bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of TransFix™ cerebrospinal fluid storage tubes prevents cellular loss and enhances flow cytometric detection of malignant hematological cells after 18 hours of storage
Authors: de Jongste Adriaan H. , Kraan Jaco , van den Broek Patricia D. , Brooimans Rik A. , Bromberg Jacoline E. , van Montfort Kees A. , Smitt Peter A. Sillevis , Gratama Jan W.
Published: May 2013

Flow cytometry is a sensitive method for detection of leptomeningeal localizations of hematological malignancies (LHM) in cerebrospinal fluid (CSF). Rapid processing of CSF is needed, as leukocyte numbers appear to decline quickly after lumbar puncture. The cell‐stabilizing agent TransFix™ may enhance the detection of LHM in CSF by preventing cellular loss. To study the effects of TransFix on leukocyte numbers and the detection of LHM, we prospectively collected 99 CSF samples from patients with suspected or proven LHM in tubes with (i) TransFix; (ii) serum‐containing medium; and (iii) no cell‐stabilizing agents (native CSF). Presence of LHM and absolute leukocyte numbers were determined by flow cytometry after 30 minutes and 18 hours of storage. Leukocyte numbers in TransFix‐stabilized CSF were higher than in the corresponding native samples at both time points (1.4× and 2.3× respectively, P < 0.0001 on each occasion). After 18 hours of storage, TransFix enhanced the detection of LHM in CSF. In all discordant paired observations (13/99, P = 0.005), the level of suspicion (classified as positive, suspicious, or negative) in CSF with TransFix was higher than in native CSF. We conclude that the use of TransFix‐containing CSF storage tubes prevents cellular loss and enhances flow cytometric detection of LHM after 18 hours of storage. © 2013 International Clinical Cytometry Society.
Antinociceptive Activity of Metamizol Metabolites in a Rat Model of Arthritic Pain
Authors: López‐Muñoz Francisco Javier , Soria‐Arteche Olivia , López José Raúl Medina , Hurtado y de la Peña Marcela , García Ma. Concepción Lozada , Moreno‐Rocha Luis Alfonso , Domínguez‐Ramírez Adriana Miriam
Published: May 2013

Preclinical Research

The aim of the present study was to evaluate the antinociceptive activity of the main metamizol (MET) metabolites, 4‐methylaminoantipyrine (MAA), 4‐aminoantipyrine (AA), 4‐formylaminoantipyrine (FAA), and 4‐acetylaminoantipyrine (AAA) using the “pain‐induced functional impairment in rat” model (PIFIR model). The antinociceptive efficacies of MAA and AA were 288.3% h and 281.1% h, respectively, close to the efficacy of MET (333.80% h). The effective dose to attain 50% of the maximum response (ED50) values for MET, MAA and AA were 126.1, 124.9, and 110.7 mg/kg, respectively. FAA and AAA were essentially inactive in this experimental model. Part of the antinociceptive effect showed by MET in this study might be attributed to the effect of the metabolites MAA and AA on cyclooxygenases COX‐1 and COX‐2 activity.
The role of water use and uptake on two Mediterranean shrubs' interaction in a brackish coastal dune ecosystem
Authors: Esquivias M. Paz , Zunzunegui María , Barradas Mari Cruz Díaz , Álvarez‐Cansino Leonor
Published: May 2013

Water relations are essential in plant–plant interactions, particularly in Mediterranean coastal sand dunes, owing to marked drought periods and the possibility of groundwater (GW) salinization. In this study, seasonal water use dynamics were explored in the interaction between a native–invasive species, Retama monosperma, and the endangered Thymus carnosus, in south‐western Spain. The following variables were measured: xylem water isotopic composition to determine water sources, predawn and midday stem water potential and free leaf proline content as stress indicator. GW electrical conductivity and stable isotopes were also analysed to assess water table salinity. In late summer and spring, the warmest seasons, Thymus beneath Retama displayed significantly lower water potential and higher leaf proline content than isolated Thymus, whereas Retama showed the highest proline content in autumn and winter. Water sources showed different patterns depending on the Thymus situation: Isolated ones always matched the brackish GW, as well as Retama plants, whereas Thymus beneath Retama switched among rainfall, soil and water table, showing a seasonal change in the water‐harvesting strategy. Overall, competition for water sources between both species was discovered, which led to a shift in water use and water uptake strategies of understorey Thymus. The results also demonstrate the importance and potential use of species interaction studies in the development of threatened species management strategies. Copyright © 2013 John Wiley & Sons, Ltd.
A Mild Method for Regioselective Labeling of Aromatics with Radioactive Iodine
Authors: Rønnest Mads H. , Nissen Felix , Pedersen Palle J. , Larsen Thomas O. , Mier Walter , Clausen Mads H.
Published: May 2013

A novel technique to label ortho‐, meta‐, and para‐trimethylsilyl‐substituted aryl substituents with radioactive iodide is described. The method takes advantage of the ipso‐directing and activating properties of trimethylsilyl substituents on the arenes. The method was demonstrated on a griseofulvin analogue with promising anticancer properties and on lidocaine, a widely used local anesthetic drug. Treatment of a trimethylsilyl precursor with Tl(OCOCF3)3 followed by Na125I consistently afforded radioactive purities over 95 % in all cases.
Holocene evolution in weathering and erosion patterns in the Pearl River delta
Authors: Hu Dengke , Clift Peter D. , Böning Philipp , Hannigan Robyn , Hillier Stephen , Blusztajn Jerzy , Wan Shiming , Fuller Dorian Q.
Published: May 2013

