bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of single point mutations in citrate synthase on binding to GroEL
Authors: Zahn Ralph , Lindner Peter , Axmann Sabine E. , Plückthun Andreas
Published: April 2003

Six single point mutants of yeast citrate synthase were analyzed for binding to the molecular chaperone GroEL. In contrast to the wild‐type and G276S, all other G276‐mutants were able to displace pre‐β‐lactamase from GroEL. The off‐rate constant for pre‐β‐lactamase must be at least partially rate‐limiting, leading to an equilibrium dissociation constant between 10−10 M and 10−12M. Direct evidence for binding of citrate synthase was obtained from gel filtration experiments. The results suggest that thermodynamic rather than structural features of the mutants determine the degree of binding to the chaperone.
Is membrane potential involved in calmodulin gene expression after external stimulation in plants?
Authors: Vian Alain , Henry-Vian Chantal , Schantz Rodolphe , Ledoigt Gérard , Frachisse Jean-Marie , Desbiez Marie-Odile , Julien Jean-Louis
Published: April 2003

In Bidens pilosa (cv. radiata), a non‐injurious stimulus induces a local and transient change in membrane potential, and an injurious stimulus induces a transmitted electrical signal described as the combination of an action potential and a slow wave. We have studied calmodulin gene expression after these stimuli. When the stimulus is non‐injurious, calmodulin mRNA accumulation is only increased in the stimulated region. In contrast, when the stimulus is injurious, mRNA accumulation takes place in both wounded and distant, unwounded tissue. We propose that the slow wave plays a role in the long‐distance transmission of a wound‐induced information in plants.
Relationship between DNA methylation and gene expression of the HOXB gene cluster in small cell lung cancers
Authors: Flagiello Domenico , Poupon Marie-France , Cillo Clemente , Dutrillaux Bernard , Malfoy Bernard
Published: April 2003

The expression pattern of the HOXB gene cluster in four xenografted small‐cell lung cancers was compared to the methylation of the DNA in the corresponding genomic regions. In 90% (17/19) of the studied cases, the expressed genes were in methylated regions whereas 70% (12/17) of the unexpressed genes were in unmethylated regions. This specific behavior could correspond to a particular gene expression regulation mechanism of the HOX gene network. Since some genes (HOXB2, HOXB4, HOXB7) were always inactive when unmethylated, this unexpected relationship might indicate their key function(s) in the HOX gene network.
Reduced‐denatured ribonuclease A is not in a compact state
Authors: Nöppert Angela , Gast Klaus , Müller-Frohne Marlies , Zirwer Dietrich , Damaschun Gregor
Published: April 2003

Dynamic light scattering and circular dichroism experiments were performed to determine the compactness and residual secondary structure of reduced and by 6 M guanidine hydrochloride denatured ribonuclease A. We find that reduction of the four disulphide bonds by dithiothreitol at 20°C leads to total unfolding and that a temperature increase has no further effect on the dimension. The Stokes' radius of ribonuclease A at 20°C is R
s = (1.90 ± 0.04) nm (native) and R
s = (3.14 ± 0.06) nm (reduced‐denatured). Furthermore, circular dichroism spectra do not indicate any residual secondary structure. We suggest that reduced‐denatured Ribonuclease A has a random coil‐like conformation and is not in a compact denatured state.
Insulin potentiates the transactivation potency of the glucocorticoid receptor
Authors: Georgakopoulos A. , Tsawdaroglou N.
Published: April 2003

A single copy of a glucocorticoid‐responsive element (GRE) is sufficient in mediating the combinatorial response of a promoter to both glucocorticoids and insulin in HepG2 cells. This requires the presence of active glucocorticoid receptor (GR) since the response is significantly inhibited by the anti‐glucocorticoid RU30406. The N′‐ and C′‐terminal parts of the GR protein are not involved in mediating the response. Insulin had no effect on GR binding to GRE but it affected both the level and the phosphorylation state of nuclear‐bound GR. Thus, insulin alters the GR transactivation potency while, concomitantly, modifies the molecule at the posttranslational level.
Epidermal growth factor, but not hepatocyte growth factor, suppresses the apoptosis induced by transforming growth factor‐beta in fetal hepatocytes in primary culture
Authors: Fabregat Isabel , Sanchez Aránzazu , Alvarez Alberto M. , Toshikazu Nakamura  , Benito Manuel
Published: April 2003

We studied whether the TGF‐β‐induced apoptosis in fetal hepatocyte primary cultures may be modulated by the presence of mitogenic stimuli, such as EGF or HGF. EGF prevented cell death, showing a dose dependence that was identical to that observed for its effect on DNA synthesis stimulation. HGF, in contrast, had no effect, even at high concentrations. EGF blocked apoptosis, since in the presence of this factor cells did not show DNA fragmentation. Moreover, EGF, but not HGF, blocked c‐fos induction associated with the apoptotic process induced by TGF‐β in these cells.
Sodium channel mRNA in the B104 neuroblastoma cell line
Authors: Dib-Hajj S.D. , Hinson A.W. , Black J.A. , Waxman S.G.
Published: April 2003

B104 neuroblastoma cells are excitable, but the ion channels underlying electrogenesis in these cells have not been identified. RT‐PCR, restriction enzyme analysis and in situ hybridization were used to study sodium channel mRNAs in B104 cells. High levels of sodium channel α‐subunit mRNAs III, NaG and Na6 and β1‐subunit mRNA were detected by RT‐PCR in B104 cells. Low levels of types I and II α‐subunit mRNAs were also present. In situ hybridization with subtype‐specific riboprobes detected sodium channel α‐subunit mRNAs III, NaG and Na6 and β1‐subunit mRNA in B104 cells; analysis of the percentage of B104 cells expressing each α‐subunit mRNA subtype suggests that some cells express the mRNAs for several α‐subunits.
Activation of mitogen‐activated protein kinase by protein kinase C isotypes α, βI and γ, but not ϵ
Authors: Young Stephen W. , Dickens Martin , Tavaré Jeremy M.
Published: April 2003

