The development of the Meaning in Life Index (MILI) and its relationship with personality and religious behaviours and beliefs among UK undergraduate students

The scales available for assessing meaning in life appear to be confounded with several related constructs, including purpose in life, satisfaction with life, and goal-directed behaviour. The Meaning in Life Index (MILI), a new instrument devised as a specific measure of meaning in life, was developed from responses to a pool of 22 items rated by a sample of 501 undergraduate students in Wales. The nine-item scale demonstrated sufficient face validity, internal consistency, and scale reliability to commend the instrument for future use. With respect to personality, the MILI scores were most strongly predicted by neuroticism (negatively), and less strongly by extraversion (positively) and psychoticism (negatively). With respect to several religious behavioural variables, those who attended church at least weekly returned significantly higher MILI scores than those who attended church less frequently. Intrinsic religiosity was the only orientation to be significantly associated with the MILI scale scores, although the magnitude of the association was smaller than anticipated. These results suggest that meaning in life is associated more strongly with individual differences in personality than with specific religious behaviours and attitudes. The implications of these results are discussed in terms of individual's personal values and attitudes that might underlie their experience of a meaning in life

Efficiency of primary saliva secretion: an analysis of parameter dependence in dynamic single-cell and acinus models, with application to aquaporin knockout studies

Secretion from the salivary glands is driven by osmosis following the establishment of osmotic gradients between the lumen, the cell and the interstitium by active ion transport. We consider a dynamic model of osmotically driven primary saliva secretion and use singular perturbation approaches and scaling assumptions to reduce the model. Our analysis shows that isosmotic secretion is the most efficient secretion regime and that this holds for single isolated cells and for multiple cells assembled into an acinus. For typical parameter variations, we rule out any significant synergistic effect on total water secretion of an acinar arrangement of cells about a single shared lumen. Conditions for the attainment of isosmotic secretion are considered, and we derive an expression for how the concentration gradient between the interstitium and the lumen scales with water- and chloride-transport parameters. Aquaporin knockout studies are interpreted in the context of our analysis and further investigated using simulations of transport efficiency with different membrane water permeabilities. We conclude that recent claims that aquaporin knockout studies can be interpreted as evidence against a simple osmotic mechanism are not supported by our work. Many of the results that we obtain are independent of specific transporter details, and our analysis can be easily extended to apply to models that use other proposed ionic mechanisms of saliva secretion

What do aquaporin knockout studies tell us about fluid transport in epithelia?

The investigation of near-isosmotic water transport in epithelia goes back over 100 years; however, debates over mechanism and pathway remain. Aquaporin (AQP) knockouts have been used by various research groups to test the hypothesis of an osmotic mechanism as well as to explore the paracellular versus transcellular pathway debate. Nonproportional reductions in the water permeability of a water-transporting epithelial cell (e.g., a reduction of around 80–90 %) compared to the reduction in overall water transport rate in the knockout animal (e.g., a reduction of 50–60 %) are commonly found. This nonproportionality has led to controversy over whether AQP knockout studies support or contradict the osmotic mechanism. Arguments raised for and against an interpretation supporting the osmotic mechanism typically have partially specified, implicit, or incorrect assumptions. We present a simple mathematical model of the osmotic mechanism with clear assumptions and, for models based on this mechanism, establish a baseline prediction of AQP knockout studies. We allow for deviations from isotonic/isosmotic conditions and utilize dimensional analysis to reduce the number of parameters that must be considered independently. This enables a single prediction curve to be used for multiple epithelial systems. We find that a simple, transcellular-only osmotic mechanism sufficiently predicts the results of knockout studies and find criticisms of this mechanism to be overstated. We note, however, that AQP knockout studies do not give sufficient information to definitively rule out an additional paracellular pathway

