bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Beef Product Physical Structure on Salmonella Thermal Inactivation
Authors: Mogollón María Avelina , Marks Bradley P. , Booren Alden M. , Orta‐Ramirez Alicia , Ryser Elliot T. 
Published: July 2009

ABSTRACT:  Numerous studies have assessed thermal inactivation of Salmonella in beef. However, the impact of muscle structure has been considered only recently, with several studies reporting enhanced thermal resistance in whole‐muscle as compared to ground meat. The functional relationship between meat product physical structure and Salmonella thermal resistance has not been reported; therefore, it is not known whether thermal resistance is affected by the degree of grinding (that is, size of resulting particles). The objective of this study was to evaluate the relationship between thermal resistance of Salmonella and degree of grinding (whole‐muscle, coarsely ground, finely ground, and beef puree). Each of the 4 product types was irradiated to sterility and inoculated with a marinade containing an 8‐serovar Salmonella cocktail to achieve approximately 107.8 CFU/g. Samples (5 g each) were packed into sterile brass tubes, which were sealed, held at 60 °C in a water bath, and removed at 30 s intervals. Samples were then serially diluted and plated on Petrifilm™ aerobic count plates to enumerate surviving salmonellae. All samples had the same composition, thermal history, and initial Salmonella counts; therefore, differences in thermal resistance were due entirely to the degree of grinding. Overall, thermal resistance of Salmonella was highest (P < 0.0001) in whole‐muscle (D = 2.7 min), but there were no differences among the 3 ground products (Dmean= 1.2 min). Therefore, it would be prudent for Salmonella thermal inactivation models to consider whether a product is whole‐muscle or ground, but not necessarily the degree of grinding.Practical Application: The results of this study suggest that thermal process validations for ready‐to‐eat meat products should also consider the structure of the product (which in this study was changed by the physical act of grinding). Salmonella was more resistant to heat in whole‐muscle beef than in ground products; however, the degree of grinding did not affect the resistance.
Probing Predispositions: The Pragmatism of a Process Perspective
Authors: Moore David S. 
Published: July 2009

Abstract—AsJ. P. Spencer et al. (2009)argue, the theories of some developmental psychologists continue to be nativistic, even though nativism is an inherently nondevelopmental school of thought. Psychologists interested in development study the emergence of human characteristics—including predispositions—and are not content to simply catalogue competences that characterize human newborns; instead, they recognize that all human characteristics, including those present at birth, reflect the circumstances of development. A truly developmental science of behavior requires rejecting the nativism–empiricism debate outright, abandoning ideas such as “core knowledge” and psychological “endowments,” and adopting a process perspective that focuses onhowtraits emerge from the co‐actions of biological and experiential factors. Unlike nativism, the process perspective advocated byJ. P. Spencer et al.encourages research that can reveal the developmental origins of psychological characteristics of interest.
Privatizing Responsibility: Public Sector Reform under Neoliberal Government
Authors: ILCAN SUZAN 
Published: July 2009

À la lumière des réformes du secteur public au Canada et ailleurs, l'auteure se concentre sur le déplacement des priorités des responsabilités sociales vers les responsabilités privées et soulève de nouvelles questions sur les forces de l'entreprise privée et des partenariats reposant sur les mécanismes du marché. D'après elle, dans les programmes néo‐libéraux du gouvernement, laresponsabilité de la privatisationest liée à trois principaux aménagements : la reconsidération des relations entre le public et le privé; la mobilisation de l'esprit de civisme; et la création d'une mentalité culturelle d'observance de la règle allant de pair avec ces transformations. La recherche qui a été effectuée pour cet article s'est fondée sur l'analyse à grande échelle de documents de politique et d'initiatives de réforme du secteur public, de même que sur des interviews de fonctionnaires fédéraux canadiens.In light of public sector reforms in Canada and elsewhere, this paper focuses on the shift of emphasis from social to private responsibilities and raises new questions about the forces of private enterprise and market‐based partnerships. Under neoliberal governmental agendas,privatizing responsibilitylinks to three main developments: the reconsideration of the relations of public and private; the mobilization of responsible citizenship; and the formation of a cultural mentality of rule that works alongside these developments. The research for this article is based on extensive analysis of policy documents and public sector reform initiatives, as well as interviews with Canadian federal public service employees.
Nocardia nova
as the Causative Agent in Spondylodiscitis and Psoas Abscess
Authors: Hamdad Farida , Vidal Barbara , Douadi Youcef , Laurans Genevieve , Canarelli Brigitte , Choukroun Gabriel , Rodriguez-Nava Veronica , Boiron Patrick , Beaman Blaine , Eb François 
Published: July 2009