Treatment of CHO.T cells with either PMA or insulin led to the activation of MAP kinase by ∼3‐fold, and p90
rsk
by ∼ 4‐fold. Over‐expression of the α, β
I or γ isoforms of protein kinase C caused a substantial enhancement of the effect of PMA on the activation of MAP kinase and p90
rsk
, however, the effect of insulin was unchanged. Over‐expression of the ϵ isoform of protein kinase C did not alter the effect of either PMA or insulin on the activation of MAP kinase and p90
rsk
. The results suggest that protein kinase C isotypes α, β
I and γ, but not ϵ, can mediate MAP kinase activation by PMA, and strongly support the hypothesis that protein kinase C isoforms can initiate distinct signalling pathways.
Construction of a fusion protein between protein A and green fluorescent protein and its application to Western blotting
Authors: Aoki Takashi , Takahashi Yasumitsu , Koch Katherine S. , Leffert Hyam L. , Watabe Hiroyuki
Published: April 2003

Aequorea green fluorescent protein (GFP) and protein A were fused and expressed in Escherichia coli. The fluorescent native fusion protein (PA‐GFP) migrated at 47 kDa in SDS‐PAGE. However, the non‐fluorescent denatured PA‐GFP migrated at 57 kDa which corresponds to the theoretical molecular mass. Although the reason(s) for this mobility shift between fluorescent and non‐fluorescent molecules remains unclear, the small ring structure within the native molecules may affect their mobility. The cell extract, prepared from an E. coli strain producing PA‐GFP, was used in Western and dot blots. The sensitivity and specificity of the PA‐GFP detection were sufficient for rapid and easy screening.
Nitric oxide induced poly(ADP‐ribose) polymerase cleavage in RAW 264.7 macrophage apoptosis is blocked by Bcl‐2
Authors: Meβmer Udo K. , Reimer Dietrich M. , Reed John C. , Brüne Bernhard
Published: April 2003

Endogenously generated or exogenously supplied nitric oxide causes cleavage of poly(ADP‐ribose) polymerase (PARP) and apoptotic cell death in RAW 264.7 macrophages. With the use of NO donors such as S‐nitrosoglutathione or spermine‐NO we established that PARP digestion occurs in parallel with DNA fragmentation, and is preceded by accumulation of the tumor suppressor gene product p53. PARP cleavage in response to lipopolysaccharide and interferon‐γ treatment is prevented by , thus proving a NO requirement. Endogenous NO generation, p53 accumulation, and PARP degradation occurred prior to the detection of significant chromatin condensation. In contrast, in stable Bcl‐2 transfected cells, NO‐initiated PARP cleavage was almost completely blocked. Our data implicate PARP as a proteolytic substrate during NO‐mediated apoptotic cell death in RAW 264.7 macrophages and establish Bcl‐2 as an efficient signal terminator in this process.
The RU5 (‘R’) region from human leukaemia viruses (HTLV‐1) contains an internal ribosome entry site (IRES)‐like sequence
Authors: Attal Joé , Théron Marie-Claire , Taboit Frédérique , Cajero-Juarez Marco , Kann Guy , Bolifraud Philippe , Houdebine Louis Marie
Published: April 2003

RNA fragments containing the complete R region and the beginning of the U5 region (‘R’) from the human T cell leukaemia virus 1 (HTLV‐1) stimulated the translation of the second cistrons in bicistronic mRNAs. The 5′ untranslated region from SV40 early genes (SU) which was unable to stimulate translation of second cistrons amplified markedly the internal ribosome entry site (IRES) effect of the HTLV‐1 ‘R’ fragments. The ‘R’ regions from HTLV‐1 have therefore properties similar to internal ribosome entry sites (IRES) originally found in picornavirus. The beginning of the U5 region from HTLV‐1 contains a polypyrimidine sequence which is known to play an essential role in the IRES activity in picornavirus. The same experiments carried out using the ‘R’ region from bovine leukaemia virus (BLV) showed that this sequence has at most a weak IRES effect. One retroviruses HTLV‐1 and perhaps others contain therefore an IRES activity. Interestingly, the combined SU ‘R’ sequence worked efficiently with different cistrons, different promoters and in all tested cell lines, whereas the poliovirus IRES was active in CHO cells but not in the mouse mammary cell line HC11. The SU ‘R’ sequence may therefore preferably be used to generate active bicistronic mRNAs.
Inhibition of cathepsin B by its propeptide: Use of overlapping peptides to identify a critical segment
Authors: Chagas Jair R. , Martino Michele Ferrer-Di , Gauthier Francis , Lalmanach Gilles
Published: April 2003

Ten overlapping 15‐mer peptides (peptidyl amides) spanning the proregion of rat cathepsin B (residues 1p–60p) were constructed to identify minimal segments having inhibitory activity towards the mature enzyme, that could be used to develop a new generation of peptide‐derived inhibitors specifically targeting the active site of the corresponding proteinase. Three synthetic peptides, containing the pentapeptide Leu‐Cys‐Gly‐Thr‐Val (residues 41p–45p) in their sequence, inhibited cathepsin B with K
i values in the micromolar range. Alkylation of the thiol group of Cys‐42p of peptide PB8 (36p–50p) resulted in its rapid proteolytic degradation, suggesting that this residue is essential for inhibition. The inhibition constant was slightly improved (K
i = 2 μM) using a longer peptide (26p–50p) which was completely resistant to cleavage even after a prolonged incubation. Alkylation of its cysteinyl residue also resulted in rapid cleavage of the peptide chain. Peptides derived from the rat cathepsin B prosequence also inhibited human cathepsin B with similar K
i values. Unlike rat cathepsin B, which cleaves peptide PB8 at the G47p–G48p bond after prolonged incubation, the human enzyme cleaved both PB8 and PB11 at the Lys‐40p‐Leu41p bond, in agreement with the different kinetic properties of these two proteinases. New probes with improved specificity for cysteine proteinases may therefore be designed based on the sequences of their propeptides.
Quo vadis photorespiration: A tale of two aldolases
Authors: Hixon Mark , Sinerius Gudrun , Schneider Achim , Walter Christiane , Fessner Wolf-Dieter , Schloss John V.
Published: April 2003

