12 research outputs found

    Emotional wellbeing as a proxy indicator for water security among pastoralists in Afar, Ethiopia

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    Recent thinking proposes a more holistic approach to measuring household water security. In addition to conventional service-level based indicators, assessments should account for broader social, political and cultural structures which shape how households interact with water. Contributing to this agenda, the paper introduces new research that aims to evaluate the relationship between emotional wellbeing and water security among pastoralists in the Afar region of Ethiopia. It is hypothesised that the measurement of emotion could have potential value as an indicator of water security among vulnerable populations who have particularly complex water use patterns that are poorly captured by conventional indicators. Within the pastoralist context, preliminary data collection has indicated an emotional response to seasonality in resource availability and distance travelled to infrastructure points. Further research is underway to explore the complexity of emotion and its interrelation with water security to better understanding the needs of pastoralists in Afar

    A simplified representation of the responsive model emphasizing that it has properties of a classical bistable switch.

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    <p>A schematic of the proposed bistable switch (center panel). The ground state at CpG island chromatin, PcG occupancy (left panel), is the default that is overcome only when TF-mediated gene activation reaches a critical threshold. Positive feedback mechanisms between PRC1 and PRC2 reinforce PcG occupancy and antagonize the TrxG state. Beyond the activation threshold, the system switches to the TrxG state (right panel) that is in turn reinforced by positive feedback mechanisms between RNAPII and TrxG factors. This, together with TrxG-mediated antagonism of PcG activities, ensures stability of the TrxG state such that stochastic fluctuations in gene activation signal would not trigger a switch back to the PcG state. However, when gene activation signals drop below a critical threshold, the CpG island will switch back to the default PcG state.</p

    Core components of the major PcG complexes in vertebrate cells overlap with CpG islands.

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    <p>(A) PRC1 complexes catalyze monoubiquitylation of histone H2A lysine 119 (H2AK119ub1). The catalytic subunits are RING1A/B and one of six PCGF protein homologues, PCGF1–6. PRC1 exists in canonical and noncanonical forms. Canonical PRC1 complexes comprise RING1A/B, PCGF2/4, the CBX protein subunit that has a chromodomain (CD) that binds specifically to PRC2-mediated H3K27me3, and the PH subunit. In noncanonical PRC1, CBX proteins are substituted by the RYBP/YAF2 subunit and the PH subunit is absent. Association of additional subunits with noncanonical PRC1 occurs in a manner dependent on the associated PCGF protein. Thus, PCGF1 complexes, discussed extensively herein, include the additional subunits BCOR and KDM2B. KDM2B has a zinc finger CxxC domain (CXXC) that mediates binding to unmethylated CpG dinucleotides. PRC2 complexes methylate histone H3 lysine 27 (H3K27me1/2/3) and comprise the catalytic EZH2 protein and the core subunits EED, SUZ12, and RBAP48. JARID2 is a substoichiometric subunit that has been implicated in PRC2 targeting. (B) PcG complexes occupy CpG islands at target gene promoters: an example from genome-wide ChIP-seq analysis of mouse embryonic stem cells illustrating a PcG target gene, Lhx4. The Bio-CAP procedure provides a molecular readout of the density of unmethylated CpG dinucleotides with peaks corresponding to CpG islands. ChIP-seq for PRC1 (RING1B) and PRC2 (EZH2) subunits illustrates that PcG protein occupancy closely mirrors unmethylated CpG density.</p

    Conidial number data

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    <p>The number of asexual spores (conidia) per mm<sup>2</sup> produced by A. <em>nidulans</em> strains MH2 (<em>xpr</em>G<sup>+</sup>), MK422 (<em>xpr</em>GΔ) and MK85 (<em>xpr</em>G1) was determined by removing three plugs from colonies on complete medium containing 2.2% agar. The conidia from each plug were suspended in a solution of 0.01% TWEEN80 and counted in a haemocytometer. The experiment was repeated a total of four times using different batches of medium.</p

