Mastication effects on carotenoid bioaccessibility from mango fruit tissue

The release of carotenoids from fresh fruits or vegetables is determined by the encapsulating plant tissue matrix, intracellular carotenoid location within the cell, and the mastication process. The objectives of this study were to assess the particle sizes obtained after mastication of mango fruit tissue, and how the resulting degree of plant tissue rupture affects carotenoid bioaccessibility. A fine and a coarse chewer were selected after screening 20 healthy volunteers for in vivo human mastication, and the collected chewed boluses were subjected to wet sieving fractionation, followed by an in vitro gastric and small intestinal digestion model. Confocal micrographs show that the smallest particle size fraction (0.075 mm) consists mostly of fragmented cells and the largest size fraction (2.8 mm) contains bulky clusters of whole cells and vascular fibers. Higher amounts of total carotenoids (211–320 μg/100 g) were observed in the larger particle size fraction (2.8 mm) relative to the 1 mm (192–249 μg/100 g) and 0.075 mm fractions (136–199 μg/100 g). Smaller particles showed a greater % release of total carotenoids after in vitro digestion. Xanthophyll derivatives are more bioaccessible than β-carotene for all particle sizes. The effects of particle size or degree of fine vs coarse chewing are unexpectedly small (p > 0.05), but the process of chewing substantially reduced the release of β-carotene and xanthophylls by 34% and 18%, respectively. While there is a (small) particle size effect, this appears to not be the primary factor controlling bioaccessibility for soft tissues such as mango, in contrast to previous reports that a single cell wall appears to be enough to prevent bioaccessibility of carotenoids in more robust carrot tissues

Commissioners, guardians and paupers : life and death in the Limerick Poor Law Union, 1838-1850

It is accepted by historians of Ireland that British government response to the potato famine in the middle of the nineteenth century was inadequate. This dissertation examines that response in the Limerick Poor Law Union of Munster province. It demonstrates that the ideological underpinnings that provided the motivation for government response to poverty had evolved as the result of a debate which had been protracted and misguided. The result was a poor law system which assumed culpability on the part of the poor and a belief that the corrective was coercion. By focussing on the application of the law in a specific area, the dissertation demonstrates that the local Board of Guardians was powerless to mitigate the law's negative effects despite having serious misgivings about its impact. It puts into sharp focus the almost weekly dilemma which they faced of having to follow the directives of the Poor Law Commissioners or defy them in order to respond more appropriately to local needs. What really went on during the famine is better understood through case studies which specifically demonstrate the effects of government decision-making and the impact the resultant policy had in the daily lives of the people who received the intended services. The purpose of this case study is to amplify the findings of famine historians so that we can appreciate the human dimensions of the crisis

The National Exercise Referral Framework

A 2013 Review of the HSE funded GP Exercise Referral Programme (GPERP) highlighted the need for a new National Exercise Referral Framework (NERF). The evidence suggests that exercise referral is an effective targeted health intervention for specific patients and with the increasing prevalence of chronic disease it is imperative that we examine, design and progress the implementation of scalable, sustainable evidence-based, interventions, integrated across the health system to improve the health and wellbeing of the population. The development of this proposed National Exercise Referral Framework, commissioned by Health Promotion and Improvement, was led by DCU involving a multi-disciplinary Working Group and supported by a HSE Cross-Divisional Group. We are grateful to the Working Group and in particular to Dr Catherine Woods and the team in DCU for their extensive work and commitment to this project. There are a number of practical steps now required to determine the feasibility of the proposed framework as a national model namely, identification of a sustainable funding model; design and development of chronic disease care pathways and a phased implementation plan that would build on the existing programmes. The Health & Wellbeing Division of the HSE will lead the next phase of this project

Biological functions at high pressure: transcriptome response of Shewanella oneidensis MR-1 to hydrostatic pressure relevant to Titan and other icy ocean worlds