An O2‐consuming side reaction of d‐ribulose 1,5‐bisphosphate carboxylase causes photorespiration in plants. This reaction may be an inevitable consequence of the enzyme's inability to protect its ene‐diolate reaction intermediate from O2, a notion that is supported by the failure of persistent efforts to eliminate selectively its oxygenase activity by genetic manipulation. We have examined two aldolases with similar ene‐diolate intermediates, l‐rhamnulose 1‐phosphate aldolase and l‐fuculose 1‐phosphate aldolase. The former enzyme has an oxygenase activity, while the latter does not, suggesting that the reaction with O2 is not inevitable.
Reactive oxygen intermediate(s) (ROI): Common mediator(s) of poly(ADP‐ribose)polymerase (PARP) cleavage and apoptosis
Authors: McGowan A.J. , Ruiz-Ruiz M.C. , Gorman A.M. , Lopez-Rivas A. , Cotter T.G.
Published: April 2003

HL‐60 acute myeloblastic and U937 monoblastoid leukaemic cell lines both cleave poly(ADP‐ribose)polymerase (PARP), at the onset of apoptosis, in response to a wide range of cytotoxic agents. This appears to be a common feature of leukaemic cell apoptosis. However, in the chronic myelogenous leukaemic (CML) derived cell line, K562, no such cleavage was detectable. This correlated with previous findings that this cell line is particularly resistant to apoptosis induced by cytotoxic agents. Proteolytic cleavage of PARP and the subsequent progression to apoptosis was inhibited by two protease inhibitors NEM and IOD. As both PARP cleavage and DNA fragmentation appeared closely linked in these cell lines, anti‐oxidants (previously shown to be effective inhibitors of DNA fragmentation and apoptosis) were also demonstrated to prevent PARP cleavage. These results combine to suggest that ROI may mediate PARP cleavage, DNA fragmentation and the eventual apoptosis of these cells following cytotoxic insult.
A novel gene codes for a putative G protein‐coupled receptor with an abundant expression in brain
Authors: O'Dowd Brian F. , Nguyen Tuan , Lynch Kevin R. , Kolakowski Lee F. , Thompson Miles , Cheng Regina , Marchese Adriano , Ng Gordon , Heng Henry H.Q. , George Susan R.
Published: April 2003

Following the cloning of the dopamine receptors we continued a search of the human genome for related genes. We searched an EST data base and discovered cDNA fragments encoding novel G protein‐coupled receptor genes. The available GenBank sequence of one of these EST fragments showed that it encoded a receptor with closest similarity to the D2 dopamine and adrenergic receptors. This cDNA was used to isolate the gene (GPR19), and the encoded receptor also demonstrated similarity with the neuropeptide Y receptor. The gene was mapped to chromosome 12, in region p13.2–12.3. Northern blot analysis revealed expression of GPR19 in peripheral regions, and brain regions significantly overlapping with the D2 receptor gene expression. A sequence of the rat orthologue of GPR19 was obtained and in situ hybridization analysis demonstrated a very abundant expression in rat brain.
Interleukin 1 activates jun N‐terminal kinases JNK1 and JNK2 but not extracellular regulated MAP kinase (ERK) in human glomerular mesangial cells
Authors: Uciechowski Peter , Saklatvala Jeremy , von der Ohe Juliane , Resch Klaus , Szamel Martha , Kracht Michael
Published: April 2003

Interleukin 1 (IL‐1) potently activates human glomerular mesangial cells (HMC). In cytosolic extracts of IL‐1‐stimulated HMC or in anion exchange chromatography fractions we could not find any change in phosphorylation of myelin basic protein (MBP), a good substrate for extracellular regulated kinase (ERK). In contrast, IL‐1 stimulated GST‐jun kinase activity at least 10‐fold. The jun kinase activity could be characterised as JNK1 and JNK2 at the protein and mRNA level. IL‐1, TNF, UV light and osmotic stress, but not PMA, LPS, IL‐3, IL‐4, IL‐6, IL‐8, IL‐10, IL‐13, GM‐CSF, PDGF, bFGF, TGF‐β and interferon‐γ were able to stimulate jun kinase activity in HMC, suggesting that jun kinase is selectively mediating signal transduction of the proinflammatory cytokines IL‐1 and TNF as well as of cellular stress in HMC.
Characterization of a human gene related to genes encoding somatostatin receptors
Authors: Kolakowski Lee F. , Jung Benjamin P. , Nguyen Tuan , Johnson Michael P. , Lynch Kevin R. , Cheng Regina , Heng Henry H.Q. , George Susan R. , O'Dowd Brian F.
Published: April 2003

