bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of aldosterone receptor blockade in patients with mild–moderate heart failure taking a beta‐blocker
Authors: Berry Colin , Murphy Niamh , De Vito Giuseppe , Galloway Stuart , Seed Alison , Fisher Carol , Sattar Naveed , Vallance Patrick , Hillis W. Sewart , McMurray John
Published: November 2006

Aims:

Spironolactone improves prognosis in severe heart failure (HF). We investigated its effects in patients with mild–moderate HF treated with an ACE inhibitor and beta‐blocker.

Methods and results:

Randomised, double‐blind, parallel‐group, 3‐month comparison of placebo and spironolactone (25 mg daily) in 40 patients in New York Heart Association (NYHA) class I (20%), II (70%) or III (10%), with a left ventricular ejection fraction of <40%.

The mean (standard error) changes from baseline in the spironolactone and placebo groups were, respectively: i) B‐type natriuretic peptide (BNP) −53.4(22.2) pg/mL and +3.3(12.1) pg/mL, P=0.04, ii) pro‐collagen type III N‐terminal amino peptide (PIIINP) −0.6(0.2) μmol/L and +0.02(0.2) μmol/L, P=0.02 and iii) creatinine +10.7(3.2) μmol/L and −0.3(2.6) μmol/L, P=0.01.

Compared with placebo, spironolactone therapy was associated with a reduction in self‐reported health‐related quality of life: change in visual analog score: −6 (3) vs. +6 (4); P=0.01.

No differences were observed on other biochemical, neurohumoral, exercise and autonomic function assessments.

Conclusion:

In patients with mild–moderate HF, spironolactone reduced neurohumoral activation (BNP) and a marker of collagen turnover (PIIINP) but impaired renal function and quality of life. The benefit–risk ratio of aldosterone blockade in mild HF is uncertain and requires clarification in a large randomised trial.
Acute muscle inflammation enhances the monosynaptic reflexes and c‐fos expression in the feline spinal cord
Authors: Schomburg Eike D. , Steffens Heinz , Maznychenko Andrey V. , Pilyavskii Alexander I. , Hellström Fredrik , Kostyukov Alexander I. , Maisky Vladimir A.
Published: November 2006

The aim of this research was to study the changes of the motor reflex activity (monosynaptic reflex (MSR) of the flexor and extensor muscles) and Fos immunoreactivity in lumbo‐sacral spinal cord after acute induced myositis of m. gastrocnemius‐soleus (GS). The experiments were carried out on ischaemic decerebrated, spinalized in C1 cats. After infiltration of the GS muscle with carrageenan (2%) MSRs of flexors and extensors showed a significant increase in amplitude +127±24.5% and +155±28.5%, respectively, p<0.05. The exposed effect was initiated within 30min and achieved a maximum 2.8h after the intramuscular injections of carrageenan. After analysis of dynamics of the MSRs, animals were perfused and c‐fos expression in the spinal segments L6–S1 was evaluated. In comparison to sham‐operated animals, the number of Fos‐immunoreactive (Fos‐ir) cells was noticeably increased in the lumbar cord of cats with carrageenan‐induced myositis. The labeled cells were concentrated in the ipsilateral laminae I/II, neck of the dorsal horn (V/VI) and intermediate zone (VII), however, clear predominance of their concentration was found in the deep laminae. The effect of muscle inflammation was also expressed as a significant decline in the number of NADPH‐d‐reactive cells (p<0.05) in ipsilateral laminae I/II of L6/L7. The results show that the input from acutely inflamed muscles may induce an increase of the reflex responsiveness of flexors and extensors which is not mediated via the gamma‐spindle‐loop and which coincides with a significant increase in c‐fos expression in the deep laminae of the lumbar spinal cord.
Long‐term reliable change of pain scores in individual myogenous TMD patients
Authors: van Grootel Robert J. , van der Bilt Andries , van der Glas Hilbert W.
Published: November 2006

A within‐patient change in pain score after treatment is statistically ‘reliable’ when it exceeds the smallest detectable difference (SDD). The aims of the present study were to: (i) determine SDDs for VAS‐scores of pain intensity, for sufficiently long test–retest intervals to include most biological fluctuations, (ii) examine whether SDD is invariant to baseline score, and (iii) discuss the value of reliable change (RC) for detecting clinically important difference (CID) or as a possible indicator of successful treatment. SDDs were determined using duplicate data from 118 patients with myogenous Temporomandibular disorders: (1) VAS‐scores of pain intensity from the masticatory system in a pre‐treatment diary, and (2) VAS‐scores of pain intensity from the hand (cold‐pressor test). RC was determined in VAS‐scores from a pre‐ and post‐treatment questionnaire. The long‐term SDD was 49 mm. A regression analysis on duplicate VAS‐scores showed that SDD was largely invariant to the baseline level. Because RC (change > SDD) exceeded CID, it might serve as an indicator of successful treatment. However, only 17% of the patients showed RC after treatment, mainly because the baseline was smaller than SDD in 67% of the patients thus making detection of any treatment effect impossible. For patients with possible detection (33%), the frequency of RC was 51%. If the detection threshold would be avoided by provoking pain in patients with a low baseline, a long‐term RC in VAS‐scores might occur in about half of all myogenous TMD patients and might then serve as an indicator of cases of treatment success.
Triton X‐100 can alter the temporal sequence of the light‐driven proton pump of archaerhodopsin 4
Authors: Ming Ming , Wang Yazhuo , Wu Jia , Ma Dewang , Li Qingguo , Ding Jiandong
Published: November 2006

