Thomas Rodger, 1832-1883 : a biography and catalogue of selected works

The aim of this study was to produce a biography and corpus of work of St. Andrews photographic pioneer Thomas Rodger, 1832-1883. Rodger's life, from a working class background can be traced from childhood, through to being thought of as an important contributor to Scottish photographic history. The circumstances in which Rodger was fortuitous enough to grow up in were also a major influence in his initial interest and success in early photography. In this study not only has his life history been recorded, but his contributions to major exhibitions, events and publications have been accounted for. Rodger's photographic studio, built in 1866, has also been researched and illustrated for the purpose of this study. With reference to the corpus of work of Rodger's photographs, this was catalogued from a selection of St. Andrews University Library's photographic collection. This was done with the view of doing justice to Rodger's reputation as a renowned and respected professional photographer not only in St. Andrews but in Scotland's history of photography

Oxidative Metabolism Genes Are Not Responsive to Oxidative Stress in Rodent Beta Cell Lines

Altered expression of oxidative metabolism genes has been described in the skeletal muscle of individuals with type 2 diabetes. Pancreatic beta cells contain low levels of antioxidant enzymes and are particularly susceptible to oxidative stress. In this study, we explored the effect of hyperglycemia-induced oxidative stress on a panel of oxidative metabolism genes in a rodent beta cell line. We exposed INS-1 rodent beta cells to low (5.6 mmol/L), ambient (11 mmol/L), and high (28 mmol/L) glucose conditions for 48 hours. Increases in oxidative stress were measured using the fluorescent probe dihydrorhodamine 123. We then measured the expression levels of a panel of 90 oxidative metabolism genes by real-time PCR. Elevated reactive oxygen species (ROS) production was evident in INS-1 cells after 48 hours (P < 0.05). TLDA analysis revealed a significant (P < 0.05) upregulation of 16 of the 90 genes under hyperglycemic conditions, although these expression differences did not reflect differences in ROS. We conclude that although altered glycemia may influence the expression of some oxidative metabolism genes, this effect is probably not mediated by increased ROS production. The alterations to the expression of oxidative metabolism genes previously observed in human diabetic skeletal muscle do not appear to be mirrored in rodent pancreatic beta cells

Nutritional status, growth and disease management in children with single and dual diagnosis of type 1 diabetes mellitus and coeliac disease

Background: The consequences of subclinical coeliac disease (CD) in Type 1 diabetes mellitus (T1DM) remain unclear. We looked at growth, anthropometry and disease management in children with dual diagnosis (T1DM + CD) before and after CD diagnosis.&lt;p&gt;&lt;/p&gt; Methods: Anthropometry, glycated haemoglobin (HbA1c) and IgA tissue transglutaminase (tTg) were collected prior to, and following CD diagnosis in 23 children with T1DM + CD. This group was matched for demographics, T1DM duration, age at CD diagnosis and at T1DM onset with 23 CD and 44 T1DM controls.&lt;p&gt;&lt;/p&gt; Results: No differences in growth or anthropometry were found between children with T1DM + CD and controls at any time point. Children with T1DM + CD, had higher BMI z-score two years prior to, than at CD diagnosis (p &#60;0.001). BMI z-score change one year prior to CD diagnosis was lower in the T1DM + CD than the T1DM group (p = 0.009). At two years, height velocity and change in BMI z-scores were similar in all groups. No differences were observed in HbA1c between the T1DM + CD and T1DM groups before or after CD diagnosis. More children with T1DM + CD had raised tTg levels one year after CD diagnosis than CD controls (CDx to CDx + 1 yr; T1DM + CD: 100% to 71%, p = 0.180 and CD: 100% to 45%, p &#60; 0.001); by two years there was no difference.&lt;p&gt;&lt;/p&gt; Conclusions: No major nutrition or growth deficits were observed in children with T1DM + CD. CD diagnosis does not impact on T1DM glycaemic control. CD specific serology was comparable to children with single CD, but those with dual diagnosis may need more time to adjust to gluten free diet

The Ageing Gut-Brain Study : Exploring the role of the gut microbiota in dementia

Alex Johnstone, Alison Donaldson, Karen Scott and Phyo Myint all contributed equally to the writing and preparation of the manuscript. This study is funded by Tenovus Scotland Research Project No. G16‐08 (start 1 June 2017, end date 31 January 2019) and NHS‐Grampian Research and Development Endowment Research Grants Project No: 16/11/043 (start date 1 April 2017, end date 31 January, 2019) and the Scottish government as part of the Strategic Research Programme at the Rowett Institute (start date 1 April 2016–31 March 2021).Peer reviewedPostprin

Transcription Is Required to Establish Maternal Imprinting at the Prader-Willi Syndrome and Angelman Syndrome Locus

The Prader-Willi syndrome (PWS [MIM 17620]) and Angelman syndrome (AS [MIM 105830]) locus is controlled by a bipartite imprinting center (IC) consisting of the PWS-IC and the AS-IC. The most widely accepted model of IC function proposes that the PWS-IC activates gene expression from the paternal allele, while the AS-IC acts to epigenetically inactivate the PWS-IC on the maternal allele, thus silencing the paternally expressed genes. Gene order and imprinting patterns at the PWS/AS locus are well conserved from human to mouse; however, a murine AS-IC has yet to be identified. We investigated a potential regulatory role for transcription from the Snrpn alternative upstream exons in silencing the maternal allele using a murine transgene containing Snrpn and three upstream exons. This transgene displayed appropriate imprinted expression and epigenetic marks, demonstrating the presence of a functional AS-IC. Transcription of the upstream exons from the endogenous locus correlates with imprint establishment in oocytes, and this upstream exon expression pattern was conserved on the transgene. A transgene bearing targeted deletions of each of the three upstream exons exhibited loss of imprinting upon maternal transmission. These results support a model in which transcription from the Snrpn upstream exons directs the maternal imprint at the PWS-IC

