The Prospectus of the Invisible University

This exhibition and research project, helped by Hardingham, is an updating of the famous Locally Available World Unseen Network (L.A.W.u.N.) project that Greene began in the late-1960s while still in Archigram. The original aim, which has now been substantially revised and mutated, was to look at how newly emerging invisible, trans-spatial communication technologies could lead to a new form of Invisible University as a model for tertiary education. In the interim, much of what was once speculation has now come to pass through the advent of the internet, intranet, text messages, etc. – hence this latest presentation for the 2006 London Architecture Biennale showed what the revised version of the project was becoming. As such it involved taking over a newspaper shop, putting up advertising holdings and posters, holding impromptu workshops, and a number of other discrete outputs. The exhibition installation featured in the local press and raised a good deal of discussion. In terms of workload, Greene was responsible for 90% of the research and presentation material used in the exhibition installation and its ancillary outputs, and Hardingham for the other 10% involved in editing it. This latest research work has constantly been disseminated across the world through exhibitions and lectures, with for instance Greene talking about the Invisible University project in connection with the Archigram exhibition in Mito, Japan (December 2004). Elements of the project have also been exhibited at the Architectural Association, ICA, etc. The ongoing scheme for the Invisible University also featured as the subject for a specially invited interdisciplinary design workshop for the ESPRC Ideas Factory in Middlesbrough (May 2006), set up to look at ideas of designing for uncertainty; this event was jointly organised by Greene and Hardingham, and was then attended by many of Britain’s leading mathematicians and scientists

Why China? A study of why foreign hotel companies are rushing to develop new luxury hotels in China

Purpose: The purpose of this professional paper is to identify why China is currently the number one recipient of foreign investment from foreign multinational luxury hotel companies. Statement of Objective: An exploratory study will be conducted in support of the purpose. With such a lack of available information relating specifically to luxury hotel development in China; published data on the current economic, cultural, and tourism environment in China will be used to support conclusions made in regard to luxury hotel development by multinational hotel companies. Justification: Deng Xiaoping’s introduction of the Open Door Policy in 1978 opened the door to what would become decades of unprecedented economic growth in China’s history. Riding along the waves of new found economic liberty and the freedom to partner with foreign investors, China’s hotel investment community seized the opportunity to welcome outside investment. The hotel industry in China quickly developed from 137 properties in 1978 to 14,237 properties in 2009. One of the main catalysts of the rapid development seen in the hotel industry has been the expansion of multinational hotel groups into China (Zhang, Guillet, & Gao, 2011). The outlook for international tourism in China remains extremely positive. In a 2010 study conducted by the World Tourism Organization, China was listed as the fourth most popular international tourism destination (in terms of arrivals) with 133 million visitors. The number of international visitors to China is expected to increase to 137 million by 2020. As positive as these numbers seems, they are dwarfed in comparison to the 2+ billion people participating in leisure travel within China already. Currently, there is little information available on what makes China an attractive target for foreign multinational luxury hotel companies. This paper will serve to address the void of information relating to this specific issue

In developing hippocampal neurons, NR2B-containing N-methyl-d-aspartate receptors (NMDARs) can mediate signaling to neuronal survival and synaptic potentiation, as well as neuronal death

It has been suggested that NR2B-containing N-methyl-d-aspartate (NMDA) receptors have a selective tendency to promote pro-death signaling and synaptic depression, compared with the survival promoting, synapse potentiating properties of NR2A-containing NMDA receptors. A preferential localization of NR2A-containing NMDA receptors at the synapse in maturing neurons could thus explain differences in synaptic vs. extrasynaptic NMDA receptor signaling. We have investigated whether NMDA receptors can mediate signaling to survival, death, and synaptic potentiation, in dissociated rat neuronal cultures at a developmental stage prior to significant NR2A expression and subunit-specific differences between synaptic and extrasynaptic NMDA receptors. We show that in developing hippocampal neurons, the progressive reduction in sensitivity of NMDA receptor currents to the NR2B antagonist ifenprodil applies to both synaptic and extrasynaptic locations. However, the reduction is less acute in extrasynaptic currents, indicating that NR2A does partition preferentially, but not exclusively, into synaptic locations at DIV>12. We then studied NMDA receptor signaling at DIV10, when both synaptic and extrasynaptic NMDA receptors are both overwhelmingly and equally NR2B-dominated. To analyze pro-survival signaling we studied the influence of synaptic NMDA receptor activity on staurosporine-induced apoptosis. Blockade of spontaneous NMDAR activity with MK-801, or ifenprodil exacerbated the apoptotic insult. Furthermore, MK-801 and ifenprodil both antagonized neuroprotection promoted by enhancing synaptic activity. Pro-death signaling induced by a toxic dose of NMDA is also blocked by NR2B-specific antagonists. Using a cell culture model of synaptic NMDA receptor-dependent synaptic potentiation, we find that this is mediated exclusively by NR2B-containing N-methyl-d-aspartate receptors, as implicated by NR2B-specific antagonists and the use of selective vs. non-selective doses of the NR2A-preferring antagonist NVP-AAM077. Therefore, within a single neuron, NR2B-NMDA receptors are able to mediate both survival and death signaling, as well as model of NMDA receptor-dependent synaptic potentiation. In this instance, subunit differences cannot account for the dichotomous nature of NMDA receptor signaling

Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration

Glia, including astrocytes, are increasingly at the forefront of neurodegenerative research for their role in the modulation of neuronal function and survival. Improved understanding of underlying disease mechanisms, including the role of the cellular environment in neurodegeneration, is central to therapeutic development for these currently untreatable diseases. In these endeavours, experimental models that more closely reproduce the human condition have the potential to facilitate the transition between experimental studies in model organisms and patient trials. In this review we discuss the growing role of astrocytes in neurodegenerative diseases, and how astrocytes generated from human pluripotent stem cells represent a useful tool for analyzing astrocytic signalling and influence on neuronal function

Optimisation of osteogenic and chondrogenic differentiation potential using clonal mesenchymal stem cell populations derived from synovial fat pad

Mesenchymal stem cells are a potential source of cells for the repair of bone and articular cartilage defects. We have previously demonstrated that the infrapatellar synovial fat pad is a rich source of mesenchymal stem cells and these cells are able to undergo osteogenic and chondrogenic differentiation. Although synovial fat pad derived mesenchymal stem cells may represent a heterogenous population, clonal populations derived from the synovial fat pad have not previously been studied

SMRT-mediated co-shuttling enables export of class IIa HDACs independent of their CaM kinase phosphorylation sites

The Class IIa histone deacetylases (HDAC)4 and HDAC5 play a role in neuronal survival and behavioral adaptation in the CNS. Phosphorylation at 2/3 N-terminal sites promote their nuclear export. We investigated whether non-canonical signaling routes to Class IIa HDAC export exist because of their association with the co-repressor Silencing Mediator Of Retinoic And Thyroid Hormone Receptors (SMRT). We found that, while HDAC5 and HDAC4 mutants lacking their N-terminal phosphorylation sites (HDAC4(MUT), HDAC5(MUT)) are constitutively nuclear, co-expression with SMRT renders them exportable by signals that trigger SMRT export, such as synaptic activity, HDAC inhibition, and Brain Derived Neurotrophic Factor (BDNF) signaling. We found that SMRT's repression domain 3 (RD3) is critical for co-shuttling of HDAC5(MUT), consistent with the role for this domain in Class IIa HDAC association. In the context of BDNF signaling, we found that HDAC5(WT), which was more cytoplasmic than HDAC5(MUT), accumulated in the nucleus after BDNF treatment. However, co-expression of SMRT blocked BDNF-induced HDAC5(WT) import in a RD3-dependent manner. In effect, SMRT-mediated HDAC5(WT) export was opposing the BDNF-induced HDAC5 nuclear accumulation observed in SMRT's absence. Thus, SMRT's presence may render Class IIa HDACs exportable by a wider range of signals than those which simpl

The influence of synaptic activity on neuronal health

According to the theory of neuronal health, neurons exist in a spectrum of states ranging from highly resilient to vulnerable. An unhealthy neuron may be rendered dysfunctional or non-viable by an insult that would ordinarily be non-toxic to a healthy neuron. Over the years it has become clear that a neuron’s health is subject to dynamic regulation by electrical or synaptic activity. This review highlights recently identified activity dependent signalling events which boost neuronal health through the transcriptional control of pro- and anti-apoptotic genes, the enhancement of antioxidant defences, and the regulation of mitochondrial and neurotrophic factor availability. Furthermore, activity dependent signals have recently been shown to influence a variety of events specific to individual neurodegenerative diseases, which will also be highlighted

Pituitary adenylate cyclase-activating peptide induces long-lasting neuroprotection through the induction of activity-dependent signaling via the cyclic AMP response element-binding protein-regulated transcription co-activator 1

Pituitary adenylate cyclase-activating peptide (PACAP) is a neuroprotective peptide which exerts its effects mainly through the cAMP-protein kinase A (PKA) pathway. Here, we show that in cortical neurons, PACAP-induced PKA signaling exerts a major part of its neuroprotective effects indirectly, by triggering action potential (AP) firing. Treatment of cortical neurons with PACAP induces a rapid and sustained PKA-dependent increase in AP firing and associated intracellular Ca(2+) transients, which are essential for the anti-apoptotic actions of PACAP. Transient exposure to PACAP induces long-lasting neuroprotection in the face of apoptotic insults which is reliant on AP firing and the activation of cAMP response element (CRE) binding protein (CREB)-mediated gene expression. Although direct, activity-independent PKA signaling is sufficient to trigger phosphorylation on CREB’s activating serine-133 site, this is insufficient for activation of CREB-mediated gene expression. Full activation is dependent on CREB-regulated transcription co-activator 1 (CRTC1), whose PACAP-induced nuclear import is dependent on firing activity-dependent calcineurin signaling. Over-expression of CRTC1 is sufficient to rescue PACAP-induced CRE-mediated gene expression in the face of activity-blockade, while dominant negative CRTC1 interferes with PACAP-induced, CREB-mediated neuroprotection. Thus, the enhancement of AP firing may play a significant role in the neuroprotective actions of PACAP and other adenylate cyclase-coupled ligands

SynGAP isoforms exert opposing effects on synaptic strength

Peer reviewedPublisher PD

Lymphomatous infilration of the peripheral nervous system in enteropathy-associated T-cell lymphoma

The document attached has been archived with permission from the editor of the Medical Journal of Australia. An external link to the publisher’s copy is included.Yoon-Sim Yap, Adrian Cummins, Peter Blumbergs, Jennifer Hardingham, Sunil Dabadghao and John Norma