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Fernandez-Ayala, Daniel J.M.,Sanz, Alberto,Vartiainen, Suvi,Kemppainen, Kia K.,Babusiak, Marek,Mustalahti, Eero,Costa, Rodolfo,Tuomela, Tea,Zeviani, Massimo,Chung, Jongkyeong,O'Dell, Kevin M.C.,Rustin Elsevier 2009 Cell metabolism Vol.9 No.5
<P><B>Summary</B></P><P>Defects in mitochondrial OXPHOS are associated with diverse and mostly intractable human disorders. The single-subunit alternative oxidase (AOX) found in many eukaryotes, but not in arthropods or vertebrates, offers a potential bypass of the OXPHOS cytochrome chain under conditions of pathological OXPHOS inhibition. We have engineered <I>Ciona intestinalis</I> AOX for conditional expression in <I>Drosophila melanogaster.</I> Ubiquitous AOX expression produced no detrimental phenotype in wild-type flies. However, mitochondrial suspensions from AOX-expressing flies exhibited a significant cyanide-resistant substrate oxidation, and the flies were partially resistant to both cyanide and antimycin. AOX expression was able to complement the semilethality of partial knockdown of both <I>cyclope</I> (COXVIc) and the complex IV assembly factor <I>Surf1</I>. It also rescued the locomotor defect and excess mitochondrial ROS production of flies mutated in <I>dj-1</I>β, a <I>Drosophila</I> homolog of the human Parkinson's disease gene <I>DJ1</I>. AOX appears to offer promise as a wide-spectrum therapeutic tool in OXPHOS disorders.</P>
Upregulation of duck interleukin-17A during Riemerella anatipestifer infection
Fernandez, C.P.,Kim, W.H.,Diaz, J.A.R.,Jeong, J.,Afrin, F.,Kim, S.,Jang, H.K.,Lee, B.H.,Yim, D.,Lillehoj, H.S.,Min, W. Pergamon Press ; Elsevier Science 2016 DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY Vol.63 No.-
<P>Although IL-17 cytokines play critical roles in host defense immunity, dysregulated expression of these cytokines is associated with inflammation and autoimmune diseases. Riemerella anatipestifer is the most important infectious bacterium in the duck industry. Interestingly, not all avian species are equally susceptible to R. anatipestifer infection. This paper reports the first description of mortality rate, bacterial burden, and expression profiles of immune-related genes between ducks and chickens infected with R. anatipestifer. Ducks exhibited increased susceptibility to R. anatipestifer infection compared to chickens, as determined by mortality rate and bacterial burden. Comparative expression analyses of immune-related genes in R. anatipestifer-infected tissues obtained from both species revealed that TLR3, TLR7, IL-2, IL-4, and IFN-gamma transcript levels were higher in chickens, whereas TLR4 and IL-17A transcript levels were higher in ducks. Marked increases in expression of IL-17A and IL-6, but not TGF-beta, were associated with Th17 cell differentiation in duck splenic lymphocytes, but not in chicken splenic lymphocytes, stimulated with R. anatipestifer. Moreover, upregulation of IL-1 beta, IL-6, and IL-17A mRNA expressions, but not TGF-beta, was confirmed in the liver and spleen of ducks infected with R. anatipestifer, indicating that IL-17A is strongly associated with Riemerella infection in ducks. (C) 2016 Elsevier Ltd. All rights reserved.</P>
Different strategies for producing naturally soluble form of common cytokine receptor γ chain
Jeong, J.,Kim, W.H.,Fernandez, C.P.,Kim, S.,Kim, Y.H.,Jang, H.K.,Lillehoj, H.S.,Woo, H.J.,Min, W. Pergamon Press ; Elsevier Science 2015 DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY Vol.48 No.1
<P>The common cytokine receptor gamma chain (gamma(c)) plays an essential role in regulating lymphoid homeostasis. In fact, alteration of this gene causes severe immunodeficiency in humans and animals. Although soluble gamma(c) (s gamma(c)) was identified in the late 1990s, much remains unknown about its production. This study describes various mechanisms underlying the generation of s gamma(c) isoforms in different species. Our data demonstrate that mouse gamma(c) and the avian ortholog gamma(c)-a did not generate s gamma(c). Moreover, two mouse isoforms, CRA-a and m gamma(c)-b, encoded by transcripts lacking a transmembrane region by alternative splicing, did not yield s gamma(c). However, in ducks, s gamma(c) was produced from a gamma(c)-b transcript lacking a transmembrane region by alternative