John Mendelsohn: The Passing Paintings Brochure

Brochure for John Mendelsohn: The Passing Paintings at the Thomas J. Walsh Art Gallery, December 2, 2014 - February 27, 2015.https://digitalcommons.fairfield.edu/mendelsohn-ephemera/1000/thumbnail.jp

Nuclear targeting of Bax during apoptosis in human colorectal cancer cells

Homeostasis in colonic epithelial cells is regulated by the balance between proliferative activity and cell loss by apoptosis. Because epithelial cells at the apex of colonic crypts undergo apoptosis and proliferative activity is usually restricted to the base of the crypts, it has been proposed that the limited availability of growth factor-signals at the upper portions of the crypts may trigger apoptosis. In the present studies, we investigate the mechanism of apoptosis mediated by growth factor deprivation in colorectal carcinoma cells by delineating the possible involvement of Bax and its subcellular localization. We report that inhibition of Epidermal Growth Factor Receptor (EGFR) tyrosine kinase activity and downregulation of EGFR by anti-EGFR mAb 225 induces apoptosis in human colorectal carcinoma DiFi and FET cells. Induction of apoptosis was preceded by enhanced expression of newly synthesized Bax protein, and required protein synthesis. In the mAb 225-treated cells, Bax was redistributed from the cytosol to the nucleus and subsequently, to the nuclear membranes. The observed induction of Bax expression by mAb 225 was not associated with p53 induction. However, mAb 225 treatment also triggered relocalization of p53 from the cytosol to a nuclear membrane-bound form. Induction of Bax and its redistribution to the nucleus of DiFi cells during apoptosis was also demonstrated in response to butyrate, a physiological relevant molecule in colonic epithelial cells as it is the principal short-chain fatty acid produced by bacterial fermentation of dietary fiber in colonic epithelium. Using immunofluorescence and confocal microscopy, we observed that Bax is predominantly localized in the cytosol, but during apoptosis it is localized both inside and along the nuclear membrane. Taken together, these findings suggest that apoptosis induced by growth factor-deprivation or butyrate may involve the subcellular redistribution of Bax in human colorectal carcinoma cells

OncoLog Volume 44, Number 12, December 1999

Collaboration Between Scientists, Clinicians Moves Apoptosis Studies Forward Answering the Who, What, and How of Medical Physics USHERING IN NEW TECHNOLOGIES: Medical Physicists Focus on IMRT, Ultrasound-Guided Brachytherapy DiaLog: Building Better Patient Care on the Foundation of Scientific Research, by John Mendelsohn, MD, President, Professor of Clinical Investigation House Call: Make Cancer Prevention Part of Your New Year\u27s Resolutionshttps://openworks.mdanderson.org/oncolog/1080/thumbnail.jp

Physical interaction between epidermal growth factor receptor and DNA-dependent protein kinase in mammalian cells

Binding of extracellular ligands to epidermal growth factor receptors (EGFR) activate signal transduction pathways associated with cell proliferation, and these events are inhibited by monoclonal antibodies against EGFR. Since efficient DNA repair in actively growing cells may require growth factor signaling, it was of interest to explore any linkage between EGFR-mediated signaling and DNA-dependent protein kinase (DNA-PK), an enzyme believed to be involved in repairing double strand breaks and V(D)J recombination. We report that anti-EGFR monoclonal antibodies (mAbs), and not EGFR ligands, trigger a specific early physical interaction between EGFR and a 350-kDa catalytic subunit of DNA or its regulatory heterodimeric complex Ku70/80, in a variety of cell types, both in vivo and in vitro. Inhibition of EGFR signaling by anti-EGFR mAb was accompanied by a reduction in the levels of the DNA-PK and its activity in the nuclear fraction. Confocal imaging revealed that a substantial amount of DNA-PK was co-localized with EGFR in anti-EGFR mAb-treated cells. Anti-EGFR mAb-induced physical interaction between EGFR and DNA-PK or Ku70/80 was dependent on the presence of EGFR, but not on the levels of EGFR. The EGFR associated with DNA-PK or Ku70/80 retains its intrinsic kinase activity. Our findings demonstrate the existence of a novel cellular pathway in mammalian cells that involves physical interactions between EGFR and DNA-PK or Ku70/80 in response to inhibition of EGFR signaling. Our present observations suggest a possible role of EGFR signaling in maintenance of the nuclear levels of DNA-PK, and interference in EGFR signaling may possibly result in the impairment of DNA repair activity in the nuclei in anti-EGFR mAb-treated cells

