bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug therapy and tinnitus: the UK experience
Authors: Hazell J. W. P. , Wood S. M.
Published: May 2011

There have been five recent studies of drug treatment in tinnitus in the UK using Class I anti-arrhythmic preparations. We present a new double-blind study of tocainide hydrochloride in severe, unmaskable tinnitus. No significant response is noted in any of the controlled trials to the active ingredient, and more work is needed on diagnostic criteria to see if those who do respond constitute a separate group. There was a surprisingly low incidence of placebo response and the importance of the side effects produced by the drugs in this group is stressed. The finding that three patients with profound hearing losses have had some continued benefit leads to the cautious conclusion that drug responders may be have a central component to their tinnitus.
Tinnitus and otosclerosis surgery
Authors: Robinson Mendell
Published: May 2011

This study attempts to correlate the relationship between clinical otosclerosis, tinnitus, and stapedectomy surgery. One hundred and thirty-five patients who recently underwent stapedectomy surgery were evaluated to determine the effects upon tinnitus and to determine if there was an association between tinnitus and the pre-operative cochlear reserve, the degree of footplate pathology, and/or the post-operative hearing result.

Diminished cochlear reserve and the post-operative audiometric result had no relationship to the tinnitus symptom. A beneficial effect on tinnitus occurred in 25 per cent of the patients requiring drilling of the stapes footplate.
The effect of endolymphatic system surgery on tinnitus in Menière's disease and hydrops
Authors: Arenberg I. Kaufman , Gibson Susan A. , de Water Sandra M. Van , Balkany Thomas J.
Published: May 2011

One hundred and seventy-two patients with Menière's disease (including tinnitus) who underwent endolymphatic system (ELS) surgery for vertigo and/or hearing loss, were evaluated to determine whether ELS surgery had an incidental effect on tinnitus. Tinnitus was eliminated in 34 patients (19.9 per cent), reduced in 64 patients (37.2 per cent), unchanged in 39 patients (22.6 per cent), and worse in 35 patients (20.3 per cent). No significant correlation existed between surgical results for hearing and an improvement in tinnitus. A successful elimination of vertigo, however, was associated with better results for tinnitus relief. Tinnitus is not considered to be an indication for ELS surgery.
Hyperlinked Suicide
Authors: Kemp Christopher G. , Collings Sunny C.
Published: May 2011

Background: The relationship between the Internet and suicide is a topic of growing concern among suicide researchers and the public, though to date few have actually attempted to investigate the accessibility and prominence of suicide-related information online, and there have been no comprehensive studies of site networking structure. Aims: To assess the visibility of various types of online information to suicide-risk individuals, and to assess the prominence and accessibility of “pro-suicide,” suicide prevention, and support sites by measuring their networking structure. Methods: Employing empirically derived search terms, we used the web-based Virtual Observatory for the Study of Online Networks (VOSON) to conduct hyperlink network analysis (HNA) of suicide-related websites. Results: Pro-suicide sites are rare and marginal, while sites dedicated to information about suicide as well as sites dedicated to prevention policy and advocacy are readily accessible. Conclusions: The networking structure of suicide-related Internet content has not been described previously. Our analysis shows that HNA is a useful method for gaining an indepth understanding of network traffic in relation to suicide-content websites. This information will be useful for strengthening the web presence of support and suicide prevention sites, and for monitoring changes over time.
Integrating Medical Examiner and Police Report Data
Authors: Ward Brian W. , Shields Ryan T. , Cramer Bert R.
Published: May 2011

Background: Recently, suicide in the United States has begun to be viewed as a preventable public health issue. This has led to the creation of a National Violent Death Reporting System that collects and integrates data on the social circumstances surrounding suicides. Aims: The study examines data on social circumstances surrounding suicides as collected by the medical examiner report (ME) and police report (PR) and subsequently integrated into the state of Maryland’s violent death reporting system. Methods: Reported data on social circumstances surrounding suicides occurring in the years 2003–2006 in Maryland (n = 1,476) were analyzed by examining their prevalence in the ME and PR, strength of association, and integration. Results: With the exception of three circumstances, there was variation among reported circumstances in the ME and PR. Furthermore, there was only a moderately strong relationship between the ME and PR for most circumstances, while a significant increase occurred in the prevalence of these circumstances when ME and PR were integrated. Conclusions: The integration of ME and PR has the potential to increase our knowledge of the circumstances surrounding suicide and to better inform prevention efforts. However, before this potential can be reached, there are still issues that must be considered.
Analysis of hydrodynamic lift on a bed sediment particle
Authors: Dwivedi Ambuj , Melville Bruce W. , Shamseldin Asaad Y. , Guha Tushar K.
Published: May 2011

