bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear Localization of PTEN Is Regulated by Ca2+ through a Tyrosil Phosphorylation–Independent Conformational Modification in Major Vault Protein
Authors: Minaguchi Takeo , Waite Kristin A. , Eng Charis 
Published: December 2006

Abstract
We have recently shown in MCF-7 cells that nuclear phosphatase and tensin homologue deleted on chromosome 10 (PTEN) down-regulates phosphorylation of p44/42 and cyclin D1 and induces G1 cell cycle arrest, whereas cytoplasmic PTEN down-regulates phosphorylation of Akt, up-regulates p27, and induces apoptosis. In this manner, nucleocytoplasmic partitioning of PTEN seems to differentially regulate the cell cycle and apoptosis. We have also reported that PTEN has nuclear localization signal–like sequences required for major vault protein (MVP)–mediated nuclear translocation. To date, several other proteins are reported to interact with MVP, including extracellular signal-regulated kinases and steroid receptors, suggesting that MVP is likely to be involved in signal transduction through nucleocytoplasmic transport. However, the exact mechanism of MVP-mediated nucleocytoplasmic shuttling remains elusive. PTEN reportedly interacts in vitro with the EF hand–like motif of MVP in a Ca2+-dependent manner. The current study shows that small interfering RNA–mediated MVP silencing decreases the nuclear localization of PTEN and increases phosphorylation of nuclear p44/42. We show in situ that PTEN-MVP interaction is Ca2+ dependent and is abolished by Mg2+. Nuclear localization of PTEN is decreased by increasing Ca2+ levels in culture medium in a dose-dependent manner. Ca2+ ionophore A23187 increases nuclear localization of PTEN and decreases phosphorylation of nuclear p44/42. Finally, we show that Ca2+-dependent PTEN-MVP interaction is not related to MVP's tyrosil phosphorylation but rather due to its conformational modification. Our observations suggest that Ca2+ regulates PTEN's nuclear entry through a tyrosil phosphorylation–independent conformational change in MVP. Collectively, our data present evidence of a novel crosstalk between the Ca2+ signaling–mediated regulation of the cell cycle and MVP-mediated nuclear PTEN localization and function. (Cancer Res 2006; 66(24): 11677-82)
Mitogenic Action of the Androgen Receptor Sensitizes Prostate Cancer Cells to Taxane-Based Cytotoxic Insult
Authors: Hess-Wilson Janet K. , Daly Hannah K. , Zagorski William A. , Montville Christopher P. , Knudsen Karen E. 
Published: December 2006

Abstract
Prostate cancer cells are dependent on androgen for growth and survival; as such, inhibition of androgen receptor (AR) activity is the first line of intervention for disseminated disease. Recently, specific cytotoxic agents have been shown to extend survival times in patients with advanced disease. Given the established ability of androgen to modify cell survival in prostate cancer cells, it is imperative to determine the effect of the hormonal environment on cytotoxic response. Here, we show that the response of prostate cancer cells to taxane-induced cell death is significantly enhanced by androgen stimulation in AR-positive, androgen-dependent prostate cancer cells. Similar results were observed on androgen-independent AR activation. By contrast, AR-positive yet androgen-independent or AR-negative cells were refractory to androgen influence on taxane function. The ability of androgen to potentiate taxane activity was dependent on its mitogenic capacity and was separable from overall AR activity, as coadministration of AR antagonists, G1 cyclin-dependent kinase inhibitors, or high-dose (growth inhibitory) androgen nullified the proapoptotic function of androgen. Observed induction of cell death was attributed to caspase-dependent apoptosis and correlated with p53 activation. Combined, these data indicate that the cytotoxic effects of taxanes are substantially influenced by the hormonal environment and/or status of AR activity in prostate cancer cells and provide the foundation for refinement and optimization of cytotoxic intervention in prostate cancer. (Cancer Res 2006; 66(24): 11998-2008)
Elevated E2F1 Inhibits Transcription of the Androgen Receptor in Metastatic Hormone-Resistant Prostate Cancer
Authors: Davis Joanne N. , Wojno Kirk J. , Daignault Stephanie , Hofer Matthias D. , Kuefer Rainer , Rubin Mark A. , Day Mark L. 
Published: December 2006

