bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutrition and Human Cancer
Authors: HILL MICHAEL J.
Published: December 2006

ABSTRACT: It is now widely accepted that nutrition is as important as tobacco as a cause of human cancer. However, whereas we can dispense with tobacco with general benefit to health, we cannot do without food. It is, therefore, necessary to determine the pattern of nutrition that is associated with the lowest overall cancer risk. This is made more difficult by the fact that some kinds of cancer are associated with overnutrition (e.g., that of the colon, breast, and prostate) and some with poor nutrition (e.g., esophagus, stomach, and liver). The tools to determine this are epidemiology, animal models, in vitro studies, and dietary intervention studies. These all have their strengths and weaknesses, which will be discussed.

It is concluded that the major nutrition factors associated with increased cancer risk are: (a) overweight [as a surrogate for excess energy intake]; (b) low intake of fresh fruit; (c) low intake intake of vegetables; and (d) low intake of whole‐grain cereals. There have been many other associations with cancer at specific sites noted in the literature. However, it is the overall risk of cancer that must be minimized.
The War on Cancer: A Reviewa
Authors: SPORN MICHAEL B.
Published: December 2006

ABSTRACT: Twenty‐five years ago, then President Nixon “declared war” on cancer. In this personal commentary, the war is reviewed. There have been obvious triumphs, for instance in cure of acute lymphocytic leukemia and other forms of childhood cancer, Hodgkin's disease, and testicular cancer. However, substantial advances in molecular oncology have yet to impinge on mortality statistics. Too many adults still die from common epithelial cancers. Failure to appreciate that local invasion and distant metastasis rather then cell proliferation itself are lethal, obsession with cure of advanced disease rather than prevention of early disease, and neglect of the need to arrest preneoplastic lesions, may all have served to make victory elusive.
Viral Theory for Ménière's Disease and Endolymphatic Hydrops: Overview and New Therapeutic Options for Viral Labyrinthitis
Authors: ARENBERG I. KAUFMAN , LEMKE CHRISTINE , SHAMBAUGH GEORGE E.
Published: December 2006

In six cases of Ménière's disease, the sac wall was definitely fibrotic and ischemic and the epithelium either absent or markedly altered. There was partial or complete obliteration of the lumen in every case. In cases where the duct was not seen by polytomography, the epithelium was usually absent in the sac. Since none of these patients had a history of suppurative otitis media or mastoiditis, the most likely etiology for the changes observed is an old viral labyrinthitis affecting especially or perhaps primarily the duct and sac, destroying or markedly impairing the normal resorption of endolymph.

—George E. Shambaugh and I. Kaufman Arenberg
Insights into the Neurobiology of Impulsive Behavior from Serotonin Receptor Knockout Mice
Authors: BRUNNER DANI , HEN RENÉ
Published: December 2006

ABSTRACT: Although the concept of impulsivity has proved useful in human and animal studies of addiction, violent aggression, and violent suicide, and has been recognized as an important component of human behavior, little research has been done to understand the underlying psychobiological mechanisms. We explore the concept of impulsivity and its relation with the neurotransmitter serotonin in the context of aggressive behavior and behavior associated with positive reinforcement using a knockout mouse that lacks one of the serotonin receptors, the 5‐HT1B receptor. This knockou mouse shows more impulsive aggression, acquires cocaine self‐administration faster, and drinks more alcohol than the corresponding wild‐type control. We show that the impulsive characteristics of these mice are not due to change in cognitive functions: in a cognitive task involving a choice between a small immediate one and a larger more delayed reward, knockout mice showed intact choice and timing capabilities and good discrimination of reward amounts. Thus, this mouse may prove an animal model of addiction and motor impulsivity.
Tenascin-C Stimulates Glioma Cell Invasion through Matrix Metalloproteinase-12
Authors: Sarkar Susobhan , Nuttall Robert K. , Liu Shuhong , Edwards Dylan R. , Yong V. Wee
Published: December 2006

