bluuebunny/crossref_metadata_2025 huggingface dataset:
RELATIONSHIP BETWEEN TUMOUR RESISTANCE AND THE IN VITRO AND IN VIVO CYTOTOXICITY ELICITED BY SALMONELLA ANTIGENS IN IMMUNIZED MICE
Authors: Ashley Michael P , Kotlarski Ieva
Published: August 2007

Immunization of mice with the attenuated 11RX strain of Salmonella enteritidis (11RX) induces resistance to intraperitoneal (i.p.) tumour growth. Tumour resistance is much greater and lasts for u longer time following i.p. immunization than following intravenous (i.v.) immunization. This paper extends our previous observations that, after this resistance is lost, it can be recalled by a T cell‐mediated reaction to an antigenic extract of the bacteria (11RX antigen) which is not protective in unimmunized mice. The duration of this sensitization to 11RX antigen was determined in mice immunized i.p. or i.v. with live 11RX by challenging them at various times after immunization with 131I (or 125I)‐labelled Ehrlich ascites tumour (EAT) cells alone or mixed with 11RX antigen. In vivo killing of EAT cells was assayed by monitoring whole‐body retention of radioactivity and this was correlated in the same mice with suppression of tumour growth and survival of the mice. The resistance recalled by 11RX antigen was short‐lived and In vivo cytotoxic activity had subsided by 6 days after antigen injection. 11RX antigen also recalled the ability of the peritoneal cells to lyse 51Cr‐labelled EAT cells in vitro and a close correlation was found between this activity and the cytotoxicity measured In vivo. The adherence properties of the cytotoxic cells and their inhibition by trypan blue indicated that they were macro‐phages
SUPERHELICAL TURNS OF CLOSED CIRCULAR DNA IN SOLUTION AND IN A GEL: EVIDENCE FOR A CONFORMATIONAL DIFFERENCE
Authors: Dougherty G
Published: August 2007

We have compared the number of superhelical turns, τ, in circular covalently closed plasmid pBRβG DNA obtained by four different methods, each based on one particular distinguishing principle. Three of the methods allow an unequivocal determination of τ under gel electrophoresis conditions, whilst the fourth enables us to determine its value in solution. We were able to detect a significant difference between the two environments, corresponding to an unwinding of the DNA duplex angle by 0·3° when a sample is transferred from solution to gel. The possible existence of such an effect has been generally overlooked by previous investigators. Our result suggests that the previously reported value for the number of base‐pairs per helical turn should be adjusted downwards by about 0·10, so that it applies to conditions in solution.
RENAL AUTOTRANSPLANTATION IN SHEEP—PREPARATION AND PHYSIOLOGY
Authors: Wright RD , McDougall JG , Coghlan JP , Denton DA , Hardy KJ , Potocnik SJ , Scoggins BA
Published: August 2007

A novel procedure for renal autotransplantation in sheep is described. The operative procedure involved two preliminary operations for preparation of carotid artery and jugular vein loops and of a Wright‐type parotid fistula. At transplantation the renal artery and vein were anastomosed end‐to‐end to carotid artery and jugular vein and the ureter was anastomosed end‐to‐end to the parotid duct. The cranial ends of the carotid artery, jugular vein and parotid duel were ligated and the parotid gland was denervated. The remaining abdominal kidney was removed 2 days after transplantation. Over periods now as long as 36 months, glomerular filtration rate was 24·1±0·7 ml/min and effective renal plasma flow was 204±6 ml/min (73 determinations in 7 sheep), compared to values of 48±4 and 305±26 ml/min previously reported for sheep with both kidneys in situ. The physiological response of the kidneys to water load and deprivation, arginine‐vasopressin injection, intravenous hypertonic sodium load and 24 h sodium depletion have been examined and show the transplanted kidneys responded in the appropriate manner. Maximum urine osmolality of up to 1000 mOsmol/kg was observed after 24 h water deprivation, and minimum osmolality of 108±25 mOsmol/kg was observed after administration of 75 ml/kg oral water load. Fractional sodium reabsorption was >99·9% after 24 h sodium depletion, whilst it fell to 92·5±0·5% after intravenous administration of a hypertonic NaCl load. All these values are in the same range as observed for normal sheep following similar treatment. This preparation provides a sole kidney with immediate access to its blood vessels and secretions for physiological and pharmacological research.
A COMPARISON OF COUNTERFLOW CENTRIFUGATION AND UNIT GRAVITY SEDIMENTATION IN THE SEPARATION OF MOUSE BONE MARROW PROGENITOR CELLS
Authors: Attwood PA , Bertoncello I , Bradley TR , Hodgson GS
Published: August 2007

Both Unit Gravity Sedimentation and Counterflow Centrifugation separate cells primarily on the basis of size, However, when performed concurrently on the same normal mouse bone marrow cell suspensions, Unit Gravity Sedimentation was found to be far superior in terms of the recovery of total nucleated tell loud and the recovery and enrichment of two classes of functional progenitors: (1)those responsive to the combined stimulus of pregnant mouse uterus extract (PMUE) plus human spleen conditioned medium (HUSPCM), and (2), those responsive to PMUE alone. Neither technique was able to resolve PMUE from PMUE + HUSPCM progenitors. The major limitation of Counterflow Centrifugatton for the separation of sub‐populations of marrow cells is related to the complexity and range of cell sizes in marrow cell suspensions which lead to significant pellet formation within the elutriator chamber. Furthermore, cells undergoing Counterflow Centrifugation are subjected to forces not encountered in Unit Gravity Sedimentation. Therefore, the basis of the separations is not identical and this is reflected in cell volume distributions of comparable fractions separated by each method.
Cardiovascular effects of cannabinoids in conscious spontaneously hypertensive rats
Authors: Wheal A J , Bennett T , Randall M D , Gardiner S M
Published: August 2007

