bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Horizon Homeopathic Dilution Experiment
Authors: Bland Martin 
Published: September 2005

Abstract
In 2002 Martin Bland made his first appearance on television, in a BBC2 Horizon programme on homeopathy. When he gives talks about this work, the list of acknowledgements includes John Enderby, Vice-President of the Royal Society, and James Randi, magician. It's not every research team that includes a magician!
Neighbourhood Watch: Population Forecasting for New Housing Developments
Authors: Garcia Paul 
Published: September 2005

Abstract
In 2003 Paul Garcia was awarded a Royal Statistical Society Campion Fellowship, with a grant of £5000, to carry out a study to try to determine the age profile of residents of new housing developments and explain how that profile changes over time. He describes why he wanted to do the work and how he set about organising the survey.
Stability of EcoRI Restriction-Modification Enzymes In Vivo Differentiates the EcoRI Restriction-Modification System from Other Postsegregational Cell Killing Systems
Authors: Ichige Asao , Kobayashi Ichizo 
Published: September 2005

ABSTRACT

Certain type II restriction modification gene systems can kill host cells when these gene systems are eliminated from the host cells. Such ability to cause postsegregational killing of host cells is the feature of bacterial addiction modules, each of which consists of toxin and antitoxin genes. With these addiction modules, the differential stability of toxin and antitoxin molecules in cells plays an essential role in the execution of postsegregational killing. We here examined in vivo stability of the EcoRI restriction enzyme (toxin) and modification enzyme (antitoxin), the gene system of which has previously been shown to cause postsegregational host killing in
Escherichia coli
. Using two different methods, namely, quantitative Western blot analysis and pulse-chase immunoprecipitation analysis, we demonstrated that both the EcoRI restriction enzyme and modification enzyme are as stable as bulk cellular proteins and that there is no marked difference in their stability. The numbers of EcoRI restriction and modification enzyme molecules present in a host cell during the steady-state growth were estimated. We monitored changes in cellular levels of the EcoRI restriction and modification enzymes during the postsegregational killing. Results from these analyses together suggest that the EcoRI gene system does not rely on differential stability between the toxin and the antitoxin molecules for execution of postsegregational cell killing. Our results provide insights into the mechanism of postsegregational killing by restriction-modification systems, which seems to be distinct from mechanisms of postsegregational killing by other bacterial addiction modules.
Periplasmic Domains Define Holin-Antiholin Interactions in T4 Lysis Inhibition
Authors: Tran Tram Anh T. , Struck Douglas K. , Young Ry 
Published: September 2005

ABSTRACT

Bacteriophage T4 effects host lysis with a holin, T, and an endolysin, E. T and E accumulate in the membrane and cytoplasm, respectively, throughout the period of late gene expression. At an allele-specific time, T triggers to disrupt the membrane, allowing E to enter the periplasm and attack the peptidoglycan. T triggering can be blocked by secondary infections, leading to the state of lysis inhibition (LIN). LIN requires the T4 antiholin, RI, and is sensitive to the addition of energy poisons. T is unusual among holins in having a large C-terminal periplasmic domain. The
rI
gene encodes a polypeptide of 97 residues, of which 72 are predicted to be a periplasmic domain. Here, we show that the periplasmic domain of RI is necessary and sufficient to block T-mediated lysis. Moreover, when overexpressed, the periplasmic domain of T (T
CTD
) was found to abolish LIN in T4 infections and to convert wild-type (wt) T4 plaques from small and fuzzy edged to the classic “
r
” large, sharp-edged plaque morphology. Although RI could be detected in whole cells, attempts to monitor it during subcellular fractionation were unsuccessful, presumably because RI is a highly unstable protein. However, fusing green fluorescence protein (GFP) to the N terminus of RI created a more stable chimera that could be demonstrated to form complexes with wild-type T
CTD
and also with its LIN-defective T75I variant. These results suggest that the function of the unusual periplasmic domain of T is to transduce environmental information for the real-time control of lysis timing.
Small Untranslated RNA Antitoxin inBacillus subtilis
Authors: Silvaggi Jessica M. , Perkins John B. , Losick Richard 
Published: September 2005

