Inference of transcriptional regulation using gene expression data from the bovine and human genomes

<p>Abstract</p> <p>Background</p> <p>Gene expression is in part regulated by sequences in promoters that bind transcription factors. Thus, co-expressed genes may have shared sequence motifs representing putative transcription factor binding sites (TFBSs). However, for agriculturally important animals the genomic sequence is often incomplete. The more complete human genome may be able to be used for this prediction by taking advantage of the expected evolutionary conservation in TFBSs between the species.</p> <p>Results</p> <p>A method of <it>de novo </it>TFBS prediction based on MEME was implemented, tested, and validated on a muscle-specific dataset.</p> <p>Muscle specific expression data from EST library analysis from cattle was used to predict sets of genes whose expression was enriched in muscle and cardiac tissues. The upstream 1500 bases from calculated orthologous genes were extracted from the human reference set. A set of common motifs were discovered in these promoters. Slightly over one third of these motifs were identified as known TFBSs including known muscle specific binding sites. This analysis also predicted several highly statistically significantly overrepresented sites that may be novel TFBS.</p> <p>An independent analysis of the equivalent bovine genomic sequences was also done, this gave less detailed results than the human analysis due to both the quality of orthologue prediction and assembly in promoter regions. However, the most common motifs could be detected in both sets.</p> <p>Conclusion</p> <p>Using promoter sequences from human genes is a useful approach when studying gene expression in species with limited or non-existing genomic sequence. As the bovine genome becomes better annotated it can in turn serve as the reference genome for other agriculturally important ruminants, such as sheep, goat and deer.</p

What Next After Metformin in Type 2 Diabetes? Selecting the Right Drug for the Right Patient

This is the final version. Available on open access from Springer via the DOI in this recordIntroduction: Metformin is the recommended initial treatment in type 2 diabetes mellitus (T2DM), but when this does not give adequate glucose control the choice of which second-line drug to use is uncertain as none have been found to have a better overall glycaemic response. In this real-world study dipeptidyl peptidase 4 inhibitors (DPP4i), sulphonylureas (SU), thiazolidinediones (TZD) and sodium glucose co-transporter 2 inhibitors (SGLT2i) were compared for their effectiveness in lowering glycated haemoglobin (HbA1c) levels for a particular individual based on their clinical characteristics. Methods: A retrospective analysis was undertaken of electronic health records of people with T2DM prescribed metformin alongside a DPP4i, SU, TZD or SGLT2i at second-line. Regression modelling was used to model the changes in HbA1c from baseline at month 6 and month 12 for the individual therapies, adjusting for demographic and clinical characteristics. Results: There were 7170 people included in the study. Treatment at second-line with SUs, DPP4i, TZDs and SGLT2i resulted in similar percentages of people achieving the recommended HbA1c target of < 7.5% (58 mmol/mol) at both 6 and 12 months. For those receiving SGLT2i and SUs, the greatest improvement in HbA1c was observed in relatively younger and older people, respectively. Trends were detected between other baseline characteristics and HbA1c improvement by drug class, but they were not statistically significant. Non-adherence rates were low for all drug classes. People with a higher medication possession ratio (≥ 80%) also had greater improvements in HbA1c at 12 months. Conclusion: This study identified patients’ phenotypic characteristics that may have the potential to influence individual treatment response. Accounting for these characteristics in clinical treatment decisions may facilitate individualised prescribing by being able to select the right drug for the right patient.Takeda UK Ltd

Detecting genetic regions associated with height in the native ponies of the British Isles by using high density SNP genotyping

Height is an important characteristic in the equine industry, although little is known about its genetic control in native British breeds of ponies. This study aimed to map QTL data with the withers height in four pony breeds native to the British Isles, including two different sections within Welsh Cobs. In this study, a genome-wide analysis approach using the Illumina Equine SNP50 Infinium BeadChip was applied to 105 ponies and cobs. Analysis identified 222 highly significant height-associated SNPs (P < 10-5), among which three SNPs on ECA9 have also been previously reported elsewhere. The highest number of significant SNPs associated to height in the native British horses were located on ECA1, ECA8 and ECA16

Nitroarylurea-terminated supramolecular polymers that exhibit facile thermal repair and aqueous swelling-induced sealing of defects

