Long-term macrolide maintenance therapy in non-CF bronchiectasis: Evidence and questions

BRCA1, a 'complex' protein involved in the maintenance of genomic stability

BRCA1 is a major breast and ovarian cancer susceptibility gene, with mutations in this gene predisposing women to a very high risk of developing breast and ovarian tumours. BRCA1 primarily functions to maintain genomic stability via critical roles in DNA repair, cell cycle checkpoint control, transcriptional regulation, apoptosis and mRNA splicing. As a result, BRCA1 mutations often result in defective DNA repair, genomic instability and sensitivity to DNA damaging agents. BRCA1 carries out these different functions through its ability to interact, and form complexes with, a vast array of proteins involved in multiple cellular processes, all of which are considered to contribute to its function as a tumour suppressor. This review discusses and highlights recent research into the functions of BRCA1-related protein complexes and their roles in maintaining genomic stability and tumour suppression.

Biosecurity and Emerging Plant Health Problems in Turf Production and Maintenance

Recent research has supported the view that the distributions of many pests and diseases have extended towards higher latitudes over the last 50 years. Probably driven by a combination of climate change and trade, this extension to the ranges of hundreds of plant pathogens may have serious implications not only for agriculture, horticulture and forestry, but also for turf production &maintenance. Here we review our data relating to the current status of three emerging pest and disease problems across North West Europe (rapid blight, Labyrinthula sp. , the root knot nematode, Meloidogyne minor and the pacific stem gall nematode, Anguina pacificae ) and discuss the factors which may be involved in their spread and increasing impact on the turf industry. With turf production and maintenance becoming an increasingly international business, we ask if biosecurity and the promotion of plant health in turf production fields and associated sport facilities should be a greater priority for the industry. We also examine if a lack of effective biosecurity measures in the materials supply chain has led to increased plant health problems.

Research-informed design, management and maintenance of infrastructure slopes: development of a multi-scalar approach

The UK’s transport infrastructure is one of the most heavily used in the world. The performance of these networks is critically dependent on the performance of cutting and embankment slopes which make up £20B of the £60B asset value of major highway infrastructure alone. The rail network in particular is also one of the oldest in the world: many of these slopes are suffering high incidents of instability (increasing with time). This paper describes the development of a fundamental understanding of earthwork material and system behaviour, through the systematic integration of research across a range of spatial and temporal scales. Spatially these range from microscopic studies of soil fabric, through elemental materials behaviour to whole slope modelling and monitoring and scaling up to transport networks. Temporally, historical and current weather event sequences are being used to understand and model soil deterioration processes, and climate change scenarios to examine their potential effects on slope performance in futures up to and including the 2080s. The outputs of this research are being mapped onto the different spatial and temporal scales of infrastructure slope asset management to inform the design of new slopes through to changing the way in which investment is made into aging assets. The aim ultimately is to help create a more reliable, cost effective, safer and more resilient transport system.

Determinants of uptake and maintenance of active commuting to school

The objective was to identify determinants of uptake and maintenance of active school travel (AST) over 4 years in children aged 9 at baseline. Data from wave 1 (n=8502) and 2 (n=7479) of the Growing Up in Ireland study were analysed. At 9- and 13-years 25% and 20% engaged in AST. Children were more likely to maintain or take-up AST if they lived in an urban area. Change in distance to school influenced both maintenance and adoption of AST, with a negative impact seen for increased distance between 9 and 13 years and a positive impact seen for decreased distance. Some factors which predict uptake and maintenance of AST are modifiable and can inform intervention development.

Small Area Estimation of the Mean Price of the Habitation Transaction in Portugal: Methodological and Practical Issues

The Portuguese National Statistical Institute intends to produce estimations for the mean price of the habitation transation.

Small area estimation for the price of habitation transaction: comparison of different uncertainty measures of temporal EBLUP

Local level planning requires statistics for small areas, but normally due to cost or logistic constraints, sample surveys are often planned to provide reliable estimates only for large geographical regions and large subgroups of a population.

