Divergence of Intracellular Trafficking of Sphingosine Kinase 1 and Sphingosine-1-Phosphate Receptor 3 in MCF-7 Breast Cancer Cells and MCF-7-Derived Stem Cell-Enriched Mammospheres

Breast cancer MCF-7 cell-line-derived mammospheres were shown to be enriched in cells with a CD44+/CD24– surface profile, consistent with breast cancer stem cells (BCSC). These BCSC were previously reported to express key sphingolipid signaling effectors, including pro-oncogenic sphingosine kinase 1 (SphK1) and sphingosine-1-phosphate receptor 3 (S1P3). In this study, we explored intracellular trafficking and localization of SphK1 and S1P3 in parental MCF-7 cells, and MCF-7 derived BCSC-enriched mammospheres treated with growth- or apoptosis-stimulating agents. Intracellular trafficking and localization were assessed using confocal microscopy and cell fractionation, while CD44+/CD24- marker status was confirmed by flow cytometry. Mammospheres expressed significantly higher levels of S1P3 compared to parental MCF-7 cells (p < 0.01). Growth-promoting agents (S1P and estrogen) induced SphK1 and S1P3 translocation from cytoplasm to nuclei, which may facilitate the involvement of SphK1 and S1P3 in gene regulation. In contrast, pro-apoptotic cytokine tumor necrosis factor α (TNFα)-treated MCF-7 cells demonstrated increased apoptosis and no nuclear localization of SphK1 and S1P3, suggesting that TNFα can inhibit nuclear translocation of SphK1 and S1P3. TNFα inhibited mammosphere formation and induced S1P3 internalization and degradation. No nuclear translocation of S1P3 was detected in TNFα-stimulated mammospheres. Notably, SphK1 and S1P3 expression and localization were highly heterogenous in mammospheres, suggesting the potential for a large variety of responses. The findings provide further insights into the understanding of sphingolipid signaling and intracellular trafficking in BCs. Our data indicates that the inhibition of SphK1 and S1P3 nuclear translocation represents a novel method to prevent BCSCs proliferation.     

A study of the plasma lipoproteins and the tissue lipids of the migrating lamprey,Mordacia mordax

Sea lampreys,Mordacia mordax, were collected in spring from the Yarra River, Victoria, during their upstream spawning migration, to study the lipid composition in their tissues and plasma and their lipid transport system. Plasma lipoproteins were isolated by preparative ultracentrifugation and their chemical compositions were analyzed. The major classes of lipoproteins were found to be similar to those of man and higher animals. Lipids from the muscle and liver were analyzed for fatty acids. The striking feature of the lipids in the migrating lamprey is the presence of very high levels of cholesterol in both plasma and muscle. The possible metabolic roles of cholesterol have been discussed.     

Water Resource Models in the Mekong Basin: A Review

Development of the water resources of the Mekong Basin is the subject of intense debate both within the Mekong region and internationally. Water resources modelling is playing an increasingly important role in the debate, with significant effort in building integrated modelling platforms to describe the hydrological, ecological, social and economic impacts of water resource development. In the hydrological domain, a comprehensive set of models has been effective in building understanding of the system, and in identifying and describing the issues and trade-offs involved in basin-scale water planning. In the ecological and social domains, quantitative modelling has not progressed very far; geo-spatial analysis and qualitative frameworks remain the most commonly used tools. Economic models have been used to assess the costs and benefits of water resources development and to describe the trade-offs between different sectors and users. These analyses are likely to play an important role in the policy and planning debate, but are hampered by uncertainties in valuation of ecosystem services. Future efforts should focus on optimising the use of existing model platforms for the Mekong, including structured comparison of multiple hydrological models to quantify errors and identify an optimum set of modelling tools for different applications. A comprehensive research effort is needed to incorporate groundwater into hydrological models for regional planning. Options for social impact assessment should be reassessed before major investments are made in complex modelling platforms, and participatory social survey methods evaluated as part of an integrated assessment framework.     

Retrieval Of Morphological Variants In Searches Of Latin Text Databases

This paper reports a detailed evaluation of the effectiveness of a system that has been developed for the identification and retrieval of morphological variants in searches of Latin text databases. A user of the retrieval system enters the principal parts of the search term (two parts for a noun or adjective, three parts for a deponent verb, and four parts for other verbs), this enabling the identification of the type of word that is to be processed and of the rules that are to be followed in determining the morphological variants that should be retrieved. Two different search algorithms are described. The algorithms are applied to the Latin portion of the Hartlib Papers Collection and to a range of classical, vulgar and medieval Latin texts drawn from the Patrologia Latina and from the PHI Disk 5.3 datasets. The effectiveness of these searches demonstrates the effectiveness of our procedures in providing access to the full range of classical and post-classical Latin text databases. This revised version was published online in July 2006 with corrections to the Cover Date.     

