bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term follow‐up in early gastric cancer: Evaluation of prognostic factors
Authors: Ranaldi Renzo , Santinelli Alfredo , Verdolini Roberto , Rezai Banafsheh , Mannello Bruno , Bearzi Italo
Published: June 2005

Four hundred and fourteen cases of early gastric cancer (EGC), diagnosed between 1977 and 1993, were studied. The percentage of EGC increased from 1977 to 1984, but thereafter remained more or less stable, despite a continuous increase in the number of endoscopic examinations. Three hundred and ninety‐six patients were followed up. Twenty‐nine patients died from the tumour, giving a 5‐year survival rate of 82·8 per cent. The ‘large’ size type of EGC, the presence of submucosal penetration, and lymph‐node metastasis showed a highly significant association with a lower survival rate. A small number of patients died despite the presence of ‘favourable’ prognostic factors. Other still unknown factors may therefore be important in determining the aggressive behaviour of certain EGCs.
Expression of basic fibroblast growth factor and fibroblast growth factor receptor in advanced gastric carcinoma
Authors: Ueki Takashi , Koji Takehiko , Tamiya Sadafumi , Nakane Paul K. , Tsuneyoshi Masazumi
Published: June 2005

The expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor (FGFR) mRNA was examined in gastric carcinomas by immunohistochemistry and in situ hybridization, respectively. In the 20 advanced carcinomas examined, bFGF was found in 14 (70·0 per cent) and was confined to the tumour cells, whereas FGFR mRNA was demonstrated in 12 (60·0 per cent) and seen in both tumour cells and endothelial cells. The bFGF and FGFR mRNA‐positive carcinomas were larger, were more frequently classified as undifferentiated adenocarcinoma, more frequently invaded the serosal layer, and had a higher rate of lymph node metastases than the bFGF and FGFR mRNA‐negative carcinomas. Patients with bFGF and FGFR mRNA‐positive carcinomas appear to die earlier than those with bFGF and FGFR mRNA‐negative tumours. The values for the carcinomas that were positive for either bFGF or FGFR mRNA fell between these two groups. The findings suggest that the autocrine/paracrine bFGF/FGFR channel is associated with undifferentiated gastric carcinomas and may lead to a poorer prognosis.
Multiple genetic alterations in malignant metastatic insulinomas
Authors: Pavelić Krešimir , Hrašćan Reno , Kapitanovića Sanja , Karapandža Nikola , Vraneš Zoran , Belicza Mladen , Krušlin Božo , Čabrijan Tomislav
Published: June 2005

Proto‐oncogenes, growth factors/receptors, and tumour suppressor genes were analysed in malignant metastatic insulinomas. Normal pancreas showed only a moderate immunoreaction for c‐myc proto‐oncogene and a strong reaction for insulin. Benign insulinomas were slightly or moderately positive for transforming growth factor a (TGFα), weakly positive for epidermal growth factor receptor (EGF‐R), and strongly positive for c‐myc and insulin. In malignant insulinomas, besides a strong immunoreaction for c‐myc and TGFα, activation of c‐K‐ras and overexpression of p53 protein were found. Insulin reaction was moderate or strong. Three out of six malignant insulinomas displayed a c‐K‐ras point mutation at codon 12. All mutations were guanine to cytosine transversion, resulting in amino acid substitution, glycine to arginine. Mutations were present in metastatic insulinomas only. Patients with mutated c‐K‐ras oncogene had overexpression of p53 protein as well as c‐myc and TGFα overexpression. Our results support the view that malignant progression is a consequence of more than one genetic lesion and suggest that activation of myc, TGFα, and ras genesα plays a role in a multistep process of tumour progression, perhaps serving as an initiating event.
Immunohistological localization of the novel epitope related to type IV collagen in normal and diseased renal tissues
Authors: Hirata Kyoji , Shikata Kenichi , Makino Hirofumi , Hayashi Toshihiko , Ota Zensuke
Published: June 2005

Type IV collagen is a major component of the renal glomerular extracellular matrix. A recently characterized monoclonal antibody, JK 132, which was originally produced by immunization with human placental type IV collagen, recognizes a new epitope which is different from α1–α6 chains of type IV collagen. Using immunofluorescence and immunogold electron microscopy, the distribution of the epitope of JK132 has been compared with the distribution of α1, α2, α3 and α4 chains of type IV collagen in normal human kidney and in the renal tissues of patients with various types of glomerulonephritis. In normal human kidney, JK132 reacted with mesangial matrix, Bowman's capsular basement membrane (BCBM), tubular basement membrane, and vessel walls, but did not react with glomerular basement membrane (GBM). This distribution is different from the distribution of α1–α4(IV) chains. In IgA nephropathy and membranoproliferative glomerulonephritis, the staining intensity for JK132 was increased in expanded mesangial matrix. In glomeruli with severe mesangial proliferation, the epitope of JK132 extended to the endothelial side of the GBM. In membranous nephropathy, staining for JK132 was virtually unchanged from normal. This study suggests that the epitope of JK132 increases in amount during the process of mesangial proliferation and could serve as a marker for mesangial matrix expansion in glomerulonephritis.
Graphical analyses of personality disorders in five‐factor model space
Authors: O'Connor Brian P.
Published: June 2005

