2gamma2l and etomidate-insensitive mutant alpha1beta2M286Wgamma2l human gamma-aminobutyric acid type A receptor activities was assessed using electrophysiologic techniques. Its potency for inhibiting in vitro cortisol synthesis was defined using a human adrenocortical cell assay. Its effects on in vivo hemodynamic and adrenocortical function were defined in rats.

Results
Carboetomidate was a potent hypnotic in tadpoles and rats. It increased currents mediated by wild-type but not etomidate-insensitive mutant gamma-aminobutyric acid type A receptors. Carboetomidate was a three orders of magnitude less-potent inhibitor of in vitro cortisol synthesis by adrenocortical cells than was etomidate. In rats, carboetomidate caused minimal hemodynamic changes and did not suppress adrenocortical function at hypnotic doses.

Conclusions
Carboetomidate is an etomidate analog that retains many beneficial properties of etomidate, but it is dramatically less potent as an inhibitor of adrenocortical steroid synthesis. Carboetomidate is a promising new sedative hypnotic for potential use in critically ill patients in whom adrenocortical suppression is undesirable.
Incidence and Root Cause Analysis of Wrong-site Pain Management Procedures
Authors: Cohen Steven P. , Hayek Salim M. , Datta Sukdeb , Bajwa Zahid H. , Larkin Thomas M. , Griffith Scott , Hobelmann Greg , Christo Paul J. , White Ronald 
Published: February 2010

Background
Medical errors exact an inordinate toll on healthcare costs. One of the most publicized and analyzed type of medical error is wrong-site surgery. Yet, despite the burgeoning number of procedures performed, no literature exists on wrong-site pain management injections. The purpose of this study was to estimate the relative incidence and determine the causes of wrong-site pain management procedures.

Methods
Quality improvement records were examined during a 2-yr period from four civilian academic teaching hospitals, three military treatment facilities, and three private practices, for "sentinel" events involving wrong-site pain management procedures. A total of 13 cases (incidence 0.027%; 95% CI 0.01-0.05%) were identified from approximately 48,941 collective procedures of which 52.4% were deemed to be "at risk" for the occurrence. Root cause analyses were then conducted to determine the origin of each error.

Results
The 13 cases included five wrong-side transforaminal epidural steroid injections, six other wrong-side injections, and two wrong-level minimally invasive surgical procedures. In only one case was the "universal protocol" completely followed, and in nine procedures, multiple lapses occurred in protocol. Three patients had bilateral pathology, and in seven cases, the patient knew at the time that the wrong side was being injected. In no instance did any technical, legal, or professional consequences ensue from the error.

Conclusions
Wrong-site nerve blocks occur more frequently in pain management centers than has previously been acknowledged. Adaptation of the universal protocol to nerve blocks and strict adherence to widely accepted guidelines may prevent wrong-site interventional pain procedures.
3D seismic expression of km‐scale fluid escape pipes from offshore Namibia
Authors: Moss J. L. , Cartwright J. 
Published: February 2010

ABSTRACTThis paper documents a large number of large km‐scale fluid escape pipes with complex seismic expression and a diatreme‐like geometry from the mapping of a 3D seismic survey, offshore Namibia. These pipes are crudely cylindrical, but occasionally have steep conical geometry either narrowing upwards or downwards. They are generally ovoid in planform and their ellipticity varies with pipe height. Vertical dimensions range from ca. 100 to >1000 m and diameters range between 50 and 600 m. The lower part of the typical pipe is characterised by a sag‐like or collapse type of structure, but this is only imaged well in the wider pipes. The upper part of the typical pipe is characterised by gently concave upwards reflections, with a negative relief of tens of metres. There is some evidence (pipe cross‐section geometrical variations and amplitude anomalies) that these concave upwards reflections are vertically stacked palaeo‐pockmarks. A conceptual model for pipe formation is proposed that involves hydraulic fracturing and localisation of focused vertical fluid escape with volume loss at the base of the pipe inducing collapse within the pipe. Continuing episodic fluid migration through the pipe produces further collapsing of the core of the pipe and pockmark structures at the top of the pipe. Longer term seepage through pipes is manifested in zones of amplification of reflections above the top of the pipe.