We report that Triton X‐100 can alter the temporal sequence of the light‐induced proton uptake and release of archaerhodopsin 4 (AR4), a proton pumping protein in a species of Halobacteria from a Tibetan salt lake. Under physiological conditions, AR4 isolated from the bacterium exhibits a reversed temporal order of proton release and uptake compared to what is observed for bacteriorhodopsin (BR). However, in the presence of Triton X‐100 early proton release was observed in AR4 at neutral pH by us. Further, this temporal order for light‐driven proton release and uptake for AR4 was found to be recovered after the removal of Triton X‐100 by Biobeads. This phenomenon of detergent‐induced alteration of the order of proton release and uptake has not yet been reported in any other retinal‐containing membrane protein such as BR. Our findings indicate that the function of AR4 is influenced by its self‐assembled state, and meanwhile imply some subtle protein–lipid interactions or protein–protein interactions in adjusting the proton pumping behavior of AR4.
Ribosomal protein S1 induces a conformational change of the 30S ribosomal subunit
Authors: Agalarov Sultan Ch. , Kalinichenko Artem A. , Kommer Aigar A. , Spirin Alexander S.
Published: November 2006

A comparative study of the 30S ribosomal subunit in the complex with protein S1 and the subunit depleted of this protein has been carried out by the hot tritium bombardment method. Differences in exposure of some ribosomal proteins within the 30S subunit depleted of S1 and within the 30S–S1 complex were found. It was concluded that protein S1 binds in the region of the neck of the 30S ribosomal subunit inducing a conformational change of its structure.
Molecular characterization of a glycerophosphoinositol transporter in mammalian cells
Authors: Mariggiò Stefania , Iurisci Cristiano , Sebastià Jordi , Patton-Vogt Jana , Corda Daniela
Published: November 2006

The glycerophosphoinositols are ubiquitous phosphoinositide metabolites involved in the control of several cell functions. They exert their actions both intracellularly and by rapidly equilibrating across the plasma membrane when added to cells, implying the existence of a transporter for their membrane permeation. Such a transporter, GIT1, has been cloned in yeast. By PSI‐BLAST analysis, we have identified the Glut2 transporter as a human‐genome candidate ortholog of GIT1. This was supported directly through the use of inhibitors, siRNAs and competition studies of specific uptake of GroPIns in HeLa cells over‐expressing human Glut2. These data identify Glut2 as a GroPIns transporter in mammals, and define a physiologically relevant cell‐permeation mechanism.
Plasma fatty acid metabolic profiling and biomarkers of type 2 diabetes mellitus based on GC/MS and PLS‐LDA
Authors: Yi Lun-Zhao , He Jun , Liang Yi-Zeng , Yuan Da-Lin , Chau Foo-Tim
Published: November 2006

Metabolic profiling has increasingly been used as a probe in disease diagnosis and pharmacological analysis. Herein, plasma fatty acid metabolic profiling including non‐esterified fatty acid (NEFA) and esterified fatty acid (EFA) was investigated using gas chromatography/mass spectrometry (GC/MS) followed by multivariate statistical analysis. Partial least squares‐linear discrimination analysis (PLS‐LDA) model was established and validated to pattern discrimination between type 2 diabetic mellitus (DM‐2) patients and health controls, and to extract novel biomarker information. Furthermore, the PLS‐LDA model visually represented the alterations of NEFA metabolic profiles of diabetic patients with abdominal obesity in the treated process with rosiglitazone. The GC/MS‐PLS‐LDA analysis allowed comprehensive detection of plasma fatty acid, enabling fatty acid metabolic characterization of DM‐2 patients, which included biomarkers different from health controls and dynamic change of NEFA profiles of patients after treated with medicine. This method might be a complement or an alternative to pathogenesis and pharmacodynamics research.
Responsiveness of the Dutch Version of the Dash as an Outcome Measure for Carpal Tunnel Syndrome
Authors: DE SMET L. , DE KESEL R. , DEGREEF I. , DEBEER P.
Published: November 2006

A cohort of 119 patients with carpal tunnel syndrome completed the questionnaire of the Dutch version of the DASH score pre-operatively and one year postoperatively. The mean DASH score decreased from 38.2 to 22.0. There was a significant correlation with the Boston carpal tunnel outcome score ( r =0.78). With an effect size of 0.87 and a standardized mean response of 0.69, the Dutch version of the DASH is highly responsive for the evaluation of the outcome of surgery for carpal tunnel syndrome.
Comparison of Forearm and Conventional Bier’s Blocks for Manipulation and Reduction of Distal Radius Fractures
Authors: CHONG A. K. S. , TAN D. M. K. , OOI B. S. , MAHADEVAN M. , LIM A. Y. T. , LIM B. H.
Published: November 2006

Forearm-based Bier’s block has been advocated as a useful anaesthesic technique in hand surgery. However, there is limited data comparing forearm blocks with the conventional Bier’s block. We conducted a randomised controlled trial ( n = 30) comparing the two techniques of anaesthesia for manipulation and reduction of closed distal radius fractures in an emergency room setting. Pain scores measured using the Visual Analogue Scale during the procedure were used as the primary outcome assessment. There was no significant difference in pain scores between the forearm and conventional Bier’s block (mean VAS 18.4 SD 22.10 versus 33.7 SD 29.6). No major complications were observed in either group. The forearm-based Bier block is an effective alternative to the conventional block.
Introduction to the special issue on innovative data sources for empirically building and validating theories in Operations Management
Authors: Gattiker Thomas F. , Parente Diane H.
Published: November 2006