Background and purpose:

In anaesthetized spontaneously hypertensive rats (SHR), there is evidence for up‐regulation of cannabinoid (CB1) receptors: antagonism of CB1receptors causes a rise in blood pressure, and administration of the endocannabinoid, anandamide, or inhibition of anandamide degradation causes hypotension. These findings have led to the suggestion that the endocannabinoid system may be a therapeutic target in hypertension. However, since the cardiovascular responses to cannabinoids are substantially influenced by anaesthesia, the purpose of this study was to assess regional haemodynamic responses to cannabinoid receptor stimulation and inhibition in conscious SHR.

Experimental approach:

Cardiovascular responses to i.v. administration of anandamide, the cannabinoid receptor agonist, WIN 55212‐2, and the CB1receptor antagonist, AM 251, were measured in male SHR, Wistar Kyoto rats and outbred Wistar rats, chronically instrumented for recording renal, mesenteric and hindquarters haemodynamics in the conscious, freely‐moving state.

Key results:

Hypotensive responses to anandamide and WIN 55212‐2 only occurred in SHR, but these were relatively modest and not associated with CB1receptor‐mediated vasodilatation. In SHR only, anandamide caused bradycardia, which was inhibited by AM 251. Furthermore, a pressor response to CB1receptor antagonism occurred only in SHR, but was not associated with vasoconstriction. Moreover, there was some evidence for CB1receptor‐mediated vasoconstrictor actions of anandamide in SHR, which was not seen in the normotensive strains.

Conclusions and implications:

The results are consistent with activation of CB1receptors in SHR by endogenous ligands exerting an antihypertensive effect, but the findings do not indicate enhanced CB1receptor‐mediated vasodilator mechanisms in SHR.

British Journal of Pharmacology(2007)152, 717–724; doi:10.1038/sj.bjp.0707410; published online 13 August 2007
Chronic exposure of sensory neurones to increased levels of nerve growth factor modulates CB1/TRPV1 receptor crosstalk
Authors: Evans R M , Scott R H , Ross R A
Published: August 2007

Background:

Anandamide (AEA) activates both cannabinoid CB1 and TRPV1 receptors, which are expressed on cultured dorsal root ganglion neurones. Increased levels of nerve growth factor (NGF) are associated with chronic pain states.

Experimental approach:

The aim of this study was to compare of the effects of AEA on CB1 receptor signalling and TRPV1‐CB1 crosstalk in low and high concentrations of NGF, using voltage‐clamp electrophysiology and Fura‐2 calcium imaging.

Key results:

Chronic exposure to high NGF (200 ng ml−1) as compared to low NGF (20 ng ml−1) increases the proportion of neurones that exhibit an inward current in response to AEA (1 μM), from 7 to 29%. In contrast, inhibition of voltage‐gated calcium currents by AEA is not significantly different in low NGF (33±9%, compared to high NGF 28±6%). Crosstalk between CB and TRPV1 receptors is modulated by exposure to high NGF. In low NGF, exposure to the CB1 receptor antagonist, SR141716A, (100 nM) increases the percentage of neurones in which AEA elicits an increase in [Ca2+]i, from 10 to 23%. In high NGF, the antagonist does not alter the percentage of responders (33 to 30%). In low NGF, exposure to the CB receptor agonist, WIN55 (1 μM) reduces capsaicin‐mediated increases in [Ca2+]i to 28±8% of control as compared to an enhancement to 172±26% of control observed in high NGF.

Conclusions and implications:

We conclude that cannabinoid‐mediated modulation of TRPV1 receptor activation is altered after exposure to high NGF.

British Journal of Pharmacology (2007) 152, 404–413; doi:10.1038/sj.bjp.0707411; published online 13 August 2007
Roscovitine, a cyclin‐dependent kinase inhibitor, affects several gating mechanisms to inhibit cardiac L‐type (Ca(V)1.2) calcium channels
Authors: Yarotskyy V , Elmslie K S
Published: August 2007

Background and purpose:

L‐type calcium channels (Ca
(V)1.2) play an important role in cardiac contraction. Roscovitine, a cyclin‐dependent kinase inhibitor and promising anticancer drug, has been shown to affect Ca
(V)1.2 by inhibiting current amplitude and slowing activation. This research investigates the mechanism by which roscovitine inhibits Ca
(V)1.2 channels.

Experimental approach:

Ca
(V)1.2 channels were transfected into HEK 293 cells, using the calcium phosphate precipitation method, and currents were measured using the whole‐cell patch clamp technique.

Key results:

Roscovitine slows activation at all voltages, which precludes one previously proposed mechanism. In addition, roscovitine enhances voltage‐dependent, but not calcium‐dependent inactivation. This enhancement resulted from both an acceleration of inactivation and a slowing of the recovery from inactivation. Internally applied roscovitine failed to affect Ca
(V)1.2 currents, which supports a kinase‐independent mechanism and extracellular binding site. Unlike the dihydropyridines, closed state inactivation was not affected by roscovitine. Inactivation was enhanced in a dose‐dependent manner with an IC50=29.5±12 μM, which is close to that for slow activation and inhibition.