Current knowledge of the associations between personality disorders (PDs) and the five‐factor model (FFM) is based largely on the results of linear correlation statistics. Yet we do not know whether FFM–PD associations are indeed linear, and correlational statistics are not directly informative regarding the FFM deviations of individuals with PDs. In this study, graphical analyses of FFM–PD associations for a large, clinical and nonclinical combined sample revealed a diversity of linear and nonlinear FFM patterns, at both the domain and facet levels, for most PDs. However, the FFM deviations from normative levels were only moderate. The discussion focuses on the strengths and weaknesses of the FFM approach to PDs. Copyright © 2005 John Wiley & Sons, Ltd.
Differentiating normal, abnormal, and disordered personality
Authors: Livesley W. John , Jang Kerry L.
Published: June 2005

Interest in the interface between normality and psychopathology was renewed with the publication of DSM‐III more than 20 years ago. The use of a separate axis to classify disorders of personality brought increased attention to these conditions. At the same time, the definition of personality disorder as inflexible and maladaptive traits stimulated interest in the relationship between normal and disordered personality structure and functioning. The evidence suggests that the traits delineating personality disorder are continuous with normal variation and that the structural relationships among these traits resemble the structures described by normative trait theories. Recognition that personality disorder represents the extremes of trait dimensions emphasizes the importance of differentiating normal, abnormal, and disordered personality. It is argued that while abnormal personality may be considered extreme variation, personality disorder is more than statistical variation. A definition of personality disorder is suggested based on accounts of the adaptive functions of personality. Copyright © 2005 John Wiley & Sons, Ltd.
Isothermal crystallization kinetics of chain‐extended PET
Authors: Sorrentino L. , Iannace S. , Di Maio E. , Acierno D.
Published: June 2005

The crystallization behavior of a commercial chain‐extended PET (foam grade) was evaluated and compared to that of bottle‐grade PET. Cold and melt isothermal crystallization were analyzed by using the Avrami' model. The foam grade PET showed a slower crystallization kinetic compared to the bottle‐grade PET. The Hoffman‐Lauritzen analysis showed that the energetic barriers to nucleation and molecular mobility were higher for the chain‐extended PET. This resulted in a lower nucleation rate in both cold and melt crystallization. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 1966–1972, 2005
Intramolecular branching distributions in metallocene short‐chain branched polyethylenes examined by crystallization and annealing at high pressure
Authors: Parker J. A. , Olley R. H.
Published: June 2005

Uniform branched polyethylenes produced by metallocene catalysts can be subjected to a limited degree of intramolecular fractionation by crystallization or annealing at pressures of 495 MPa. Longer stem lengths in lamellae are more achievable by this process than by treatments at atmospheric pressure. Although the intervention of the hexagonal phase allows greater lamellar stem lengths to be achieved, the small proportion of longer methylene sequence lengths in the melt imposes limitations on the degree of isothermal thickening achievable. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 1986–1996, 2005
hScrib interacts with ZO‐2 at the cell–cell junctions of epithelial cells
Authors: Métais Jean-Yves , Navarro Christel , Santoni Marie-Josée , Audebert Stéphane , Borg Jean-Paul
Published: June 2005

In Drosophila, the tumor suppressor Scribble is localized at the septate junctions of epithelial cells. Its mammalian homologue, hScrib, is a basolateral protein likely associated to proteins of the cell–cell junctions. We report the direct interaction between hScrib and ZO‐2, a junction‐associated protein. This interaction relies on two PDZ domains of hScrib and on the C‐terminal motif of ZO‐2. Both proteins localise at cell–cell junctions of epithelial cells. A point mutation in the LRR of hScrib delocalises the protein from the plasma membrane and abrogates the interaction with ZO‐2 but not with βPIX. Tyrosine phosphorylation of hScrib does not impair the interaction with ZO‐2. We show a direct link between two junctional proteins that are down‐regulated during cancer progression.
Variations in case fatality and fatality risk factors of meningococcal disease in Western Norway, 1985–2002
Authors: SMITH I. , BJØRNEVIK A. T. , AUGLAND I. M. B. , BERSTAD A. , WENTZEL-LARSEN T. , HALSTENSEN A.
Published: June 2005

In a retrospective epidemiological study, 293 meningococcal disease patients hospitalized during 1985–2002, were examined for fatality and risk factors related to death. The overall case fatality rate (CFR) was 8·2%, but increased from 4% during 1985–1993 to 17% during 1994–2002. The latter 9-year period was characterized by more serogroup C infections and more patients with thrombocytopenia on admission to hospital. All patients categorized as meningitis on admission survived. Of the 24 patients who died, 21 had meningococcal skin rash on admission, 23 had an onset to admission time of ⩽24 h, and 16 had severe septicaemia with hypotension and/or ecchymoses without meningitis on admission. By multivariate analyses, a short onset to admission time, >50 petechiae, thrombocytopenia and severe septicaemia on admission were associated with fatality. More lives could be saved through earlier admission to hospital. This can be achieved through more information to the public about the early signs of meningococcal septicaemia, with the recommendation to look for skin rash in patients with acute fever during the first day and night.
Steroid-induced hippocampal synaptic plasticity: sex differences and similarities
Authors: ROMEO RUSSELL D. , WATERS ELIZABETH M. , MCEWEN BRUCE S.
Published: June 2005