The capacity of glioma cells to invade extensively within the central nervous system is a major cause of the high morbidity rate of primary malignant brain tumors. Glioma cell invasion involves the attachment of tumor cells to extracellular matrix (ECM), degradation of ECM components, and subsequent penetration into adjacent brain structures. These processes are accomplished in part by matrix metalloproteinases (MMP) within a three-dimensional milieu of the brain parenchyma. As the majority of studies have used a two-dimensional monolayer culture system, we have used a three-dimensional matrix of collagen type I gel to address glioma-secreted proteases, ECM, and invasiveness of glioma cells. We show that in a three-dimensional collagen type I matrix, the presence of tenascin-C, commonly elevated in high-grade gliomas, increased the invasiveness of glioma cells. The tenascin-C–mediated invasiveness was blocked by metalloproteinase inhibitors, but this did not involve the gelatinases (MMP-2 and MMP-9) commonly implicated in two-dimensional glioma growth. A thorough analysis of 21 MMPs and six members of a disintegrin and metalloproteinase domain showed that MMP-12 was increased in gliomas by tenascin-C in three-dimensional matrix. Furthermore, examinations of resected specimens revealed high MMP-12 levels in the high-grade glioblastoma multiforme tumors. Finally, a function-blocking antibody as well as small interfering RNA to MMP-12 attenuated the tenascin-C–stimulated glioma invasion. These results identify a new factor, MMP-12, in regulating glioma invasiveness through interaction with tenascin-C. (Cancer Res 2006; 66(24): 11771-80)
Cross-talk between Peroxisome Proliferator-Activated Receptor δ and Cytosolic Phospholipase A2α/Cyclooxygenase-2/Prostaglandin E2 Signaling Pathways in Human Hepatocellular Carcinoma Cells
Authors: Xu Lihong , Han Chang , Lim Kyu , Wu Tong
Published: December 2006

Peroxisome proliferator-activated receptor δ (PPARδ) is a nuclear transcription factor that is recently implicated in tumorigenesis besides lipid metabolism. This study describes the cross-talk between the PPARδ and prostaglandin (PG) signaling pathways that coordinately regulate human hepatocellular carcinoma (HCC) cell growth. Activation of PPARδ by its pharmacologic ligand, GW501516, enhanced the growth of three human HCC cell lines (HuH7, HepG2, and Hep3B), whereas inhibition of PPARδ by small interfering RNA prevented growth. PPARδ activation up-regulates the expression of cyclooxygenase (COX)-2, a rate-limiting enzyme for PG synthesis, and tumor growth. PPARδ activation or PGE2 treatment also induced the phosphorylation of cytosolic phospholipase A2α (cPLA2α), a key enzyme that releases arachidonic acid substrate for PG production via COX. Activation of cPLA2α by the calcium ionophore A23187 enhanced PPARδ binding to PPARδ response element (DRE) and increased PPARδ reporter activity, which was blocked by the selective cPLA2α inhibitors. Consistent with this, addition of arachidonic acid to isolated nuclear extracts enhanced the binding of PPARδ to DRE in vitro, suggesting a direct role of arachidonic acid for PPARδ activation in the nucleus. Thus, PPARδ induces COX-2 expression and the COX-2–derived PGE2 further activates PPARδ via cPLA2α. Such an interaction forms a novel feed-forward growth-promoting signaling that may play a role in hepatocarcinogenesis. (Cancer Res 2006; 66(24): 11859-68)
A Ras Inhibitor Tilts the Balance between Rac and Rho and Blocks Phosphatidylinositol 3-Kinase–Dependent Glioblastoma Cell Migration
Authors: Goldberg Liat , Kloog Yoel
Published: December 2006