Sediments in the Pearl River delta have the potential to record the weathering response of this river basin to climate change since 9.5 ka, most notably weakening of the Asian monsoon since the Early Holocene (∼8 ka). Cores from the Pearl River delta show a clear temporal evolution of weathering intensity, as measured by K/Al, K/Rb, and clay mineralogy, that shows deposition of less weathered sediment at a time of weakening monsoon rainfall in the Early‐Mid Holocene (6.0–2.5 ka). This may reflect an immediate response to a less humid climate, or more likely reduced reworking of older deposits from river terraces as the monsoon weakened. Human settlement of the Pearl River basin may have had a major impact on landscape and erosion as a result of the establishment of widespread agriculture. After around 2.5 ka weathering intensity sharply increased, despite limited change in the monsoon, but at a time when anthropogenic pollutants (e.g., Cu, Zn, and Pb) increased and when the flora of the basin changed. 87Sr/86Sr covaries with these other proxies but is also partly influenced by the presence of carbonate. The sediments in the modern Pearl River are even more weathered than the youngest material from the delta cores. We infer that the spread of farming into the Pearl River basin around 2.7 ka was followed by a widespread reworking of old, weathered soils after 2.5 ka, and large‐scale disruption of the river system that was advanced by 2.0 ka.
Increased frequency of cluster of differentiation 14 (CD14+) monocytes expressing interleukin 1 beta (IL‐1β) in Alzheimer's disease patients and intermediate levels in late‐onset depression patients
Authors: Torres Karen Cecília , Lima Giselle Sabrina , Fiamoncini Carolina Maciel , Rezende Vitor Bortolo , Pereira Patrícia Araújo , Bicalho Maria Aparecida , Moraes Edgar Nunes , Romano‐Silva Marco Aurélio
Published: May 2013

Objective

Depression might be a prodromal stage of dementia. Many factors contribute to the etiology of depression and dementia, being inflammation one of those. The present work measured and analyzed immune molecules involved in the innate immunity on cluster of differentiation 14 (CD14+) monocytes trying to investigate any relationship among late‐onset depression (LOD) and Alzheimer's disease (AD).

Methods

Immune molecules were evaluated in monocytes of AD, LOD patients, and controls using flow cytometry.

Results

Interestingly, interleukin 1 beta (IL‐1β) expressing CD14+ monocytes were increased in AD patients compared with controls. LOD presented intermediate frequency of CD14+ monocytes expressing IL‐1β between controls and AD patients.

Conclusion

Results suggest that an increased frequency of CD14+ monocytes expressing IL‐1β level could be a stage marker related to the pathophysiology of dementia process between normal aging and AD. Copyright © 2013 John Wiley & Sons, Ltd.
Limb imaging of the Venus O2 visible nightglow with the Venus Monitoring Camera
Authors: García Muñoz A. , Hueso R. , Sánchez‐Lavega A. , Markiewicz W. J. , Titov D. V. , Witasse O. , Opitz A.
Published: May 2013

We investigated the Venus O2 visible nightglow with imagery from the Venus Monitoring Camera on Venus Express. Drawing from data collected between April 2007 and January 2011, we study the global distribution of this emission, discovered in the late 1970s by the Venera 9 and 10 missions. The inferred limb‐viewing intensities are on the order of 150 kR at the lower latitudes and seem to drop somewhat toward the poles. The emission is generally stable, although there are episodes when the intensities rise up to 500 kR. We compare a set of Venus Monitoring Camera observations with coincident measurements of the O2 nightglow at 1.27 µm made with the Visible and Infrared Thermal Imaging Spectrometer, also on Venus Express. From the evidence gathered in this and past works, we suggest a direct correlation between the instantaneous emissions from the two O2 nightglow systems. Possible implications regarding the uncertain origin of the atomic oxygen green line at 557.7 nm are noted.
Assessing the potential improvement in short‐term earthquake forecasts from incorporation of GPS data
Authors: Wang Ting , Zhuang Jiancang , Kato Teruyuki , Bebbington Mark
Published: May 2013

We validate that changes of ground deformation recorded by GPS contain useful information for earthquake forecasting. A moving rate of variation filter is used to extract short‐term signals from GPS time series in New Zealand, California, and Japan. The precursory information of these signals for large earthquakes is evaluated using Molchan's error diagram. The results suggest that the GPS signals provide a probability gain of 2–4 for forecasting large earthquakes against a Poisson model. Further tests show that the GPS signals are not triggered by large earthquakes, and that the probability gain is not derived from forecasting aftershocks. This demonstrates that noncatalog information, such as GPS data, can be used to augment probabilistic models based on seismic catalog data to improve forecasting of large earthquakes.
Hydrological modeling of stalagmite δ18O response to glacial‐interglacial transitions
Authors: Baker Andy , Bradley Chris , Phipps Steven J.
Published: May 2013

