What is a Man, What Has He Got?

This issue Elie Ayache returns to complete his alternative reading of Bergomi which sheds new perspectives on Rough Volatility in relation to the meaning of the Options Market

Limited, but potentially functional translation of non-coding transcripts in the HEK293T cellular cytosol

Ribosome profiling has revealed translation outside of canonical coding sequences (CDSs) including translation of short upstream ORFs, long non-coding RNAs, overlapping ORFs, ORFs in UTRs or ORFs in alternative reading frames. Studies combining mass spectrometry, ribosome profiling and CRISPR-based screens showed that hundreds of ORFs derived from non-coding transcripts produce (micro)proteins, while other studies failed to find evidence for such types of non-canonical translation products. Here, we attempted to discover translation products from non-coding regions by strongly reducing the complexity of the sample prior to mass spectrometric analysis. We used an extended database as the search space and applied stringent filtering of the identified peptides to find evidence for novel translation events. Theoretically, we show that our strategy facilitates the detection of translation events of transcripts from non-coding regions, but experimentally only find 19 peptides (less than 1% of all identified peptides) that might originate from such translation events. Virotrap based interactome analysis of two N-terminal proteoforms originating from non-coding regions finally showed the functional potential of these novel proteins.

Does God Command and Punish in the Garden of Eden?

Most interpretations of Gen 2–3 center the motifs of divine command, human obedience, and divine punishment. These ideas, however, are not intrinsic to the narrative. They represent only one possible way of interpreting certain semantic and narrative ambiguities in the story. One can also read Gen 2–3 as a story about a divine warning and a consequential decision. This alternative reading does a better job making sense of the narrative details and better reflects the unique way the J source of the Pentateuch understands how God interacts with humanity.

Tove Janssons bildebok Vem ska trösta knyttet? som heltedikt

Tove Jansson’s Picturebook Who Will Comfort Toffle? as a Heroic Poem This article offers an analysis of Tove Jansson’s picturebook Vem ska trösta knyttet? (Who Will Comfort Toffle?) from 1960 as a heroic poem and dramatic monologue, representing an alternative reading to earlier studies of this picturebook as a coherent narrative. Drawing on theory about heroic poetry, poetry and picturebook analysis, we provide a reading that expands those interpretations of Vem ska trösta knyttet? that emphasize the romantic and psychological projects of the book when read as a narrative story. By reading Vem ska trösta knyttet? as a heroic poem, we explore the text as an uttered, ritualistic, and iterative event rather than solely a narrative with fictional characters. Read in the tradition of the heroic poem, Toffle is (still) the hero, where lyrical language and structures allow the reader to remember and retell the poem, letting Toffle’s deeds live on beyond the alleged time of events and the performative declaration by Toffle.

Foucault’s Outside: Contingency, May-Being, and Revolt

In this paper, I argue for an alternative reading of Michel Foucault as an anti-correlationist thinker. Specifically, I position him as aligned with what philosopher Quentin Meillassoux calls speculative materialism (an offshoot of speculative realism). Given the resurgent and exciting prioritization of speculative ontology over concrete politics among these thinkers, coupled with the need for a revolutionary anti-capitalist political movement, my approach aims to take speculative materialists’ claims regarding access to the in-itself seriously while also devoting attention to their (underdeveloped) political dimension. It is in this latter realm Foucault proves particularly helpful to think alongside. Though Foucault has often and convincingly been portrayed as an anti-universalist, postmodern, and epistemologically-oriented figure, I present him as concerned with the subject’s access to the Outside (the great outdoors, things-in-themselves) as well as the politics of such access. I do so through a study of a wide selection of his works (books, essays, interviews, articles), a comparison between his philosophical position and that of Meillassoux’s, and an expansion upon Foucault’s analysis of Diego Velázquez’s “Las Meninas” in The Order of Things, positing the artwork as a speculative object. I suggest, in short, that Foucault’s concepts of thought, force, and the subject have surprisingly striking similarities to Meillassoux’s absolute contingency and his political subject (the ‘vectoral militant’). We can, then, begin to see a revolutionary politics arising out of what I understand as Foucault’s speculative stance—hopefully providing an opportunity to both (re)consider Foucault and highlight the politics incipient in contemporary explorations into the Outside.

The short isoform of the host antiviral protein ZAP acts as an inhibitor of SARS-CoV-2 programmed ribosomal frameshifting

Programmed ribosomal frameshifting (PRF) is a fundamental gene expression event in many viruses, including SARS-CoV-2. It allows production of essential viral, structural and replicative enzymes that are encoded in an alternative reading frame. Despite the importance of PRF for the viral life cycle, it is still largely unknown how and to what extent cellular factors alter mechanical properties of frameshift elements and thereby impact virulence. This prompted us to comprehensively dissect the interplay between the SARS-CoV-2 frameshift element and the host proteome. We reveal that the short isoform of the zinc-finger antiviral protein (ZAP-S) is a direct regulator of PRF in SARS-CoV-2 infected cells. ZAP-S overexpression strongly impairs frameshifting and inhibits viral replication. Using in vitro ensemble and single-molecule techniques, we further demonstrate that ZAP-S directly interacts with the SARS-CoV-2 RNA and interferes with the folding of the frameshift RNA element. Together, these data identify ZAP-S as a host-encoded inhibitor of SARS-CoV-2 frameshifting and expand our understanding of RNA-based gene regulation.