Abstract
Activation of E2F transcription factors, through disruption of the retinoblastoma (Rb) tumor-suppressor gene, is a key event in the development of many human cancers. Previously, we showed that homozygous deletion of Rb in a prostate tissue recombination model exhibits increased E2F activity, activation of E2F-target genes, and increased susceptibility to hormonal carcinogenesis. In this study, we examined the expression of E2F1 in 667 prostate tissue cores and compared it with the expression of the androgen receptor (AR), a marker of prostate epithelial differentiation, using tissue microarray analysis. We show that E2F1 expression is low in benign and localized prostate cancer, modestly elevated in metastatic lymph nodes from hormone-naïve patients, and significantly elevated in metastatic tissues from hormone-resistant prostate cancer patients (P = 0.0006). In contrast, strong AR expression was detected in benign prostate (83%), localized prostate cancer (100%), and lymph node metastasis (80%), but decreased to 40% in metastatic hormone-resistant prostate cancer (P = 0.004). Semiquantitative reverse transcription-PCR analysis showed elevated E2F1 mRNA levels and increased levels of the E2F-target genes dihyrofolate reductase and proliferating cell nuclear antigen in metastatic hormone–independent prostate cancer cases compared with benign tissues. To identify a role of E2F1 in hormone-independent prostate cancer, we examined whether E2F1 can regulate AR expression. We show that exogenous expression of E2F1 significantly inhibited AR mRNA and AR protein levels in prostate epithelial cells. E2F1 also inhibited an AR promoter-luciferase construct that was dependent on the transactivation domain of E2F1. Furthermore, using chromatin immunoprecipitation assays, we show that E2F1 and the pocket protein family members p107 and p130 bind to the AR promoter in vivo. Taken together, these results show that elevated E2F1, through its ability to repress AR transcription, may contribute to the progression of hormone-independent prostate cancer. (Cancer Res 2006; 66(24): 11897-906)
Tumor Necrosis Factor-α Is a Potent Endogenous Mutagen that Promotes Cellular Transformation
Authors: Yan Bin , Wang Huili , Rabbani Zahid N. , Zhao Yulin , Li Wenrong , Yuan Yuqing , Li Fang , Dewhirst Mark W. , Li Chuan-Yuan 
Published: December 2006

AbstractTumor necrosis factor-α (TNF-α) is an important inflammation cytokine without known direct effect on DNA. In this study, we found that TNF-α can cause DNA damages through reactive oxygen species. The mutagenic effect of TNF-α is comparable with that of ionizing radiation. TNF-α treatment in cultured cells resulted in increased gene mutations, gene amplification, micronuclei formation, and chromosomal instability. Antioxidants significantly reduced TNF-α–induced genetic damage. TNF-α also induced oxidative stress and nucleotide damages in mouse tissues in vivo. Moreover, TNF-α treatment alone led to increased malignant transformation of mouse embryo fibroblasts, which could be partially suppressed by antioxidants. As TNF-α is involved in chronic inflammatory diseases, such as chronic hepatitis, ulcerative colitis, and chronic skin ulcers, and these diseases predispose the patients to cancer development, our results suggest a novel pathway through which TNF-α promotes cancer development through induction of gene mutations, in addition to the previously reported mechanisms, in which nuclear factor-κB activation was implicated. (Cancer Res 2006; 66(24): 11565-70)
Cross-talk between G Protein–Coupled Receptor and Epidermal Growth Factor Receptor Signaling Pathways Contributes to Growth and Invasion of Head and Neck Squamous Cell Carcinoma
Authors: Thomas Sufi Mary , Bhola Neil E. , Zhang Qing , Contrucci Sarah C. , Wentzel Abbey L. , Freilino Maria L. , Gooding William E. , Siegfried Jill M. , Chan Daniel C. , Grandis Jennifer Rubin 
Published: December 2006

