Mass Spectrometry and Genetic Analysis of Biological Barrier Lipids

Malnutrition during embryonic development can have significant health ramifications for the adult organism. Such developmental programming effects have been studied in a variety of different organs but no research to date has looked at the largest organ in the body, the skin. One important and evolutionarily conserved role of the skin is to provide a lipid barrier against stresses in the external environment. Here, I utilise the short lifespan and powerful genetics of Drosophila melanogaster to investigate how cuticular barrier lipids are regulated by developmental diet and environmental stresses in the adult. The Drosophila cuticle is significantly different from the mammalian skin, yet both are coated with a waterproof lipid blend synthesised by specialised subepidermal cells - sebocytes in mammals and oenocytes in Drosophila. Research on the composition and regulation of lipid barriers has been hampered, at least in part, by the lack of methods for resolving surface lipids from intracellular lipids. I therefore optimise several techniques for analysing surface lipids, including a new cryogenic platform for mass spectrometry imaging. I demonstrate that developmental diet programmes the blend of adult cuticular lipids in both Drosophila and mice by increasing the adult skin wax esters. In Drosophila, I also show how adult environmental stresses impact upon the cuticle lipid blend. Combining mass spectrometry imaging with genetic analysis in Drosophila, I then identify a physiological feedback circuit that regulates the blend of adult cuticular hydrocarbons in response to increased housing density. This circuit involves the detection of housing density by an as yet unknown mechanism, information relay to oenocytes, and export of hydrocarbons to the cuticle surface via Obp99b/Obp99d odorant-binding proteins. Finally, I discuss the wider implications of this study and how mammals may regulate their skin lipids in line with a changing environment

Navigating Pandemic Schooling for Novice Teachers

Teachers navigated a vast set of challenges during the 2019-20 school year when a pandemic shut down school and changed the face of classrooms. The challenges that emerged during this time were heaped upon the already full plates of the novice teachers featured in this study who were just gaining confidence in the classroom. This article highlights the six themes that emerged from interviews done in spring of 2020 as part of a larger longitudinal study following teacher education graduates. This snapshot of the data provides inside into the effect of the early stages of the pandemic on these teachers classrooms, perspectives, roles, and impact on their students

Dissection of the Human Multipotent Adult Progenitor Cell (MAPC) Secretome by Proteomic Analysis

Digitalitzat per Artypla

Tumor Necrosis Factor Polymorphism Affects Transplantation Outcome in Patients with Myelodysplastic Syndrome but Not in Those with Chronic Myelogenous Leukemia, Independent of the Presence of HLA-DR15

Both the presence of HLA-DR15 and tumor necrosis factor (TNF)-α levels have been reported to affect outcome after hematopoietic cell transplantation (HCT). Patients with a myelodysplastic syndrome (MDS) show a high prevalence of HLA-DR15 and express high levels of TNF-α in the bone marrow. The present analysis involving 7950 patients showed an HLA-DR15 frequency of 31% in patients with MDS, compared with only 23% in patients with chronic myelogenous leukemia (CML). HLA-DR15 was more prevalent in Caucasian patients than in non-Caucasian patients (P = .01). The numbers of patients in the non-Caucasian subgroups were too small to allow further analysis. Among Caucasian patients with MDS and CML, the presence of HLA-DR15 did not significantly affect the occurrence of graft-versus-host disease, relapse, nonrelapse mortality (NRM), or survival. However, there was a significant correlation between DR15 and TNF polymorphisms at position -308 among patients with MDS, and the TNF-308 AG genotype conferred an increased risk of NRM compared with the GG genotype (hazard ratio [HR], 1.49; P = .02), even after adjusting for DR15. Conversely, the TNF-863 AA genotype was correlated with decreased overall mortality and NRM compared with the CC genotype (HR, 0.36, P = .04 vs HR, 0.13, P = .04), even after adjusting for DR15. There was no significant association between TNF-308 or -863 polymorphisms and transplantation outcome in CML patients. These results suggest that TNF polymorphisms, but not DR15, affect transplantation outcome in a disease-dependent manner

Facilitators and Barriers to Uptake of an Extended Seasonal Malaria Chemoprevention Programme in Ghana: A Qualitative Study of Caregivers and Community Health Workers.

BACKGROUND: Seasonal Malaria Chemoprevention (SMC) is currently recommended for children under five in areas where malaria transmission is highly seasonal. We explored children's caregivers' and community health workers' (CHWs) responses to an extended 5-month SMC programme. METHODS: Thirteen in-depth interviews and eight focus group discussions explored optimal and suboptimal 'uptake' of SMC to examine facilitators and barriers to caregivers' uptake. RESULTS: There did not appear to be major differences between caregivers of children with optimal and sub-optimal SMC uptake in terms of their knowledge of malaria, their perceptions of the effect of SMC on a child's health, nor their understanding of chemoprevention. Caregivers experienced difficulty in prioritising SMC for well children, perceiving medication being for treatment rather than prevention. Prior to the study, caregivers had become accustomed to rapid diagnostic testing (RDT) for malaria, and therefore blood testing for malaria during the baseline survey at the start of the SMC programme may have positively influenced uptake. Facilitators of uptake included caregivers' trust in and respect for administrators of SMC (including CHWs), access to medication and supportive (family) networks. Barriers to uptake related to poor communication of timings of community gatherings, travel distances, absence during SMC home deliveries, and limited demand for SMC due to lack of previous experience. Future delivery of SMC by trained CHWs would be acceptable to caregivers. CONCLUSION: A combination of caregivers' physical access to SMC medication, the drug regimen, trust in the medical profession and perceived norms around malaria prevention all likely influenced caregivers' level of uptake. SMC programmes need to consider: 1) developing supportive, accessible and flexible modes of drug administration including home delivery and village community kiosks; 2) improving demand for preventive medication including the harnessing of learnt trust; and 3) developing community-based networks for users to support optimal uptake of SMC

Qualitative impact assessment of land management interventions on ecosystem services (“QEIA”). Report-3 theme-3: soils

This project assessed the impacts of 741 potential land management actions, suitable for agricultural land in England, on the Farming & Countryside Programme’s Environmental Objectives (and therefore Environment Act targets and climate commitments) through 53 relevant environmental and cultural service indicators. The project used a combination of expert opinion and rapid evidence reviews, which included 1000+ pages of evidence in 10 separate reports with reference to over 2400 published studies, and an Integrated Assessment comprising expert-derived qualitative impact scores. The project has ensured that ELM schemes are evidence-based, offer good value for money, and contribute to SoS priorities for farming

Does liming grasslands increase biomass productivity without causing detrimental impacts on net greenhouse gas emissions?

Acknowledgements This work contributes to the SUPER-G project (funded under EU Horizon 2020 programme). We appreciate the support from the Estonian Research Council (PRG352) and the European Regional Development Fund (Centre of Excellence EcolChange, Estonia).We are grateful to Sarah Perryman for proving us with pictures from the Park Grass Experiment.Peer reviewedPublisher PD