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The lysine acetyltransferase (KAT) Rtt109 forms a complex with Vps75 and catalyzes the acetylation of histone H3 lysine 56 (H3K56ac) in the Asf1-H3-H4 complex. Rtt109 and H3K56ac are vital for replication-coupled nucleosome assembly and genotoxic resistance in yeast and pathogenic fungal species such as Candida albicans. Remarkably, sequence homologs of Rtt109 are absent in humans. Therefore, inhibitors of Rtt109 are hypothesized as potential and minimally toxic antifungal agents. Herein, we report the development and optimization of a cell-free fluorometric high-throughput screen (HTS) for small-molecule inhibitors of Rtt109-catalyzed histone acetylation. The KAT component of the assay consists of the yeast Rtt109-Vps75 complex, while the histone substrate complex consists of full-length Drosophila histone H3-H4 bound to yeast Asf1. Duplicated assay runs of the LOPAC demonstrated day-to-day and plate-to-plate reproducibility. Approximately 225,000 compounds were assayed in a 384-well plate format with an average Z' factor of 0.71. Based on a 3σ cut-off criterion, 1,587 actives (0.7%) were identified in the primary screen. The assay method is capable of identifying previously reported KAT inhibitors such as garcinol. We also observed several prominent active classes of pan-assay interference compounds such as Mannich bases, catechols and p-hydroxyarylsulfonamides. The majority of the primary active compounds showed assay signal interference, though most assay artifacts can be efficiently removed by a series of straightforward counter-screens and orthogonal assays. Post-HTS triage demonstrated a comparatively small number of confirmed actives with IC50 values in the low micromolar range. This assay, which utilizes five label-free proteins involved in H3K56 acetylation in vivo, can in principle identify compounds that inhibit Rtt109-catalyzed H3K56 acetylation via different mechanisms. Compounds discovered via this assay or adaptations thereof could serve as chemical probes or leads for a new class of antifungals targeting an epigenetic enzyme.

This book, comprising approximately 300 letters, provides access to the voice of Robert Sobukwe via the single most poignant resource of Sobukwe’s voice that exists: his prison letters. Not only do the letters evince Sobukwe’s storytelling abilities, they convey the complexity of a man who defied easy categorization. More than this: they are testimony both to the desolate conditions of his imprisonment and to Sobukwe’s unbending commitment to the cause of African liberation. The memory of Robert Mangaliso Sobukwe, inspirational political leader and first President of the Pan-Africanist Congress, has been sadly neglected in post-apartheid South Africa. In 1960, Sobukwe led the Anti-Pass Protests, which culminated in the Sharpeville Massacre, which proved a crucial turning point in the eventual demise of apartheid. Nevertheless, Sobukwe – a man once thought to hold greater promise for the liberation of South Africa than even Nelson Mandela – has been consistently marginalised in histories of the liberation struggle. Jailed for nine years, including a six-year period of near complete solitary confinement on Robben Island, Sobukwe was silenced throughout his life, a condition that has been extended into the post-apartheid present, so much so that we can say that Sobukwe was better known during rather than after apartheid. Given Sobukwe’s antagonistic relations both to white liberalism and to the African National Congress (whom he felt had betrayed the principles of African Nationalism), it is unsurprising that he has been subjected to a ‘consensus of forgetting’. With the changing political climate of recent years, the decline of the African National Congress’s hegemonic hold on power, the re-emergence of Black Consciousness and Africanist political discourse, the growth of student protests, Sobukwe is being looked to once again. Robert Sobukwe, the founder and first leader of the Pan Africanist Congress (PAC), was silenced throughout his life, a condition which has been extended into the post-apartheid present. This book, comprising approximately 300 letters, provides access to his words via the single most poignant resource of Sobukwe’s own voice that exists: his prison letters. Not only do the letters evince Sobukwe’s storytelling abilities, they convey the complexity of a man who defied easy categorisation. More than this: they are testimony both to the desolate conditions of his imprisonment and to Sobukwe’s unbending commitment to the cause of African liberation. Although jailed for nine years, including a six-year period of near complete solitary confinement on Robben Island, Sobukwe was better known during rather than after apartheid. Given his antagonistic views to both white liberalism and the African National Congress (ANC) it is unsurprising that he has been subjected to a ‘consensus of forgetting’. With the changing political climate of recent years, the decline of the ANC’s hegemonic hold on power, the re-emergence of Black Consciousness and Africanist political discourse and the growth of student protests, Sobukwe is being looked to as a leader once again.

