bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parental region of birth, socio‐economic status and infants' exposure to second‐hand smoke
Authors: Wallby Thomas , Hjern Anders 
Published: August 2008

AbstractAim: To investigate the impact of parental region of birth on the risk of exposure to second‐hand smoke for infants.Methods: The smoking habits, according to child health records, of parents of 14 431 infants in Uppsala county, Sweden, born during 1997–2001, were investigated with logistic regression in the presence of socio‐economic and demographic confounders from national registers.Results: Fathers born outside of Sweden smoked more often than Swedish‐born fathers irrespective of region of birth (adjusted odds ratios [ORs] 1.77–3.02). Mothers born in Africa (adjusted OR 0.29, 95% CI 0.15–0.58) and Asia (adjusted OR 0.53, 95% CI 0.40–0.70) smoked less often than Swedish‐born mothers. Single parenthood, low income and mother's age ≤24 years increased the risk for parental smoking.Conclusion: The present study indicates that the risk of smoking in immigrant parents of infants is influenced by the smoking patterns in the region of birth. Smoke cessation interventions targeting fathers are particularly important in immigrant‐dense neighbourhoods in Sweden.
On buckyonions as an interstellar grain component
Authors: Li Aigen , Chen J. H. , Li M. P. , Shi Q. J. , Wang Y. J. 
Published: August 2008

Abstract
The carrier of the 2175 Å interstellar extinction feature remains unidentified since its first detection over 40 yr ago. In recent years, carbon buckyonions have been proposed as a carrier of this feature, based on the close similarity between the electronic transition spectra of buckyonions and the 2175 Å interstellar feature. We examine this hypothesis by modelling the interstellar extinction with buckyonions as a dust component. It is found that dust models containing buckyonions (in addition to amorphous silicates, polycyclic aromatic hydrocarbon molecules, graphite) can closely reproduce the observed interstellar extinction curve. To further test this hypothesis, we call for experimental measurements and/or theoretical calculations of the infrared vibrational spectra of hydrogenated buckyonions. By comparing the infrared emission spectra predicted for buckyonions vibrationally excited by the interstellar radiation with the observed emission spectra of the diffuse interstellar medium, we will be able to derive (or place an upper limit on) the abundance of interstellar buckyonions.
Frege on Definitions
Authors: Shieh Sanford 
Published: August 2008

AbstractThis article treats three aspects of Frege's discussions of definitions. First, I survey Frege's main criticisms of definitions in mathematics. Second, I consider Frege's apparent change of mind on the legitimacy of contextual definitions and its significance for recent neo‐Fregean logicism. In the remainder of the article I discuss a critical question about the definitions on which Frege's proofs of the laws of arithmetic depend: do the logical structures of the definientia reflect the understanding of arithmetical terms prevailing prior to Frege's analyses? Unless they do, it is unclear how Frege's proofs demonstrate the analyticity of the arithmetic in use before logicism. Yet, especially in late writings, Frege characterizes definitions as arbitrary stipulations of the senses or references of expressions unrelated to pre‐definitional understanding. I conclude by examining some options for conceiving of the status of Frege's logicism in light of this apparent tension, and outline a suggestion for a philosophically fruitful way of resolving this tension.
Protein kinase A modulates A‐type potassium currents of larval zebrafish (Danio rerio) white muscle fibres
Authors: Coutts C. A. , Balt L. N. , Ali D. W. 
Published: August 2008