Stalagmite δ18Ο series currently provide the most robustly dated characterization of glacial terminations. However, uncertainties associated with the stalagmite δ18Ο proxy record arise due to the complexity of flow within karst aquifers. Here we use an integrated climate‐soil‐groundwater lumped parameter hydrological model to demonstrate the range of potential stalagmite δ18Ο hydrological responses to significant global climate changes. Pseudoproxy stalagmite δ18Ο series were generated for millennial length model simulations, using general circulation model time‐slice data for 12, 11, and 10 ka for eastern China. Our model demonstrates that the variability within published δ18Ο records from Chinese stalagmites falls within that of modeled pseudoproxy series. We utilize model output to (i) quantify hydrological uncertainty (specifically the relative importance of changing precipitation amount, isotopic composition, and water balance); (ii) identify any nonstationarity in δ18O variability and its relationship to climate change; and (iii) demonstrate the processes that produce low‐frequency power in stalagmite δ18Ο.
Common and unique gray matter correlates of episodic memory dysfunction in frontotemporal dementia and alzheimer's disease
Authors: Irish Muireann , Piguet Olivier , Hodges John R. , Hornberger Michael
Published: May 2013

Conflicting evidence exists regarding the integrity of episodic memory in the behavioral variant of frontotemporal dementia (bvFTD). Recent converging evidence suggests that episodic memory in progressive cases of bvFTD is compromised to the same extent as in Alzheimer's disease (AD). The underlying neural substrates of these episodic memory deficits, however, likely differ contingent on dementia type. In this study we sought to elucidate the neural substrates of episodic memory performance, across recall and recognition tasks, in both patient groups using voxel‐based morphometry (VBM) analyses. We predicted that episodic memory dysfunction would be apparent in both patient groups but would relate to divergent patterns of neural atrophy specific to each dementia type. We assessed episodic memory, across verbal and visual domains, in 19 bvFTD, 18 AD patients, and 19 age‐ and education‐matched controls. Behaviorally, patient groups were indistinguishable for immediate and delayed recall, across verbal and visual domains. Whole‐brain VBM analyses revealed regions commonly implicated in episodic retrieval across groups, namely the right temporal pole, right frontal lobe, left paracingulate gyrus, and right anterior hippocampus. Divergent neural networks specific to each group were also identified. Whereas a widespread network including posterior regions such as the posterior cingulate cortex, parietal and occipital cortices was exclusively implicated in AD, the frontal and anterior temporal lobes underpinned the episodic memory deficits in bvFTD. Our results point to distinct neural changes underlying episodic memory decline specific to each dementia syndrome. Hum Brain Mapp 35:1422–1435, 2014. © 201 Wiley Periodicals, Inc.
FROM SOCIAL CAPITAL TO HEALTH – AND BACK
Authors: Rocco Lorenzo , Fumagalli Elena , Suhrcke Marc
Published: May 2013

We assess the causal relationship between health and social capital, measured by generalized trust, both at the individual and the community level. The paper contributes to the literature in two ways: it tackles the problems of endogeneity and reverse causation between social capital and health by estimating a simultaneous equation model, and it explicitly accounts for mis‐reporting in self‐reported trust.

The inter‐relationship is tested using data from the first four waves of the European Social Survey for 25 European countries, supplemented by regional data from Eurostat. Our estimates show that a causal and positive relationship between self‐perceived health and social capital does exist and that it acts in both directions. In addition, the magnitude of the structural coefficients suggests that individual social capital is a strong determinant of health, whereas community level social capital plays a considerably smaller role in determining health. Copyright © 2013 John Wiley & Sons, Ltd.
Groundwater modelling with limited data sets: the Chari–Logone area (Lake Chad Basin, Chad)
Authors: Candela L. , Elorza F. J. , Tamoh K. , Jiménez‐Martínez J. , Aureli A.
Published: May 2013

One of the most important issues for water resource management is developing strategies for groundwater modelling that are adaptable to data scarcity. These strategies are particularly important in arid and semi‐arid areas where access to data is poor and data collection is difficult, such as the Lake Chad Basin in Africa. In the present study, we establish a numerical groundwater flow model and evaluate the effects of dry and wet periods on groundwater recharge in the Chari–Logone area (96 000 km2) of the Lake Chad Basin. Boundary conditions, flow direction, sources, and sinks for the Chari–Logone local model were obtained by revising and remodelling the Lake Chad Basin regional hydrogeological model (508 400 km2) developed by the BRGM (Bureau de Recherches Géologiques et Minières) in the 1990s. The simulated aquifer water level showed good agreement with observed levels. Aquifer recharge is primarily determined by river–aquifer interactions and mostly occurs in the southern section of the study area. In wet years, groundwater recharge also occurs in the N'Djamena area. The approach we adopted provided relevant results and was useful as an initial step in more detailed modelling of the area. It also proved to be a useful method for groundwater modelling in large semi‐arid and arid regions where available data are scarce. Copyright © 2013 John Wiley & Sons, Ltd.
Use of soil‐streamwater relationships to assess regional patterns of acidic deposition effects in the northeastern USA
Authors: Siemion Jason , Lawrence Gregory B. , Murdoch Peter S.
Published: May 2013

Declines of acidic deposition levels by as much as 50% since 1990 have led to partial recovery of surface waters in the northeastern USA but continued depletion of soil calcium through this same period suggests a disconnection between soil and surface water chemistry. To investigate the role of soil‐surface water interactions in recovery from acidification, the first regional survey to directly relate soil chemistry to stream chemistry during high flow was implemented in a 4144‐km2 area of the Catskill region of New York, where acidic deposition levels are among the highest in the East.