Early in development, steroid hormones structurally organize various regions of the CNS. However, steroid hormones continue to affect the structure and function of the CNS throughout the life of the individual. In this review, we discuss sex differences and similarities in steroid-induced synaptic plasticity in the adult brain. Particular emphasis is placed on steroid-induced plasticity in the hippocampus, a brain region important in learning and memory. This topic is relevant to the growing evidence for the actions of sex hormones outside of the reproductive neuroendocrine axis. It also tells an important and emerging story about non-genomic and genomic actions of steroids at the cellular and molecular levels. Specifically, the effects of estrogen and progesterone as well as the androgens and glucocorticoids are discussed. The influence of steroids on hippocampal structure and function can differ vastly between the sexes. However, there are certain similarities that might aid in our understanding of how steroids affect CNS plasticity in general. Although future studies will undoubtedly lead us to a greater understanding of these phenomena, the data reviewed indicate that when studying synaptic plasticity, the sex and hormonal milieu of the individual might significantly influence the outcome and interpretation of the research.
Minocycline attenuates nitric oxide-mediated neuronal and axonal destruction in vitro
Authors: WILKINS ALASTAIR , NIKODEMOVA MARIA , COMPSTON ALASTAIR , DUNCAN IAN
Published: June 2005

Minocycline, a tetracycline derivative with pleiotropic biological effects, exhibits anti-inflammatory properties in several models of CNS disease. In addition to reducing production of inflammatory mediators, it has been postulated that minocycline might also be directly neuroprotective under these circumstances. Therefore, we investigated the effect of minocycline on primary cortical neuronal cultures exposed to a nitric oxide (NO)-donor. Cultures were assessed for neuronal survival, axon survival and markers of intracellular signaling pathways. The NO donor significantly increased neuronal death and minocycline was protective under these conditions. Furthermore NO-induced reductions in axonal length were significantly attenuated by minocycline. Improvements in axonal length were dependent on mitogen-activated protein kinase (MAP kinase)/extracellular signal-related kinase (Erk) signaling, whereas phosphatidylinositol 3-kinase (PI 3-kinase)/Akt signaling was important in neuronal survival. Further investigation into MAP kinase signaling pathways revealed inhibition of p38 MAP kinase and c-jun N-terminal kinase (JNK) signaling by minocycline. JNK pathways were activated by trophic factor-withdrawal and minocycline attenuated neuronal death induced by trophic withdrawal. These results indicate that, in addition to anti-inflammatory properties, minocycline has direct protective effects on neurons and provides further evidence for its use in disorders of the CNS.
MHC class I in activity-dependent structural and functional plasticity
Authors: BOULANGER LISA M.
Published: June 2005

Members of the major histocompatibility complex (MHC) class I family of proteins are well known for their central role in the adaptive immune system, where they present self and non-self peptides for immune surveillance. Although the brain has been long considered immune privileged, in part because of an apparent lack of neuronal MHC class I, it has since been shown that MHC class I proteins are expressed by normal, uninfected neurons. Moreover, expression of MHC class I is unusually dynamic in the developing and adult brain, and MHC class I levels in neurons can be regulated by endogenous and exogenous electrical activity. Unexpectedly, several recent studies find that MHC class I is required for distinct activity-dependent events during brain development, adult plasticity, and in response to injury. Together, these studies indicate a novel role for MHC class I proteins in translating electrical activity into changes in synaptic strength and neuronal connectivity in vivo.
A dialogue between glia and neurons in the retina: modulation of neuronal excitability
Authors: NEWMAN ERIC A.
Published: June 2005

Bidirectional signaling between neurons and glial cells has been demonstrated in brain slices and is believed to mediate glial modulation of synaptic transmission in the CNS. Our laboratory has characterized similar neuron–glia signaling in the mammalian retina. We find that light-evoked neuronal activity elicits Ca2+ increases in Müller cells, which are specialized retinal glial cells. Neuron to glia signaling is likely mediated by the release of ATP from neurons and is potentiated by adenosine. Glia to neuron signaling has also been observed and is mediated by several mechanisms. Stimulation of glial cells can result in either facilitation or depression of synaptic transmission. Release of D-serine from Müller cells might also potentiate NMDA receptor transmission. Müller cells directly inhibit ganglion cells by releasing ATP, which, following hydrolysis to adenosine, activates neuronal A1 receptors. The existence of bidirectional signaling mechanisms indicates that glial cells participate in information processing in the retina.
D-Serine as a putative glial neurotransmitter
Authors: MUSTAFA ASIF K. , KIM PAUL M. , SNYDER SOLOMON H.
Published: June 2005

Abundant recent evidence favors a neurotransmitter/neuromodulator role for D-serine. D-serine is synthesized from L-serine by serine racemase in astrocytic glia that ensheath synapses, especially in regions of the brain that are enriched in NMDA-glutamate receptors. D-serine is more potent than glycine at activating the ‘glycine’ site of these receptors. Moreover, selective degradation of D-serine but not glycine by D-amino acid oxidase markedly reduces NMDA neurotransmission. D-serine appears to be released physiologically in response to activation by glutamate of AMPA-glutamate receptors on D-serine-containing glia. This causes glutamate-receptor-interacting protein, which binds serine racemase, to stimulate enzyme activity and D-serine release. Thus, glutamate triggers the release of D-serine so that the two amino acids can act together on postsynaptic NMDA receptors. D-serine also plays a role in neural development, being released from Bergmann glia to chemokinetically enhance the migration of granule cell cerebellar neurons from the external to the internal granular layer.
TNFα-induced AMPA-receptor trafficking in CNS neurons; relevance to excitotoxicity?
Authors: LEONOUDAKIS DMITRI , BRAITHWAITE STEVEN P. , BEATTIE MICHAEL S. , BEATTIE ERIC C.
Published: June 2005

