91 research outputs found
Impaired ATP synthase assembly associated with a mutation in the human ATP synthase subunit 6 gene
Mutations in human mitochondrial DNA are a well recognized cause of disease. A mutation at nucleotide position 8993 of human mitochondrial DNA, located within the gene for ATP synthase subunit 6, is associated with the neurological muscle weakness, ataxia, and retinitis pigmentosa (NARP) syndrome. To enable analysis of this mutation in control nuclear backgrounds, two different cell lines were transformed with mitochondria carrying NARP mutant mitochondrial DNA. Transformant cell lines had decreased ATP synthesis capacity, and many also had abnormally high levels of two ATP synthase sub-complexes, one of which was F1-ATPase. A combination of metabolic labeling and immunoblotting experiments indicated that assembly of ATP synthase was slowed and that the assembled holoenzyme was unstable in cells carrying NARP mutant mitochondrial DNA compared with control cells. These findings indicate that altered assembly and stability of ATP synthase are underlying molecular defects associated with the NARP mutation in subunit 6 of ATP synthase, yet intrinsic enzyme activity is also compromised
Design management: changing roles of the professions
This paper sets out to explore how recent changes in
procurement in construction have affected the roles that
professions play in the design process. It discusses how
professions that traditionally took the role of design
manager now find themselves participating within
previously unforeseen contexts, working in multidisciplinary
teams led by contractors and with changed
responsibilities at the design stage. Supply chain members
who were not previously involved during the early project
phases are being engaged at the earliest phases of the
project life cycle and even taking leadership roles while
designers sometimes work as supply chain partners.
A study of design in construction and other sectors shows
that in dealing with design management issues it is critical
to deepen appreciation for the unique characteristics of
design and the design process. The paper argues that
contractors and designers taking on design management
roles in a dynamic industry seeking to explore best
practice and innovative approaches to procurement and in
the delivery of projects need to acquire new skills,
management education and develop the necessary
qualities
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