Evolution of matrix and bone gamma-carboxyglutamic acid proteins in vertebrates

The evolution of calcified tissues is a defining feature in vertebrate evolution. Investigating the evolution of proteins involved in tissue calcification should help elucidate how calcified tissues have evolved. The purpose of this study was to collect and compare sequences of matrix and bone γ-carboxyglutamic acid proteins (MGP and BGP, respectively) to identify common features and determine the evolutionary relationship between MGP and BGP. Thirteen cDNAs and genes were cloned using standard methods or reconstructed through the use of comparative genomics and data mining. These sequences were compared with available annotated sequences (a total of 48 complete or nearly complete sequences, 28 BGPs and 20 MGPs) have been identified across 32 different species (representing most classes of vertebrates), and evolutionarily conserved features in both MGP and BGP were analyzed using bioinformatic tools and the Tree-Puzzle software. We propose that: 1) MGP and BGP genes originated from two genome duplications that occurred around 500 and 400 million years ago before jawless and jawed fish evolved, respectively; 2) MGP appeared first concomitantly with the emergence of cartilaginous structures, and BGP appeared thereafter along with bony structures; and 3) BGP derives from MGP. We also propose a highly specific pattern definition for the Gla domain of BGP and MGP. Previous Section Next Section BGP1 (bone Gla protein or osteocalcin) and MGP (matrix Gla protein) belong to the growing family of vitamin K-dependent (VKD) proteins, the members of which are involved in a broad range of biological functions such as skeletogenesis and bone maintenance (BGP and MGP), hemostasis (prothrombin, clotting factors VII, IX, and X, and proteins C, S, and Z), growth control (gas6), and potentially signal transduction (proline-rich Gla proteins 1 and 2). VKD proteins are characterized by the presence of several Gla residues resulting from the post-translational vitamin K-dependent γ-carboxylation of specific glutamates, through which they can bind to calcium-containing mineral such as hydroxyapatite. To date, VKD proteins have only been clearly identified in vertebrates (1) although the presence of a γ-glutamyl carboxylase has been reported in the fruit fly Drosophila melanogaster (2) and in marine snails belonging to the genus Conus (3). Gla residues have also been found in neuropeptides from Conus venoms (4), suggesting a wider prevalence of γ-carboxylation.

Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults.

OBJECTIVE: The colonic microbiota ferment dietary fibres, producing short chain fatty acids. Recent evidence suggests that the short chain fatty acid propionate may play an important role in appetite regulation. We hypothesised that colonic delivery of propionate would increase peptide YY (PYY) and glucagon like peptide-1 (GLP-1) secretion in humans, and reduce energy intake and weight gain in overweight adults. DESIGN: To investigate whether propionate promotes PYY and GLP-1 secretion, a primary cultured human colonic cell model was developed. To deliver propionate specifically to the colon, we developed a novel inulin-propionate ester. An acute randomised, controlled cross-over study was used to assess the effects of this inulin-propionate ester on energy intake and plasma PYY and GLP-1 concentrations. The long-term effects of inulin-propionate ester on weight gain were subsequently assessed in a randomised, controlled 24-week study involving 60 overweight adults. RESULTS: Propionate significantly stimulated the release of PYY and GLP-1 from human colonic cells. Acute ingestion of 10 g inulin-propionate ester significantly increased postprandial plasma PYY and GLP-1 and reduced energy intake. Over 24 weeks, 10 g/day inulin-propionate ester supplementation significantly reduced weight gain, intra-abdominal adipose tissue distribution, intrahepatocellular lipid content and prevented the deterioration in insulin sensitivity observed in the inulin-control group. CONCLUSIONS: These data demonstrate for the first time that increasing colonic propionate prevents weight gain in overweight adult humans.

Context-aware Approach for Determining the Threshold Price in Name-Your-Own-Price Channels

Key feature of a context-aware application is the ability to adapt based on the change of context. Two approaches that are widely used in this regard are the context-action pair mapping where developers match an action to execute for a particular context change and the adaptive learning where a context-aware application refines its action over time based on the preceding action’s outcome. Both these approaches have limitation which makes them unsuitable in situations where a context-aware application has to deal with unknown context changes. In this paper we propose a framework where adaptation is carried out via concurrent multi-action evaluation of a dynamically created action space. This dynamic creation of the action space eliminates the need for relying on the developers to create context-action pairs and the concurrent multi-action evaluation reduces the adaptation time as opposed to the iterative approach used by adaptive learning techniques. Using our reference implementation of the framework we show how it could be used to dynamically determine the threshold price in an e-commerce system which uses the name-your-own-price (NYOP) strategy.