The in Vitro Protection of Human Decay Accelerating Factor and Hdaf/Heme Oxygenase-1 Transgenes in Porcine Aortic Endothelial Cells against Sera of Formosan Macaques

To mitigate hyperacute rejection, pigs have been generated with a-Gal transferase gene knockout and transgenic expression of human decay accelerating factor (hDAF), MCP, and CD59. Additionally, heme-oxygenase-1 (HO-1) has been suggested to defend endothelial cells. Sera (MS) (0%, 1%, 5% , 10%, and 15%) from Formosan macaques (Macaca cyclopis, MC) , an Old World monkey wildly populated in Taiwan, was used to test the protective in vitro, effects of hDAF or hDAF/hHO -1 on porcine aortic endothelial cells (pAEC) derived from hDAF(+), hDAF(+)/hHO-1(+), and hDAF(+)/hHO-1(-) and 1 nontransgenic pAEC. Ten percent human serum (HS) served as a positive control. When MS addition increased to 10% or 15%, all transgenic pAEC exhibited a greater survival than nontransgenic pAEC. Noticeably, 15 % MS reduced survived to 40% in nontransgenic and transgenic pAEC, respectively. These results revealed that hDAF exerted protective effects against MC complement activation. However , comparing with 10% MS and HS in pAEC of nontransgenic pigs , the survivability was higher in HS, suggesting that complement activation by MS was more toxic than that by HS. Furthermore, hDAF(+)/hHO-1(+) showed no further protection against effects of MS on transgenic pAEC

The in Vitro Protection of Human Decay Accelerating Factor and Hdaf/Heme Oxygenase-1 Transgenes in Porcine Aortic Endothelial Cells against Sera of Formosan Macaques

To mitigate hyperacute rejection, pigs have been generated with a-Gal transferase gene knockout and transgenic expression of human decay accelerating factor (hDAF), MCP, and CD59. Additionally, heme-oxygenase-1 (HO-1) has been suggested to defend endothelial cells. Sera (MS) (0%, 1%, 5% , 10%, and 15%) from Formosan macaques (Macaca cyclopis, MC) , an Old World monkey wildly populated in Taiwan, was used to test the protective in vitro, effects of hDAF or hDAF/hHO -1 on porcine aortic endothelial cells (pAEC) derived from hDAF(+), hDAF(+)/hHO-1(+), and hDAF(+)/hHO-1(-) and 1 nontransgenic pAEC. Ten percent human serum (HS) served as a positive control. When MS addition increased to 10% or 15%, all transgenic pAEC exhibited a greater survival than nontransgenic pAEC. Noticeably, 15 % MS reduced survived to 40% in nontransgenic and transgenic pAEC, respectively. These results revealed that hDAF exerted protective effects against MC complement activation. However , comparing with 10% MS and HS in pAEC of nontransgenic pigs , the survivability was higher in HS, suggesting that complement activation by MS was more toxic than that by HS. Furthermore, hDAF(+)/hHO-1(+) showed no further protection against effects of MS on transgenic pAEC

Human Leukocyte Antigen-Dr Matching Improved Skin Graft Survival from Transgenic Pigs to Accommodate Scid Mice Reconstituted with Human Peripheral Blood Mononuclear Cells

The shortage of human organs has encouraged scientists to develop genetically modified pigs for xenotransplantation, such as CD55 or CD46, and CD59 transgenesis as well as ce- galactosyl transferase gene knockouts . In allotransplantation, the match of human leukocyte antigen class II ( HLA-II) may improve graft survival although the role of HLA-II in xenotransplantation is unknown. HLA-II transgenic pigs, including DP, DQ, and DR, have been successfully generated and HLA-DR15(+) transgenic pig skin pieces grafted onto severe congenital immunodeficiency (SCID ) mice reconstituted intraperitoneally with HLA-DR15(+) or HLA-DR15(-) human peripheral blood mononuclear cells (hPBMCs ). This study sought to develop an animal model to evaluate the effects of HLA-DR matching on xenograft survival. Human CD4(+) and CD8(+) were detected from days 7 to 29 after hPBMC reconstitution in SCID mice. Both CD4(+) and CD8(+) cells of HLA-DR 15(-) reconstituted SCID mice were significantly higher at day 29 postgrafting compared with HI -A-DR15(+) reconstituted SCID mice. An HLA- DR15(+) transgenic pig dermal graft survived and integrated into SCID mice reconstituted with hPBMCs/HLA-DR15(+) as proven by the histopathological finding that the collagen layer remained intact with little lymphocytic response. In contrast, the transgenic pig dermal graft showed more collagen disruption as well as mild to moderate lymphocytic infiltration when reconstituted in an hPBMC/HLA-DR15(-) SCID mouse. The results suggested that HLA-DR matching eased xenograft rejection; however, it was not yet clear that the response was mediated by T cells

JUNO Sensitivity on Proton Decay p→νˉK+p\to \bar\nu K^+ Searches

The Jiangmen Underground Neutrino Observatory (JUNO) is a large liquid scintillator detector designed to explore many topics in fundamental physics. In this paper, the potential on searching for proton decay in $p\to \bar\nu K^+$ mode with JUNO is investigated.The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification. Moreover, the excellent energy resolution of JUNO permits to suppress the sizable background caused by other delayed signals. Based on these advantages, the detection efficiency for the proton decay via $p\to \bar\nu K^+$ is 36.9% with a background level of 0.2 events after 10 years of data taking. The estimated sensitivity based on 200 kton-years exposure is $9.6 \times 10^{33}$ years, competitive with the current best limits on the proton lifetime in this channel