ABSTRACT

We describe here the first case of
Nocardia nova
spondylodiscitis accompanied by a psoas abscess due to spreading from pulmonary nocardiosis.
Nocardia
was cultured from all affected sites. After 1 year of an appropriate antimicrobial therapy and a surgical drainage of the abscess that was required, the patient's clinical condition had improved.
The Cell Fate Determination Factor DACH1 Is Expressed in Estrogen Receptor-α–Positive Breast Cancer and Represses Estrogen Receptor-α Signaling
Authors: Popov Vladimir M. , Zhou Jie , Shirley L. Andrew , Quong Judy , Yeow Wen-Shuz , Wright Jennifer A. , Wu Kongming , Rui Hallgeir , Vadlamudi Ratna K. , Jiang Jie , Kumar Rakesh , Wang Chenguang , Pestell Richard G. 
Published: July 2009

Abstract
The Dachshund (dac) gene, initially cloned as a dominant inhibitor of the Drosophila hyperactive EGFR mutant ellipse, encodes a key component of the cell fate determination pathway involved in Drosophila eye development. Analysis of more than 2,200 breast cancer samples showed improved survival by some 40 months in patients whose tumors expressed DACH1. Herein, DACH1 and estrogen receptor-α (ERα) expressions were inversely correlated in human breast cancer. DACH1 bound and inhibited ERα function. Nuclear DACH1 expression inhibited estradiol (E2)-induced DNA synthesis and cellular proliferation. DACH1 bound ERα in immunoprecipitation-Western blotting, associated with ERα in chromatin immunoprecipitation, and inhibited ERα transcriptional activity, requiring a conserved DS domain. Proteomic analysis identified proline, glutamic acid, and leucine rich protein 1 (PELP1) as a DACH1-binding protein. The DACH1 COOH terminus was required for binding to PELP1. DACH1 inhibited induction of ERα signaling. E2 recruited ERα and disengaged corepressors from DACH1 at an endogenous ER response element, allowing PELP1 to serve as an ERα coactivator. DACH1 expression, which is lost in poor prognosis human breast cancer, functions as an endogenous inhibitor of ERα function. [Cancer Res 2009;69(14):5752–60]
Targeted In vivo Imaging of Integrin αvβ6 with an Improved Radiotracer and Its Relevance in a Pancreatic Tumor Model
Authors: Hausner Sven H. , Abbey Craig K. , Bold Richard J. , Gagnon M. Karen , Marik Jan , Marshall John F. , Stanecki Cathy E. , Sutcliffe Julie L. 
Published: July 2009

Abstract
The cell surface receptor αvβ6 is epithelial specific, and its expression is tightly regulated; it is low or undetectable in adult tissues but has been shown to be increased in many different cancers, including pancreatic, cervical, lung, and colon cancers. Studies have described αvβ6 as a prognostic biomarker linked to poor survival. We have recently shown the feasibility of imaging αvβ6 in vivo by positron emission tomography (PET) using the peptide [18F]FBA-A20FMDV2. Here, we describe improved αvβ6 imaging agents and test their efficacy in a mouse model with endogenous αvβ6 expression. The modified compounds maintained high affinity for αvβ6 and &gt;1,000-fold selectivity over related integrins (by ELISA) and showed significantly improved αvβ6-dependent binding in cell-based assays (&gt;60% binding versus &lt;10% for [18F]FBA-A20FMDV2). In vivo studies using either a melanoma cell line (transduced αvβ6 expression) or the BxPC-3 human pancreatic carcinoma cell line (endogenous αvβ6 expression) revealed that the modified compounds showed significantly improved tumor retention. This, along with good clearance of nonspecifically bound activity, particularly for the new radiotracer [18F]FBA-PEG28-A20FMDV2, resulted in improved PET imaging. Tumor/pancreas and tumor/blood biodistribution ratios of &gt;23:1 and &gt;47:1, respectively, were achieved at 4 hours. Significantly, [18F]FBA-PEG28-A20FMDV2 was superior to 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) in imaging the BxPC-3 tumors. Pancreatic ductal adenocarcinoma is highly metastatic and current preoperative evaluation of resectability using noninvasive imaging has limited success, with most patients having metastases at time of surgery. The fact that these tumors express αvβ6 suggests that this probe has significant potential for the in vivo detection of this malignancy, thus having important implications for patient care and therapy. [Cancer Res 2009;69(14):5843–50]
Overexpression of DPAGT1 Leads to Aberrant N-Glycosylation of E-Cadherin and Cellular Discohesion in Oral Cancer
Authors: Nita-Lazar Mihai , Noonan Vikki , Rebustini Ivan , Walker Janice , Menko A. Sue , Kukuruzinska Maria A. 
Published: July 2009

