An evaluation of the performance of HapMap SNP data in a Shanghai Chinese population: Analyses of allele frequency, linkage disequilibrium pattern and tagging SNPs transferability on chromosome 1q21-q25

<p>Abstract</p> <p>Background</p> <p>The HapMap project aimed to catalog millions of common single nucleotide polymorphisms (SNPs) in the human genome in four major populations, in order to facilitate association studies of complex diseases. To examine the transferability of Han Chinese in Beijing HapMap data to the Southern Han Chinese in Shanghai, we performed comparative analyses between genotypes from over 4,500 SNPs in a 21 Mb region on chromosome 1q21-q25 in 80 unrelated Shanghai Chinese and 45 HapMap Chinese data.</p> <p>Results</p> <p>Three thousand and forty-two SNPs were analyzed after removal of SNPs that failed quality control and those not in the HapMap panel. We compared the allele frequency distributions, linkage disequilibrium patterns, haplotype frequency distributions and tagging SNP sets transferability between the HapMap population and Shanghai Chinese population. Among the four HapMap populations, Beijing Chinese showed the best correlation with Shanghai population on allele frequencies, linkage disequilibrium and haplotype frequencies. Tagging SNP sets selected from four HapMap populations at different thresholds were evaluated in the Shanghai sample. Under the threshold of r²equal to 0.8 or 0.5, both HapMap Chinese and Japanese data showed better coverage and tagging efficiency than Caucasian and African data.</p> <p>Conclusion</p> <p>Our study supported the applicability of HapMap Beijing Chinese SNP data to the study of complex diseases among southern Chinese population.</p

Multiple mesodermal lineage differentiation of Apodemus sylvaticus embryonic stem cells in vitro

<p>Abstract</p> <p>Background</p> <p>Embryonic stem (ES) cells have attracted significant attention from researchers around the world because of their ability to undergo indefinite self-renewal and produce derivatives from the three cell lineages, which has enormous value in research and clinical applications. Until now, many ES cell lines of different mammals have been established and studied. In addition, recently, AS-ES1 cells derived from <it>Apodemus sylvaticus </it>were established and identified by our laboratory as a new mammalian ES cell line. Hence further research, in the application of AS-ES1 cells, is warranted.</p> <p>Results</p> <p>Herein we report the generation of multiple mesodermal AS-ES1 lineages via embryoid body (EB) formation by the hanging drop method and the addition of particular reagents and factors for induction at the stage of EB attachment. The AS-ES1 cells generated separately in vitro included: adipocytes, osteoblasts, chondrocytes and cardiomyocytes. Histochemical staining, immunofluorescent staining and RT-PCR were carried out to confirm the formation of multiple mesodermal lineage cells.</p> <p>Conclusions</p> <p>The appropriate reagents and culture milieu used in mesodermal differentiation of mouse ES cells also guide the differentiation of in vitro AS-ES1 cells into distinct mesoderm-derived cells. This study provides a better understanding of the characteristics of AS-ES1 cells, a new species ES cell line and promotes the use of Apodemus ES cells as a complement to mouse ES cells in future studies.</p

A compact core-jet structure in the changing-look Seyfert NGC 2617

The nearby face-on spiral galaxy NGC 2617 underwent an unambiguous 'inside-out' multi-wavelength outburst in Spring 2013, and a dramatic Seyfert type change probably between 2010 and 2012, with the emergence of broad optical emission lines. To search for the jet activity associated with this variable accretion activity, we carried out multi-resolution and multi-wavelength radio observations. Using the very long baseline interferometric (VLBI) observations with the European VLBI Network (EVN) at 1.7 and 5.0 GHz, we find that NGC 2617 shows a partially synchrotron self-absorbed compact radio core with a significant core shift, and an optically thin steep-spectrum jet extending towards the north up to about two parsecs in projection. We also observed NGC 2617 with the electronic Multi-Element Remotely Linked Interferometer Network (e-MERLIN) at 1.5 and 5.5 GHz, and revisited the archival data of the Very Large Array (VLA) and the Very Long Baseline Array (VLBA). The radio core had a stable flux density of about 1.4 mJy at 5.0 GHz between 2013 June and 2014 January, in agreement with the expectation of a supermassive black hole in the low accretion rate state. The northern jet component is unlikely to be associated with the 'inside-out' outburst of 2013. Moreover, we report that most optically selected changing-look AGN at z<0.83 are sub-mJy radio sources in the existing VLA surveys at 1.4 GHz, and it is unlikely that they are more active than normal AGN at radio frequencies.Comment: 10 pages, 7 figures, accepted for publication in MNRA

