A novel, non-apoptotic role for Scythe/BAT3: a functional switch between the pro- and anti-proliferative roles of p21 during the cell cycle.

BACKGROUND: Scythe/BAT3 is a member of the BAG protein family whose role in apoptosis has been extensively studied. However, since the developmental defects observed in Bat3-null mouse embryos cannot be explained solely by defects in apoptosis, we investigated whether BAT3 is also involved in cell-cycle progression. METHODS/PRINCIPAL FINDINGS: Using a stable-inducible Bat3-knockdown cellular system, we demonstrated that reduced BAT3 protein level causes a delay in both G1/S transition and G2/M progression. Concurrent with these changes in cell-cycle progression, we observed a reduction in the turnover and phosphorylation of the CDK inhibitor p21, which is best known as an inhibitor of DNA replication; however, phosphorylated p21 has also been shown to promote G2/M progression. Our findings indicate that in Bat3-knockdown cells, p21 continues to be synthesized during cell-cycle phases that do not normally require p21, resulting in p21 protein accumulation and a subsequent delay in cell-cycle progression. Finally, we showed that BAT3 co-localizes with p21 during the cell cycle and is required for the translocation of p21 from the cytoplasm to the nucleus during the G1/S transition and G2/M progression. CONCLUSION: Our study reveals a novel, non-apoptotic role for BAT3 in cell-cycle regulation. By maintaining a low p21 protein level during the G1/S transition, BAT3 counteracts the inhibitory effect of p21 on DNA replication and thus enables the cells to progress from G1 to S phase. Conversely, during G2/M progression, BAT3 facilitates p21 phosphorylation by cyclin A/Cdk2, an event required for G2/M progression. BAT3 modulates these pro- and anti-proliferative roles of p21 at least in part by regulating cyclin A abundance, as well as p21 translocation between the cytoplasm and the nucleus to ensure that it functions in the appropriate intracellular compartment during each phase of the cell cycle.

Popular culture, relational history, and the question of power in Palestine and Israel

The marginalization of popular culture in radical scholarship on Palestine and Israel is symptomatic of the conceptual limits that still define much Middle East studies scholarship: namely, the prevailing logic of the nation-state on the one hand and the analytic tools of classical Marxist historiography and political economy on the other. This essay offers a polemic about the form that alternative scholarly projects might take through recourse to questions of popular culture. The authors argue that close allention to the ways that popular culture "articulates" with broader political, social, and economic processes can expand scholarly understandings of the terrain of power in Palestine and Israel, and hence the possible arenas and modalities of struggle. © 2004 by the Institute for Palestine Studies. All rights reserved.

R5 clade C SHIV strains with tier 1 or 2 neutralization sensitivity: tools to dissect env evolution and to develop AIDS vaccines in primate models.

BACKGROUND: HIV-1 clade C (HIV-C) predominates worldwide, and anti-HIV-C vaccines are urgently needed. Neutralizing antibody (nAb) responses are considered important but have proved difficult to elicit. Although some current immunogens elicit antibodies that neutralize highly neutralization-sensitive (tier 1) HIV strains, most circulating HIVs exhibiting a less sensitive (tier 2) phenotype are not neutralized. Thus, both tier 1 and 2 viruses are needed for vaccine discovery in nonhuman primate models. METHODOLOGY/PRINCIPAL FINDINGS: We constructed a tier 1 simian-human immunodeficiency virus, SHIV-1157ipEL, by inserting an "early," recently transmitted HIV-C env into the SHIV-1157ipd3N4 backbone [1] encoding a "late" form of the same env, which had evolved in a SHIV-infected rhesus monkey (RM) with AIDS. SHIV-1157ipEL was rapidly passaged to yield SHIV-1157ipEL-p, which remained exclusively R5-tropic and had a tier 1 phenotype, in contrast to "late" SHIV-1157ipd3N4 (tier 2). After 5 weekly low-dose intrarectal exposures, SHIV-1157ipEL-p systemically infected 16 out of 17 RM with high peak viral RNA loads and depleted gut CD4+ T cells. SHIV-1157ipEL-p and SHIV-1157ipd3N4 env genes diverge mostly in V1/V2. Molecular modeling revealed a possible mechanism for the increased neutralization resistance of SHIV-1157ipd3N4 Env: V2 loops hindering access to the CD4 binding site, shown experimentally with nAb b12. Similar mutations have been linked to decreased neutralization sensitivity in HIV-C strains isolated from humans over time, indicating parallel HIV-C Env evolution in humans and RM. CONCLUSIONS/SIGNIFICANCE: SHIV-1157ipEL-p, the first tier 1 R5 clade C SHIV, and SHIV-1157ipd3N4, its tier 2 counterpart, represent biologically relevant tools for anti-HIV-C vaccine development in primates.

Informatic Opacity: Biometric Facial Recognition and the Aesthetics and Politics of Defacement

Confronting the rapidly increasing, worldwide reliance on biometric technologies to surveil, manage, and police human beings, my dissertation Informatic Opacity: Biometric Facial Recognition and the Aesthetics and Politics of Defacement charts a series of queer, feminist, and anti-racist concepts and artworks that favor opacity as a means of political struggle against surveillance and capture technologies in the 21st century. Utilizing biometric facial recognition as a paradigmatic example, I argue that today's surveillance requires persons to be informatically visible in order to control them, and such visibility relies upon the production of technical standardizations of identification to operate globally, which most vehemently impact non- normative, minoritarian populations. Thus, as biometric technologies turn exposures of the face into sites of governance, activists and artists strive to make the face biometrically illegible and refuse the political recognition biometrics promises through acts of masking, escape, and imperceptibility. Although I specifically describe tactics of making the face unrecognizable as "defacement," I broadly theorize refusals to visually cohere to digital surveillance and capture technologies' gaze as "informatic opacity," an aesthetic-political theory and practice of anti- normativity at a global, technical scale whose goal is maintaining the autonomous determination of alterity and difference by evading the quantification, standardization, and regulation of identity imposed by biometrics and the state. My dissertation also features two artworks: Facial Weaponization Suite, a series of masks and public actions, and Face Cages, a critical, dystopic installation that investigates the abstract violence of biometric facial diagramming and analysis. I develop an interdisciplinary, practice-based method that pulls from contemporary art and aesthetic theory, media theory and surveillance studies, political and continental philosophy, queer and feminist theory, transgender studies, postcolonial theory, and critical race studies.