An experimental study of lift force on a spherical sediment particle at different exposures was conducted in a laboratory flume. It is found that the functional form of the theoretical probability density function (pdf) of lift force similar to that of drag force is inadequate. An improved expression for the pdf based on the normal error law is provided which matches the measured data up to ±3 times the standard deviation of lift force for all exposures. The skewness of the measured lift force is found to increase with increase in exposure. In addition, the kurtosis of the measured lift force is found to be higher than that for a normal distribution for all exposures, resulting in higher probability of occurrence of extreme events (beyond ±3 times standard deviation). A spectral density function of lift force as a function of streamwise and stream‐normal velocity is developed and validated using the measured lift force data. The spectrum predicted by the proposed model closely follows the measured spectrum for exposures 7.5 mm and 10 mm while it over predicts at frequencies below 1 Hz for exposures 0 mm and 2.5 mm because of poor coherence between lift force and streamwise velocity. The time history plots of measured lift at lower exposures showed that the high‐frequency positive and negative fluctuations of lift correspond to strongly positive streamwise velocity fluctuations, a phenomenon not captured by the predictive model. Predominance of fluctuating Bernoulli's lift over lift due to stream‐normal velocity fluctuations is observed at all exposures, more so in the case of lower exposures.
Land water storage variability over West Africa estimated by Gravity Recovery and Climate Experiment (GRACE) and land surface models
Authors: Grippa M. , Kergoat L. , Frappart F. , Araud Q. , Boone A. , de Rosnay P. , Lemoine J.‐M. , Gascoin S. , Balsamo G. , Ottlé C. , Decharme B. , Saux‐Picart S. , Ramillien G.
Published: May 2011

Land water storage plays a fundamental role in the West African water cycle and has an important impact on climate and on the natural resources of this region. However, measurements of land water storage are scarce at regional and global scales and especially in poorly instrumented endorheic regions, such as most of the Sahel, where little useful information can be derived from river flow measurements and basin water budgets. The Gravity Recovery and Climate Experiment (GRACE) satellite mission provides an accurate measurement of the terrestrial gravity field variations from which land water storage variations can be derived. However, their retrieval is not straightforward, and different methods are employed, which results in different water storage GRACE products. On the other hand, water storage can be estimated by land surface modeling forced with observed or satellite‐based boundary conditions, but such estimates can be highly model dependent. In this study, land water storage by six GRACE products and soil moisture estimations by nine land surface models (run within the framework of the African Monsoon Multidisciplinary Analysis Land Surface Intercomparison Project (ALMIP)) are evaluated over West Africa, with a particular focus on the Sahelian area. The water storage spatial distribution, including zonal transects, its seasonal cycle, and its and interannual variability, are analyzed for the years 2003–2007. Despite the nonnegligible differences among the various GRACE products and among the different models, a generally good agreement between satellite and model estimates is found over the West Africa study region. In particular, GRACE data are shown to reproduce well the water storage interannual variability over the Sahel for the 5 year study period. The comparison between satellite estimates and ALMIP results leads to the identification of processes needing improvement in the land surface models. In particular, our results point out the importance of correctly simulating slow water reservoirs as well as evapotranspiration during the dry season for accurate soil moisture modeling over West Africa.
Phosphorus fractionation and distribution in sediments from wetlands and canals of a water conservation area in the Florida Everglades
Authors: Wang Qingren , Li Yuncong , Ouyang Ying
Published: May 2011

Phosphorus (P) fractionation and distribution in sediments are of great concern in the Florida Everglades ecosystem because potential eutrophication of surface waters usually results from P external loading and stability. Intact core sediment samples were collected to a depth of 35 cm from wetlands and canals across Water Conservation Area 3 (WCA‐3) of the Florida Everglades. These sediment cores were sliced into 5 cm increments and analyzed for P contents in different fractions by sequential extraction. These fractions mainly included total P (TP), readily available P (Pi‐KCl), Fe/Al‐bound P (Pi‐NaOH), Ca/Mg‐bound P (Pi‐HCl), organic P (Po‐NaOH), and residual P (PoResidue). Results showed that the canal sediments had the highest concentrations of TP, with about 87% in the form of Ca/Mg‐bound fraction, and the concentrations of TP in these sediments increased with depth. In contrast, the wetland sediments contained the lowest concentrations of TP (predominantly in the organic fraction), with 43% residual P and 27% Po‐NaOH, and the concentrations of TP in these sediments decreased with depth. In addition, a large amount of the readily available P (up to 1500 mg kg−1) in the canal sediments was accumulated at the top layer of 0–5 cm. This study suggests that any disturbance and/or environmental alterations, such as high canal flow and dredging in canal sediments, could pose a potential risk of a P increase in the water column and, consequently, in the wetlands because of the release of readily available P despite the relatively stable nature of such P fractions in these sediments.
How does the Interdecadal Pacific Oscillation affect design floods in Australia?
Authors: Pui A. , Lal A. , Sharma A.
Published: May 2011

Previous studies have shown significant dependence of annual maximum floods in eastern Australia on the Interdecadal Pacific Oscillation (IPO), a low‐frequency mode of natural climatic variability. However, the causative factors behind differences in flood risk observed during contrasting phases of the IPO remain poorly understood. In particular, an important question that stems from a practical flood hydrology perspective is: Does maximum precipitation exhibit a similar level of dependence on the IPO as that observed in the floods? If not, then what are the factors responsible for this disparity, and are there significant ramifications for the conventional approach of estimating design floods through a predefined design rainfall? This paper investigates the possible reasons for the disparate relationship of IPO on rainfall and streamflow design events; that is, why do flood characteristics for contrasting IPO phases differ significantly compared to less notable changes in the corresponding rainfall intensities? We hypothesize that this difference in flood characteristics as a function of the IPO is a result of catchment antecedent or wetness conditions prior to the design storm. This hypothesis is tested using data from 166 high‐quality daily rainfall stations across Australia along with catchment‐averaged rainfall and resulting flows across an additional 128 catchments from the same region. In addition, 35 subdaily rainfall stations with long records in east Australia were also used to support our arguments. The results of these tests suggest that catchment antecedent conditions prior to design storm events were found to vary significantly across the two IPO phases, leading to the significant differences in flood characteristics across the two phases.
New collector efficiency equation for colloid filtration in both natural and engineered flow conditions
Authors: Nelson Kirk E. , Ginn Timothy R.
Published: May 2011

