Becoming Racially Aware: A Social Process of (Re)constructing an Alternative White Identity

Structural and systemic mechanisms reinforce institutionalized racism, whiteness, and white supremacy in the United States. These mechanisms prove adaptable and resilient, shifting and changing to continuously restructure and reinforce the material reality that people experience within a racialized social order. White people\u27s incomprehension of complicity in racism and privilege, along with color-blind ideologies, perpetuate racialized disparities resulting from this social order and render white superiority as normal and universal. This underlies an often internalized sense of normative, white American identity interconnected with racism and white supremacy. In a society where many white Americans remain sheltered from and/or resistant to acknowledging the material realities of institutionalized racism and white supremacy, how and why do some white people become racially aware and take action in favor of equity? That was the focus of this research project. In applying a multifaceted theoretical and methodological framework rooted in critical race theory, critical whiteness studies, grounded theory, and narrative approaches to the analysis of 33 interviews of white Americans, it emerged that the process of becoming racially aware is a complex process of ongoing identity (re)construction. Participants actively push against a normalized white identity to (re)construct an alternative white, racially aware identity, making sense of this identity (re)construction through three components of this process: (1) becoming aware through several stages; (2) making sense of the meaning of being racially aware; and (3) engaging in social action. Together, these components formulate this process of identity work and expand existing critical whiteness studies scholarship by deepening our understanding of how some white Americans attempt to deconstruct systemic inequities through their own identity (re)construction. Such understandings inform potential interventions that could be utilized for collective social change

Führen alle Wege zum CREB?

Conditions of pathological thyroid growth are extremely common, and currently they are one of the most frequently encountered problems in endocrinological practice. While TSH and its mediator cAMP are well-established regulators of normal thyroid growth, the last decade has provided evidence that pathological growth may instead involve disturbances in tyrosine kinase and PKC activities. In this study, the activation of CRE-binding protein family of transcription factors upon exposure to established thyroid growth factors was examined. CREB/M phosphorylation was found to occur in a time- and dosage-dependent manner, not only upon induction of cAMP signalling with forskolin and TSH, but also upon stimulation with TPA, EGF or insulin, the latter requiring a minimal concentration of 1 μg/mL, indicating the employment of IGF receptor types. Semiquantitative RT-PCR of ICER and transient transfection with a CRE-reporter construct were employed to investigate transcriptional activation upon CREB/M- phosphorylation. Surprisingly, there was a striking difference in the kinetics of TSH/forskolin induction of CRE-mediated gene induction (5-fold increase, maximal at 8 hours), and EGF/TPA (2.5-fold, maximal at 24 hours). Application of specific kinase inhibitors revealed the involvement of PKA and PKC in CREB/M-KID phosphorylation by both types of mediators, whereas neither p70S6K nor Camk II were found to be required. Interestingly, the response towards TSH was biphasic, with the first phosphorylation peak seen at 10 min and coinciding with maximal sensitivity to the PKA inhibitor H89, and the second peak seen at 30 minutes with simultaneously maximal sensitivity to PKC inhibition by GFX. In contrast, during EGF- mediated CREB/M-phosphorylation PKC and PKA appeared to act within a single pathway. Comparing CRE-binding factor activation in thyroid primary cells with that seen in several thyroid carcinoma cell lines, an increasing reactivity towards EGF was found to accompany a concomitant loss to TSH/insulin-responsiveness and differentiation. Taken together, the results of this study thus support the idea of TSH/insulin and PKA being the main mediators in normal and benign thyroid growth, whereas EGF and PKC are the predominant triggers in malignant transformation.Problematik: Erkrankungen der Schilddrüse, im allgemeinen und solche pathologischen Wachstums im besonderen, sind extrem verbreitet und stellen ein in der endokrinologischen Praxis häufig angetroffenes Problem dar. Jodmangel, begleitet von chronisch erhöhten Spiegeln des Schilddrüsen stimulierenden Hormons (TSH) mit folgender Aktivierung des TSH-Rezeptor-cAMP Signaltransduktionsweges, scheint die treibende Kraft hinter der diffusen Schilddrüsenvergrößerung zu sein. Dagegen ist es wahrscheinlich, daß der spätere noduläre Umbau sowie die maligne Entartung auf Störungen der Funktion von Tyrosinkinase-Rezeptoren und der PKC beruhen. Die Familie CRE-bindender Transkriptionsfaktoren wurde ursprünglich als Effektoren des cAMP-PKA-Weges beschrieben, jedoch später auch in vielen Zellarten als Endpunkte von Tyrosinkinase-Rezeptor-Kaskaden identifiziert. Das Ziel dieser Arbeit war daher abzuklären, ob (1) CRE-bindende Proteine auch in der Schilddrüse Endpunkte von Tyrosinkinase-Rezeptor-Signaltransduktionswegen sind, (2) ob in Schilddrüsenkarzinomzellen aberrante CREB/M-Phosphorylierungsmuster vorliegen, (3) ob die Phosphorylierung über diese Wege auch zur Induktion CRE-regulierter Gene führt, und (4) unter Anwendung spezifischer Inhibitoren, die beteiligten Proteinkinase-Kaskaden zumindest in Teilen zu identifizieren. Methodik: Primäre Thyrozyten wurden mit TSH, EGF oder Insulin in unterschiedlichen Konzentrationen sowie für verschiedene Zeiträume stimuliert. Die Aktivierung CRE-bindender Proteine wurde im Western-Blot durch Verwendung eines gegen das regulatorische Serin gerichteten phospho-spezifischen Antikörpers untersucht. Die erhaltenen Aktivierungsprofile wurden dann mit denen vierer humaner Karzinomzellinien (zwei follikuläre, zwei anaplastische) sowie einer Rattenadenomzellinie verglichen. Auf Transkriptionsebene wurde die Induktion des negativen Feedback Regulators inducible cAMP early repressor (ICER) in der RT-PCR sowie die Luciferaseaktivität nach transienter Transfektion mit dem CRE-regulierten Reporterplasmid 4xSCE1/2T81 untersucht. Um die beteiligten Signaltransduktionswege zu identifizieren, wurden die spezifischen Inhibitoren H89 (PKA), GFX (PKC), Rapamycin (mTOR/p70S6K) sowie KN62 (CamKII) eingesetzt. Zusätzlich wurden PKC- und cAMP-abhängige Wege direkt mit TPA bzw. Forskolin aktiviert. Schließlich wurde das Expressionsprofil bestimmter PKC- Isoformen während der prolongierten Stimulation im Western-Blot untersucht

