Location, abundance and phenotype of follicular simian immunodeficiency virus-specific CD8 T lymphocytes

University of Minnesota Ph.D. dissertation. May 2018. Major: Comparative and Molecular Biosciences. Advisor: Pamela Skinner. 1 computer file (PDF); x, 159 pages.CD8 T cells play a critical role in controlling and eradicating virus-infected cells. Although many studies demonstrated the notable anti-viral effect of HIV-specific CD8 T cells during HIV infection, these cells fail to fully eliminate viral replication. The phenomenon that only a small population of HIV-specific CD8 T cells migrate into B cell follicles where HIV-producing cells are most highly concentrated during chronic infection is one major mechanism account for the failure of these cells to fully suppress HIV replication. It is not known whether this phenomenon also occurs during early infection. Moreover, whether follicular HIV-specific CD8 T cells are functional in suppressing viral replication is not fully understood. Simian immunodeficiency virus (SIV)-infected rhesus macaques are a good animal model for HIV research. In the present study, we determined the location, abundance and phenotype of follicular SIV-specific CD8 T cells in lymph nodes from SIV-infected rhesus macaques using in situ tetramer staining combined immunohistochemistry, confocal microscopy and quantitative image analysis. We found that during chronic SIV infection, despite high levels of exhaustion and likely inhibition by Foxp3+ cells, a subset of follicular SIV-specific CD8 T cells are functional and suppress viral replication in vivo. Similar to chronic infection, low levels of SIV-specific CD8 T cells migrate into B cell follicles during early stages of infection and a subset of these cells likely possess cytolytic function and suppress viral replication. In addition, low levels of follicular SIV-specific CD8 T cells from GCs during early infection may set the stage for the establishment of persistent chronic infection. These findings provide important insights into HIV immunopathogenesis and support HIV cure strategies that augment functional follicular virus-specific CD8 T cells to enhance viral control. We also evaluated the effect of ALT-803, a novel human IL-15 superagonist and potent immunostimulatory molecule, on SIV-specific CD8 T cells in chronically SIV-infected rhesus macaques. We found that ALT-803 drives dramatic expansion of SIV-specific CD8 T cells in lymphoid tissues and, importantly, induces significant accumulation of SIV-specific CD8 T cells in B cell follicles, reducing the number of SIV-producing cells within B cell follicles. These data justify the further evaluation of ALT-803 for eradication of HIV-infected cells

Draft Genome of the Leopard Gecko, \u3cem\u3eEublepharis Macularius\u3c/em\u3e

Background Geckos are among the most species-rich reptile groups and the sister clade to all other lizards and snakes. Geckos possess a suite of distinctive characteristics, including adhesive digits, nocturnal activity, hard, calcareous eggshells, and a lack of eyelids. However, one gecko clade, the Eublepharidae, appears to be the exception to most of these ‘rules’ and lacks adhesive toe pads, has eyelids, and lays eggs with soft, leathery eggshells. These differences make eublepharids an important component of any investigation into the underlying genomic innovations contributing to the distinctive phenotypes in ‘typical’ geckos. Findings We report high-depth genome sequencing, assembly, and annotation for a male leopard gecko, Eublepharis macularius (Eublepharidae). Illumina sequence data were generated from seven insert libraries (ranging from 170 to 20 kb), representing a raw sequencing depth of 136X from 303 Gb of data, reduced to 84X and 187 Gb after filtering. The assembled genome of 2.02 Gb was close to the 2.23 Gb estimated by k-mer analysis. Scaffold and contig N50 sizes of 664 and 20 kb, respectively, were compble to the previously published Gekko japonicus genome. Repetitive elements accounted for 42 % of the genome. Gene annotation yielded 24,755 protein-coding genes, of which 93 % were functionally annotated. CEGMA and BUSCO assessment showed that our assembly captured 91 % (225 of 248) of the core eukaryotic genes, and 76 % of vertebrate universal single-copy orthologs. Conclusions Assembly of the leopard gecko genome provides a valuable resource for future comptive genomic studies of geckos and other squamate reptiles

Polymorphism Profile of Nine Short Tandem Repeat Loci in the Han Chinese

Nine short tandem repeat (STR) markers (D3S1358, VWA, FGA, THO1, TPOX, CSFIPO, D5S818, D13S317, and D7S820) and a sex-identification marker (Amelogenin locus) were amplified with multiplex PCR and were genotyped with a four-color fluorescence method in samples from 174 unrelated Han individuals in North China. The allele frequencies, genotype frequencies, heterozygosity, probability of discrimination powers, probability of paternity exclusion and Hardy-Weinberg equilibrium expectations were determined. The results demonstrated that the genotypes at all these STR loci in Han population conform to Hardy-Weinberg equilibrium expectations. The combined discrimination power (DP) was 1.05×10−10 within nine STR loci analyzed and the probability of paternity exclusion (EPP) was 0.9998. The results indicate that these nine STR loci and the Amelogenin locus are useful markers for human identification, paternity and maternity testing and sex determination in forensic sciences