Higher total faecal short chain fatty concentrations correlate with increasing proportions of butyrate and decreasing proportions of branched chain fatty acids across multiple human studies

The Rowett Institute (University of Aberdeen) receives financial support from the Scottish Government Rural and Environmental Sciences and Analytical Services (RESAS). Studies 779 and 780 were supported by a grant from the World Cancer Research Fund.Peer reviewedPublisher PD

Daily Fermented Whey Consumption Alters the Fecal Short-Chain Fatty Acid Profile in Healthy Adults

FUNDING: This study was funded by A.Vogel Bioforce AG, Roggwil, Switzerland. NS was co-funded by the School of Medicine, Medical Sciences and Nutrition (University of Aberdeen) and A.Vogel Bioforce AG. The Rowett Institute (University of Aberdeen) receives financial support from the Scottish Government Rural and Environmental Sciences and Analytical Services (RESAS). ACKNOWLEDGMENTS: We thank all the volunteers which contributed their time and efforts into enrolling and completing the trial. Further, we are grateful for the staff at the Human Nutrition Unit and Analytical Services at the Rowett Institute for supporting the research and assisting when needed. We would like to thank Brennan Martin at the Center for Genome Enabled Biology of Medicine for his assistance in DNA sequencingPeer reviewedPublisher PD

Safety, Tolerability, Pharmacokinetics, and Antimalarial Activity of the Novel Plasmodium Phosphatidylinositol 4-Kinase Inhibitor MMV390048 in Healthy Volunteers.

MMV390048 is a novel antimalarial compound that inhibits Plasmodium phosphatidylinositol-4-kinase. The safety, tolerability, pharmacokinetic profile, and antimalarial activity of MMV390048 were determined in healthy volunteers in three separate studies. A first-in-human, double-blind, randomized, placebo-controlled, single-ascending-dose study was performed. Additionally, a volunteer infection study investigated the antimalarial activity of MMV390048 using the Plasmodium falciparum induced blood-stage malaria (IBSM) model. Due to the high pharmacokinetic variability with the powder-in-bottle formulation used in both of these studies, a third study was undertaken to select a tablet formulation of MMV390048 to take forward into future studies. MMV390048 was generally well tolerated when administered as a single oral dose up to 120 mg, with rapid absorption and a long elimination half-life. Twelve adverse events were considered to be potentially related to MMV390048 in the first-in-human study but with no obvious correlation between these and MMV390048 dose or exposure. Although antimalarial activity was evident in the IBSM study, rapid recrudescence occurred in most subjects after treatment with 20 mg MMV390048, a dose expected to be subtherapeutic. Reformulation of MMV390048 into two tablet formulations (tartaric acid and Syloid) resulted in significantly reduced intersubject pharmacokinetic variability. Overall, the results of this study suggest that MMV390048 is well tolerated in humans, and the pharmacokinetic properties of the compound indicate that it has the potential to be used for antimalarial prophylaxis or inclusion in a single-dose cure. MMV390048 is currently being tested in a phase 2a study in Ethiopian adults with acute, uncomplicated falciparum or vivax malaria monoinfection. (The three clinical trials described here were each registered with ClinicalTrials.gov as follows: first-in-human study, registration no. NCT02230579; IBSM study, registration no. NCT02281344; and formulation optimization study, registration no. NCT02554799.)

Higher total faecal short-chain fatty acid concentrations correlate with increasing proportions of butyrate and decreasing proportions of branched-chain fatty acids across multiple human studies

Metabolites produced by microbial fermentation in the human intestine, especially short-chain fatty acids (SCFAs), are known to play important roles in colonic and systemic health. Our aim here was to advance our understanding of how and why their concentrations and proportions vary between individuals. We have analysed faecal concentrations of microbial fermentation acids from 10 human volunteer studies, involving 163 subjects, conducted at the Rowett Institute, Aberdeen, UK over a 7-year period. In baseline samples, the % butyrate was significantly higher, whilst % iso-butyrate and % iso-valerate were significantly lower, with increasing total SCFA concentration. The decreasing proportions of iso-butyrate and iso-valerate, derived from amino acid fermentation, suggest that fibre intake was mainly responsible for increased SCFA concentrations. We propose that the increase in % butyrate among faecal SCFA is largely driven by a decrease in colonic pH resulting from higher SCFA concentrations. Consistent with this, both total SCFA and % butyrate increased significantly with decreasing pH across five studies for which faecal pH measurements were available. Colonic pH influences butyrate production through altering the stoichiometry of butyrate formation by butyrate-producing species, resulting in increased acetate uptake and butyrate formation, and facilitating increased relative abundance of butyrate-producing species (notably Roseburia and Eubacterium rectale).The Rowett Institute (University of Aberdeen) receives financial support from the Scottish Government Rural and Environmental Sciences and Analytical Services (RESAS). Studies 779 and 780 were supported by a grant from the World Cancer Research Fund.Peer reviewe