A new equation for the collector efficiency (η) of the colloid filtration theory (CFT) is developed via nonlinear regression on the numerical data generated by a large number of Lagrangian simulations conducted in Happel's sphere‐in‐cell porous media model over a wide range of environmentally relevant conditions. The new equation expands the range of CFT's applicability in the natural subsurface primarily by accommodating departures from power law dependence of η on the Peclet and gravity numbers, a necessary but as of yet unavailable feature for applying CFT to large‐scale field transport (e.g., of nanoparticles, radionuclides, or genetically modified organisms) under low groundwater velocity conditions. The new equation also departs from prior equations for colloids in the nanoparticle size range at all fluid velocities. These departures are particularly relevant to subsurface colloid and colloid‐facilitated transport where low permeabilities and/or hydraulic gradients lead to low groundwater velocities and/or to nanoparticle fate and transport in porous media in general. We also note the importance of consistency in the conceptualization of particle flux through the single collector model on which most η equations are based for the purpose of attaining a mechanistic understanding of the transport and attachment steps of deposition. A lack of sufficient data for small particles and low velocities warrants further experiments to draw more definitive and comprehensive conclusions regarding the most significant discrepancies between the available equations.
Urban water demand modeling: Review of concepts, methods, and organizing principles
Authors: House‐Peters Lily A. , Chang Heejun
Published: May 2011

In this paper, we use a theoretical framework of coupled human and natural systems to review the methodological advances in urban water demand modeling over the past 3 decades. The goal of this review is to quantify the capacity of increasingly complex modeling techniques to account for complex human and natural processes, uncertainty, and resilience across spatial and temporal scales. This review begins with coupled human and natural systems theory and situates urban water demand within this framework. The second section reviews urban water demand literature and summarizes methodological advances in relation to four central themes: (1) interactions within and across multiple spatial and temporal scales, (2) acknowledgment and quantification of uncertainty, (3) identification of thresholds, nonlinear system response, and the consequences for resilience, and (4) the transition from simple statistical modeling to fully integrated dynamic modeling. This review will show that increasingly effective models have resulted from technological advances in spatial science and innovations in statistical methods. These models provide unbiased, accurate estimates of the determinants of urban water demand at increasingly fine spatial and temporal resolution. Dynamic models capable of incorporating alternative future scenarios and local stochastic analysis are leading a trend away from deterministic prediction.
Impact of low‐temperature electrical resistance heating on subsurface flow and transport
Authors: Krol M. M. , Sleep B. E. , Johnson R. L.
Published: May 2011

The effects of subboiling electrical resistance heating (ERH) on subsurface flow and transport were examined in a series of two‐dimensional tank experiments, with temperatures reaching 50°C. To analyze the experiments and determine the dominant mechanisms affecting flow and transport, a fully coupled two‐dimensional finite difference electrothermal model was developed to simulate electrical current flow, temperature‐dependent fluid flow, and mass transport. The model incorporates temperature‐dependent equations for density, viscosity, diffusion coefficient, and electrical conductivity, capturing the nonisothermal processes dominant in the subsurface. The model was validated with laboratory‐scale experiments in which voltage distribution, instantaneous electrical power, temperature, and tracer transport were measured. Tracer experiments and transport modeling indicated that temperature‐induced buoyant flow and contaminant movement could be significant when applying ERH in the subsurface, even at 50°C. A sensitivity study was performed to assess the impact of including temperature‐dependent properties such as water density, viscosity, and electrical conductivity. A change in water density of 1.3% (at 50°C) resulted in buoyant flow and increased velocity through the heated zone, indicating that heating contaminated zones to 50°C can have a large impact on mass transport. Temperature‐dependent electrical conductivity had a direct impact on ERH power consumption as well as the time to reach desired temperatures.
A watershed‐scale assessment of a process soil CO2 production and efflux model
Authors: Riveros‐Iregui Diego A. , McGlynn Brian L. , Marshall Lucy A. , Welsch Daniel L. , Emanuel Ryan E. , Epstein Howard E.
Published: May 2011