All research methods have strengths and weaknesses. The two dominant empirical methodologies in operations management are the survey and the case study. Reliance on a limited number of methodologies can influence the body of knowledge that that a field generates – and even the problems that the field collectively chooses to investigate or not investigate. The special issue attempts to “push the envelope” in terms of the data sources used in operations management. In particular, the following data sources are used: laboratory study, customer comment data, third‐party web site quality ratings, process characteristics collected from e‐commerce web sites themselves, environmental performance reports, and a publicly available research database. Researchers contemplating their data gathering strategy must consider the strengths and weaknesses of each approach. The introduction to special issue discusses positives and negatives of both conventional and innovative data sources.
Environmental change recorded in sediments from the Marmes rockshelter archaeological site, southeastern Washington state, USA
Authors: Huckleberry Gary , Fadem Cynthia
Published: November 2006

The Marmes Rockshelter archaeological site in southeastern Washington state contains a > 11 kyr stratigraphic record that was excavated in the 1960s but only recently analyzed in detail. We present the results of physical, chemical, and isotopic analyses of archived Marmes sediments from rockshelter, hillslope, and floodplain locations. Multiple lines of evidence including éboulis production, soil chemistry, and δ13C and δ18O signatures in soil organic matter and calcium carbonate suggest that relatively cool, moist conditions 10,600 to 9700 14C yr BP were followed by relatively warm and dry conditions as early as 9000 14C yr BP. Warm and dry conditions extended to the late Holocene, followed by a return to cooler and moister climate. The limited range of δ13C and δ18O values in Marmes paleosols suggests that the magnitude of moisture and temperature shifts was locally buffered in the lower Snake River Canyon but adequate to generate significant changes in sedimentation and soil formation, possibly due to nonlinear geological and pedological processes. These buffered canyon environments were well suited for establishing residential bases associated with foraging and logistical collecting strategies and may have minimized the influence of climate changes in food resource abundance.
Valedictory
Authors: PAYKEL EUGENE S.
Published: November 2006

This issue is my last as editor of Psychological Medicine. It is time to wrap up and to say thank you.
IN THIS ISSUE
Authors: MORGAN CRAIG
Published: November 2006

This issue contains three reviews, one on SSRI use in late pregnancy, one on dimensional approaches to psychiatric diagnoses, and one on resource utilization in the short-term management of deliberate self-harm (DSH). Other sets of papers examine various aspects of substance use and dependence, depression, and suicide, and two individual papers examine further topics.
Estimated net community production during the summertime at the SEATS time‐series study site, northern South China Sea: Implications for nitrogen fixation
Authors: Chou Wen‐Chen , Chen Yuh‐Ling Lee , Sheu David D. , Shih Yung‐Yen , Han Chia‐An , Cho Chung Lung , Tseng Chun‐Mao , Yang Yiing‐Jang
Published: November 2006

The continuous summertime drawdown of normalized dissolved inorganic carbon has been observed repeatedly in the mixed‐layer at the South East Asia Time‐series Study (SEATS) site, northern South China Sea (SCS) between March 2002 and November 2004. Mass balance calculation reveals that a net community production (NCP) of −4.47 mmolC m−2 day−1 is responsible for this drawdown. Nonetheless, bioavailable nitrogen (Nbio) from atmospheric deposition, vertical diffusion, and N2‐fixation by Trichodesmium and Richelia together could only account for ∼55% of Nbio required for the calculated NCP. Unicellular cyanobacteria, which are identified unambiguously by the presence of nitrogenase genes (nifH) in 1–10 μm fraction of planktons collected at SEATS, may account for the Nbio deficit. Our results, thus, support the potential importance of unicellular cyanobacteria in providing an additional Nbio source in oligotrophic waters such as the SCS.
Magnus force in the Venus ionosphere
Authors: Pérez‐de‐Tejada H.
Published: November 2006

The retrograde superrotation motion of the Venus ionosphere is included in a study of the configuration of the ionospheric transterminator flow by using a fluid‐dynamic interpretation of the interaction that takes place between both flow motions. It is argued that the interaction leads to a fluid dynamic force (Magnus force) that produces an overall (∼10°) dawnward directed deflection of the transterminator flow which is comparable to that implied from the PVO observations. The Magnus force results from a pressure difference that is set across the planet by the difference in the speed of the plasma when both the rotation motion and the transterminator flow are in the same sense (dusk side terminator) to that where both motions are opposite to each other (dawn side terminator). The dawnward deflection of the ionospheric plasma in the transterminator flow also deviates the plasma channels (which serve to account for the ionospheric holes) that extend downstream from the magnetic polar regions and is responsible as well for that of the peak of the histogram of the electron density profiles with an upper ionospheric plateau that are seen near the midnight plane. The effects of the Magnus force are also related to the strong difference in the ionopause altitude observed between the dusk and the dawn side terminator (with higher altitudes seen in the dawn side) and to the larger ionospheric transterminator flow speeds measured at high altitudes by the dawn side terminator.
A multistep approach for joint modeling of surface wave dispersion and teleseismic receiver functions: Implications for lithospheric structure of the Arabian Peninsula
Authors: Tkalčić H. , Pasyanos M. E. , Rodgers A. J. , Gök R. , Walter W. R. , Al‐Amri A.
Published: November 2006