AbstractAims:  Potassium (K+) channels are involved in regulating cell excitability and action potential shape. To our knowledge, very little is known about the modulation of A‐type K+ currents in skeletal muscle fibres. Therefore, we sought to determine whether K+ currents of zebrafish white skeletal muscle were modulated by protein kinase A (PKA).Methods:  Pharmacology and whole‐cell patch clamp were used to examine A‐type K+ currents and action potentials associated with zebrafish white skeletal muscle fibres.Results:  Activation of PKA by a combination of forskolin + 3‐isobutyl‐1‐methylxanthine (Fsk + IBMX) decreased the peak current density by ∼60% and altered the inactivation kinetics of A‐type K+ currents. The specific PKA inhibitor H‐89 partially blocked the Fsk + IBMX‐induced reduction in peak current density, but had no effect on the change in decay kinetics. Fsk + IBMX treatment did not shift the activation curve, but it significantly reduced the slope factor of activation. Activation of PKA by Fsk + IBMX resulted in a negative shift in the V50 of inactivation. H‐89 prevented all Fsk + IBMX‐induced changes in the steady‐state properties of K+ currents. Application of Fsk + IBMX increased action potential amplitude, but had no significant effect on action potential threshold, half width or recovery rate, when fibres were depolarized with single pulses, paired pulses or with high‐frequency stimuli.Conclusion:  PKA modulates the A‐type K+ current in zebrafish skeletal muscle and affects action potential properties. Our results provide new insights into the role of A‐type K+ channels in muscle physiology.
Dynamics of Trace Element Concentration During Development and Excitotoxic Cell Death in the Cerebellum of Lurcher Mutant Mice
Authors: Bäurle Jörg , Kučera Jan , Frischmuth Sabine , Lambertz Manfred , Kranda Karel 
Published: August 2008

AbstractElevated concentrations of Zn, Cu and Fe, observed in biopsied or post‐mortem tissue from diseased human brains, have often been considered as some of the major factors in the etiology of excitotoxic neuronal death but without any direct evidence for the causal role of metals. Although elevated metal concentrations that precede or coincide with the onset of neurodegeneration may provide such evidence, the dynamics of metal concentrations during excitotoxic cell death has never been established. Hence, we measured time‐resolved Zn, Cu and Fe concentrations during the course of excitotoxic cell death in the Lurcher (Lc/+) mutant mouse with neutron activation analysis. In the Lc/+ cerebellum, Fe and Zn but not Cu concentrations were substantially lower than in normal cerebellum before the onset of neurodegeneration; then the concentration of all three metals doubled during excitotoxic Purkinje cell (PC) death, before stabilizing at abnormally high levels at the end of cell death progression. The rise in metal concentrations followed the onset and progression of PC loss after a delay of almost a week. This temporal correlation between neurodegenerative progression and metal concentrations indicates that elevated metal concentrations are the consequence of metabolic overload and glial activation during excitotoxicity rather than the primary cause of PC death.
On the Motivational Primacy of the Individual Self: ‘I’ Is Stronger than ‘We’
Authors: Gaertner Lowell , Sedikides Constantine , O'Mara Erin M. 
Published: August 2008

AbstractThe self‐concept is dynamic, with momentary definition shifting from a representation of self as a unique and independent social agent to an undifferentiated and interchangeable group member. Indeed, the individual self and collective self are fundamental components of the self‐concept, with each being important and meaningful to human experience. However, are those selves equally important and meaningful? We review a program of research empirically testing three competing hypotheses that suggests that the motivational core of human experience is (a) the individual self, (b) the collective self, or (c) determined by contextual factors that make a given self momentarily accessible. The research furnished unanimous and consistent evidence that the individual self is the motivationally primary form of self‐definition.
Memantine Protects Against Secondary Neuronal Degeneration in Lateral Geniculate Nucleus and Superior Colliculus after Retinal Damage in Mice
Authors: Ito Yasushi , Nakamura Shinsuke , Tanaka Hirotaka , Shimazawa Masamitsu , Araie Makoto , Hara Hideaki 
Published: August 2008

The purpose of this study, on mice, was to determine whether memantine, a glutamate‐receptor antagonist of the N‐methyl‐d‐aspartate (NMDA) subtype, protects against neuronal degeneration in the dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC) after the induction of retinal damage by intravitreal injection of NMDA.NMDA (20 mM/2 μl) was injected into the vitreous body of the left eye in mice (day 0). To evaluate the neuroprotective effect of memantine, mice were assigned to one of two memantine‐treated groups: receiving a daily administration of memantine at 30 mg/kg/day, p.o. either from day 0 (administered at 1 h before NMDA injection) to day 90 (pretreated group) or from day 7 to day 90 (post‐treated group).The pretreated group exhibited significant suppression of the retinal damage induced by intravitreal injection of NMDA and significant prevention of transsynaptic neuronal degeneration in the dLGN and SC on the contralateral side. Although the mice of the post‐treated group displayed no reversion of such retinal damage, they did exhibit protection against neuronal degeneration in the LGN and SC on the contralateral side. These data indicate that memantine can protect against transsynaptic neuronal degeneration in the murine brain (LGN and SC) even if treatment is begun after retinal ganglion cell (RGC) death has started.Memantine protects against the secondary neuronal degeneration in brain regions in the visual pathway that occurs after retinal damage in mice.
p70 S6 Kinase Promotes Epithelial to Mesenchymal Transition through Snail Induction in Ovarian Cancer Cells
Authors: Pon Yuen L. , Zhou Hong Y. , Cheung Annie N.Y. , Ngan Hextan Y.S. , Wong Alice S.T. 
Published: August 2008