Injury and disease in the CNS increases the amount of tumor necrosis factor α (TNFα) that neurons are exposed to. This cytokine is central to the inflammatory response that occurs after injury and during prolonged CNS disease, and contributes to the process of neuronal cell death. Previous studies have addressed how long-term apoptotic-signaling pathways that are initiated by TNFα might influence these processes, but the effects of inflammation on neurons and synaptic function in the timescale of minutes after exposure are largely unexplored. Our published studies examining the effect of TNFα on trafficking of AMPA-type glutamate receptors (AMPARs) in hippocampal neurons demonstrate that glial-derived TNFα causes a rapid (<15 minute) increase in the number of neuronal, surface-localized, synaptic AMPARs leading to an increase in synaptic strength. This indicates that TNFα-signal transduction acts to facilitate increased surface localization of AMPARs from internal postsynaptic stores. Importantly, an excess of surface localized AMPARs might predispose the neuron to glutamate-mediated excitotoxicity and excessive intracellular calcium concentrations, leading to cell death. This suggests a new mechanism for excitotoxic TNFα-induced neuronal death that is initiated minutes after neurons are exposed to the products of the inflammatory response.

Here we review the importance of AMPAR trafficking in normal neuronal function and how abnormalities that are mediated by glial-derived cytokines such as TNFα can be central in causing neuronal disorders. We have further investigated the effects of TNFα on different neuronal cell types and present new data from cortical and hippocampal neurons in culture. Finally, we have expanded our investigation of the temporal profile of the action of this cytokine relevant to neuronal damage. We conclude that TNFα-mediated effects on AMPAR trafficking are common in diverse neuronal cell types and very rapid in their onset. The abnormal AMPAR trafficking elicited by TNFα might present a novel target to aid the development of new neuroprotective drugs.
A composite study on the structure and formation of ozone miniholes and minihighs over central Europe
Authors: Koch G. , Wernli H. , Schwierz C. , Staehelin J. , Peter T.
Published: June 2005

Two different mechanisms have been proposed to be important for the formation of extreme total ozone events in mid‐latitudes, so‐called miniholes: (A) far‐range meridional transport of air masses from regions with different climatological ozone mixing ratios, and (B) (local) adiabatic vertical displacement of isentropes. Here, the relative importance of these two mechanisms is studied using two different ozone profile reconstruction techniques for all miniholes and minihighs (events with anomalously high ozone) during the time period 1980–1989 over Switzerland. Composites for the two types of events of their vertical potential vorticity (PV) reveal a vertical dipole structure of PV anomalies in the lower and middle stratosphere. They, in agreement with the profile reconstructions, highlight the importance of fast far‐range transport (mechanism A). Dynamically consistent with this PV structure is a relatively weak vertical displacement of isentropes between the PV dipole, that provides an additional but less important contribution (mechanism B).
Change in ozone trends at southern high latitudes
Authors: Yang E.‐S. , Cunnold D. M. , Newchurch M. J. , Salawitch R. J.
Published: June 2005

Long‐term ozone variations at 60–70°S in spring are investigated using ground‐based and satellite measurements. Strong positive correlation is shown between year‐to‐year variations of ozone and temperature in the Antarctic collar region in Septembers and Octobers. Based on this relationship, the effect of year‐to‐year variations in vortex dynamics has been filtered out. This process results in an ozone time series that shows increasing springtime ozone losses over the Antarctic until the mid‐1990s. Since approximately 1997 the ozone losses have leveled off. The analysis confirms that this change is consistent across all instruments and is statistically significant at the 95% confidence level. This analysis quantifies the beginning of the recovery of the ozone hole, which is expected from the leveling off of stratospheric halogen loading due to the ban on CFCs and other halocarbons initiated by the Montreal Protocol.
The spin state of iron in minerals of Earth's lower mantle
Authors: Sturhahn Wolfgang , Jackson Jennifer M. , Lin Jung‐Fu
Published: June 2005

The spin state of Fe(II) and Fe(III) at temperatures and pressures typical for the Earth's lower mantle is discussed. We predict an extended high‐spin to low‐spin crossover region along the geotherm for Fe‐dilute systems depending on crystal‐field splitting, pairing energy, and cooperative interactions. In particular, spin transitions in ferromagnesium silicate perovskite and ferropericlase, the dominant lower mantle components, should occur in a wide temperature‐pressure range. We also derive a gradual volume change associated with such transitions in the lower mantle. The gradual density changes and the wide spin crossover regions seem incompatible with lower mantle stratification resulting from a spin transition.
EOS Microwave Limb Sounder observations of the Antarctic polar vortex breakup in 2004
Authors: Manney G. L. , Santee M. L. , Livesey N. J. , Froidevaux L. , Read W. G. , Pumphrey H. C. , Waters J. W. , Pawson S.
Published: June 2005