Abstract
Cancer cells are frequently characterized by aberrant increases in protein N-glycosylation and by disruption of E-cadherin–mediated adherens junctions. The relationship between altered N-glycosylation and loss of E-cadherin adhesion in cancer, however, remains unclear. Previously, we reported that complex N-glycans on the extracellular domains of E-cadherin inhibited the formation of mature adherens junctions. Here, we examined whether dysregulated N-glycosylation was one of the underlying causes for cellular discohesion in oral cancer. We show that dense cultures of human salivary epidermoid carcinoma A253 cells exhibited elevated expression of DPAGT1, the gene that initiates protein N-glycosylation. Overexpression of DPAGT1 correlated with the production of E-cadherin–bearing complex N-glycans in nascent adherens junctions. Partial inhibition of DPAGT1 with small interfering RNA reduced the complex N-glycans of E-cadherin and increased the abundance of α-catenin and stabilizing proteins in adherens junctions. This was associated with the assembly of functional tight junctions. The inverse relationship between DPAGT1 expression and intercellular adhesion was a feature of oral squamous cell carcinoma. Oral squamous cell carcinomas displayed overexpression of DPAGT1 that correlated with diminished localization of E-cadherin and α-catenin at the sites of adherens junctions. Our studies show for the first time that DPAGT1 is an upstream regulator of E-cadherin N-glycosylation status and adherens junction composition and suggest that dysregulation of DPAGT1 causes disturbances in intercellular adhesion in oral cancer. [Cancer Res 2009;69(14):5673–80]
MUC1, a New Hypoxia Inducible Factor Target Gene, Is an Actor in Clear Renal Cell Carcinoma Tumor Progression
Authors: Aubert Sébastien , Fauquette Valérie , Hémon Brigitte , Lepoivre Réjane , Briez Nicolas , Bernard David , Van Seuningen Isabelle , Leroy Xavier , Perrais Michaël 
Published: July 2009

Abstract
The hypoxia inducible factor (HIF) signaling pathway is known as the main renal carcinogenetic pathway. MUC1, an O-glycoprotein membrane-bound mucin, is overexpressed in clear renal cell carcinomas (cRCC) with correlation to two major prognostic factors: tumor-node-metastasis stage and nuclear Fürhman grade. We questioned whether there is a direct link between the HIF pathway and MUC1 overexpression in renal tumors. Interestingly, we observed concomitant increase of HIF-1α and MUC1 in metastatic cRCC group versus nonmetastatic cRCC group. Using different renal cell models and small interfering RNA assays targeting either HIF-1α or YC-1, a HIF-1 pharmacologic inhibitor, we showed induction of MUC1 expression under hypoxia by a HIF-dependent mechanism. Chromatin immunoprecipitation assay showed a direct binding of HIF-1α at the MUC1 promoter. In addition, combined site-directed mutagenesis and gel shift assay allowed the identification of two functional putative hypoxia responsive elements at −1488/−1485 and at −1510/−1507 in the promoter. Using a rat kidney model of ischemia/reperfusion, we confirmed in vivo that clamping renal pedicle for 1 hour followed by 2 hours of reperfusion induced increased MUC1 expression. Furthermore, MUC1 knockdown induced significant reduction of invasive and migration properties of renal cancer cells under hypoxia. Altogether, these results show that MUC1 is directly regulated by HIF-1α and affects the invasive and migration properties of renal cancer cells. Thus, MUC1 could serve as a potential therapeutic target in cRCC. [Cancer Res 2009;69(14):5707–15]
Xenoestrogen-Induced Epigenetic Repression of microRNA-9-3 in Breast Epithelial Cells
Authors: Hsu Pei-Yin , Deatherage Daniel E. , Rodriguez Benjamin A.T. , Liyanarachchi Sandya , Weng Yu-I , Zuo Tao , Liu Joseph , Cheng Alfred S.L. , Huang Tim H-M. 
Published: July 2009

