Differential p38-dependent signalling in response to cellular stress and mitogenic stimulation in fibroblasts

p38 MAP kinase is known to be activated by cellular stress finally leading to cell cycle arrest or apoptosis. Furthermore, a tumour suppressor role of p38 MAPK has been proposed. In contrast, a requirement of p38 for proliferation has also been described. To clarify this paradox, we investigated stress- and mitogen-induced p38 signalling in the same cell type using fibroblasts. We demonstrate that - in the same cell line - p38 is activated by mitogens or cellular stress, but p38-dependent signalling is different. Exposure to cellular stress, such as anisomycin, leads to a strong and persistent p38 activation independent of GTPases. As a result, MK2 and downstream the transcription factor CREB are phosphorylated. In contrast, mitogenic stimulation results in a weaker and transient p38 activation, which upstream involves small GTPases and is required for cyclin D1 induction. Consequently, the retinoblastoma protein is phosphorylated and allows G1/S transition. Our data suggest a dual role of p38 and indicate that the level and/or duration of p38 activation determines the cellular response, i.e either proliferation or cell cycle arrest

PrPCWD lymphoid cell targets in early and advanced chronic wasting disease of mule deer

Up to 15% of free-ranging mule deer in northeastern Colorado and southeastern Wyoming, USA, are afflicted with a prion disease, or transmissible spongiform encephalopathy (TSE), known as chronic wasting disease (CWD). CWD is similar to a subset of TSEs including scrapie and variant Creutzfeldt¿Jakob disease in which the abnormal prion protein isoform, PrPCWD, accumulates in lymphoid tissue. Experimental scrapie studies have indicated that this early lymphoid phase is an important constituent of prion replication interposed between mucosal entry and central nervous system accumulation. To identify the lymphoid target cells associated with PrPCWD, we used triple-label immunofluorescence and high-resolution confocal microscopy on tonsils from naturally infected deer in advanced disease. We detected PrPCWD primarily extracellularly in association with follicular dendritic and B cell membranes as determined by frequent co-localization with antibodies against membrane bound immunoglobulin and CD21. There was minimal co-localization with cytoplasmic labels for follicular dendritic cells (FDC). This finding could indicate FDC capture of PrPCWD, potentially in association with immunoglobulin or complement, or PrPC conversion on FDC. In addition, scattered tingible body macrophages in the germinal centre contained coarse intracytoplasmic aggregates of PrPCWD, reflecting either phagocytosis of PrPCWD on FDC processes, apoptotic FDC or B cells, or actual PrPCWD replication within tingible body macrophages. To compare lymphoid cell targets in early and advanced disease, we also examined: (i) PrPCWD distribution in lymphoid cells of fawns within 3 months of oral CWD exposure and (ii) tonsil biopsies from preclinical deer with naturally acquired CWD. These studies revealed that the early lymphoid cellular distribution of PrPCWD was similar to that in advanced disease, i.e. in a pattern suggesting FDC association. We conclude that in deer, PrPCWD accumulates primarily extracellularly and associated with FDCs and possibly B cells ¿ a finding which raises questions as to the cells responsible for pathological prion productio

Microstructure of melt-processed Bi2Sr2CaCu2Oy and reaction mechanisms during post heat treatment

Phase compositions and microstructures of melt processed 2212 were studied. 2212 starting powder was cooled from temperatures between 910 °C and 1100 °C in air at rates ranging from 350 K/min to 0.083 K/min. The solidification sequence was established for all cooling rates. Under all conditions the Bi-free (Sr, Ca)CuO2 (01x1) is the primary phase. The one-layer solid solution 11905 nucleates on this phase. The residual liquid solidifies to a glassy state, decomposes into the eutectic of Cu2O and Bi2Sr2.1Ca0.9Ox, or reacts with the primary phase and the 11905 forming 2212 at high, intermediate, or low cooling rates, respectively. Post solidification heat treatment at 850 °C in air leads to partial remelting. The Cu-rich liquid reacts with 11905 and 01x1 forming 2212. Subsequent solid/solid reactions lead to a high volume fraction of 2212 with almost ideal 2 : 2 : 1 : 2 stoichiometr