New observations from the Microwave Limb Sounder (MLS) on NASA's Aura satellite give a detailed picture of the spring Antarctic polar vortex breakup throughout the stratosphere, with the first daily global HCl profiles providing an unprecedentedly clear view of transport in the lower stratosphere. Poleward transport at progressively lower levels, filamentation, and mixing are detailed in MLS HCl, N2O, H2O, and O3 as the 2004 Antarctic vortex broke up from the top down in early October through late December. Improved MLS H2O data show the subvortex, below the tropical tropopause, breaking up almost simultaneously with the lower stratospheric vortex in December. Vortex remnants persisted in MLS tracers for over a month after the breakup in the midstratosphere, but no more than a week in the lower stratosphere. MLS observations show diabatic descent continuing throughout November, but weak ascent after late October in the lower stratospheric vortex core. Our results extend previous observational transport studies and show consistency with mixing and vortex evolution in meteorological analyses, and with model studies.
The N(2D°–4S°) 520 nm forbidden doublet in the nightglow: An experimental test of the theoretical intensity ratio
Authors: Sharpee B. D. , Slanger T. G. , Cosby P. C. , Huestis D. L.
Published: June 2005

The ratio of intensities of the optically forbidden lines N(2D°–4S°) 519.8, 520.0 nm has been measured with high precision in the nightglow in repeated observations made with the High Resolution Echelle Spectrophotometer (HIRES) and Echellette Spectrograph and Imager (ESI) on the Keck I and Keck II telescopes, respectively, at the W.M. Keck Observatory on Mauna Kea, Hawaii. The observed intensity ratio, I(519.8 nm)/I(520.0 nm), is seen to vary little over the bulk of any particular night, with a value of 1.759 ± 0.014 determined over all observations. Among theoretical predictions of the ratio, this agrees best with a value of 1.788 determined from the ratio of products of recent Breit‐Pauli calculation‐derived spontaneous emission coefficients (Froese Fischer and Tachiev, 2004) and statistical weights of the fine structure levels of the 2D° term, under the assumption that these levels' populations are thermalized by rapid mixing through collisions with N2.
A model intercomparison of changes in the Atlantic thermohaline circulation in response to increasing atmospheric CO2 concentration
Authors: Gregory J. M. , Dixon K. W. , Stouffer R. J. , Weaver A. J. , Driesschaert E. , Eby M. , Fichefet T. , Hasumi H. , Hu A. , Jungclaus J. H. , Kamenkovich I. V. , Levermann A. , Montoya M. , Murakami S. , Nawrath S. , Oka A. , Sokolov A. P. , Thorpe R. B.
Published: June 2005

As part of the Coupled Model Intercomparison Project, integrations with a common design have been undertaken with eleven different climate models to compare the response of the Atlantic thermohaline circulation (THC) to time‐dependent climate change caused by increasing atmospheric CO2 concentration. Over 140 years, during which the CO2 concentration quadruples, the circulation strength declines gradually in all models, by between 10 and 50%. No model shows a rapid or complete collapse, despite the fairly rapid increase and high final concentration of CO2. The models having the strongest overturning in the control climate tend to show the largest THC reductions. In all models, the THC weakening is caused more by changes in surface heat flux than by changes in surface water flux. No model shows a cooling anywhere, because the greenhouse warming is dominant.
Aβ25–35 Alters AKT Activity, Resulting in Bad Translocation and Mitochondrial Dysfunction in Cerebrovascular Endothelial Cells
Authors: Yin Ke-Jie , Lee Jin-Moo , Hong Cheng , Xu Jan , Hsu Chung Y
Published: June 2005

The amyloid-beta peptide (Aβ) induces apoptosis in cerebrovascular endothelial cells (CECs), contributing to the pathogenesis of cerebral amyloid angiopathy. We have previously shown that Aβ induces apoptosis in CECs. In the present study, we report that Aβ25–35-induced CEC apoptosis involves the inactivation of Akt, a signaling kinase important in maintaining cell viability. Akt prevents the activation of death-signaling events by facilitating the inactivation of proapoptotic proteins such as Bad. We applied three strategies to show that Aβ25–35 inactivation of Akt is causally related to Aβ25–35-induced CEC death by preventing Bad activation and subsequent mitochondrial dysfunction (reflected by the release of endonuclease G and Smac, two proapoptotic intermembranous proteins of the mitochondria). Wortmannin, a PI3-kinase inhibitor, enhanced Aβ25–35-induced Bad activation, mitochondrial dysfunction and CEC death. Enhancement of Akt activity by a Tat—Akt fusion protein, or by viral gene transfer of a constitutively active mutant of akt, reduced Bad activation, mitochondrial dysfunction, and CEC death. Using a siRNA strategy to knock down the bad gene, we showed that Bad activation is causally related to Aβ25–35-induced mitochondrial dysfunction and CEC death. Together, these results establish that the Akt—Bad cascade is altered by Aβ25–35, resulting in CEC apoptosis.
A Multiparametric Assessment of Oxygen Efflux from the Brain
Authors: Hermán Peter , Trübel Hubert KF , Hyder Fahmeed
Published: June 2005