Regulation of cyclooxygenase-2 pathway by HER2 receptor

Emerging lines of evidence suggest that in addition to growth factors, the process of colorectal tumorigenesis may also be driven by the upregulation of the inducible form of cyclooxygenase-2 (COX-2), an enzyme responsible for the conversion of arachidonic acid to PGEs. The present study was undertaken to investigate the expression and activation of the HER family members, and to explore the regulation of COX-2 expression by the HER2 pathway in human colorectal cancer cells. Here, we report that human colorectal cancer cell lines express abundant levels of HER2 and HER3 receptors, and are growth-stimulated by recombinant neu-differentiation factor-beta 1 (NDF). NDF-treatment of colorectal cancer cells was accompanied by increased tyrosine phosphorylation and heterodimerization of HER3 with HER2. In addition, we demonstrated that HER2 and HER3 receptors in colorectal cancer cells are constitutively phosphorylated on tyrosine residues and form heterodimeric complexes in the absence of exogenous NDF. Inhibition of HER2/HER3 signaling by an anti-HER3 mAb against the ligand binding site resulted in a decrease in the levels of constitutively activated HER2/HER3 heterodimers, and the unexpected reduction of COX-2 expression. Activation of the HER2/HER3 pathway by NDF induced the activation of COX-2 promoter, expression of COX-2 mRNA, COX-2 protein and accumulation of prostaglandin E2 in the culture medium. Finally, we demonstrated that NDF promotes the ability of colorectal cancer cells to survive in an extracellular matrix milieu, such as Matrigel, and also to invade through a 8 μm porous membrane. These biological activities of NDF and its stimulation of cell proliferation are blocked by a specific inhibitor of COX-2. Taken together, our findings provide the first biochemical evidence of a possible role of the COX-2 pathway in the mitogenic action of NDF in colorectal cancer cells where it may be constitutively upregulated due to the autocrine/paracrine activation of HER2/HER3 heterodimers

Histoire des " Big Five " : OCEAN des cinq grands facteurs de la personnalité. Introduction du Big Five Inventory français ou BFI-FR

International audienceLa description de la personnalité a été conçue à partir d'une variété de points de vue théoriques et à différents niveaux d'abstraction. Dans l'étude de la personnalité, l'unité la plus fréquemment utilisée pour mesurer les différences individuelles a été le trait. Un consensus semble se dégager actuellement sur une taxonomie générale des traits de la personnalité, les cinq facteurs de la personnalité, connus sous le nom des " Big Five ", expression introduite par Goldberg. Le but de cet article est de resituer l'élaboration de la version originale du Big Five Inventory (BFI) de John, Donahue et Kentle (1991) dans son histoire, et parmi les autres tests disponibles le " TDA ou trait descriptive adjective " de Goldberg et le " NEO PI-R ou NEO personality inventory revised " de Costa et McCrae. La revue reprend les différents stades de conceptualisation des catégories qui furent élaborées à partir d'une sélection d'adjectifs de dictionnaires permettant de différencier un individu d'un autre. Seuls les traits seront utilisés pour l'élaboration des trois tests mentionnés. Les " Big Five " retrouvés à partir d'analyses factorielles peuvent se résumer en cinq facteurs réplicables connus sous le nom de OCEAN ou CANOE de la personnalité, moyen mnémotechnique pour E (Extraversion, Énergie, Enthousiasme) ; A (Agréabilité, Altruisme, Affection) ; C (Conscience, Contrôle, Contrainte) ; N (Émotions Négatives, Névrosisme, Nervosité) ; O (Ouverture, Originalité, Ouverture d'esprit), ordre établi par les auteurs du BFI. La structure des " Big Five " regroupe à un haut niveau d'abstraction les points communs de la plupart des systèmes existant sur la description de la personnalité et met à disposition un modèle descriptif intégré pour des recherches sur la personnalité

