CCL19-sorted mature dendritic cells have enhanced lymph node migratory capacity and function

No abstract available

A SQUAMOSA MADS-box gene involved in the regulation of anthocyanin accumulation in bilberry fruits

Anthocyanins are important health promoting phytochemicals that are abundant in many fleshy fruits. Bilberry (Vaccinium myrtillus L.) is one of the best sources of these compounds. Here we report on the expression pattern and functional analysis of a SQUAMOSA (SQUA) class MADS-box transcription factor, VmTDR4, associated with anthocyanin biosynthesis in bilberry. Levels of VmTDR4 expression were spatially and temporally linked with colour development and anthocyanin-related gene expression. Virus induced gene silencing (VIGS) was used to suppress VmTDR4 expression in bilberry resulting in substantial reduction in anthocyanin levels in fully ripe fruits. Chalcone synthase was used a positive control in the VIGS experiments. Additionally, in sectors of fruit tissue in which the expression of the VmTDR4 gene was silenced, the expression of R2R3 MYB family transcription factors related to the biosynthesis of flavonoids were also altered. We conclude that VmTDR4 plays an important role in the accumulation of anthocyanins during normal ripening in bilberry; probably through direct or indirect control of transcription factors belonging to the R2R3 MYB family

Conceptualisations of children’s wellbeing at school: the contribution of recognition theory

A large study in Australian schools aimed to elucidate understandings of ‘wellbeing’ and of factors in school life that contribute to it. Students and teachers understood wellbeing primarily, and holistically, in terms of interpersonal relationships, in contrast to policy documents which mainly focused on ‘problem areas’ such as mental health. The study also drew on recognition theory as developed by the social philosopher Axel Honneth. Results indicate that recognition theory may be useful in understanding wellbeing in schools, and that empirical research in schools may give rise to further questions regarding theory

Expression of KOC, S100P, mesothelin and MUC1 in pancreatico-biliary adenocarcinomas: development and utility of a potential diagnostic immunohistochemistry panel

<b>Background</b> Pancreatico-biliary adenocarcinomas (PBA) have a poor prognosis. Diagnosis is usually achieved by imaging and/or endoscopy with confirmatory cytology. Cytological interpretation can be difficult especially in the setting of chronic pancreatitis/cholangitis. Immunohistochemistry (IHC) biomarkers could act as an adjunct to cytology to improve the diagnosis. Thus, we performed a meta-analysis and selected KOC, S100P, mesothelin and MUC1 for further validation in PBA resection specimens.<p></p> <b>Methods</b> Tissue microarrays containing tumour and normal cores in a ratio of 3:2, from 99 surgically resected PBA patients, were used for IHC. IHC was performed on an automated platform using antibodies against KOC, S100P, mesothelin and MUC1. Tissue cores were scored for staining intensity and proportion of tissue stained using a Histoscore method (range, 0–300). Sensitivity and specificity for individual biomarkers, as well as biomarker panels, were determined with different cut-offs for positivity and compared by summary receiver operating characteristic (ROC) curve.<p></p> <b>Results</b> The expression of all four biomarkers was high in PBA versus normal ducts, with a mean Histoscore of 150 vs. 0.4 for KOC, 165 vs. 0.3 for S100P, 115 vs. 0.5 for mesothelin and 200 vs. 14 for MUC1 (p < .0001 for all comparisons). Five cut-offs were carefully chosen for sensitivity/specificity analysis. Four of these cut-offs, namely 5%, 10% or 20% positive cells and Histoscore 20 were identified using ROC curve analysis and the fifth cut-off was moderate-strong staining intensity. Using 20% positive cells as a cut-off achieved higher sensitivity/specificity values: KOC 84%/100%; S100P 83%/100%; mesothelin 88%/92%; and MUC1 89%/63%. Analysis of a panel of KOC, S100P and mesothelin achieved 100% sensitivity and 99% specificity if at least 2 biomarkers were positive for 10% cut-off; and 100% sensitivity and specificity for 20% cut-off.<p></p> <b>Conclusion</b> A biomarker panel of KOC, S100P and mesothelin with at least 2 biomarkers positive was found to be an optimum panel with both 10% and 20% cut-offs in resection specimens from patients with PBA.<p></p&gt

