Connection of core and tail Mediator modules restrains transcription from TFIID-dependent promoters

The Mediator coactivator complex is divided into four modules: head, middle, tail, and kinase. Deletion of the architectural subunit Med16 separates core Mediator (cMed), comprising the head, middle, and scaffold (Med14), from the tail. However, the direct global effects of tail/cMed disconnection are unclear. We find that rapid depletion of Med16 downregulates genes that require the SAGA complex for full expression, consistent with their reported tail dependence, but also moderately overactivates TFIID-dependent genes in a manner partly dependent on the separated tail, which remains associated with upstream activating sequences. Suppression of TBP dynamics via removal of the Mot1 ATPase partially restores normal transcriptional activity to Med16-depleted cells, suggesting that cMed/tail separation results in an imbalance in the levels of PIC formation at SAGA-requiring and TFIID-dependent genes. We propose that the preferential regulation of SAGA-requiring genes by tailed Mediator helps maintain a proper balance of transcription between these genes and those more dependent on TFIID.

An Opuscule on Method, or how Philosophers Mark out Textually their Methodological Stance (a Text Following up a Text)

The present paper is a practical supplement to an earlier theoretical work by the author, published in a preceding issue, on methodological foundations of the European philosophizing in the aspect of sophical synthesis. Building upon understanding of general philosophical methodologies (methodological attitudes) and their ‘epochal’ implementations as presented there, the author makes use of a cross-cutting example, to show ‘zones of responsibility’ and onto-gnoseo-epistemological limits for every mentioned ‘way towards the thing.’ Six marker packages (by the number of methodologies and variants of sophical viz. life-knowledge synthesis) should be of special professional interest as proposed by the author to identify methodological attitudes and ‘edge’ cases ranging from Antiquity to nowadays. Validity of each and all of these packages has been illustrated with proper textual material, i. e. fragments from essays by renowned European philosophers.In § 1, the naturalistic methodological attitude is considered, as focused on the proper vital aspect of sophical synthesis; its characteristic reliance on experience, fact, belief, opinion, and authority, and thereby on the rhetorical aspect of philosophizing, is explained.In § 2, the phenomenological methodological attitude is considered, as focused on the proper knowledge aspect of sophical synthesis; its characteristic reliance on knowledge and sense beyond any non-essential per se factual ways things are given, is explained.In § 3, the transcendental methodological attitude is considered, as focused on the synthesis of knowledge and life by means of knowledge in the aspect of logos of the logos per se; its characteristic reliance on sense being a sense in the making, and on fact as the bearer of a sense, with their integration in a common logical-conceptual thing structure, is explained.In § 4, the dialectic methodological attitude is considered, as focused on the synthesis of knowledge and life by means of knowledge in the aspect of logos of the eidos; its characteristic reliance on intelligent thing as a unit of sense and a product of senseful self-development wherein not only the thing is posited, but the entire otherness as defined by it as well, is explained.In § 5, the mythological methodological attitude is considered, as focused on the synthesis of knowledge and life in the aspect of their integral arrangement as vivid mind; its characteristic reliance on intelligent thing as a real and self-evident in its unicity live being, is explained.In § 6, the hermeneutical (= onomatological and overall symbolic) methodological attitude, as focused on the synthesis of knowledge and life in the aspect of its naming as an intelligent expression of thing for the other; its characteristic reliance on the name and text as a full expression of sense and a full knowledge of fact being revealed in the truth of thing, is explained.

Subleading corrections in $$ \mathcal{N} $$ = 3 Gaiotto-Tomasiello theory

We study subleading corrections to the genus-zero free energy of the $$ \mathcal{N} $$ N = 3 Gaiotto-Tomasiello theory. In general, we obtain the endpoints and free energy as a set of parametric equations via contour integrals of the planar resolvent, up to exponentially suppressed corrections. In the particular case that the two gauge groups in the quiver are of equal rank, we find an explicit (perturbative) expansion for the free energy. If, additionally, both groups have equal levels, then we find the full expression for the genus-zero free energy, modulo exponentially suppressed corrections. We also verify our results numerically.

Connection of core and tail Mediator modules restrains transcription from TFIID-dependent promoters

The Mediator coactivator complex is divided into four modules: head, middle, tail, and kinase. Deletion of the architectural subunit Med16 separates core Mediator (cMed), comprising the head, middle, and scaffold (Med14), from the tail. However, the direct global effects of tail/cMed disconnection are unclear. We find that rapid depletion of Med16 downregulates genes that require the SAGA complex for full expression, consistent with their reported tail dependence, but also moderately overactivates TFIID-dependent genes in a manner partly dependent on the separated tail, which remains associated with upstream activating sequences. Suppression of TBP dynamics via removal of the Mot1 ATPase partially restores normal transcriptional activity to Med16-depleted cells, suggesting that cMed/tail separation results in an imbalance in the levels of PIC formation at SAGA-requiring and TFIID-dependent genes. We suggest that the preferential regulation of SAGA-requiring genes by tailed Mediator helps maintain a proper balance of transcription between these genes and those more dependent on TFIID.

“Who’s got bars?”: Remixing Intergroup Dialogue Pedagogy through Hip-Hop Feminism

Hip-hop culture serves as a space to correct, prescribe, make known, and show up. Additionally, it offers its users opportunities to do what other spaces cannot, and that is to present a remix of a previously accepted script. Reintroduction can help Black lives, survive, dismantle, and escape systems of thinking that render them invisible and unheard. In this conceptually grounded manuscript, I discuss intergroup dialogue (IGD), with particular attention to IGD pedagogy. Though an important pedagogical strategy in and outside of higher education, IGD pedagogy may be operating to stifle the full expression of Black participants. By way of intervention, I point to possibilities within hip-hop feminism and hip-hop aesthetics to assist educators and facilitators in reimagining IGD pedagogical practice.

A Dynamic Interpretation of Nietzsche’s “The Greatest Weight”

GS 341 is one of the most familiar of Nietzsche’s writings. This article proposes a new reading that stands in contrast with most English-language Nietzsche scholarship. The text presents a communication and its reception. A ‘demon’ makes an announcement, and a hearer responds in one way or another. But there is also another narrative altogether, whose conceptual vocabulary comes from a dynamic world-view. In this an interaction of forces leads to a new situation. If the hearer is not crushed by the ‘greatest weight’, there must be an inner force that counteracts its impact. I argue that what Nietzsche calls amor fati is a state that allows our drives to achieve full expression, and so makes possible a collective strength able to withstand the greatest impact. The final sentence refers to a “confirmation and sealing”. What happens is that the demon’s message makes an impression on the receptive hearer. For Nietzsche this is a working metaphor, not a turn of phrase. In a draft from this period he writes: “Let us stamp the image of eternity on our life!” That sudden and forceful act, embodying an evaluative judgement, is the event that GS 341 is all about.