ABSTRACTToxin-antitoxin (TA) modules are pairs of genes in which one member encodes a toxin that is neutralized or whose synthesis is prevented by the action of the product of the second gene, an antitoxin, which is either protein or RNA. We now report the identification of a TA module in the chromosome ofBacillus subtilisin which the antitoxin is an antisense RNA. The antitoxin, which is called RatA (for RNA antitoxin A), is a small (222 nucleotides), untranslated RNA that blocks the accumulation of the mRNA for a toxic peptide TxpA (for toxic peptide A; formerly YqdB). ThetxpAandratAgenes are in convergent orientation and overlap by ca. 75 nucleotides, such that the 3′ region ofratAis complementary to the 3′ region oftxpA. Deletion ofratAled to increased levels oftxpAmRNA and lysis of the cells. Overexpression oftxpAalso caused cell lysis and death, a phenotype that was prevented by simultaneous overexpression ofratA. We propose that theratAtranscript is an antisense RNA that anneals to the 3′ end of thetxpAmRNA, thereby triggering its degradation.
The Ability ofProteus mirabilisTo Sense Surfaces and Regulate Virulence Gene Expression Involves FliL, a Flagellar Basal Body Protein
Authors: Belas Robert , Suvanasuthi Rooge 
Published: September 2005

ABSTRACTProteus mirabilisis a urinary tract pathogen that differentiates from a short swimmer cell to an elongated, highly flagellated swarmer cell. Swarmer cell differentiation parallels an increased expression of several virulence factors, suggesting that both processes are controlled by the same signal. The molecular nature of this signal is not known but is hypothesized to involve the inhibition of flagellar rotation. In this study, data are presented supporting the idea that conditions inhibiting flagellar rotation induce swarmer cell differentiation and implicating a rotating flagellar filament as critical to the sensing mechanism. Mutations in three genes,fliL,fliF, andfliG, encoding components of the flagellar basal body, result in the inappropriate development of swarmer cells in noninducing liquid media or hyperelongated swarmer cells on agar media. ThefliLmutation was studied in detail. FliL−mutants are nonmotile and fail to synthesize flagellin, while complementation offliLrestores wild-type cell elongation but not motility. Overexpression offliL+in wild-type cells prevents swarmer cell differentiation and motility, a result also observed whenP. mirabilis fliL+was expressed inEscherichia coli. These results suggest that FliL plays a role in swarmer cell differentiation and implicate FliL as critical to transduction of the signal inducing swarmer cell differentiation and virulence gene expression. In concert with this idea, defects infliLup-regulate the expression of two virulence genes,zapAandhpmB. These results support the hypothesis thatP. mirabilisascertains its location in the environment or host by assessing the status of its flagellar motors, which in turn control swarmer cell gene expression.
Block observations of neighbourhood physical disorder are associated with neighbourhood crime, firearm injuries and deaths, and teen births
Authors: Wei Evelyn , Hipwell Alison , Pardini Dustin , Beyers Jennifer M , Loeber Rolf 
Published: September 2005

Study objective:To provide reliability information for a brief observational measure of physical disorder and determine its relation with neighbourhood level crime and health variables after controlling for census based measures of concentrated poverty and minority concentration.Design:Psychometric analysis of block observation data comprising a brief measure of neighbourhood physical disorder, and cross sectional analysis of neighbourhood physical disorder, neighbourhood crime and birth statistics, and neighbourhood level poverty and minority concentration.Setting:Pittsburgh, Pennsylvania, US (2000 population = 334 563).Participants:Pittsburgh neighbourhoods (n = 82) and their residents (as reflected in neighbourhood level statistics).Main results:The physical disorder index showed adequate reliability and validity and was associated significantly with rates of crime, firearm injuries and homicides, and teen births, while controlling for concentrated poverty and minority population.Conclusions:This brief measure of neighbourhood physical disorder may help increase our understanding of how community level factors reflect health and crime outcomes.
CHARACTERIZATION OF OPERATORS ON A KONDRATIEV SPACE IN THE NON-GAUSSIAN SETTING: BIORTHOGONAL APPROACH
Authors: YABLONSKY EUGENE 
Published: September 2005

A linear bounded operator on a test space of white noise functionals can be characterized in terms of growth conditions imposed on the operator's symbol. This paper extends such characterization to operators on the Kondratiev's test space [Formula: see text] of random variables over a general non-Gaussian probability space. We follow the biorthogonal approach of Yu. Daletsky and his colleagues. In particular, the test space under consideration is generated by the system of multivariate Appell polynomials defined on the underlying infinite dimensional co-nuclear probability space. We further extend this biorthogonal approach to operators by providing a biorthogonal chaos decomposition for operators and by giving a biorthogonal construction for an operator's symbol.
PIK3CA Mutations Correlate with Hormone Receptors, Node Metastasis, and ERBB2, and Are Mutually Exclusive with PTEN Loss in Human Breast Carcinoma
Authors: Saal Lao H. , Holm Karolina , Maurer Matthew , Memeo Lorenzo , Su Tao , Wang Xiaomei , Yu Jennifer S. , Malmström Per-Olof , Mansukhani Mahesh , Enoksson Jens , Hibshoosh Hanina , Borg Åke , Parsons Ramon 
Published: September 2005