We report the identification of a gene, named SLC‐1
1, encoding a novel G protein‐coupled receptor (GPCR). A customized search procedure of a database of expressed sequence tags (dbEST) retrieved a human cDNA sequence that partially encoded a GPCR. A genomic DNA fragment identical to the cDNA was obtained and used to screen a library to isolate the full‐length coding region of the gene. This gene was intronless in its open reading frame, and encoded a receptor of 402 amino acids, and shared −40% amino acid identity in the transmembrane (TM) regions to the five known human somatostatin receptors. Northern blot analysis revealed that SLC‐1 is expressed in human brain regions, including the forebrain and hypothalamus. Expression in the rat was highest in brain, followed by heart, kidney, and ovary. Expression of SLC‐1 in COS‐7 cells failed to show specific binding to radiolabelled Tyr1‐somatostatin‐14, naloxone, bremazocine, 1,3‐di(2‐tolyl)‐guanidine (DTG), or haloperidol. A repeat polymorphism of the form (CA)
n
was discovered in the 5′‐untranslated region (UTR) of the gene and SLC‐1 was mapped to chromosome 22, q13.3.
Interaction between left‐handed Z‐DNA and polyamine — 3 The crystal structure of the d(CG)3 and thermospermine complex
Authors: Ohishi Hirofumi , Terasoma Noriko , Nakanishi Isao , van der Marel Gijs , Van Boom Jacques H. , Rich Alexander , Wang Andrew H.-J. , Hakoshima Toshio , Tomita Ken-ichi
Published: April 2003

The DNA fragment, d(CG)3, was co‐crystallized with N‐(3‐amino‐propyl)‐N‐(5‐aminopropyl)‐1,4‐diaminobutane (thermospermine; PA(334)), a polyamine metabolized from the nucleic acid. By using a good crystal with dimensions of 0.5 × 0.5 × 0.5 mm3, X‐ray intensity data were collected up to 1.0 Å resolution. Two thermospermine molecules and a magnesium cation were bound to the left‐handed double‐helical d(CG)3 molecule. The d(CG)3 molecule adopted the left‐handed Z‐conformation and two thermospermine molecules and a magnesium cation neutralized the negative charges of the phosphate groups of the d(CG)3 molecule. Furthermore, the binding modes between d(CG)3 and thermospermine were different from those of d(CG)3 complexes with PA(24), spermidine and spermine. This is the first case in which it was determined by X‐ray crystallographic analysis that one of two thermospermine molecules bound three d(CG)3 duplexes which were symmetrically related to each other, and the other formed two hydrogen bonds at the N(5) and N(9) atoms with two adjacent nucleotide phosphate groups of a single d(CG)3 strand at the minor groove. Furthermore, no direct coordination bond was found between the d(CG)3 molecule and the magnesium cation.
A nuclear RNA‐binding cyclophilin in human T cells
Authors: Mi Huaifeng , Kops Oliver , Zimmermann Esther , Jäschke Anja , Tropschug Maximilian
Published: April 2003

Cyclophilins (CyPs) are binding proteins for the immunosuppressive drug cyclosporin A (CsA). CyPs are evolutionarily highly conserved proteins present in both pro‐and eukaryotes as well as in different subcellular locations. Cyps possess enzymatic activity, namely peptidyl‐prolyl cis‐trans isomerase (PPIase) activity; CyPs are involved in cellular protein folding and protein interactions. To date, only cyclosporins and proteins are known to interact with CyPs. Here we describe a novel nuclear cyclophilin (hCyP33) from human T cells with an additional RNA‐binding domain. This combines for the first time RNA binding and protein folding in one protein.
Molecular cloning and nucleotide sequence of the gene encoding phosphate‐inducible pectin lyase of Bacillus subtilis
Authors: Sakamoto Tatsuji , Kawasaki Haruhiko , Sakai Takuo
Published: April 2003

The gene encoding the pectin lyase (PNL; EC 4.2.2.10) of Bacillus subtilis has been cloned, sequenced, and characterized. A coding sequence for the PNL composed of 345 amino acids including a 24‐amino‐acid signal peptide was assigned. No sequence resembling a LexA binding site was found upstream of the structural gene. Furthermore, PNL activity of the gene product expressed in Escherichia coli DH5α was detected intracellularly, which might suggest that expression of the gene was not controlled by RecA. Regulation of the gene expression seemed to be quite different from that of other bacterial PNL genes previously reported.
The relationship of placenta previa and history of induced abortion
Authors: Johnson L.G. , Mueller B.A. , Daling J.R.
Published: April 2003

Objectives: We evaluated the risk of placenta previa being associated with a history of induced abortion by different surgical procedures. Methods: Cases (n=192) were women who had a singleton delivery complicated by placenta previa at a major obstetric care hospital in western Washington state between April 1, 1990 and December 31, 1992. Controls (n=622) were women with singleton deliveries not complicated by placenta previa or abruption. Odds ratios, determined by logistic regression, approximate the relative risks. Results: Vacuum aspiration abortion was not associated with an increased risk of placenta previa (OR 0.9, 95% CI 0.6–1.5). However, the risk of placenta previa increased with the number of sharp curettage abortions (OR 2.9, 95% CI 1.0–8.5 for ≥3). Conclusions: Risk of placenta previa may be increased in a dose response fashion by multiple sharp curettage abortions. However, vacuum aspiration does not confer an increased risk, and may be a better alternative.
Management of diabetic pregnant patients in a tertiary center in the developing world
Authors: Daponte A , Guidozzi F , Moisuc D , Marineanu A
Published: April 2003

Objectives: To audit our insulin regimen in our antenatal diabetics. Methods: 170 pregnant diabetic patients were retrospectively analyzed. Results: The perinatal mortality rate was 37/1000, vs. a perinatal mortality rate of 30/1000 in our setting. Cesarean section rate was 49%. Strict blood‐glucose control reduced the incidence of macrosomia and polyhydramnios. Routine amniocentesis for fetal‐lung maturity was not practiced. Conclusion: Satisfactory results in pregnant diabetic patients are achievable with an established insulin regimen in a developing country.
Mathematical relationships between uterine contractions, cervical dilatation, descent and rotation in spontaneous vertex deliveries
Authors: Sallam H.N , Abdel‐Dayem A , Sakr R.A , Sallam A , Loutfy I
Published: April 2003