Growing season soil CO2 efflux is known to vary laterally by as much as seven fold within small subalpine watersheds (<5 km2), and such degree of variability has been strongly related to the landscape‐imposed redistribution of soil water. Current empirical or process models offer low potential to simulate this variability or to simulate watershed‐scale dynamics of soil CO2 efflux. We modified an existing process soil CO2 production and efflux model to include spatially variable soil moisture, and applied it to a well‐studied and moderately complex watershed of the northern Rocky Mountains. We started at the point scale and progressively modeled processes up to the watershed scale. We corroborated model performance using an independent data set of soil CO2 efflux measurements from 53 sites distributed across the 393 ha watershed. Our approach (1) simulated the seasonality of soil CO2 efflux at riparian sites; (2) reproduced short‐term (diel) dynamics of soil CO2 concentration ([CO2]) at riparian sites, particularly observed hysteresis patterns in the soil [CO2]–soil temperature relationship; and (3) simulated growing season estimates of soil CO2 efflux at dry sites across the landscape (98% of area). Model limitations included poor simulation of growing season (cumulative) soil CO2 efflux at sites with a large drainage area, likely as a result of poorly modeled soil water content and challenges in parametrization of root and microbial activities. Our study provides important insight into coupling hydrological and biogeochemical models at landscape scales, and highlights the role of landscape structure and heterogeneity when modeling spatial variability of biogeochemical processes.
How evaporative water losses vary between wet and dry water years as a function of elevation in the Sierra Nevada, California, and critical factors for modeling
Authors: Lundquist Jessica D. , Loheide Steven P.
Published: May 2011

High altitude basins in the Sierra Nevada, California, have negligible summer precipitation and very little groundwater storage, making them ideal laboratories for indirectly monitoring changes in evaporative losses between wet and dry years. Dry years typically have greater potential evapotranspiration (ET) due to warmer June and July air temperatures, warmer summer water/soil temperatures, greater solar radiation exposure due to less frequent cloud cover, greater vapor pressure deficit, and longer growing seasons. However, dry years also have limited moisture availability compared to wetter years, and thus actual evapotranspiration is much less than the potential in dry years. The balance of these factors varies with elevation. Here, we use gridded temperature, precipitation, and snow data, along with historic streamflow records in two nested basins of the Merced River, California, and a simple model to determine the following: Annual ET increases in wetter years at midelevations (2100–2600 m), but this pattern can only be represented in model simulations that include some representation of water transfer between higher and lower elevation soil reservoirs. At higher elevations (>2600 m), greater water availability in wet years is offset by shorter growing seasons due to longer snow cover duration. These results suggest that models seeking to represent changes in ET in mountainous terrain must, at a minimum, include both hillslope processes (water transfer down steep slopes) and snow processes (timing of water and energy supply).
Evaluation of the heat pulse probe method for determining frozen soil moisture content
Authors: Zhang Yinsuo , Treberg Michael , Carey Sean K.
Published: May 2011

Heat pulse probes (HPP) have been widely utilized to determine soil thermal properties and water content in unfrozen soils; however, their applications in frozen soils are largely restricted by phase change and the presence of unfrozen water. This study explores the possibility of using HPP to determine total water content of frozen soils by (1) establishing the optimum heat applications to limit melting, (2) improving the mathematical representations for frozen conditions, and (3) evaluating the applicability of HPP methods under various temperature and moisture conditions. A custom‐built HPP was tested at total moisture levels that varied from full saturation to oven dry and initial soil temperatures from 20°C to −11°C. The applied heat pulse durations varied from 8 to 60 s, with total heat strength varying from 100 to 2000 J m−1. Comparison of mathematical methods involved two analytical solutions and a one‐dimensional finite difference numerical model. While both analytical methods assumed no phase change, the numerical model considered ice melting and unfrozen water. Conclusions include the following: (1) the numerical model with phase change is the only appropriate method to represent the temperature change curve once melting occurs; (2) below −4°C, ice melting could be limited, and measurement errors of total moisture content were within ±0.05 m3 m−3; (3) application of HPP between −2°C and 0°C is difficult because of the retarded response of probe temperature to changing moisture contents and heat applications; and (4) probe spacing is a sensitive parameter requiring calibration once reinstallation of the probe or the thawing and freezing process occurs.
Phosphorylation of JDP2 on threonine-148 by the c-Jun N-terminal kinase targets it for proteosomal degradation
Authors: Weidenfeld-Baranboim Keren , Koren Lilach , Aronheim Ami
Published: May 2011

JDP2 (c-Jun dimerization protein 2) is a member of the basic leucine zipper family of transcription factors that is ubiquitously expressed in all examined cell types. JDP2 is phosphorylated on Thr148 by JNK (c-Jun N-terminal kinase) and p38 kinase, although the functional role of its phosphorylation is unknown. In the present paper we show that the JDP2 protein level is dramatically reduced in response to serum stimulation, anisomycin treatment, ultraviolet light irradiation and cycloheximide treatment, all of which activate the JNK pathway. In addition, endogenous and overexpressed JDP2 are phosphorylated in response to these stimuli. Replacement of Thr148 with an alanine residue stabilizes ectopically expressed JDP2 in the presence of the stimuli; conversely, substitution with glutamic acid destabilizes it. Serum-induced phosphorylation and degradation of JDP2 are specific to JNK activation since a JNK inhibitor (SP600125) abolishes these effects, whereas p38 and MEK inhibitors (SB203580 and UO126) have no effect. In the presence of cycloheximide, JDP2 is rapidly phosphorylated and degraded due to the combined effects of protein synthesis inhibition and activation of JNK. Pre-treatment of cells with SP600125 prior to cycloheximide treatment significantly prolongs the half-life of JDP2 that is found mainly in the unphosphorylated form. Lastly, the proteasome inhibitor (MG132) rescues JDP2 degradation following cycloheximide treatment and increases the expression of the JDP2 phospho-mimetic T148E mutant. Collectively, these results suggest that phosphorylation of JDP2 on thr148 by JNK targets it to the proteasome for degradation.
Thermostable HIV-1 group O reverse transcriptase variants with the same fidelity as murine leukaemia virus reverse transcriptase
Authors: Barrioluengo Verónica , Álvarez Mar , Barbieri Daniela , Menéndez-Arias Luis
Published: May 2011

