Preferential Binding to Elk-1 by SLE-Associated <i>IL10</i> Risk Allele Upregulates <i>IL10</i> Expression

Sakurai, Daisuke,Zhao, Jian,Deng, Yun,Kelly, Jennifer A.,Brown, Elizabeth E.,Harley, John B.,Bae, Sang-Cheol,Alarc&#x3cc,n-Riquelme, Marta E.,Edberg, Jeffrey C.,Kimberly, Robert P.,Ramsey-Goldman, Ros Public Library of Science 2013 PLoS genetics Vol.9 No.10

<▼1><P>Immunoregulatory cytokine interleukin-10 (IL-10) is elevated in sera from patients with systemic lupus erythematosus (SLE) correlating with disease activity. The established association of <I>IL10</I> with SLE and other autoimmune diseases led us to fine map causal variant(s) and to explore underlying mechanisms. We assessed 19 tag SNPs, covering the <I>IL10</I> gene cluster including <I>IL19</I>, <I>IL20</I> and <I>IL24</I>, for association with SLE in 15,533 case and control subjects from four ancestries. The previously reported <I>IL10</I> variant, rs3024505 located at 1 kb downstream of <I>IL10</I>, exhibited the strongest association signal and was confirmed for association with SLE in European American (EA) (<I>P</I> = 2.7×10<SUP>−8</SUP>, OR = 1.30), but not in non-EA ancestries. SNP imputation conducted in EA dataset identified three additional SLE-associated SNPs tagged by rs3024505 (rs3122605, rs3024493 and rs3024495 located at 9.2 kb upstream, intron 3 and 4 of <I>IL10</I>, respectively), and SLE-risk alleles of these SNPs were dose-dependently associated with elevated levels of <I>IL10</I> mRNA in PBMCs and circulating IL-10 protein in SLE patients and controls. Using nuclear extracts of peripheral blood cells from SLE patients for electrophoretic mobility shift assays, we identified specific binding of transcription factor Elk-1 to oligodeoxynucleotides containing the risk (G) allele of rs3122605, suggesting rs3122605 as the most likely causal variant regulating <I>IL10</I> expression. Elk-1 is known to be activated by phosphorylation and nuclear localization to induce transcription. Of interest, phosphorylated Elk-1 (p-Elk-1) detected only in nuclear extracts of SLE PBMCs appeared to increase with disease activity. Co-expression levels of p-Elk-1 and IL-10 were elevated in SLE T, B cells and monocytes, associated with increased disease activity in SLE B cells, and were best downregulated by ERK inhibitor. Taken together, our data suggest that preferential binding of activated Elk-1 to the <I>IL10</I> rs3122605-G allele upregulates <I>IL10</I> expression and confers increased risk for SLE in European Americans.</P></▼1><▼2><P><B>Author Summary</B></P><P>Systemic lupus erythematosus (SLE), a debilitating autoimmune disease characterized by the production of pathogenic autoantibodies, has a strong genetic basis. Variants of the <I>IL10</I> gene, which encodes cytokine interleukin-10 (IL-10) with known function of promoting B cell hyperactivity and autoantibody production, are associated with SLE and other autoimmune diseases, and serum IL-10 levels are elevated in SLE patients correlating with increased disease activity. In this study, to discover SLE-predisposing causal variant(s), we assessed variants within the genomic region containing <I>IL10</I> and its gene family member <I>IL19</I>, <I>IL20</I> and <I>IL24</I> for association with SLE in case and control subjects from diverse ancestries. We identified SLE-associated SNP rs3122605 located at 9.2 kb upstream of <I>IL10</I> as the most likely causal variant in subjects of European ancestry. The SLE-risk allele of rs3122605 was dose-dependently associated with elevated <I>IL10</I> expression at both mRNA and protein levels in peripheral blood samples from SLE patients and controls, which could be explained, at least in part, by its preferential binding to Elk-1, a transcription factor activated in B cells during active disease of SLE patients. Elk-1-mediated IL-10 overexpression could be downregulated by inhibiting activation of mitogen-activated protein kinases, suggesting a potential therapeutic target for SLE.</P></▼2>