We present a multiple step procedure for joint modeling of surface wave group velocity dispersion curves and teleseismic receiver functions for lithospheric velocity structure. The method relies on an initial grid search for a simple crustal structure, followed by a formal iterative inversion, an additional grid search for shear wave velocity in the mantle, and finally, forward modeling of transverse isotropy to resolve Love‐Rayleigh surface wave dispersion discrepancy. It considers longer‐period surface wave group velocity (SWGV) dispersion, allowing for the resolution of deeper structure compared to previous joint inversions. The grid search for simple crustal structure is facilitated using a library of precomputed receiver functions and SWGV dispersion curves. The iterative inversion improves fit to the data by increasing the number of layers in the crust when necessary. In order to fit the SWGV for periods greater than about 50 s, we perform a grid search over mantle velocities including the mantle lid and low‐velocity zone, keeping the crustal structure fixed to the values from the previous step. In some cases a clear Love‐Rayleigh discrepancy prevents a simultaneous fit of the group velocities with an isotropic model. The Love‐Rayleigh discrepancy can be resolved by allowing shear wave transverse isotropy with a vertical symmetry axis (vSH − vSV differences) in the uppermost mantle. The method is applied to 10 stations in the Arabian Peninsula sampling various tectonic environments including active continental rifting and stable regions. The resulting shear velocity models confirm rapid crustal thinning of the Arabian Shield toward the Red Sea; however, we do not find strong evidence for crustal thickening toward the Arabian Platform. Our results suggest that the mantle lithosphere thickness varies regionally but that the mantle shear velocities beneath the Arabian Shield and Red Sea coast are generally anomalously low. Furthermore, our results indicate the presence of strong polarization anisotropy (up to about 10%) in the lithospheric upper mantle, in the vicinity of, as well as farther away from, the Red Sea. Our modeling yields vSV > vSH in the southwestern part of the Arabian Peninsula, consistent with vertical flow, and vSH > vSV in the northwestern part of the Arabian Peninsula and the continental interior, consistent with horizontal flow, indicating that the mantle flow pattern is not uniform along the axis of the Red Sea.
Whistler waves observed near lunar crustal magnetic sources
Authors: Halekas J. S. , Brain D. A. , Mitchell D. L. , Lin R. P.
Published: November 2006

We present Lunar Prospector Magnetometer (LP MAG) observations of monochromatic circularly polarized low frequency waves at frequencies of 0.4–4 Hz near the Moon. We observe such waves on about 6.6% of LP orbits in the solar wind, outside of the lunar wake. About a third of them occur on orbits when we also observe external magnetic enhancements (“limb shocks”), and most are clearly associated with lunar crustal magnetic sources, indicating an origin related to solar wind interaction with lunar magnetic fields. The inferred propagation vectors and polarizations of these waves are consistent with the expected characteristics of whistler‐mode waves. These observations could indicate either upstream whistler waves produced at shock surfaces above lunar crustal magnetic sources, or phase‐standing whistler wakes formed by direct solar wind interaction with lunar crustal magnetic fields.
Reduction in the westward auroral electrojet by a southward turning of the interplanetary magnetic field: A new interpretation
Authors: Shue J.‐H. , Kamide Y.
Published: November 2006

The development of auroral electrojets is known to be mainly controlled by the north‐south component (Bz) of the interplanetary magnetic field (IMF). One of the auroral electrojet indices, AL, is commonly used to monitor the westward electrojet. By studying events for which only the IMF Bz varied significantly, it is found that, for some events, ∣AL∣ can be reduced by a southward turning of the IMF. We interpret this reduction in the westward electrojet by the southward turning as a new electrojet response to the IMF Bz, in addition to previously documented responses of the electrojets to the directly‐driven process, an internal process of the magnetosphere, or a northward turning of the IMF.
A well‐mixed warm water column in the central Bohai Sea in summer: Effects of tidal and surface wave mixing
Authors: Lin Xiaopei , Xie Shang‐Ping , Chen Xinping , Xu Lingling
Published: November 2006

A well‐mixed water column is observed over a 20 m ridge in the central Bohai Sea, surrounded by stratified water of much colder temperatures. We use a three‐dimensional model to investigate its formation mechanisms. The results show that both tidal and surface wave mixing are important for homogenizing the water column, the former reaching 10 m above the bottom and the latter penetrating 10 m beneath the sea surface. The ridge enhances the intensity and vertical extent of tidal mixing, allowing it to connect with the downward penetration of wave mixing. Removing either the bathymetric ridge or wave mixing fails to reproduce this well‐mixed water column. The inclusion of the surface wave mixing warms the bottom water by 5–6°C in both the warm water column and surrounding cold water. Wave mixing displays a maximum in the central Bohai Sea basin, which is confirmed by satellite altimeter data and a wave model simulation.
Upregulation of MIP‐2 (CXCL2) expression by 15‐deoxy‐Δ12,14‐prostaglandin J2 in mouse peritoneal macrophages
Authors: Kim Hyo Y , Kim Hee S
Published: November 2006

