A population of HLA-DR+ immature cells accumulates in the blood dendritic cell compartment of patients with different types of cancer

Dendritic cell (DC) defects are an important component of immunosuppression in cancer. Here, we assessed whether cancer could affect circulating DC populations and its correlation with tumor progression. The blood DC compartment was evaluated in 136 patients with breast cancer, prostate cancer, and malignant glioma. Phenotypic, quantitative, and functional analyses were performed at various stages of disease. Patients had significantly fewer circulating myeloid (CD11c(+)) and plasmacytoid (CD123(+)) DC, and a concurrent accumulation of CD11c(-)CD123(-) immature cells that expressed high levels of HLA-DR+ immature cells (DR+IC). Although DR+IC exhibited a limited expression of markers ascribed to mature hematopoietic lineages, expression of HLA-DR, CD40, and CD86 suggested a role as antigen-presenting cells. Nevertheless, DR+IC had reduced capacity to capture antigens and elicited poor proliferation and interferon-gamma secretion by T-lymphocytes. Importantly, increased numbers of DR+IC correlated with disease status. Patients with metastatic breast cancer showed a larger number of DR+IC in the circulation than patients with local/nodal disease. Similarly, in patients with fully resected glioma, the proportion of DR+IC in the blood increased when evaluation indicated tumor recurrence. Reduction of blood DC correlating with accumulation of a population of immature cells with poor immunologic function may be associated with increased immunodeficiency observed in cancer.

Direct continuities between cisternae at different levels of the Golgi complex in glucose-stimulated mouse islet beta cells

Direct continuity between the membranes of cisternae in the Golgi complex in mammalian cells rarely has been observed; when seen, its documentation has been equivocal. Here we have used dual-axis electron microscope tomography to examine the architecture of the Golgi in three dimensions at approximate to6-nm resolution in rapidly frozen, freeze-substituted murine cells that make and secrete insulin in response to glucose challenge. Our data show three types of direct connections between Golgi cisternae that are normally distinct from one another. These connections all bypass interceding cisternae. We propose that when pancreatic beta cells are stimulated to synthesize and secrete insulin rapidly in vivo, such connections provide a continuous lumen that facilitates the rapid transit of large amounts of newly made protein for secretion. The heterotypic fusion of cisternae, even transiently, raises important questions about the molecular mechanisms that (i) facilitate the fusion/fission of cisternal membranes and control the directionality and specificity of such events, and (it) retain Golgi processing enzymes at specific places within individual cisternae when two cisternae at different levels in the Golgi have fused, maintaining the sequential processing hierarchy that is a hallmark of Golgi organization.

Effects of pravastatin on coronary events in 2073 patients with low levels of both low-density lipoprotein cholesterol and high-density lipoprotein cholesterol: results from the LIPID study

Aims Fibrates or nicotinic acid are usually recommended for secondary prevention of coronary heart disease in patients with low plasma levels of both low-density tipoprotein cholesterol (LDL-C) less than or equal to140 mg/dL (less than or equal to3.6 mmol/L) and high-density lipoprotein cholesterol (HDL-C) less than or equal to40 mg/dL (less than or equal to1.03 mmol/L). The LIPID trial, a randomised, placebo-controlled trial in 9014 patients at 87 centres in Australia and New Zealand, provided an opportunity to investigate the effects of an HMG-CoA reductase inhibitor in patients with tow LDL-C and tow HDL-C. Methods and results Participants in this post hoc substudy were 2073 patients aged 31-75 years with baseline LDL-C less than or equal to140 mg/dL (less than or equal to3.6 mmoL/L), HDL-C less than or equal to40 mg/dL (less than or equal to1.03 mmol/L), and triglyceride less than or equal to300 mg/dL (less than or equal to3.4 mmol/L). The relative risk reduction with pravastatin treatment was 27% for major coronary events (95% Cl 8-42%), 27% for coronary heart disease mortality (95% CI 0-47%), 21% for all-cause mortality (95% Cl 0-38%), and 51% for stroke (95% CI 24-69%). The number needed to treat to prevent a major coronary event over 6 years was 22. Conclusions Treatment with pravastatin in patients with both low LDL-C and low HDL-C significantly reduced major coronary events, stroke, and all-cause mortality. The level of HDL-C is crucial to the risk of recurrent CHD events and, consequently, the benefit of lowering LDL-C. (C) 2004 Published by Elsevier Ltd on behalf of The European Society of Cardiology.

