Large Logarithms in the Beam Normal Spin Asymmetry of Elastic Electron--Proton Scattering

We study a parity-conserving single-spin beam asymmetry of elastic electron-proton scattering induced by an absorptive part of the two-photon exchange amplitude. It is demonstrated that excitation of inelastic hadronic intermediate states by the consecutive exchange of two photons leads to logarithmic and double-logarithmic enhancement due to contributions of hard collinear quasi-real photons. The asymmetry at small electron scattering angles is expressed in terms of the total photoproduction cross section on the proton, and is predicted to reach the magnitude of 20-30 parts per million. At these conditions and fixed 4-momentum transfers, the asymmetry is rising logarithmically with increasing electron beam energy, following the high-energy diffractive behavior of total photoproduction cross section on the proton.Comment: 10 pages, 6 figures; typos fixed, a reference adde

p53-paralog DNp73 oncogene is repressed by IFNα/STAT2 through the recruitment of the Ezh2 polycomb group transcriptional repressor

The DNp73 proteins act as trans-repressors of p53 and p73-dependent transcription and exert both anti-apoptotic activity and pro-proliferative activity. DNp73s are frequently up-regulated in a variety of human cancers, including human hepatocellular carcinomas (HCCs). Increased levels of DNp73 proteins confer to HCC cells resistance to apoptosis and, irrespective to p53 status, a chemoresistant phenotype. Here, we show that interferon (IFN)α down-regulates DNp73 expression in primary human hepatocytes (PHHs) and HCC cell lines. IFNα has been used as pro-apoptotic agent in the treatment of malignancies and there is increasing evidence of IFNα effectiveness in HCC treatment and prevention of recurrence. The precise mechanisms by which class I IFNs exert their anti-proliferative and anti-tumor activity remain unclear. IFNα binding to its receptor activates multiple intracellular signaling cascades regulating the transcription of numerous direct target genes through the recruitment of a complex comprising of STAT1, STAT2 and IFN regulatory factor (IRF)9 to their promoters. We found that, in response to IFNα, the P2p73 promoter undergoes substantial chromatin remodeling. Histone deacetylases (HDACs) replace histone acetyl transferases. STAT2 is recruited onto the endogenous P2p73 promoter together with the polycomb group protein Ezh2, leading to increased H3K27 methylation and transcriptional repression. The reduction of DNp73 levels by IFNα is paralleled by an increased susceptibility to IFNα-triggered apoptosis of Huh7 hepatoma cells. Our results show, for the first time, that IFN-stimulated gene factor 3 recruitment may serve both in activating and repressing gene expression and identify the down-regulation of DNp73 as an additional mechanism to counteract the chemoresistance of liver cancer cells

Rethinking soil water repellency and its management

Soil water repellency (SWR) is a widespread challenge to plant establishment and growth. Despite considerable research, it remains a recalcitrant problem for which few alleviation technologies or solutions have been developed. Previous research has focused on SWR as a problem to be overcome, however, it is an inherent feature of many native ecosystems where it contributes to ecosystem functions. Therefore, we propose a shift in the way SWR is perceived in agriculture and in ecological restoration, from a problem to be solved, to an opportunity to be harnessed. A new focus on potential ecological benefits of SWR is particularly timely given increasing incidence, frequency and severity of hotter droughts in many regions of the world. Our new way of conceptualising SWR seeks to understand how SWR can be temporarily alleviated at a micro-scale to successfully establish plants, and then harnessed in the longer term and at larger spatial scales to enhance soil water storage to act as a “drought-proofing” tool for plant survival in water-limited soils. For this to occur, we suggest research focusing on the alignment of physico-chemical and microbial properties and dynamics of SWR and, based on this mechanistic understanding, create products and interventions to improve success of plant establishment in agriculture, restoration and conservation contexts. In this paper, we outline the rationale for a new way of conceptualising SWR, and the research priorities needed to fill critical knowledge gaps in order to harness the ecological benefits from managing SWR

PSG does not require IL-4Rα signalling to exacerbate cutaneous leishmaniasis in mice.