Dependence of the properties of hydrothermally grown ZnO on precursor concentration

Zhao, X.,Lee, J.Y.,Kim, C.-R.,Heo, J.,Shin, C.M.,Leem, J.-Y.,Ryu, H.,Chang, J.-H.,Lee, H.C.,Jung, W.-G.,Son, C.-S.,Shin, B.C.,Lee, W.-J.,Tan, S.T.,Zhao, J.,Sun, X. North-Holland 2009 Physica E, Low-dimensional systems & nanostructure Vol.41 No.8

This study evaluated the effects of precursor concentration ranging from 0.06 to 1.5M on the properties of hydrothermally grown ZnO on annealed ZnO buffered Si substrates. At relatively low concentrations (no more than 0.5M), well-aligned ZnO arrays were grown on ZnO/Si(100) due to heterogeneous nucleation. As the concentration was increased to 1.0M, the morphologies changed to randomly accumulated particles as a result of homogeneous nucleation. The crystal and optical properties of the materials were investigated by X-ray diffractometer (XRD) and photoluminescence (PL) measurement, respectively. It was found that the best crystal and optical properties were obtained with concentrations of 0.5 and 0.3M, respectively. These properties were observed to degrade when the concentration was raised to more than 1.0M.

Transcriptomic profiling reveals hepatic stem‐like gene signatures and interplay of miR‐200c and epithelial‐mesenchymal transition in intrahepatic cholangiocarcinoma

Oishi, Naoki,Kumar, Mia R.,Roessler, Stephanie,Ji, Junfang,Forgues, Marshonna,Budhu, Anuradha,Zhao, Xuelian,Andersen, Jesper B.,Ye, Qing&#x2010,Hai,Jia, Hu&#x2010,Liang,Qin, Lun&#x2010,Xiu,Yamashita, Wiley Subscription Services, Inc., A Wiley Company 2012 Hepatology Vol.56 No.5

<P><B>Abstract</B></P><P>Intrahepatic cholangiocellular carcinoma (ICC) is the second most common type of primary liver cancer. However, its tumor heterogeneity and molecular characteristics are largely unknown. In this study, we conducted transcriptomic profiling of 23 ICC and combined hepatocellular cholangiocarcinoma tumor specimens from Asian patients using Affymetrix messenger RNA (mRNA) and NanoString microRNA microarrays to search for unique gene signatures linked to tumor subtypes and patient prognosis. We validated the signatures in an additional 68 ICC cases derived from Caucasian patients. We found that both mRNA and microRNA expression profiles could independently classify Asian ICC cases into two main subgroups, one of which shared gene expression signatures with previously identified hepatocellular carcinoma (HCC) with stem cell gene expression traits. ICC‐specific gene signatures could predict survival in Asian HCC cases and independently in Caucasian ICC cases. Integrative analyses of the ICC‐specific mRNA and microRNA expression profiles revealed that a common signaling pathway linking miR‐200c signaling to epithelial‐mesenchymal transition (EMT) was preferentially activated in ICC with stem cell gene expression traits. Inactivation of miR‐200c resulted in an induction of EMT, whereas activation of miR‐200c led to a reduction of EMT including a reduced cell migration and invasion in ICC cells. We also found that miR‐200c and neural cell adhesion molecule 1 (NCAM1) expression were negatively correlated and their expression levels were predictive of survival in ICC samples. NCAM1, a known hepatic stem/progenitor cell marker, was experimentally demonstrated to be a direct target of miR‐200c. Conclusion: Our results indicate that ICC and HCC share common stem‐like molecular characteristics and poor prognosis. We suggest that the specific components of EMT may be exploited as critical biomarkers and clinically relevant therapeutic targets for an aggressive form of stem cell‐like ICC. (H<SMALL>EPATOLOGY</SMALL> 2012;56:1792–1803)</P>

Influence of Microstructure Evolution on Mechanical Properties, Wear Resistance and Corrosion Resistance of Ti(C,N)-Based Cermet Tools with Various WC Additions