A quantitative understanding of unidirectional versus net extraction of oxygen in the brain is required because an important factor in calculating oxidative metabolism by calibrated functional magnetic resonance imaging (fMRI) as well as oxygen inhalation methods of positron emission tomography (15O2-PET) and nuclear magnetic resonance (17O2-NMR)) is the degree of oxygen efflux from the brain back into the blood. Because mechanisms of oxygen transport from blood to brain are dependent on cerebral metabolic rate of oxygen consumption ( CMRO2), cerebral blood flow ( CBF), and oxygen partial pressure (pO2) values in intravascular ( Piv) and extravascular ( Pev) compartments, we implemented multimodal measurements of these parameters into a compartmental model of oxygen transport and metabolism (i.e., hemoglobin-bound oxygen, oxygen dissolved in plasma and tissue spaces, oxygen metabolized in the mitochondria). In the α-chloralose anesthetized rat brain, we used magnetic resonance (7.0 T) and fluorescence quenching methods to measure CMRO2 (2.5 ± 1.0 μmol/g min), CBF(0.7 ± 0.2 mL/g min), Piv (74 ± 10 mm Hg), and Pev(16 ± 5 mm Hg) to estimate the degree of oxygen efflux from the brain. In the axially distributed compartmental model, oxygen molecules in blood had two possible fates: enter the tissue space or remain in the same compartment; while in tissue there were three possible fates: enter the blood or the mitochondrial space, or remain in the same compartment. The multiparametric results indicate that the probability of unmetabolized (i.e., dissolved) oxygen molecules reentering the blood from the tissue is negligible and thus its inclusion may unnecessarily complicate calculations of CMRO2 for 15O-PET, 17O-NMR, and calibrated fMRI methods.
NF-κB activation and potentiation of proinflammatory responses by theHelicobacter pyloriCagA protein
Authors: Brandt Sabine , Kwok Terry , Hartig Roland , König Wolfgang , Backert Steffen
Published: June 2005

TheHelicobacter pyloriimmunodominant protein, CagA, is associated with severe gastritis and carcinoma. Injection of CagA into gastric epithelial cells by type IV secretion leads to actin-cytoskeletal rearrangements and cell scattering. CagA has been reported to have no role in the induction of transcription factor NF-κB and IL-8, which are crucial determinants for chronic inflammation. Here, we provide several lines of evidence showing that CagA is able to induce IL-8 in a time- and strain-dependent manner. We also show that by exchanging specificcagAgenes, high IL-8-inducingH. pyloristrains could be converted into low inducing strains and vice versa. Our results suggest that IL-8 release induced by CagA occurs via a Ras→Raf→Mek→Erk→NF-κB signaling pathway in a Shp-2- and c-Met-independent manner. Thus, CagA is a multifunctional protein capable of effecting both actin remodeling and potentiation of chemokine release.
Aryl hydrocarbon receptor activation by cAMP vs. dioxin: Divergent signaling pathways
Authors: Oesch-Bartlomowicz Barbara , Huelster Andrea , Wiss Oliver , Antoniou-Lipfert Patricia , Dietrich Cornelia , Arand Michael , Weiss Carsten , Bockamp Ernesto , Oesch Franz
Published: June 2005

Even before the first vertebrates appeared on our planet, the aryl hydrocarbon receptor (
AHR
) gene was present to carry out one or more critical life functions. The vertebrate AHR then evolved to take on functions of detecting and responding to certain classes of environmental toxicants. These environmental pollutants include polycyclic aromatic hydrocarbons (e.g., benzo[
a
]pyrene), polyhalogenated hydrocarbons, dibenzofurans, and the most potent small-molecular-weight toxicant known, 2,3,7,8-tetrachlorodibenzo-
p
-dioxin (TCDD or dioxin). After binding of these ligands, the activated AHR translocates rapidly from the cytosol to the nucleus, where it forms a heterodimer with aryl hydrocarbon nuclear translocator, causing cellular responses that lead to toxicity, carcinogenesis, and teratogenesis. The nuclear form of the activated AHR/aryl hydrocarbon nuclear translocator complex is responsible for alterations in immune, endocrine, reproductive, developmental, cardiovascular, and central nervous system functions whose mechanisms remain poorly understood. Here, we show that the second messenger, cAMP (an endogenous mediator of hormones, neurotransmitters, and prostaglandins), activates the AHR, moving the receptor to the nucleus in some ways that are similar to and in other ways fundamentally different from AHR activation by dioxin. We suggest that this cAMP-mediated activation may reflect the true endogenous function of AHR; disruption of the cAMP-mediated activation by dioxin, binding chronically to the AHR for days, weeks, or months, might be pivotal in the mechanism of dioxin toxicity. Understanding this endogenous activation of the AHR by cAMP may help in developing methods to counteract the toxicity caused by numerous environmental and food-borne toxic chemicals that act via the AHR.
Genomic structure and functional characterization of the human ADAM10 promoter
Authors: Prinzen Claudia , Müller Ulrich , Endres Kristina , Fahrenholz Falk , Postina Rolf
Published: June 2005

