GRB 980425 host: [C II], [O I], and CO lines reveal recent enhancement of star formation due to atomic gas inflow

Context. Accretion of gas from the intergalactic medium is required to fuel star formation in galaxies. We have recently suggested that this process can be studied using host galaxies of gamma-ray bursts (GRBs). Aims. Our aim is to test this possibility by studying in detail the properties of gas in the closest galaxy hosting a GRB (980425). Methods. We obtained the first ever far-infrared (FIR) line observations of a GRB host, namely Herschel/PACS resolved [C ii] 158 μm and [O i] 63 μm spectroscopy, and an APEX/SHeFI CO(2-1) line detection and ALMA CO(1-0) observations of the GRB 980425 host. Results. The GRB 980425 host has elevated [C ii]/FIR and [O i]/FIR ratios and higher values of star formation rates (SFR) derived from line ([C ii], [O i], Hα) than from continuum (UV, IR, radio) indicators. [C ii] emission exhibits a normal morphology, peaking at the galaxy centre, whereas [O i] is concentrated close to the GRB position and the nearby Wolf-Rayet region. The high [O i] flux indicates that there is high radiation field and high gas density at these positions, as derived from modelling of photo-dissociation regions. The [C ii]/CO luminosity ratio of the GRB 980425 host is close to the highest values found for local star-forming galaxies. Indeed, its CO-derived molecular gas mass is low given its SFR and metallicity, but the [C ii]-derived molecular gas mass is close to the expected value. Conclusions. The [O i] and H i concentrations and the high radiation field and density close to the GRB position are consistent with the hypothesis of a very recent (at most a few tens of Myr ago) inflow of atomic gas triggering star formation. In this scenario dust has not had time to build up (explaining high line-to-continuum ratios). Such a recent enhancement of star formation activity would indeed manifest itself in high SFR/SFR ratios because the line indicators are sensitive only to recent (∼ 10 Myr) activity, whereas the continuum indicators measure the SFR averaged over much longer periods (~100 Myr). Within a sample of 32 other GRB hosts, 20 exhibit SFR/SFR> 1 with a mean ratio of 1.74 ± 0.32. This is consistent with a very recent enhancement of star formation that is common among GRB hosts, so galaxies that have recently experienced inflow of gas may preferentially host stars exploding as GRBs. Therefore GRBs may be used to select a unique sample of galaxies that is suitable for the investigation of recent gas accretion.J.L.W. is supported by a European Union COFUND/Durham Junior Research Fellowship under EU grant agreement number 267209, and acknowledges additional support from STFC (ST/L00075X/1). A.K. acknowledges support from the Foundation for Polish Science (FNP) and the Polish National Science Center grant 2013/11/N/ST9/00400. A.J.C.T. acknowledges support from the Spanish Ministry Project AYA2015-71718-R. D.X. acknowledges the support by the One-Hundred-Talent Program of the Chinese Academy of Sciences, and by the Strategic Priority Research Program >Multi-wavelength Gravitational Wave Universe> of the Chinese Academy of Sciences (No. XDB23000000).Peer Reviewe

Association between COX-2 rs 6681231 Genotype and Interleukin-6 in Periodontal Connective Tissue. A Pilot Study

This study was partially undertaken at the UCL Eastman Dental Institute, which received a proportion of funding from the Department of Health’s National Institute of Health Research (NIHR) Biomedical Research Centres funding scheme

The androgen receptor can signal through Wnt/β-Catenin in prostate cancer cells as an adaptation mechanism to castration levels of androgens

<p>Abstract</p> <p>Background</p> <p>A crucial event in Prostate Cancer progression is the conversion from a hormone-sensitive to a hormone-refractory disease state. Correlating with this transition, androgen receptor (AR) amplification and mutations are often observed in patients failing hormonal ablation therapies. β-Catenin, an essential component of the canonical Wnt signaling pathway, was shown to be a coactivator of the AR signaling in the presence of androgens. However, it is not yet clear what effect the increased levels of the AR could have on the Wnt signaling pathway in these hormone-refractory prostate cells.</p> <p>Results</p> <p>Transient transfections of several human prostate cancer cell lines with the AR and multiple components of the Wnt signaling pathway demonstrate that the AR overexpression can potentiate the transcriptional activities of Wnt/β-Catenin signaling. In addition, the simultaneous activation of the Wnt signaling pathway and overexpression of the AR promote prostate cancer cell growth and transformation at castration levels of androgens. Interestingly, the presence of physiological levels of androgen or other AR agonists inhibits these effects. These observations are consistent with the nuclear co-localization of the AR and β-Catenin shown by immunohistochemistry in human prostate cancer samples. Furthermore, chromatin immunoprecipitation assays showed that Wnt3A can recruit the AR to the promoter regions of Myc and Cyclin D1, which are well-characterized downstream targets of the Wnt signalling pathway. The same assays demonstrated that the AR and β-Catenin can be recruited to the promoter and enhancer regions of a known AR target gene PSA upon Wnt signaling. These results suggest that the AR is promoting Wnt signaling at the chromatin level.</p> <p>Conclusion</p> <p>Our findings suggest that the AR signaling through the Wnt/β-Catenin pathway should be added to the well established functional interactions between both pathways. Moreover, our data show that via this interaction the AR could promote prostate cell malignancy in a ligand-independent manner.</p

Host-parasite co-metabolic activation of antitrypanosomal aminomethyl-benzoxaboroles

<div><p>Recent development of benzoxaborole-based chemistry gave rise to a collection of compounds with great potential in targeting diverse infectious diseases, including human African Trypanosomiasis (HAT), a devastating neglected tropical disease. However, further medicinal development is largely restricted by a lack of insight into mechanism of action (MoA) in pathogenic kinetoplastids. We adopted a multidisciplinary approach, combining a high-throughput forward genetic screen with functional group focused chemical biological, structural biology and biochemical analyses, to tackle the complex MoAs of benzoxaboroles in <i>Trypanosoma brucei</i>. We describe an oxidative enzymatic pathway composed of host semicarbazide-sensitive amine oxidase and a trypanosomal aldehyde dehydrogenase TbALDH3. Two sequential reactions through this pathway serve as the key underlying mechanism for activating a series of 4-aminomethylphenoxy-benzoxaboroles as potent trypanocides; the methylamine parental compounds as pro-drugs are transformed first into intermediate aldehyde metabolites, and further into the carboxylate metabolites as effective forms. Moreover, comparative biochemical and crystallographic analyses elucidated the catalytic specificity of TbALDH3 towards the benzaldehyde benzoxaborole metabolites as xenogeneic substrates. Overall, this work proposes a novel drug activation mechanism dependent on both host and parasite metabolism of primary amine containing molecules, which contributes a new perspective to our understanding of the benzoxaborole MoA, and could be further exploited to improve the therapeutic index of antimicrobial compounds.</p></div

Taxonomy based on science is necessary for global conservation

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