L. B. Zhao,N. Lin,X. Q. Han,C. Ma,Z. Y. Wang,Y. H. He 대한금속·재료학회 2021 METALS AND MATERIALS International Vol.27 No.8

The efects of tungsten carbide addition on the microstructure, mechanical properties and corrosion resistance of Ti(C,N)-based cermets prepared by the sinter-HIP method are investigated through scanning electron microscope, X-ray difraction,electron back scattered difraction, mechanical test and electrochemical method. The results show that the appropriate WCaddition has an important infuence on promoting the formation of core-rim microstructure of cermet, increasing the wettability of ceramic phase and binder phase, and improving the mechanical properties. Ti(C,N)-based cermet with 5 wt% WCaddition has the highest hardness of 92.4 HRA and excellent wear resistance. However, excessive WC addition causes theappearance of slight white core phase containing plenty of W and Ti element in microstructure, which increases the fracturetoughness, and reduces the hardness and wear resistance of cermet. Additionally, the electrochemical result shows that theaddition of 5 wt% WC in cermet has the optimal corrosion resistance in 1 mol/L hydrochloric acid solution.

Effects of galacto-oligosaccharides and a bifidobacteria lactis-based probiotic strain on the growth performance and fecal microflora of broiler chickens.

Jung, S J,Houde, R,Baurhoo, B,Zhao, X,Lee, B H Poultry Science Association, etc 2008 Poultry science Vol.87 No.9

<P>A galacto-oligosaccharide (GOS) prebiotic was prepared by reacting a high concentration of lactose (40% wt/vol) with a beta-galactosidase enzyme for 24 h at 37 degrees C. The enzyme was produced from recombinant Pichia pastoris X-33 cells. The study aimed at evaluating the effects of the prebiotic, a Bifidobacterium lactis-based probiotic, and the combination of these dietary additives on BW, feed intake, feed conversion ratio, and fecal counts of total anaerobic bacteria, lactobacilli, and bifidobacteria in broiler chickens. No significant differences in BW, feed intake and feed conversion ratio were found among the various groups. The study showed that GOS selectively stimulated the fecal microflora of broiler chickens. Total anaerobic bacteria and lactobacilli were increased by 3.4- and 3.56-fold, respectively, in chickens fed the diet containing GOS (3 kg per 25 kg) and B. lactis for 40 d compared with those fed the control diet. The bifidobacteria population in chickens fed the diet containing GOS (3 kg per 25 kg) and B. lactis significantly increased 21-fold in comparison to the control-fed birds. In particular, increasing the dietary concentration of GOS was accompanied by significant increases (P < 0.05) in bifidobacteria counts. The detectable population of bifidobacteria was also greater (P < 0.05) in chickens fed the diet containing GOS and bifidobacteria when compared with chickens fed a bifidobacteria-containing ration only. These results suggest that using GOS in combination with a B. lactis-based probiotic favored intestinal growth of bifidobacteria in broiler chickens.</P>

Influences of the Irradiation of Intense Pulsed Ion Beam (IPIB) on the Surface of Ni₃Al Base Alloy IC6

X. Y. Le,S. Yan,W. J. Zhao,B. H. Han,Y. G. Wang,J. M. Xue,H. T. Zhang 한국진공학회(ASCT) 2002 Journal of Korean Vacuum Science & Technology Vol.6 No.2

In this paper, we treated the Ni₃Al based alloy samples with intense pulsed ion beams (IPIB) at the beam parameters of 250KV acceleration voltage, 100 - 200 A/㎤ current density and 60 ㎱ pulse duration. We simulated the thermal-mechanical process near the surface of Ni₃Al based alloy with our STEIPIB codes. The surface morphology and the cross-section microstructures of samples were observed with SEM, the composition of the sample surface layer was determined by X-ray Energy Dispersive Spectrometry (XEDS) and the microstructure on the surface was observed by Transmission Electron Microscope (TEM). The results show that heating rate increases with the current density of IPIB and cooling rate reached highest value less than 150 A/㎤. The irradiation of IPIB induced the segregation of Mo and adequate beam parameter can improve anti-oxidation property of IC6 alloy. Some craters come from extraneous debris and liquid droplets, and some maybe due to the melting of the intersection region of interphase. Increasing the pulse number enlarges average size of craters and decreases number density of craters.