The notion of \"enjoyment as a political factor\" is a key motif in Lacanian psychoanalytic social theory. This article explores the notion of enjoyment/jouissance—a type of \"negative pleasure\" or intense libidina arousal—as an instrument of political analysis. Crucial here are a series of qualifications that refine an understanding of the concept. The article clarifies that enjoyment is: sexual (or libidinal) in nature; bodily rather than unconscious; necessarily excessive (since it is \"beyond the pleasure principle\" and linked to the functioning of the death drive); and illicit, incurred in acts that apparently transgress laws or socially prescribed limits. A series of critical arguments are noted, such as the idea that jouissance cannot be extrapolated to the level of the social, and the contention that as \"extradiscursive,\" modes of enjoyment float free of the symbolic. Contrary to such contentions, I offer a series of examples—most typically of racism—to demonstrate how jouissance occurs within the symbolic, implies a dialectic of possession, involves the functioning of the law and superego, entails particular rules and contracts of enjoyment, and is structured b fantasy. Jouissance understood in these ways necessarily supports and extend social structure.

Swiss Army Knives is the comprehensive guide for Swiss Army Knives no collector should live without. This fascinating, colorfully illustrated book is a celebration of one of the great icons of Swiss culture. Swiss Army Knives catalogs each gadget, beginning with the simple Soldier's knife, later developed into the Student Knife, the Cadet Knife, and Farmer's Knife. Each model is accompanied with a narrative. For example, the Soldier's knife was heavy, which led developers to create the lighter Officer's knife, with an added second blade and a corkscrew. The book includes hundreds of illustrated examples of Swiss Army Knives and anecdotes from military personnel and other owners and a comprehensive model identification system, for the dedicated collectors. This fascinating, colorfully illustrated celebration of one of the great icons of Swiss culture--in France it's the Couteau Swiss, in Germany the Schweizer Messer, and to the English-speaking world it's the Victorinox Swiss Army Knife--used by military programs the world over and given away as gifts to guests by the White House (Lyndon Johnson did it first).

This paper focusses on a series of online attacks that the author was subjected to after comments he had made in a closed lecture on the topic of ‘white anxiety’ were cut from the zoom recording and distributed widely online with the clear intent of causing outrage. The analysis of the material, which combines thematic, discourse analytic and personal reflections, yielded a series of core themes: 1) the role of the messages in consolidating an identity, 2) performative offensiveness, 3) perverse intimidations, 4) accusations/denials/expressions of racism, 5) the race-traitor as ideological dilemma, 6) antisemitism and 7) aggressive cordiality. The paper closes with a few reflections on the author’s enunciative position in respect of the attacks.

\"This book of approximately 300 letters provides access to the voice of Robert Mangaliso Sobukwe via the single most poignant resource that exists: his prison letters. Not only do these letters evince Sobukwe's storytelling abilities, they convey the complexity of a man who defied easy categorisation. More than this: they are testimony to both the desolate conditions of his imprisonment and to Sobukwe's unbending commitment to the cause of African liberation. The memory of Sobukwe, inspirational political leader and first President of the Pan Africanist Congress, has been consistently marginalized in histories of the liberation struggle. Given Sobukwe's antagonistic relations both to white liberalism and the African National Congress, it is unsurprising that he has been subjected to a 'consensus of forgetting'. This collection of letters brings Sobukwe's voice back to the fore\"--Back cover.

Comments on Jean-Paul Baldacchino's \"The eidetic of belonging: Towards a phenomenological psychology of affect and ethno-national identity.\". [Reprinted by permission of Sage Publications Ltd., copyright holder.]