The ADAM10 gene encodes a membrane‐bound disintegrin‐metalloproteinase, which, after overexpression in an Alzheimer disease (AD) mouse model, prevents amyloid pathology and improves long‐term potentiation and memory. Because enhancing ADAM10 expression appears to be a reasonable approach for treatment of AD, we functionally analyzed the ADAM10 gene. Both human and mouse ADAM10 genes comprise ∼160 kbp, are composed of 16 exons, and are evolutionarily highly conserved within 500 bp upstream of either translation initiation site. By using luciferase reporter assays, we demonstrate that nucleotides −2179 to −1 upstream of the human ADAM10 translation initiation site represent a functional TATA‐less promoter. Within this region we identified and examined several single nucleotide polymorphisms, but did not detect significant differences in their appearance between AD and nondemented control subjects. By deletion analysis, site‐directed mutagenesis, transcription factor overexpression and electrophoretic mobility shift assays, we identified nucleotides −508 to −300 as the core promoter and found Sp1, USF, and retinoic acid‐responsive elements to modulate its activity. Finally, we identified vitamin A acid (RA) as an inducer of human ADAM10 promoter activity. This finding suggests that pharmacologic targeting of RA receptors may increase the expression of the α‐secretase ADAM10 with beneficial effects on AD pathology.
Serotonergic‐like progenitor cells propagated from neural stem cells in vitro: survival with SERT protein expression following implantation into brains of mice lacking SERT
Authors: Ren‐Patterson Renee F. , Kim Dong‐Kyu , Zheng Xiu , Sherrill Suzanne , Huang Su‐Jan , Tolliver Teresa , Murphy Dennis L.
Published: June 2005

Neural stem cells (NSCs) obtained from the midbrain region of embryonic (E14) mice were initially cultured with basic fibroblast growth factor (bFGF), Sonic hedgehog, and FGF‐8 in a serum‐free N‐2 culture medium to foster differentiation into a serotonergic‐like phenotype. During the initial differentiating phase, these progenitor cells expressed En1, Pax3, and Pax5 mRNA. Subsequently, a single serotonin [5‐hydroxytryptamine (5‐HT)] and tryptophan hydroxylase‐positive clone was isolated, which gave rise to cells that developed serotonergic properties. Sixty percent of these progenitor cells expressed the serotonin transporter (SERT), as indicated by specific ligand binding of [125I]‐RTI‐55. To further evaluate SERT functionality, we showed that these progenitor cells possessed specific [3H]‐5‐HT uptake activity. Implantation of the serotonergic‐like progenitors into the hippocampus of adult mice genetically lacking SERT was followed by migration of these cells into adjacent brain regions, and survival of the cells at 8 weeks was accompanied by a gradual increase in density of SERT protein expression, which was not found in vehicle‐injected, control mice. These findings suggest that this serotonergic‐like NSC model will be a useful contribution to the development of cell biotechnology in regard to the expression of missing genes such as SERT in the adult brain.
In vitro reconstruction of an endothelialized skin substitute provided with a microcapillary network using biopolymer scaffolds
Authors: Tonello Carolin , Vindigni Vincenzo , Zavan Barbara , Abatangelo Silvio , Abatangelo Giovanni , Brun Paola , Cortivo Roberta
Published: June 2005

Successful in vitro reconstruction of skin requires the inclusion of several cell types that give rise in coculture to the specific elements present in native skin, and the appropriate scaffolding structure to house and support these cells. In addition to the two main structural components, epidermis and dermis, one critical apparatus of the skin is a capillary network that guarantees adequate perfusion of nutrients and oxygen. The aim of the present study was to develop an in vitro coculture system that assumed the human dermal‐epidermal architecture and included a microcapillary network in a three‐dimensional biomaterial that guaranteed ease of handling in a clinical setting. Endothelialized skin (ES) was prepared by coculturing three human cell types: keratinocytes, fibroblasts, and endothelial cells, obtained from human full‐thickness skin samples, in scaffolds produced from modified hyaluronic acid. Results were evaluated by histological and immunohistochemical analyses at different time points. In vitro, engineered skin obtained with this composite culture developed into a well‐differentiated upper layer of stratified keratinocytes lining a dermal‐like structure, in which fibroblasts, extracellular matrix and a microvascular network were present. Furthermore, the biodegradable fabric produced from hyaluronic acid and used as the scaffolding support for this in vitro constructed skin graft greatly facilitated handling in the perioperative period.
Electric organ discharge patterns during group hunting by a mormyrid fish
Authors: Arnegard Matthew E , Carlson Bruce A
Published: June 2005

Weakly electric fish emit and receive low-voltage electric organ discharges (EODs) for electrolocation and communication. Since the discovery of the electric sense, their behaviours in the wild have remained elusive owing to their nocturnal habits and the inaccessible environments in which they live. The transparency of Lake Malawi provided the first opportunity to simultaneously observe freely behaving mormyrid fish and record their EODs. We observed a piscivorous mormyrid,Mormyrops anguilloides, hunting in small groups in Lake Malawi while feeding on rock-frequenting cichlids of the largest known vertebrate species flock. Video recordings yielded the novel and unexpected finding that these groups resembled hunting packs by being largely composed of the same individuals across days. We show that EOD accelerations accompany prey probing and size estimation byM. anguilloides. In addition, group members occasionally synchronize bursts of EODs with an extraordinary degree of precision afforded by the mormyrid echo response. The characteristics and context of burst synchronization suggest that it may function as a pack cohesion signal. Our observations highlight the potential richness of social behaviours in a basal vertebrate lineage, and provide a framework for future investigations of the neural mechanisms, behavioural rules and ecological significance of social predation inM. anguilloides.
A comparative study on the corrosion behaviour of simulated archaeological iron in Cl−, NO3− and HSO3− bearing pollutants
Authors: Cao Xia , Xu Chunchun , Ouyang Weizhen , Yue Lijie
Published: June 2005

Purpose

The main purpose of this study was to investigate the corrosion behaviour of simulated archaeological iron in Cl−, NO3− and HSO3− bearing pollutants.

