bluuebunny/crossref_metadata_2025 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.
Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency
Authors: Hu Bao-Yang , Weick Jason P. , Yu Junying , Ma Li-Xiang , Zhang Xiao-Qing , Thomson James A. , Zhang Su-Chun
Published: February 2010

For the promise of human induced pluripotent stem cells (iPSCs) to be realized, it is necessary to ask if and how efficiently they may be differentiated to functional cells of various lineages. Here, we have directly compared the neural-differentiation capacity of human iPSCs and embryonic stem cells (ESCs). We have shown that human iPSCs use the same transcriptional network to generate neuroepithelia and functionally appropriate neuronal types over the same developmental time course as hESCs in response to the same set of morphogens; however, they do it with significantly reduced efficiency and increased variability. These results were consistent across iPSC lines and independent of the set of reprogramming transgenes used to derive iPSCs as well as the presence or absence of reprogramming transgenes in iPSCs. These findings, which show a need for improving differentiation potency of iPSCs, suggest the possibility of employing human iPSCs in pathological studies, therapeutic screening, and autologous cell transplantation.
Promoting social behavior with oxytocin in high-functioning autism spectrum disorders
Authors: Andari Elissar , Duhamel Jean-René , Zalla Tiziana , Herbrecht Evelyn , Leboyer Marion , Sirigu Angela
Published: February 2010

Social adaptation requires specific cognitive and emotional competences. Individuals with high-functioning autism or with Asperger syndrome cannot understand or engage in social situations despite preserved intellectual abilities. Recently, it has been suggested that oxytocin, a hormone known to promote mother-infant bonds, may be implicated in the social deficit of autism. We investigated the behavioral effects of oxytocin in 13 subjects with autism. In a simulated ball game where participants interacted with fictitious partners, we found that after oxytocin inhalation, patients exhibited stronger interactions with the most socially cooperative partner and reported enhanced feelings of trust and preference. Also, during free viewing of pictures of faces, oxytocin selectively increased patients’ gazing time on the socially informative region of the face, namely the eyes. Thus, under oxytocin, patients respond more strongly to others and exhibit more appropriate social behavior and affect, suggesting a therapeutic potential of oxytocin through its action on a core dimension of autism.
Regulation of synaptic vesicle recycling by complex formation between intersectin 1 and the clathrin adaptor complex AP2
Authors: Pechstein Arndt , Bacetic Jelena , Vahedi-Faridi Ardeschir , Gromova Kira , Sundborger Anna , Tomlin Nikolay , Krainer Georg , Vorontsova Olga , Schäfer Johannes G. , Owe Simen G. , Cousin Michael A. , Saenger Wolfram , Shupliakov Oleg , Haucke Volker
Published: February 2010

Clathrin-mediated synaptic vesicle (SV) recycling involves the spatiotemporally controlled assembly of clathrin coat components at phosphatidylinositiol (4, 5)-bisphosphate [PI(4,5)P
2
]-enriched membrane sites within the periactive zone. Such spatiotemporal control is needed to coordinate SV cargo sorting with clathrin/AP2 recruitment and to restrain membrane fission and synaptojanin-mediated uncoating until membrane deformation and clathrin coat assembly are completed. The molecular events underlying these control mechanisms are unknown. Here we show that the endocytic SH3 domain-containing accessory protein intersectin 1 scaffolds the endocytic process by directly associating with the clathrin adaptor AP2. Acute perturbation of the intersectin 1-AP2 interaction in lamprey synapses in situ inhibits the onset of SV recycling. Structurally, complex formation can be attributed to the direct association of hydrophobic peptides within the intersectin 1 SH3A-B linker region with the “side sites” of the AP2 α- and β-appendage domains. AP2 appendage association of the SH3A-B linker region inhibits binding of the inositol phosphatase synaptojanin 1 to intersectin 1. These data identify the intersectin-AP2 complex as an important regulator of clathrin-mediated SV recycling in synapses.
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.
Operation of the voltage sensor of a human voltage- and Ca
2+
-activated K
+
channel
Authors: Pantazis Antonios , Gudzenko Vadym , Savalli Nicoletta , Sigg Daniel , Olcese Riccardo
Published: February 2010