Improvement of lower hybrid current drive systems for high-power and long-pulse operation on EAST

Wang M.,Liu L.,Zhao L.M.,Li M.H.,Ma W.D.,Hu H.C.,Wu Z.G.,Feng J.Q.,Yang Y.,Zhu L.,Chen M.,Zhou T.A.,Jia H.,Zhang J.,Cao L.,Zhang L.,Liang R.R.,Ding B.J.,Zhang X.J.,Shan J.F.,Liu F.K.,Ekedahl A.,Gonich 한국원자력학회 2022 Nuclear Engineering and Technology Vol.54 No.11

Aiming at high-power and long-pulse operation up to 1000 s, some improvements have been made for both 2.45 GHz and 4.6 GHz lower hybrid (LH) systems during the recent 5 years. At first, the guard limiters of the LH antennas with graphite tiles were upgraded to tungsten, the most promising material for plasma facing components in nuclear fusion devices. These new guard limiters can operate at a peak power density of 12.9 MW/m2 . Strong hot spots were usually observed on the old graphite limiters when 4.6 GHz system operated with power >2.0 MW [B. N. Wan et al., Nucl. Fusion 57 (2017) 102019], leading to a reduction of the maximum power capability. With the new limiters, 4.6 GHz LH system, the main current drive (CD) and electron heating tool for EAST, can be operated with power >2.5 MW routinely. Long-pulse operation up to 100 s with 4.6 GHz LH power of 2.4 MW was achieved in 2021 and the maximal temperature on the guard limiters measured by an infrared (IR) camera was about 540 C, much below the permissible value of tungsten material (~1200 C). A discharge with a duration of 1056 s was achieved and the 4.6 GHz LH energy injected into the plasma was up to 1.05 GJ. Secondly, the fully-activemultijunction (FAM) launcher of 2.45 GHz system was upgraded to a passive-active-multijunction (PAM), for which the density of optimum coupling was relatively low (below the cut-off value). Good coupling with reflection coefficient ~3% has been achieved with plasma-antenna distance up to 11 cm for the new PAM. Finally, in order to eliminate the effect of ion cyclotron range of frequencies (ICRF) wave on 4.6 GHz LH wave coupling, the location of the ICRF launcher was changed to a port that is located 157.5 toroidally from the 4.6 GHz LH system and is not magnetically connected

Effects of L-tryptophan, Fructan, and Casein on Reducing Ammonia, Hydrogen Sulfide, and Skatole in Fermented Swine Manure

Q.K. Sheng,Z.J. Yang,H.B. Zhao,X.L. Wang,J.F. Guo 아세아·태평양축산학회 2015 Animal Bioscience Vol.28 No.8

The effects of daily dietary Bacillus subtilis (Bs), and adding L-tryptophan, fructan, or casein to fecal fermentation broths were investigated as means to reduce the production of noxious gas during manure fermentation caused by ammonia, hydrogen sulfide (H2S), and 3-methylindole (skatole). Eighty swine (50.0±0.5 kg) were equally apportioned to an experimental group given Bs in daily feed, or a control group without Bs. After 6 weeks, fresh manure was collected from both groups for fermentation studies using a 3×3 orthogonal array, in which tryptophan, casein, and fructan were added at various concentrations. After fermentation, the ammonia, H2S, L-tryptophan, skatole, and microflora were measured. In both groups, L-tryptophan was the principle additive increasing skatole production, with significant correlation (r = 0.9992). L-tryptophan had no effect on the production of ammonia, H2S, or skatole in animals fed Bs. In both groups, fructan was the principle additive that reduced H2S production (r = 0.9981). Fructan and Bs significantly interacted in H2S production (p = 0.014). Casein was the principle additive affecting the concentration of ammonia, only in the control group. Casein and Bs significantly interacted in ammonia production (p = 0.039). The predominant bacteria were Bacillus spp. CWBI B1434 (26%) in the control group, and Streptococcus alactolyticus AF201899 (36%) in the experimental group. In summary, daily dietary Bs reduced ammonia production during fecal fermentation. Lessening L-tryptophan and increasing fructan in the fermentation broth reduced skatole and H2S.

