Action Learning as a Mindset—The Evolution of PICCO

This paper investigates action learning as a maintenance of mindset. It is an account of a personal evolution from a 4-year work in progress Action Research (AR) study exploring organizational viability. That study, involving two separate organizations and four cycles of AR, has seen the researcher and to some extent the organizations develop action-learning mindsets. The paper is an attempt to step outside the study and its associated learning from an organizational perspective and to link the threads of learning from the mindset of an action researcher. The paper suggests that adopting the mindset of an action researcher favors the transfer of learning from one organizational situation to another. Advocating that action researchers do not restart their initial methodologies, it is contended that the second organization has gained advantage of learning from the first. It is concluded that action learning mindsets articulate cumulative wisdom from organizational and methodological perspectives.     

Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness

Asthma is a common respiratory disorder characterized by recurrent episodes of coughing, wheezing and breathlessness. Although environmental factors such as allergen exposure are risk factors in the development of asthma, both twin and family studies point to a strong genetic component. To date, linkage studies have identified more than a dozen genomic regions linked to asthma. In this study, we performed a genome-wide scan on 460 Caucasian families and identified a locus on chromosome 20p13 that was linked to asthma (log(10) of the likelihood ratio (LOD), 2.94) and bronchial hyperresponsiveness (LOD, 3.93). A survey of 135 polymorphisms in 23 genes identified the ADAM33 gene as being significantly associated with asthma using case-control, transmission disequilibrium and haplotype analyses (P = 0.04 0.000003). ADAM proteins are membrane-anchored metalloproteases with diverse functions, which include the shedding of cell-surface proteins such as cytokines and cytokine receptors. The identification and characterization of ADAM33, a putative asthma susceptibility gene identified by positional cloning in an outbred population, should provide insights into the pathogenesis and natural history of this common disease.     

Occupational Health and Safety Systems,Corporate Governance and Viable Systems Diagnosis: An Action Research Approach

This paper establishes a theoretical basis for the implementation of governance systems in Occupational Health and Safety (OHS). This arose when a complex government organization reviewed the usage of its OHS computer system. This review precipitated several cycles of Action Research (AR). The AR allowed the recognition that the organization needed to define its OHS strategy, clarify its commitment to OHS, and examine its OHS systems in order to provide an effective OHS management and corporate governance system. As part of the review, a Viable Systems Diagnosis was done on the OHS function. It was recognized that Stafford Beer provided valuable insights into the information needs and communication flows of OHS information throughout this complex organization. Action research appears to be a particularly useful method for examining and implementing OHS management systems.     

Rapid leukocyte migration by integrin-independent flowing and squeezing

All metazoan cells carry transmembrane receptors of the integrin family, which couple the contractile force of the actomyosin cytoskeleton to the extracellular environment. In agreement with this principle, rapidly migrating leukocytes use integrin-mediated adhesion when moving over two-dimensional surfaces. As migration on two-dimensional substrates naturally overemphasizes the role of adhesion, the contribution of integrins during three-dimensional movement of leukocytes within tissues has remained controversial. We studied the interplay between adhesive, contractile and protrusive forces during interstitial leukocyte chemotaxis in vivo and in vitro. We ablated all integrin heterodimers from murine leukocytes, and show here that functional integrins do not contribute to migration in three-dimensional environments. Instead, these cells migrate by the sole force of actin-network expansion, which promotes protrusive flowing of the leading edge. Myosin II-dependent contraction is only required on passage through narrow gaps, where a squeezing contraction of the trailing edge propels the rigid nucleus.     

Structural basis for the regulated protease and chaperone function of DegP

All organisms have to monitor the folding state of cellular proteins precisely. The heat-shock protein DegP is a protein quality control factor in the bacterial envelope that is involved in eliminating misfolded proteins and in the biogenesis of outer-membrane proteins. Here we describe the molecular mechanisms underlying the regulated protease and chaperone function of DegP from Escherichia coli. We show that binding of misfolded proteins transforms hexameric DegP into large, catalytically active 12-meric and 24-meric multimers. A structural analysis of these particles revealed that DegP represents a protein packaging device whose central compartment is adaptable to the size and concentration of substrate. Moreover, the inner cavity serves antagonistic functions. Whereas the encapsulation of folded protomers of outer-membrane proteins is protective and might allow safe transit through the periplasm, misfolded proteins are eliminated in the molecular reaction chamber. Oligomer reassembly and concomitant activation on substrate binding may also be critical in regulating other HtrA proteases implicated in protein-folding diseases.