A genomics-informed, SNP association study reveals FBLN1 and FABP4 as contributing to resistance to fleece rot in Australian Merino sheep

<p>Abstract</p> <p>Background</p> <p>Fleece rot (FR) and body-strike of Merino sheep by the sheep blowfly <it>Lucilia cuprina </it>are major problems for the Australian wool industry, causing significant losses as a result of increased management costs coupled with reduced wool productivity and quality. In addition to direct effects on fleece quality, fleece rot is a major predisposing factor to blowfly strike on the body of sheep. In order to investigate the genetic drivers of resistance to fleece rot, we constructed a combined ovine-bovine cDNA microarray of almost 12,000 probes including 6,125 skin expressed sequence tags and 5,760 anonymous clones obtained from skin subtracted libraries derived from fleece rot resistant and susceptible animals. This microarray platform was used to profile the gene expression changes between skin samples of six resistant and six susceptible animals taken immediately before, during and after FR induction. Mixed-model equations were employed to normalize the data and 155 genes were found to be differentially expressed (DE). Ten DE genes were selected for validation using real-time PCR on independent skin samples. The genomic regions of a further 5 DE genes were surveyed to identify single nucleotide polymorphisms (SNP) that were genotyped across three populations for their associations with fleece rot resistance.</p> <p>Results</p> <p>The majority of the DE genes originated from the fleece rot subtracted libraries and over-representing gene ontology terms included defense response to bacterium and epidermis development, indicating a role of these processes in modulating the sheep's response to fleece rot. We focused on genes that contribute to the physical barrier function of skin, including keratins, collagens, fibulin and lipid proteins, to identify SNPs that were associated to fleece rot scores.</p> <p>Conclusions</p> <p>We identified FBLN1 (fibulin) and FABP4 (fatty acid binding protein 4) as key factors in sheep's resistance to fleece rot. Validation of these markers in other populations could lead to vital tests for marker assisted selection that will ultimately increase the natural fleece rot resistance of Merino sheep.</p

Adenosine receptor expression and function in rat striatal cholinergic interneurons

1. Cholinergic neurons were identified in rat striatal slices by their size, membrane properties, sensitivity to the NK(1) receptor agonist (Sar(9), Met(O(2))(11)) Substance P, and expression of choline acetyltransferase mRNA. A(1) receptor mRNA was detected in 60% of the neurons analysed, and A(2A) receptor mRNA in 67% (n=15). 2. The A(1) receptor agonist R-N(6)-(2-phenylisopropyl)adenosine (R-PIA) hyperpolarized cholinergic neurons in a concentration dependent manner sensitive to the A(1) antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 nM). 3. In dual stimulus experiments, the A(2A) receptor antagonist 8-(3-chlorostyryl)caffeine (CSC, 500 nM) decreased release of [(3)H]-acetylcholine from striatal slices (S2/S1 0.78±0.07 versus 0.95±0.05 in control), as did adenosine deaminase (S2/S1 ratio 0.69±0.05), whereas the A(1) receptor antagonist DPCPX (100 nM) had no effect (S2/S1 1.05±0.14). 4. In the presence of adenosine deaminase the adenosine A(2A) receptor agonist 2-p-((carboxyethyl)phenylethylamino)-5′-N-ethylcarboxamidoadenosine (CGS21680, 10 nM) increased release (S2/S1 ratio 1.03±0.05 versus 0.88±0.05 in control), an effect blocked by the antagonist CSC (500 nM, S2/S1 0.68±0.05, versus 0.73±0.08 with CSC alone). The combined superfusion of bicuculline (10 μM), saclofen (1 μM) and naloxone (10 μM) had no effect on the stimulation by CGS21680 (S2/S1 ratio 0.99±0.04). 5. The A(1) receptor agonist R-PIA (100 nM) inhibited the release of [(3)H]-acetylcholine (S2/S1 ratio 0.70±0.03), an effect blocked by DPCPX (S2/S1 ratio 1.06±0.07). 6. It is concluded that both A(1) and A(2A) receptors are expressed on striatal cholinergic neurons where they are functionally active

a4-Containing GABA _A Receptors on DRD2 Neurons of the Nucleus Accumbens Mediate Instrumental Responding for Conditioned Reinforcers and Its Potentiation by Cocaine

Extrasynaptic GABA A receptors (GABA ARs) composed of a4, b, and d subunits mediate GABAergic tonic inhibition and are potential molecular targets in the modulation of behavioral responses to natural and drug rewards. These GABA ARs are highly expressed within the nucleus accumbens (NAc), where they influence the excitability of the medium spiny neurons. Here, we explore their role in modulating behavioral responses to food-conditioned cues and the behavior-potentiating effects of cocaine. a4-Subunit constitutive knock-out mice (a4 /) showed higher rates of instrumental responding for reward-paired stimuli in a test of conditioned reinforcement (CRf). A similar effect was seen fol-lowing viral knockdown of GABA AR a4 subunits within the NAc. Local infusion of the a4b d-GABA AR-preferring agonist THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol; Gaboxadol) into the NAc had no effect on responding when given alone but reduced cocaine potentiation of responding for conditioned reinforcers in wild-type, but not a4 / mice. Finally, specific deletion of a4-subunits from dopamine D2, but not D1, receptor-expressing neurons (DRD2 and DRD1 neurons), mimicked the phenotype of the constitutive knockout, potentiating CRf responding, and blocking intra-accumbal THIP attenuation of cocaine-potentiated CRf responding. These data demonstrate that a4-GABA AR-mediated inhibition of DRD2 neurons reduces instrumental responding for a conditioned reinforcer and its po-tentiation by cocaine and emphasize the importance of GABAergic signaling within the NAc in mediating the effects of cocaine.</p