A peroxisome proliferator‐activated receptor γ (PPARγ) ligand, 15‐deoxy‐Δ12,14‐prostaglandin J2 (15d‐PGJ2), has been reported to possess anti‐inflammatory activity in activated monocytes/macrophages. In this study, we investigated the effect of 15d‐PGJ2 on the lipopolysaccharide (LPS)‐induced expression of chemokine mRNAs, especially macrophage inhibitory protein (MIP)‐2 (CXCL2), in mouse peritoneal macrophages. The inhibitory actions of the natural PPARγ ligands, 15d‐PGJ2 and prostaglandin A1 (PGA1), on the expression of RANTES (regulated upon activation, normal T expressed and secreted; CCL5), MIP‐1β (CCL4), MIP‐1α (CCL3), IFN‐γ‐inducible protein 10 kilodaltons (IP‐10; CXCL10) and monocyte chemoattractant protein‐1 (MCP‐1; CCL2) mRNA in LPS‐treated cells were stronger than those of the synthetic PPARγ ligands troglitazone and ciglitazone. However, 15d‐PGJ2 enhanced the expression of LPS‐induced MIP‐2 (CXCL2) mRNA. A specific PPARγ antagonist (GW9662) had no effect on the inhibitory action of 15d‐PGJ2 and PGA1 in LPS‐induced chemokine mRNA expression and on the synergistic action of 15d‐PGJ2 in LPS‐induced MIP‐2 (CXCL2) expression. Moreover, LPS itself reduced the expression of PPARγ. Although the synergistic effect of 15d‐PGJ2 on LPS‐induced MIP‐2 (CXCL2) mRNA expression was remarkable, the production of MIP‐2 (CXCL2) in cells treated with 15d‐PGJ2 and LPS did not increase compared to the production in cells treated with LPS alone. The synergistic action of 15d‐PGJ2 on LPS‐induced MIP‐2 (CXCL2) mRNA expression was dependent on the activation of nuclear factor‐κB (NF‐κB), and 15d‐PGJ2 increased the phosphorylation of p38 and stress‐activated protein kinase/c‐Jun N‐terminal kinase (SAPK/JNK) in cells stimulated with LPS. These results suggest that the synergistic effect of 15d‐PGJ2 on LPS‐induced MIP‐2 (CXCL2) expression is PPARγ‐independent, and is mediated by the p38 and SAPK/JNK pathway in mitogen‐activated protein kinase signaling pathways, which activates NF‐κB. Our data may give more insights into the different mechanisms contrary to the anti‐inflammatory effect of 15d‐PGJ2 on the expression of chemokine genes.
Phosphorylation inhibits turnover of the tau protein by the proteasome: influence of RCAN1 and oxidative stress
Authors: Poppek Diana , Keck Susi , Ermak Gennady , Jung Tobias , Stolzing Alexandra , Ullrich Oliver , Davies Kelvin J. A. , Grune Tilman
Published: November 2006

Hyperphosphorylated tau proteins accumulate in the paired helical filaments of neurofibrillary tangles seen in such tauopathies as Alzheimer's disease. In the present paper we show that tau turnover is dependent on degradation by the proteasome (inhibited by MG132) in HT22 neuronal cells. Recombinant human tau was rapidly degraded by the 20 S proteasome in vitro, but tau phosphorylation by GSK3β (glycogen synthase kinase 3β) significantly inhibited proteolysis. Tau phosphorylation was increased in HT22 cells by OA [okadaic acid; which inhibits PP (protein phosphatase) 1 and PP2A] or CsA [cyclosporin A; which inhibits PP2B (calcineurin)], and in PC12 cells by induction of a tet-off dependent RCAN1 transgene (which also inhibits PP2B). Inhibition of PP1/PP2A by OA was the most effective of these treatments, and tau hyperphosphorylation induced by OA almost completely blocked tau degradation in HT22 cells (and in cell lysates to which purified proteasome was added) even though proteasome activity actually increased. Many tauopathies involve both tau hyperphosphorylation and the oxidative stress of chronic inflammation. We tested the effects of both cellular oxidative stress, and direct tau oxidative modification in vitro, on tau proteolysis. In HT22 cells, oxidative stress alone caused no increase in tau phosphorylation, but did subtly change the pattern of tau phosphorylation. Tau was actually less susceptible to direct oxidative modification than most cell proteins, and oxidized tau was degraded no better than untreated tau. The combination of oxidative stress plus OA treatment caused extensive tau phosphorylation and significant inhibition of tau degradation. HT22 cells transfected with tau–CFP (cyan fluorescent protein)/tau–GFP (green fluorescent protein) constructs exhibited significant toxicity following tau hyperphosphorylation and oxidative stress, with loss of fibrillar tau structure throughout the cytoplasm. We suggest that the combination of tau phosphorylation and tau oxidation, which also occurs in tauopathies, may be directly responsible for the accumulation of tau aggregates.
Regulation of the cardiac L-type calcium channel in L6 cells by arginine-vasopressin
Authors: Hantash Basil M. , Thomas Andrew P. , Reeves John P.
Published: November 2006

L-type Ca2+ channel activity was measured in L6 cells as nifedipine-sensitive barium (Ba2+; 5 mM) influx in a depolarizing salt solution containing 140 mM KCl. Addition of AVP (arginine-vasopressin) during Ba2+ uptake reduced the rate of Ba2+ influx by 60–100%; this was followed by a gradual restoration of the initial rate of Ba2+ uptake. Blockade of PKC (protein kinase C) by pretreatment with 10 μM bisindolylmaleimide did not affect the initial inhibition of Ba2+ influx, but completely abolished the recovery phase. The effect of AVP was half-maximal at 10 nM AVP and was blocked by the V1a receptor antagonist d-(CH2)5-Tyr(Me)-AVP. Activation of Gαs by isoprenaline or cholera toxin antagonized the actions of AVP on Ba2+ uptake. This protection persisted in the presence of the PKA (protein kinase A) inhibitor KT5720, and was not mimicked by agents that increase cAMP. Inhibition of Ba2+ influx was also elicited by ATP and ET (endothelin 1) with an order of effectiveness ET<ATP<AVP. Each of these agents has been reported to act through Gq-coupled receptors. We conclude that activation of Gq-coupled receptors produces a rapid inhibition of the cardiac L-type Ca2+ channel, which is subsequently overcome by activation of PKC.
Characterization of A-kinase-anchoring disruptors using a solution-based assay
Authors: Stokka Anne J. , Gesellchen Frank , Carlson Cathrine R. , Scott John D. , Herberg Friedrich W. , Taskén Kjetil
Published: November 2006

