Intranet and Knowledge Management: Putting the Cart Before the Horse?

This paper explores the use of intranet-technology to support knowledge intensive decision-making in a technical service delivery process of a major oilfield services company. Our findings show that creating, mobilizing, and exchanging knowledge through an intranet-technology based system delivers forms of benefits to both the organization and its clients, and understanding what organizational knowledge is to be managed and the process of managing it define the role of technology that enables knowledge management

Organizational knowledge transfer through creation, mobilization and diffusion: A case analysis of InTouch within Schlumberger

There is a paucity of theory for the effective management of knowledge transfer within large organisations. Practitioners continue to rely upon ‘experimental’ approaches to address the problem. This research attempts to reduce the gap between theory and application, thereby improving conceptual clarity for the transfer of knowledge. The paper, through an in-depth case analysis conducted within Schlumberger, studies the adoption of an intranet-based knowledge management (KM) system (called InTouch) to support, strategically align and transfer knowledge resources. The investigation was undertaken through the adoption of a robust methodological approach (abductive strategy) incorporating the role of technology as an enabler of knowledge management application. Consequently, the study addressed the important question of translating theoretical benefits of KM into practical reality. The research formulates a set of theoretical propositions which are seen as key to the development of an effective knowledge based infrastructure. The findings identify 30 generic attributes that are essential to the creation, mobilisation and diffusion of organisational knowledge. The research makes a significant contribution to identifying a theoretical and empirically based agenda for successful intranet-based KM which will be of benefit to both the academic and practitioner communities. The paper also highlights and proposes important areas for further research

Inhibition of tumour necrosis factor alpha in the R6/2 mouse model of Huntington’s disease by etanercept treatment

Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by the expansion of the CAG repeat in exon 1 of the huntingtin (HTT) gene, which results in a mutant protein with an extended polyglutamine tract. Inflammation occurs in both the brain and the periphery of HD patients and mouse models, with increases in brain and/or plasma levels of neurotoxic TNFα and several other proinflammatory cytokines. TNFα promotes the generation of many of these cytokines, such as IL6, which raises the possibility that TNFα is central to the inflammatory milieu associated with HD. A number of mouse studies have reported that the suppression of chronic immune activation during HD has beneficial consequences. Here, we investigated whether TNFα contributes to the peripheral inflammation that occurs in the R6/2 mouse model, and whether the in vivo blockade of TNFα, via etanercept treatment, can modify disease progression. We found that etanercept treatment normalised the elevated plasma levels of some cytokines. This did not modify the progression of certain behavioural measures, but slightly ameliorated brain weight loss, possibly related to a reduction in the elevated striatal level of soluble TNFα

Inhibition of tumour necrosis factor alpha in the R6/2 mouse model of Huntington’s disease by etanercept treatment

Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by the expansion of the CAG repeat in exon 1 of the huntingtin (HTT) gene, which results in a mutant protein with an extended polyglutamine tract. Inflammation occurs in both the brain and the periphery of HD patients and mouse models, with increases in brain and/or plasma levels of neurotoxic TNFα and several other proinflammatory cytokines. TNFα promotes the generation of many of these cytokines, such as IL6, which raises the possibility that TNFα is central to the inflammatory milieu associated with HD. A number of mouse studies have reported that the suppression of chronic immune activation during HD has beneficial consequences. Here, we investigated whether TNFα contributes to the peripheral inflammation that occurs in the R6/2 mouse model, and whether the in vivo blockade of TNFα, via etanercept treatment, can modify disease progression. We found that etanercept treatment normalised the elevated plasma levels of some cytokines. This did not modify the progression of certain behavioural measures, but slightly ameliorated brain weight loss, possibly related to a reduction in the elevated striatal level of soluble TNFα

Phenotypic manifestation of α-synuclein strains derived from Parkinson’s disease and multiple system atrophy in human dopaminergic neurons

α-Synuclein is critical in the pathogenesis of Parkinson’s disease and related disorders, yet it remains unclear how its aggregation causes degeneration of human dopaminergic neurons. In this study, we induced α-synuclein aggregation in human iPSC-derived dopaminergic neurons using fibrils generated de novo or amplified in the presence of brain homogenates from Parkinson’s disease or multiple system atrophy. Increased α-synuclein monomer levels promote seeded aggregation in a dose and time-dependent manner, which is associated with a further increase in α-synuclein gene expression. Progressive neuronal death is observed with brain-amplified fibrils and reversed by reduction of intraneuronal α-synuclein abundance. We identified 56 proteins differentially interacting with aggregates triggered by brain-amplified fibrils, including evasion of Parkinson’s disease-associated deglycase DJ-1. Knockout of DJ-1 in iPSC-derived dopaminergic neurons enhance fibril-induced aggregation and neuronal death. Taken together, our results show that the toxicity of α-synuclein strains depends on aggregate burden, which is determined by monomer levels and conformation which dictates differential interactomes. Our study demonstrates how Parkinson’s disease-associated genes influence the phenotypic manifestation of strains in human neurons