Abstract
p70 S6 kinase (p70S6K) is a downstream effector of phosphatidylinositol 3-kinase and is frequently activated in human ovarian cancer. Here we show that p70S6K functions in epithelial to mesenchymal transition (EMT) responsible for the acquisition of invasiveness during tumor progression. This tumorigenic activity is associated with the ability of p70S6K to repress E-cadherin through the up-regulation of Snail. p70S6K activation induced phenotypic changes consistent with EMT in ovarian cancer cells: The cells lost epithelial cell morphology, acquired fibroblast-like properties, and showed reduced intercellular adhesion. Western blot showed that p70S6K activation led to decreased expression of the epithelial marker E-cadherin and increased expression of mesenchymal markers N-cadherin and vimentin. Inhibition of p70S6K by a specific inhibitor or small interfering RNA reversed the shift of EMT markers. Importantly, p70S6K activation also stimulated the expression of Snail, a repressor of E-cadherin and an inducer of EMT, but not other family members such as Slug. This induction of Snail was regulated at multiple levels by increasing transcription, inhibiting protein degradation, and enhancing nuclear localization of Snail. RNA interference–mediated knockdown of Snail suppressed p70S6K-induced EMT, confirming that the effect was Snail specific. Furthermore, phospho (active)-p70S6K staining correlated with higher tumor grade. We also showed a significant positive correlation between p70S6K activation and Snail expression in ovarian cancer tissues. These results indicate that p70S6K may play a critical role in tumor progression in ovarian cancer through the induction of EMT. Targeting p70S6K may thus be a useful strategy to impede cancer cell invasion and metastasis. [Cancer Res 2008;68(16):6524–32]
Re-Expression of Transcription FactorATF5in Hepatocellular Carcinoma Induces G2-M Arrest
Authors: Gho Jennifer W-M. , Ip Wai-Ki , Chan Kathy Y-Y. , Law Priscilla T-Y. , Lai Paul B-S. , Wong Nathalie 
Published: August 2008

AbstractTranscription factors represent an important class of genes that play key roles in controlling cellular proliferation, cell cycle modulation, and attractive targets for cancer therapy. Here, we report on the novel finding of common ATF5 down-regulations in hepatocellular carcinoma (HCC), a highly malignant tumor with a dismal clinical course. Array-based mapping in HCC highlighted a high and consistent incidence of transcription factor ATF5 repressions on regional chr.19q13. By quantitative reverse transcription-PCR, profound down-regulations of ATF5 were further suggested in 78% of HCC tumors (60 of 77 cases) compared to their adjacent nontumoral liver (P = 0.0004). Restoration of ATF5 expression in 3 nonexpressing HCC cell lines demonstrated a consistent growth inhibitory effect (P &lt; 0.029) but minimal induction on cellular apoptosis. Subsequent flow cytometric investigations revealed a G2-M cell cycle arrest in HCC cells that were ectopically transfected with ATF5 (P &lt; 0.002). The differential expressed genes from the functional effects of ATF5 were examined by array profiling. Over a hundred genes were identified, among which ID1 contains the ATF/CREB target binding sequences within its promoter region. An inverse relationship between ATF5 expressions with ID1 transcriptions was verified in HCC (P = 0.019), and a direct interaction of ATF5 on the promoter of ID1 was further demonstrated from electromobility shift assay. Examination of causal events underlying the silencing of ATF5 in HCC suggested copy number losses, promoter hypermethylation, histone deacetylation, and DNA mutations to be the likely inactivating mechanisms. In conclusion, our finding supports a tumor suppressive role for ATF5 in HCC, and highlighted ID1 as a potential downstream target. [Cancer Res 2008;68(16):6743–51]
CHR-2797: An Antiproliferative Aminopeptidase Inhibitor that Leads to Amino Acid Deprivation in Human Leukemic Cells
Authors: Krige David , Needham Lindsey A. , Bawden Lindsay J. , Flores Nicolas , Farmer Hannah , Miles Lauren E.C. , Stone Erica , Callaghan Juliana , Chandler Stephen , Clark Vanessa L. , Kirwin-Jones Patricia , Legris Valérie , Owen Jo , Patel Thakor , Wood Steve , Box Gary , Laber David , Odedra Rajesh , Wright Annette , Wood L. Michael , Eccles Suzanne A. , Bone Elisabeth A. , Ayscough Andrew , Drummond Alan H. 
Published: August 2008