<p>A and B) Footpad infections of WT (A) and IL-4Rα^-/- (B) BALB/c mice with 1 x 10³ <i>L</i>. <i>mexicana</i> metacyclic promastigotes intradermally injected with PBS or 0.5 μg <i>L</i>. <i>mexicana</i> PSG, 6 mice per group. C) Final parasite burdens of footpads from B) at the end of the experiment (WT: 80 d post-infection, IL-4Rα^-/-: 151 d post-infection). Data pooled from two replicate experiments. A&B) Averages ±SEM are shown, C) Each point represent individual mice, bars indicate the mean (*: p<0.05; **: p<0.005; ***: p<0.0005 by Mann Whitney <i>t</i>-test).</p

PSG improves wound healing <i>in vitro</i> and in skin.

<p>Monolayers of L929 fibroblasts were scratched in the presence of culture media supplemented with or without 0.5 μg/ml <i>L</i>. <i>mexicana</i> PSG. Positive controls were treated with 10 μg/ml TGFβ2 and 10 μg/ml EGF. A) At 0, 12 and 24 hours post-wound, photomicrographs were taken and scratch closure was determined from using ImageJ. B) Representative images for the closure of a PSG-treated scratch. C) In replicate experiments, cell proliferation of fibroblasts was determined by measuring the incorporation of the fluorescent thymidine analogue, BrdU. Statistical analyses were performed between Media vs. PSG at each time point. Each in condition was performed in quadruplicate, data is pooled from 3 experiments. D) Daily wound closure following intradermal injection of PBS (open symbols) or 0.5 μg <i>L</i>. <i>mexicana</i> PSG (closed symbols) in the ears of BALB/c mice. Ears were wounded with a 2 mm diameter full-thickness ear punch 6 hours after the intra-dermal injection of PBS or PSG. Inset photographs are ears representative of each group at day 10 post-wound. Average wound closure ±SEM is shown from 12 mice per group (*: p<0.05; **: p<0.005; ***: p<0.0005 by Mann Whitney <i>t</i>-test); data is pooled from duplicate experiments.</p

Insulin-like growth factor 1-signalling controls the wound healing and <i>Leishmania</i>-exacerbating properties of PSG in mice.

<p>A) Rate of 2 mm diameter wound closure in BALB/c ears preconditioned with PBS, 0.5 μg <i>L</i>. <i>mexicana</i> PSG or 0.5 μg <i>L</i>. <i>mexicana</i> PSG + 1:50 anti-IGF1R antibody, 12 mice per group. B) Single <i>L</i>. <i>mexicana</i>-infected sand fly bite infections in footpads of BALB/c mice treated with or without 1:50 anti-IGF1R antibody, 6 mice per group. C) Final parasite burdens of footpads from B) at the end of the experiment. Data pooled from two replicate experiments. A&B) Averages ±SEM are shown, C) Each point represent individual mice, bars indicate the mean (*: p<0.05; **: p<0.005; ***: p<0.0005 by Mann Whitney <i>t</i>-test).</p

PSG enhances IGF1 expression in skin following an infected fly bite and enhances macrophage alternative activation.

<p>A) IGF1, IGF1R and IL-10 expression in BALB/c mouse ears 6 hours post-bite from single uninfected or <i>L</i>. <i>mexicana</i>-infected <i>Lu</i>. <i>longipalpis</i> sand flies (Day 8 post-infection), one bite per ear (12 uninfected bites, 35 infected bites). B) IGF1, IGF1R and IL-10 expression in bitten ears in relation to the dose of transmitted parasites, determined from <i>Leishmania ssrRNA</i> expression in ears. C) IGF1, IGF1R and IL-10 expression in BALB/c ears 6 hours following intradermal injection of with PBS, 0.5 μg <i>L</i>. <i>mexicana</i> PSG, 0.5 μg <i>Lu</i>. <i>longipalpis</i> saliva or PSG and saliva combined. Data is pooled from duplicate experiments with 12 mice per group. Relative expression was normalised to the housekeeping genes <i>nono</i> and <i>l19</i> and is presented as the mean ±SD (*: p<0.05, **: p<0.005 by Mann Whitney <i>t</i>-test).</p