"Conducted Properly, Published Incorrectly": The Evolving Status of Gel Electrophoresis Images Along Instrumental Transformations in Times of Reproducibility Crisis.

For the last ten years, within molecular life sciences, the reproducibility crisis discourse has been embodied as a crisis of trust in scientific images. Beyond the contentious perception of "questionable research practices" associated with a digital turn in the production of images, this paper highlights the transformations of gel electrophoresis as a family of experimental techniques. Our aim is to analyze the evolving epistemic status of generated images and its connection with a crisis of trust in images within that field. From the 1980s to the 2000s, we identify two key innovations (precast gels and gel docs) leading to a "two-tiered" gel electrophoresis with different standardization procedures, different epistemic statuses of the produced images and different ways of generating (dis)trust in images. The first tier, exemplified by differential gel electrophoresis (DIGE), is characterized by specialized devices processing images as quantitative data. The second tier, exemplified by polyacrylamide gel electrophoresis (PAGE), is described as a routine technique making use of image as qualitative "virtual witnessing." The difference between these two tiers is particularly apparent in the ways images are processed, even though both tiers involve image digitization. Our account thus highlights different views on reproducibility within the two tiers. Comparability of images is insisted upon in the first tier while traceability is expected in the second tier. It is striking that these differences occur not only within the same scientific field, but even within the same family of experimental techniques. In the second tier, digitization entails distrust, whereas it implies a collective sentiment of trust in the first tier.

"We were here before the Web and hype ": a brief history of and tribute to the Computational Chemistry List.

The Computational Chemistry List is a mailing list, portal, and community which brings together people interested in computational chemistry, mostly practitioners. It was formed in 1991 and continues to exist as a vibrant discussion space, highly valued by its members, and serving both its original and new functions. Its duration has been unusual for online communities. We analyze some of its characteristics, the reasons for its duration, value, and resilience, the ways it embodies and preceded the affordances of online communities recognized elsewhere long after its foundations, and project some aspects into the future. We also highlight its value as a corpus for historians of science.

Strategy to discriminate between high and low affinity bindings of human immunodeficiency virus, type 1 integrase to viral DNA.

The last decade has contributed to our understanding of the three-dimensional structure of the human immunodeficiency virus, type 1 (HIV-1) integrase (IN) and to the description of how the enzyme catalyzes the viral DNA integration into the host DNA. Recognition of the viral DNA termini by IN is sequence-specific, and that of the host DNA does not require particular sequence, although in physicochemical studies IN fails to discriminate between the two interactions. Here, such discrimination was allowed thanks to a model system using designed oligonucleotides and peptides as binding structures. Spectroscopic (circular dichroism, NMR, and fluorescence anisotropy) techniques and biochemical (enzymatic and filter binding) assays clearly indicated that the amphipathic helix alpha4, located at the catalytic domain surface, is responsible for the specific high affinity binding of the enzyme to viral DNA. Analogues of the alpha4 peptide having increased helicity and still bearing the biologically relevant lysines 156 and 159 on the DNA binding face, and oligonucleotides conserving an intact attachment site, are required to achieve high affinity complexes (Kd of 1.5 nm). Data corroborate previous in vivo results obtained with mutated viruses.