Abstract
CHR-2797 is a novel metalloenzyme inhibitor that is converted into a pharmacologically active acid product (CHR-79888) inside cells. CHR-79888 is a potent inhibitor of a number of intracellular aminopeptidases, including leucine aminopeptidase. CHR-2797 exerts antiproliferative effects against a range of tumor cell lines in vitro and in vivo and shows selectivity for transformed over nontransformed cells. Its antiproliferative effects are at least 300 times more potent than the prototypical aminopeptidase inhibitor, bestatin. However, the mechanism by which inhibition of these enzymes leads to proliferative changes is not understood. Gene expression microarrays were used to profile changes in mRNA expression levels in the human promyelocytic leukemia cell line HL-60 treated with CHR-2797. This analysis showed that CHR-2797 treatment induced a transcriptional response indicative of amino acid depletion, the amino acid deprivation response, which involves up-regulation of amino acid synthetic genes, transporters, and tRNA synthetases. These changes were confirmed in other leukemic cell lines sensitive to the antiproliferative effects of CHR-2797. Furthermore, CHR-2797 treatment inhibited phosphorylation of mTOR substrates and reduced protein synthesis in HL-60 cells, both also indicative of amino acid depletion. Treatment with CHR-2797 led to an increase in the concentration of intracellular small peptides, the substrates of aminopeptidases. It is suggested that aminopeptidase inhibitors, such as CHR-2797 and bestatin, deplete sensitive tumor cells of amino acids by blocking protein recycling, and this generates an antiproliferative effect. CHR-2797 is orally bioavailable and currently undergoing phase II clinical investigation in the treatment of myeloid leukemia. [Cancer Res 2008;68(16):6669–79]
Leptin Enhances Cholangiocarcinoma Cell Growth
Authors: Fava Giammarco , Alpini Gianfranco , Rychlicki Chiara , Saccomanno Stefania , DeMorrow Sharon , Trozzi Luciano , Candelaresi Cinzia , Venter Julie , Di Sario Antonio , Marzioni Marco , Bearzi Italo , Glaser Shannon , Alvaro Domenico , Marucci Luca , Francis Heather , Svegliati-Baroni Gianluca , Benedetti Antonio 
Published: August 2008

Abstract
Cholangiocarcinoma is a strongly aggressive malignancy with a very poor prognosis. Effective therapeutic strategies are lacking because molecular mechanisms regulating cholangiocarcinoma cell growth are unknown. Furthermore, experimental in vivo animal models useful to study the pathophysiologic mechanisms of malignant cholangiocytes are lacking. Leptin, the hormone regulating caloric homeostasis, which is increased in obese patients, stimulates the growth of several cancers, such as hepatocellular carcinoma. The aim of this study was to define if leptin stimulates cholangiocarcinoma growth. We determined the expression of leptin receptors in normal and malignant human cholangiocytes. Effects on intrahepatic cholangiocarcinoma (HuH-28) cell proliferation, migration, and apoptosis of the in vitro exposure to leptin, together with the intracellular pathways, were then studied. Moreover, cholangiocarcinoma was experimentally induced in obese fa/fa Zucker rats, a genetically established animal species with faulty leptin receptors, and in their littermates by chronic feeding with thioacetamide, a potent carcinogen. After 24 weeks, the effect of leptin on cholangiocarcinoma development and growth was assessed. Normal and malignant human cholangiocytes express leptin receptors. Leptin increased the proliferation and the metastatic potential of cholangiocarcinoma cells in vitro through a signal transducers and activators of transcription 3–dependent activation of extracellular signal-regulated kinase 1/2. Leptin increased the growth and migration, and was antiapoptotic for cholangiocarcinoma cells. Moreover, the loss of leptin function reduced the development and the growth of cholangiocarcinoma. The experimental carcinogenesis model induced by thioacetamide administration is a valid and reproducible method to study cholangiocarcinoma pathobiology. Modulation of the leptin-mediated signal could be considered a valid tool for the prevention and treatment of cholangiocarcinoma. [Cancer Res 2008;68(16):6752–61]
Identification of a Novel Recepteur d'Origine Nantais/c-Met Small-Molecule Kinase Inhibitor with Antitumor Activity In vivo
Authors: Zhang Yihong , Kaplan-Lefko Paula J. , Rex Karen , Yang Yajing , Moriguchi Jodi , Osgood Tao , Mattson Bethany , Coxon Angela , Reese Monica , Kim Tae-Seong , Lin Jasmine , Chen April , Burgess Teresa L. , Dussault Isabelle 
Published: August 2008