Nightingallery: theatrical framing and orchestration in participatory performance

The Nightingallery project encouraged participants to converse, sing, and perform with a musically responsive animatronic bird, playfully interacting with the character while members of the public could look on and observe. We used Nightingallery to frame an HCI investigation into how people would engage with one another when confronted with unfamiliar technologies in conspicuously public, social spaces. Structuring performances as improvisational street theatre, we styled our method of exhibiting the bird character. We cast ourselves in supporting roles as carnival barkers and minders of the bird, presenting him as if he were a fantastical creature in a fairground sideshow display, allowing him the agency to shape and maintain dialogues with participants, and positioning him as the focal character upon which the encounter was centred. We explored how the anthropomorphic nature of the bird itself, along with the cultural connotations associated with the carnival/sideshow tradition helped signpost and entice participants through the trajectory of their encounters with the exhibit. Situating ourselves as secondary characters within the narrative defining the performance/use context, our methods of mediation, observation, and evaluation were integrated into the performance frame. In this paper, we explore recent HCI theories in mixed reality performance to reflect upon how genre-based cultural connotations can be used to frame trajectories of experience, and how manipulation of roles and agency in participatory performance can facilitate HCI investigation of social encounters with playful technologies.     

Cell Type-Specific Induction of Inflammation-Associated Genes in Crohn’s Disease and Colorectal Cancer

Based on the rapid increase in incidence of inflammatory bowel disease (IBD), the identification of susceptibility genes and cell populations contributing to this condition is essential. Previous studies suggested multiple genes associated with the susceptibility of IBD; however, due to the analysis of whole-tissue samples, the contribution of individual cell populations remains widely unresolved. Single-cell RNA sequencing (scRNA-seq) provides the opportunity to identify underlying cellular populations. We determined the enrichment of Crohn’s disease (CD)-induced genes in a publicly available Crohn’s disease scRNA-seq dataset and detected the strongest induction of these genes in innate lymphoid cells (ILC1), highly activated T cells and dendritic cells, pericytes and activated fibroblasts, as well as epithelial cells. Notably, these genes were highly enriched in IBD-associated neoplasia, as well as sporadic colorectal cancer (CRC). Indeed, the same six cell populations displayed an upregulation of CD-induced genes in a CRC scRNA-seq dataset. Finally, after integrating and harmonizing the CD and CRC scRNA-seq data, we demonstrated that these six cell types display a gradual increase in gene expression levels from a healthy state to an inflammatory and tumorous state. Together, we identified cell populations that specifically upregulate CD-induced genes in CD and CRC patients and could, therefore, contribute to inflammation-associated tumor development.     

Effect of dietary selenium on the progression of heart failure in the ageing spontaneously hypertensive rat

Oxidative stress has been directly implicated in hypertension and myocardial remodelling, two pathologies fundamental to the development of chronic heart failure. Selenium (Se) can act directly and indirectly as an antioxidant and a lowered Se status leads to a higher risk of cardiovascular disease. This study examined the role of Se on the development of hypertension and subsequent progression to chronic heart failure in spontaneously hypertensive rats (SHR). Three dietary groups were studied: (i) Se‐free; (ii) normal Se (50 μg Se/kg food); and (iii) high Se (1000 μg Se/kg food). Systolic blood pressure and echocardiography were used to detect cardiac changes in vivo. At study end, cardiac tissues were assayed for glutathione peroxidase activity, thioredoxin reductase activity, and protein carbonyls. The major finding of this study was the high heart failure‐related mortality rate in SHRs fed an Se‐free diet (70%). Normal and high levels of dietary Se resulted in higher survival rates of 78 and 100%, respectively. Furthermore, high dietary Se was clearly associated with lower levels of cardiac oxidative damage and increased antioxidant expression, as well as a reduction in disease severity and mortality in the SHR.     

Posttraumatic stress disorder patients' readiness to change alcohol and anger problems.

Notes that recovery from combat-related posttraumatic stress disorder (PTSD) is often complicated by unacknowledged problems with alcohol and anger. 102 males combat veterans (aged 42–63 yrs) entering a residential PTSD rehabilitation program completed University of Rhode Island Change Assessment and process-of-change questionnaires based on J. O. Prochaska and C. C. DiClemente's transtheoretical model (TTM; J. O. Prochaska et al, 1992). Separate assessments were made for alcohol abuse and anger control. Four motivational subtypes were identified for both problems. Motivation to change alcohol problems was independent of that for anger. Relative to less-motivated peers highly motivated patients were more like to spontaneously identify alcohol or anger as problems in their life and made greater use of change strategies specified by the TTM. These results support extension of the TTM to anger management and to PTSD management. Treatment implications are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Tenderness, ageing rate and meat quality of pork M. longissimus thoracis et lumborum after accelerated boning

The impact of accelerated boning on tenderness, ageing rate and meat quality of pork longissimus muscle was investigated. Accelerated boning of eight Large White×Landrace pork carcasses at 30 min post-mortem followed by chilling at 0°C resulted in tougher pork with higher drip loss and a darker surface lightness relative to conventional boning at 24 h post-mortem. The increased toughness was still observed at 4 days post-mortem, a time by which 80% of ageing generally had occurred as seen in experiment 2. The increased toughness could be attributed to cold shortening and a reduction in proteolysis.     

The impact of stress on mothers' memory of a natural disaster.

The effects of stress on mothers' recall for a major hurricane were studied. Stress was objectively defined as low, moderate, or high according to the severity of home damage. This study of 96 mothers was conducted concurrently with L. E. Bahrick, J. F. Parker, R. Fivush, and M. Levitt (1998), allowing the authors to compare child and adult recall as a function of the same stressor. There was a quadratic relationship between storm severity and total recall for adults, similar to their children. Mothers' recall increased from low to moderate severity, but recall at moderate severity did not differ from high severity. These findings help clarify the effects of stress on the amount and type of information adults recall in retrospective accounts of naturalistic, temporally extended events. (PsycINFO Database Record (c) 2010 APA, all rights reserved)