Conclusions and implications:

We conclude that roscovitine binds to an extracellular site on Ca
(V)1.2 channels to inhibit current by both slowing activation and enhancing inactivation. Purine‐based drugs could become a new option for treatment of diseases that benefit from L‐channel inhibition such as cardiac arrhythmias and hypertension.

British Journal of Pharmacology (2007) 152, 386–395; doi:10.1038/sj.bjp.0707414; published online 13 August 2007
Agonist potency at P2X7 receptors is modulated by structurally diverse lipids
Authors: Michel A D , Fonfria E
Published: August 2007

Background and purpose:

The P2X7 receptor exhibits a high degree of plasticity with agonist potency increasing after prolonged receptor activation. In this study we investigated the ability of lipids to modulate agonist potency at P2X7 receptors.

Experimental approach:

A variety of lipids, including lysophosphatidylcholine, sphingosylphosphorylcholine and hexadecylphosphorylcholine were studied for their effect on P2X7 receptor‐stimulated ethidium bromide accumulation in cells expressing human recombinant P2X7 receptors and on P2X7 receptor‐stimulated interleukin‐1β (IL1β) release from THP‐1 cells. The effects of the lipids were also assessed in radioligand binding studies on human P2X7 receptors.

Key results:

At concentrations (3‐30 μM) below the threshold to cause cell lysis, the lipids increased agonist potency and/or maximal effects at P2X7 receptors in both ethidium accumulation and IL1β release studies. There was little structure activity relationship (SAR) for this effect and sub‐lytic concentrations of Triton X‐100 partially mimicked the effects of the lipids. The lipids caused cell lysis and increased intracellular calcium at higher concentrations (30‐100 μM) which complicated interpretation of their effects in functional studies. However, the lipids (3‐100 μM) also increased agonist potency 30‐100 fold in radioligand binding studies.

Conclusions and implications:

This study demonstrates that a diverse range of lipids increase agonist potency at the P2X7 receptor in functional and binding studies. The broad SAR, including the effect of Triton X‐100, suggests this may reflect changes in membrane properties rather than a direct effect on the P2X7 receptor. Since many of the lipids studied accumulate in disease states they may enhance P2X7 receptor function under pathophysiological conditions.

British Journal of Pharmacology (2007) 152, 523–537; doi:10.1038/sj.bjp.0707417; published online 13 August 2007
The inhibition of monoacylglycerol lipase by URB602 showed an anti‐inflammatory and anti‐nociceptive effect in a murine model of acute inflammation
Authors: Comelli F , Giagnoni G , Bettoni I , Colleoni M , Costa B
Published: August 2007

Background and purpose:

2‐arachidonoylglycerol (2‐AG) is an endocannabinoid whose hydrolysis is predominantly catalysed by the enzyme monoacylglycerol lipase (MAGL). The development of MAGL inhibitors could offer an opportunity to investigate the anti‐inflammatory and anti‐nociceptive role of 2‐AG, which have not yet been elucidated. On these bases, URB602, a MAGL inhibitor, was tested in a murine model of inflammation/inflammatory pain.

Experimental approach:

Acute inflammation was induced by intraplantar injection of λ‐carrageenan into mice. The highest dose to be employed has been selected performing the tetrad assays for cannabimimetic activity in mice. URB602 anti‐inflammatory and anti‐nociceptive efficacy (assessed by plethysmometer and plantar test, respectively) was evaluated both in a preventive regimen (drug administered 30 min before carrageenan) and in a therapeutic regimen (URB602 administered 30 min after carrageenan). To elucidate the cannabinoid receptor involvement, rimonabant and SR144528, CB1and CB2selective antagonists, respectively, were given 15 min before URB602.

Key results:

Systemic administration of URB602 elicited a dose‐dependent anti‐oedemigen and anti‐nociceptive effect that was reversed exclusively by the CB2receptor antagonist. The efficacy of URB602 persisted also when the compound was administered in a therapeutic regimen, suggesting the ability of URB602 to improve established disease.

Conclusions and implications:

The present report highlighted the ability of the selective MAGL inhibitor, URB602, to prevent and treat an acute inflammatory disease without producing adverse psychoactive effects. The data presented herein also contributed to clarify the physiological role of 2‐AG in respect to inflammatory reactions, suggesting its protective role in the body.

British Journal of Pharmacology(2007)152, 787–794; doi:10.1038/sj.bjp.0707425; published online 13 August 2007
Characterization of atypical antipsychotic drugs by a late decrease of striatal alpha1 spectral power in the electropharmacogram of freely moving rats
Authors: Dimpfel W
Published: August 2007

Background and purpose:

Drug administration modifies the balance of neurotransmitter‐controlled ion channel activity and consequently the firing pattern of local neuronal populations and intracerebral field potentials. Fast Fourier Transformation of these field potentials provides an electropharmacogram depicting drug‐induced changes within defined frequency ranges. The present investigation was undertaken to investigate the difference between atypical and typical antipsychotic drugs.

Experimental approach:

Adult Fisher rats were implanted with 4 bipolar concentric steel electrodes using a stereotactic surgical procedure. Field potentials from four selected brain areas in freely moving rats were used to analyse the frequency content of the electropharmacogram after administration of 4 clinically used atypical antipsychotic drugs.

Key results:

Atypical antipsychotics exerted effects similar to those reported for typical antipsychotics, on the electropharmacogram during the first hour after administration, whereas clear differences emerged during the second and third hour after dosing. During the latter period, only atypical antipsychotic drugs produced a statistically significant decrease in alpha1 and beta1 spectral power, especially within the striatum, somewhat less in the cortex.

