46 research outputs found
The importance of trust in management education
There are few practical tools for how we can develop the trust needed to be able to work with ourselves and our colleagues, nor on how
we can develop the organisational conditions that enable us to trust ourselves and others, and allow us to make meaning of our working lives. Katalin Illes offers some pointers
IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome
Expansion of the polyglutamine repeat within the protein Huntingtin (Htt) causes Huntington's disease, a neurodegenerative disease associated with aging and the accumulation of mutant Htt in diseased neurons. Understanding the mechanisms that influence Htt cellular degradation may target treatments designed to activate mutant Htt clearance pathways. We find that Htt is phosphorylated by the inflammatory kinase IKK, enhancing its normal clearance by the proteasome and lysosome. Phosphorylation of Htt regulates additional post-translational modifications, including Htt ubiquitination, SUMOylation, and acetylation, and increases Htt nuclear localization, cleavage, and clearance mediated by lysosomal-associated membrane protein 2A and Hsc70. We propose that IKK activates mutant Htt clearance until an age-related loss of proteasome/lysosome function promotes accumulation of toxic post-translationally modified mutant Htt. Thus, IKK activation may modulate mutant Htt neurotoxicity depending on the cell's ability to degrade the modified species
SUMO-2 and PIAS1 Modulate Insoluble Mutant Huntingtin Protein Accumulation
SUMMARY A key feature in Huntington disease (HD) is the accumulation of mutant Huntingtin (HTT) protein, which may be regulated by posttranslational modifications. Here, we define the primary sites of SUMO modification in the amino-terminal domain of HTT, show modification downstream of this domain, and demonstrate that HTT is modified by the stress-inducible SUMO-2. A systematic study of E3 SUMO ligases demonstrates that PIAS1 is an E3 SUMO ligase for both HTT SUMO-1 and SUMO-2 modification and that reduction of dPIAS in a mutant HTT Drosophila model is protective. SUMO-2 modification regulates accumulation of insoluble HTT in HeLa cells in a manner that mimics proteasome inhibition and can be modulated by overexpression and acute knockdown of PIAS1. Finally, the accumulation of SUMO-2-modified proteins in the insoluble fraction of HD postmortem striata implicates SUMO-2 modification in the age-related pathogenic accumulation of mutant HTT and other cellular proteins that occurs during HD progression
Changing management style in central and eastern Europe: the case of Hungary
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Comparative study of Electrolux's marketing strategies in Hungary and Britain
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Ethnography: the use of observation and action research for intercultural learning
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Promoting and Assessing Integrity in the Research Degree
Although postgraduate research is
increasingly supported through the
formalisation of supervision and
programs providing generic support,
those programs have seldom
addressed the intention, often stated
by universities in their graduate
profiles, that postgraduates should
have integrity, and ethical values.
What methodology is required
– how will universities support
students to cultivate such sensitivity,
assess this, and fulfill the expectation?
The paper provides evidence
that quality statements including
some aspect of integrity are used in
many UK and Australian universities.
The importance of integrity, or
ethical behaviour more generally,
in postgraduate degrees and in
professional practice is confirmed by
reference to Sandor Kopatsy’s model
of intellectual capital, where knowledge,
morality, talent and effort are
multiplied together to determine
the level of intellectual capital. The
main section of the paper considers
how assessment might be achieved
and the desired qualities fostered.
Three distinct forms of moral qualities
or skills can be found among
those identified by the universities
– some refer to technical skills, some
describe graduates sensitive to ethical
and social issues and some talk
of graduates committed to ethical
action and social responsibility. The
paper draws on the authors’ experience
in Europe, Australia and Asia
Cultural and intercultural negotiation aspects: United Kingdom
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