Abstract
G protein–coupled receptors (GPCR) and the epidermal growth factor receptor (EGFR) are often both overexpressed and contribute to the growth of cancers by activating autocrine pathways. GPCR ligands have been reported to trigger EGFR signaling via receptor cross-talk in cancer cells. Here, we show that GPCR ligands prostaglandin E2 (PGE2) and bradykinin (BK) activate EGFR signaling. Inhibition of EGFR using several strategies, including small-molecule inhibitors and an EGFR-specific antibody, resulted in partial attenuation of signaling downstream of EGFR. PGE2 and BK triggered EGFR signaling by increasing selective autocrine release of transforming growth factor-α (TGF-α). Inhibition of tumor necrosis factor-α–converting enzyme abrogated BK- or PGE2-mediated activation of EGFR signaling. Both PGE2 and BK stimulated head and neck squamous cell carcinoma (HNSCC) invasion via EGFR. Treatment of HNSCC cells with the BK antagonist CU201 resulted in growth inhibition. The combination of CU201 with the EGFR small-molecule inhibitor erlotinib resulted in additive inhibitory effects on HNSCC cell growth in vitro. Inhibition of the PGE2 synthesis pathway with sulindac induced HNSCC cytotoxicity at high doses (EC50, 620 μmol/L). However, combined inhibition of both EGFR with the tyrosine kinase inhibitor erlotinib and GPCR with sulindac at low doses of 6 and 310 μmol/L, respectively, resulted in synergistic killing of HNSCC tumor cells. Combined blockade of both EGFR and GPCRs may be a rational strategy to treat cancers, including HNSCC that shows cross-talk between GPCR and EGFR signaling pathways. (Cancer Res 2006; 66(24): 11831-9)
Endocytic Ark/Prk Kinases Play a Critical Role in Adriamycin Resistance in Both Yeast and Mammalian Cells
Authors: Takahashi Tsutomu , Furuchi Takemitsu , Naganuma Akira 
Published: December 2006

Abstract
To elucidate the mechanism of acquired resistance to Adriamycin, we searched for genes that, when overexpressed, render Saccharomyces cerevisiae resistant to Adriamycin. We identified AKL1, a gene of which the function is unknown but is considered, nonetheless, to be a member of the Ark/Prk kinase family, which is involved in the regulation of endocytosis, on the basis of its deduced amino acid sequence. Among tested members of the Ark/Prk kinase family (Ark1, Prk1, and Akl1), overexpressed Prk1 also conferred Adriamycin resistance on yeast cells. Prk1 is known to dissociate the Sla1/Pan1/End3 complex, which is involved in endocytosis, by phosphorylating Sla1 and Pan1 in the complex. We showed that Akl1 promotes phosphorylation of Pan1 in this complex and reduces the endocytic ability of the cell, as does Prk1. Sla1- and End3-defective yeast cells were also resistant to Adriamycin and overexpression of Akl1 in these defective cells did not increase the degree of Adriamycin resistance, suggesting that Akl1 might reduce Adriamycin toxicity by reducing the endocytic ability of cells via a mechanism that involves the Sla1/Pan1/End3 complex and the phosphorylation of Pan1. We also found that HEK293 cells that overexpressed AAK1, a member of the human Ark/Prk family, were Adriamycin resistant. Our findings suggest that endocytosis might be involved in the mechanism of Adriamycin toxicity in yeast and human cells. (Cancer Res 2006; 66(24): 11932-7)
KAP1, a Novel Substrate for PIKK Family Members, Colocalizes with Numerous Damage Response Factors at DNA Lesions
Authors: White David E. , Negorev Dmitri , Peng Hongzhuang , Ivanov Alexey V. , Maul Gerd G. , Rauscher Frank J. 
Published: December 2006

Abstract
The DNA damage response requires a coordinated nucleo-cytoplasmic cascade of events, which ultimately converge on damaged DNA packaged in chromatin. Few connections between the proteins that remodel chromatin and the proteins that mediate this damage response have been shown. We have investigated the DNA damage–induced phosphorylation of the KRAB-ZFP–associated protein 1 (KAP1), the dedicated corepressor for Krüppel-associated box (KRAB) zinc finger protein (ZFP) proteins. We show that KAP1 is rapidly phosphorylated following DNA damage by members of the phosphatidylinositol-3 kinase–like family of kinases. This phosphorylation occurs at a single amino acid residue that is conserved from mice to humans and is located adjacent to the bromodomain, suggesting that it may regulate chromatin recognition by that module. Phosphorylated KAP1 rapidly localizes to sites of DNA strand breaks in the nucleus in response to ionizing radiation. This discovery provides a novel link between chromatin-mediated transcriptional repression and the recognition/repair of DNA, which must be accomplished by the cellular DNA damage response. (Cancer Res 2006; 66(24): 11594-9)
Seasonal Prediction of Sea Surface Temperature Anomalies Using a Suite of 13 Coupled Atmosphere–Ocean Models
Authors: Krishnamurti T. N. , Chakraborty Arindam , Krishnamurti Ruby , Dewar William K. , Clayson Carol Anne 
Published: December 2006