Glioblastoma multiforme are highly aggressive tumors for which no adequate treatment has yet been developed. Glioblastoma multiforme show large amounts of active Ras, considered an appropriate target for directed therapy. Here, we show that the Ras inhibitor S-trans, trans-farnesyl thiosalicylic acid (FTS) can avert the transformation of human glioblastoma multiforme cells by inhibiting both their migration and their anchorage-independent proliferation. FTS, by down-regulating Ras activity in glioblastoma multiforme cells, inhibited phosphatidylinositol 3-kinase signaling, resulting in decreased activity of Rac-1. At the same time, activation of RhoA was increased. These two small GTPases are known to control the arrangement of the actin cytoskeleton. By tilting the balance between Rac-1 and RhoA activities, FTS caused the glioblastoma multiforme cells to undergo profound changes in morphology, including rearrangement of actin into stress fibers and assembly of focal adhesions, both of which are governed by RhoA signaling. These morphologic changes allowed strong attachment of the cells to the matrix, rendering them immobile. The results show that FTS should be considered as a candidate drug for glioblastoma multiforme therapy because it targets not only cell proliferation but also cell migration and invasion, which together constitute the most problematic aspect of these malignancies. (Cancer Res 2006; 66(24): 11709-17)
N-Glycosylation of MDA-7/IL-24 Is Dispensable for Tumor Cell–Specific Apoptosis and “Bystander” Antitumor Activity
Authors: Sauane Moira , Gupta Pankaj , Lebedeva Irina V. , Su Zao-zhong , Sarkar Devanand , Randolph Aaron , Valerie Kristoffer , Gopalkrishnan Rahul V. , Fisher Paul B.
Published: December 2006

Biochemical and genetic mutation–based analyses confirm that the MDA-7/IL-24 protein can induce transformed cell–specific apoptosis through a mechanism involving endoplasmic reticulum (ER) stress–associated pathways. Covalent modifications by N-linked glycans in the ER contribute to the conformational maturation and biological functions of many proteins. Because MDA-7/IL-24 is a glycosylated protein, we investigated the role of glycosylation in mediating the specific biological and “bystander” antitumor activities of this cytokine. An adenovirus vector expressing a nonsecreted and nonglycosylated version of MDA-7/IL-24 protein was generated via deletion of its signal peptide and point mutations of its three N-glycosylated sites. In this study, we showed that this intracellular nonglycosylated protein was as effective as wild-type MDA-7/IL-24 protein in inducing apoptosis in multiple tumor cell lines. Both constructs (a) displayed transformed cell specificity and localization to the ER compartment, (b) mediated apoptosis through JAK/STAT-independent and p38MAPK-dependent pathways, (c) induced sustained ER stress as evidenced by expression of ER stress markers (BiP/GRP78, GRP94, XBP-1, and eIF2α), and (d) generated proteins that physically interacted with BiP/GRP78. Additionally, an expression construct containing the mda-7/IL-24 signal peptide linked to the mutated nonglycosylated mda-7/IL-24 gene retained the ability to induce bystander antitumor activity. These studies reveal that MDA-7/IL-24 glycosylation is not mandatory for inducing cell death or bystander activities in different cancer cells, providing new insights into the mechanism by which MDA-7/IL-24 induces apoptosis and ER stress. (Cancer Res 2006; 66(24): 11869-77)
Dendrimer-Encapsulated Camptothecins: Increased Solubility, Cellular Uptake, and Cellular Retention Affords Enhanced Anticancer Activity In vitro
Authors: Morgan Meredith T. , Nakanishi Yuka , Kroll David J. , Griset Aaron P. , Carnahan Michael A. , Wathier Michel , Oberlies Nicholas H. , Manikumar Govindarajan , Wani Mansukh C. , Grinstaff Mark W.
Published: December 2006

