Digital image profilers for detecting faint sources which have bright companions, phase 2

A breadboard image profiling system developed for the first phase of this project demonstrated the potential for detecting extremely faint optical sources in the presence of light companions. Experimental data derived from laboratory testing of the device supports the theory that image profilers of this type may approach the theoretical limit imposed by photon statistics. The objective of Phase 2 of this program is the development of a ground-based multichannel image profiling system capable of detecting faint stellar objects slightly displaced from brighter stars. We have finalized the multichannel image profiling system and attempted three field tests

Management and birth outcomes of pregnant women with Chiari malformations : a 14 years retrospective case series

Objective The management of Chiari malformations in pregnancy is challenging due to the perceived risk of adverse maternal neurological outcomes and raising intracranial pressure during labour. Our aim was to evaluate the management and health outcomes of pregnant women cared for at a regional referral center and highlight elements of best practice. Study Design A retrospective case series of all pregnant women diagnosed with Chiari malformation over fourteen years (January 2004- June 2018) at the Birmingham Women’s Hospital – UK. Results Twenty-one women (23 pregnancies) with Chiari malformation were included, four had syringomyelia (4/21,19%) and six had previously undergone craniovertebral decompression (6/21, 29%). The median age was 34-years (range 20-41), the median gravidity was two (range 1-8), the median parity was one (range 0-6), and the median extent of tonsillar herniation was 11 mm (range 9-18). The majority of women received their preferred mode of delivery (15 normal vaginal deliveries (15/23, 65.2%) and 6 elective Caesarean sections (6/23, 26.1%)) with two pregnancies ending with an emergency caesarean section for obstetric complications (2/23, 8.7%). Five Caesarean section were performed under general anaesthetic, two under spinal (2/23, 8.7%) and one under epidural anaesthesia (1/23, 4.3%) with no neurological sequelae. There were no adverse neurological outcomes at discharge postnatally. Conclusions Offering normal vaginal delivery with effective analgesia, for women with Chiari malformation, appears to be safe. Pregnancy care should be provided by a multi-disciplinary team with experience in managing Chiari malformation

Biofilm Formation by Listeria monocytogenes 15G01, a Persistent Isolate from a Seafood-Processing Plant, Is Influenced by Inactivation of Multiple Genes Belonging to Different Functional Groups

Listeria monocytogenes is a ubiquitous foodborne pathogen that results in a high rate of mortality in sensitive and immunocompromised people. Contamination of food with L. monocytogenes is thought to occur during food processing, most often as a result of the pathogen producing a biofilm that persists in the environment and acting as the source for subsequent dispersal of cells onto food. A survey of seafoodprocessing plants in New Zealand identified the persistent strain 15G01, which has a high capacity to form biofilms. In this study, a transposon library of L. monocytogenes 15G01 was screened for mutants with altered biofilm formation, assessed by a crystal violet assay, to identify genes involved in biofilm formation. This screen identified 36 transposants that showed a significant change in biofilm formation compared to the wild type. The insertion sites were in 27 genes, 20 of which led to decreased biofilm formation and seven to an increase. Two insertions were in intergenic regions. Annotation of the genes suggested that they are involved in diverse cellular processes, including stress response, autolysis, transporter systems, and cell wall/membrane synthesis. Analysis of the biofilms produced by the transposants using scanning electron microscopy and fluorescence microscopy showed notable differences in the structure of the biofilms compared to the wild type. In particular, inactivation of uvrB and mltD produced coccoid-shaped cells and elongated cells in long chains, respectively, and the mgtB mutant produced a unique biofilm with a sandwich structure which was reversed to the wild-type level upon magnesium addition. The mltD transposant was successfully complemented with the wild-type gene, whereas the phenotypes were not or only partially restored for the remaining mutants. IMPORTANCE The major source of contamination of food with Listeria monocytogenes is thought to be due to biofilm formation and/or persistence in food-processing plants. By establishing as a biofilm, L. monocytogenes cells become harder to eradicate due to their increased resistance to environmental threats. Understanding the genes involved in biofilm formation and their influence on biofilm structure will help identify new ways to eliminate harmful biofilms in food processing environments. To date, multiple genes have been identified as being involved in biofilm formation by L. monocytogenes; however, the exact mechanism remains unclear. This study identified four genes associated with biofilm formation by a persistent strain. Extensive microscopic analysis illustrated the effect of the disruption of mgtB, clsA, uvrB, and mltD and the influence of magnesium on the biofilm structure. The results strongly suggest an involvement in biofilm formation for the four genes and provide a basis for further studies to analyze gene regulation to assess the specific role of these biofilm-associated genes.Peer reviewe

Rates of production and utilisation of lactate by microbial communities from the human colon