Objective: To determine the mathematical relationships between the strength and duration of the uterine contractions, the descent and rotation of the fetal head and the degree of cervical dilatation in 50 multiparous women with spontaneous vaginal deliveries using a simple device applied to the fetal vertex. Method: A simple device for monitoring the progress of labor was applied to the fetal vertex. The device allows the continuous monitoring of descent and rotation of the fetal head. The amount of descent and the degree of rotation were also determined by repeated vaginal examinations as well as the degree of cervical dilatation. The frequency of uterine contractions was also recorded on a partogram. Result: A good correlation was found between the amount of descent of the fetal vertex (r=0.975) and between the degree of rotation of the fetal head (0.83) determined by both methods. Multiple regression analysis was then performed and the degree of cervical dilatation in cm at any given time during the first stage of labor was found to be equal to 2.859+0.583 fetal head station in (cm) +0.1983 internal rotation in degrees −0.0493 (station × internal rotation) +0.1599 station2 +0.3622 uterine contractions per 10 min. A nomogram was constructed allowing the calculation of cervical dilatation for a given station of the head, degree of rotation and frequency of uterine contractions. Conclusion: There is a defined mathematical relationship between the degree of descent and rotation of the fetal head, the degree of cervical dilatation and the frequency of uterine contractions in multiparous women with vertex presentation. The first three variables can be continuously determined by using the described device. Incorporation of the device into a reusable fetal scalp electrode allows the dual mechanical and electronic monitoring during labor with minimal vaginal examinations.
Dating fluvial terraces by230Th/U on pedogenic carbonate, Wind River Basin, Wyoming
Authors: Sharp Warren D. , Ludwig Kenneth R. , Chadwick Oliver A. , Amundson Ronald , Glaser Laura L.
Published: April 2003

Reliable and precise ages of Quaternary pedogenic carbonate can be obtained with230Th/U dating by thermal ionization mass spectrometry applied to carefully selected milligram-size samples. Datable carbonate can form within a few thousand years of surface stabilization allowing ages of Quaternary deposits and surfaces to be closely estimated. Pedogenic carbonate clast-rinds from gravels of glacio-fluvial terraces in the Wind River Basin have median concentrations of 14 ppm U and 0.07 ppm232Th, with median (230Th/232Th) = 270, making them well suited for230Th/U dating. Horizons as thin as 0.5 mm were sampled from polished slabs to reduce averaging of long (≥105yr), and sometimes visibly discontinuous, depositional histories. Dense, translucent samples with finite230Th/U ages preserve within-rind stratigraphic order in all cases. Ages for terraces WR4 (167,000 ± 6,400 yr) and WR2 (55,000 ± 8600 yr) indicate a mean incision rate of 0.26 ± 0.05 m per thousand years for the Wind River over the past glacial cycle, slower than inferred from cosmogenic-nuclide dating. Terrace WR3, which formed penecontemporaneously with the final maximum glacial advance of the penultimate Rocky Mountain (Bull Lake) glaciation, has an age of 150,000 ± 8300 yr indicating that it is broadly synchronous with the penultimateglobalice volume maximum.
Vegetation response to rapid climate change in Central Europe during the past 140,000 yr based on evidence from the Füramoos pollen record
Authors: Müller Ulrich C , Pross Jörg , Bibus Erhard
Published: April 2003

The response of Central European vegetation to rapid climate change during the late Quaternary period (Eemian to Holocene) is assessed by data from the new pollen record of Füramoos, southwestern Germany. This record represents the longest late Quaternary pollen record north of the Alps as currently known. Its high degree of completeness allows detailed correlations with Greenland ice cores and sea–surface temperature records from the North Atlantic. Our data show that if climate deteriorations were not long or severe enough to extirpate refugia of arboreal taxa north of the Alps such as during marine oxygen isotope stage (MIS) 5 (i.e., Würm Stadial A, Stadial B, and Stadial C), reforestation with the onset of warmer conditions in Central Europe occurred on a centennial scale. If arboreal taxa became completely extinct north of the Alps such as during MIS 4 (i.e., Würm Stadial D), several thousand years were necessary for the reimmigration from refugia situated in regions south of the Alps. Thus, Dansgaard–Oeschger interstades (DOIS) 24 to 20 and 15 to 11 are expressed in Central European pollen records, whereas DOIS 19 to 16 are not recorded due to migration lags.
Accuracy of cosmogenic ages for moraines
Authors: Putkonen Jaakko , Swanson Terry
Published: April 2003

Analyses of all published cosmogenic exposure ages for moraine boulders show an average age range of 38% between the oldest and youngest boulders from each moraine. This range conflicts with the common assumption that ages of surface boulders are the same as the age of the landform. The wide spread in boulder ages is caused by erosion of the moraine surface and consequent exhumation of fresh boulders. A diffusion model of surface degradation explains the age range and shows that a randomly sampled small set of boulders (n = 3–7) will always yield a lower age limit for the moraine. The model indicates that for identical dating accuracy, six to seven boulders are needed from old and tall moraines (40,000–100,000 yr, 50–100 m initial height) but only one to four boulders from small moraines (20,000–100,000 yr, 10–20 m). By following these guidelines the oldest obtained boulder age will be ≥90% of the moraine age (95% probability). This result is only weakly sensitive to a broad range of soil erosion rates. Our analysis of published boulder ages indicates that <3% of all moraine boulders have prior exposure, and 85% of these boulders predate the dated moraine.
Electromyography of scoliotic patients treated with a brace
Authors: Odermatt Daniel , Mathieu Pierre A. , Beauséjour Marie , Labelle Hubert , Aubin Carl‐Éric
Published: April 2003