Conclusions and implications:

Previous studies have attributed alpha1 frequency changes to the influence of 5‐hydroxytryptamine (5‐HT) and the present data are consistent with additional binding of atypical drugs to 5‐HT receptors. This implies that a change in the balance between dopaminergic and 5‐hydroxytryptaminergic neurotransmission (activation of both) is likely to underlie the relative lack of extrapyramidal side effects characteristic of atypical antipsychotics and also for their higher efficacy in the treatment of mood and cognition deficits in schizophrenics.

British Journal of Pharmacology (2007) 152, 538–548; doi:10.1038/sj.bjp.0707427; published online 13 August 2007
Self-organization of 6H-SiC (0001) surface under keV ion irradiation
Authors: Katharria Y. S. , Kumar Sandeep , Lakshmy P. S. , Kanjilal D. , Sharma A. T.
Published: August 2007

In the present study, we have investigated the temporal evolution of 6H-SiC (0001) surface under 100keV Ar+ ion irradiation at oblique incidence (θ=60°). The topographical changes introduced by ion beam were examined using scanning force microscopy, and it is demonstrated that while at short time scales, surface morphology is dominated by dots with average diameter of 30nm, periodic height modulations or ripples emerge at the later time scales. Existing theories of ripple formation have been invoked to explain various features of the observed ripples. Ripple structures developed on a physically stable material such as SiC are expected to show very small time degradation and therefore, would be more advantageous for various technological applications as compared to those grown on conventional semiconductors such as Si, GaAs, InP, etc.
X-ray magnetic circular dichroism characterization of GaN∕Ga1−xMnxN digital ferromagnetic heterostructure
Authors: Hwang J. I. , Kobayashi M. , Song G. S. , Fujimori A. , Tanaka A. , Yang Z. S. , Lin H. J. , Huang D. J. , Chen C. T. , Jeon H. C. , Kang T. W.
Published: August 2007

The authors have investigated the magnetic properties of a GaN∕Ga1−xMnxN (x=0.1) digital ferromagnetic heterostructure (DFH) showing ferromagnetic behavior using soft x-ray absorption spectroscopy (XAS) and x-ray magnetic circular dichroism (XMCD). The Mn L2,3-edge XAS spectra were similar to those of Ga1−xMnxN random alloy thin films, indicating a substitutional doping of high concentration Mn into GaN. From the XMCD measurements, it was revealed that paramagnetic and ferromagnetic Mn atoms coexisted in the Ga1−xMnxN digital layers. Subtle differences were also found from the XMCD spectra between the electronic states of the ferromagnetic and paramagnetic Mn2+ ions. The ferromagnetic moment per Mn atom estimated from XMCD agreed well with that estimated from superconducting quantum interference device measurements, indicating that the ferromagnetic behavior of the GaN∕Ga1−xMnxN DFH sample arises only from substitutional Mn2+ ions in the Ga1−xMnxN digital layers and not from ferromagnetic precipitates.
High-speed growth and photoluminescence of porous anodic alumina films with controllable interpore distances over a large range
Authors: Li Y. B. , Zheng M. J. , Ma L.
Published: August 2007

Highly ordered porous anodic alumina (PAA) films are fabricated with high efficiency by stable high-field anodization in oxalic acid/ethanol/water electrolytes at 100–180V and sulfuric acid/oxalic acid/ethanol/water electrolytes at 30–80V, giving interpore distances in the range of 225–450nm and 70–140nm, respectively. The photoluminescence of PAA films prepared by high-field anodization shows remarkable redshift of the peak position and decrease of the intensity compared to that of PAA films formed by conventional low-field anodization.
Globalisation and Industrial Change in the Clothing Industry of Transcarpathia, Western Ukraine: A Microlevel View
Authors: Kalantaridis Christos , Slava Svitlana , Vassilev Ivaylo
Published: August 2007

This paper sets out to examine the integration of a region (Transcarpathia), undergoing a process of postsocialist transformation, in the global marketplace. In doing so, it deploys a microlevel approach in deciphering the findings of extensive fieldwork investigation. The argument advanced here is that the phenomenon reported does not fit well within the confines of the global commodity chain literature. The pursuit of patterns and regularities, as well as the overwhelming economic development focus of this approach tend to obscure differences, and restrict our understanding of globalisation and industrial dynamics, especially in the case of areas undergoing a process of postsocialist transformation.
Vitrification-based shoot tip cryopreservation of Carica papaya and a wild relative Vasconcellea pubescens
Authors: Ashmore Sarah E. , Drew Roderick A. , Azimi Mahmoud
Published: August 2007

This paper reports on the effects of pre- and post-liquid nitrogen modifications to a previously published protocol for vitrification-based cryopreservation of papaya (Carica papaya L.) shoot tips. The aim was to improve the protocol for application across a wider range of papaya genotypes. Results showed that recovery from cryopreservation is genotype dependent, but the post-subculture age of the shoot tips was not significant in the two genotypes tested. Pre-culture for 2 days gave greater recovery than that for 0, 1 or 4 days. The duration and temperature of exposure to plant vitrification solution 2 (PVS2) had the most significant impact, with optimal recovery of 60 and 64% with 10 min at room temperature or 20 min at 0°C, respectively. Exposure to PVS2 for greater than 30 min reduced recovery to below 20%. Post-cryopreservation recovery was highest in media containing 1.0 µm 6-benzylaminopurine (BAP) or a combination of BAP and gibberellic acid (GA3) (1.0 and 0.5 µm, respectively). Incubation in the dark for the first 24–48 h had no significant effect on recovery. A refined protocol was developed based on these results and application of this protocol proved to be effective across seven papaya genotypes and one related species, Vasconcellea pubescens V.M.Badillo. Genotypes previously showing no survival on an unrefined protocol recovered using this revised protocol.
Extent of clonality, genetic diversity and decline in the endangered mallee Eucalyptus imlayensis
Authors: James Elizabeth A. , McDougall Keith L.
Published: August 2007