Wild-type HIV-1 group O RT (reverse transcriptase) shows increased thermostability in comparison with HIV-1 group M subtype B RT and MLV (murine leukaemia virus) RT. However, its utility in the amplification of RNA targets is limited by the reduced accuracy of lentiviral RTs compared with oncoretroviral RTs (i.e. MLV RT). The effects of the mutations K65R, R78A and K65R/V75I on the fidelity of HIV-1 group O RTs were studied using gel-based and M13mp2 lacZ forward-mutation fidelity assays. Forward-mutation assays demonstrated that mutant RTs K65R, R78A and K65R/V75I showed >9-fold increased accuracy in comparison with the wild-type enzyme and were approximately two times more faithful than the MLV RT. Compared with MLV RT, all of the tested HIV-1 group O RT variants showed decreased frameshift fidelity. However, K65R RT showed a higher tendency to introduce one-nucleotide deletions in comparison with other HIV-1 group O RT variants. R78A had a destabilizing effect on the RT, either in the presence or absence of V75I. At temperatures above 52 °C, K65R and K65R/V75I retained similar levels of DNA polymerase activity to the wild-type HIV-1 group O RT, but were more efficient than HIV-1 group M subtype B and MLV RTs. K65R, K65R/V75I and R78A RTs showed decreased misinsertion and mispair extension fidelity in comparison with the wild-type enzyme for most base pairs studied. These assays revealed that nucleotide selection is mainly governed by kpol (pol is polymerization) in the case of K65R, whereas both kpol and Kd affect nucleotide discrimination in the case of K65R/V75I.
Effects on antigen-presenting cells of short-term interaction with the human host defence peptide β-defensin 2
Authors: Morgera Francesca , Pacor Sabrina , Creatti Luisa , Antcheva Nikolinka , Vaccari Lisa , Tossi Alessandro
Published: May 2011

β-Defensins are antimicrobial peptides that exert their host-defence functions at the interface between the host and microbial biota. They display a direct, salt- and medium-sensitive cidal activity, in vitro, against a broad spectrum of bacteria and fungi, and there is increasing evidence that they also play a role in alerting and enhancing cellular components of innate and adaptive immunity. Their interaction with biological membranes plays a central role in both of these types of activities. In the present study, we have investigated the interaction of fluorescently labelled hBD2 (human β-defensin 2) with monocytes, macrophages and iDCs (immature dendritic cells), observing a differential capacity to be rapidly internalized into these cells. Complementary microscopy techniques [TEM (transmission electron microscopy), optical microscopy and IR microspectroscopy] were used to explore the functional and biological implications of these interactions on iDCs. Short-term exposure to the peptide resulted in significant alterations in membrane composition and re-organization of the endomembrane system, with the induction of degranulation. These events may be associated with the antigen-presenting activities or the chemotaxis of iDCs, which appears to occur via both CCR6 (CC chemokine receptor 6)-dependent and -independent mechanisms.
Hepatic reduction of the secondary bile acid 7-oxolithocholic acid is mediated by 11β-hydroxysteroid dehydrogenase 1
Authors: Odermatt Alex , Da Cunha Thierry , Penno Carlos A. , Chandsawangbhuwana Charlie , Reichert Christian , Wolf Armin , Dong Min , Baker Michael E.
Published: May 2011

The oxidized bile acid 7-oxoLCA (7-oxolithocholic acid), formed primarily by gut micro-organisms, is reduced in human liver to CDCA (chenodeoxycholic acid) and, to a lesser extent, UDCA (ursodeoxycholic acid). The enzyme(s) responsible remained unknown. Using human liver microsomes, we observed enhanced 7-oxoLCA reduction in the presence of detergent. The reaction was dependent on NADPH and stimulated by glucose 6-phosphate, suggesting localization of the enzyme in the ER (endoplasmic reticulum) and dependence on NADPH-generating H6PDH (hexose-6-phosphate dehydrogenase). Using recombinant human 11β-HSD1 (11β-hydroxysteroid dehydrogenase 1), we demonstrate efficient conversion of 7-oxoLCA into CDCA and, to a lesser extent, UDCA. Unlike the reversible metabolism of glucocorticoids, 11β-HSD1 mediated solely 7-oxo reduction of 7-oxoLCA and its taurine and glycine conjugates. Furthermore, we investigated the interference of bile acids with 11β-HSD1-dependent interconversion of glucocorticoids. 7-OxoLCA and its conjugates preferentially inhibited cortisone reduction, and CDCA and its conjugates inhibited cortisol oxidation. Three-dimensional modelling provided an explanation for the binding mode and selectivity of the bile acids studied. The results reveal that 11β-HSD1 is responsible for 7-oxoLCA reduction in humans, providing a further link between hepatic glucocorticoid activation and bile acid metabolism. These findings also suggest the need for animal and clinical studies to explore whether inhibition of 11β-HSD1 to reduce cortisol levels would also lead to an accumulation of 7-oxoLCA, thereby potentially affecting bile acid-mediated functions.
Binding to lipid membrane induces conformational changes in RPE65: implications for its isomerohydrolase activity
Authors: Nikolaeva Olga , Moiseyev Gennadiy , Rodgers Karla K. , Ma Jian-xing
Published: May 2011