A biocompatible polyester dendrimer composed of the natural metabolites, glycerol and succinic acid, is described for the encapsulation of the antitumor camptothecins, 10-hydroxycamptothecin and 7-butyl-10-aminocamptothecin. The cytotoxicity of the dendrimer-drug complex toward four different human cancer cell lines [human breast adenocarcinoma (MCF-7), colorectal adenocarcinoma (HT-29), non–small cell lung carcinoma (NCI-H460), and glioblastoma (SF-268)] is also reported, and low nmol/L IC50 values are measured. Cellular uptake and efflux measurements in MCF-7 cells show an increase of 16-fold for cellular uptake and an increase in drug retention within the cell when using the dendrimer vehicle. (Cancer Res 2006; 66(24): 11913-21)
A Novel Pathway Involving Melanoma Differentiation Associated Gene-7/Interleukin-24 Mediates Nonsteroidal Anti-inflammatory Drug–Induced Apoptosis and Growth Arrest of Cancer Cells
Authors: Zerbini Luiz F. , Czibere Akos , Wang Yihong , Correa Ricardo G. , Otu Hasan , Joseph Marie , Takayasu Yuko , Silver Moriah , Gu Xuesong , Ruchusatsawat Kriangsak , Li Linglin , Sarkar Devanand , Zhou Jin-Rong , Fisher Paul B. , Libermann Towia A.
Published: December 2006

Numerous studies show that nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in chemoprevention or treatment of cancer. Nevertheless, the mechanisms underlying these antineoplastic effects remain poorly understood. Here, we report that induction of the cancer-specific proapoptotic cytokine melanoma differentiation associated gene-7/interleukin-24 (MDA-7/IL-24) by several NSAIDs is an essential step for induction of apoptosis and G2-M growth arrest in cancer cells in vitro and inhibition of tumor growth in vivo. We also show that MDA-7/IL-24–dependent up-regulation of growth arrest and DNA damage inducible 45 α (GADD45α) and GADD45γ gene expression is sufficient for cancer cell apoptosis via c-Jun NH2-terminal kinase (JNK) activation and growth arrest induction through inhibition of Cdc2-cyclin B checkpoint kinase. Knockdown of GADD45α and GADD45γ transcription by small interfering RNA abrogates apoptosis and growth arrest induction by the NSAID treatment, blocks JNK activation, and restores Cdc2-cyclin B kinase activity. Our results establish MDA-7/IL-24 and GADD45α and GADD45γ as critical mediators of apoptosis and growth arrest in response to NSAIDs in cancer cells. (Cancer Res 2006; 66(24): 11922-31)
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

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

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

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

Tumor 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

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

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

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

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

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

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

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

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.
Note on the crystallization of potassium bichromate
Authors: Miers H. A.
Published: December 2006

If a drop of strong solution of potassium bichromate, placed upon a microscope-slide, be observed under the microscope as it crystallizes, and if the drop be sufficiently thin, it will generally be found that the following events take place: The first crystals make their appearance at the edges of the drop and after growing rapidly for a short period as branching fibres, they begin to grow quietly in the form of plates or flattened rods presenting the characteristic form of the crystals of this substance. These crystals continue to grow uniformly, but after a short period, at a distance from the growing crystals, and at some spot where the drop is thin, a fresh crystalline growth starts suddenly from a point, and extends with great rapidity in all directions in the form again of branching needles and fibres.
On some twins of calcite; and on a simple method of drawing crystals of calcite and other rhombohedral crystals, and of deducing the relations of their symbols
Authors: Lewis W. J.
Published: December 2006

Having had occasion recently to draw the twins of calcite, I noticed the advantage of the twin-axes being all placed in the plane of the paper. The representation of the rhombohedron which results from this condition is so unsatisfactory that, obvious as the idea must have been to all crystal draughtsmen, few, if any, seem to have tested the utility of the projection. I desire to point out a few of its advantages.
Scorodite from Kiura mine, Japan
Authors: Ito T. , Shiga T.
Published: December 2006

Scorodite from Kiura mine, Bungo, Japan, has been known for many years. However, owing to its diversity in crystallographical and optical properties as well as chemical composition from those of other localities there appears to be some doubts as to the identity of the mineral. It has even been suggested to be possibly a new mineral having a composition akin to that of scorodite. Some time ago a number of fine crystals were placed at our disposal by the courtesy of Dr. Kô, in addition to the recent acquisition by our Institute of a few rarely found beautiful druses of the mineral. It will therefore be worth while to describe some of its main features in detail.
Studies on the zeolites. Part V. Mesolite
Authors: Hey Max H.
Published: December 2006