Bi- and tri-armed polyethylene glycol units endcapped with nitroaryl urea units have been synthesised. These endcapped polymers are able to self-assemble via complementary supramolecular interactions, specifically urea-urea and nitro-urea hydrogen bonding, to afford materials with dramatically increased mechanical and thermal properties when compared to those of the uncapped polyethylene glycol precursors. Thin films of the capped polymeric systems are able to self-repair following defect creation. Control over the mechanical and thermal characteristics (in terms of bulk viscosity) of the self-assembled networks was achieved by varying the proportion of tri-armed to bi-armed self-assembly units included in the polymer. These systems demonstrate water absorption and swelling capabilities that are also controllable by varying the ratio of the two types of unit. These physical properties have been optimised to realise a secondary pathway to puncture-repair as a result of swelling on water contact

Aging time affects color stability and sensory properties of ground beef patties adjusted

Palatability traits of flavor, juiciness, and tenderness are associated with consumer satisfaction. Although grinding offers an opportunity to mechanically minimize differences in tenderness, muscle source and product quality may still affect the sensory properties of ground beef. The objective of this study was to determine the effects of two quality grades (Premium Choice and Select) and vacuum storage aging time (7, 21, and 42 days) before processing on ground beef patty display color from chuck roll and knuckle subprimals combined to obtain a common percentage of fat

Solar energy for all? Understanding the successes and shortfalls through a critical comparative assessment of Bangladesh, Brazil, India, Mozambique, Sri Lanka and South Africa

Lanterns, homes systems, hot water systems and micro-grids based on small-scale solar have become prominent ways to address the energy access challenge. As momentum grows for this form of energy transition this paper draws together research on small-scale solar in six different countries – Bangladesh, Brazil, India, Mozambique, Sri Lanka and South Africa – to argue for a need to understand how, when, and for whom solar provides energy access. It argues that an assemblage perspective can provide vital insights into the diversity and dynamism of energy access. The paper demonstrates that the diverse ways in which solar provides energy access is a function of the flexibility/fixity of the socio-technical assemblage and the de/centralisation of agency. The central thesis of this paper is that energy access is fluid and ever changing and we need fluid, easily maintainable, locally modifiable ‘assemblages’ for providing such access. Using this perspective, we find three common features of solar energy access across our case studies. First, there are significant gaps between what solar projects are designed to achieve and what they deliver, which are highly contingent on the flexibility of their structure and the decentralisation of agency within them. Second, access needs to endure continuously. Third, to foster enduring access, projects should embed logics of improvisation. This paper is based on six separate qualitative research projects conducted during 2010–2016. It draws data from 482 interviews, 91 home tours and 12 group discussions

Shmapped: development of an app to record and promote the well-being benefits of noticing urban nature

The majority of research to date on the links between well-being and green spaces comes from cross-sectional studies. Shmapped is an app that allows for the collection of well-being and location data live in the field and acts as a novel dual data collection tool and well-being intervention, which prompts users to notice the good things about their surroundings. We describe the process of developing Shmapped from storyboarding, budgeting, and timescales; selecting a developer; drawing up data protection plans; and collaborating with developers and end-user testers to ultimately publishing Shmapped. The development process and end-user testing resulted in a highly functional app. Limitations and future uses of such novel dual data collection and intervention apps are discussed and recommendations are made for prospective developers and researchers

Saltation transport on Mars

We present the first calculation of saltation transport and dune formation on Mars and compare it to real dunes. We find that the rate at which grains are entrained into saltation on Mars is one order of magnitude higher than on Earth. With this fundamental novel ingredient, we reproduce the size and different shapes of Mars dunes, and give an estimate for the wind velocity on Mars.Comment: 4 pages, 3 figure

Gated rotation mechanism of site-specific recombination by ϕC31 integrase

Integrases, such as that of the Streptomyces temperate bacteriophage ϕC31, promote site-specific recombination between DNA sequences in the bacteriophage and bacterial genomes to integrate or excise the phage DNA. ϕC31 integrase belongs to the serine recombinase family, a large group of structurally related enzymes with diverse biological functions. It has been proposed that serine integrases use a “subunit rotation” mechanism to exchange DNA strands after double-strand DNA cleavage at the two recombining att sites, and that many rounds of subunit rotation can occur before the strands are religated. We have analyzed the mechanism of ϕC31 integrase-mediated recombination in a topologically constrained experimental system using hybrid “phes” recombination sites, each of which comprises a ϕC31 att site positioned adjacent to a regulatory sequence recognized by Tn3 resolvase. The topologies of reaction products from circular substrates containing two phes sites support a right-handed subunit rotation mechanism for catalysis of both integrative and excisive recombination. Strand exchange usually terminates after a single round of 180° rotation. However, multiple processive “360° rotation” rounds of strand exchange can be observed, if the recombining sites have nonidentical base pairs at their centers. We propose that a regulatory “gating” mechanism normally blocks multiple rounds of strand exchange and triggers product release after a single round