Eucalyptus imlayensis Crisp & Brooker is a rare mallee known from one location in south-eastern Australia. Discovered in 1977, the population has declined in number and health of stems since 1998. Inter-simple sequence repeat (ISSR) markers were used to assess genetic variation and clonality. Only five multilocus genotypes were distinguished from 27 samples and the proximity of like genotypes within the population is consistent with the population being largely clonal. This means that the species has a much lower number of genetic individuals than is suggested from a census of the number of stems present. The implications of this finding for ex situ conservation of the species are discussed.
Microsatellite and cpDNA variation in island and mainland populations of a regionally rare eucalypt, Eucalyptus perriniana (Myrtaceae)
Authors: Rathbone Damien A. , McKinnon Gay E. , Potts Brad M. , Steane Dorothy A. , Vaillancourt René E.
Published: August 2007

Eucalyptus perriniana F.Muell. ex Rodway is distributed over a wide geographic range in south-eastern Australia as a series of small and isolated populations. In Tasmania, there are only three known populations that are separated by 511 km from the closest population on mainland Australia, which is one of the largest disjunctions observed for any eucalypt species. This project utilised eight nuclear microsatellites and one chloroplast DNA marker to study the genetic diversity in E. perriniana and determine the affinities between the populations. In all, 302 individuals in nine populations across the whole range of the species were sampled. The overall nuclear microsatellite diversity in E. perriniana (Ht = 0.85), as well as the diversity in each population (He = 0.73), was comparable to that found in widespread eucalypt species that have much larger population sizes. The microsatellites revealed that the isolated Tasmanian populations were significantly differentiated from mainland populations (FST between regions = 0.08), although the mainland Baw Baw population was the most differentiated. Most populations harboured different chloroplast DNA haplotypes, but in general, there were more mutational differences among haplotypes found in Tasmania than between Tasmanian and mainland populations. The Tasmanian populations often shared chloroplast DNA haplotypes with other eucalypts from south-eastern Tasmania. In conclusion, the populations of E. perriniana are genetically variable and significantly differentiated, with geographic separation being a poor predictor of the amount of genetic divergence. The most divergent populations are those in Tasmania and on Mt Baw Baw and their conservation is important to capture the genetic diversity in the species.
Gravity segregation during miscible displacement—re-investigation and re-interpretation
Authors: Rose D. A. , Abbas F.
Published: August 2007

When the liquid residing in a horizontal bed of porous material is displaced by another liquid of different density, the resulting hydrodynamic dispersion is modified by the formation of a tongue of denser liquid undershooting the less dense liquid, a phenomenon known as gravity segregation. An earlier account of gravity segregation contained a substantial error (that of an incorrect frame of reference for flow) and several printing mistakes. In this paper we (i) correct these errors, (ii) extend the analysis to describe the course of breakthrough in beds of rectangular and circular cross-sections, (iii) re-interpret the existing experimental evidence, and (iv) present new experimental results on the vertical and horizontal transport of ionic solutions of different concentrations and densities through inert and reactive porous materials, ballotini, and sepiolite, respectively. The behaviour of immiscible liquids is predicted by the non-dimensional gravity segregation number, β, segregation becoming more extreme as β increases. With miscible liquids, however, breakthrough starts later and ends earlier then predicted for immiscible liquids, mixing by hydrodynamic dispersion moderating the effect of segregation. Breakthrough curves are well fitted by CXTFIT 2.0; apparent coefficients of hydrodynamic dispersion vary much less with pore-water velocity in horizontal than in vertical flow, but retardation factors are not influenced by orientation. Although a formal analysis of the combined effect of gravity segregation and hydrodynamic dispersion was not possible, the statistically significant inverse relation between β and column Peclet number was explained qualitatively. Gravity segregation occurs during the intrusion of saline groundwater into coastal aquifers. The simple theory for immiscible displacement overestimates the actual intrusion that occurs with miscible liquids and so provides an effective safety margin.
A laboratory and glasshouse evaluation of chicken litter ash, wood ash, and iron smelting slag as liming agents and P fertilisers
Authors: Yusiharni B. E. , Ziadi H. , Gilkes R. J.
Published: August 2007