Design/methodology/approach

Periodic wet‐dry test, potentiodynamic polarization experiments and surface tension tests were used to study the rule of corrosion rate. Scanning Electron microscopy with EDAX, stereoscopic microscopy and X‐ray diffraction were also used to identify the corrosion products and mechanism. Weight loss measurement, electrochemical theory, as well as ions adsorption theory and penetration theory were used to explain the different corrosion behaviour.

Findings

The experimental results demonstrated that the attack of anodic ions to the metal at the initial corrosion stage showed great agreement with their surface activity. However, as corrosion progressed, the different reaction mechanisms and the penetration effect of anions as well as the characteristics of the corrosion products (intermediate products and final products) begin to control the corrosion process.

Originality/value

The initial corrosion rate was found to show agreement with the surface activity of anions. From a new viewpoint, this paper explains the different corrosion behaviour of Cl−, NO3− and HSO3− anions to simulated archaeological iron and offers reference to the individual who pursues in corrosion and protection of metal.
The effect of isomers of some organic compounds as inhibitors for the corrosion of carbon steel in sulfuric acid
Authors: Ramesh Babu B. , Thangavel K.
Published: June 2005

Purpose

To study the effects of isomers of organic compounds such as phenylenediamine, toluidine and nitroaniline as inhibitors for the corrosion of carbon steel in sulfuric acid.

Design/methodology/approach

Standard methods have been adopted in this study such as weight loss, polarization tests, impedance measurements and hydrogen permeation studies to find out the corrosion behavior of carbon steel in sulfuric acid with and without inhibitors.

Findings

All the selected isomers inhibited the corrosion. The best performance was found in ortho‐phenylenediamine when compared with other inhibitors under study.

Originality/value

It clearly shows the effect of isomers of phenylenediamine, toluidine and nitroaniline. The method of study may be applicable to find out the performance of other isomers of organic compounds. As these isomers behave as good inhibitors in sulfuric acid, these may be tried as inhibitors in other acids. Hence, this study is useful to academics and researchers in the field of corrosion science and engineering.
Leadership effectiveness, leadership style and employee readiness
Authors: Chen Jui‐Chen , Silverthorne Colin
Published: June 2005

Purpose

This study aims to test the Hersey and Blanchard Situation Leadership Theory (SLT) of leadership effectiveness and the impact of the degree of match between leadership style and employee readiness level on a variety of measures of leadership outcomes.

Design/methodology/approach

The measures used were employee job satisfaction, job performance, job stress, and turnover intention. SLT argues that an effective leader adopts a leadership style according to the ability and willingness of subordinates for a given task.

Findings

The results did not support SLT predictions that an appropriate match between leadership style and subordinate readiness results in higher levels of subordinate job satisfaction and performance and lower levels of job stress and intention to leave. However, the results did partially support SLT in that, the higher the leader's leadership score, the more effective is the leader's influence. However, the leadership score did not predict job performance. There was a positive correlation between ability and willingness, employee job satisfaction, and job performance. Employee willingness positively correlated with job satisfaction and job performance and was negatively correlated with turnover intention.

Research limitations/implications

The findings from this study apply to the Taiwan culture and may or may not apply to other “Chinese” and non‐Chinese cultures.

Practical implications

The use of the SLT in Taiwan is very widespread, so this study provides empirical evidence of its value when used in Taiwan as a tool to develop and use effective and appropriate leadership abilities.

Originality/value

Few studies have attempted to explore the value of SLT in general and in non‐Western cultures in particular. This study expands our knowledge of leadership issues to an Eastern culture and explores the theory's effectiveness related to several organizational factors.
Promoting business/IT fusion: an OD perspective
Authors: Evans Nina , Hoole Crystal
Published: June 2005

Purpose

It is generally accepted that new information technologies are an integral part of most forms of business initiatives. Evidence suggests that many of these innovations are ineffective and under‐utilised. The information systems/information technology (IS/IT) industry often does not seem to be capable of delivering what business clients expect. Owing to this “expectation gap” and various behavioural issues, business experts have a negative perception of the IS/IT function. It is proposed that a new way of alignment between IT and business is necessary The research aims to address two problems, namely, what factors are influencing business‐IT interface within organisations, and how the IT executive could contribute towards fusion fulfilling an organisational development (OD) role.

Design/methodology/approach

A triangular and qualitative research approach was followed, including a literature study, questionnaire and interview.

Findings

Results indicated a number of reasons leading to IT/business failure and also indicate how fusion can be created by fulfilling an OD role.

Research limitations/implications

Only companies in the Gauteng region, which is considered to be the economic heart of South Africa, have been included in the study. The small sample size might hinder the generalisation of the results and could be further extended.

Originality/value

The research indicates how a healthy business‐IT interface can be achieved through the fusion of the IT function and the rest of the business by integrating OD initiatives.