Abstract
Improved seasonal prediction of sea surface temperature (SST) anomalies over the global oceans is the theme of this paper. Using 13 state-of-the-art coupled global atmosphere–ocean models and 13 yr of seasonal forecasts, the performance of individual models, the ensemble mean, the bias-removed ensemble mean, and the Florida State University (FSU) superensemble are compared. A total of 23 400 seasonal forecasts based on 1-month lead times were available for this study. Evaluation metrics include both deterministic and probabilistic skill measures, such as verification of anomalies based on model and observed climatology, time series of specific climate indices, standard deterministic ensemble mean scores including anomaly correlations, root-mean-square (RMS) errors, and probabilistic skill measures such as equitable threat scores for seasonal SST forecasts. This study also illustrates the Niño-3.4 SST forecast skill for the equatorial Pacific Ocean and for the dipole index for the Indian Ocean. The relative skills of total SST fields and of the SST anomalies from the 13 coupled atmosphere–ocean models are presented. Comparisons of superensemble-based seasonal forecasts with recent studies on SST anomaly forecasts are also shown.
Overall it is found that the multimodel superensemble forecasts are characterized by considerable RMS error reductions and increased accuracy in the spatial distribution of SST. Superensemble SST skill also persists for El Niño and La Niña forecasts since the large comparative skill of the superensemble is retained across such years. Real-time forecasts of seasonal sea surface temperature anomalies appear to be possible.
Seasonal-to-Decadal Predictability and Prediction of North American Climate—The Atlantic Influence
Authors: Van den Dool H. M. , Peng Peitao , Johansson Åke , Chelliah Muthuvel , Shabbar Amir , Saha Suranjana 
Published: December 2006

Abstract
The question of the impact of the Atlantic on North American (NA) seasonal prediction skill and predictability is examined. Basic material is collected from the literature, a review of seasonal forecast procedures in Canada and the United States, and some fresh calculations using the NCEP–NCAR reanalysis data.
The general impression is one of low predictability (due to the Atlantic) for seasonal mean surface temperature and precipitation over NA. Predictability may be slightly better in the Caribbean and the (sub)tropical Americas, even for precipitation. The NAO is widely seen as an agent making the Atlantic influence felt in NA. While the NAO is well established in most months, its prediction skill is limited. Year-round evidence for an equatorially displaced version of the NAO (named ED_NAO) carrying a good fraction of the variance is also found.
In general the predictability from the Pacific is thought to dominate over that from the Atlantic sector, which explains the minimal number of reported Atmospheric Model Intercomparison Project (AMIP) runs that explore Atlantic-only impacts. Caveats are noted as to the question of the influence of a single predictor in a nonlinear environment with many predictors. Skill of a new one-tier global coupled atmosphere–ocean model system at NCEP is reviewed; limited skill is found in midlatitudes and there is modest predictability to look forward to.
There are several signs of enthusiasm in the community about using “trends” (low-frequency variations): (a) seasonal forecast tools include persistence of last 10 years’ averaged anomaly (relative to the official 30-yr climatology), (b) hurricane forecasts are based largely on recognizing a global multidecadal mode (which is similar to an Atlantic trend mode in SST), and (c) two recent papers, one empirical and one modeling, giving equal roles to the (North) Pacific and Atlantic in “explaining” variations in drought frequency over NA on a 20 yr or longer time scale during the twentieth century.
The Physical Basis for Predicting Atlantic Sector Seasonal-to-Interannual Climate Variability*
Authors: Kushnir Yochanan , Robinson Walter A. , Chang Ping , Robertson Andrew W. 
Published: December 2006