Standard AOAC methods of chemical analysis have been used to characterise the industrial byproducts partly burnt chicken litter ash (CLA), totally burnt chicken litter ash (CLAT), wood ash (WA), and iron smelting slag, for use as a combined liming agent and phosphate (P) fertiliser. These materials are effective liming agents with calcium carbonate equivalence of 93–99%. Total P concentrations of CLA (3.6% P), CLAT (4.75% P), slag (0.26% P), and WA (0.44% P) indicate that they would function as P fertilisers when applied at the high rates required for liming soils. The form of P in slag is unknown; CLA and CLAT consist mostly of mixtures of the phosphate mineral apatite with calcite and quartz. WA consists mostly of calcite, quartz, and various salts. For long extraction times, total P dissolved increased in the sequence CA (citric acid) > NAC (neutral ammonium citrate) > AAC (alkaline ammonium citrate). Little apatite persisted in residues of CLA and CLAT after 120 h of CA extraction but considerable amounts of apatite remained in NAC and AAC residues. A glasshouse P-response experiment was carried out with ryegrass on an acid lateritic soil with the application of various levels of phosphate as chicken litter ash, iron smelting slag, and wood ash. Monocalcium phosphate (MCP), dicalcium phosphate (DCP), and rock phosphate (RP) were included for comparison purposes. Based on plant yield data, the relative agronomic effectiveness (RE) of DCP compared to MCP was 57%, 72%, 73%, and 94%, respectively, for 4 successive harvests, for RP was 24%, 34%, 70%, and 56%, for chicken litter ash was 13%, 16%, 33%, and 39%, for slag was 8%, 9%, 16%, and 10%, for WA was 6%, 9%, and was effectively zero for the final 2 harvests. For no extraction time was the P soluble in the 3 citrate extractants a reliable predictor of the agronomic effectiveness of these materials as P fertilisers established by plant growth measurements.
A comparison of some surface soil phosphorus tests that could be used to assess P export potential
Authors: Nash David , Hannah Murray , Barlow Kirsten , Robertson Fiona , Mathers Nicole , Butler Craig , Horton Jessie
Published: August 2007

Phosphorus (P) exports from agricultural land are a problem world-wide and soil tests are often used to identify high risk areas. A recent study investigated changes in soil (0–20 mm), soil water and overland flow in 4 recently laser-graded (<1 year) and 4 established (laser-graded >10 years) irrigated pastures in south-eastern Australia before and after 3 years of irrigated dairy production. We use the results from that study to briefly examine the relationships between a series of ‘agronomic’ (Olsen P, Colwell P), environmental (water-extractable P, calcium chloride extractable P, P sorption saturation, and P sorption), and other (total P, organic P) soil P tests.
Of the 2 ‘agronomic’ soil P tests, Colwell P explained 91% of the variation in Olsen P, and Colwell P was better correlated with the other soil tests. With the exception of P sorption, all soil P tests explained 57% or more of the total variation in Colwell P, while they explained 61% or less of Olsen P possibly due to the importance of organic P in this soil. Variations in total P were best explained by the organic P (85%), Calcium chloride extractable P (83%), water-extractable P (78%), and P sorption saturation (76%). None of the tests adequately predicted the variation in P sorption at 5 mg P/L equilibrating solution concentration.
The results of this limited study highlight the variability between soil P tests that may be used to estimate P loss potential. Moreover, these results suggest that empirical relationships between specific soil P tests and P export potential will have limited resolution where different soil tests are used, as the errors in the relationship between soil test P and P loss potential are compounded by between test variation. We conclude that broader study is needed to determine the relationships between soil P tests for Australian soils, and based on that study a standard protocol for assessing the potential for P loss should be developed.
Lack of CD47 on nonhematopoietic cells induces split macrophage tolerance to CD47nullcells
Authors: Wang Hui , Madariaga Maria Lucia , Wang Shumei , Van Rooijen Nico , Oldenborg Per-Arne , Yang Yong-Guang
Published: August 2007

Macrophages recognize CD47 as a marker of “self” and phagocytose CD47nullhematopoietic cells. Using CD47 chimera models, here, we show that the phagocytic activity of macrophages against CD47nullhematopoietic cells is conferred by CD47 expression on nonhematopoietic cells, and this “education” process is hematopoietic cell-independent. Macrophages in the chimeras where nonhematopoietic cells express CD47 phagocytose CD47nullcells, whereas those in the chimeras lacking CD47 on nonhematopoietic cells are tolerant to CD47nullcells. However, macrophages in the latter chimeras retain phagocytic activity against CD47nullRBCs, demonstrating a split macrophage tolerance to CD47nullhematopoietic cells. The findings highlight the potential importance of nonhematopoietic cells in the regulation of macrophage function, and suggest a previously uncharacterized mechanism of macrophage tolerance.
On the importance of a funneled energy landscape for the assembly and regulation of multidomain Src tyrosine kinases
Authors: Faraldo-Gómez José D. , Roux Benoît
Published: August 2007

Regulation of signaling pathways in the cell often involves multidomain allosteric enzymes that are able to adopt alternate active or inactive conformations in response to specific stimuli. It is therefore of great interest to elucidate the energetic and structural determinants that govern the conformational plasticity of these proteins. In this study, free-energy computations have been used to address this fundamental question, focusing on one important family of signaling enzymes, the Src tyrosine kinases. Inactivation of these enzymes depends on the formation of an assembly comprising a tandem of SH3 and SH2 modules alongside a catalytic domain. Activation results from the release of the SH3 and SH2 domains, which are then believed to be structurally uncoupled by virtue of a flexible peptide link. In contrast to this view, this analysis shows that inactivation depends critically on the intrinsic propensity of the SH3–SH2 tandem to adopt conformations that are conducive to the assembled inactive state, even when no interactions with the rest of the kinase are possible. This funneling of the available conformational space is encoded within the SH3–SH2 connector, which appears to have evolved to modulate the flexibility of the tandem in solution. To further substantiate this notion, we show how constitutively activating mutations in the SH3–SH2 connector shift the assembly equilibrium toward the disassembled, active state. Based on a similar analysis of several constructs of the kinase complex, we propose that assembly is characterized by the progressive optimization of the protein's conformational energy, with little or no energetic frustration.
The role of fluctuations in tRNA selection by the ribosome
Authors: Lee Tae-Hee , Blanchard Scott C. , Kim Harold D. , Puglisi Joseph D. , Chu Steven
Published: August 2007

