Application of Scenario-based Approaches in Leadership Research: An Action Research Intervention as Three Sets of Interlinked Practices

© 2013, Springer Science+Business Media New York. This article illustrates how scenario planning (SP) and scenario analysis as can be conceptualised as practices contributing to an action research (AR) investigation of leadership development. The project described in this article was intended to strengthen leadership capacity in Australia’s rapidly changing aged care and community care sector. A research team comprising academics from three universities and managers from two faith-based not-for-profit organisations providing aged and community care participated in this study. As part of the research, two sets of scenario-based workshops were held: the first, to identify possible futures using SP; and the second, to deal with plausible scenarios these organisations are likely to face with the changes happening in the aged care environment in Australia by using scenario analysis. Although the researchers did not consider a link between practice theory and AR during the SP phase, practice theory became useful during the scenario analysis phase. The article includes a brief literature review followed by a discussion on the relationship between AR and practice theory. The processes used in the two sets of scenario workshops are then described in detail along with the data collected and analysed. The article concludes with some reflections on the use of scenarios in practice as well as an acknowledgment that practice theory would be useful in investigating leadership capability development

Apoptosis signal-regulating kinase 1 inhibition attenuates human airway smooth muscle growth and migration in chronic obstructive pulmonary disease

© 2018 The Author(s). Increased airway smooth muscle (ASM) mass is observed in chronic obstructive pulmonary disease (COPD), which is correlated with disease severity and negatively affects lung function in these patients. Thus, there is clear unmet clinical need for finding new therapies which can target airway remodeling and disease progression in COPD. Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K) activated by various stress stimuli, including reactive oxygen species (ROS), tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS) and is known to regulate cell proliferation. ASM cells from COPD patients are hyperproliferative to mitogens in vitro. However, the role of ASK1 in ASM growth is not established. Here, we aim to determine the effects of ASK1 inhibition on ASM growth and pro-mitogenic signaling using ASM cells from COPD patients. We found greater expression of ASK1 in ASM bundles of COPD lung when compared with non-COPD. Pre-treatment of ASM cells with highly selective ASK1 inhibitor, TC ASK 10 resulted in a dose-dependent reduction in mitogen (FBS, PDGF, and EGF; 72 h)-induced ASM growth as measured by CyQUANT assay. Further, molecular targetting of ASK1 using siRNA in ASM cells prevented mitogen-induced cell growth. In addition, to anti-mitogenic potential, ASK1 inhibitor also prevented TGFβ1-induced migration of ASM cells in vitro. Immunoblotting revealed that anti-mitogenic effects are mediated by C-Jun N-terminal kinase (JNK) and p38MAP kinase-signaling pathways as evident by reduced phosphorylation of downstream effectors JNK1/2 and p38MAP kinases, respectively, with no effect on extracellular signal-regulated kinase (ERK) 1/2 (ERK1/2). Collectively, these findings establish the anti-mitogenic effect of ASK1 inhibition and identify a novel pathway that can be targetted to reduce or prevent excessive ASM mass in COPD

The Experience of Learning to Drive for People With Autism Spectrum Disorder

Gaining a driver’s license can be difficult for student drivers with autism spectrum disorder (ASD), yet little is known about their experiences of learning to drive. In this qualitative study, focus groups and individual interviews were employed to ascertain the perceptions of three participant groups, including people with ASD, parents of people with ASD, and driving instructors with experience teaching people with ASD to drive. Participants in each group were asked to discuss their feelings, concerns, and barriers, encountered while learning to drive, along with the driving behaviors, challenges, and strategies used when supporting people with ASD to learn to drive. Grounded theory analysis was used to shed light on the experience of learning to drive for people with ASD. Five themes emerged supporting the core construct that targeted support ameliorates intrinsic driving complexities, generating success: (a) challenges that increase the complexity of learning to drive, (b) external challenges to overcome, (c) concerns about the reality of driving, (d) the need for a specialized model of training, and (e) success is possible. These findings highlight the importance of developing an autism-specific driving training intervention designed for people with ASD, their families, and driving instructors

A Driver Training Program Intervention for Student Drivers with Autism Spectrum Disorder: A Multi-site Randomised Controlled Trial