More than 40% of 95 streams sampled in the southern Catskill Mountains were determined to be acidified and had inorganic monomeric aluminum concentrations that exceeded a threshold that is toxic to aquatic biota. More than 80% likely exceeded this threshold during the highest flows, but less than 10% of more than 100 streams sampled were acidified in the northwestern portion of the region. Median Oa horizon soil base saturation ranged from 50% to 80% at 200 sites across the region, but median base saturation in the upper 10 cm of the B horizon was less than 20% across the region and was only 2% in the southern area. Aluminum is likely to be interfering with root uptake of calcium in the mineral horizon in approximately half the sampled watersheds. Stream chemistry was highly variable over the Catskill region and, therefore, did not always reflect the calcium depletion of the B horizon that our sampling suggested was nearly ubiquitous throughout the region. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.
Uridine adenosine tetraphosphate induces contraction of circular and longitudinal gastric smooth muscle by distinct signaling pathways
Authors: Yuan Wensu , Wang Zengyong , Li Jingjing , Li Dong , Liu Deliang , Bai Gang , Walsh Michael P. , Gui Yu , Zheng Xi‐Long
Published: May 2013

Extracellular nucleotides uridine‐5′‐triphosphate (UTP) and adenosine‐5′‐triphosphate (ATP) induce contraction of gastric smooth muscle (SM). The dinucleotide uridine adenosine tetraphosphate (Up4A), an endothelium‐derived contraction factor, induces vascular SM contraction. Its effect on gastric SM contractions, however, is unknown. We addressed the hypothesis that Up4A induces gastric SM contraction via a mechanism that may differ between circular and longitudinal muscle (CM and LM, respectively). CM and LM were isolated from rat gastric fundus for the measurement of isometric tension. Up4A induced transient contractile responses in both CM and LM, which were similar to those induced by ATP and UTP. Up4A failed to induce contraction of either LM or CM in the absence of extracellular Ca2+ or in the presence of nimodipine, an inhibitor of voltage‐gated Ca2+ channels. P2X1, 2, 4, 5 and 7 and P2Y1, 2, 4 and 6 receptor expression was detected in gastric SM by reverse transcription‐polymerase chain reaction. IP5I (a P2X receptor antagonist) and α,β‐methylene‐ATP (a P2X receptor agonist) had no effect on Up4A‐induced contractions of either LM or CM, and α,β‐methylene‐ATP alone failed to induce a contractile response in either tissue. Suramin (a P2Y receptor antagonist), on the other hand, significantly inhibited Up4A‐induced contraction of CM, but not LM. Up4A‐induced contraction of CM, but not LM, was also inhibited by pretreatment with Y‐27632, an inhibitor of Rho‐associated kinase. We conclude that Up4A induces extracellular Ca2+‐dependent contractions of rat gastric LM and CM, and Up4A‐induced contraction of CM is mediated by suramin‐sensitive P2Y receptors and subsequent activation of the Rho‐associated kinase pathway. © 2013 IUBMB Life, 65(7):623–632, 2013.
Cytoplasmic reactive oxygen species and SOD1 regulate bone mass during mechanical unloading
Authors: Morikawa Daichi , Nojiri Hidetoshi , Saita Yoshitomo , Kobayashi Keiji , Watanabe Kenji , Ozawa Yusuke , Koike Masato , Asou Yoshinori , Takaku Tomoiku , Kaneko Kazuo , Shimizu Takahiko
Published: May 2013

Oxidative stress contributes to the pathogenesis of age-related diseases as well as bone fragility. Our previous study demonstrated that copper/zinc superoxide dismutase (Sod1)-deficient mice exhibit the induction of intracellular reactive oxygen species (ROS) and bone fragility resulting from low-turnover bone loss and impaired collagen cross-linking (Nojiri et al. J Bone Miner Res. 2011;26:2682–94). Mechanical stress also plays an important role in the maintenance of homeostasis in bone tissue. However, the molecular links between oxidative and mechanical stresses in bone tissue have not been fully elucidated. We herein report that mechanical unloading significantly increased intracellular ROS production and the specific upregulation of Sod1 in bone tissue in a tail-suspension experiment. We also reveal that Sod1 loss exacerbated bone loss via reduced osteoblastic abilities during mechanical unloading. Interestingly, we found that the administration of an antioxidant, vitamin C, significantly attenuated bone loss during unloading. These results indicate that mechanical unloading, in part, regulates bone mass via intracellular ROS generation and the Sod1 expression, suggesting that activating Sod1 may be a preventive strategy for ameliorating mechanical unloading–induced bone loss. © 2013 American Society for Bone and Mineral Research.
Cytochrome P450 compound I in the plane wave pseudopotential framework: GGA electronic and geometric structure of thiolate‐ligated iron(IV)–oxo porphyrin
Authors: Elenewski Justin E. , Hackett John C
Published: May 2013