Mesolite was first recognized as a separate species by J. N. Fuchs (1816), being one of the three species into which he subdivided R. J. Haüy's species mesotype (1801). Its individuality has been repeatedly doubted, many workers regarding the mesotype group as an isomorphous series with natrolite and scolecite as the endmembers, and mesolite merely an intermediate isomorphous mixture. The frequent occurrence of intergrowths of mesolite with natrolite or scolecite is largely responsible for this confusion, these intergrowths frequently passing for single minerals, and being adduced as evidence of the occurrence of all intermediate compositions in the supposed isomorphous series. Faroelites, and mixtures containing faroelite, have also been analysed as mesolite from time to time.
Clay minerals and bauxitic minerals. A review and classification based on a statistical method
Authors: Tomkeieff S. I.
Published: December 2006

A 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.
Beryllium minerals (euclase and phenakite) from Africa
Authors: Spencer L. J.
Published: December 2006

With the exception of beryl, there are very few recorded occurrences of beryllium minerals in the whole of Africa. Phenakite is represented by a single small crystal from Tanganyika Territory which was described in this Magazine in 1906. Chrysoberyl has been found in small amount in the Somabula diamond field in Southern Rhodesia, and in Belgian Congo and Gold Coast; and gadolinite a in Gordonia in Cape Province.
A radioactive mineral from Mozambique related to davidite
Authors: Bannister F. A. , Horne J. E. T.
Published: December 2006

Early in 1947 a black, opaque, radioactive mineral resembling samarskite in appearance was discovered at Mavnzi in the Tete distrier of Mozambique, Portuguese East Africa. Two small specimens, one a rough twinned crystal with trigonal symmetry (fig. 3), were sent by h. M. Macgregor; then Director of the Geological Survey of Southern Rhodesia, to the British Museum (Natural History) for investigation, and a chemical analysis by E. Golding (table I, no. 2) followed later in the same year. X-ray photographs of fragments and powder from both specimens were taken, but revealed on development no diffraction spots, lines, or haloes. Only after prolonged heat-treatment could powder lines characteristic of crystalline material be obtained. The metamict nature of the mineral before heat-treatment is not unexpected in view of its chemical composition, optical isotropy, and glassy fracture.
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.
Priderite, a new mineral from the leucite-lamproites of the west Kimberley area, Western Australia
Authors: Norrish K.
Published: December 2006

During an analysis by X-ray diffraction techniques of some fine-grained leucite-lamproites from the west Kimberley area of Western Australia the author became interested in the rntile in these rocks. Although rutile had been repeatedly observed under the microscope (1, 2), its presence could not be confirmed using X-ray diffraction methods. At the author's request, Professor R. T. Prider supplied a small amount of the mineral which had been identified as rutile. A study of this mineral showed it to be a new mineral similar to rutile in its optical properties.
The crystal structure of some chamosite minerals (With Plate XII)
Authors: Brindley G. W. , Dunham K. C. , Eyles V. A. , Taylor J. H.
Published: December 2006

Chamosite is a commonly occurring hydrous ferrous silicate frequently found in close association with chalybite in marine mudstone deposits, the composition of different beds ranging from almost pure chamosite to pure chalybite. In oolitic ironstones chamosite is found both in the ooliths themselves and also in the groundmass. It occurs as a constituent in shales, as a cementing mineral in sandstones, and is occasionally found in lateritic and other deposits. Mineralogically it is usually regarded as a chlorite, or akin to the chlorites, but evidence has been accumulating which tends to show that some varieties may not be chlorites at all, but are probably closely related to the kaolin group of minerals (Brindley, 1949).
The zoned contact-skarns of the Broadford area, Skye: a study of boron-fluorine metasomatism in dolomites
Authors: Tilley C. E.
Published: December 2006