Subcellular localization of PKA (cAMP-dependent protein kinase or protein kinase A) is determined by protein–protein interactions between its R (regulatory) subunits and AKAPs (A-kinase-anchoring proteins). In the present paper, we report the development of the Amplified Luminescent Proximity Homogeneous Assay (AlphaScreen™) as a means to characterize AKAP-based peptide competitors of PKA anchoring. In this assay, the prototypic anchoring disruptor Ht31 efficiently competed in RIIα isoform binding with RII-specific and dual-specificity AKAPs (IC50 values of 1.4±0.2 nM and 6±1 nM respectively). In contrast, RIα isoform binding to a dual-specific AKAP was less efficiently competed (IC50 of 156±10 nM). Characterization of two RI-selective anchoring disruptors, RIAD (RI-anchoring disruptor) and PV-38 revealed that RIAD (IC50 of 13±1 nM) was 20-fold more potent than PV-38 (IC50 of 304±17 nM) and did not compete in the RIIα–AKAP interaction. We also observed that the kinetics of RII displacement from pre-formed PKA–AKAP complexes and competition of RII–AKAP complex formation by Ht31 differed by an order of magnitude when the component parts were mixed in vitro. No such difference in potency was seen for RIα–AKAP complexes. Thus the AlphaScreen assay may prove to be a valuable tool for detailed characterization of a variety of PKA–AKAP complexes.
Germination and dormancy states of seeds in the environmental weed Rumex vesicarius (Polygonaceae). II. Germination and dormancy of seeds enclosed within the fruit
Authors: Schatral Andrea , Osborne Joan M.
Published: November 2006

Rumex vesicarius (Ruby dock; subgenus Acetosa, section Vesicarii, family Polygonaceae) shows fascinating ways of controlling and staggering seed germination throughout the year. Seeds within the large inflated fruiting valves (fruits) display variations in their ability to germinate, which are related to the time of the year and depend on the presence of light. Perianth-imposed dormancy appears to undergo one distinct seasonal cycle under laboratory conditions. Our results suggest that germination is best during the autumn and winter months but poor during the rest of the year. In the natural environment (fruits either remain on the soil surface or are buried) dormancy release may be occurring several times during the year under appropriate light, temperature and moisture conditions. Preliminary experiments indicate that the fruiting valves produce chemical substances that inhibit seed germination, and their break down appears to be affected by light.
A Colorimetric Ditopic Receptor Modulated by Fluoride Anion and Sodium Cation Binding
Authors: Yen Yao-Pin , Chen Chia-Lan , Fu Tung-Ming , Wu Chen-Yu , Lin Chi-Yung
Published: November 2006

A new colorimetric ditopic receptor (1) was synthesized and characterized. Upon investigation of a series of anions, the appearance of the solution of receptor 1 with F– showed a colour change from light-yellowish to orange-red which can be detected by the naked eye. Upon subsequent addition of Na+ or Li+ to the solution, the orange-red colour was no longer observable. The remarkable colour switching (ON and OFF) is thus controlled by the anion and cation recognition.
A review of nitrogen and phosphorus export to waterways: context for catchment modelling
Authors: Drewry J. J. , Newham L. T. H. , Greene R. S. B. , Jakeman A. J. , Croke B. F. W.
Published: November 2006

This paper reviews knowledge of nitrogen and phosphorus generation from land use and export to waterways, including studies relevant to Australia. It provides a link between current and future modelling requirements, and the context for incorporation of this knowledge into catchment models for use by catchment managers. Selected catchment models used by catchment managers are reviewed, and factors limiting their application are addressed. The review highlights the importance of dissolved N and P for overland flow and groundwater pathways, for sheep, beef and dairy grazing land use. Consequently, the effectiveness of riparian buffers to remove N and P may not be adequate. Consideration of the effects of rainfall and hydrology, dissolved P and N losses from pastures and event-based catchment-scale loads are therefore important factors that should be incorporated into catchment models. The review shows that it is likely that nutrient losses under Australian dairying conditions have many similarities to worldwide studies. Catchment models need to represent the importance of event-based loads, intensively farmed land use, management and forms of nutrients. Otherwise there is a likelihood of either underestimating nutrient losses, or potentially overestimating the effectiveness of riparian buffers.
Sulfidic materials in dryland river wetlands
Authors: Lamontagne S. , Hicks W. S. , Fitzpatrick R. W. , Rogers S.
Published: November 2006

Due to a combination of river regulation, dryland salinity and irrigation return, lower River Murray floodplains (Australia) and associated wetlands are undergoing salinisation. It was hypothesised that salinisation would provide suitable conditions for the accumulation of sulfidic materials (soils and sediments enriched in sulfides, such as pyrite) in these wetlands. A survey of nine floodplain wetlands representing a salinity gradient from fresh to hypersaline determined that surface sediment sulfide concentrations varied from <0.05% to ~1%. Saline and permanently flooded wetlands tended to have greater sulfide concentrations than freshwater ones or those with more regular wetting–drying regimes. The acidification risk associated with the sulfidic materials was evaluated using field peroxide oxidations tests and laboratory measurements of net acid generation potential. Although sulfide concentration was elevated in many wetlands, the acidification risk was low because of elevated carbonate concentration (up to 30% as CaCO3) in the sediments. One exception was Bottle Bend Lagoon (New South Wales), which had acidified during a draw-down event in 2002 and was found to have both actual and potential acid sulfate soils at the time of the survey (2003). Potential acid sulfate soils also occurred locally in the hypersaline Loveday Disposal Basin. The other environmental risks associated with sulfidic materials could not be reliably evaluated because no guideline exists to assess them. These include the deoxygenation risk following sediment resuspension and the generation of foul odours during drying events. The remediation of wetland salinity in the Murray–Darling Basin will require that the risks associated with disturbing sulfidic materials during management actions be evaluated.
Do sand dunes of the lower Lachlan floodplain contain the same dust that produced parna?
Authors: Ryan Adrienne L. , Cattle Stephen R.
Published: November 2006