The cytochromes P450 constitute a ubiquitous family of metalloenzymes, catalyzing manifold reactions of biological and synthetic importance via a thiolate‐ligated iron‐oxo (IV) porphyrin radical species denoted compound I (Cpd I). Experimental investigations have implicated this intermediate in a broad spectrum of biophysically interesting phenomena, further augmenting the importance of a Cpd I model system. Ab initio molecular dynamics, including Car–Parrinello and path integral methods, conjoin electronic structure theory with finite temperature simulation, affording tools most valuable to approach such enzymes. These methods are typically driven by density functional theory (DFT) in a plane‐wave pseudopotential framework; however, existing studies of Cpd I have been restricted to localized Gaussian basis sets. The appropriate choice of density functional and pseudopotential for such simulations is accordingly not obvious. To remedy this situation, a systematic benchmarking of thiolate‐ligated Cpd I is performed using several generalized‐gradient approximation (GGA) functionals in the Martins–Troullier and Vanderbilt ultrasoft pseudopotential schemes. The resultant electronic and structural parameters are compared to localized–basis DFT calculations using GGA and hybrid density functionals. The merits and demerits of each scheme are presented in the context of reproducing existing experimental and theoretical results for Cpd I. © 2013 Wiley Periodicals, Inc.
Effects of Rifampin, a Potent Inducer of Drug‐Metabolizing Enzymes and an Inhibitor of OATP1B1/3 Transport, on the Single Dose Pharmacokinetics of Anacetrapib
Authors: Anderson Matt S. , Cote Josee , Liu Yang , Stypinski Daria , Auger Patrice , Hohnstein Anne , Rasmussen Scott , Johnson‐Levonas Amy O. , Gutstein David E.
Published: May 2013

Anacetrapib is a novel cholesteryl ester transfer protein (CETP) inhibitor in development for treatment of dyslipidemia. This open‐label, fixed‐sequence, 3‐period study was intended to evaluate the potential of anacetrapib to be a victim of OATP1B1/3 inhibition and strong CYP3A induction using acute and chronic dosing of rifampin, respectively, as a probe. In this study, 16 healthy subjects received 100 mg anacetrapib administered without rifampin (Day 1, Period 1), with single‐dose (SD) 600 mg rifampin (Day 1, Period 2), and with multiple‐dose (MD) 600 mg rifampin for 20 days (Day 14, Period 3). Log‐transformed anacetrapib AUC0−∞ and Cmax were analyzed by a linear mixed effects model. The GMRs and 90% CIs for anacetrapib AUC0‐∞ and Cmax were 1.25 (1.04, 1.51) and 1.43 (1.13, 1.82) for SD rifampin (Period 2/Period 1) and 0.35 (0.29, 0.42) and 0.26 (0.21, 0.32) for MD rifampin (Period 3/Period 1), respectively. Anacetrapib was generally well tolerated in both the absence/presence of SD and MD rifampin. In conclusion, treatment with SD rifampin, which inhibits the OATP1B1/3 transporter system, did not substantially influence the SD pharmacokinetics of anacetrapib, while chronic (20 days) administration of rifampin, which strongly induces CYP3A isozymes, reduced mean systemic exposure to SD anacetrapib by 65%.
Performance improvement of Bacillus aryabhattaiITBHU02 for high‐throughput production of a tumor‐inhibitory L‐asparaginase using a kinetic model based approach
Authors: Singh Yogendra , Srivastava S. K.
Published: May 2013

BACKGROUND

An unstructured model for batch culture production of L‐asparaginase by Bacillus aryabhattai ITBHU02, by means of the Luedeking–Piret incorporated logistic equation, was developed explaining the correlation between growth dynamics and enzyme production kinetics with respect to glucose depletion at different levels. The main goal was to build up a means for process optimization, design, control and analysis of L‐asparaginase production. Various thermodynamic parameters were estimated to comprehend enzyme stability and affiliated industrial applicability.

RESULTS

Specific growth rate maxima were increased with increasing initial glucose concentration, whereas the specific productivity was best supported at a glucose concentration 5.0 g L‐1. The fermentative production of L‐asparaginase was greatly influenced by oxygen supply, reaching a maximum level at an aeration rate of 0.6 vvm. The activation energies for growth and death rate were 33.8±6.0 and 99.8±9.0 kJ mol‐1, respectively, with activation enthalpy values of enzyme formation and thermal deactivation 70.2±9.0 and 46.1±11.0 kJ mol‐1, respectively.

CONCLUSION

The economic production of L‐asparaginase by B. aryabhattai was achieved efficiently at low glucose concentration and mild aeration. Endogenous metabolism of the strain for L‐asparaginase synthesis was thermostable up to 40°C, which makes the strain commercially important as it can be utilized for cost‐effective L‐asparaginase production within countries such as India, where 35–40°C temperatures are quite common. © 2013 Society of Chemical Industry
Large‐scale flow vortices following a magnetospheric sudden impulse
Authors: Samsonov A. A. , Sibeck D. G.
Published: May 2013

Global MHD simulations predict the generation of flow vortices on the magnetospheric flanks near the equatorial plane after the impact of solar wind dynamic pressure pulses on the magnetosphere. These vortices are associated with field‐aligned currents, having similar senses to those responsible for the main impulse, i.e., the second impulse of the well‐known sudden impulse variations at high geomagnetic latitudes. We investigate the evolution of the vortices and show that they result from the interaction of a fast MHD wave and the inner (near‐Earth) boundary of numerical models. Near the inner boundary, the Ampere force decelerates plasma flow resulting in two closely related phenomena: the generation of flow vortices and the launch of a reflected fast wave moving sunward. The vortices propagate antisunward and split into several parts during several minutes. The reflected wave interacts with the magnetopause and bow shock and changes its velocity. The interaction between the reflected wave and bow shock results in two new discontinuities moving earthward through the magnetosheath. The first is either a very weak fast rarefaction wave or a weak fast shock, and the second is either a tangential discontinuity or a compound discontinuity with a decrease of the density and magnetic field and an increase of the temperature. We speculate that the inner boundary in simulations may correspond to either the plasmasphere or ionosphere.
Effects of dietary phytophenols on the expression of microRNAs involved in mammalian cell homeostasis
Authors: Lançon Allan , Michaille Jean‐Jacques , Latruffe Norbert
Published: May 2013