Acute rejection is associated with antibodies to non-Gal antigens in baboons using Gal-knockout pig kidneys

We transplanted kidneys from α1,3-galactosyltransferase knockout (GalT-KO) pigs into six baboons using two different immunosuppressive regimens, but most of the baboons died from severe acute humoral xenograft rejection. Circulating induced antibodies to non-Gal antigens were markedly elevated at rejection, which mediated strong complement-dependent cytotoxicity against GalT-KO porcine target cells. These data suggest that antibodies to non-Gal antigens will present an additional barrier to transplantation of organs from GalT-KO pigs to humans. © 2005 Nature Publishing Group

Mucosal-Associated Invariant T Cells Improve Nonalcoholic Fatty Liver Disease Through Regulating Macrophage Polarization

Mucosal-associated invariant T (MAIT) cells, a novel population of innate-like lymphocytes, have been involved in various inflammatory and autoimmune diseases. However, their role in the development of nonalcoholic fatty liver disease (NAFLD) remains unclear. In this study, we investigated the alterations of phenotype and immunological function of MAIT cells in NAFLD. Analysis of PBMCs in 60 patients with NAFLD and 48 healthy controls (HC) revealed that circulating MAIT cell frequency decreased in NAFLD, especially in the patients with higher serum levels of γ-glutamyl transferase or total triglyceride. Functional alterations of circulating MAIT cells were also detected in NAFLD patients, such as the increased production of IL-4 whereas the decreased production of IFN-γ and TNF-α. Furthermore, elevated expression of CXCR6 was observed in circulating MAIT cells of patients. Meanwhile, we found an increased number of MAIT cells in the livers of NAFLD, and the number was even greater in patients with higher NAFLD activity score. Moreover, activated MAIT cells induced monocytes/macrophages differentiation into M2 phenotype in vitro. Additionally, MAIT cells were enriched and displayed Th2 type cytokines profile in livers of wild type mice fed with methionine and choline deficient diet (MCD). Notably, mice deficient of MAIT cells exhibited more severe hepatic steatosis and inflammation upon MCD, accompanied with more CD11c+ proinflammatory macrophages (M1) and less CD206+ anti-inflammatory macrophages (M2) in livers. Our results indicate that MAIT cells protect against inflammation in NAFLD through producing regulatory cytokines and inducing anti-inflammatory macrophage polarization, which may provide novel therapeutic strategies for NAFLD

VLBI observations of 10 CSO candidates: expansion velocities of hot spots

Observations of ten Compact Symmetric Objects ({\rm CSO}) candidates have been made with the Very Long Baseline Array at 8.4 GHz in 2005 and with a combined Chinese and European VLBI array at 8.4 GHz in 2009. The 2009 observations incorporate for the first time the two new Chinese telescopes at Miyun and Kunming for international astrophysical observations. The observational data, in combination with archival VLBA data from previous epochs, have been used to derive the proper motions of the VLBI components. Because of the long time baseline of $\sim$16 years of the VLBI data sets, the expansion velocities of the hot spots can be measured at an accuracy as high as $\sim$1.3 $\mu$as yr$^{-1}$. Six of the ten sources are identified as CSOs with a typical double or triple morphology on the basis of both spectral index maps and their mirror-symmetry of proper motions of the terminal hot spots. The compact double source J1324+4048 is also identified as a CSO candidate. Among the three remaining sources, J1756+5748 and J2312+3847 are identified as core-jet sources with proper motions of their jet components relating to systemic source expansion. The third source J0017+5312 is likely also a core-jet source, but a robust detection of a core is needed for an unambiguous identification. The kinematic ages of the CSOs derived from proper motions range from 300 to 2500 years. The kinematic age distribution of the CSOs confirm an overabundance of compact young CSOs with ages less than 500 years. CSOs with known kinematic ages may be used to study the dynamical evolution of extragalactic radio sources at early stages.Comment: 20 pages, 11 figures, accepted for publication in The Astrophysical Journal Supplemen