Effects of L-tryptophan, Fructan, and Casein on Reducing Ammonia, Hydrogen Sulfide, and Skatole in Fermented Swine Manure

Sheng, Q.K.,Yang, Z.J.,Zhao, H.B.,Wang, X.L.,Guo, J.F. Asian Australasian Association of Animal Productio 2015 Animal Bioscience Vol.28 No.8

The effects of daily dietary Bacillus subtilis (Bs), and adding L-tryptophan, fructan, or casein to fecal fermentation broths were investigated as means to reduce the production of noxious gas during manure fermentation caused by ammonia, hydrogen sulfide ($H_2S$), and 3-methylindole (skatole). Eighty swine ($50.0{\pm}0.5kg$) were equally apportioned to an experimental group given Bs in daily feed, or a control group without Bs. After 6 weeks, fresh manure was collected from both groups for fermentation studies using a $3{\times}3$ orthogonal array, in which tryptophan, casein, and fructan were added at various concentrations. After fermentation, the ammonia, $H_2S$, L-tryptophan, skatole, and microflora were measured. In both groups, L-tryptophan was the principle additive increasing skatole production, with significant correlation (r = 0.9992). L-tryptophan had no effect on the production of ammonia, $H_2S$, or skatole in animals fed Bs. In both groups, fructan was the principle additive that reduced $H_2S$ production (r = 0.9981). Fructan and Bs significantly interacted in $H_2S$ production (p = 0.014). Casein was the principle additive affecting the concentration of ammonia, only in the control group. Casein and Bs significantly interacted in ammonia production (p = 0.039). The predominant bacteria were Bacillus spp. CWBI B1434 (26%) in the control group, and Streptococcus alactolyticus AF201899 (36%) in the experimental group. In summary, daily dietary Bs reduced ammonia production during fecal fermentation. Lessening L-tryptophan and increasing fructan in the fermentation broth reduced skatole and $H_2S$.

Unusual magnetic order in the pseudogap region of the superconductor HgBa₂CuO_4+δ

Li, Y.,Balé,dent, V.,Bari&#x161,i&#x107,, N.,Cho, Y.,Fauqué,, B.,Sidis, Y.,Yu, G.,Zhao, X.,Bourges, P.,Greven, M. Macmillan Publishers Limited. All rights reserved 2008 Nature Vol.455 No.7211

The pseudogap region of the phase diagram is an important unsolved puzzle in the field of high-transition-temperature (high-T<SUB>c</SUB>) superconductivity, characterized by anomalous physical properties. There are open questions about the number of distinct phases and the possible presence of a quantum-critical point underneath the superconducting dome. The picture has remained unclear because there has not been conclusive evidence for a new type of order. Neutron scattering measurements for YBa<SUB>2</SUB>Cu<SUB>3</SUB>O<SUB>6+δ</SUB> (YBCO) resulted in contradictory claims of no and weak magnetic order, and the interpretation of muon spin relaxation measurements on YBCO and of circularly polarized photoemission experiments on Bi<SUB>2</SUB>Sr<SUB>2</SUB>CaCu<SUB>2</SUB>O<SUB>8+δ</SUB>(refs 12, 13) has been controversial. Here we use polarized neutron diffraction to demonstrate for the model superconductor HgBa<SUB>2</SUB>CuO<SUB>4+δ</SUB> (Hg1201) that the characteristic temperature T* marks the onset of an unusual magnetic order. Together with recent results for YBCO, this observation constitutes a demonstration of the universal existence of such a state. The findings appear to rule out theories that regard T* as a crossover temperature rather than a phase transition temperature. Instead, they are consistent with a variant of previously proposed charge-current-loop order that involves apical oxygen orbitals, and with the notion that many of the unusual properties arise from the presence of a quantum-critical point.