Voltage sensor domains (VSDs) are structurally and functionally conserved protein modules that consist of four transmembrane segments (S1–S4) and confer voltage sensitivity to many ion channels. Depolarization is sensed by VSD-charged residues residing in the membrane field, inducing VSD activation that facilitates channel gating. S4 is typically thought to be the principal functional component of the VSD because it carries, in most channels, a large portion of the VSD gating charge. The VSDs of large-conductance, voltage- and Ca
2+
-activated K
+
channels are peculiar in that more gating charge is carried by transmembrane segments other than S4. Considering its “decentralized” distribution of voltage-sensing residues, we probed the BK
Ca
VSD for evidence of cooperativity between charge-carrying segments S2 and S4. We achieved this by optically tracking their activation by using voltage clamp fluorometry, in channels with intact voltage sensors and charge-neutralized mutants. The results from these experiments indicate that S2 and S4 possess distinct voltage dependence, but functionally interact, such that the effective valence of one segment is affected by charge neutralization in the other. Statistical-mechanical modeling of the experimental findings using allosteric interactions demonstrates two mechanisms (mechanical coupling and dynamic focusing of the membrane electric field) that are compatible with the observed cross-segment effects of charge neutralization.
Learning as a phenomenon occurring in a critical state
Authors: de Arcangelis Lucilla , Herrmann Hans J.
Published: February 2010

Recent physiological measurements have provided clear evidence about scale-free avalanche brain activity and EEG spectra, feeding the classical enigma of how such a chaotic system can ever learn or respond in a controlled and reproducible way. Models for learning, like neural networks or perceptrons, have traditionally avoided strong fluctuations. Conversely, we propose that brain activity having features typical of systems at a critical point represents a crucial ingredient for learning. We present here a study that provides unique insights toward the understanding of the problem. Our model is able to reproduce quantitatively the experimentally observed critical state of the brain and, at the same time, learns and remembers logical rules including the exclusive OR, which has posed difficulties to several previous attempts. We implement the model on a network with topological properties close to the functionality network in real brains. Learning occurs via plastic adaptation of synaptic strengths and exhibits universal features. We find that the learning performance and the average time required to learn are controlled by the strength of plastic adaptation, in a way independent of the specific task assigned to the system. Even complex rules can be learned provided that the plastic adaptation is sufficiently slow.
Phenotypic plasticity facilitates recurrent rapid adaptation to introduced predators
Authors: Scoville Alison G. , Pfrender Michael E.
Published: February 2010

A central role for phenotypic plasticity in adaptive evolution is often posited yet lacks empirical support. Selection for the stable production of an induced phenotype is hypothesized to modify the regulation of preexisting developmental pathways, producing rapid adaptive change. We examined the role of plasticity in rapid adaptation of the zooplankton
Daphnia melanica
to novel fish predators. Here we show that plastic up-regulation of the arthropod melanin gene dopa decarboxylase (
Ddc
) in the absence of UV radiation is associated with reduced pigmentation in
D. melanica
.
Daphnia
populations coexisting with recently introduced fish exhibit environmentally invariant up-regulation of
Ddc
, accompanied by constitutive up-regulation of the interacting arthropod melanin gene
ebony
. Both changes in regulation are associated with adaptive reduction in the plasticity and mean expression of melanin. Our results provide evidence that the developmental mechanism underlying ancestral plasticity in response to an environmental factor has been repeatedly co-opted to facilitate rapid adaptation to an introduced predator.
Caspase 3/caspase-activated DNase promote cell differentiation by inducing DNA strand breaks
Authors: Larsen Brian D. , Rampalli Shravanti , Burns Leanne E. , Brunette Steve , Dilworth F. Jeffrey , Megeney Lynn A.
Published: February 2010