The visual cycle is a multi-step pathway to recycle 11-cis retinal, the chromophore for both rod and cone visual pigments. The isomerohydrolase RPE65, a membrane-associated enzyme, converts atRE (all-trans-retinyl ester) to 11-cis-retinol, a key step in the visual cycle. Previously, it has been shown that membrane association of RPE65 is essential for its catalytic activity. Using purified recombinant chicken RPE65 and an in vitro liposome-based floatation assay, we present evidence that the RPE65 membrane-binding affinity was significantly facilitated by incorporation of atRE, the substrate of RPE65, into liposomal membrane. Using tryptophan emission fluorescence quenching and CD spectroscopy, we showed that, upon membrane binding, RPE65 undergoes conformational changes at both the tertiary and secondary structural levels. Specifically, tryptophan fluorescence quenching showed that the tertiary RPE65 structure became more open towards the hydrophilic environment upon its association with the membrane. Simultaneously, a decrease in the α-helix content of RPE65 was revealed upon binding with the lipid membrane containing atRE. These results demonstrated that RPE65's functional activity depends on its conformational changes caused by its association with the membrane.
Rapid and flexible biochemical assays for evaluating 4′-phosphopantetheinyl transferase activity
Authors: Owen Jeremy G. , Copp Janine N. , Ackerley David F.
Published: May 2011

PPTases (phosphopantetheinyl transferases) are of great interest owing to their essential roles in activating fatty acid, polyketide and non-ribosomal peptide synthetase enzymes for both primary and secondary metabolism, as well as an increasing number of biotechnological applications. However, existing techniques for PPTase characterization and development are cumbersome and technically challenging. To address this, we have developed the indigoidine-synthesizing non-ribosomal peptide synthetase BpsA as a reporter for PPTase activity. Simple co-transformation allows rapid assessment of the ability of a PPTase candidate to activate BpsA in vivo. Kinetic parameters with respect to either CoA or BpsA as variable substrate can then be derived in vitro by continuously measuring the rate of indigoidine synthesis as the PPTase progressively converts BpsA from its apo into holo form. Subsequently, a competition assay, in which BpsA and purified carrier proteins compete for a limited pool of CoA, enables elucidation of kinetic parameters for a PPTase with those carrier proteins. We used this system to conduct a rapid characterization of three different PPTase enzymes: Sfp of Bacillus subtilis A.T.C.C.6633, PcpS of Pseudomonas aeruginosa PAO1, and the putative PPTase PP1183 of Ps. putida KT2440. We also demonstrate the utility of this system for discovery and characterization of PPTase inhibitors.
The special systems biology of the sperm
Authors: Anand-Ivell Ravinder , Ivell Richard
Published: May 2011

Spermatozoa represent a highly specialized cell type, with a minimalist structure designed to fulfil a single principal function: the transport of an intact single-copy haploid genome to the site of fertilization in the oviduct, and consequent zygote formation. They have lost most of their original cytoplasm, and remaining organelles are extremely modified. One result of this is that biochemical dynamics are restricted by a lack of cytoplasmic diffusion and a dramatic compartmentalization, with an increased emphasis on the physicochemical modulation of membranes. This is also reflected in a truncated apoptotic pathway, described in this issue of the Biochemical Journal in an article by Koppers et al., which leads to a so-called ‘silent response’ in the female tract, whereby unused sperm are removed without inflammatory consequences that might otherwise be detrimental to the new embryo. This new study shows that sperm have not simply jettisoned unwanted cellular components, but have evolved a very appropriate systems biology adapted to the specialist role they have to perform.
Omega-3 polyunsaturated fatty acids augment the muscle protein anabolic response to hyperinsulinaemia–hyperaminoacidaemia in healthy young and middle-aged men and women
Authors: Smith Gordon I. , Atherton Philip , Reeds Dominic N. , Mohammed B. Selma , Rankin Debbie , Rennie Michael J. , Mittendorfer Bettina
Published: May 2011