Abstract
This paper reviews the observational and theoretical basis for the prediction of seasonal-to-interannual (S/I) climate variability in the Atlantic sector. The emphasis is on the large-scale picture rather than on regional details. The paper is divided into two main parts: a discussion of the predictability of the North Atlantic Oscillation (NAO)—the dominant pattern of variability in the North Atlantic—and a review of the tropical Atlantic prediction problem. The remote effects of El Niño are also mentioned as an important factor in Atlantic climate variability. Only a brief discussion is provided on the subject of South Atlantic climate predictability.
Because of its chaotic dynamical nature, the NAO and its related rainfall and temperature variability, while highly significant over Europe and North America, are largely unpredictable. This also affects the predictive skill over the tropical Atlantic, because the NAO interferes with the remote influence of El Niño. That said, there appears to be an insufficiently understood, marginal signal in the NAO behavior that may be predictable and thus useful to certain end users. It is manifested in the deviation of the NAO temporal behavior from first-order autoregressive behavior.
Tropical Atlantic climate variability centers on the sensitivity of the marine ITCZ to remote forcing from the equatorial Pacific and interactions with underlying sea surface temperature (SST) variability. Both mechanisms are potentially predictable—that is, given the underlying SSTs and the strength of El Niño, one could determine with a high degree of skill the anomalies in ITCZ position and intensity. However, local SSTs are easily affected by largely unpredictable North and South Atlantic phenomena, such as the NAO. In addition, the local ocean–atmosphere coupling in the Atlantic acts on relatively short time scales. Thus, in reality the level of skill indicated by forced model simulations are difficult to achieve. The use of coupled models may improve the prospects of tropical Atlantic prediction.
Seasonal-to-Decadal Predictability and Prediction of South American Climate
Authors: Nobre P. , Marengo J. A. , Cavalcanti I. F. A. , Obregon G. , Barros V. , Camilloni I. , Campos N. , Ferreira A. G. 
Published: December 2006

Abstract
The dynamical basis for seasonal to decadal climate predictions and predictability over South America is reviewed. It is shown that, while global tropical SSTs affect both predictability and predictions over South America, the current lack of SST predictability over the tropical Atlantic represents a limiting factor to seasonal climate predictions over some parts of the continent. The model’s skill varies with the continental region: the highest skill is found in the “Nordeste” region and the lowest skill over southeastern Brazil. It is also suggested that current two-tier approaches to predict seasonal climate variations might represent a major limitation to forecast coupled ocean–atmosphere phenomena like the South Atlantic convergence zone. Also discussed are the possible effects of global climate change on regional predictability of seasonal climate.
Climate-Driven Variability and Trends in Mountain Snowpack in Western North America*
Authors: Mote Philip W. 
Published: December 2006

Abstract
Records of 1 April snow water equivalent (SWE) are examined here using multiple linear regression against reference time series of temperature and precipitation. This method permits 1) an examination of the separate roles of temperature and precipitation in determining the trends in SWE; 2) an estimation of the sensitivity of SWE to warming trends, and its distribution across western North America and as a function of elevation; and 3) inferences about responses of SWE to future warming. These results emphasize the sensitivity to warming of the mountains of northern California and the Cascades of Oregon and Washington. In addition, the contribution of modes of Pacific climate variability is examined and found to be responsible for about 10%–60% of the trends in SWE, depending on the period of record and climate index.
Clay minerals and bauxitic minerals. A review and classification based on a statistical method
Authors: Tomkeieff S. I. 
Published: December 2006

SummaryA statistical study of clay and bauxitic minerals, which consisted of plotting all available analyses of these minerals on two triangular diagrams (figs. 1 and 7) and constructing frequency curves for the cardinal ratios, led to a classification of these minerals on a purely chemical basis. The suggestion is also made that among substances claimed to be minerals we can select only a few as belonging to definite mineral species, and that the others are probably mixtures of these selected minerals, or their hydration products, or colloidal hydrates of variable composition. The distinct crystalline mineral species thus singled out are as follows :Besides these minerals, other substances, such as termierite, anauxite, allophane, &c., are suggested as probable species, without, however, any clear statistical evidence. The bentonitic minerals, not belonging strictly to the pure hydrous aluminium silicates, are placed in a separate group.In conclusion, I should like to thank Dr. G. Hickling and Mr. G. S. Mockler for reading the MS. of this paper and for their valuable suggestions.
An improved polarizing microscope IV. The Fedorov Stage (Three-Axis)
Authors: Hallimond A. F. , Taylor E. Wilfred 
Published: December 2006

In the microscope designed by G. B. Amici (1844), which seems to be the very earliest polarizing microscope, the stage already possessed not only graduated concentric rotation, but also a horizontal tilting axis. It was, in fact, a built-in two-axis universal stage. Glass hemispheres were introduced at a much later date by W. G. Adams (1875) for use in a specially designed conoscope, but the Adams stage seems to have been little used (see, however, H. Schumann, 1949).The two-axis stage as now known was designed by E. S. Fedorov (1893) and was soon followed by other forms. It is a curious fact that the four-axis stage was used almost from the beginning, though it was for some time known as the three-axis stage.