Æolian dust deposits are known to be widespread in south-eastern Australia, with the dominant model being that of ‘parna’, an aggregated material comprising clay, calcium carbonate, and silt-sized quartz. Despite a general acceptance of the parna model, there is surprisingly little evidence of silt-sized clay aggregates remaining in parna profiles. To investigate a relatively pure æolian dust deposit within the proposed zone of parna distribution, we examined the various phases of 3 source-bordering sand dunes on the lower Lachlan River floodplain of south-western NSW. In each dune exists an upper-slope phase of coarse brown sand, a mid-slope layer of reddish, clay-enriched sand, and a lower-slope phase of coarse sand dominated by an accumulation of carbonate glaebules. Granulometric analyses of the clay-enriched phase(s) of each dune identified a conspicuous particle population in the 20–60 μm range, and another in the fine-silt/clay range (<10 μm). Mineralogical characterisation revealed an abundance of illite and kaolinite in the upper 2 dune phases, coupled with a minor amount of smectite, further suggesting an allochthonous æolian origin, as the surrounding floodplain is smectite-rich and relatively poor in illite. Micromorphological features within the clay-enriched phase, including abundant argillans and laminar bands of well-sorted fine quartz grains, indicate that this clay is a depositional feature, illuviated from surface horizons and re-deposited at depth. A similar illuvial origin is suggested by the fine crystalline nature of the calcium carbonate accumulation, ubiquitously coating the matrix mineral grains of the lower dune phase. No discrete clay aggregates were identified; however, all the assumed components of parna (silt-sized quartz grains, clay, and calcium carbonate) were identified, spatially separated within each dune. The consistency of these features among the 3 dunes indicates an analogous æolian dust accession, but it is not clear whether the clay component of this dust was transported as coatings on quartz grains, or as silt-sized clay aggregates accompanied by silt-sized quartz grains.
A BTB/POZ protein, NAC-1, is related to tumor recurrence and is essential for tumor growth and survival
Authors: Nakayama Kentaro , Nakayama Naomi , Davidson Ben , Sheu Jim J.-C. , Jinawath Natini , Santillan Antonio , Salani Ritu , Bristow Robert E. , Morin Patrice J. , Kurman Robert J. , Wang Tian-Li , Shih Ie-Ming
Published: November 2006

Recent studies have suggested an oncogenic role of the BTB/POZ-domain genes in hematopoietic malignancy. The aim of this study is to identify and characterize BTB/POZ-domain genes in the development of human epithelial cancers, i.e., carcinomas. In this study, we focused on ovarian carcinoma and analyzed gene expression levels using the serial analysis of gene expression (SAGE) data in all 130 deduced BTB/POZ genes. Our analysis reveals that NAC-1 is significantly overexpressed in ovarian serous carcinomas and several other types of carcinomas. Immunohistochemistry studies in ovarian serous carcinomas demonstrate that NAC-1 is localized in discrete nuclear bodies (tentatively named NAC-1 bodies), and the levels of NAC-1 expression correlate with tumor recurrence. Furthermore, intense NAC-1 immunoreactivity in primary tumors predicts early recurrence in ovarian cancer. Both coimmunoprecipitation and double immunofluorescence staining demonstrate that NAC-1 molecules homooligomerize through the BTB/POZ domain. Induced expression of the NAC-1 mutant containing only the BTB/POZ domain disrupts NAC-1 bodies, prevents tumor formation, and promotes tumor cell apoptosis in established tumors in a mouse xenograft model. Overexpression of full-length NAC-1 enhanced tumorigenicity of ovarian surface epithelial cells and NIH 3T3 cells in athymic
nu
/
nu
mice. In summary, NAC-1 is a tumor recurrence-associated gene with oncogenic potential, and the interaction between BTB/POZ domains of NAC-1 proteins is critical to form the discrete NAC-1 nuclear bodies and essential for tumor cell proliferation and survival.
Neutron diffraction studies of
Escherichia coli
dihydrofolate reductase complexed with methotrexate
Authors: Bennett Brad , Langan Paul , Coates Leighton , Mustyakimov Marat , Schoenborn Benno , Howell Elizabeth E. , Dealwis Chris
Published: November 2006

Hydrogen atoms play a central role in many biochemical processes yet are difficult to visualize by x-ray crystallography. Spallation neutron sources provide a new arena for protein crystallography with TOF measurements enhancing data collection efficiency and allowing hydrogen atoms to be located in smaller crystals of larger biological macromolecules. Here we report a 2.2-Å resolution neutron structure of
Escherichia coli
dihydrofolate reductase (DHFR) in complex with methotrexate (MTX). Neutron data were collected on a 0.3-mm
3
D
2
O-soaked crystal at the Los Alamos Neutron Scattering Center. This study provides an example of using spallation neutrons to study protein dynamics, to identify protonation states directly from nuclear density maps, and to analyze solvent structure. Our structure reveals that the occluded loop conformation [monomer (mon.) A] of the DHFR·MTX complex undergoes greater H/D exchange compared with the closed-loop conformer (mon. B), partly because the Met-20 and β(F-G) loops readily exchange in mon. A. The eight-stranded β sheet of both DHFR molecules resists H/D exchange more than the helices and loops. However, the C-terminal strand, βH, in mon. A is almost fully exchanged. Several D
2
Os form hydrogen bonds with exchanged amides. At the active site, the N1 atom of MTX is protonated and thus charged when bound to DHFR. Several D
2
Os are observed at hydrophobic surfaces, including two pockets near the MTX-binding site. A previously unidentified D
2
O hydrogen bonds with the catalytic D27 in mon. B, stabilizing its negative charge.
Sensory integration does not lead to sensory calibration
Authors: Smeets Jeroen B. J. , van den Dobbelsteen John J. , de Grave Denise D. J. , van Beers Robert J. , Brenner Eli
Published: November 2006