The atypical chemokine receptor Ackr2 constrains NK cell migratory activity and promotes metastasis

Chemokines have been shown to be essential players in a range of cancer contexts. In this study, we demonstrate that mice deficient in the atypical chemokine receptor Ackr2 display impaired development of metastasis in vivo in both cell line and spontaneous models. Further analysis reveals that this relates to increased expression of the chemokine receptor CCR2, specifically by KLRG1+ NK cells from the Ackr2−/− mice. This leads to increased recruitment of KLRG1+ NK cells to CCL2-expressing tumors and enhanced tumor killing. Together, these data indicate that Ackr2 limits the expression of CCR2 on NK cells and restricts their tumoricidal activity. Our data have important implications for our understanding of the roles for chemokines in the metastatic process and highlight Ackr2 and CCR2 as potentially manipulable therapeutic targets in metastasis

Tsunami awareness and preparedness in Aotearoa New Zealand:The evolution of community understanding

After catastrophic events such as the 2004 Indian Ocean tsunami and the 2011 Great East Japan earthquake and tsunami there is a clear need for vulnerable countries like Aotearoa New Zealand to get prepared for tsunami. In the last ten years, the New Zealand government initiated major efforts to raise awareness of tsunami risk among coastal residents. This study explores tsunami awareness, preparedness, and evacuation intentions among residents of the East Coast of the North Island in a 2015 survey. The ten chosen locations also participated in a tsunami survey in 2003, with results demonstrating that tsunami awareness rose in the twelve years between the surveys. The 2015 survey also included questions on preparedness and intended action. Even though coastal residents know they live in a tsunami prone area, preparedness is relatively low and high expectations of a formal warning remain, even for a local source tsunami scenario. Furthermore, survey respondents had unrealistic ideas of evacuation procedures. When asked about their evacuation intentions, respondents intended to undertake a number of different actions before evacuating their homes, which could cause significant delays in the evacuation process. Most respondents were also reluctant to evacuate on foot and prefer using their vehicles instead, which could create dangerous traffic congestion. These surveyed intentions are consistent with a study of actual evacuation behaviours in the subsequent 2016 Kaikōura earthquake and tsunami, providing validation for the survey indicators. This paper identifies the procedures least understood by the public and offers some solutions to improve tsunami preparedness.</p

Exploration of chronic kidney disease prevalence estimates using new measures of kidney function in the health survey for England

Background: chronic kidney disease (CKD) diagnosis relies on glomerular filtration rate (eGFR) estimation, traditionally using the creatinine-based Modification of Diet in Renal Disease (MDRD) equation. The Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) equation performs better in estimating eGFR and predicting mortality and CKD progression risk. Cystatin C is an alternative glomerular filtration marker less influenced by muscle mass. CKD risk stratification is improved by combining creatinine eGFR with cystatin C and urinary albumin to creatinine ratio (uACR). We aimed to identify the impact of introducing CKDEPI and cystatin C on the estimated prevalence and risk stratification of CKD in England and to describe prevalence and associations of cystatin C.Methods and findings: cross sectional study of 5799 people in the nationally representative 2009 and 2010 Health Surveys for England. Primary outcome measures: prevalence of MDRD, CKDEPI and cystatin C-defined eGFR&lt;60ml/min/1.73m2; prevalence of CKD biomarker combinations (creatinine, cystatin C, uACR). Using CKDEPI instead of MDRD reduced the prevalence of eGFR&lt;60ml/min/1.73m2 from 6.0% (95% CI 5.4–6.6%) to 5.2% (4.7–5.8%) equivalent to around 340,000 fewer individuals in England. Those reclassified as not having CKD evidenced a lower risk profile. Prevalence of cystatin C eGFR&lt;60ml/min/1.73m2 was 7.7% and independently associated with age, lack of qualifications, being an ex-smoker, BMI, hypertension, and albuminuria. Measuring cystatin C in the 3.9% people with CKDEPI-defined eGFR&lt;60ml/min/1.73m2 without albuminuria (CKD Category G3a A1) reclassified about a third into a lower risk group with one of three biomarkers and two thirds into a group with two of three. Measuring cystatin C in the 6.7% people with CKDEPI eGFR &gt;60ml/min/1.73m2 with albuminuria (CKD Category G1-2) reclassified almost a tenth into a higher risk group.Limitations: cross sectional study, single eGFR measure, no measured (‘true’) GFR.Conclusions: introducing the CKDEPI equation and targeted cystatin C measurement reduces estimated CKD prevalence and improves risk stratification<br/