When a brace is used to correct spinal deviation, patients may seek to ease the discomfort from the pressure exerted by the orthosis by actively recruiting specific trunk muscles. The effect of bracing on trunk electromyography (EMG) has been reported in only one study where a limited number of electrodes were placed mainly in the thoracic region. Our hypothesis was that a multi‐electrode mapping of the activity of the thoracic, lumbar, and abdominal trunk muscles would provide a more representative picture of the muscular reaction in response to bracing. With a larger number of EMG measuring sites, the presence of any brace‐induced trunk muscle activity should be detected. Therefore, EMG signals of 11 adolescent idiopathic scoliosis patients who had been undergoing Boston brace treatment for 0.7‐3 years were collected during four isometric tasks to evaluate the response of trunk muscles in the minutes following the application of the brace. Twenty‐two pairs of bipolar electrodes were used to measure the EMG signals of the main superficial trunk muscles during four isometric tasks. EMG signals of trunk muscles were compared in braced and unbraced conditions. Brace‐induced increases in EMG activity were significant in 43% of the individual measurements and in three of the four tasks for the group mean values. Increases were greater in the lumbar area, especially on the convex side of the secondary (lumbar) curve. These results thus suggest that immediately following the application of the brace, significant muscular responses can be observed in some patients. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Chemotherapeutic agents sensitize sarcoma cell lines to tumor necrosis factor‐related apoptosis‐inducing ligand‐induced caspase‐8 activation, apoptosis and loss of mitochondrial membrane potential
Authors: Hotta Takahito , Suzuki Hidekazu , Nagai Shuzou , Yamamoto Kengo , Imakiire Atsuhiro , Takada Eiko , Itoh Mizue , Mizuguchi Junichiro
Published: April 2003

Chemotherapeutic agents have been used for the treatment of patients with osteosarcoma (OS). However, inherent or acquired resistance to these agents is a serious problem in the management of OS patients. Tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) is considered to induce apoptosis in a variety of cancer cells but not normal cells. In the present study, we examined whether chemotherapeutic agents enhance TRAIL‐induced apoptosis in the sarcoma cell lines MG‐63 and SaOS‐2. Pretreatment with sub‐toxic or slightly toxic concentrations of chemotherapeutic agents (cis‐diammine dichloroplatinum, CDDP and doxorubicin, DXR) sensitized both cell lines to TRAIL‐induced apoptosis, as assessed by the propidium iodide or Annexin V‐Cy5 staining method. These cell lines expressed death receptors TRAIL‐receptor 1 (TRAIL‐R1) and TRAIL‐R2, which were unaltered by treatment with CDDP, as assessed by flow cytometry. The decoy receptors TRAIL‐R3 and ‐R4 were barely detected in both cell lines. CDDP down‐regulated c‐FLIP, tending to lower the activation threshold required for TRAIL‐induced caspase‐8 activation. The CDDP‐pretreated cells indeed demonstrated more increased TRAIL‐mediated caspase‐8 activation, loss of mitochondrial membrane potential (ΔΨm), and apoptosis than untreated cells. Consequently, the activated caspase‐8 might lead to either activation of effector caspases such as caspase‐3 or loss in ΔΨm. Both the increased caspase activation and mitochondrial dysfunction induced by combination of CDDP and TRAIL would contribute to enhanced apoptotic cell death. The results of the present study would be valuable for the design of novel treatment modalities for patients with OS. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
The Level and Sources of Popular Support for China's Current Political Regime
Authors: Chen Jie , Zhong Yang , Hillard Jan William
Published: April 2003

This article assumes that whether the current Chinese authoritarian government can maintain socio-political stability during the potentially turbulent transition to the post-Deng Xiaoping era depends, at least in part, upon the level of popular support for the political regime (or regime legitimacy). Based on data derived from a sample survey of Beijing residents, this study seeks to address two fundamental questions: “To what extent does the current Chinese communist regime enjoy public support?” and “What are the possible sources of popular support for the political regime in contemporary China?” The findings in this study suggest that (1) the current communist regime still enjoys a moderately high level of popular support, and (2) popular support for the regime is most likely to be found among those who are optimistic about the country's economic and political futures, who are most satisfied with their life, who give high evaluations of incumbent policies, who often follow public affairs, and who are older. Based on these findings, the article concludes that the current communist regime seems to have a good chance of remaining legitimate among a majority of the Chinese people, while it is still facing serious challenges from its policy performance in some major public policy areas.
A Tale of Dvo Metallurgical Enterprises: Marketization and the Social Contract in Russian Industry
Authors: Baglione Lisa A. , Clark Carol L.
Published: April 2003

Students of post-communist labor relations have argued that the social contract would deteriorate with privatization, as managers secured ownership rights and enterprises reoriented toward the market. To examine this expectation, we investigated the state of labor relations in two enterprises in the metallurgical industry. In St Petersburg, marketization brought little positive change in production and the social contract decayed, while Tula's management embarked on an ambitious reform program, rewriting the social contract. We attribute the variations in the outcomes to differing regional conditions that affected the mutual dependence of labor and management and, hence, “exit options” of both parties.
Slovakia and the Triumph of Nationalist Populism
Authors: Carpenter Michael
Published: April 2003

Since the collapse of communism in 1989, two dominant political orders have been established in Eastern Europe: nationalist populism and social democracy. This paper argues that the division of Eastern Europe into a nationalist-populist South and a social democratic North is the result of the evolution of two different types of political cultures and political institutions. These two types of political cultures and institutions, which I call “traditional” and “civic,” arose as a result of different historical experiences. The paper argues that traditional political cultures and institutions are the legacies of political subjugation and backward socio-economic conditions, while civic political cultures and institutions arose as a result of greater political autonomy and industrialization. The paper concludes that, by suppressing democratic norms and perpetuating a vast network of patronage, Slovakia's traditional legacy has facilitated the rise of a nationalist-populist regime.
Forms and Characteristics of China's Corruption in the 1990s: Change With Continuity
Authors: Ting Gong
Published: April 2003