Abstract
Early exposure to xenoestrogens may predispose to breast cancer risk later in adult life. It is likely that long-lived, self-regenerating epithelial progenitor cells are more susceptible to these exposure injuries over time and transmit the injured memory through epigenetic mechanisms to their differentiated progeny. Here, we used progenitor-containing mammospheres as an in vitro exposure model to study this epigenetic effect. Expression profiling identified that, relative to control cells, 9.1% of microRNAs (82 of 898 loci) were altered in epithelial progeny derived from mammospheres exposed to a synthetic estrogen, diethylstilbestrol. Repressive chromatin marks, trimethyl Lys27 of histone H3 (H3K27me3) and dimethyl Lys9 of histone H3 (H3K9me2), were found at a down-regulated locus, miR-9-3, in epithelial cells preexposed to diethylstilbestrol. This was accompanied by recruitment of DNA methyltransferase 1 that caused an aberrant increase in DNA methylation of its promoter CpG island in mammosphere-derived epithelial cells on diethylstilbestrol preexposure. Functional analyses suggest that miR-9-3 plays a role in the p53-related apoptotic pathway. Epigenetic silencing of this gene, therefore, reduces this cellular function and promotes the proliferation of breast cancer cells. Promoter hypermethylation of this microRNA may be a hallmark for early breast cancer development, and restoration of its expression by epigenetic and microRNA-based therapies is another viable option for future treatment of this disease. [Cancer Res 2009;69(14):5936–45]
Cetuximab/C225-Induced Intracellular Trafficking of Epidermal Growth Factor Receptor
Authors: Liao Hong-Jun , Carpenter Graham 
Published: July 2009

Abstract
The monoclonal antibody C225 interacts with the ectodomain of the epidermal growth factor (EGF) receptor (EGFR) to block ligand binding and initiates receptor endocytosis and intracellular trafficking. The data herein show that C225-dependent EGFR trafficking relocalizes the receptor to the endoplasmic reticulum (ER) and nucleus. This mechanism, which also involves interaction of the C225-internalized receptor with the Sec61 translocon within the ER, is, in most respects, analogous to the pathway previously described for EGF-induced trafficking to the ER and nucleus. However, although inhibition of receptor tyrosine kinase activity blocks EGF-induced nuclear localization of the receptor, the same kinase inhibitors stimulate C225-dependent nuclear localization of EGFR in the nucleus. In contrast, the kinase inhibitor Lapatinib fails to stimulate nuclear accumulation of the receptor in C225-treated cells and does not provoke receptor dimerization as do inhibitors that recognize the open conformation of the receptor kinase. This suggests that inhibitor-dependent receptor dimerization may facilitate C225-induced receptor trafficking. [Cancer Res 2009;69(15):6179–83]
Polycomb CBX7 Promotes Initiation of Heritable Repression of Genes Frequently Silenced with Cancer-Specific DNA Hypermethylation
Authors: Mohammad Helai P. , Cai Yi , McGarvey Kelly M. , Easwaran Hariharan , Van Neste Leander , Ohm Joyce E. , O'Hagan Heather M. , Baylin Stephen B. 
Published: July 2009

AbstractEpigenetic silencing of genes in association with aberrant promoter DNA hypermethylation has emerged as a significant mechanism in the development of human cancers. Such genes are also often targets of the polycomb group repressive complexes in embryonic cells. The polycomb repressive complex 2 (PRC2) has been best studied in this regard. We now examine a link between PRC1 and cancer-specific gene silencing. Here, we show a novel and direct association between a constituent of the PRC1 complex, CBX7, with gene repression and promoter DNA hypermethylation of genes frequently silenced in cancer. CBX7 is able to complex with DNA methyltransferase (DNMT) enzymes, leading us to explore a role for CBX7 in maintenance and initiation of gene silencing. Knockdown of CBX7 was unable to relieve suppression of deeply silenced genes in cancer cells; however, in embryonal carcinoma (EC) cells, CBX7 can initiate stable repression of genes that are frequently silenced in adult cancers. Furthermore, we are able to observe assembly of DNMTs at CBX7 target gene promoters. Sustained expression of CBX7 in EC cells confers a growth advantage and resistance to retinoic acid–induced differentiation. In this setting, especially, there is increased promoter DNA hypermethylation for many genes by analysis of specific genes, as well as through epigenomic studies. Our results allow us to propose a potential mechanism through assembly of novel repressive complexes, by which the polycomb component of PRC1 can promote the initiation of epigenetic changes involving abnormal DNA hypermethylation of genes frequently silenced in adult cancers. [Cancer Res 2009;69(15):6322–30]
Tumor Repressive Functions of Estrogen Receptor β in SW480 Colon Cancer Cells
Authors: Hartman Johan , Edvardsson Karin , Lindberg Karolina , Zhao Chunyan , Williams Cecilia , Ström Anders , Gustafsson Jan-Åke 
Published: July 2009