High hydrostatic pressure (HHP) is a key driver of life's evolution and diversification on Earth. Icy moons such as Titan, Europa, and Enceladus harbor potentially habitable high-pressure environments within their subsurface oceans. Titan, in particular, is modeled to have subsurface ocean pressures ≥ 150 MPa, which are above the highest pressures known to support life on Earth in natural ecosystems. Piezophiles are organisms that grow optimally at pressures higher than atmospheric (0.1 MPa) pressure and have specialized adaptations to the physical constraints of high-pressure environments – up to ~110 MPa at Challenger Deep, the highest pressure deep-sea habitat explored. While non-piezophilic microorganisms have been shown to survive short exposures at Titan relevant pressures, the mechanisms of their survival under such conditions remain largely unelucidated. To better understand these mechanisms, we have conducted a study of gene expression for Shewanella oneidensis MR-1 using a high-pressure experimental culturing system. MR-1 was subjected to short-term (15 min) and long-term (2 h) HHP of 158 MPa, a value consistent with pressures expected near the top of Titan's subsurface ocean. We show that MR-1 is metabolically active in situ at HHP and is capable of viable growth following 2 h exposure to 158 MPa, with minimal pressure training beforehand. We further find that MR-1 regulates 264 genes in response to short-term HHP, the majority of which are upregulated. Adaptations include upregulation of the genes argA, argB, argC, and argF involved in arginine biosynthesis and regulation of genes involved in membrane reconfiguration. MR-1 also utilizes stress response adaptations common to other environmental extremes such as genes encoding for the cold-shock protein CspG and antioxidant defense related genes. This study suggests Titan's ocean pressures may not limit life, as microorganisms could employ adaptations akin to those demonstrated by terrestrial organisms

The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer

The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4), and particularly its adaptor protein MyD88, as one potential mediator of this resistance. This study aims to provide further evidence that MyD88 positive cancer cells are clinically significant, stem-like and reproducibly detectable for the purposes of prognostic stratification. Expression of TLR4 and MyD88 was assessed immunohistochemically in 198 paraffin-embedded ovarian tissues and in an embryonal carcinoma model of cancer stemness. In parallel, expression of TLR4 and MyD88 mRNA and regulatory microRNAs (miR-21 and miR-146a) was assessed, as well as in a series of chemosensitive and resistant cancer cells lines. Functional analysis of the pathway was assessed in chemoresistant SKOV-3 ovarian cancer cells. TLR4 and MyD88 expression can be reproducibly assessed via immunohistochemistry using a semi-quantitative scoring system. TLR4 expression was present in all ovarian epithelium (normal and neoplastic), whereas MyD88 was restricted to neoplastic cells, independent of tumour grade and associated with reduced progression-free and overall survival, in an immunohistological specific subset of serous carcinomas, p<0.05. MiR-21 and miR-146a expression was significantly increased in MyD88 negative cancers (p<0.05), indicating their participation in regulation. Significant alterations in MyD88 mRNA expression were observed between chemosensitive and chemoresistant cells and tissue. Knockdown of TLR4 in SKOV-3 ovarian cells recovered chemosensitivity. Knockdown of MyD88 alone did not. MyD88 expression was down-regulated in differentiated embryonal carcinoma (NTera2) cells, supporting the MyD88+ cancer stem cell hypothesis. Our findings demonstrate that expression of MyD88 is associated with significantly reduced patient survival and altered microRNA levels and suggest an intact/functioning TLR4/MyD88 pathway is required for acquisition of the chemoresistant phenotype. Ex vivo manipulation of ovarian cancer stem cell (CSC) differentiation can decrease MyD88 expression, providing a potentially valuable CSC model for ovarian cancer

Fluorescence strategies for high-throughput quantification of protein interactions