Caspase 3 is required for the differentiation of a wide variety of cell types, yet it remains unclear how this apoptotic protein could promote such a cell-fate decision. Caspase signals often result in the activation of the specific nuclease caspase-activated DNase (CAD), suggesting that cell differentiation may be dependent on a CAD-mediated modification in chromatin structure. In this study, we have investigated if caspase 3/CAD plays a role in initiating the DNA strand breaks that are known to occur during the terminal differentiation of skeletal muscle cells. Here, we show that inhibition of caspase 3 or reduction of CAD expression leads to a dramatic loss of strand-break formation and a block in the myogenic program. Caspase-dependent induction of differentiation results in CAD targeting of the p21 promoter, and loss of caspase 3 or CAD leads to a significant down-regulation in p21 expression. These results show that caspase 3/CAD promotes cell differentiation by directly modifying the DNA/nuclear microenvironment, which enhances the expression of critical regulatory genes.
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.
Vaccination with partial knowledge of external effectiveness
Authors: Manski Charles F.
Published: February 2010

Economists studying public policy have generally assumed that the relevant planner knows how policy affects population behavior. Planners typically do not possess all of this knowledge, so there is reason to consider policy formation with partial knowledge of policy impacts. Here I consider choice of a vaccination policy when a planner has partial knowledge of the effect of vaccination on illness rates. To begin, I pose a planning problem whose objective is to minimize the utilitarian social cost of illness and vaccination. The consequences of candidate vaccination rates depend on the extent to which vaccination prevents illness. I study the planning problem when the planner has partial knowledge of the external-response function, which expresses how the illness rate of unvaccinated persons varies with the vaccination rate. I suppose that the planner observes the illness rate of a study population whose vaccination rate has been chosen previously. He knows that the illness rate of unvaccinated persons weakly decreases as the vaccination rate increases, but he does not know the magnitude of the preventive effect of vaccination. In this setting, I first show how the planner can eliminate dominated vaccination rates and then how he can use the minimax or minimax-regret criterion to choose an undominated vaccination rate.
Public and private schoolteachers’ differences in terms of job attitudes in Albania
Authors: Buka Migena , Bilgiç Reyhan
Published: February 2010

In the present study, the attitudinal differences between public and private schoolteachers in Albania were investigated. Since the type of the organization varies, one would expect different climates for the emergence of job attitudes—mainly job satisfaction, job involvement, and organizational commitment, the most frequently studied job attitudes in the industrial and organizational psychology literature. It was hypothesized that the private schoolteachers would be more satisfied than public schoolteachers, especially due to high levels of payment and other desirable conditions. However, the public schoolteachers will be more involved than the private schoolteachers since they have to justify their continued work under the undesirable conditions. The commitment level of the private schoolteachers will be higher than the public schoolteachers since there is usually high correlation between job satisfaction and organizational commitment. Data were gathered from a total of 429 teachers working in public (n = 254) and private (n = 175) schools in Albania, in high and middle schools. The data were analyzed using multivariate analysis of covariance with age as a covariate. The results indicated that the private schoolteachers were more satisfied, as expected, revealed a weaker job involvement and were more committed to their school than their colleagues in the public sector. The results were found to be in line with previous studies conducted in the west. However, this study is believed to have a potential contribution to the literature in general, and to the Albanian local literature in particular. To the knowledge of the authors, there has been no similar study in Albania. Discussion is provided along with the limitations of the study and suggestions for future research.
Trial after trial: General processing consequences as a function of repetition and change in multidimensional sound
Authors: Dyson Benjamin J.
Published: February 2010

While there are pointers relating to the consequences of repetition, a general framework regarding the cognitive implications of processing multidimensional stimuli as a function of previous stimulus history is currently lacking. Three experiments using sounds varying in location and pitch were carried out, in which the immediate consequences of repeating or changing task-relevant and task-irrelevant attributes were orthogonally examined. A consistent pattern of data was shown, in that the magnitude of selective attention failure was larger when the task-relevant value repeated across trials, while differences between dimensions were larger when the task-relevant value changed across trials. These effects of irrelevance and dimension as a function of intertrial contingency are summarized in a model depicting the dynamic allocation of processing resource.
p23/Tmp21 Differentially Targets the Rac-GAP β2-Chimaerin and Protein Kinase C via Their C1 Domains
Authors: Wang HongBin , Kazanietz Marcelo G.
Published: February 2010