The Impact of Strong Gravitational Lensing on Observed Lyman-Break Galaxy Numbers at 4<z<8 in the GOODS and the XDF Blank Fields

Detection of Lyman-Break Galaxies (LBGs) at high-redshift can be affected by gravitational lensing induced by foreground deflectors not only in galaxy clusters, but also in blank fields. We quantify the impact of strong magnification in the samples of $B$, $V$, $i$, $z$ $\&$ $Y$ LBGs ($4\lesssim z \lesssim8$) observed in the XDF and GOODS/CANDELS fields, by investigating the proximity of dropouts to foreground objects. We find that $\sim6\%$ of bright LBGs ($m_{H_{160}}2$) by foreground objects. This fraction decreases from $\sim 3.5\%$ at $z\sim6$ to $\sim1.5\%$ at $z\sim4$. Since the observed fraction of strongly lensed galaxies is a function of the shape of the luminosity function (LF), it can be used to derive Schechter parameters, $\alpha$ and $M_{\star}$, independently from galaxy number counts. Our magnification bias analysis yields Schechter-function parameters in close agreement with those determined from galaxy counts albeit with larger uncertainties. Extrapolation of our analysis to $z\gtrsim 8$ suggests that future surveys with JSWT, WFIRST and EUCLID should find excess LBGs at the bright-end, even if there is an intrinsic exponential cutoff of number counts. Finally, we highlight how the magnification bias measurement near the detection limit can be used as probe of the population of galaxies too faint to be detected. Preliminary results using this novel idea suggest that the magnification bias at $M_{UV}\sim -18$ is not as strong as expected if $\alpha\lesssim -1.7$ extends well below the current detection limits in the XDF. At face value this implies a flattening of the LF at $M_{UV}\gtrsim-16.5$. However, selection effects and completeness estimates are difficult to quantify precisely. Thus, we do not rule out a steep LF extending to $M_{UV}\gtrsim -15$.Comment: Submitted to ApJ on 18/12/201

Owner reported clinical signs and -treatment decisions in equine pastern dermatitis.

INTRODUCTION Equine pastern dermatitis has a high prevalence in the equine population, especially in draft breeds. This skin condition is difficult to treat, and it is suspected that owners often decide on a treatment without consulting a veterinarian. The objectives of this study were to describe owner-reported clinical signs, severity, and reasons to consult a veterinarian. Moreover, we inquired about preventive measures and treatments, both instituted by owners without previous consultation or prescribed by their veterinarians. A total of 123 horses (owners recruited over social media) were included in the study. All horses suffered from equine pastern dermatitis at least once in the two years preceding the study. Standardized questionnaires collecting information on management, housing conditions, clinical signs as well as preventive measures and treatments were filled out by participants. The data was recorded, and descriptive statistics were performed. Most horses (71 out of 115 available answers, 62 %) had shown clinical signs of equine pastern dermatitis at least four times in their lives. A total of 113 horses (92 % of all included horses) were affected by equine pastern dermatitis at the time of the interview. For 37 horses (32 %) out of 114 available answers the owners consulted their veterinarian only after the horse showed signs of pain or lameness. Usually, treatments that did not require a medical prescription were applied without consulting their veterinarian (e. g. only 9 % (14 out of 150 prescriptions) of topical creams promoting wound healing were prescribed by a veterinarian). A total of 31 treatment decisions (55 %) with creams containing anti-bacterial, anti-mycotic and/or anti-inflammatory agents and 100 % of systemic medications containing anti-bacterial, anti-parasitic or anti-inflammatory agents were prescribed by veterinarians. Overall, 69 % of treatment decisions were made without consulting a veterinarian, making it then more difficult to determine underlying causes for the pastern dermatitis and rendering the treatment often longer and more onerous. To raise owner awareness of possible consequences if a veterinarian is consulted too late in the disease process, specific information campaigns to improve animal welfare should be considered