The detailed mechanism of how the ribosome decodes protein sequence information with an abnormally high accuracy, after 40 years of study, remains elusive. A critical element in selecting correct transfer RNA (tRNA) transferring correct amino acid is “induced fit” between the ribosome and tRNA. By using single-molecule methods, the induced fit mechanism is shown to position favorably the correct tRNA after initial codon recognition. We provide evidence that this difference in positioning and thermal fluctuations constitutes the primary mechanism for the initial selection of tRNA. This work demonstrates thermal fluctuations playing a critical role in the substrate selection by an enzyme.
Induction of autoimmune disease in CTLA-4−/−mice depends on a specific CD28 motif that is required forin vivocostimulation
Authors: Tai Xuguang , Van Laethem Francois , Sharpe Arlene H. , Singer Alfred
Published: August 2007

CTLA-4-deficient mice develop a lethal autoimmune lymphoproliferative disorder that is strictly dependent onin vivoCD28 costimulation. Nevertheless, it is not known whether there is a specific site on the CD28 molecule that is required for induction of autoimmunity. Using CTLA-4-deficient mice expressing CD28 molecules with various point mutations in the CD28 cytosolic tail, the present study documents thatin vivocostimulation for induction of autoimmune disease strictly requires an intact C-terminal proline motif that promotes lymphocyte-specific protein tyrosine kinase Lck binding to the CD28 cytosolic tail, because point mutations in C-terminal proline residues (Pro-187 and Pro-190) completely prevented disease induction. In contrast,in vivocostimulation for disease induction did not require either an intact YMNM motif or an intact N-terminal proline motif, which, respectively, promote phosphoinositide 3-kinase and IL2-inducible T cell kinase binding to the CD28 cytosolic tail. Thus,in vivoCD28 costimulation for induction of autoimmune disease is strictly and specifically dependent on an intact C-terminal proline motif that serves as a lymphocyte-specific protein tyrosine Lck kinase binding site in the CD28 cytosolic tail.
Electron cyclotron wave power loss in fusion plasmas: a model comparison*
Authors: Albajar F. , Bornatici M. , Engelmann F.
Published: August 2007

For the modelling of hot reactor-grade plasmas a way to compute local electron cyclotron wave losses efficiently and with good accuracy is required. Thereby the approach to calculating the electron cyclotron absorption coefficient is an essential element. A comparison of three available analytical forms (a ‘quasi-exact’ one and the asymptotic forms due to Trubnikov and to Robinson) shows that, overall, the use of Robinson's formula is the most suitable choice.
FGF-2 Release from the Lens Capsule by MMP-2 Maintains Lens Epithelial Cell Viability
Authors: Tholozan Frederique M.D. , Gribbon Christopher , Li Zheng , Goldberg Martin W. , Prescott Alan R. , McKie Norman , Quinlan Roy A.
Published: August 2007

The lens is an avascular tissue, separated from the aqueous and vitreous humors by its own extracellular matrix, the lens capsule. Here we demonstrate that the lens capsule is a source of essential survival factors for lens epithelial cells. Primary and immortalized lens epithelial cells survive in low levels of serum and are resistant to staurosporine-induced apoptosis when they remain in contact with the lens capsule. Physical contact with the capsule is required for maximal resistance to stress. The lens capsule is also a source of soluble factors including fibroblast growth factor 2 (FGF-2) and perlecan, an extracellular matrix component that enhances FGF-2 activity. Matrix metalloproteinase 2 (MMP-2) inhibition as well as MMP-2 pretreatment of lens capsules greatly reduced the protective effect of the lens capsule, although this could be largely reversed by the addition of either conditioned medium or recombinant FGF-2. These data suggest that FGF-2 release from the lens capsule by MMP-2 is essential to lens epithelial cell viability and survival.
Rabaptin-5-independent Membrane Targeting and Rab5 Activation by Rabex-5 in the Cell
Authors: Zhu Huaiping , Zhu Guangyu , Liu Jay , Liang Zhimin , Zhang Xuejun C. , Li Guangpu
Published: August 2007

Rabex-5 is a guanine nucleotide exchange factor (GEF) for Rab5. Here, we report the identification of a novel functional domain of Rabex-5 that is essential for its membrane targeting and Rab5 GEF activity in vivo. The data show that full-length Rabex-5 efficiently activates Rab5 in the cell. However, the GEF domain itself (residues 135–399) is inactive in this respect, despite its activity in vitro. Generation and characterization of a series of Rabex-5 constructs reveal that the GEF domain is unable to target to early endosomes and that a sequence N-terminal to the GEF domain can restore its early endosomal targeting and its ability to activate Rab5 in the cell. This region (residues 81–135) is termed membrane-binding motif, which together with the downstream helical bundle domain (residues 135–230) forms an early endosomal targeting (EET) domain necessary and sufficient for association with early endosomes. Furthermore, several active Rabex-5 constructs do not contain the Rabaptin-5-binding domain in the C-terminal region. Thus, Rabex-5 can target to early endosomes via the EET domain and activate Rab5 in a Rabaptin-5–independent manner in vivo. We discuss a model to reconcile these in vivo data with previous in vitro results on Rabex-5 function and its interaction with Rabaptin-5.
Protein Kinase A and Sch9 Cooperatively Regulate Induction of Autophagy inSaccharomyces cerevisiae
Authors: Yorimitsu Tomohiro , Zaman Shadia , Broach James R. , Klionsky Daniel J.
Published: August 2007