Abstract
Deregulation of the phosphatidylinositol 3-kinase (PI3K) pathway either through loss of PTEN or mutation of the catalytic subunit α of PI3K (PIK3CA) occurs frequently in human cancer. We identified PIK3CA mutations in 26% of 342 human breast tumor samples and cell lines at about equal frequency in tumor stages I to IV. To investigate the relationship between PTEN and PIK3CA, we generated a cohort of tumors that had lost PTEN expression and compared it with a matched control set that had retained PTEN. A highly significant association between PIK3CA mutations and retention of PTEN protein expression was observed. In addition, PIK3CA mutations were associated with expression of estrogen and progesterone receptors (ER/PR), lymph node metastasis, and ERBB2 overexpression. The fact that PIK3CA mutations and PTEN loss are nearly mutually exclusive implies that deregulated phosphatidylinositol-3,4,5-triphosphate (PIP3) is critical for tumorigenesis in a significant fraction of breast cancers and that loss of PIP3 homeostasis by abrogation of either PIK3CA or PTEN relieves selective pressure for targeting of the other gene. The correlation of PIK3CA mutation to ER/PR-positive tumors and PTEN loss to ER/PR-negative tumors argues for disparate branches of tumor evolution. Furthermore, the association between ERBB2 overexpression and PIK3CA mutation implies that more than one input activating the PI3K/AKT pathway may be required to overcome intact PTEN. Thus, mutation of PIK3CA is frequent, occurs early in carcinoma development, and has prognostic and therapeutic implications.
Heightened Expression of CTCF in Breast Cancer Cells Is Associated with Resistance to Apoptosis
Authors: Docquier France , Farrar Dawn , D'Arcy Vivien , Chernukhin Igor , Robinson Abigail F. , Loukinov Dmitry , Vatolin Sergei , Pack Svetlana , Mackay Alan , Harris Robert A. , Dorricott Heather , O'Hare Michael J. , Lobanenkov Victor , Klenova Elena 
Published: September 2005

Abstract
CTCF is a candidate tumor suppressor gene encoding a multifunctional transcription factor. Surprisingly for a tumor suppressor, the levels of CTCF in breast cancer cell lines and tumors were found elevated compared with breast cell lines with finite life span and normal breast tissues. In this study, we aimed to investigate the possible cause for this increase in CTCF content and in particular to test the hypothesis that up-regulation of CTCF may be linked to resistance of breast cancer cells to apoptosis. For this purpose, apoptotic cell death was monitored following alterations of CTCF levels induced by transient transfection and conditional knockdown of CTCF in various cell lines. We observed apoptotic cell death in all breast cancer cell lines examined following CTCF down-regulation. In addition, overexpression of CTCF partially protected cells from apoptosis induced by overexpression of Bax or treatment with sodium butyrate. To elucidate possible mechanisms of this phenomenon, we used a proteomics approach and observed that levels of the proapoptotic protein, Bax, were increased following CTCF down-regulation in MCF7 cells. Taken together, these results suggest that in some cellular contexts CTCF shows antiapoptotic characteristics, most likely exerting its functions through regulation of apoptotic genes. We hypothesize that CTCF overexpression may have evolved as a compensatory mechanism to protect breast cancer cells from apoptosis, thus providing selective survival advantages to these cells. The observations reported in this study may lead to development of therapies based on selective reduction of CTCF in breast cancer cells.
Ron Receptor Signaling Augments Mammary Tumor Formation and Metastasis in a Murine Model of Breast Cancer
Authors: Peace Belinda E. , Toney-Earley Kenya , Collins Margaret H. , Waltz Susan E. 
Published: September 2005