In a preliminary note on the dolomite contaet-skarns of the Broadford area, Skye (Tilley, 1948, a), a brief account was given of the constitution and environment of these multizoned assemblages at the contact of the Durness limestone succession with the Tertiary Beinn an Dubhaich granite.1 No detailed survey of the numerous parageneses was then attempted, and it is the purpose of the present paper to fill this gap and to discuss the genetic problems of these skarn assemblages.
X-ray determination of centrosymmetry in three felspars
Authors: Bailey S. W. , Ferguson R. B. , Taylor W. H.
Published: December 2006

Three statistical tests, depending upon the probability distribution of X-ray intensities, have been applied to orthoclase, sanidine, and albite. It is concluded that these three felspars posses centres of symmetry, justifying the assumption of holohedral symmetry made in earlier structure analyses.
Nacrite from Hirvivaara, northern Karelia, Finland. (With Plate XXVIII)
Authors: von Knorring Oleg , Brindley G. W. , Hunter K.
Published: December 2006

Nacrite is the rarest member of the kaolin group of minerals. The name was first applied by Brongniart in 1807 to a mineral (talc granuleux of Haüy, 1801) the properties of which were not then adequately described. In 1832 Breithaupt recorded a mineral from an ore vein near Freiberg in Saxony, which has since been called nacrite. In the past, however, 'nacrite' has been applied quite frequently to different nacreous and micaceous minerals, not necessarily of kaolin composition, and the authenticity of the species was not definitely established until 1931 when Ross and Kerr, on the basis of an X-ray study of nacrite from the locality Brand near Freiberg in Saxony, proved the mineral to be a distinct species of the kaolin group.
The Eskdalemuir tholeiite and its contribution to an understanding of tholeiite genesis
Authors: Elliott R. B.
Published: December 2006

The Eskdalemuir tholeiite has the following modal composition: glass 42·2 %, felspar 24·4 %, pyroxene 30·6 %), magnetite 2 %, chlorite 1%. The glass has been separated and analysed. It has 70% SiO2 and is of granitic composition. On a selected triangular diagram the plots of the Eskdalemuir rock, its residual glass, and its crystallinc portion are spread along a narrow belt marking the compositions of the Tertiary tholeiites. Because the differences in the chemical compositions of the phrases of the Eskdalemuir tholeiite are produced by crystallization, it is concluded that the variety of composition of the other Tertiary tholeiites is consistent with a genesis controlled by crystallization differentiation.
New occurrences of vanadium minerals (mottramite, descloizite, and vanadinite) in the Caldbeck area of Cumberland
Authors: Kingsbury Arthur W. G. , Hartley J.
Published: December 2006

Four new occurrences of vanadium minerals are described. New X-ray powder data are given for descloizite and mottramite, and show appreciable differences. Evidence is brought that the original occurrence of mottramite was not at Mottram St. Andrew, Cheshire, but Pim Hill, Shropshire, and that most if not all specimens labelled Mottram St. Andrew or Cheshire really came from Pim Hill.
The structures of the plagioclase felspars: VII. The heat treatment of intermediate plagioclases
Authors: Gay P. , Bown M. G.
Published: December 2006

Previous work has established that natural ‘low-temperature’ intermediate plagioclases show single-crystal diffraction patterns in which the subsidiary reflections are split into two; the separation of these split reflections appears to be dependent on the composition of the felspar. Several of these specimens have been subjected to varying heat treatments and their diffraction patterns examined.

It is found that over the whole composition range the split subsidiary reflections have disappeared after treatment at high temperatures, and only the principal felspar reflections, which are characteristic of an albite-like structure, remain. Natural specimens initially showing anomalous patterns can also be homogenized in this way by suitable heat treatments. A careful study of the mode of disappearance shows that the separation of the subsidiary reflections is unchanged as long as they remain visible.

The structural and petrological implications of this work are discussed.