Besides synthesizing nutritive substances (proteins, fats and carbohydrates) for energy and growth, plants produce numerous non‐energetic so‐called secondary metabolites (mainly polyphenols) that allow them to protect themselves against infections and other types of hostile environments. Interestingly, these polyphenols often provide cells with valuable bioactive properties for the maintenance of their functions and homeostasis (signaling, gene regulation, protection against acquired or infectious diseases, etc.) both in humans and animals. Namely, from a nutritional point of view, and based on epidemiological data, it is now well accepted that the regular consumption of green vegetables, fruits and fibers has protective effects against the onset of cancer as well as of inflammatory, neurodegenerative, metabolic and cardiovascular diseases, and consequently increases the overall longevity. In particular, grapevine plants produce large amounts of a wide variety of polyphenols. The most prominent of those—resveratrol—has been shown to impair or delay cardiovascular alterations, cancer, inflammation, aging, etc. Until recently, the molecular bases of the pleiotropic effects of resveratrol remained largely unclear despite numerous studies on a variety of signaling pathways and the transcriptional networks that they control. However, it has been recently proposed that the protective properties of resveratrol may arise from its modulation of small non‐coding regulatory RNAs, namely microRNAs. The aim of this review is to present up‐to‐date data on the control of microRNA expression by dietary phytophenols in different types of human cells, and their impact on cell differentiation, cancer development and the regulation of the inflammatory response. © 2013 Society of Chemical Industry
Prospective clinical investigation of the relationship between idiopathic benign paroxysmal positional vertigo and bone turnover
Authors: Parham Kourosh , Leonard Gerald , Feinn Richard S. , Lafreniere Denis , Kenny Anne M.
Published: May 2013

Objective/Hypothesis

Idiopathic benign paroxysmal positional vertigo (BPPV) is a strong indicator of decreased bone density (osteopenia/osteoporosis) in postmenopausal women, and there is a correlation between BPPV and serum levels of biochemical markers of bone turnover.

Study Design

Prospective pilot clinical trial.

Methods

Two groups of postmenopausal women were recruited. The BPPV group consisted of 16 women with a diagnosis of BPPV. The OSTEO group consisted of 13 women with history of osteopenia/osteoporosis. Dual‐energy x‐ray absorptiometry scan results were compared, along with serum levels of ionized calcium (iCa), vitamin D, aminoterminal propeptide of protocollagen type I (P1NP), and aminoterminal telopeptides of collagen (sNTX).

Results

Prevalence of decreased bone mass density among BPPV subjects was 81%, and prevalence of BPPV among OSTEO subjects was 31%. BPPV subjects had higher P1NP levels. Multiple regression analysis showed that among BPPV subjects, there was positive correlation between P1NP and sNTX and a negative correlation between P1NP and vitamin D level. Age was positively correlated with serum levels of both biomarkers among the BPPV subjects. T score, serum iCa, and serum vitamin D levels did not appear to correlate with presence of BPPV.

Conclusions

Idiopathic BPPV subjects have a high prevalence of osteopenia/osteoporosis. Levels of biochemical markers of bone turnover correlate with presence of BPPV. Our results, based on a sample of U.S. subjects, support an association between idiopathic BPPV and disorders of bone turnover.

Level of Evidence

2b. Laryngoscope, 123:2834–2839, 2013
Producing the omega‐3 fatty acids DHA and EPA in oilseed crops
Authors: Walsh Terence A. , Metz James G.
Published: May 2013

There is increasing consumer demand for the omega‐3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) because of their well‐recognized benefits for human health and the observation that current western diets are deficient in these important polyunsaturated fatty acids (PUFAs). This has led to the need for additional cost‐effective and sustainable dietary sources of DHA and EPA beyond the traditional resource, oceanic fish. Recent advances in plant biotechnology have shown that DHA and EPA can be produced in vegetable oils using two approaches involving different sets of genes. One approach incorporates genes that direct sequential rounds of desaturation and elongation of native plant fatty acids. The other approach uses microalgal PUFA synthase genes to make DHA de novo without the need for native fatty acid precursors. These strategies offer the potential for sustainable production methods for DHA and EPA via land‐based oilseed crops.
Diffusion tensor imaging of Parkinson's disease, atypical parkinsonism, and essential tremor
Authors: Prodoehl Janey , Li Hong , Planetta Peggy J. , Goetz Christopher G. , Shannon Kathleen M. , Tangonan Ruth , Comella Cynthia L. , Simuni Tanya , Zhou Xiaohong Joe , Leurgans Sue , Corcos Daniel M. , Vaillancourt David E.
Published: May 2013