The purpose of this multi-site randomised controlled trial was to evaluate the effectiveness of a Driving Training Program, an intervention designed for student drivers with autism spectrum disorder (ASD). Participants were 72 student drivers with ASD (ages 16–31) who were randomly assigned to an intervention or control group. Student drivers received ten driving lessons with a professional driving instructor via a standardised driving route. The Driving Performance Checklist was used as the outcome measure to evaluate the driving performance of student drivers during on-road pre- and post-observational drives. Both groups showed an improvement in driving performance, however, the extent of improvement between groups was not significant. Findings showed promising intervention efficacy for training student drivers with ASD to drive

Purification of Tropomyosin Br-3 and 5NM1 and Characterization of Their Interactions with Actin

Tropomyosins were first identified in neuronal systems in 1973. Although numerous isoforms were found and described since then, many aspects of their function and interactions remained unknown. Tropomyosin isoforms show different sorting pattern in neurogenesis. As one example, TM5NM1/2 is present in developing axons, but it is replaced by TMBr-3 in mature neurons, suggesting that these tropomyosin isoforms contribute differently to the establishment of the functional features of the neuronal actin networks. We developed a method for the efficient purification of TMBr-3 and TM5NM1 as recombinant proteins using bacterial expression system and investigated their interactions with actin. We found that both isoforms bind actin filaments, however, the binding of TM5NM1 was much stronger than that of TMBr-3. TMBr-3 and TM5NM1 modestly affected actin assembly kinetics, in an opposite manner. Consistently with the higher affinity of TM5NM1 it inhibited actin filament disassembly more efficiently than TMBr-3. Similarly to other previously studied tropomyosins TM5NM1 inhibited the Arp2/3 complex-mediated actin assembly. Notably, TMBr-3 did not influence the Arp2/3 complex-mediated polymerization. This is a unique feature of TMBr-3, since so far it is the only known tropomyosin supporting the activity of the Arp2/3 complex, indicating that TMBr-3 may colocalize and work simultaneously with Arp2/3 complex in neuronal cells

Tropomyosin - master regulator of actin filament function in the cytoskeleton.

Tropomyosin (Tpm) isoforms are the master regulators of the functions of individual actin filaments in fungi and metazoans. Tpms are coiled-coil parallel dimers that form a head-to-tail polymer along the length of actin filaments. Yeast only has two Tpm isoforms, whereas mammals have over 40. Each cytoskeletal actin filament contains a homopolymer of Tpm homodimers, resulting in a filament of uniform Tpm composition along its length. Evidence for this ‘master regulator’ role is based on four core sets of observation. First, spatially and functionally distinct actin filaments contain different Tpm isoforms, and recent data suggest that members of the formin family of actin filament nucleators can specify which Tpm isoform is added to the growing actin filament. Second, Tpms regulate whole-organism physiology in terms of morphogenesis, cell proliferation, vesicle trafficking, biomechanics, glucose metabolism and organ size in an isoform-specific manner. Third, Tpms achieve these functional outputs by regulating the interaction of actin filaments with myosin motors and actin-binding proteins in an isoform-specific manner. Last, the assembly of complex structures, such as stress fibers and podosomes involves the collaboration of multiple types of actin filament specified by their Tpm composition. This allows the cell to specify actin filament function in time and space by simply specifying their Tpm isoform composition

High content imaging of unbiased chemical perturbations reveals that the phenotypic plasticity of the actin cytoskeleton is constrained

Although F-actin has a large number of binding partners and regulators, the number of phenotypic states available to the actin cytoskeleton is unknown. Here, we quantified 74 features defining filamentous actin (F-actin) and cellular morphology in >25 million cells after treatment with a library of 114,400 structurally diverse compounds. After reducing the dimensionality of these data, only ∼25 recurrent F-actin phenotypes emerged, each defined by distinct quantitative features that could be machine learned. We identified 2,003 unknown compounds as inducers of actin-related phenotypes, including two that directly bind the focal adhesion protein, talin. Moreover, we observed that compounds with distinct molecular mechanisms could induce equivalent phenotypes and that initially divergent cellular responses could converge over time. These findings suggest a conceptual parallel between the actin cytoskeleton and gene regulatory networks, where the theoretical plasticity of interactions is nearly infinite, yet phenotypes in vivo are constrained into a limited subset of practicable configurations

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research