A spectroscopically confirmed z=1.327 galaxy-scale deflector magnifying a z~8 Lyman-Break galaxy in the Brightest of Reionizing Galaxies survey

We present a detailed analysis of an individual case of gravitational lensing of a $z\sim8$ Lyman-Break galaxy (LBG) in a blank field, identified in Hubble Space Telescope imaging obtained as part of the Brightest of Reionizing Galaxies survey. To investigate the close proximity of the bright ($m_{AB}=25.8$) $Y_{098}$-dropout to a small group of foreground galaxies, we obtained deep spectroscopy of the dropout and two foreground galaxies using VLT/X-Shooter. We detect H-$\alpha$, H-$\beta$, [OIII] and [OII] emission in the brightest two foreground galaxies (unresolved at the natural seeing of $0.8$ arcsec), placing the pair at $z=1.327$. We can rule out emission lines contributing all of the observed broadband flux in $H_{160}$ band at $70\sigma$, allowing us to exclude the $z\sim8$ candidate as a low redshift interloper with broadband photometry dominated by strong emission lines. The foreground galaxy pair lies at the peak of the luminosity, redshift and separation distributions for deflectors of strongly lensed $z\sim8$ objects, and we make a marginal detection of a demagnified secondary image in the deepest ($J_{125}$) filter. We show that the configuration can be accurately modelled by a singular isothermal ellipsoidal deflector and a S\'{e}rsic source magnified by a factor of $\mu=4.3\pm0.2$. The reconstructed source in the best-fitting model is consistent with luminosities and morphologies of $z\sim8$ LBGs in the literature. The lens model yields a group mass of $9.62\pm0.31\times10^{11} M_{\odot}$ and a stellar mass-to-light ratio for the brightest deflector galaxy of $M_{\star}/L_{B}=2.3^{+0.8}_{-0.6} M_{\odot}/L_{\odot}$ within its effective radius. The foreground galaxies' redshifts would make this one of the few strong lensing deflectors discovered at $z>1$.Comment: Accepted for publication in MNRAS. 16 pages, 11 figures, 3 table

Rest-Frame Optical Emission Lines in z~3.5 Lyman Break selected Galaxies: The Ubiquity of Unusually High [OIII]/Hbeta Ratios at 2 Gyr

We present K-band spectra of rest-frame optical emission lines for 24 star-forming galaxies at z~3.2-3.7 using MOSFIRE on the Keck 1 telescope. Strong rest-frame optical [O III] and Hbeta emission lines were detected in 18 LBGs. The median flux ratio of [O III]5007 to Hbeta is 5.1+/-0.5, a factor of 5-10x higher than in local galaxies with similar stellar masses. The observed Hbeta luminosities are in good agreement with expectations from the estimated star-formation rates, and none of our sources are detected in deep X-ray stacks, ruling out significant contamination by active galactic nuclei. Combining our sample with a variety of LBGs from the literature, including 49 galaxies selected in a very similar manner, we find a high median ratio of [OIII]/Hbeta = 4.8+0.8-1.7. This high ratio seems to be an ubiquitous feature of z~3-4 LBGs, very different from typical local star-forming galaxies at similar stellar masses. The only comparable systems at z~0 are those with similarly high specific star-formation rates, though ~5x lower stellar masses. High specific star-formation rates either result in a much higher ionization parameter or other unusual conditions for the interstellar medium, which result in a much higher [OIII]/Hbeta line ratio. This implies a strong relation between a global property of a galaxy, the specific star-formation rate, and the local conditions of ISM in star-forming regions.Comment: 14 pages, 8 figures, 5 color, published in ApJ, updated to reflect published versio