The Politics of Pain in Immigration Detention

In this paper I draw on qualitative material from the first complete data set of the ‘ Measure of the Quality of Life in Detention’ (MQLD) survey in the UK to reflect on its implication for understanding and challenging these sites. While similarities between immigration detention centres and prisons make it tempting to place the testimonies from people in detention within the framework of the ‘pains of imprisonment’, I propose an alternative reading of these first-hand accounts. Rather than approaching them as sociological statements of suffering, caused by the loss of liberty, I interpret them as political statements which, in turn, demand a political response. Immigration removal centres (IRCs), these people assert, are fundamentally at odds with key values of a liberal democracy. Those detained within them are not considered to be equal members of a shared community of value; rather, their incarceration marks them out symbolically and, quite practically, as outsiders to these ideas. The pain people describe illuminates the need for a new politics of detention.

Diosgenin inhibits the proliferation of gastric cancer cells via inducing mesoderm posterior 1 down-regulation-mediated alternative reading frame expression

Introduction Whether and how mesoderm posterior 1 (MESP1) plays a role in the proliferation of gastric cancer cells remain unclear. Methods The expression of MESP1 was compared in 48 human gastric cancer tissues and adjacent normal tissues. Knockdown of MESP1 was performed to investigate the role of MESP1 in the proliferation and apoptosis of BGC-823 and MGC-803 gastric cancer cells. Knockdown of alternative reading frame (ARF) was performed to study the role of ARF in the inhibitory effect of MESP1 knockdown on cell proliferation in gastric cancer cells. Mouse subcutaneous xenograft tumor model bearing BGC-823 cells was used to investigate the role of MESP1 in the growth of gastric tumor in vivo. The effect of seven active ingredients from T. terrestris on MESP1 expression was tested. The anti-cancer effect of diosgenin was confirmed in gastric cancer cells. MESP1 dependence of the anti-cancer effect of diosgenin was confirmed by MESP1 knockdown. Results MESP1 was highly expressed in human gastric cancer tissues ( p < 0.05). MESP1 knockdown induced apoptosis and up-regulated the expression of ARF in gastric cancer cells ( p < 0.05). Knockdown of ARF attenuated the anti-cancer effect of MESP1 knockdown ( p < 0.05). In addition, MESP1 knockdown also suppressed tumor growth in vivo ( p < 0.05). Diosgenin inhibits both mRNA and protein expression of MESP1 ( p < 0.05). MESP1 knockdown attenuated the anti-cancer effect of diosgenin ( p < 0.05). Conclusions MESP1 promotes the proliferation of gastric cancer cells via inhibiting ARF expression. Diosgenin exerts anti-cancer effect through inhibiting MESP1 expression in gastric cancer cells.

Times as Task, Not Timing: Reconsidering Qoheleth’s Catalogue of the Times

This essay examines Qoheleth’s Catalogue of the Times poem in Eccl 3:2–8. I argue that the two most common scholarly interpretations of the poem’s overall meaning fail to sufficiently account for its literary context and that an underdeveloped alternative reading is to be preferred. When we read the poem in light of two other closely related passages, 1:4–11 and 3:9–15, it becomes clear that a poem ostensibly about “time” is much less concerned with “timing” than is typically thought, but instead signifies Qoheleth’s frustration with the inevitable equilibrating tendency embedded into every human task.

An HLA-A*11:01-Binding Neoantigen from Mutated NPM1 as Target for TCR Gene Therapy in AML

Acute myeloid leukemia (AML) is a hematological malignancy caused by clonal expansion of myeloid progenitor cells. Most patients with AML respond to chemotherapy, but relapses often occur and infer a very poor prognosis. Thirty to thirty-five percent of AMLs carry a four base pair insertion in the nucleophosmin 1 gene (NPM1) with a C-terminal alternative reading frame of 11 amino acids. We previously identified various neopeptides from the alternative reading frame of mutant NPM1 (dNPM1) on primary AML and isolated an HLA-A*02:01-restricted T-cell receptor (TCR) that enables human T-cells to kill AML cells upon retroviral gene transfer. Here, we isolated T-cells recognizing the dNPM1 peptide AVEEVSLRK presented in HLA-A*11:01. The TCR cloned from a T-cell clone recognizing HLA-A*11:01+ primary AML cells conferred in vitro recognition and lysis of AML upon transfer to CD8 cells, but failed to induce an anti-tumor effect in immunodeficient NSG mice engrafted with dNPM1 OCI-AML3 cells. In conclusion, our data show that AVEEVSLRK is a dNPM1 neoantigen on HLA-A*11:01+ primary AMLs. CD8 cells transduced with an HLA-A*11:01-restricted TCR for dNPM1 were reactive against AML in vitro. The absence of reactivity in a preclinical mouse model requires further preclinical testing to predict the potential efficacy of this TCR in clinical development.