The C1 domains in protein kinase C (PKC) isozymes and other signaling molecules are responsible for binding the lipid second messenger diacylglycerol and phorbol esters, and for mediating translocation to membranes. Previous studies revealed that the C1 domain in α- and β-chimaerins, diacylglycerol-regulated Rac-GAPs, interacts with the endoplasmic reticulum/Golgi protein p23/Tmp21. Here, we found that p23/Tmp21 acts as a C1 domain-docking protein that mediates perinuclear translocation of β2-chimaerin. Glu227 and Leu248 in the β2-chimaerin C1 domain are crucial for binding p23/Tmp21 and perinuclear targeting. Interestingly, isolated C1 domains from individual PKC isozymes differentially interact with p23/Tmp21. For PKCε, it interacts with p23/Tmp21 specifically via its C1b domain; however, this association is lost in response to phorbol esters. These results demonstrate that p23/Tmp21 acts as an anchor that distinctively modulates compartmentalization of C1 domain-containing proteins, and it plays an essential role in β2-chimaerin relocalization. Our study also highlights the relevance of C1 domains in protein–protein interactions in addition to their well-established lipid-binding properties.
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.
Ultrasound Imaging for Regional Anesthesia in Infants, Children, and Adolescents
Authors: Tsui Ban C. H. , Suresh Santhanam
Published: February 2010

Complementary to a previous publication related to pediatric extremity and trunk blockade, the authors present a comprehensive narrative review of the literature pertaining to techniques described and outcomes evaluated for ultrasound imaging in pediatric neuraxial anesthesia. The sonoanatomy related to each block is also described and illustrated to serve as a foundation for better understanding the block techniques described. For neuraxial blockade, ultrasound may fairly reliably predict the depth to loss of resistance and can enable a dynamic view of the needle and catheter after entry into the spinal canal. Particularly, in young infants, direct visualization of the needle and catheter tip may be possible, whereas in older children surrogate markers including the displacement of dura mater by the injection of fluid may be necessary for confirming needle and catheter placement. More outcome-based, prospective, randomized, controlled trials are required to prove the benefits of ultrasound when compared with conventional methods.
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.
Electrical structures of interfaces: a Painlevé II model
Authors: Bass L. , Nimmo J. J. C. , Rogers C. , Schief W. K.
Published: February 2010

A Painlevé II model derived out of the classical Nernst–Planck system is applied in the context of boundary value problems that describe the electric field distribution in a regionx>0 occupied by an electrolyte. For privileged flux ratios of the ion concentrations, the auto-Bäcklund transformation admitted by the Painlevé II equation may be applied iteratively to construct exact solutions to classes of physically relevant boundary value problems. These representations involve, in turn, either Yablonskii–Vorob’ev polynomials or classical Airy functions. The requirement that the electric field distribution and ion concentrations in these representations be non-singular imposes constraints on the physical parameters. These are investigated in detail along with asymptotic properties.
Ultrafast X-ray diffraction in liquid, solution and gas: present status and future prospects
Authors: Kim Jeongho , Kim Kyung Hwan , Lee Jae Hyuk , Ihee Hyotcherl
Published: February 2010

In recent years, the time-resolved X-ray diffraction technique has been established as an excellent tool for studying reaction dynamics and protein structural transitions with the aid of 100 ps X-ray pulses generated from third-generation synchrotrons. The forthcoming advent of the X-ray free-electron laser (XFEL) will bring a substantial improvement in pulse duration, photon flux and coherence of X-ray pulses, making time-resolved X-ray diffraction even more powerful. This technical breakthrough is envisioned to revolutionize the field of reaction dynamics associated with time-resolved diffraction methods. Examples of candidates for the first femtosecond X-ray diffraction experiments using highly coherent sub-100 fs pulses generated from XFELs are presented in this paper. They include the chemical reactions of small molecules in the gas and solution phases, solvation dynamics and protein structural transitions. In these potential experiments, ultrafast reaction dynamics and motions of coherent rovibrational wave packets will be monitored in real time. In addition, high photon flux and coherence of XFEL-generated X-ray pulses give the prospect of single-molecule diffraction experiments.
Analysis of time-resolved X-ray scattering data from solution-state systems
Authors: Haldrup Kristoffer , Christensen Morten , Meedom Nielsen Martin
Published: February 2010