Abstract
The tyrosine kinase receptor Ron has been implicated in several types of cancer, including overexpression in human breast cancer. This is the first report describing the effect of Ron signaling on tumorigenesis and metastasis in a mouse model of breast cancer. Mice with a targeted deletion of the Ron tyrosine kinase signaling domain (TK−/−) were crossed to mice expressing the polyoma virus middle T antigen (pMT) under the control of the mouse mammary tumor virus promoter. Both pMT-expressing wild-type control (pMT+/− TK+/+) and pMT+/− TK−/− mice developed mammary tumors and lung metastases. However, a significant decrease in mammary tumor initiation and growth was found in the pMT+/− TK−/− mice compared with controls. An examination of mammary tumors showed that there was a significant decrease in microvessel density, significantly decreased cellular proliferation, and a significant increase in terminal deoxynucleotidyl transferase–mediated nick end labeling–positive staining in mammary tumor cells from the pMT+/− TK−/− mice compared with the pMT+/− TK+/+ mice. Biochemical analyses on mammary tumor lysates showed that whereas both the pMT-expressing TK+/+ and TK−/− tumors have increased Ron expression compared with normal mammary glands, the pMT-expressing TK−/− tumors have deficits in mitogen-activated protein kinase and AKT activation. These results indicate that Ron signaling synergizes with pMT signaling to induce mammary tumor formation, growth, and metastasis. This effect may be mediated in part through the regulation of angiogenesis and through proliferative and cell survival pathways regulated by mitogen-activated protein kinase and AKT.
CCAAT/Enhancer-Binding Protein δ: A Molecular Target of 1,25-Dihydroxyvitamin D3 in Androgen-Responsive Prostate Cancer LNCaP Cells
Authors: Ikezoe Takayuki , Gery Sigal , Yin Dong , O'Kelly James , Binderup Lise , Lemp Nathan , Taguchi Hirokuni , Koeffler H. Phillip 
Published: September 2005

Abstract
1,25-Dihydroxyvitamin D3 [1,25(OH)2D3], the active metabolite of vitamin D3, inhibits the proliferation of prostate cancer cells. However, the molecular mechanisms by which 1,25(OH)2D3 inhibits the proliferation of these cells remain to be fully elucidated. In this study, we used microarray technology to identify target genes of 1,25(OH)2D3 in androgen-responsive prostate cancer LNCaP cells. 1,25(OH)2D3 up-regulated CCAAT/enhancer-binding protein δ (C/EBPδ) by ∼5-fold in these cells. Knockdown of C/EBPδ expression by RNA interference showed that C/EBPδ is essential for the significant growth inhibition of LNCaP cells in response to 1,25(OH)2D3 treatment. Moreover, we found that 1,25(OH)2D3 induced C/EBPδ in other cancer cells, including the estrogen receptor (ER)–expressing MCF-7 and T47D breast cancer cells that are sensitive to the growth inhibitory effects of 1,25(OH)2D3. On the other hand, 1,25(OH)2D3 was not able to induce C/EBPδ in either androgen receptor–negative PC-3 and DU145 or ER-negative breast cancer MDA-MB-231 cells that were relatively resistant to growth inhibition by 1,25(OH)2D3. Furthermore, forced expression of C/EBPδ in prostate cancer LNCaP as well as breast cancer MCF-7 and T47D cells dramatically reduced their clonal growth. Taken together, forced expression of C/EBPδ in cancer cells may be a promising therapeutic strategy.
Human Splicing Factor SPF45 (RBM17) Confers Broad Multidrug Resistance to Anticancer Drugs When Overexpressed— a Phenotype Partially Reversed By Selective Estrogen Receptor Modulators
Authors: Perry William L. , Shepard Robert L. , Sampath Janardhan , Yaden Benjamin , Chin William W. , Iversen Philip W. , Jin Shengfang , Lesoon Andrea , O'Brien Kathryn A. , Peek Victoria L. , Rolfe Mark , Shyjan Andrew , Tighe Michelle , Williamson Mark , Krishnan Venkatesh , Moore Robert E. , Dantzig Anne H. 
Published: September 2005