Diffusion tensor imaging could be useful in characterizing movement disorders because it noninvasively examines multiple brain regions simultaneously. We report a multitarget imaging approach focused on the basal ganglia and cerebellum in Parkinson's disease, parkinsonian variant of multiple system atrophy, progressive supranuclear palsy, and essential tremor and in healthy controls. Seventy‐two subjects were studied with a diffusion tensor imaging protocol at 3 Tesla. Receiver operating characteristic analysis was performed to directly compare groups. Sensitivity and specificity values were quantified for control versus movement disorder (92% sensitivity, 88% specificity), control versus parkinsonism (93% sensitivity, 91% specificity), Parkinson's disease versus atypical parkinsonism (90% sensitivity, 100% specificity), Parkinson's disease versus multiple system atrophy (94% sensitivity, 100% specificity), Parkinson's disease versus progressive supranuclear palsy (87% sensitivity, 100% specificity), multiple system atrophy versus progressive supranuclear palsy (90% sensitivity, 100% specificity), and Parkinson's disease versus essential tremor (92% sensitivity, 87% specificity). The brain targets varied for each comparison, but the substantia nigra, putamen, caudate, and middle cerebellar peduncle were the most frequently selected brain regions across classifications. These results indicate that using diffusion tensor imaging of the basal ganglia and cerebellum accurately classifies subjects diagnosed with Parkinson's disease, atypical parkinsonism, and essential tremor and clearly distinguishes them from control subjects. © 2013 International Parkinson and Movement Disorder Society
Pharmacological treatment of chorea in Huntington's disease–good clinical practice versus evidence‐based guideline
Authors: Reilmann Ralf
Published: May 2013

Recently, the American Academy of Neurology published an evidence‐based guideline for the pharmacological treatment of chorea in Huntington's disease. Although the progress in medical care because of the implementation of criteria of evidence‐based medicine is undisputed, the guideline classifies the level of evidence for drugs to reduce chorea based on anchors in the Unified Huntington's Disease Rating Scale‐Total Motor Score chorea sum score, which were chosen arbitrarily and do not reflect validated or generally accepted levels of clinical relevance. Thus, the guideline faces several serious limitations and delivers clinical recommendations that do not represent current clinical practice; these are reviewed in detail, and arguments are presented why these recommendations should not be followed. To remedy the lack of evidence‐based recommendations and provide guidance to a pragmatic symptomatic therapy of chorea in HD, a flow‐chart pathway that follows currently established clinical standards based on expert opinion is presented. © 2013 Movement Disorder Society
Muscle weakness, fatigue, and torque variability: Effects of age and mobility status
Authors: Kent‐Braun Jane A. , Callahan Damien M. , Fay Jessica L. , Foulis Stephen A. , Buonaccorsi John P.
Published: May 2013

Introduction: Whereas deficits in muscle function, particularly power production, develop in old age and are risk factors for mobility impairment, a complete understanding of muscle fatigue during dynamic contractions is lacking. We tested hypotheses related to torque‐producing capacity, fatigue resistance, and variability of torque production during repeated maximal contractions in healthy older, mobility‐impaired older, and young women. Methods: Knee extensor fatigue (decline in torque) was measured during 4 min of dynamic contractions. Torque variability was characterized using a novel 4‐component logistic regression model. Results: Young women produced more torque at baseline and during the protocol than older women (P < 0.001). Although fatigue did not differ between groups (P = 0.53), torque variability differed by group (P = 0.022) and was greater in older impaired compared with young women (P = 0.010). Conclusions: These results suggest that increased torque variability may combine with baseline muscle weakness to limit function, particularly in older adults with mobility impairments. Muscle Nerve 49: 209–217, 2014
Chemical and Functional Characterisation of Propolis Collected from East Andalusia (Southern Spain)
Authors: Kumazawa Shigenori , Bonvehí Josep Serra , Torres Cristina , Mok‐Ryeon Ahn , Bermejo Francisco José Orantes
Published: May 2013

Introduction

Propolis is a complex mixture of natural sticky, gummy and resinous components produced by honeybees (Apis mellifera L.) from plant materials. However, phytochemical data of the Andalusian (southern Spain) propolis are scant.

Objective

The primary objectives of this study were to chemically characterise the compounds and evaluate the anti‐oxidant activity found in 28 Andalusian propolis samples.

Methods

Ethanol extracts of propolis (EEP) were prepared and examined for their anti‐oxidant activity by 2,2′‐azinobis(3‐ethylbenzothiazoline‐6‐sulphonic acid) and 2,2‐diphenyl‐1‐picrylhydrazyl assays. To characterise the phenolic composition, the presence of 11 compounds was identified by HPLC analysis with photodiode array and mass spectrometric detection.

Results

All propolis samples had strong anti‐oxidant activity, accompanied by high total phenolic content. The most abundant compounds were flavonoids. Concerning the phenolic compounds content, our results showed that the 75% of the samples analysed contained at least 80 mg/g of flavonoids, primarily pinobanksin 3‐acetate, pinocembrin, chrysin, galangin and pinobanksin. Caffeic acid phenethyl ester was detected in almost all EEP samples but in smaller proportions (mean 12.9 ± 2.8 mg/g).

Conclusion

The present investigation constitutes the first comprehensive report on the phenolics identified in southern Spanish propolis. The results revealed that the samples tested showed a high scavenging activity and therefore indicate the possible use of Andalusian propolis as an important source of natural anti‐oxidants. Copyright © 2013 John Wiley & Sons, Ltd.
Pilot evaluation of an automated method to decrease false‐positive signals induced by co‐prescriptions in spontaneous reporting databases
Authors: Avillach Paul , Salvo Francesco , Thiessard Frantz , Miremont‐Salamé Ghada , Fourrier‐Reglat Annie , Haramburu Françoise , Bégaud Bernard , Moore Nicholas , Pariente Antoine ,   on behalf of l'Association des Centres Régionaux de Pharmacovigilance
Published: May 2013

Purpose

To test an automated method to decrease the number of false‐positive (FP) signals of disproportionate reportings (SDRs) generated by co‐prescription.

