AKT inhibition is associated with chemosensitisation in the pancreatic cancer cell line MIA-PaCa-2

Activation of the serine/threonine kinase AKT is common in pancreatic cancer; inhibition of which sensitises cells to the apoptotic effect of chemotherapy. Of the various downstream targets of AKT, we examined activation of the NF-kappaB transcription factor and subsequent transcriptional regulation of BCL-2 gene family in pancreatic cancer cells. Inhibition of either phosphatidylinositol-3 kinase or AKT led to a decreased protein level of the antiapoptotic gene BCL-2 and an increased protein level of the proapoptotic gene BAX. Furthermore, inhibition of AKT decreased the function of NF-kappaB, which is capable of transcriptional regulation of the BCL-2 gene. Inhibiting this pathway had little effect on the basal level of apoptosis in pancreatic cancer cells, but increased the apoptotic effect of chemotherapy. The antiapoptotic effect of AKT activation in pancreatic cancer cells may involve transcriptional induction of a profile of BCL-2 proteins that confer resistance to apoptosis; alteration of this balance allows sensitisation to the apoptotic effect of chemotherapy

Galectin-4 Controls Intestinal Inflammation by Selective Regulation of Peripheral and Mucosal T Cell Apoptosis and Cell Cycle

Galectin-4 is a carbohydrate-binding protein belonging to the galectin family. Here we provide novel evidence that galectin-4 is selectively expressed and secreted by intestinal epithelial cells and binds potently to activated peripheral and mucosal lamina propria T-cells at the CD3 epitope. The carbohydrate-dependent binding of galectin-4 at the CD3 epitope is fully functional and inhibited T cell activation, cycling and expansion. Galectin-4 induced apoptosis of activated peripheral and mucosal lamina propria T cells via calpain-, but not caspase-dependent, pathways. Providing further evidence for its important role in regulating T cell function, galectin-4 blockade by antisense oligonucleotides reduced TNF-alpha inhibitor induced T cell death. Furthermore, in T cells, galectin-4 reduced pro-inflammatory cytokine secretion including IL-17. In a model of experimental colitis, galectin-4 ameliorated mucosal inflammation, induced apoptosis of mucosal T-cells and decreased the secretion of pro-inflammatory cytokines. Our results show that galectin-4 plays a unique role in the intestine and assign a novel role of this protein in controlling intestinal inflammation by a selective induction of T cell apoptosis and cell cycle restriction. Conclusively, after defining its biological role, we propose Galectin-4 is a novel anti-inflammatory agent that could be therapeutically effective in diseases with a disturbed T cell expansion and apoptosis such as inflammatory bowel disease

Rethinking 'risk' and self-management for chronic illness

Self-management for chronic illness is a current high profile UK healthcare policy. Policy and clinical recommendations relating to chronic illnesses are framed within a language of lifestyle risk management. This article argues the enactment of risk within current UK self-management policy is intimately related to neo-liberal ideology and is geared towards population governance. The approach that dominates policy perspectives to ‘risk' management is critiqued for positioning people as rational subjects who calculate risk probabilities and act upon them. Furthermore this perspective fails to understand the lay person's construction and enactment of risk, their agenda and contextual needs when living with chronic illness. Of everyday relevance to lay people is the management of risk and uncertainty relating to social roles and obligations, the emotions involved when encountering the risk and uncertainty in chronic illness, and the challenges posed by social structural factors and social environments that have to be managed. Thus, clinical enactments of self-management policy would benefit from taking a more holistic view to patient need and seek to avoid solely communicating lifestyle risk factors to be self-managed

Marine influence in the Barreiras Formation, State of Alagoas, northeastern Brazil

Tidal processes were important for deposition of the Barreiras Formation located in northern Brazil, while correlatable deposits in northeastern Brazil have been traditionally related to continental environments. Facies analysis in southern Alagoas revealed that the Barreiras Formation consists of cross-stratified conglomerates and sandstones (facies Sx and Cgx), compound cross-stratified sandstones (facies Cx), and heterolithic beddings (facies H). A significant portion of these deposits occurs within channel morphologies displaying fining and thinning upward successions. An abundance of sedimentary features is comparable to those from the northern Brazilian counterpart. These include: tidal bundles; herringbone cross-stratification; heterolithic beddings with sandstone and mudstone beds in sharp contacts; and ichnofossils mostly consisting of Ophiomorpha nodosa, Skolithos and Planolites. Altogether, these features point to a marginal marine depositional setting dominated by tidal processes, which are related to an estuarine system, an interpretation also provided for the Barreiras Formation in northern Brazil. The widespread occurrence of deposits with unambiguous evidence of tidal processes in the Barreiras Formation of northern Brazil, and now in the State of Alagoas, leads to argue that the early/middle Miocene worldwide marine transgression might have left a much more widespread sedimentary record along the Brazilian coast than currently regarded.<br>Processos de maré foram importantes na deposição da Formação Barreiras localizada no norte do Brasil, enquanto depósitos correlatos do nordeste brasileiro têm sido tradicionalmente relacionados a ambientes continentais. Análise de fácies no sul de Alagoas revelou que a Formação Barreiras consiste em conglomerados e arenitos com estratificações cruzadas (facies Sx e Cgx), arenitos com estratificação cruzada composta (facies Cx), e acamamentos heterolíticos (facies H). Uma porção significativa desses depósitos ocorre inserida em morfologias de canal, internamente contendo sucessões de granocrescência e adelgaçamento ascendentes. A abundância de feições sedi-mentares é comparável àquelas documentadas em depósitos correlatos do norte do Brasil. Estas incluem: bandamentos de maré; estratificações cruzadas espinha-de-peixe; acamamen-tos heterolíticos contendo camadas de arenitos e argilitos em contato brusco; e icnofósseis consistindo principalmente em Ophiomorpha nodosa, Skolithos e Planolites. Estas feições apontam para ambiente deposicional marinho marginal dominado por processos de maré, possivelmente relacionado a sistema estuarino. Esta interpretação é similar à atribuída para a Formação Barreiras no norte do Brasil. A ampla ocorrência de depósitos contendo evidência inequívoca de processos de maré na Formação Barreiras no norte do Brasil, e agora também no Estado de Alagoas, leva a propor que o período de transgressão marinha registrada globalmente no eo/meso Mioceno pode ter deixado um registro sedimentar muito mais amplo ao longo da costa brasileira do que até então considerado