Abstract
The splicing factor SPF45 (RBM17) is frequently overexpressed in many solid tumors, and stable expression in HeLa cells confers resistance to doxorubicin and vincristine. In this study, we characterized stable transfectants of A2780 ovarian carcinoma cells. In a 3-day cytotoxicity assay, human SPF45 overexpression conferred 3- to 21-fold resistance to carboplatin, vinorelbine, doxorubicin, etoposide, mitoxantrone, and vincristine. In addition, resistance to gemcitabine and pemetrexed was observed at the highest drug concentrations tested. Knockdown of SPF45 in parental A2780 cells using a hammerhead ribozyme sensitized A2780 cells to etoposide by ∼5-fold relative to a catalytically inactive ribozyme control and untransfected cells, suggesting a role for SPF45 in intrinsic resistance to some drugs. A2780-SPF45 cells accumulated similar levels of doxorubicin as vector-transfected and parental A2780 cells, indicating that drug resistance is not due to differences in drug accumulation. Efforts to identify small molecules that could block SPF45-mediated drug resistance revealed that the selective estrogen receptor (ER) modulators tamoxifen and LY117018 (a raloxifene analogue) partially reversed SPF45-mediated drug resistance to mitoxantrone in A2780-SPF45 cells from 21-fold to 8- and 5-fold, respectively, but did not significantly affect the mitoxantrone sensitivity of vector control cells. Quantitative PCR showed that ERβ but not ERα was expressed in A2780 transfectants. Coimmunoprecipitation experiments suggest that SPF45 and ERβ physically interact in vivo. Thus, SPF45-mediated drug resistance in A2780 cells may result in part from effects of SPF45 on the transcription or alternate splicing of ERβ-regulated genes.
Angiogenesis Inhibition by Vascular Endothelial Growth Factor Receptor-2 Blockade Reduces Stromal Matrix Metalloproteinase Expression, Normalizes Stromal Tissue, and Reverts Epithelial Tumor Phenotype in Surface Heterotransplants
Authors: Vosseler Silvia , Mirancea Nicolae , Bohlen Peter , Mueller Margareta M. , Fusenig Norbert E. 
Published: September 2005

AbstractInhibition of vascular endothelial growth factor (VEGF) signaling, a key regulator of tumor angiogenesis, through blockade of VEGF receptor (VEGFR)-2 by the monoclonal antibody DC101 inhibits angiogenesis, tumor growth, and invasion. In a surface xenotransplant assay on nude mice using a high-grade malignant squamous cell carcinoma cell line (A-5RT3), we show that DC101 causes vessel regression and normalization as well as stromal maturation resulting in a reversion to a noninvasive tumor phenotype. Vessel regression is followed by down-regulation of expression of both VEGFR-2 and VEGFR-1 on endothelial cells and increased association of α-smooth muscle actin–positive cells with small vessels indicating their normalization, which was further supported by a regular ultrastructure. The phenotypic regression of an invasive carcinoma to a well-demarcated dysplastic squamous epithelium is accentuated by the establishment of a clearly structured epithelial basement membrane and the accumulation of collagen bundles in the stabilized connective tissue. This normalization of the tumor-stroma border coincided with down-regulated expression of the stromal matrix metalloproteinases 9 and 13, which supposedly resulted in attenuated turnover of extracellular matrix components permitting their structural organization. Thus, in this mouse model of a human squamous cell carcinoma cell line, blockade of VEGF signaling resulted in the reversion of the epithelial tumor phenotype through stromal normalization, further substantiating the crucial role of stromal microenvironment in regulating the tumor phenotype.
Gene Expression Profiling Reveals Cross-talk between Melanoma and Fibroblasts: Implications for Host-Tumor Interactions in Metastasis
Authors: Gallagher Paul G. , Bao Yongde , Prorock Alyson , Zigrino Paola , Nischt Roswitha , Politi Vincenzo , Mauch Cornelia , Dragulev Bojan , Fox Jay William 
Published: September 2005

Abstract
Host-tumor interaction is considered critical in carcinogenesis, tumor invasion, and metastasis. To explore the reciprocal effects of host-tumor interaction, we developed a system to assess the gene expression patterns of A2058 human melanoma cells cocultured in fibrillar collagen with HS-68 primary human fibroblasts. The gene expression pattern of the cocultured A2058 cells was only modestly affected, whereas the HS-68 fibroblast gene expression pattern was significantly altered. Interleukin-11 and inhibitor of DNA-binding domain-1 gene expression in the cocultured A2058 cells was down-regulated, indicative of a proinflammatory response and resistance to apoptosis, respectively. The overall pattern of up-regulated genes indicated triggering of the proinflammatory process. In addition, the melanoma growth and migration stimulatory chemokines CXCL1 and CXCL2 were significantly up-regulated in the cocultured fibroblasts. These results were corroborated by additional coculture experiments with the melanoma cell lines WM-164, BLM, and SK-Mel-28 and immunohistochemistry on invasive human melanoma sections. Taken together, these results indicate that tumor cells cause a proinflammatory and melanoma growth-promoting response in stromal fibroblasts. The role of inflammation in carcinogenesis, tumor promotion, invasion, and metastasis is viewed as being increasingly important and the results of these studies underscore this as well as identify certain key proteins that are expressed as a result of the complex interactive processes in the host-tumor microenvironment.