Clinical value of the systemic immune-inflammation index in moyamoya disease

BackgroundMoyamoya disease (MMD) is a rare cerebrovascular disorder with unknown etiology. The underlying pathophysiological mechanism of moyamoya disease remains to be elucidated, but recent studies have increasingly highlighted that abnormal immune response may be a potential trigger for MMD. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) are inflammatory markers that can reflect the immune-inflammation state of the disease.ObjectiveThe purpose of this study was to investigate SII, NLR, and PLR in patients with moyamoya disease.MethodsA total of 154 patients with moyamoya disease (MMD group) and 321 age- and sex-matched healthy subjects (control group) were included in this retrospective case–control study. Complete blood count parameters were assayed to calculate the SII, NLR, and PLR values.ResultsThe SII, NLR, and PLR values in the moyamoya disease group were significantly higher than those in the control group [754 ± 499 vs. 411 ± 205 (P &lt; 0.001), 2.83 ± 1.98 vs. 1.81 ± 0.72 (P &lt; 0.001), and 152 ± 64 vs. 120 ± 42 (P &lt; 0.001), respectively]. The SII in the medium-moyamoya vessels of moyamoya disease was higher than that in the high-moyamoya vessels and low-moyamoya vessels (P = 0.005). Using the receiver operating characteristic (ROC) curve analysis to predict MMD, the highest area under the curve (AUC) was determined for SII (0.76 for SII, 0.69 for NLR, and 0.66 for PLR).ConclusionBased on the results of this study, patients with moyamoya disease admitted for inpatient care due to acute or chronic stroke have significantly higher SII, NLR, and PLR when compared to blood samples drawn from completely healthy controls in a non-emergent outpatient setting. While the findings may suggest that inflammation plays a role in moyamoya disease, further studies are warranted to corroborate such an association. In the middle stage of moyamoya disease, there may be a more intense imbalance of immune inflammation. Further studies are needed to determine whether the SII index contributes to the diagnosis or serves as a potential marker of an inflammatory response in patients with moyamoya disease

RIG-I, MDA5 and TLR3 Synergistically Play an Important Role in Restriction of Dengue Virus Infection

Dengue virus (DV) infection is one of the most common mosquito-borne viral diseases in the world. The innate immune system is important for the early detection of virus and for mounting a cascade of defense measures which include the production of type 1 interferon (IFN). Hence, a thorough understanding of the innate immune response during DV infection would be essential for our understanding of the DV pathogenesis. A recent application of the microarray to dengue virus type 1 (DV1) infected lung carcinoma cells revealed the increased expression of both extracellular and cytoplasmic pattern recognition receptors; retinoic acid inducible gene-I (RIG-I), melanoma differentiation associated gene-5 (MDA-5) and Toll-like receptor-3 (TLR3). These intracellular RNA sensors were previously reported to sense DV infection in different cells. In this study, we show that they are collectively involved in initiating an effective IFN production against DV. Cells silenced for these genes were highly susceptible to DV infection. RIG-I and MDA5 knockdown HUH-7 cells and TLR3 knockout macrophages were highly susceptible to DV infection. When cells were silenced for only RIG-I and MDA5 (but not TLR3), substantial production of IFN-β was observed upon virus infection and vice versa. High susceptibility to virus infection led to ER-stress induced apoptosis in HUH-7 cells. Collectively, our studies demonstrate that the intracellular RNA virus sensors (RIG-I, MDA5 and TLR3) are activated upon DV infection and are essential for host defense against the virus