Methods

Automated backward stepwise removal of reports concerning the drug associated with the highest ranked SDR for an event was tested for gastric and oesophageal haemorrhages (GOH), central nervous system haemorrhages and cerebrovascular accidents (CNSH), ischaemic coronary artery disorders and muscle pains (MP) using the reporting odds ratio in the French spontaneous reporting research database. After ranking SDRs detected in the complete dataset on the lower limit of the reporting odds ratio 95% confidence interval, reports concerning the drug with the highest ranked SDR were removed. In the dataset thus generated, SDRs were again identified, ranked and reports related to the drug involved in the newly highest ranked SDR removed. The process was repeated until no signal was detected. Initially detected SDRs eliminated using this technique were assessed regarding the summary of products characteristics and the literature to determine their FP nature.

Results

Seventeen SDRs were successively eliminated for GOH, 37 for CNSH, 15 for ischaemic coronary artery disorders, and 36 for MP. Four were FP for GOH, 29 for CNSH, 7 for ACI and none were FP for MP. The positive predictive value of the backward stepwise removal procedure in identifying FP SDRs ranged from 0% (MP) to 78.4% (CNSH).

Conclusions

Although further adjustment is needed to improve the method presented herein, our results suggest that numerous FP signals because of co‐prescription bias could be eliminated using an automated method. Copyright © 2013 John Wiley & Sons, Ltd.
Alternative zinc‐binding sites explain the redox sensitivity of zinc‐containing anti‐sigma factors
Authors: Heo Lim , Cho Yoo‐Bok , Lee Myeong Sup , Roe Jung‐Hye , Seok Chaok
Published: May 2013

Certain bacterial zinc‐containing anti‐sigma (ZAS) factors respond sensitively to thiol‐induced oxidative stress by undergoing conformational changes, which in turn reduce binding affinities for their cognate sigma factors. This redox sensitivity provides a mechanism for coping with oxidative stress by activating the transcription of antioxidant genes. Not all ZAS proteins are redox‐sensitive, but the mechanism of redox sensitivity is not fully understood. Here we propose that alternative zinc‐binding sites determine redox sensitivity. To support this proposal, we performed protein modeling and zinc docking on redox‐sensitive and redox‐insensitive ZAS proteins complexed with their cognate sigma factors. At least one strong alternative zinc‐binding pocket was detected for all known redox‐sensitive ZAS factors in actinomycetes, while no strong alternative zinc‐binding pocket was identified in redox‐insensitive ZAS factors, except for one controversial case. This hypothesis of alternative zinc‐binding sites can also explain residue‐specific contributions to the redox sensitivity of RsrA, a redox‐sensing ZAS protein from Streptomyces coelicolor, for which alanine mutagenesis experiments are available. Our results suggest a mechanistic model for redox sensitivity as follows: zinc ion can probabilistically occupy multiple sites in redox‐sensitive ZAS proteins, increasing the susceptibility of zinc‐coordinating cysteine residues to oxidation. This picture of probabilistic zinc occupation agrees with a previous structure and energy analysis on zinc finger proteins, and thus it may be more widely applicable to other classes of reactive zinc‐binding proteins. © 2013 Wiley Periodicals, Inc.
Transmission mode direct analysis in real time mass spectrometry for fast untargeted metabolic fingerprinting
Authors: Jones Christina M. , Fernández Facundo M.
Published: May 2013

RATIONALE

Untargeted metabolic fingerprinting is a discovery tool to better understand biochemical processes involved in detecting and characterizing disease states and responses to environmental stressors. Although current mass spectrometric (MS) methods are very powerful, there is a clear need for more rapid, high‐throughput MS approaches for metabolomics studies.

METHODS

A rapid metabolic fingerprinting method for human blood sera that utilizes a new transmission mode direct analysis in real time (TM‐DART) sampling technique coupled with quadrupole time of flight mass spectrometry (QTOFMS) is presented. In this approach, the sample is deposited directly on a stainless steel mesh that is held in the ionization region by a custom‐built module. As a result, the DART plasma gas stream interacts with the sample in a flow‐through fashion, which maximizes the interaction between the sample and ionizing species and minimizes variance in sample positioning.

RESULTS

The optimization of TM‐DART parameters directly affecting metabolite desorption and ionization, such as sample position and ionizing gas desorption temperature, was critical in achieving high sensitivity and detecting a broad mass range of metabolites. Ramping the ionizing gas desorption temperature further enhanced analysis by adding a simple separation dimension to this ambient approach. In terms of reproducibility, TM‐DART compared favorably with traditional probe mode (PM‐) DART analysis, with coefficients of variation as low as 16%. The longer‐lasting TM‐DART signals enabled the acquisition of metabolite full scan and product ion accurate mass spectra in a single experiment, resulting in greater confidence in metabolite identification.

CONCLUSIONS

TM‐DART MS proved to be a powerful analytical technique for rapid metabolome analysis of human blood sera. Copyright © 2013 John Wiley & Sons, Ltd.