Increased dietary LCn−3PUFA (long-chain n−3 polyunsaturated fatty acid) intake stimulates muscle protein anabolism in individuals who experience muscle loss due to aging or cancer cachexia. However, it is not known whether LCn−3PUFAs elicit similar anabolic effects in healthy individuals. To answer this question, we evaluated the effect of 8 weeks of LCn−3PUFA supplementation (4 g of Lovaza®/day) in nine 25–45-year-old healthy subjects on the rate of muscle protein synthesis (by using stable isotope-labelled tracer techniques) and the activation (phosphorylation) of elements of the mTOR (mammalian target of rapamycin)/p70S6K (p70 S6 kinase) signalling pathway during basal post-absorptive conditions and during a hyperinsulinaemic–hyperaminoacidaemic clamp. We also measured the concentrations of protein, RNA and DNA in muscle to obtain indices of the protein synthetic capacity, translational efficiency and cell size. Neither the basal muscle protein fractional synthesis rate nor basal signalling element phosphorylation changed in response to LCn−3PUFA supplementation, but the anabolic response to insulin and amino acid infusion was greater after LCn−3PUFA [i.e. the muscle protein fractional synthesis rate during insulin and amino acid infusion increased from 0.062±0.004 to 0.083±0.007%/h and the phospho-mTOR (Ser2448) and phospho-p70S6K (Thr389) levels increased by ∼50%; all P<0.05]. In addition, the muscle protein concentration and the protein/DNA ratio (i.e. muscle cell size) were both greater (P<0.05) after LCn−3PUFA supplementation. We conclude that LCn−3PUFAs have anabolic properties in healthy young and middle-aged adults.
Nitric oxide is an essential mediator of the protective effects of remote ischaemic preconditioning in a mouse model of liver ischaemia/reperfusion injury
Authors: Abu-Amara Mahmoud , Yang Shi Yu , Quaglia Alberto , Rowley Peter , De Mel Achala , Tapuria Niteen , Seifalian Alexander , Davidson Brian , Fuller Barry
Published: May 2011

NO (nitric oxide) may protect the liver from IR (ischaemia/reperfusion) injury. RIPC (remote ischaemic preconditioning) also protects against liver IR injury; however, the molecular mediator(s) of RIPC are currently unknown. The aim of the present study was to assess the role of NO in hindlimb RIPC-induced protection against liver IR injury. Mice were allocated to the following groups: sham group; RIPC group (six cycles of 4×4 min IR of hindlimb); IR group [40 min lobar (70%) hepatic ischaemia and 2-h reperfusion]; RIPC+IR group (RIPC followed by IR group procedures); and C-PTIO [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt]+RIPC+IR group [C-PTIO (a direct NO scavenger) was administered, followed by the RIPC+IR group procedure]. Hepatic MBF (microcirculatory blood flow) was measured throughout the experiment. Circulating NOx (nitrite and nitrate) levels, plasma liver transaminases, hepatic histopathological and TEM (transmission electron microscopy) studies were performed at the end of the experiment. NOx concentrations were significantly elevated (P<0.05) in the RIPC and RIPC+IR groups. Compared with liver IR alone, RIPC+IR preserved hepatic MBF during liver reperfusion (P<0.05). In contrast, C-PTIO+RIPC+IR reduced MBF compared with RIPC+IR (P<0.05). RIPC+IR reduced plasma transaminases (P<0.05), and histopathological and ultrastructural features of injury compared with IR alone. The protective effects of RIPC+IR in reducing liver IR injury were abrogated in the group that received antecedent C-PTIO (C-PTIO+RIPC+IR). In conclusion, NO is an essential mediator of the protection afforded by hindlimb RIPC against liver IR injury. The mechanisms underlying this protection involve preservation of the sinusoidal structure and maintenance of blood flow through the hepatic microcirculation.
TGF-β/TGF-β receptor system and its role in physiological and pathological conditions
Authors: Santibañez Juan F. , Quintanilla Miguel , Bernabeu Carmelo
Published: May 2011

The TGF-β (transforming growth factor-β) system signals via protein kinase receptors and Smad mediators to regulate a plethora of biological processes, including morphogenesis, embryonic development, adult stem cell differentiation, immune regulation, wound healing and inflammation. In addition, alterations of specific components of the TGF-β signalling pathway may contribute to a broad range of pathologies such as cancer, cardiovascular pathology, fibrosis and congenital diseases. The knowledge about the mechanisms involved in TGF-β signal transduction has allowed a better understanding of the disease pathogenicity as well as the identification of several molecular targets with great potential in therapeutic interventions.
Full-field drift Hamiltonian particle orbits in axisymmetric tokamak geometry
Authors: Cooper W. A. , Cooper G. A. , Graves J. P. , Isaev M. Yu.
Published: May 2011

A Hamiltonian/Lagrangian theory to describe guiding center orbit drift motion that is canonical in Boozer magnetic coordinates is developed to include full electrostatic and electromagnetic perturbed fields in axisymmetric tokamak geometry. Furthermore, the radial component of the equilibrium magnetic field in the covariant representation is retained and the background equilibrium state extends to anisotropic plasma pressure conditions. A gauge transformation on the perturbed vector potential is imposed to guarantee canonical structure in the Boozer frame. Perturbed field nonlinear wave-wave interactions affect only the evolution of the guiding center particle parallel gyroradius. The evolution of the particle coordinate positions retains only linear wave-particle interactions. For particle motion in magnetohydrodynamic (MHD) instability structures, the electrostatic potential is linked mainly to the binormal component of the perturbed displacement vector when finite δA⊥ components are included.
Nonlinear beam generated plasma waves as a source for enhanced plasma and ion acoustic lines
Authors: Daldorff L. K. S. , Pécseli H. L. , Trulsen J. K. , Ulriksen M. I. , Eliasson B. , Stenflo L.
Published: May 2011

