Play, Learn, and Teach Outdoors—Network (PLaTO-Net): terminology, taxonomy, and ontology

Background: A recent dialogue in the feld of play, learn, and teach outdoors (referred to as “PLaTO” hereafter) demonstrated the need for developing harmonized and consensus-based terminology, taxonomy, and ontology for PLaTO. This is important as the feld evolves and diversifes in its approaches, contents, and contexts over time and in diferent countries, cultures, and settings. Within this paper, we report the systematic and iterative processes under‑taken to achieve this objective, which has built on the creation of the global PLaTO-Network (PLaTO-Net). Methods: This project comprised of four major methodological phases. First, a systematic scoping review was conducted to identify common terms and defnitions used pertaining to PLaTO. Second, based on the results of the scoping review, a draft set of key terms, taxonomy, and ontology were developed, and shared with PLaTO members, who provided feedback via four rounds of consultation. Third, PLaTO terminology, taxonomy, and ontology were then fnalized based on the feedback received from 50 international PLaTO member participants who responded to≥3 rounds of the consultation survey and dialogue. Finally, eforts to share and disseminate project outcomes were made through diferent online platforms. Results: This paper presents the fnal defnitions and taxonomy of 31 PLaTO terms along with the PLaTO-Net ontol‑ogy model. The model incorporates other relevant concepts in recognition that all the aspects of the model are interrelated and interconnected. The fnal terminology, taxonomy, and ontology are intended to be applicable to, and relevant for, all people encompassing various identities (e.g., age, gender, culture, ethnicity, ability). Conclusions: This project contributes to advancing PLaTO-based research and facilitating intersectoral and inter‑disciplinary collaboration, with the long-term goal of fostering and strengthening PLaTO’s synergistic linkages with healthy living, environmental stewardship, climate action, and planetary health agendas. Notably, PLaTO terminology, taxonomy and ontology will continue to evolve, and PLaTO-Net is committed to advancing and periodically updating harmonized knowledge and understanding in the vast and interrelated areas of PLaTO

Kinase pathways involved in insulin gene regulation

Understanding how the insulin gene is regulated is essential to developing new treatments for diabetes mellitus. The aim of this study was to characterise, in detail, the effect of stress, glucose and insulin on three protein kinases, p38, JNK and PKB in pancreatic β cells. p38 was found to be active in both INS-1 and MIN-6 cells in response to the stress inducing agents anisomycin, UV and sodium arsenite. Physiologically high levels of glucose failed to result in p38 activation. Experiments were undertaken to characterise the effect of p38 overexpression on the activity of the rat insulin promoter. p38 overexpression resulted in a 10 fold increase in rat insulin promoter activity under conditions of high glucose however cells treated with the stress inducing agents UV and sodium arsenite showed a decrease in rat insulin promoter activity relative to controls. JNK was also detected in INS-1 and MIN-6 cells. JNK activity was increased by the cellular stresses of UV, sodium arsenite and anisomycin, but not by physiologically high levels of glucose. Overexpression of the transcription factor c-Jun inhibited the rat insulin gene promoter's response to glucose but overexpression of JNK had no effect. Furthermore JNK and c-Jun overexpression did not alter the size of the transcription factor PDX-1. PKB activity was found to be high in untreated INS-1 cells and could only be activated using significant quantities of insulin over a long time period. PKB overexpression in INS-1 cells led to a 10-20 fold increase in the activity of the rat insulin promoter under conditions of both low and high glucose. Further experiments were undertaken to evaluate the use of an adenoviral system to overexpress PKB in β cells in a controlled manner. Finally, a pilot study was undertaken to examine the effect of overexpressing Ngn3, a transcription factor essential to the development of the pancreas in rat liver cells.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Presence of WT1 in nuclear messenger RNP particles in the human acute myeloid leukemia cell lines HL60 and K562