As ultrafast time-resolved studies of liquid systems with the laser pump/X-ray scattering probe method have come of age over the past decade, several groups have developed methods for the analysis of such X-ray scattering data. The present article describes a method developed primarily with a focus on determining structural parameters in the excited states of medium-sized molecules (~30 atoms) in solution. The general methodology is set in a maximum-likelihood framework and is introduced through the analysis of the photoactive platinum compound PtPOP, in particular the structure of its lowest triplet excited state (3A2u). Emphasis is put on structure determination in terms of model comparisons and on the information content of difference scattering signals as well as the related experimental variables. Several suggestions for improving the accuracy of these types of measurements are presented.
Time-resolved synchrotron diffraction and theoretical studies of very short-lived photo-induced molecular species
Authors: Coppens Philip , Benedict Jason , Messerschmidt Marc , Novozhilova Irina , Graber Tim , Chen Yu-Sheng , Vorontsov Ivan , Scheins Stephan , Zheng Shao-Liang
Published: February 2010

Definitive experimental results on the geometry of fleeting species are at the time of writing still limited to monochromatic data collection, but methods for modifications of the polychromatic Laue data to increase their accuracy and their suitability for pump–probe experiments have been implemented and are reviewed. In the monochromatic experiments summarized, excited-state conversion percentages are small when neat crystals are used, but are higher when photoactive species are embedded in an inert framework in supramolecular crystals. With polychromatic techniques and increasing source brightness, smaller samples down to tenths of a micrometre or less can be used, increasing homogeneity of exposure and the fractional population of the excited species. Experiments described include a series of transition metal complexes and a fully organic example involving excimer formation. In the final section, experimental findings are compared with those from theoretical calculations on the isolated species. Qualitative agreement is generally obtained, but the theoretical results are strongly dependent on the details of the calculation, indicating the need for further systematic analysis.
3D seismic expression of km‐scale fluid escape pipes from offshore Namibia
Authors: Moss J. L. , Cartwright J.
Published: February 2010

This 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.
Clinical applicability of the World Health Organization Quality of Life Scale Brief Version (WHOQOL‐BREF) to mothers of children with asthma in Taiwan
Authors: Gau Bih‐Shya , Chen Yueh‐Chih , Lo Li‐Hua , Chang Mei , Chao Yu‐Mei (Yu) , Chiang Bor‐Luen , Yao Grace
Published: February 2010

Aims.  This study examined the clinical applicability of the World Health Organization Quality of Life Scale brief version (WHOQOL‐BREF) to mothers of children with asthma in Taiwan.

Background.  The WHOQOL‐BREF scale has been culturally adapted for Taiwan and applied to a variety of ill and healthy subjects in hospitals and the community and to the general population in the 2001 National Health Interview Survey in Taiwan. Its application to explore the QOL of mothers of children with asthma in Taiwan allows future cross‐population comparisons.

Design.  A cross‐sectional survey.

Methods.  Internal consistency, test–retest reliability; content validity, criterion‐related validity and discriminant validity were assessed. A total of 229 mothers participated in the study.

Results.  The WHOQOL‐BREF showed acceptable psychometric properties. Internal consistency of 0·63–0·84, content validity r = 0·39–0·65 (p < 0·01) and criterion‐related validity r = 0·28–0·65 (p < 0·05) were reported. Discriminant validity was also found, especially in the domain of physical health. Issues of QOL for mothers, especially in the realm of physical health need more support and attention from health professionals.

Conclusions.  This study supports the clinical applicability of the WHOQOL‐BREF scale as a measure of QOL of mothers of children with asthma. Future studies to compare the QOL measured by WHOQOL‐BREF in female caregivers of children with other chronic health conditions are suggested.

Relevance to clinical practice.  Our findings show that mothers are hardly ever free from the strains of the daily‐care of an asthmatic and bear the uncertainties for the unending illness. The health care team is responsible for providing collaborative care approaches in hospital, home and school health care settings for children with asthma and their mothers.