Conversation with Lisa Garforth / Conversatorio con Lisa Garforth

\ua9 2023, Universidad Compultense Madrid. All rights reserved. Julia Ram\uedrez-Blanco interviews Lisa Garforth, author of the book Green Utopias and specialist in environmental utopias. With her, we talk about the possible ways of defining ecotopias, and how they manifest themselves both in literature and in different forms of social practice

Affective practices, care and bioscience: a study of two laboratories

Scientific knowledge-making is not just a matter of experiments, modelling and fieldwork. It also involves affective, embodied and material practices (Wetherell 2012) which can be understood together as 'matters of care' (Puig de la Bellacasa, 2011). In this paper we explore how affect spans and connects material, subjective and organisational practices, focusing in particular on the patterns of care we encountered in an observational study of two bioscience laboratories. We explore the preferred emotional subjectivities of each lab and their relation to material practice. We go on to consider flows and clots in the circulation of affect and their relation to care through an exploration of belonging and humour in the labs. We show how being a successful scientist or group of researchers involves a careful choreography of affect in relation to materials, colleagues and others to produce scientific results, subjects and workplaces. We end by considering how thinking with care troubles dominant constructions of scientific practice, successful scientific selves and collectives

Executive attention, task selection and attention-based learning in a neurally controlled simulated robot

We describe the design and implementation of an integrated neural architecture, modelled on human executive attention, which is used to control both automatic (reactive) and willed action selection in a simulated robot. The model, based upon Norman and Shallice's supervisory attention system, incorporates important features of human attentional control: selection of an intended task over a more salient automatic task; priming of future tasks that are anticipated; and appropriate levels of persistence of focus of attention. Recognising that attention-based learning, mediated by the limbic system, and the hippocampus in particular, plays an important role in adaptive learning, we extend the Norman and Shallice model, introducing an intrinsic, attention-based learning mechanism that enhances the automaticity of willed actions and reduces future need for attentional effort. These enhanced features support a new level of attentional autonomy in the operation of the simulated robot. Some properties of the model are explored using lesion studies, leading to the identification of a correspondence between the behavioural pathologies of the simulated robot and those seen in human patients suffering dysfunction of executive attention. We discuss briefly the question of how executive attention may have arisen due to selective pressure

Understanding student use of resources in "rich-media" courses

There is a current trend in course development to increase the number of “rich-media” items available to students; these include items like key-concept videos, interactive activities and quizzes, and even captures of the full lectures. It is therefore important to understand which of these resources students use and gain value from so that we can target the best resources for student learning. This paper looks at several courses taught in the School of Chemical Engineering and Analytical Science at The University of Manchester to several year groups; including lecture based courses, distance learning courses, and non-lecture based activities; that contain “rich-media” resources. The use of these items by students is examined; including number of uses, time of use, and local retention. The student opinion on the items and how they felt has affected their learning is also analysed. This allows results to be presented on the most useful types of resource for students providing information for future development

A model for transition of 5 '-nuclease domain of DNA polymerase I from inert to active modes

Bacteria contain DNA polymerase I (PolI), a single polypeptide chain consisting of similar to 930 residues, possessing DNA-dependent DNA polymerase, 3'-5' proofreading and 5'-3' exonuclease (also known as flap endonuclease) activities. PolI is particularly important in the processing of Okazaki fragments generated during lagging strand replication and must ultimately produce a double-stranded substrate with a nick suitable for DNA ligase to seal. PolI's activities must be highly coordinated both temporally and spatially otherwise uncontrolled 5'-nuclease activity could attack a nick and produce extended gaps leading to potentially lethal double-strand breaks. To investigate the mechanism of how PolI efficiently produces these nicks, we present theoretical studies on the dynamics of two possible scenarios or models. In one the flap DNA substrate can transit from the polymerase active site to the 5'-nuclease active site, with the relative position of the two active sites being kept fixed; while the other is that the 5'-nuclease domain can transit from the inactive mode, with the 5'-nuclease active site distant from the cleavage site on the DNA substrate, to the active mode, where the active site and substrate cleavage site are juxtaposed. The theoretical results based on the former scenario are inconsistent with the available experimental data that indicated that the majority of 5'-nucleolytic processing events are carried out by the same PolI molecule that has just extended the upstream primer terminus. By contrast, the theoretical results on the latter model, which is constructed based on available structural studies, are consistent with the experimental data. We thus conclude that the latter model rather than the former one is reasonable to describe the cooperation of the PolI's polymerase and 5'-3' exonuclease activities. Moreover, predicted results for the latter model are presented

Direct observation of DNA threading in flap endonuclease complexes

Maintenance of genome integrity requires that branched nucleic acid molecules are accurately processed to produce double-helical DNA. Flap endonucleases are essential enzymes that trim such branched molecules generated by Okazaki fragment synthesis during replication. Here, we report crystal structures of bacteriophage T5 flap endonuclease in complexes with intact DNA substrates, and products, at resolutions of 1.9–2.2 Å. They reveal single-stranded DNA threading through a hole in the enzyme enclosed by an inverted Vshaped helical arch straddling the active site. Residues lining the hole induce an unusual barb-like conformation in the DNA substrate juxtaposing the scissile phosphate and essential catalytic metal ions. A series of complexes and biochemical analyses show how the substrate’s single-stranded branch approaches, threads through, and finally emerges on the far side of the enzyme. Our studies suggest that substrate recognition involves an unusual “flycasting, thread, bend and barb” mechanis

Development of a Novel Virtual Screening Cascade Protocol to Identify Potential Trypanothione Reductase Inhibitors

The implementation of a novel sequential computational approach that can be used effectively for virtual screening and identification of prospective ligands that bind to trypanothione reductase (TryR) is reported. The multistep strategy combines a ligand-based virtual screening for building an enriched library of small molecules with a docking protocol (AutoDock, X-Score) for screening against the TryR target. Compounds were ranked by an exhaustive conformational consensus scoring approach that employs a rank-by-rank strategy by combining both scoring functions. Analysis of the predicted ligand-protein interactions highlights the role of bulky quaternary amine moieties for binding affinity. The scaffold hopping (SHOP) process derived from this computational approach allowed the identification of several chemotypes, not previously reported as antiprotozoal agents, which includes dibenzothiepine, dibenzooxathiepine, dibenzodithiepine, and polycyclic cationic structures like thiaazatetracyclo-nonadeca-hexaen-3-ium. Assays measuring the inhibiting effect of these compounds on T. cruzi and T. brucei TryR confirm their potential for further rational optimization

Architecture and utopia, 2015

No abstract available