The WT1 gene is a key player in acute myeloid leukaemia, in which it is frequently over-expressed. WT1 encodes a multifunctional zinc finger protein transcription factor, which also binds mRNA. Thus increasing evidence suggests that WT1 works both at the DNA and mRNA level, not only in the urogenital system but also in other contexts. Nuclear poly(A)+ mRNP particles were isolated by oligo(dT) chromatography from the human acute myeloid leukemia cell lines HL60 and K562, and analysed by Western blotting and 2D minigels. MALDI-TOF demonstrated the presence of hnRNP proteins, splice factors, and unexpectedly vimentin in the mRNP fraction. WT1 was also shown to be present in nuclear mRNP particles suggesting that in leukaemia, and by extension in all cancers in which it is involved, WT1 works both at the DNA and mRNA target level. © 2006 Elsevier Ireland Ltd. All rights reserved

The post-transcriptional roles of WT1, a multifunctional zinc-finger protein

WT1 was first described in 1990 as a tumour suppressor gene associated with Wilms tumour (nephroblastoma). It encodes a typical transcription factor with four C2-H2 zinc fingers in the C-terminus. However WT1 is surprisingly complex at multiple levels: it is involved in the development of several organ systems; and is both a tumour suppressor and oncogene. Here we review evidence that has accumulated over the past decade to suggest that as well as binding DNA, WT1 also binds mRNA targets via its zinc fingers and interacts with several splice factors. WT1's first reported post-transcriptional function is also reviewed. WT1's complex roles in development and disease now need to be understood in terms of both DNA and mRNA targets. © 2007 Elsevier B.V. All rights reserved

The synthesis of isotopically labelled glucosinolates for analysis and metabolic studies

Glucosinolates are dietary natural products with important cancer chemoprevention proper-ties. The syntheses of a number of stable isotopically labelled ((2) H, C-13) glucosinolates, and their desulfo-analogues, are described. These compounds are used as internal standards for analysis and for metabolic studies. Copyright (c) 2007 John Wiley &amp; Sons, Ltd.</p

New insights into the function of the Wilms tumor suppressor gene WT1 in podocytes

The Wilms tumor suppressor gene WT1 is essential for early urogenital development: homozygous mutations in WT1 result in embryonic lethality due to a failure in the development of kidneys and gonads. In the adult kidney, WT1 expression is limited to the glomerular podocytes. Several human nephrotic diseases arise from mutations of the WT1 gene, including mutations that affect its zinc-fingers and alternative splicing of +/-KTS isoforms. These include WAGR (for Wilms tumor, aniridia, genitourinary anomalies, and mental retardation), and Frasier and Denys-Drash syndromes. Recent advances including the development of transgenic mouse models and conditionally immortalized podocyte cell lines are beginning to shed light on WT1's crucial role in podocyte function. Copyright © 2008 the American Physiological Society

The Wilms’ tumor 1 (WT1) gene (+KTS isoform) functions with a CTE to enhance translation from an unspliced RNA with a retained intron

The Wilms’ tumor 1 (WT1) gene plays an important role in mammalian urogenital development, and dysregulation of this gene is observed in many human cancers. Alternative splicing of WT1 RNA leads to the expression of two major protein isoforms, WT1(+KTS) and WT1(−KTS). Whereas WT1(−KTS) acts as a transcriptional regulator, no clear function has been ascribed to WT1(+KTS), despite the fact that this protein is crucial for normal development. Here we show that WT1(+KTS) functions to enhance expression from RNA possessing a retained intron and containing either a cellular or viral constitutive transport element (CTE). WT1(+KTS) expression increases the levels of unspliced RNA containing a CTE and specifically promotes the association of this RNA with polyribosomes. These studies provide further support for links between different steps in RNA metabolism and for the existence of post-transcriptional operons

Sudden rise in uptake of hepatitis B vaccination among injecting drug users associated with a universal vaccine programme in prisons

Hitherto, services have failed to deliver the UK Government’s 1988 recommendation to vaccinate injecting drug users (IDUs) against hepatitis B virus (HBV). In April 1999, the Scottish Prison Service implemented an initiative to offer HBV vaccination to all inmates; we sought to determine the impact of this initiative on the IDU population. Among community-recruited IDUs (who had injected for ≤5 years) in Glasgow, vaccine uptake was significantly higher among those surveyed in 2001–2002 (52% of 387) than in 1993 (16% of 166), 1994 (19% of 138) or January–March 1999 (15% of 128); of the 2001–2002 vaccinees, 56% had been vaccinated in prison. Our results indicate that the universal offer of vaccination to all prisoners, within two years of the initiative’s implementation, has had a dramatic impact on uptake among IDUs