Advances in high-throughput characterization of protein networks in vivo have resulted in large databases of unexplored protein interactions that occur during normal cell function. Their further characterization requires quantitative experimental strategies that are easy to implement in laboratories without specialized equipment. We have overcome many of the previous limitations to thermodynamic quantification of protein interactions, by developing a series of in-solution fluorescence-based strategies. These methods have high sensitivity, a broad dynamic range, and can be performed in a high-throughput manner. In three case studies we demonstrate how fluorescence (de)quenching and fluorescence resonance energy transfer can be used to quantitatively probe various high-affinity protein–DNA and protein–protein interactions. We applied these methods to describe the preference of linker histone H1 for nucleosomes over DNA, the ionic dependence of the DNA repair enzyme PARP1 in DNA binding, and the interaction between the histone chaperone Nap1 and the histone H2A–H2B heterodimer

The effect of major depression on participation in preventive health care activities

<p>Abstract</p> <p>Background</p> <p>The objective of this study was to determine whether major depressive episodes (MDE) contribute to a lower rate of participation in three prevention activities: blood pressure checks, mammograms and Pap tests.</p> <p>Methods</p> <p>The data source for this study was the Canadian National Population Health Survey (NPHS), a longitudinal study that started in 1994 and has subsequently re-interviewed its participants every two years. The NPHS included a short form version of the Composite International Diagnostic Interview (CIDI-SF) to assess past year MDE and also collected data on participation in preventive activities. Initially, we examined whether respondents with MDE in a particular year were less likely to participate in screening during that same year. In order to assess whether MDE negatively altered the pattern of participation, those successfully screened at the baseline interview in 1994 were identified and divided into cohorts depending on their MDE status. Proportional hazard models were used to quantify the effect of MDE on subsequent participation in screening.</p> <p>Results</p> <p>No effect of MDE on participation in the three preventive activities was identified either in the cross-sectional or longitudinal analysis. Adjustment for a set of relevant covariates did not alter this result.</p> <p>Conclusion</p> <p>Whereas MDE might be expected to reduce the frequency of participation in screening activities, no evidence for this was found in the current analysis. Since people with MDE may contact the health system more frequently, this may offset any tendency of the illness itself to reduce participation in screening.</p

Thiolutin is a zinc chelator that inhibits the Rpn11 and other JAMM metalloproteases

Thiolutin is a disulfide-containing antibiotic and anti-angiogenic compound produced by Streptomyces. Its biological targets are not known. We show that reduced thiolutin is a zinc chelator that inhibits the JAB1/MPN/Mov34 (JAMM) domain–containing metalloprotease Rpn11, a deubiquitinating enzyme of the 19S proteasome. Thiolutin also inhibits the JAMM metalloproteases Csn5, the deneddylase of the COP9 signalosome; AMSH, which regulates ubiquitin-dependent sorting of cell-surface receptors; and BRCC36, a K63-specific deubiquitinase of the BRCC36-containing isopeptidase complex and the BRCA1–BRCA2-containing complex. We provide evidence that other dithiolopyrrolones also function as inhibitors of JAMM metalloproteases

Charlson index scores from administrative data and case-note review compared favourably in a renal disease cohort

Background: The Charlson index is a widely used measure of comorbidity. The objective was to compare Charlson index scores calculated using administrative data to those calculated using case-note review (CNR) in relation to all-cause mortality and initiation of renal replacement therapy (RRT) in the Grampian Laboratory Outcomes Mortality and Morbidity Study (GLOMMS-1) chronic kidney disease cohort. Methods: Modified Charlson index scores were calculated using both data sources in the GLOMMS-1 cohort. Agreement between scores was assessed using the weighted Kappa. The association with outcomes was assessed using Poisson regression, and the performance of each was compared using net reclassification improvement. Results: Of 3382 individuals, median age 78.5 years, 56% female, there was moderate agreement between scores derived from the two data sources (weighted kappa 0.41). Both scores were associated with mortality independent of a number of confounding factors. Administrative data Charlson scores were more strongly associated with death than CNR scores using net reclassification improvement. Neither score was associated with commencing RRT. Conclusion: Despite only moderate agreement, modified Charlson index scores from both data sources were associated with mortality. Neither was associated with commencing RRT. Administrative data compared favourably and may be superior to CNR when used in the Charlson index to predict mortality