One generally has the impression that one feels one's hand at the same location as one sees it. However, because our brain deals with possibly conflicting visual and proprioceptive information about hand position by combining it into an optimal estimate of the hand's location, mutual calibration is not necessary to achieve such a coherent percept. Does sensory integration nevertheless entail sensory calibration? We asked subjects to move their hand between visual targets. Blocks of trials without any visual feedback about their hand's position were alternated with blocks with veridical visual feedback. Whenever vision was removed, individual subjects' hands slowly drifted toward the same position to which they had drifted on previous blocks without visual feedback. The time course of the observed drift depended in a predictable manner (assuming optimal sensory combination) on the variable errors in the blocks with and without visual feedback. We conclude that the optimal use of unaligned sensory information, rather than changes within either of the senses or an accumulation of execution errors, is the cause of the frequently observed movement drift. The conclusion that seeing one's hand does not lead to an alignment between vision and proprioception has important consequences for the interpretation of previous work on visuomotor adaptation.
Toxicity of Cerium Oxide Nanoparticles in Human Lung Cancer Cells
Authors: Lin Weisheng , Huang Yue-wern , Zhou Xiao-Dong , Ma Yinfa
Published: November 2006

With the fast development of nanotechnology, the nanomaterials start to cause people’s attention for potential toxic effect. In this paper, the cytotoxicity and oxidative stress caused by 20-nm cerium oxide (CeO2) nanoparticles in cultured human lung cancer cells was investigated. The sulforhodamine B method was employed to assess cell viability after exposure to 3.5, 10.5, and 23.3 μg/ml of CeO2 nanoparticles for 24, 48, and 72 h. Cell viability decreased significantly as a function of nanoparticle dose and exposure time. Indicators of oxidative stress and cytotoxicity, including total reactive oxygen species, glutathione, malondialdehyde, α-tocopherol, and lactate dehydrogenase, were quantitatively assessed. It is concluded from the results that free radicals generated by exposure to 3.5 to 23.3 μg/ml CeO2 nanoparticles produce significant oxidative stress in the cells, as reflected by reduced glutathione and α-tocopherol levels; the toxic effects of CeO2 nanoparticles are dose dependent and time dependent; elevated oxidative stress increases the production of malondialdehyde and lactate dehydrogenase, which are indicators of lipid peroxidation and cell membrane damage, respectively.
The Protective Effect of Melatonin against Fumonisin-Induced Renal Damage in Rats
Authors: Morsy Fatma A. , Badawy Manal A. , Farrag Abdel Razik H.
Published: November 2006

The present study was designed to investigate the potential protective effect of melatonin against the renal toxicity of fumonisin in female rats. Six groups of animals were used in this study. The first group served as control. The second group was given melatonin only at a dose level of 10 mg/kg. The third group was fed ration contaminated with fumonisin (100 mg/kg diet). The fourth group was fed ration contaminated with fumonisin (200 mg/kg diet). The fifth group was given daily interperitoneal injection (IP) 10 mg/kg melatonin and fed ration contaminated with fumonisin (100 mg/kg diet). The sixth group was given daily interperitoneal injection of 10 mg/kg melatonin and fed ration contaminated with fumonisin (200 mg/kg diet). The rats were treated for 1 month. Histopathological and histochemical changes in the kidney were investigated. In addition, DNA ploidy was measured in the kidney. Fumonisin administration (100 or 200 mg/Kg diet) to unpretreated control rats caused extensive renal damage as evaluated by histopathology, histochemistry, and/or DNA ploidy measurement. No apparent changes following administration of melatonin. Melatonin coadministration to the fumonisin-administered rats reduced kidney damage and the tissues appeared more or less like the normal. The present study indicates that melatonin has a protective effect in fumonisin-induced renal damage.
An FHA domain–mediated protein interaction network of Rad53 reveals its role in polarized cell growth
Authors: Smolka Marcus B. , Chen Sheng-hong , Maddox Paul S. , Enserink Jorrit M. , Albuquerque Claudio P. , Wei Xiao X. , Desai Arshad , Kolodner Richard D. , Zhou Huilin
Published: November 2006

The DNA damage checkpoint kinase Rad53 is important for the survival of budding yeast under genotoxic stresses. We performed a biochemical screen to identify proteins with specific affinity for the two Forkhead associated (FHA) domains of Rad53. The N-terminal FHA1 domain was found to coordinate a complex protein interaction network, which includes nuclear proteins involved in DNA damage checkpoints and transcriptional regulation. Unexpectedly, cytosolic proteins involved in cytokinesis, including septins, were also found as FHA1 binding proteins. Consistent with this interaction, a Rad53 mutant defective in its nuclear localization was found to localize to the bud neck. Abnormal morphology was observed in cells overexpressing the FHA1 domain and in rad53Δ cells under DNA replication stress. Further, septin Shs1 appears to have an important role in the response to DNA replication stress. Collectively, the results suggest a novel function of Rad53 in the regulation of polarized cell growth in response to DNA replication stress.