Experimental modulation of capsule size in Cryptococcus neoformans

Experimental modulation of capsule size is an important technique for the study of the virulence of the encapsulated pathogen Cryptococcus neoformans. In this paper, we summarize the techniques available for experimental modulation of capsule size in this yeast and describe improved methods to induce capsule size changes. The response of the yeast to the various stimuli is highly dependent on the cryptococcal strain. A high CO(2) atmosphere and a low iron concentration have been used classically to increase capsule size. Unfortunately, these stimuli are not reliable for inducing capsular enlargement in all strains. Recently we have identified new and simpler conditions for inducing capsule enlargement that consistently elicited this effect. Specifically, we noted that mammalian serum or diluted Sabouraud broth in MOPS buffer pH 7.3 efficiently induced capsule growth. Media that slowed the growth rate of the yeast correlated with an increase in capsule size. Finally, we summarize the most commonly used media that induce capsule growth in C. neoformans

Critical Issues in the Development of Health Information Systems in Supporting Environmental Health: A Case Study of Ciguatera

Emerging environmental pressures resulting from climate change and globalization challenge the capacity of health information systems (HIS) in the Pacific to inform future policy and public health interventions. Ciguatera, a globally common marine food-borne illness, is used here to illustrate specific HIS challenges in the Pacific and how these might be overcome proactively to meet the changing surveillance needs resulting from environmental change.We review and highlight inefficiencies in the reactive nature of existing HIS in the Pacific to collect, collate, and communicate ciguatera fish poisoning data currently used to inform public health intervention. Further, we review the capacity of existing HIS to respond to new data needs associated with shifts in ciguatera disease burden likely to result from coral reef habitat disruption.Improved knowledge on the ecological drivers of ciguatera prevalence at local and regional levels is needed, combined with enhanced surveillance techniques and data management systems, to capture environmental drivers as well as health outcomes data.The capacity of public HIS to detect and prevent future outbreaks is largely dependent on the future development of governance strategies that promote proactive surveillance and health action. Accordingly, we present an innovative framework from which to stimulate scientific debate on how this might be achieved by using existing larger scale data sets and multidisciplinary collaborations

Operational approach to open dynamics and quantifying initial correlations

A central aim of physics is to describe the dynamics of physical systems. Schrodinger's equation does this for isolated quantum systems. Describing the time evolution of a quantum system that interacts with its environment, in its most general form, has proved to be difficult because the dynamics is dependent on the state of the environment and the correlations with it. For discrete processes, such as quantum gates or chemical reactions, quantum process tomography provides the complete description of the dynamics, provided that the initial states of the system and the environment are independent of each other. However, many physical systems are correlated with the environment at the beginning of the experiment. Here, we give a prescription of quantum process tomography that yields the complete description of the dynamics of the system even when the initial correlations are present. Surprisingly, our method also gives quantitative expressions for the initial correlation.Comment: Completely re-written for clarity of presentation. 15 pages and 2 figure

Targeted knock-down of miR21 primary transcripts using snoMEN vectors induces apoptosis in human cancer cell lines

We have previously reported an antisense technology, 'snoMEN vectors', for targeted knock-down of protein coding mRNAs using human snoRNAs manipulated to contain short regions of sequence complementarity with the mRNA target. Here we characterise the use of snoMEN vectors to target the knock-down of micro RNA primary transcripts. We document the specific knock-down of miR21 in HeLa cells using plasmid vectors expressing miR21-targeted snoMEN RNAs and show this induces apoptosis. Knock-down is dependent on the presence of complementary sequences in the snoMEN vector and the induction of apoptosis can be suppressed by over-expression of miR21. Furthermore, we have also developed lentiviral vectors for delivery of snoMEN RNAs and show this increases the efficiency of vector transduction in many human cell lines that are difficult to transfect with plasmid vectors. Transduction of lentiviral vectors expressing snoMEN targeted to pri-miR21 induces apoptosis in human lung adenocarcinoma cells, which express high levels of miR21, but not in human primary cells. We show that snoMEN-mediated suppression of miRNA expression is prevented by siRNA knock-down of Ago2, but not by knock-down of Ago1 or Upf1. snoMEN RNAs colocalise with Ago2 in cell nuclei and nucleoli and can be co-immunoprecipitated from nuclear extracts by antibodies specific for Ago2