Autophagy is a highly conserved, degradative process in eukaryotic cells. The rapamycin-sensitive Tor kinase complex 1 (TORC1) has a major role in regulating induction of autophagy; however, the regulatory mechanisms are not fully understood. Here, we find that the protein kinase A (PKA) and Sch9 signaling pathways regulate autophagy cooperatively in yeast. Autophagy is induced in cells when PKA and Sch9 are simultaneously inactivated. Mutant alleles of these kinases bearing a mutation that confers sensitivity to the ATP-analogue inhibitor C3-1′-naphthyl-methyl PP1 revealed that autophagy was induced independently of effects on Tor kinase. The PKA–Sch9-mediated autophagy depends on the autophagy-related 1 kinase complex, which is also essential for TORC1-regulated autophagy, the transcription factors Msn2/4, and the Rim15 kinase. The present results suggest that autophagy is controlled by the signals from at least three partly separate nutrient-sensing pathways that include PKA, Sch9, and TORC1.
Epidermal ‘alarm substance’ cells of fishes maintained by non-alarm functions: possible defence against pathogens, parasites and UVB radiation
Authors: Chivers Douglas P , Wisenden Brian D , Hindman Carrie J , Michalak Tracy A , Kusch Robin C , Kaminskyj Susan G.W , Jack Kristin L , Ferrari Maud C.O , Pollock Robyn J , Halbgewachs Colin F , Pollock Michael S , Alemadi Shireen , James Clayton T , Savaloja Rachel K , Goater Cameron P , Corwin Amber , Mirza Reehan S , Kiesecker Joseph M , Brown Grant E , Adrian James C , Krone Patrick H , Blaustein Andrew R , Mathis Alicia
Published: August 2007

Many fishes possess specialized epidermal cells that are ruptured by the teeth of predators, thus reliably indicating the presence of an actively foraging predator. Understanding the evolution of these cells has intrigued evolutionary ecologists because the release of these alarm chemicals is not voluntary. Here, we show that predation pressure does not influence alarm cell production in fishes. Alarm cell production is stimulated by exposure to skin-penetrating pathogens (water moulds:Saprolegnia feraxandSaprolegnia parasitica), skin-penetrating parasites (larval trematodes:Teleorchissp. andUvulifersp.) and correlated with exposure to UV radiation. Suppression of the immune system with environmentally relevant levels of Cd inhibits alarm cell production of fishes challenged withSaprolegnia. These data are the first evidence that alarm substance cells have an immune function against ubiquitous environmental challenges to epidermal integrity. Our results indicate that these specialized cells arose and are maintained by natural selection owing to selfish benefits unrelated to predator–prey interactions. Cell contents released when these cells are damaged in predator attacks have secondarily acquired an ecological role as alarm cues because selection favours receivers to detect and respond adaptively to public information about predation.
Global warming in the public sphere
Authors: Corfee-Morlot Jan , Maslin Mark , Burgess Jacquelin
Published: August 2007

Although the science of global warming has been in place for several decades if not more, only in the last decade and a half has the issue moved clearly into the public sphere as a public policy issue and a political priority. To understand how and why this has occurred, it is essential to consider the history of the scientific theory of the greenhouse effect, the evidence that supports it and the mechanisms through which science interacts with lay publics and other elite actors, such as politicians, policymakers and business decision makers. This article reviews why and how climate change has moved from the bottom to the top of the international political agenda. It traces the scientific discovery of global warming, political and institutional developments to manage it as well as other socially mediated pathways for understanding and promoting global warming as an issue in the public sphere. The article also places this historical overview of global warming as a public issue into a conceptual framework for understanding relationships between society and nature with emphasis on the co-construction of knowledge.
Future economic damage from tropical cyclones: sensitivities to societal and climate changes
Authors: Pielke Roger A
Published: August 2007

This paper examines future economic damages from tropical cyclones under a range of assumptions about societal change, climate change and the relationship of climate change to damage in 2050. It finds in all cases that efforts to reduce vulnerability to losses, often called climate adaptation, have far greater potential effectiveness to reduce damage related to tropical cyclones than efforts to modulate the behaviour of storms through greenhouse gas emissions reduction policies, typically called climate mitigation and achieved through energy policies. The paper urges caution in using economic losses of tropical cyclones as justification for action on energy policies when far more potentially effective options are available.
Living cell motility
Authors: Coelho Neto José , Mesquita Oscar Nassif
Published: August 2007

The motility of living eukaryotic cells is a complex process driven mainly by polymerization and depolymerization of actin filaments underneath the plasmatic membrane (actin cytoskeleton). However, the exact mechanisms through which cells are able to control and employ ‘actin-generated’ mechanical forces, in order to change shape and move in a well-organized and coordinated way, are not quite established. Here, we summarize the experimental results obtained by our research group during recent years in studying the motion of living cells, such as macrophages and erythrocytes. By using our recently developed defocusing microscopy technique, which allows quantitative analysis of membrane surface dynamics of living cells using a simple bright-field optical microscope, we were able to analyse morphological and dynamical parameters of membrane ruffles and small membrane fluctuations, study the process of phagocytosis and also measure values for cell refractive index, membrane bending modulus and cell viscosity. Although many questions still remain unanswered, our data seem to corroborate some aspects of recent physical models of cell membranes and motility.