General self-concept and life satisfaction for boys with differing levels of physical coordination: The role of goal orientations and leisure participation

Participation in leisure-time activities, self-concept perceptions and individual dispositional goal orientations were examined as mediators of relationships between physical coordination and self-evaluations of life satisfaction and general self-concept for 173 boys aged 10-13 years. Participants completed seven-day activity diaries and 12-month retrospective recall questionnaires recording participation in leisure-time activities. Self-report measures of self-concept, global life satisfaction and dispositional goal orientations were also completed. Results showed that boys with moderate to severe physical coordination difficulties had significantly lower self-concept perceptions of physical ability and appearance, peer and parent relations and general self-concept, as well as lower life satisfaction than boys with medium to high levels of physical coordination. The relationships between boys' physical coordination and their self-perceptions of life satisfaction and general self-concept were significantly influenced by individual self-concept appraisals of physical ability and appearance, peer and parent relations. Adopting task-oriented goals was found to positively change the relationship between physical coordination and both general self-concept and life satisfaction. Team sport participation positively mediated the relationship between physical coordination and life satisfaction. The potential for team sport participation and adoption of task-oriented goals to influence life satisfaction for boys with differing levels of physical coordination was discussed. (c) 2006 Elsevier B.V.. All rights reserved.

A polymorphism in the agouti signalling protein (ASIP) is associated with decreased levels of mRNA

To date, a role for agouti signalling protein (ASIP) in human pigmentation has not been well characterized. It is known that agouti plays a pivotal role in the pigment switch from the dark eumelanin to the light pheomelanin in the mouse. However, because humans do not have an agouti banded hair pattern, its role in human pigmentation has been questioned. We previously identified a single polymorphism in the 3'-untranslated region (UTR) of ASIP that was found at a higher frequency in African-Americans compared with other population groups. To compare allele frequencies between European-Australians and indigenous Australians, the g.8818A -> G polymorphism was genotyped. Significant differences were seen in allele frequencies between these groups (P < 0.0001) with carriage of the G allele highest in Australian Aborigines. In the Caucasian sample set a strong association was observed between the G allele and dark hair colour (P = 0.004) (odds ratio 4.6; 95% CI 1.4-15.27). The functional consequences of this polymorphism are not known but it was postulated that it might result in message instability and premature degradation of the transcript. To test this hypothesis, ASIP mRNA levels were quantified in melanocytes carrying the variant and non-variant alleles. Using quantitative real-time polymerase chain reaction the mean ASIP mRNA ratio of the AA genotype to the AG genotype was 12 (P < 0.05). This study suggests that the 3'-UTR polymorphism results in decreased levels of ASIP and therefore less pheomelanin production.

Habitat selection and breeding success in a forest-nesting Alcid, the marbled murrelet, in two landscapes with different degrees of forest fragmentation

We studied habitat selection and breeding success in marked populations of a protected seabird (family Alcidae), the marbled murrelet (Brachyramphus marmoratus), in a relatively intact and a heavily logged old-growth forest landscape in south-western Canada. Murrelets used old-growth fragments either proportionately to their size frequency distribution (intact) or they tended to nest in disproportionately smaller fragments (logged). Multiple regression modelling showed that murrelet distribution could be explained by proximity of nests to landscape features producing biotic and abiotic edge effects. Streams, steeper slopes and lower elevations were selected in both landscapes, probably due to good nesting habitat conditions and easier access to nest sites. In the logged landscape, the murrelets nested closer to recent clearcuts than would be expected. Proximity to the ocean was favoured in the intact area. The models of habitat selection had satisfactory discriminatory ability in both landscapes. Breeding success (probability of nest survival to the middle of the chick rearing period), inferred from nest attendance patterns by radio-tagged parents, was modelled in the logged landscape. Survivorship was greater in areas with recent clearcuts and lower in areas with much regrowth, i.e. it was positively correlated with recent habitat fragmentation. We conclude that marbled murrelets can successfully breed in old-growth forests fragmented by logging.

Scaling and non-scaling of muscle activity, kinematics, and dynamics in sit-ups with different degrees of difficulty

The purpose of this study was to investigate how the CNS adjusts motor patterns for variants of a complex axial movement-the situp. Adjustments were induced by changing the support surface contact and mass distribution of the body. Healthy adults performed straight-legged sit-ups, 3 s in duration, with support added to or removed from the lumbar trunk, or with mass added to the head or to the legs. Each of these interventions either increased or decreased the difficulty of the task. The study addressed the extent to which changes in sit-up difficulty are compensated by scaling of muscle activity, kinematics, and dynamics versus the extent to which they are compensated by changing discretely the motor pattern. The analysis of muscle activity, kinematics, and dynamics focused on the first 30-40% of the sit-up-the trunk flexion phase-since this is the most critical part of the movement. Our results demonstrate that, in some respects, sit-up kinematics and dynamics scaled with difficulty, but in other respects, they did not. Muscle activity also scaled, in many respects, but in more difficult sit-ups, abdominal flexor activity decreased instead of increased. Non-scaling changes in these parameters suggest that complex movements, such as the sit-up, may require discrete changes in motor pattern in order to deal with large loads, which challenge the available leverage. (C) 2005 Elsevier Ltd. All rights reserved.

