Altered formalin-induced pain and Fos induction in the periaqueductal grey of preadolescent rats following neonatal LPS exposure

Animal and human studies have demonstrated that early pain experiences can produce alterations in the nociceptive systems later in life including increased sensitivity to mechanical, thermal, and chemical stimuli. However, less is known about the impact of neonatal immune challenge on future responses to noxious stimuli and the reactivity of neural substrates involved in analgesia. Here we demonstrate that rats exposed to Lipopolysaccharide (LPS; 0.05 mg/kg IP, Salmonella enteritidis) during postnatal day (PND) 3 and 5 displayed enhanced formalin-induced flinching but not licking following formalin injection at PND 22. This LPS-induced hyperalgesia was accompanied by distinct recruitment of supra-spinal regions involved in analgesia as indicated by significantly attenuated Fos-protein induction in the rostral dorsal periaqueductal grey (DPAG) as well as rostral and caudal axes of the ventrolateral PAG (VLPAG). Formalin injections were associated with increased Fos-protein labelling in lateral habenula (LHb) as compared to medial habenula (MHb), however the intensity of this labelling did not differ as a result of neonatal immune challenge. These data highlight the importance of neonatal immune priming in programming inflammatory pain sensitivity later in development and highlight the PAG as a possible mediator of this process

Developing organisational change capability

Oxtoby, B.; McGuinness, T.; and Morgan, R. (2002). Developing organisational change capability. European Management Journal. 20(3), pp.310-320 RAE2008

CD33 reponses are blocked by SOCS3 through accelerated proteasomal-mediated turnover

CD33 is a member of the sialic acid–binding immunoglobulin-like lectin (Siglec) family of inhibitory receptors and a therapeutic target for acute myeloid leukemia (AML). CD33 contains a cytoplasmic immunoreceptor tyrosine-based inhibitory motif (ITIM), which can recruit SHP-1 and SHP-2. How CD33 expression is regulated is unclear. Suppressor of cytokine signaling 3 (SOCS3) is expressed in response to cytokines, LPS, and other PAMPs, and competes with SHP-1/2 binding to ITIMs of cytokine receptors, thereby inhibiting signaling. In this study, using peptide pull-down experiments, we found that SOCS3 can specifically bind to the phosphorylated ITIM of CD33. Additionally, following cross-linking SOCS3 can recruit the ECS E3 ligase resulting in accelerated proteasomal degradation of both CD33 and SOCS3. Our data suggest that the tyrosine motifs in CD33 are not important for internalization, while they are required for degradation. Moreover, SOCS3 inhibited the CD33-induced block on cytokine-induced proliferation. This is the first receptor shown to be degraded by SOCS3 and where SOCS3 and its target protein are degraded concomitantly. Our findings clearly suggest that during an inflammatory response, the inhibitory receptor CD33 is lost by this mechanism. Moreover, this has important clinical implications as tumors expressing SOCS3 may be refractory to -CD33 therapy.

Regional implications of macro-economic, sectoral and company changes in the development of technopoles in Britain and France

This paper reports the proceedings of a conference held at Reading University in 1993 which addressed the issues of new technological developments at the regional and sub-regional levels in Britain and France. These new technological clusters - the `Technopoles' - are investigated in a series of papers in both English and French which examines their spatial, sectoral and economic aspects to determine what lessons can be learned from their development and what their future economic significance is likely to be. Two recurring themes are of particular significance in the papers - the link between R& D and regional development, and the different forms which innovation assumes within the various technopoles under scrutiny.

A comparative study on the "American innocence" issue : Henry Jame's The American and Daisy Miller : a study

Esta dissertação aborda a questão da “inocência americana” em duas obras do escritor norte-americano Henry James, empregando conceitos da Literatura Comparada como base para a análise dos textos escolhidos: The American e Daisy Miller: A Study. Portanto, os conceitos de intertextualidade, influência e alteridade são fundamentais para o estabelecimento das confluências e divergências entre as duas obras. Este trabalho também apresenta uma análise, com base na teoria comparatista da interdisciplinaridade, entre a obra literária Daisy Miller: A Study e o filme Daisy Miller, dirigido por Peter Bogdanovich. O tema recorrente nas obras analisadas, o da “inocência americana”, foi abordado por Henry James em grande parte de sua produção literária, sendo um reflexo de sua própria experiência como o “outro”, bem como de suas observações sobre seus compatriotas, quando confrontados com os valores e tradições vigentes na Europa, no século XIX. James alcançou seu merecido lugar no cânone literário ocidental, graças ao seu estilo incomparável, o qual foi aperfeiçoando durante toda sua carreira e até hoje é parâmetro para escritores contemporâneos.

Literatura e cinema: representações do feminino em Washington Square, Daisy Miller e The Europeans

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Los oráculos de la sibila mexicana, recogidos é interpretados

Mode of access: Internet.

The spoils of Poynton.

Mode of access: Internet.

The spoils of Poynton.

Originally appeared in the Atlantic monthly from Apr. to Oct. 1896 under the title: The old things.

The American essays,

Mode of access: Internet.

Watch and ward.

Mode of access: Internet.

The spoils of Poynton.

Originally appeared in the Atlantic monthly from Apr. to Oct. 1896 under the title: The old things.

Roderick Hudson /

Mode of access: Internet.