Observations by, for instance, the EISCAT Svalbard Radar (ESR) demonstrate that the symmetry of the naturally occurring ion line in the polar ionosphere can be broken by an enhanced, nonthermal, level of fluctuations (naturally enhanced ion-acoustic lines, NEIALs). It was in many cases found that the entire ion spectrum can be distorted, also with the appearance of a third line, corresponding to a propagation velocity significantly slower than the ion acoustic sound speed. It has been argued that selective decay of beam excited primary Langmuir waves can explain some phenomena similar to those observed. We consider a related model, suggesting that a primary nonlinear process can be an oscillating two-stream instability, generating a forced low frequency mode that does not obey any ion sound dispersion relation. At later times, the decay of Langmuir waves can give rise also to enhanced asymmetric ion lines. The analysis is based on numerical results, where the initial Langmuir waves are excited by a cold dilute electron beam. By this numerical approach, we can detect fine details of the physical processes, in particular, demonstrate a strong space-time intermittency of the electron waves in agreement with observations. Our code solves the full Vlasov equation for electrons and ions, with the dynamics coupled through the electrostatic field derived from Poisson’s equation. The analysis distinguishes the dynamics of the background and beam electrons. This distinction simplifies the analysis for the formulation of the weakly nonlinear analytical model for the oscillating two-stream instability. The results have general applications beyond their relevance for the ionospheric observations.
Nonlinear excitation of zonal flows and streamers in plasmas
Authors: Benkadda S. , Klochkov D. N. , Popel S. I. , Izvekova Yu. N.
Published: May 2011

Nonlinear excitation of zonal flows and streamers in plasmas is considered. The emphasis is given to the nonlinear interaction of low- and high-frequency drift waves which can result in the excitation of zonal flows and streamers in a plasma of fusion devices. For this purpose, an inhomogeneous nonisothermal plasma in a strong external magnetic field whose characteristic frequencies are lower than the ion Langmuir frequency but higher than the collision frequency is studied. The excitation of a long-wavelength low-frequency drift wave during the development of the nonlinear modulational interaction of a high-frequency drift pump wave is investigated. The growth rates of the modulational instability are obtained, and the conditions for its development are determined. Self-organized structures described by solutions of evolutionary equations for the modulational interaction are associated with zonal flows and streamers. A possible relation of the modulational interaction in Earth’s ionospheric plasma to the formation of dust flows and transport of dust particles in the ionosphere is also discussed. It is shown that one of the ways of transport of dust particles in the ionosphere is vertical flows (streamers), which are generated by dust vortices as a result of development of the modulational instability.
Exact asymptotic behavior of the Pekar–Tomasevich functional
Authors: Benguria Rafael D. , Bley Gonzalo A.
Published: May 2011

An explicit asymptotic expression for the ground-state energy of the Pekar–Tomasevich functional for the N-polaron is found, when the repulsion parameter U of the electrons satisfies the inequality 0 ⩽ U ⩽ 2α, where α is the coupling constant of the polaron. If \documentclass[12pt]{minimal}\begin{document}$\mathcal {E}_U^N$\end{document}EUN denotes this ground-state energy for the case of N electrons and repulsion parameter U, we prove that \documentclass[12pt]{minimal}\begin{document}$\mathcal {E}_U^N/N^3 \rightarrow -c_p(U - 2\alpha )^2/4$\end{document}EUN/N3→−cp(U−2α)2/4 as N → ∞, where, cp = 0.10851…. Moreover, we show that \documentclass[12pt]{minimal}\begin{document}$\mathcal {E}_0^N = -c_p\alpha ^2N^3$\end{document}E0N=−cpα2N3, for all N.
Planar and cylindrical magnetosonic solitary and shock waves in dissipative, hot electron-positron-ion plasma
Authors: Jehan Nusrat , Mirza Arshad M. , Salahuddin M.
Published: May 2011

Planar and cylindrical magnetosonic solitary and shock structures are studied in a hot and dissipative plasma consisting of electrons, positrons, and ions. By employing the reductive perturbative method, a modified Korteweg-de Vries Burgers (mKdVB) equation is derived in the limit of low frequency and long wavelength by taking into account viscous dissipation of the three species. The effects of variation of various plasma parameters on the profiles of planar and cylindrical solitary and shock structures are discussed. In the limit, when certain terms of the mKdVB equation are small enough to be treated as perturbation, analytical solutions are obtained and compared with the corresponding numerical ones.
Local control of non-adiabatic dissociation dynamics
Authors: Bomble L. , Chenel A. , Meier C. , Desouter-Lecomte M.
Published: May 2011

We present a theoretical approach which consists of applying the strategy of local control to projectors based on asymptotic scattering states. This allows to optimize final state distributions upon laser excitation in cases where strong non-adiabatic effects are present. The approach, despite being based on a time-local formulation, can take non-adiabatic transitions that appear at later times fully into account and adopt a corresponding control strategy. As an example, we show various dissociation channels of HeH+, a system where the ultrafast dissociation dynamics is determined by strong non-Born-Oppenheimer effects.