The proapoptotic influenza A virus protein PB1-F2 forms a nonselective ion channel

Background: PB1-F2 is a proapoptotic influenza A virus protein of approximately 90 amino acids in length that is located in the nucleus, cytosol and in the mitochondria membrane of infected cells. Previous studies indicated that the molecule destabilizes planar lipid bilayers and has a strong inherent tendency for multimerization. This may be correlate with its capacity to induce mitochondrial membrane depolarization. Methodology/Principal Findings: Here, we investigated whether PB1-F2 is able to form ion channels within planar lipid bilayers and microsomes. For that purpose, a set of biologically active synthetic versions of PB1-F2 (sPB1-F2) derived from the IAV isolates A/Puerto Rico/8/34(H1N1)( IAV(PR8)), from A/Brevig Mission/1/1918( H1N1) (IAV(SF2)) or the H5N1 consensus sequence (IAV(BF2)) were used. Electrical and fluorimetric measurements show that all three peptides generate in planar lipid bilayers or in liposomes, respectively, a barely selective conductance that is associated with stochastic channel type fluctuations between a closed state and at least two defined open states. Unitary channel fluctuations were also generated when a truncated protein comprising only the 37 c-terminal amino acids of sPB1-F2 was reconstituted in bilayers. Experiments were complemented by extensive molecular dynamics simulations of the truncated fragment in a lipid bilayer. The results indicate that the c-terminal region exhibits a slightly bent helical fold, which is stable and remains embedded in the bilayer for over 180 ns. Conclusion/Significance: The data support the idea that PB1-F2 is able to form protein channel pores with no appreciable selectivity in membranes and that the c-terminus is important for this function. This information could be important for drug development

Auto-tuned and R-squared:Reflecting audience quality evaluations in the creative process in music production and cancer research

While audiences play a key role in the implementation and ultimate success of novel ideas, how audiences are reflected in negotiations about quality within the creative process remains under-theorized. We examine this question through a comparative ethnography of two settings where the use of digital technology magnifies the countless micro-decisions involved in producing a creative output and therefore considerations of audience evaluation throughout the creative process—Nashville music production and systems biology cancer research. We find that actors encounter a fundamental tension between two competing standards of quality: the technically perfect, processed and ideal versus the empirically grounded, unprocessed and real. We show how actors navigate this tension vis-á-vis three different audiences—internal peers, extended community, and external reviewers—and how this manifests differently across audiences and the arts and sciences, depending on the audience’s expertise. Our study illuminates the tension between the “ideal versus real” in creative processes that is brought to the fore when creating with digital technology, extends extant research on audiences and organizing for creativity, and offers unique insights from our comparative ethnography across the arts and sciences

DNA and Lovesongs:Optimization within the Collective Creative Process

Contemporary creative work often brings together multiple experts to realize a novel outcome, and each area of expertise is associated with unique aspirations, requirements and standards. How does the collective creative process unfold when these are conflicting? We harness the institutional logics literature as a lens to highlight cognitive and behavioral implications of larger institutional dynamics that shape and constrain the collective creative process. Based on a comparative ethnography of creative work in the science and music industries, we demonstrate that a significant portion of the collective creative process consists of optimization work. More specifically, we find that actors in both settings developed an approach of optimization – shaping their work so as to integrate and satisfy the requirements of conflicting logics to the greatest extent possible. This study illuminates a critical part of the collective creative process that has so far been unarticulated, and adds to best practices of comparative ethnography

Optimizing Multiple Institutional Logics within the Collective Creative Process

Institutional logics form the foundational building blocks for understanding organizational life and work. While earlier conceptions portrayed institutional logics as static and monolithic, scholars have more recently embraced an action perspective that views logics as fluid and dynamic. With this lens, organizations, fields and professions are seen as rife with a plurality of logics that are continuously contested and negotiated. Our research sheds light on how a multiplicity of logics are navigated over time beyond the context of a single organization or profession, and how micro-level action in the context of the collective creative process may inform, and is informed by, the larger field or industry context

sj-pdf-1-asq-10.1177_00018392231208190 – Supplemental material for Tedious Work: Developing Novel Outcomes with Digitization in the Arts and Sciences

Supplemental material, sj-pdf-1-asq-10.1177_00018392231208190 for Tedious Work: Developing Novel Outcomes with Digitization in the Arts and Sciences by Hille C. Bruns and Elizabeth Long Lingo in Administrative Science Quarterly</p