Abstract
Recepteur d'origine nantais (RON) is a receptor tyrosine kinase closely related to c-Met. Both receptors are involved in cell proliferation, migration, and invasion, and there is evidence that both are deregulated in cancer. Receptor overexpression has been most frequently described, but other mechanisms can lead to the oncogenic activation of RON and c-Met. They include activating mutations or gene amplification for c-Met and constitutively active splicing variants for RON. We identified a novel inhibitor of RON and c-Met, compound I, and characterized its in vitro and in vivo activities. Compound I selectively and potently inhibited the kinase activity of RON and c-Met with IC50s of 9 and 4 nmol/L, respectively. Compound I inhibited hepatocyte growth factor–mediated and macrophage-stimulating protein–mediated signaling and cell migration in a dose-dependent manner. Compound I was tested in vivo in xenograft models that either were dependent on c-Met or expressed a constitutively active form of RON (RONΔ160 in HT-29). Compound I caused complete tumor growth inhibition in NIH3T3 TPR-Met and U-87 MG xenografts but showed only partial inhibition in HT-29 xenografts. The effect of compound I in HT-29 xenografts is consistent with the expression of the activating b-Raf V600E mutation, which activates the mitogen-activated protein kinase pathway downstream of RON. Importantly, tumor growth inhibition correlated with the inhibition of c-Met–dependent and RON-dependent signaling in tumors. Taken together, our results suggest that a small-molecule dual inhibitor of RON/c-Met has the potential to inhibit tumor growth and could therefore be useful for the treatment of patients with cancers where RON and/or c-Met are activated. [Cancer Res 2008;68(16):6680–7]
The Nuclear Factor-κB Pathway Controls the Progression of Prostate Cancer to Androgen-Independent Growth
Authors: Jin Ren Jie , Lho Yongsoo , Connelly Linda , Wang Yongqing , Yu Xiuping , Saint Jean Leshana , Case Thomas C. , Ellwood-Yen Katharine , Sawyers Charles L. , Bhowmick Neil A. , Blackwell Timothy S. , Yull Fiona E. , Matusik Robert J. 
Published: August 2008

Abstract
Typically, the initial response of a prostate cancer patient to androgen ablation therapy is regression of the disease. However, the tumor will progress to an “androgen-independent” stage that results in renewed growth and spread of the cancer. Both nuclear factor-κB (NF-κB) expression and neuroendocrine differentiation predict poor prognosis, but their precise contribution to prostate cancer progression is unknown. This report shows that secretory proteins from neuroendocrine cells will activate the NF-κB pathway in LNCaP cells, resulting in increased levels of active androgen receptor (AR). By blocking NF-κB signaling in vitro, AR activation is inhibited. In addition, the continuous activation of NF-κB signaling in vivo by the absence of the IκBα inhibitor prevents regression of the prostate after castration by sustaining high levels of nuclear AR and maintaining differentiated function and continued proliferation of the epithelium. Furthermore, the NF-κB pathway was activated in the ARR2PB-myc-PAI (Hi-myc) mouse prostate by cross-breeding into a IκBα+/− haploid insufficient line. After castration, the mouse prostate cancer continued to proliferate. These results indicate that activation of NF-κB is sufficient to maintain androgen-independent growth of prostate and prostate cancer by regulating AR action. Thus, the NF-κB pathway may be a potential target for therapy against androgen-independent prostate cancer. [Cancer Res 2008;68(16):6762–9]