Associations of vitamin D pathway genes with circulating 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and prostate cancer:a nested case-control study

Vitamin D pathway single nucleotide polymorphisms (SNPs) are potentially useful proxies for investigating whether circulating vitamin D metabolites [total 25-hydroxyvitamin-D, 25(OH)D; 1,25-dihydroxyvitamin, 1,25(OH)2D] are causally related to prostate cancer. We investigated associations of sixteen SNPs across seven genes with prostate-specific antigen-detected prostate cancer

Strain dependent differences in glucocorticoid-induced bone loss between C57BL/6J and CD-1 mice

We have investigated the effect of long-term glucocorticoid (GC) administration on bone turnover in two frequently used mouse strains; C57BL/6J and CD1, in order to assess the influence of their genetic background on GC-induced osteoporosis (GIO). GIO was induced in 12 weeks old female C57BL/6J and CD1 mice by subcutaneous insertion of long-term release prednisolone or placebo pellets. Biomechanical properties as assessed by three point bent testing revealed that femoral elasticity and strength significantly decreased in CD1 mice receiving GC, whereas C57BL/6J mice showed no differences between placebo and prednisolone treatment. Bone turnover assessed by microcomputer tomography revealed that contrary to C57BL/6J mice, prednisolone treated CD1 mice developed osteoporosis. In vitro experiments have underlined that, at a cellular level, C57BL/6J mice osteoclasts and osteoblasts were less responsive to GC treatment and tolerated higher doses than CD1 cells. Whilst administration of long-term release prednisolone pellets provided a robust GIO animal model in 12 weeks old CD1 mice, age matched C57BL/6J mice were not susceptible to the bone changes associated with GIO. This study indicates that for the induction of experimental GIO, the mouse strain choice together with other factors such as age should be carefully evaluated

Route of antigen delivery impacts the immunostimulatory activity of dendritic cell-based vaccines for hepatocellular carcinoma

Background: Dendritic cells (DC) are uniquely equipped to capture, process, and present antigens from their environment. The context in which an antigen is acquired by DC helps to dictate the subsequent immune response. Cancer vaccination promotes antitumor immunity by directing an immune response to antigens expressed by tumors. We have tested the tumor-associated antigen alpha-fetoprotein (AFP) as an immunotherapy target. The majority of hepatocellular carcinomas (HCC) upregulate and secrete this oncofetal antigen. Methods: To develop cancer vaccines for HCC capable of promoting potent tumor-specific T cell responses, we tested adenovirally-encoded synthetic AFP, with or without its signal sequence, as well as protein forms of AFP and compared intracellular routing and subsequent antigen-specific CD8+ and CD4+ T cell responses. Results: Surprisingly, the secreted form of antigen was superior for both CD4+ and CD8+ T cell activation. We also examined the mechanism through which AFP protein is endocytosed and trafficked in human DC. We identify the mannose receptor (MR/CD206) as the primary uptake pathway for both normal cord blood-derived AFP (nAFP) and tumor-derived AFP (tAFP) proteins. While in healthy donors, nAFP and tAFP were cross-presented to CD8+ T cells similarly and CD4+ T cell responses were dependent upon MR-mediated uptake. In HCC patient cells, tAFP was more immunogenic, and CD4+ T cell responses were not MR-dependent. Conclusions: Secreted, cytoplasmically retained, and endocytosed forms of AFP utilize unique uptake and processing pathways, resulting in different immunologic responses from the induced antigen-specific CD4+ and CD8+ T cells and between healthy donors and HCC patients. Collectively, these data elucidate pathways of spontaneous and induced anti-tumor immunity in HCC patients to this secreted antigen