    Autolysis data

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    <p>To monitor autolysis, six flasks containing 50 mL of minimal medium, 10 mM ammonium tartrate and vitamin supplements were each inoculated with 3 x 10<sup>8</sup> conidia and placed on an orbital shaker. Flasks were removed at 24 or 48 h intervals, the submerged mycelia harvested using Miracloth (Calbiochem/Merck). The dry weights of the mycelia are recorded in this file.</p

    Glucose uptake raw data

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    <p>The uptake of D-[U-<sup>14</sup>C] glucose (10.6 GBq/mmol, Amersham) was measured in germinating conidia of A. <em>nidulans</em> strains MH2 (<em>xpr</em>G<sup>+</sup>), MK422 (<em>xpr</em>GΔ) and MK85 (<em>xpr</em>G1) as described previously by McCabe <em>et al</em>. (2003). Glucose uptake was measured in aliquots of 2.5 x 10<sup>7</sup> germinating conidia after transfer to media containing 0.025, 0.125, 0.5 or 2 mM glucose.</p

    Mucosal atrophy predicts poorer outcomes in pediatric ulcerative colitis - a national inception cohort study

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    Background: Outcomes in pediatric ulcerative colitis (UC) are heterogeneous and predictors of disease course eagerly sought. Mucosal atrophy (MA) is characterized by histological abnormalities of colonic intestinal glands. Objective: To determine the prevalence of MA in a national inception cohort of pediatric UC and its impact on outcomes. Methods: Irish children Results: Of 251 pediatric patients with UC (mean age 11.8 years, 55% male), 38 (15%) had MA on diagnostic biopsy. Baseline characteristics were similar between groups with/without MA and there was no difference in steroid-free remission or rates of moderate-severe UC at 1 year. Patients with MA had higher use of steroids (29% vs 15%, P = 0.04) and immunomodulators (40% vs 21%, P = 0.04) at 6 months, higher biologic use at 1 year (34% vs 16%, P = 0.03), earlier first relapse (mean ± SD 29.4 ± 26.1 vs 46.7 ± 43.4 weeks after diagnosis, P = 0.02), and higher colectomy rates by 2 years (21% vs 8%, P = 0.01). Conclusions: Children with MA at diagnosis had higher colectomy rates despite earlier treatment escalation and similar baseline severity scores. We identify MA as a promising new prognostic marker in children with newly diagnosed UC.</p

    Harmonising the human biobanking consent process: an Irish experience [version 3; peer review: 2 approved]

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    Biobanks are repositories of human biological samples and data. They are an important component of clinical research in many disease areas and often represent the first step toward innovative treatments. For biobanks to operate, researchers need human participants to give their samples and associated health data. In Ireland, research participants must provide their freely given informed consent for their samples and data to be taken and used for research purposes. Biobank staff are responsible for communicating the relevant information to participants prior to obtaining their consent, and this communication process is supported by the Participant Information Leaflets and Informed Consent Form (PI/ICFs). PILs/ICFs should be concise, intelligible, and contain relevant information. While not a substitute for layperson and research staff discussions, PILs and ICFs ensure that a layperson has enough information to make an informed choice to participate or not. However, PILs/ICFs are often lengthy, contain technical language and can be complicated and onerous for a layperson to read. The introduction of the General Data Protection Regulation and the related Irish Health Research Regulation presented additional challenges to the Irish biobank community. In May 2019, the National Biobanking Working Group (NBWG) was established in Ireland. It consists of members from diverse research backgrounds located in universities, hospitals and research centres across Ireland and a public/patient partner. The NBWG aimed to develop a suite of resources for health research biobanks via robust and meaningful patient engagement, which are accessible, General Data Protection Regulation/Health Research Regulation-compliant and could be used nationally, including a PIL/ICF template. This open letter describes the process whereby this national biobank PIL/ICF template was produced. The development of this template included review by the Patient Voice in Cancer Research, led by Professor Amanda McCann at University College Dublin and the Health Research Data Protection Network.</p
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