Gluon fusion contribution to W+W- + jet production

We describe the computation of the $gg \to W^+W^-g$ process that contributes to the production of two $W$-bosons and a jet at the CERN Large Hadron Collider (LHC). While formally of next-to-next-to-leading order (NNLO) in QCD, this process can be evaluated separately from the bulk of NNLO QCD corrections because it is finite and gauge-invariant. It is also enhanced by the large gluon flux and by selection cuts employed in the Higgs boson searches in the decay channel $H \to W^+W^-$, as was first pointed out by Binoth {\it et al.} in the context of $gg \to W^+W^-$ production. For cuts employed by the ATLAS collaboration, we find that the gluon fusion contribution to $pp \to W^+W^-j$ enhances the background by about ten percent and can lead to moderate distortions of kinematic distributions which are instrumental for the ongoing Higgs boson searches at the LHC. We also release a public code to compute the NLO QCD corrections to this process, in the form of an add-on to the package {\tt MCFM}.Comment: 13 pages, 4 figures, 3 table

Ramond-Ramond Fields, Fractional Branes and Orbifold Differential K-Theory

We study D-branes and Ramond-Ramond fields on global orbifolds of Type II string theory with vanishing H-flux using methods of equivariant K-theory and K-homology. We illustrate how Bredon equivariant cohomology naturally realizes stringy orbifold cohomology. We emphasize its role as the correct cohomological tool which captures known features of the low-energy effective field theory, and which provides new consistency conditions for fractional D-branes and Ramond-Ramond fields on orbifolds. We use an equivariant Chern character from equivariant K-theory to Bredon cohomology to define new Ramond-Ramond couplings of D-branes which generalize previous examples. We propose a definition for groups of differential characters associated to equivariant K-theory. We derive a Dirac quantization rule for Ramond-Ramond fluxes, and study flat Ramond-Ramond potentials on orbifolds.Comment: 46 pages; v2: typos correcte

Assessment of ground-based monitoring techniques applied to landslide investigations

A landslide complex in the Whitby Mudstone Formation at Hollin Hill, North Yorkshire, UK is periodically re-activated in response to rainfall-induced pore-water pressure fluctuations. This paper compares long-term measurements (i.e., 2009 – 2014) obtained from a combination of monitoring techniques that have been employed together for the first time on an active landslide. The results highlight the relative performance of the different techniques, and can provide guidance for researchers and practitioners for selecting and installing appropriate monitoring techniques to assess unstable slopes. Particular attention is given to the spatial and temporal resolution offered by the different approaches that include: Real Time Kinematic-GPS (RTK-GPS) monitoring of a ground surface marker array, conventional inclinometers, Shape Acceleration Arrays (SAA), tilt meters, active waveguides with Acoustic Emission (AE) monitoring, and piezometers. High spatial resolution information has allowed locating areas of stability and instability across a large slope. This has enabled identification of areas where further monitoring efforts should be focused. High temporal resolution information allowed the capture of S’-shaped slope displacement-time behaviour (i.e. phases of slope acceleration, deceleration and stability) in response to elevations in pore-water pressures. This study shows that a well-balanced suite of monitoring techniques that provides high temporal and spatial resolution on both measurement and slope scale is necessary to fully understand failure and movement mechanisms of slopes. In the case of the Hollin Hill landslide it enabled detailed interpretation of the geomorphological processes governing landslide activity. It highlights the benefit of regularly surveying a network of GPS markers to determine areas for installation of movement monitoring techniques that offer higher resolution both temporally and spatially. The small sensitivity of tilt meter measurements to translational movements limited the ability to record characteristic ‘S’-shaped landslide movements at Hollin Hill, which were identified using SAA and AE measurements. This high sensitivity to landslide movements indicates the applicability of SAA and AE monitoring to be used in early warning systems, through detecting and quantifying accelerations of slope movement

Lime stabilisation for earthworks: a UK perspective

Lime stabilisation is a versatile technique applied during earthworks operations. Modern soil recycling units are much more efficient at pulverising fill material and intermixing the added binder/water than machinery available 20 years ago. While supplier innovation adds flexibility to the site working method, specifications have not been sufficiently updated to permit optimal application. This review paper details the physico-chemical changes instigated through the lime-clay soil reaction, updating previous reviews. It aims to assist scientific debate, current practitioners and future specification changes. For example, the application of the minimum 24 h mellowing periods (mandatory to UK specifications) with high reactivity, quicklime powders is concluded to cause increased air voids in the compacted fill. Increased air voids are associated with reduced long-term strength and potential volume change from water ingress, which is of particular concern for sulfate swelling. Shorter mellowing periods and/or use of hydrated lime may lesson this issue; however, a 'one size fits all' approach is discouraged in preference to site-specific methodologies refined to suit the fill material and project requirements. The discussion also summarises working methods which may lower the risk of sulfate swell and defines areas requiring further practical research

W+W-, WZ and ZZ production in the POWHEG BOX

We present an implementation of the vector boson pair production processes ZZ, W+W- and W Z within the POWHEG framework, which is a method that allows the interfacing of NLO calculations to shower Monte Carlo programs. The implementation is built within the POWHEG BOX package. The Z/\gamma^* interference, as well as singly resonant contributions, are properly included. We also considered interference terms arising from identical leptons in the final state. As a result, all contributions leading to the desired four-lepton system have been included in the calculation, with the sole exception of the interference between ZZ and W+W- in the production of a pair of same-flavour, oppositely charged fermions and a pair of neutrinos, which we show to be fully negligible. Anomalous trilinear couplings can be also set in the program, and we give some examples of their effect at the LHC. We have made the relevant code available at the POWHEG BOX web site.Comment: 20 pages, 9 figures, 2 tables. Minor corrections and updated references in revised versio