Social richness, socio-technical tension and the virtual commissioning of NHS research

<p>Abstract</p> <p>Background</p> <p>This paper draws on a recent study that evaluated the process of commissioning NHS funded research using virtual committees. Building on an earlier paper that reported our evaluation, here we focus on the effects of asynchronous computer mediated communication (CMC) when used to support group work.</p> <p>Methods</p> <p>To do this the discussion focuses on how CMC affected three key group factors, building relationships, group cohesion and group commitment. The notion of socio-technical tension is elaborated and the paper explores how social richness can act to counter the socially impoverishing and time extending effects of asynchronous CMC.</p> <p>Results</p> <p>We argue that social richness in this context results from the presence of five principal influences. These are: a dynamic range of participant aspirations and personal agendas; participant commitment to and identification with the work and ideals of the group; a rich diversity of social, professional and work-related backgrounds; a website designed to enhance participation and interaction and the mediating effects of an effective chairperson.</p> <p>Conclusion</p> <p>If virtual work groups are to be used by the NHS in the future, then there is a need for more research into the role of social context and its relationship to the effectiveness of newly formed virtual groups. Equally as important are studies that examine the effects of socio-technical interaction on groups undertaking tasks in the real world of work.</p

Huntingtin mediates dendritic transport of β-actin mRNA in rat neurons

Transport of mRNAs to diverse neuronal locations via RNA granules serves an important function in regulating protein synthesis within restricted sub-cellular domains. We recently detected the Huntington's disease protein huntingtin (Htt) in dendritic RNA granules; however, the functional significance of this localization is not known. Here we report that Htt and the huntingtin-associated protein 1 (HAP1) are co-localized with the microtubule motor proteins, the KIF5A kinesin and dynein, during dendritic transport of β-actin mRNA. Live cell imaging demonstrated that β-actin mRNA is associated with Htt, HAP1, and dynein intermediate chain in cultured neurons. Reduction in the levels of Htt, HAP1, KIF5A, and dynein heavy chain by lentiviral-based shRNAs resulted in a reduction in the transport of β-actin mRNA. These findings support a role for Htt in participating in the mRNA transport machinery that also contains HAP1, KIF5A, and dynein

A Computational and Experimental Study of the Regulatory Mechanisms of the Complement System

The complement system is key to innate immunity and its activation is necessary for the clearance of bacteria and apoptotic cells. However, insufficient or excessive complement activation will lead to immune-related diseases. It is so far unknown how the complement activity is up- or down- regulated and what the associated pathophysiological mechanisms are. To quantitatively understand the modulatory mechanisms of the complement system, we built a computational model involving the enhancement and suppression mechanisms that regulate complement activity. Our model consists of a large system of Ordinary Differential Equations (ODEs) accompanied by a dynamic Bayesian network as a probabilistic approximation of the ODE dynamics. Applying Bayesian inference techniques, this approximation was used to perform parameter estimation and sensitivity analysis. Our combined computational and experimental study showed that the antimicrobial response is sensitive to changes in pH and calcium levels, which determines the strength of the crosstalk between CRP and L-ficolin. Our study also revealed differential regulatory effects of C4BP. While C4BP delays but does not decrease the classical complement activation, it attenuates but does not significantly delay the lectin pathway activation. We also found that the major inhibitory role of C4BP is to facilitate the decay of C3 convertase. In summary, the present work elucidates the regulatory mechanisms of the complement system and demonstrates how the bio-pathway machinery maintains the balance between activation and inhibition. The insights we have gained could contribute to the development of therapies targeting the complement system.Singapore. Ministry of Education (Grant T208B3109)Singapore. Agency for Science, Technology and Research (BMRC 08/1/21/19/574)Singapore-MIT Alliance (Computational and Systems Biology Flagship Project)Swedish Research Counci

Pathogenic huntingtin inhibits fast axonal transport by activating JNK3 and phosphorylating kinesin

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Nature America for personal use, not for redistribution. The definitive version was published in Nature Neuroscience 12 (2009): 864-871, doi:10.1038/nn.2346.Selected vulnerability of neurons in Huntington’s disease (HD) suggests alterations in a cellular process particularly critical for neuronal function. Supporting this idea, pathogenic Htt (polyQ-Htt) inhibits fast axonal transport (FAT) in various cellular and animal HD models (mouse and squid), but the molecular basis of this effect remains unknown. Here we show that polyQ-Htt inhibits FAT through a mechanism involving activation of axonal JNK. Accordingly, increased activation of JNK was observed in vivo in cellular and animal HD models. Additional experiments indicate that polyQ-Htt effects on FAT are mediated by the neuron-specific JNK3, and not ubiquitously expressed JNK1, providing a molecular basis for neuron-specific pathology in HD. Mass spectrometry identified a residue in the kinesin-1 motor domain phosphorylated by JNK3, and this modification reduces kinesin-1 binding to microtubules. These data identify JNK3 as a critical mediator of polyQ-Htt toxicity and provides a molecular basis for polyQ-Htt-induced inhibition of FAT.This work was supported by 2007/2008 MBL summer fellowship to GM; an HDSA grant to GM; NIH grants MH066179 to GB; and ALSA, Muscular Dystrophy Association, and NIH (NS23868, NS23320, NS41170) grants to STB

Anthelmintic Prescribing Patterns of a Sample of General Practitioners from Selected Areas in the Colombo District of Sri Lanka

General Practitioners (GPs) provide first contact care of children and pregnant mothers in the community. This study ascertained the prescribing pattern of anthelmintics to children and pregnant women by a sample of GPs from the district of Colombo. Two hundred medical practitioners engaged in full-time General Practice (100 urban and 100 rural), were selected randomly. A pre-tested interviewer-administered questionnaire was used to collect data. A total of 183 GPs aged between 26 and 72 years (median 38) participated with 94 coming from urban areas. Seventy percent of the GPs were male. Almost 13% of GPs from urban areas had a Postgraduate degree in comparison to 4.5% from the rural areas (P < 0.05). Over 50% of GPs had 6-20 years of service and over 30% treated 16-30 patients daily. Seventy-three percent of GPs from rural areas accessed health-related reading material either daily or weekly in contrast to only 40% from urban areas (P < 0.001). All GPs prescribed anthelmintics to children. Pyrantel pamoate was the preferred anthelmintic used for children by both groups. Approximately 55% and 64% of GPs from urban and rural areas, respectively, prescribed anthelmintics during pregnancy. A majority of GPs prescribed drugs after the first trimester. However, 25% from urban areas gave drugs during any trimester (P < 0.001). Regression analysis revealed that GPs with postgraduate qualifications, those having frequent access to health-related material and those seeing more than 30 patients daily, prescribed anthelmintics to pregnant women more often. Although routine de-worming of pregnant women and children should occur through government antenatal and well-baby clinics, and through the schools de-worming programme, it may not happen due to various reasons. Thus, GPs play a vital role in achieving good coverage of anthelmintics among children and pregnant women. Making available clear national guidelines on prescribing anthelmintics in Sri Lanka would improve the prescribing patterns of anthelmintics among GPs