splicing. In chickens, s gamma(c) was produced in normal cells and cell lines by proteolytic shedding of the gamma(c)-b isoform containing intron 5, which displayed a relatively high probability of proteolytic cleavage of the ectodomain. This shedding was suppressed by leupeptin, serine and cysteine protease inhibitor. Compared to the chicken ortholog gamma(c)-a, expression of gamma(c)-b mRNA was differentially regulated according to tissue type, developmental stage, and antigen stimulation. These data demonstrate several mechanisms for producing s gamma(c) and suggest a potential role for s gamma(c) in avian lymphoid homeostatic responses to environmental antigens. (C) 2014 Elsevier Ltd. All rights reserved.</P>
Identification and expression analysis of duck interleukin-17D in Riemerella anatipestifer infection
Diaz, J.A.R.,Kim, W.H.,Fernandez, C.P.,Jeong, J.,Afrin, F.,Lillehoj, H.S.,Kim, S.,Kim, S.,Dalloul, R.A.,Min, W. Pergamon Press ; Elsevier Science 2016 DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY Vol.61 No.-
<P>Interleukin (IL)-17D is a proinfiammatory cytokine with currently largely unknown biological functions. Here we provide the description of the sequence, bioactivity, and mRNA expression profile of duck IL-17D homologue. A full-length duck IL-17D (duIL-17D) cDNA with a 624-bp coding region was identified from the large intestine. dull-17D shares approximately 94.7% identity with its chicken counterpart, which is also identified in this work. duIL-17D exhibits 62.6-68.4% and 52.1-53.1% identity with mammalian and piscine homologues. Recombinant duIL-17D promoted the expression of proinfiammatory cytokines such as IL-6, IL-8, and IL-1 beta in duck embryo fibroblast cells. Very low levels of dull-17D transcript were observed in healthy lymphoid tissues, including bursa, thymus, and spleen, while duIL-17D expression was relatively high in the heart. The dull-17D expression profiles were examined in mitogen-stimulated splenic lymphocytes, as well as tissues affected by Riemerella anatipestifer infection. The levels of duIL-17D were mostly upregulated in mitogen-activated splenic lymphocytes but downregulated in the liver and spleen of R. anatipestifer-infected ducks. These results provide new insights into the roles of IL-17D in host protective immune responses to Riemerella infection, which can therefore lead to further studies of its biological functions in different disease models of ducks and other avian species. (C) 2016 Elsevier Ltd. All rights reserved.</P>
Identification of alternatively spliced isoforms of interleukin-2/15 receptor β chain in ducks
Jeong, J.,Kim, W.H.,Yeo, J.,Fernandez, C.P.,Kim, S.,Lee, Y.J.,Lillehoj, H.S.,Min, W. Elsevier 2014 Veterinary immunology and immunopathology Vol. No.
Interleukin (IL)-2 and IL-15 receptor β (IL-2/15Rβ, CD122) play important roles in signal transduction for biological functions of IL-2 and IL-15. We found that ducks possess three different IL-2/15Rβ transcripts, a conventional form (duIL-2/15Rβ) and two variants. Comparisons between the cDNA and genomic sequences revealed that the two variants, duIL-2/15Rβ-d7 and duIL-2/15Rβ-d9, were novel spliced transcripts resulting from skipping exons 7 and 9, respectively. Expression profiles of duIL-2/15Rβ and its isoforms were examined in healthy tissues, concanavalin A (ConA)-stimulated splenic lymphocytes and in livers and spleens of Riemerella anatipestifer-infected ducks using quantitative real-time PCR (qRT-PCR). Generally, duIL-2/15Rβ-d9 expression was undetectable in healthy tissues, ConA-activated samples, and R. anatipestifer-infected ducks. Expression levels of duIL-2/15Rβ transcript were relatively high to moderate in all healthy tissues tested, while duIL-2/15Rβ-d7 expression was low. Compared to untreated controls, expression levels of duIL-2/15Rβ were elevated in ConA-activated splenic lymphocytes and in livers on day 7 in R. anatipestifer-infected ducks, while duIL-2/15Rβ-d7 expression was unchanged. Additionally, COS-7 cells transfected with duIL-2/15Rβ, duIL-2/15Rβ-d7, or duIL-2/15Rβ-d9 constructs generated 73 kilodalton (kDa), 31kDa, and 40kDa proteins, respectively. This study identified three different IL-2/15Rβ transcripts, including two isoforms generated by alternative splicing and their gene expression patterns in stimulated conditions.