Abstract
Estrogen receptor β (ERβ) is the predominant ER in the colorectal epithelium. Compared with normal colon tissue, ERβ expression is reduced in colorectal cancer. Our hypothesis is that ERβ inhibits proliferation of colon cancer cells. Hence, the aim of this study has been to investigate the molecular function of ERβ in colon cancer cells, focusing on cell cycle regulation. SW480 colon cancer cells have been lentivirus transduced with ERβ expression construct with or without mutated DNA-binding domain or an empty control vector. Expression of ERβ resulted in inhibition of proliferation and G1 phase cell cycle arrest and this effect was dependent on a functional DNA-binding region. c-Myc is overexpressed in an overwhelming majority of colorectal tumors. By Western blot and real-time PCR, we found c-Myc to be down-regulated in the ERβ-expressing cells. Furthermore, the c-Myc target gene p21(Waf1/Cip1) was induced and Cdc25A was reduced by ERβ at the transcriptional level. The second cdk2-inhibitor, p27Kip1, was induced by ERβ, but this regulation occurred at the posttranscriptional level, probably through ERβ-mediated repression of the F-box protein p45Skp2. Expression of the ERβ-variant with mutated DNA binding domain resulted in completely different cell cycle gene regulation. We performed in vivo studies with SW480 cells ± ERβ transplanted into severe combined immunodeficient/beige mice; after three weeks of ERβ-expression, a 70% reduction of tumor volume was seen. Our results show that ERβ inhibits proliferation as well as colon cancer xenograft growth, probably as a consequence of ERβ-mediated inhibition of cell-cycle pathways. Furthermore, this ERβ-mediated cell cycle repression is dependent on functional ERE binding. [Cancer Res 2009;69(15):6100–6]
Cucurbitacin B Induces Apoptosis by Inhibition of the JAK/STAT Pathway and Potentiates Antiproliferative Effects of Gemcitabine on Pancreatic Cancer Cells
Authors: Thoennissen Nils H. , Iwanski Gabriela B. , Doan Ngan B. , Okamoto Ryoko , Lin Patricia , Abbassi Sam , Song Jee Hoon , Yin Dong , Toh Melvin , Xie Wei Dong , Said Jonathan W. , Koeffler H. Phillip 
Published: July 2009

Abstract
Pancreatic cancer is an aggressive malignancy that is generally refractory to chemotherapy, thus posing experimental and clinical challenges. In this study, the antiproliferative effect of the triterpenoid compound cucurbitacin B was tested in vitro and in vivo against human pancreatic cancer cells. Dose-response studies showed that the drug inhibited 50% growth of seven pancreatic cancer cell lines at 10−7 mol/L, whereas clonogenic growth was significantly inhibited at 5 × 10−8 mol/L. Cucurbitacin B caused dose- and time-dependent G2-M-phase arrest and apoptosis of pancreatic cancer cells. This was associated with inhibition of activated JAK2, STAT3, and STAT5, increased level of p21WAF1 even in cells with nonfunctional p53, and decrease of expression of cyclin A, cyclin B1, and Bcl-XL with subsequent activation of the caspase cascade. Interestingly, the combination of cucurbitacin B and gemcitabine synergistically potentiated the antiproliferative effects of gemcitabine on pancreatic cancer cells. Moreover, cucurbitacin B decreased the volume of pancreatic tumor xenografts in athymic nude mice by 69.2% (P &lt; 0.01) compared with controls without noticeable drug toxicities. In vivo activation of JAK2/STAT3 was inhibited and expression of Bcl-XL was decreased, whereas caspase-3 and caspase-9 were up-regulated in tumors of drug-treated mice. In conclusion, we showed for the first time that cucurbitacin B has profound in vitro and in vivo antiproliferative effects against human pancreatic cancer cells, and the compound may potentate the antiproliferative effect of the chemotherapeutic agent gemcitabine. Further clinical studies are necessary to confirm our findings in patients with pancreatic cancer. [Cancer Res 2009;69(14):5876–84]