13 páginas, 7 tablas, 3 figuras.Lactate metabolism was studied in mixed bacterial communities using single-stage continuous flow fermentors inoculated with faecal slurries from four different volunteers and run for 6 days at pH 5.5 and 6.0, using carbohydrates, mainly starch, as substrates. A continuous infusion of [U-13C]starch and l-[3-13C]lactate was performed on day 5 and a bolus injection of l-[3-13C]lactate plus dl-lactate on day 6. Short-chain fatty acids and lactate concentrations plus enrichments and numbers of lactate-producing and -utilizing bacteria on day 5 were measured. Faecal samples were also collected weekly over a 3-month period to inoculate 24-h batch culture incubation at pH 5.9 and 6.5 with carbohydrates alone or with 35 mmol L-1 lactate. In the fermentors, the potential lactate disposal rates were more than double the formation rates, and lactate concentrations usually remained below detection. Lactate formation was greater (P < 0.05) at the lower pH, with a similar tendency for utilization. Up to 20% of butyrate production was derived from lactate. In batch cultures, lactate was also efficiently used at both pH values, especially at 6.5, although volunteer and temporal variability existed. Under healthy gut environmental conditions, bacterial lactate disposal seems to exceed production markedly.The Rowett Research Institute and Biomathematics and Statistics Scotland are supported by the Scottish Executive Environment and Rural Affairs Department. A. Belenguer received financial support from Spanish Ministry of Education and Science

Vitamin biosynthesis by human gut butyrate-producing bacteria and cross-feeding in synthetic microbial communities

ACKNOWLEDGMENTS This project was funded by Danone Nutricia Research. F.M.F., G.H., H.J.F., S.H.D., and P.L. receive support from the Scottish Government Rural and Environment Sciences and Analytical Services. Method development for coculture microbial analysis was partially supported by European 7th Framework grant (289517) “Dietary fibres supporting gut and immune function; from polysaccharide compound to health claim (Fibebiotics).” We thank Timo Kramer for his technical support with the in silico analyses. M.D., J.-M.F., H.J.F., S.H.D., and P.L. conceived and designed the study. E.C.S.-M., I.W., F.M.F., and M.C. acquired data and contributed to interpreting the results. G.H. performed statistical analysis. E.C.S.-M. and P.L. drafted the manuscript. All authors contributed to revising the manuscript and approved the final version.Peer reviewedPublisher PD

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

Dominance is common in mammals and is associated with trans-acting gene expression and alternative splicing

Background: Dominance and other non-additive genetic effects arise from the interaction between alleles, and historically these phenomena play a major role in quantitative genetics. However, most genome-wide association studies (GWAS) assume alleles act additively. // Results: We systematically investigate both dominance—here representing any non-additive within-locus interaction—and additivity across 574 physiological and gene expression traits in three mammalian stocks: F2 intercross pigs, rat heterogeneous stock, and mice heterogeneous stock. Dominance accounts for about one quarter of heritable variance across all physiological traits in all species. Hematological and immunological traits exhibit the highest dominance variance, possibly reflecting balancing selection in response to pathogens. Although most quantitative trait loci (QTLs) are detectable as additive QTLs, we identify 154, 64, and 62 novel dominance QTLs in pigs, rats, and mice respectively that are undetectable as additive QTLs. Similarly, even though most cis-acting expression QTLs are additive, gene expression exhibits a large fraction of dominance variance, and trans-acting eQTLs are enriched for dominance. Genes causal for dominance physiological QTLs are less likely to be physically linked to their QTLs but instead act via trans-acting dominance eQTLs. In addition, thousands of eQTLs are associated with alternatively spliced isoforms with complex additive and dominant architectures in heterogeneous stock rats, suggesting a possible mechanism for dominance. // Conclusions: Although heritability is predominantly additive, many mammalian genetic effects are dominant and likely arise through distinct mechanisms. It is therefore advantageous to consider both additive and dominance effects in GWAS to improve power and uncover causality

Lactate signalling regulates fungal β-glucan masking and immune evasion

AJPB: This work was supported by the European Research Council (STRIFE, ERC- 2009-AdG-249793), The UK Medical Research Council (MR/M026663/1), the UK Biotechnology and Biological Research Council (BB/K017365/1), the Wellcome Trust (080088; 097377). ERB: This work was supported by the UK Biotechnology and Biological Research Council (BB/M014525/1). GMA: Supported by the CNPq-Brazil (Science without Borders fellowship 202976/2014-9). GDB: Wellcome Trust (102705). CAM: This work was supported by the UK Medical Research Council (G0400284). DMM: This work was supported by UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC/K000306/1). NARG/JW: Wellcome Trust (086827, 075470,101873) and Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology (097377). ALL: This work was supported by the MRC Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1).Peer reviewedPostprin

Role of frailty assessment in patients undergoing cardiac interventions.

Average life expectancy is increasing in the western world resulting in a growing number of frail individuals with coronary heart disease, often associated with comorbidities. Decisions to proceed to invasive interventions in elderly frail patients is challenging because they may gain benefit, but are also at risk of procedure-related complications. Current risk scores designed to predict mortality in cardiac procedures are mainly based on clinical and angiographic factors, with limitations in the elderly because they are mainly derived from a middle-aged population, do not account for frailty and do not predict the impact of the procedure on quality of life which often matters more to elderly patients than mortality. Frailty assessment has emerged as a measure of biological age that correlates well with quality of life, hospital admissions and mortality. Potentially, the incorporation of frailty into current risk assessment models will cause a shift towards more appropriate care. The need for a more accurate method of risk stratification incorporating frailty, particularly for elderly patients is pressing. This article reviews the association between frailty and cardiovascular disease, the impact of frailty on outcomes of cardiac interventions and suggests ways in which frailty assessment could be incorporated into cardiology clinical practice