The effect of different levels of dietary crude protein on urea metabolism of rusa deer (Cervus timorensis)

Two experiments were conducted to measure urea recycling and rumen flow dynamics in young rusa deer fed low (LP) or high (HP) protein diets. Pool size and flux rate of labelled urea. into and out of the blood pool were measured using single intravenous (i.v.) injection solutions containing [C-14] - and [N-15]-urea. A curve peeling technique was used to fit the enrichment of N-15 or specific radioactivity (SRA) of C-14 to exponential equations. Body urea-N pool size was significantly greater (P < 0.05) when a HP, compared to a LP diet, was fed. Urea space, expressed as a percent of live weight, total flux rate of urea through the blood pool and the irreversible loss of urea was similar for both diets. The mean (+/- S.E.M.) concentration of plasma urea-N was greater when animals were fed the HP diet compared to the LP diet (2 1.1 +/- 0.3 versus 14.4 +/- 1.4 mg/100 ml, respectively). Voluntary feed intake and digestibility of dietary components were also measured. Daily dry matter intakes were not affected by the crude protein (CP) content of the diet, although apparent DM digestibility was significantly greater for HP diet fed in both experiments. An intraruminal infusion of CrEDTA was used to determine rumen flow dynamics. Ruminal mean retention time, relative net outflow rate of water and passage rate constant (k(w)) were significantly greater (P < 0.05) when the HP diet was fed compared to the LP diet. The extent of urea metabolism and flux rates of urea between the blood and secondary pools appear similar to those previously reported for other ruminants fed diets contrasting in CP content. (c) 2005 Elsevier B.V. All rights reserved.

Dual adaptation to two opposing visuomotor rotations when each is associated with different regions of workspace

Studies examining dual adaptation to opposing novel environments have yielded contradictory results, with previous evidence supporting both successful dual adaptation and interference leading to poorer adaptive performance. Whether or not interference is observed during dual adaptation appears to be dependent on the method used to allow the performer of the task to distinguish between two novel environments. This experiment tested if colour cues, a separation in workspace, and presentation schedule, could be used to distinguish between two opposing visuomotor rotations and enable dual adaptation. Through the use of a purpose designed manipulandum, each visuomotor rotation was either presented in the same region of workspace and associated with colour cues (Group 1), different regions of workspace in addition to colour cues (Groups 2 and 3) or different regions of workspace only (Groups 4 and 5). We also assessed the effectiveness of the workspace separation with both randomised and alternating presentation schedules (Groups 4 and 5). The results indicated that colour cues were not effective at enabling dual adaptation when each of the visuomotor rotations was associated with the same region of workspace. When associated with different regions of workspace, however, dual adaptation to the opposing rotations was successful regardless of whether colour cues were present or the type of presentation schedule.

Self-efficacy and task performance: An investigation from two levels of analysis and specificity

This research adopts a resource allocation theoretical framework to generate predictions regarding the relationship between self-efficacy and task performance from two levels of analysis and specificity. Participants were given multiple trials of practice on an air traffic control task. Measures of task-specific self-efficacy and performance were taken at repeated intervals. The authors used multilevel analysis to demonstrate dynamic main effects, dynamic mediation and dynamic moderation. As predicted, the positive effects of overall task specific self-efficacy and general self-efficacy on task performance strengthened throughout practice. In line with these dynamic main effects, the effect of general self-efficacy was mediated by overall task specific self-efficacy; however this pattern emerged over time. Finally, changes in task specific self-efficacy were negatively associated with changes in performance at the within-person level; however this effect only emerged towards the end of practice for individuals with high levels of overall task specific self-efficacy. These novel findings emphasise the importance of conceptualising self-efficacy within a multi-level and multi-specificity framework and make a significant contribution to understanding the way this construct relates to task performance.

Concept-based document readability in domain specific information retrieval

Domain specific information retrieval has become in demand. Not only domain experts, but also average non-expert users are interested in searching domain specific (e.g., medical and health) information from online resources. However, a typical problem to average users is that the search results are always a mixture of documents with different levels of readability. Non-expert users may want to see documents with higher readability on the top of the list. Consequently the search results need to be re-ranked in a descending order of readability. It is often not practical for domain experts to manually label the readability of documents for large databases. Computational models of readability needs to be investigated. However, traditional readability formulas are designed for general purpose text and insufficient to deal with technical materials for domain specific information retrieval. More advanced algorithms such as textual coherence model are computationally expensive for re-ranking a large number of retrieved documents. In this paper, we propose an effective and computationally tractable concept-based model of text readability. In addition to textual genres of a document, our model also takes into account domain specific knowledge, i.e., how the domain-specific concepts contained in the document affect the document’s readability. Three major readability formulas are proposed and applied to health and medical information retrieval. Experimental results show that our proposed readability formulas lead to remarkable improvements in terms of correlation with users’ readability ratings over four traditional readability measures.