Nitroxoline induces apoptosis and slows glioma growth in vivo

BACKGROUND: Nitroxoline is an FDA-approved antibiotic with potential antitumor activity. Here we evaluated whether nitroxoline has antiproliferative properties on glioma cell growth in vitro and in vivo using glioma cell lines and a genetically engineered PTEN/KRAS mouse glioma model. METHODS: The effect of nitroxoline treatment on U87 and/or U251 glioma cell proliferation, cell-cycle arrest, invasion, and ability to induce an apoptotic cascade was determined in vitro. Magnetic resonance imaging was used to measure glioma volumes in genetically engineered PTEN/KRAS mice prior to and after nitroxoline therapy. Induction of apoptosis by nitroxoline was evaluated at the end of treatment using terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick end labeling (TUNEL). RESULTS: Nitroxoline inhibited the proliferation and invasion of glioblastoma cells in a time- and dose-dependent manner in vitro. Growth inhibition was associated with cell-cycle arrest in G(1)/G(0) phase and induction of apoptosis via caspase 3 and cleaved poly(ADP-ribose) polymerase. In vivo, nitroxoline-treated mice had no increase in tumor volume after 14 days of treatment, whereas tumor volumes doubled in control mice. Histological examination revealed 15%–20% TUNEL-positive cells in nitroxoline-treated mice, compared with ∼5% in the control group. CONCLUSION: Nitroxoline induces apoptosis and inhibits glioma growth in vivo and in vitro. As an already FDA-approved treatment for urinary tract infections with a known safety profile, nitroxoline could move quickly into clinical trials pending confirmatory studies