Equality of Participation Online Versus Face to Face: Condensed Analysis of the Community Forum Deliberative Methods Demonstration

Online deliberation may provide a more cost-effective and/or less inhibiting environment for public participation than face to face (F2F). But do online methods bias participation toward certain individuals or groups? We compare F2F versus online participation in an experiment affording within-participants and cross-modal comparisons. For English speakers required to have Internet access as a condition of participation, we find no negative effects of online modes on equality of participation (EoP) related to gender, age, or educational level. Asynchronous online discussion appears to improve EoP for gender relative to F2F. Data suggest a dampening effect of online environments on black participants, as well as amplification for whites. Synchronous online voice communication EoP is on par with F2F across individuals. But individual-level EoP is much lower in the online forum, and greater online forum participation predicts greater F2F participation for individuals. Measured rates of participation are compared to self-reported experiences, and other findings are discussed.Comment: 14 pages, 10 tables, to appear in Efthimios Tambouris, Panos Panagiotopoulos, {\O}ystein S{\ae}b{\o}, Konstantinos Tarabanis, Michela Milano, Theresa Pardo, and Maria Wimmer (Editors), Electronic Participation: Proceedings of the 7th IFIP WG 8.5 International Conference, ePart 2015 (Thessaloniki, August 30-September 2), Springer LNCS Vol. 9249, 201

Salt stress in the renal tubules is Linked to TAL specific expression of uromodulin and an upregulation of heat shock genes

Previously, our comprehensive cardiovascular characterisation study validated Uromodulin as a blood pressure gene. Uromodulin is a glycoprotein exclusively synthesised at the thick ascending limb of the loop of Henle and is encoded by the Umod gene. Umod(-/-) mice have significantly lower blood pressure than Umod(+/+) mice, are resistant to salt-induced changes in blood pressure, and show a leftward shift in pressure-natriuresis curves reflecting changes of sodium reabsorption. Salt stress triggers transcription factors and genes that alter renal sodium reabsorption. To date there are no studies on renal transcriptome responses to salt stress. Here we aimed to delineate salt stress pathways in tubules isolated from Umod(+/+) mice (a model of sodium retention) and Umod(-/-) mice (a model of sodium depletion) +/-300mOsmol sodium chloride (n=3 per group) performing RNA-Seq. In response to salt stress, the tubules of Umod(+/+) mice displayed an up regulation of heat shock transcripts. The greatest changes occurred in the expression of: Hspa1a (Log2 fold change 4.35, p=2.48e-12) and Hspa1b (Log2 fold change 4.05, p=2.48e-12). This response was absent in tubules of Umod(-/-) mice. Interestingly, 7 of the genes discordantly expressed in the Umod(-/-) tubules were electrolyte transporters. Our results are the first to show that salt stress in renal tubules alters the transcriptome, increasing the expression of heat shock genes. This direction of effect in Umod(+/+) tubules suggest the difference is due to the presence of Umod facilitating greater sodium entry into the tubule cell reflecting a specific response to salt stress