Creating a Culture of Mentoring @ Your Library

The need to find and retain high quality leadership for libraries is one of the top seven issues for academic libraries. With a significant percentage of librarians planning to retire in the next decade, retaining professionals is imperative. Librarians must not only be retained, but mentored and developed for future leadership roles in the academic library community (Hisle, 2002). Creating a “culture of mentoring” helps the organization, individuals in the organization, and those with whom they interact. This culture provides integrity (accountability) throughout the organization, and opportunities for learning, for feedback and for improvement of performance throughout the organization. Libraries are using mentoring to orient new librarians, to assist them through the promotion and tenure process, and to provide information to librarians interested in advancement

Communal Land Tenure Security for Widows in the Eenhana Constituency of the Ohangwena Region, Namibia

Namibia is characterized by a history of discriminatory customary practices against women with regards to access to land, rights over land, and security of land tenure. Since independence in 1990, the country has adopted policies and legislative frameworks to bring about gender equality in all spheres of life, including the transformation of land tenure rights. These policies and acts give effect to the constitutional provisions that accord both men and women equal opportunities for access to land, rights over land and security of tenure. Widows are a particularly singled-out social group for legal protection, land security and rights to land enjoyed during their spouses’ lifetimes, and are granted protection, at least on paper, from discriminatory practices such as unlawful land evictions. This article evaluates and analyses the current status of land tenure security for widows in the Eenhana Constituency of the Ohangwena Region in Namibia. The study employed both quantitative and qualitative methods through questionnaires, interviews and focus group discussions with widows, as well as key informant interviews with Communal Land Board representatives, members of the traditional authorities, as well as the Ministry of Land Reform’s regional office officials. Through this case study, the findings establish that even though Namibia acclaims progressive policies and legislative frameworks on gender equality, there are still pockets of discrimination against widows where they continue to be at risk of losing their land rights in some of Namibia’s communal areas. Addressing the land tenure insecurities and a guarantee of legal land rights for widows is key to reducing vulnerabilities within female-headed households in the communal areas. Traditional authorities remain a key governance structure in communal areas, particularly in relation to access to land, and land rights inheritance issues, amongst others. Similarly, the Communal Land Boards are statutory institutions mandated to ensure implementation of the provisions of the Communal Land Reform Act of 2002, including the protection of land rights for widows. The study therefore recommends three main measures: the removal of all forms of discriminatory customary practices against widows; continued awareness-raising initiatives on the rights of widows; and full implementation of legal provisions for the protection of widows’ land rights and security of tenure

Growth factors regulate heterogeneous nuclear ribonucleoprotein K expression and function

Epidermal Growth Factor (EGF) family of growth factors and their receptors regulate normal and cancerous epithelial cell proliferation, a process that can be suppressed by antireceptor blocking antibodies. To identify genes whose expression may be modulated by antireceptor blocking antibodies, we performed a differential display screen with cells grown in the presence or absence of antireceptor blocking antibodies; isolates from one cDNA clone were 100% identical to human heterogeneous nuclear ribonucleoprotein K (hnRNP K), a protein with a conserved KH motif and RGG boxes, has been implicated in such functions as sequence-specific DNA binding, transcription, RNA binding and nucleocytoplasmic shuttling. Both EGF and heregulin-β1 induced expression of hnRNP K mRNA and protein in human breast cancer cells. This growth factor-mediated hnRNP K expression was effectively blocked by pretreatment of cultures with humanized anti-EGF Receptor (EGFR) antibody C225, or anti-human epidermal growth factor receptor-2 (HER2) antibody. Anti-EGFR monoclonal antibody also caused regression of human tumor xenografts and reduction in hnRNP K levels in athymic mice. Samples from grade III human breast cancer contained more hnRNP K protein than samples from grade II cancer. Finally, overexpression of hnRNP K in breast cancer cells significantly increased target c-myc promoter activity and c-Myc protein, hnRNP K protein levels, and enhanced breast cancer cell proliferation and growth in an anchorage-independent manner. These results suggested that the activity of human EGF receptor family members regulates hnRNP K expression by extracellular growth promoting signals and that therapeutic humanized antibodies against EGFR and HER2 can effectively block this function