Equity in use of maternal health services in Western Rural China: a survey from Shaanxi province

BACKGROUND: The 20(th) century was marked by a significant improvement in worldwide human health and access to healthcare. However, these improvements were not completely or uniformly distributed among, or even within, nations. This study was designed to assess the use of maternal health services by pregnant women in China, with a focus on the inequity related to family income level. METHODS: Two population-based cross-sectional surveys were carried out in the Zhenan and Lantian counties in March 2007 and from December 2008 to March 2009. A total of 2562 women completed the questionnaires, including 948 who were pregnant in 2006 and 1614 from 2008–2009. The concentration index (CI) was calculated and used to analyze the parameters of maternal health care in the two counties surveyed. RESULTS: The responses in both 2006 and 2008–2009 indicated a bias towards higher (rich) economic statuses for the use of maternal and child health services. The CI of ‘delivery at health facility’ was 0.0206 (95% confidence interval between 0.0114 and 0.0299) for 2006 and 0.0053 (95% confidence interval between 0.0015 and 0.0091) for 2008, which represented a statistically significant inequity for women of lower (poor) economic statuses. Similar CI was observed in ‘receiving antenatal care within 12 weeks’ for 2006 (CI(2006) = 0.0956, 95% confidence interval between 0.0516 and 0.1396). The CIs of ‘postnatal visit’ and ‘postnatal visit >3-times’ was positive (except for 2006), indicating that the poor used postnatal care less than the non-poor. In 2008, poor women had C-sections more often than non-poor women (CI(2008) = −0.0629, 95% confidence interval between-0.1165 and −0.0093), but such a difference was not observed in 2006. CONCLUSIONS: In 2006 and 2008, the use of maternal health services in western rural China was significantly unequal between pregnant women of poor and non-poor economic statuses. Financial support that enables poorer pregnant women to use health services will be beneficial. Utilization of maternal healthcare services can be improved if out-of-pocket expenses can be minimized

A quantum circuit simulator and its applications on Sunway TaihuLight supercomputer

Classical simulation of quantum computation is vital for verifying quantum devices and assessing quantum algorithms. We present a new quantum circuit simulator developed on the Sunway TaihuLight supercomputer. Compared with other simulators, the present one is distinguished in two aspects. First, our simulator is more versatile. The simulator consists of three mutually independent parts to compute the full, partial and single amplitudes of a quantum state with different methods. It has the function of emulating the effect of noise and support more kinds of quantum operations. Second, our simulator is of high efficiency. The simulator is designed in a two-level parallel structure to be implemented efficiently on the distributed many-core Sunway TaihuLight supercomputer. Random quantum circuits can be simulated with 40, 75 and 200 qubits on the full, partial and single amplitude, respectively. As illustrative applications of the simulator, we present a quantum fast Poisson solver and an algorithm for quantum arithmetic of evaluating transcendental functions. Our simulator is expected to have broader applications in developing quantum algorithms in various fields.Comment: 21 pages, 9 figure

Draft genome of the leopard gecko, <i>Eublepharis macularius</i>

BACKGROUND: Geckos are among the most species-rich reptile groups and the sister clade to all other lizards and snakes. Geckos possess a suite of distinctive characteristics, including adhesive digits, nocturnal activity, hard, calcareous eggshells, and a lack of eyelids. However, one gecko clade, the Eublepharidae, appears to be the exception to most of these ‘rules’ and lacks adhesive toe pads, has eyelids, and lays eggs with soft, leathery eggshells. These differences make eublepharids an important component of any investigation into the underlying genomic innovations contributing to the distinctive phenotypes in ‘typical’ geckos. FINDINGS: We report high-depth genome sequencing, assembly, and annotation for a male leopard gecko, Eublepharis macularius (Eublepharidae). Illumina sequence data were generated from seven insert libraries (ranging from 170 to 20 kb), representing a raw sequencing depth of 136X from 303 Gb of data, reduced to 84X and 187 Gb after filtering. The assembled genome of 2.02 Gb was close to the 2.23 Gb estimated by k-mer analysis. Scaffold and contig N50 sizes of 664 and 20 kb, respectively, were comparable to the previously published Gekko japonicus genome. Repetitive elements accounted for 42 % of the genome. Gene annotation yielded 24,755 protein-coding genes, of which 93 % were functionally annotated. CEGMA and BUSCO assessment showed that our assembly captured 91 % (225 of 248) of the core eukaryotic genes, and 76 % of vertebrate universal single-copy orthologs. CONCLUSIONS: Assembly of the leopard gecko genome provides a valuable resource for future comparative genomic studies of geckos and other squamate reptiles. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13742-016-0151-4) contains supplementary material, which is available to authorized users