Characterization of ovine hepatic gene expression profiles in response to Escherichia coli lipopolysaccharide using a bovine cDNA microarray

BACKGROUND: During systemic gram-negative bacterial infections, lipopolysaccharide (LPS) ligation to the hepatic Toll-like receptor-4 complex induces the production of hepatic acute phase proteins that are involved in the host response to infection and limit the associated inflammatory process. Identifying the genes that regulate this hepatic response to LPS in ruminants may provide insight into the pathogenesis of bacterial diseases and eventually facilitate breeding of more disease resistant animals. The objective of this research was to profile the expression of ovine hepatic genes in response to Escherichia coli LPS challenge (0, 200, 400 ng/kg) using a bovine cDNA microarray and quantitative real-time PCR (qRT-PCR). RESULTS: Twelve yearling ewes were challenged iv with E. coli LPS (0, 200, 400 ng/kg) and liver biopsies were collected 4–5 hours post-challenge to assess hepatic gene expression profiles by bovine cDNA microarray and qRT-PCR analyses. The expression of CD14, C3, IL12R, NRAMP1, SOD and IGFBP3 genes was down regulated, whereas the expression of ACTHR, IFNαR, CD1, MCP-1 and GH was increased during LPS challenge. With the exception of C3, qRT-PCR analysis of 7 of these genes confirmed the microarray results and demonstrated that GAPDH is not a suitable housekeeping gene in LPS challenged sheep. CONCLUSION: We have identified several potentially important genes by bovine cDNA microarray and qRT-PCR analyses that are differentially expressed during the ovine hepatic response to systemic LPS challenge. Their potential role in regulating the inflammatory response to LPS warrants further investigation

Polymorphisms in the gene encoding bovine interleukin-10 receptor alpha are associated with Mycobacterium avium ssp. paratuberculosis infection status

<p>Abstract</p> <p>Background</p> <p>Johne's disease is a chronic inflammatory bowel disease (IBD) of ruminants caused by <it>Mycobacterium avium </it>ssp. <it>paratuberculosis </it>(MAP). Since this pathogen has been implicated in the pathogenesis of human IBDs, the goal of this study was to assess whether single nucleotide polymorphism (SNPs) in several well-known candidate genes for human IBD are associated with susceptibility to MAP infection in dairy cattle.</p> <p>Methods</p> <p>The bovine candidate genes, <it>interleukin-10 (IL10), IL10 receptor alpha/beta (IL10RA/B), transforming growth factor beta 1 (TGFB1)</it>, <it>TGFB receptor class I/II (TGFBR1/2)</it>, and <it>natural resistance-associated macrophage protein 1 (SLC11A1) </it>were sequenced for SNP discovery using pooled DNA samples, and the identified SNPs were genotyped in a case-control association study comprised of 242 MAP negative and 204 MAP positive Holstein dairy cattle. Logistic regression was used to determine the association of SNPs and reconstructed haplotypes with MAP infection status.</p> <p>Results</p> <p>A total of 13 SNPs were identified. Four SNPs in <it>IL10RA </it>(984G > A, 1098C > T, 1269T > C, and 1302A > G) were tightly linked, and showed a strong additive and dominance relationship with MAP infection status. Haplotypes AGC and AAT, containing the SNPs <it>IL10RA </it>633C > A, 984G > A and 1185C > T, were associated with an elevated and reduced likelihood of positive diagnosis by serum ELISA, respectively.</p> <p>Conclusions</p> <p>SNPs in <it>IL10RA </it>are associated with MAP infection status in dairy cattle. The functional significance of these SNPs warrants further investigation.</p

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

When idiopathic multicentric Castleman disease meets COVID-19: a multicenter retrospective study from China

Idiopathic multicentric Castleman disease (iMCD) is a rare and cytokine storm-driven inflammatory disorder. The exact cause of iMCD is still unknown, although several hypotheses have been proposed. However, regardless of the underlying cause, the ultimate result is the activation of the inflammatory pathway, which can lead to damage in multiple organs. Currently, there have been several reports highlighting the intricate link between coronavirus disease 2019 (COVID-19) and iMCD. To better understand the impact of COVID-19-induced immune storm on iMCD, we conducted a multicenter retrospective study in three hospitals in China. A total of 28 patients with iMCD were included, among whom 25 had confirmed COVID-19 infection, and we presented 4 cases that showed different disease progression after the infection of COVID-19, including 2 who did not receive any treatment for Castleman disease before. Our findings underscore the necessity of carefully monitoring iMCD patients with COVID-19 and promptly intervening to address any changes in their condition. Besides, this study also summarized the shared cytokines between COVID-19 and iMCD. Recent studies have shown promising results in treating severe COVID-19 and iMCD using tocilizumab, an interleukin-6 receptor antagonist. Therefore, it suggests that other potential cytokine storm therapy targets that have been effective in COVID-19 may also be explored for the treatment of iMCD

Effects of different Chinese herbal prescriptions on cytokines in autoimmune prostatitis rats

AbstractObjectiveTo observe and compare the effects of Chinese herbal prescriptions for promoting blood circulation, clearing heat, removing toxicity, and dispersing stagnated liver-Qi on cytokines in model rats with experimental autoimmune prostatitis (EAP) to provide an experimental basis for the use of Chinese herbal prescriptions in the treatment of chronic prostatitis.MethodsOne-hundred and ten male Wistar rats were randomly divided into 11 groups: blank group; model group; Huoxuehuayu (promoting blood circulation to remove blood stasis) high, middle, and low dose groups; Qingrejiedu (clearing heat and removing toxicity) high, middle, and low dose groups; and Shuganliqi (dispersing stagnated liver-Qi) high, middle, and low dose groups. Except the blank group, rats in all groups were injected subcutaneously in multiple points on days 0 and 30 with prostatic protein extractive solution (60 mg/mL), and intraperitoneally injected with diphtheria-pertussis and tetanus vaccine (DPT vaccine) to establish the EAP model. Model rats were administrated high, middle, and low doses of Chinese herbal prescriptions and were sacrificed after 4 weeks. Pathological changes in the prostate gland were observed with HE staining and changes in serum interleukin-6 (IL-6), interleukin-8 (IL-8), and prostaglandin E2 (PGE2) levels were detected with enzyme-linked immunosorbent assay.ResultsCompared with the blank group, serum PGE2, IL-6, and IL-8 levels in the model group were significantly higher (P < 0.05). Compared with the model group, serum PGE2, IL-6, and IL-8 levels in the Qingrejiedu low dose and middle dose groups were significantly lower (P < 0.05), with the lower dose having a more obvious effect. Serum PGE2, IL-6, and IL-8 levels in the Huoxuehuayu high dose group (P < 0.05), IL-6 and IL-8 levels in the Huoxuehuayu middle dose group (P < 0.05), and the IL-8 level in the Huoxuehuayu low dose group were significantly lower than those in the model group (P < 0.05). There were significant differences in PGE2 and IL-6 levels among the different dose groups of Shuganliqi drugs (P < 0.05). Compared with the model group, serum PGE2, IL-6, and IL-8 levels in the Shuganliqi high dose group (P < 0.05) and IL-8 level in the Shuganliqi low dose group were significantly lower (P < 0.05), while the Shuganliqi middle dose group did not change significantly (P > 0.05).ConclusionTherefore, in TCM treatment of autoimmune prostatitis, different treatment methods should select different doses. For prescriptions that clear heat and remove toxicity, low doses should be used. For prescriptions that promote blood circulation to remove blood stasis and for prescriptions that disperse stagnated liver-Qi, high doses should be used