ITER vacuum vessel structural analysis completion during manufacturing phase
Martinez, J.M.,Alekseev, A.,Sborchia, C.,Choi, C.H.,Utin, Y.,Jun, C.H.,Terasawa, A.,Popova, E.,Xiang, B.,Sannazaro, G.,Lee, A.,Martin, A.,Teissier, P.,Sabourin, F.,Caixas, J.,Fernandez, E.,Zarzalejos, North-Holland 2016 Fusion engineering and design Vol.109 No.1
Some years ago, analyses were performed by ITER Organization Central Team (IO-CT) to verify the structural integrity of the ITER vacuum vessel baseline design fixed in 2010 and classified as a Protection Important Component (PIC). The manufacturing phase leads the ITER Organization domestic agencies (IO-DA) and their contracted manufacturers to propose detailed design improvements to optimize the manufacturing or inspection process. These design and quality inspection changes can affect the structural margins with regards to the Codes&Standards and thus oblige to evaluate one more time the modified areas. This paper proposes an overview of the additional analyses already performed to guarantee the structural integrity of the manufacturing designs. In this way, CT and DAs have been strongly involved to keep the considerable margins obtained previously which were used to fix reasonable compensatory measures for the lack of In Service Inspections of a Nuclear Pressure Equipment (NPE).
Induced quadrupolar singlet ground state of praseodymium in a modulated pyrochlore
van Duijn, J.,Kim, K. H.,Hur, N.,Ruiz-Bustos, R.,Adroja, D. T.,Bridges, F.,Daoud-Aladine, A.,Fernandez-Alonso, F.,Wen, J. J.,Kearney, V.,Huang, Q. Z.,Cheong, S.-W.,Perring, T. G.,Broholm, C. American Physical Society 2017 Physical Review B Vol.96 No.9
<P>The complex structure and magnetism of Pr2-xBixRu2O7 was investigated by neutron scattering and extended x-ray absorption fine structure. Pr has an approximate doublet ground state and the first excited state is a singlet. While the B-site (Ru) is well ordered throughout, this is not the case for the A-site (Pr/Bi). A broadened distribution for the Pr-O-2 bond length at low temperature indicates the Pr environment varies from site to site even for x = 0. The environment about the Bi site is highly disordered ostensibly due to the 6s lone pairs on Bi3+. Correspondingly, we find that the non-Kramers doublet ground-state degeneracy, otherwise anticipated for Pr in the pyrochlore structure, is lifted so as to produce a quadrupolar singlet ground statewith a spatially varying energy gap. For x = 0, below TN, the Ru sublattice orders antiferromagnetically, with propagation vector k = (0,0,0) as forY(2)Ru(2)O(7). No ordering associated with the Pr sublattice is observed down to 100 mK. The low-energy magnetic response of Pr2-xBixRu2O7 features a broad spectrum of magnetic excitations associated with inhomogeneous splitting of the Pr quasidoublet ground state. For x = 0 (x = 0.97), the spectrum is temperature dependent (independent). It appears disorder associated with Bi alloying enhances the inhomogeneous Pr crystal-field level splitting so that intersite interactions become irrelevant for x = 0.97. The structural complexity for the A-site may be reflected in the hysteretic uniform magnetization of B-site ruthenium in the Neel phase.</P>
RESULTS OF THERMAL CREEP TEST ON HIGHLY IRRADIATED ZIRLO
Quecedo, M.,Lloret, M.,Conde, J.M.,Alejano, C.,Gago, J.A.,Fernandez, F.J. Korean Nuclear Society 2009 Nuclear Engineering and Technology Vol.41 No.2
This paper presents a thermal creep test under internal pressure and post-test characterization performed on high burnup (68 MWd/kgU) ZIRLO. This research has been done by the CSN, ENRESA, and ENUSA in order to investigate the behavior of advanced cladding materials in contemporary PWRs at higher burnup under dry cask storage conditions. Also, to investigate the hydride reorientation, the cool-down of the samples after the test has been done in a coordinated manner with the internal pressure. The creep results obtained are consistent with the expected behavior from reference CWSR material, Zr-4. During the test, the material retained significant ductility: one specimen leaked during the test at an engineering strain of the tube section of 17%; remarkably, the crack closed due to de-pressurization. Although significant hydride reorientation occurred during the cool-down under pressure, no specimen failed during the cool-down.