In contrast to the conventional wisdom that marketization is essential for reducing corruption, the sources of corruption are many and complex. This paper focuses on recent patterns of China's corruption to see how new and different, if not more, corruption has occurred despite the gradual shrinking of non-market elements in the economy. The further market reforms in the 1990s do not reduce corruption so much as they merely alter its characteristics. Corruption is a kind of behaviour which responds to political and economic changes and hence whose forms vary with social climates. Such a complex issue requires comprehensive treatments and it is naive to assume that a market economy alone could free China from corruption.
Institutional Choice and Democratic Consolidation: The Experience of the Russian Successor States, 1918-19391
Authors: Metcalf Lee Kendall
Published: April 2003

The breakup of the Soviet Union led to the emergence of 15 states which are trying to create democratic institutions. Based on Latin American experience, most analysts argue that the combination of presidentialism and proportional representation leads to democratic failure. Yet few of the Soviet successor states have chosen pure parliamentarism. I argue that the experience of the post World War I Russian successor states provides a better framework for examining the democratization of these new states because they were trying to build democracy under similar conditions. Their experience indicates that the choice of PR and semi-presidentialism does not necessarily doom democracy.
On the Road to Collaboration: Nurses and Newly Regulated Midwives in British Columbia, Canada
Authors: Kornelsen Jude , Dahinten V. Susan , Carty Elaine
Published: April 2003

This study describes some of the results of a survey conducted shortly after the introduction of midwives as a regulated and publicly funded provider within the British Columbia health care system. The survey asked hospital‐based perinatal nurses about their knowledge and attitudes of midwifery and their experiences with midwives. Results suggest that nurses, for the most part, had a negative view of midwives and their practice and that inattention to the necessary conditions for interprofessional collaboration and positive interprofessional relationships have resulted in parallel practice between the professions instead of interdisciplinary practice.
Mobbingmaße und -faktoren sowie bestehende Zusammenhänge mit sozialen Arbeitsplatzbedingungen
Authors: Willingstorfer Betty , Schaper Niclas , Sonntag Karlheinz
Published: April 2003

Zusammenfassung. Zur Erfassung von Mobbing wurden bislang unterschiedliche Methoden verwendet. Dabei wurde meist die Auftretenshäufigkeit einzelner Mobbinghandlungen erfasst. In Untersuchung I wurden 61 Betroffene zur Häufigkeit, Dauer und Anzahl unterschiedlicher Mobbinghandlungen sowie zur Betroffenheitsstärke durch diese Handlungen befragt. In dieser Studie sollte die Reliabilität und Validität dieser unterschiedlichen Maße zur Bestimmung der Mobbingintensität untersucht werden. Die unterschiedlichen Maße wurden daher in Beziehung gesetzt zu verschiedenen Kriterien: Skala zu sozialen Stressoren, Selbstschätzung der Mobbingbetroffenheit insgesamt und Beanspruchungsreaktionen wie psychosomatische Beschwerden und Belastetheit/Gereiztheit. Es zeigte sich, dass die Häufigkeitsskala der Mobbingitems ein durchaus valides und ökonomisches Maß zur Bestimmung der Mobbingintensitäten darstellt. In Untersuchung II wurden 150 Mitarbeiter eines Dienstleistungsunternehmens mittels Work-Harassment-Scale von Björkqvist und Österman (1992 ) zur Mobbingbetroffenheit, zu sozialen Stressoren, dem Betriebsklima und der Arbeitszufriedenheit befragt. Es wurden unterschiedliche Betroffenengruppen gebildet und miteinander verglichen. In der Untersuchung zeigte sich eine stärkere Betroffenheit der Männer im Vergleich zu den Frauen. Außerdem machten die Mobbingbetroffenen im Vergleich zu den Nicht-Betroffenen negativere Angaben hinsichtlich der Arbeitszufriedenheit, der Einschätzung der Vorgesetzten, Kollegen, der Mitsprache und der Organisation. Beobachter von Mobbingsituationen im Unternehmen wiesen meist eine Zwischenposition in der Beschreibung der Arbeitsbedingungen und insbesondere in der Beschreibung des Führungsverhaltens auf.
The Extrinsic Affective Simon Task
Authors: De Houwer Jan
Published: April 2003

Abstract. A modified version of the Implicit Association Test (IAT) is described that is based on a comparison of performance on trials within a single task rather than on a comparison of performance on different tasks. In two experiments, participants saw white words that needed to be classified on the basis of stimulus valence and colored words that were to be classified on the basis of color. On trials where the colored word referred to a positive target concept (e.g., “flowers,” “self”), performance was superior when the correct response was the response that was also assigned to positive white words. The reverse was true on trials where the colored word represented a negative target concept (e.g., “insect”). This variant of the IAT is less susceptible to nonassociative effects of task recoding and can be used to assess single and multiple attitudes.
Substance P modulates localized calcium transients and membrane current responses in murine colonic myocytes
Authors: Bayguinov Orline , Hagen Brian , Sanders Kenton M
Published: April 2003

Neurokinins contribute to the neural regulation of gastrointestinal (GI) smooth muscles. We studied responses of murine colonic smooth muscle cells to substance P (SP) and NK1 and NK2 agonists using confocal microscopy and the patch clamp technique.

Colonic myocytes generated localized Ca2+ transients that were coupled to spontaneous transient outward currents (STOCs). SP (10−10 M) increased Ca2+ transients and STOCs. Higher concentrations of SP (10−6 M) increased basal Ca2+ and inhibited Ca2+ transients and STOCs.

Effects of SP were due to increased Ca2+ entry via L‐type Ca2+ channels, and were mediated by protein kinase C (PKC). Nifedipine (10−6 M) and the PKC inhibitor, GF 109203X (10−6 M) reduced L‐type Ca2+ current and blocked the effects of SP.

SP responses depended upon parallel stimulation of NK1 and NK2 receptors. NK1 agonist ([Sar9,Met(O2)11]‐substance P; SSP) and NK2 agonists (neurokinin A (NKA) or GR‐64349) did not mimic the effects of SP alone, but NK1 and NK2 agonists were effective when added in combination (10−10–10−6 M). Consistent with this, either an NK1‐specific antagonist (GR‐82334; 10−7 M) or an NK2‐specific antagonist (MEN 10,627; 10−7 M) blocked responses to SP (10−6 M).

Ryanodine (10−5 M) blocked the increase in Ca2+ transients and STOCs in response to SP (10−10 M).

Our findings show that low concentrations of SP, via PKC‐dependent enhancement of L‐type Ca2+ current and recruitment of ryanodine receptors, stimulate Ca2+ transients. At higher concentrations of SP (10−6 M), basal Ca2+ increases and spontaneous Ca2+ transients and STOCs are inhibited.

British Journal of Pharmacology (2003) 138, 1233–1243. doi:10.1038/sj.bjp.0705139
Stimulation of P2 purinergic receptors induces the release of eosinophil cationic protein and interleukin‐8 from human eosinophils
Authors: Idzko Marco , Panther Elisabeth , Bremer Hinrich C , Sorichter Stephan , Luttmann Werner , Virchow Christian J , Di Virgilio Francesco , Herouy Yared , Norgauer Johannes , Ferrari Davide
Published: April 2003

Extracellular nucleotides are the focus of increasing attention for their role as extracellular mediators since they are released into the extracellular environment in a regulated manner and/or as a consequence of cell damage.

Here, we show that human eosinophils stimulated with different nucleotides release eosinophil cationic protein (ECP) and the chemokine interleukin 8 (IL‐8), and that release of these two proteins has a different nucleotide requirement.

Release of ECP was triggered in a dose‐dependent manner by ATP, UTP and UDP, but not by 2′‐&3′‐o‐(4‐benzoyl‐benzoyl)adenosine 5′‐triphosphate (BzATP), ADP and α,β‐methylene adenosine 5′ triphosphate (α,β‐meATP). Release of IL‐8 was triggered by UDP, ATP, α,β‐meATP and BzATP, but not by UTP or ADP. Pretreatment with pertussis toxin abrogated nucleotide‐stimulated ECP but not IL‐8 release.

Release of IL‐8 stimulated by BzATP was fully blocked by the P2X7 blocker KN‐62, while release triggered by ATP was only partially inhibited. IL‐8 secretion due to UDP was fully insensitive to KN‐62 inhibition.

Priming of eosinophils with GM‐CSF increased IL‐8 secretion irrespectively of the nucleotide used as a stimulant.

It is concluded that extracellular nucleotides trigger secretion of ECP by stimulating a receptor of the P2Y subfamily (possibly P2Y2), while, on the contrary, nucleotide‐stimulated secretion of IL‐8 can be due to activation of both P2Y (P2Y6) and P2X (P2X1 and P2X7) receptors.

British Journal of Pharmacology (2003) 138, 1244–1250. doi:10.1038/sj.bjp.0705145
Effect of tumour necrosis factor‐α and interleukin 1β on endothelium‐dependent relaxation in rat mesenteric resistance arteries in vitro
Authors: Wimalasundera R , Fexby S , Regan L , Thom S A McG , Hughes A D
Published: April 2003

Pre‐eclampsia is associated with elevated proinflammatory cytokine levels and endothelial dysfunction. This study examined the effect of two cytokines, tumour necrosis factor‐α (TNF) and interleukin‐1β (IL‐1) on endothelium‐dependent relaxation in response to acetylcholine (ACH), bradykinin (BK) and histamine (HIS) in rat mesenteric small arteries in vitro.

Rat mesenteric arteries were mounted in an isometric myograph. Tone was induced with phenylephrine (PE) or a depolarizing solution containing 80 mM KCl (K80). Relaxation was measured in response to ACH, BK, HIS and sodium nitroprusside (SNP), an endothelium‐independent relaxant. Inhibition of NO synthase by a combination of Nω‐monomethyl‐L‐arginine (L‐NMMA) and Nω‐nitro‐L‐arginine methyl ester (L‐NAME) significantly inhibited relaxation in response to ACH and BK. Addition of an inhibitor of cyclooxygenase, indomethacin, had no additional effect when added to L‐NMMA and L‐NAME. Inhibition of endothelium‐derived hyperpolarizing factor (EDHF) by K80 partially reduced responses to ACH and BK. Inhibition of HIS‐induced relaxation was more marked with K80. L‐NMMA and L‐NAME largely abolished the remaining relaxation to ACH, BK and HIS in arteries contracted with K80.

Preincubation with TNF for 30 min caused an inhibition of relaxation in response to ACH and BK in arteries contracted with PE. Responses to HIS and SNP were not affected by TNF under these conditions. TNF also inhibited ACH‐induced relaxation in arteries contracted with K80. IL‐1 had no effect on responses to ACH and the combination of TNF and IL‐1 was not more effective than TNF alone.

The inhibitory effect of TNF on ACH‐induced relaxation was abolished by coincubation with superoxide dismutase (SOD) and was not seen if NO synthase was inhibited by L‐NMMA and L‐NAME.

TNF inhibits the NO‐dependent component of endothelium‐dependent relaxation in response to ACH and BK, but does not inhibit the EDHF‐dependent component. This effect may be attributable to the ability of TNF to increase levels of superoxide anions (O2−) and the ability of O2− to inactivate NO. This mechanism could contribute to the endothelial dysfunction seen in situations where TNF is elevated, such as pre‐eclampsia.

British Journal of Pharmacology (2003) 138, 1285–1294. doi:10.1038/sj.bjp.0705168