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991.
Hui Mao Gen Kano Sherry A. Hudson Mary Brummet Nives Zimmermann Zhou Zhu Bruce S. Bochner 《PloS one》2013,8(6)
Background
Siglec-F and Siglec-8 are functional paralog proapoptotic cell surface receptors expressed on mouse and human eosinophils, respectively. Whereas Siglec-8 mediated death involves caspases and/or reactive oxygen species (ROS) generation and mitochondrial injury, very little is known about Siglec-F-mediated signaling and apoptosis. Therefore the objective of the current experiments was to better define apoptosis pathways mediated by Siglec-F and Siglec-8. Given that Siglec-F-induced apoptosis is much less robust than Siglec-8-induced apoptosis, we hypothesized that mechanisms involved in cell death via these receptors would differ.Methods
Consequences of engagement of Siglec-F on mouse eosinophils were studied by measuring ROS production, and by performing apoptosis assays using eosinophils from normal, hypereosinophilic, NADPH oxidase-deficient, src homology domain-containing protein tyrosine phosphatase (SHP)-1-deficient, and Lyn kinase-deficient mice. Inhibitors of caspase and Src family kinase activity were also used.Results
Engagement of Siglec-F induced mouse eosinophil apoptosis that was modest in magnitude and dependent on caspase activity. There was no detectable ROS generation, or any role for ROS, NADPH oxidase, SHP-1, or Src family kinases in this apoptotic process.Conclusions
These data suggest that Siglec-F-mediated apoptosis is different in both magnitude and mechanisms when compared to published data on Siglec-8-mediated human eosinophil apoptosis. One likely implication of this work is that models targeting Siglec-F in vivo in mice may not provide identical mechanistic predictions for consequences of Siglec-8 targeting in vivo in humans. 相似文献992.
Yi-Yan Chen Ying Zhu Qiu-Hong Wan Ji-Kang Lou Wen-Jing Li Yun-Fa Ge Sheng-Guo Fang 《PloS one》2013,8(7)
Genetic variation plays a significant role in maintaining the evolutionary potential of a species. Comparing the patterns of adaptive and neutral diversity in extant populations is useful for understanding the local adaptations of a species. In this study, we determined the fine-scale genetic structure of 6 extant populations of the giant panda (Ailuropoda melanoleuca) using mtDNA and DNA fingerprints, and then overlaid adaptive variations in 6 functional Aime-MHC class II genes (DRA, DRB3, DQA1, DQA2, DQB1, and DQB2) on this framework. We found that: (1) analysis of the mtDNA and DNA fingerprint-based networks of the 6 populations identified the independent evolutionary histories of the 2 panda subspecies; (2) the basal (ancestral) branches of the fingerprint-based Sichuan-derived network all originated from the smallest Xiaoxiangling (XXL) population, suggesting the status of a glacial refuge in XXL; (3) the MHC variations among the tested populations showed that the XXL population exhibited extraordinary high levels of MHC diversity in allelic richness, which is consistent with the diversity characteristics of a glacial refuge; (4) the phylogenetic tree showed that the basal clades of giant panda DQB sequences were all occupied by XXL-specific sequences, providing evidence for the ancestor-resembling traits of XXL. Finally, we found that the giant panda had many more DQ alleles than DR alleles (33∶13), contrary to other mammals, and that the XXL refuge showed special characteristics in the DQB loci, with 7 DQB members of 9 XXL-unique alleles. Thus, this study identified XXL as a glacial refuge, specifically harboring the most number of primitive DQB alleles. 相似文献
993.
Can traces of rapid socio-economic changes within a society be reflected in experimental games? The post-Mao reforms in China provide a unique natural quasi-experiment to study people from the same society who were raised with radically different values about distribution of wealth and altruistic behavior. We tested whether the size of offers in the ultimatum and dictator games are an increasing function of the number of years Chinese citizens experienced of the Mao era (“planned economy”). For the cohort that lived throughout the entire Mao era, we found that mean offers in the two games were substantially higher than what is typically offered in laboratory studies. These offers were also higher than those of two younger Chinese cohorts. In general, the amount offered decreased with less time spent under Mao, while in the oldest group in which every member spent the same amount of time under Mao, the younger members tended to offer more, suggesting an additional effect of early education under Mao and contradicting the alternative hypothesis that generosity increases with age. These results suggest that some of the observed individual differences in the offers made in experimental games can be traced back to the values of the socio-economic era in which individuals grew up. 相似文献
994.
Joseph McEvoy Rebecca A. Baillie Hongjie Zhu Peter Buckley Matcheri S. Keshavan Henry A. Nasrallah George G. Dougherty Jeffrey K. Yao Rima Kaddurah-Daouk 《PloS one》2013,8(7)
There is a critical need for mapping early metabolic changes in schizophrenia to capture failures in regulation of biochemical pathways and networks. This information could provide valuable insights about disease mechanisms, trajectory of disease progression, and diagnostic biomarkers. We used a lipidomics platform to measure individual lipid species in 20 drug-naïve patients with a first episode of schizophrenia (FE group), 20 patients with chronic schizophrenia that had not adhered to prescribed medications (RE group), and 29 race-matched control subjects without schizophrenia. Lipid metabolic profiles were evaluated and compared between study groups and within groups before and after treatment with atypical antipsychotics, risperidone and aripiprazole. Finally, we mapped lipid profiles to n3 and n6 fatty acid synthesis pathways to elucidate which enzymes might be affected by disease and treatment. Compared to controls, the FE group showed significant down-regulation of several n3 polyunsaturated fatty acids (PUFAs), including 20:5n3, 22:5n3, and 22:6n3 within the phosphatidylcholine and phosphatidylethanolamine lipid classes. Differences between FE and controls were only observed in the n3 class PUFAs; no differences where noted in n6 class PUFAs. The RE group was not significantly different from controls, although some compositional differences within PUFAs were noted. Drug treatment was able to correct the aberrant PUFA levels noted in FE patients, but changes in re patients were not corrective. Treatment caused increases in both n3 and n6 class lipids. These results supported the hypothesis that phospholipid n3 fatty acid deficits are present early in the course of schizophrenia and tend not to persist throughout its course. These changes in lipid metabolism could indicate a metabolic vulnerability in patients with schizophrenia that occurs early in development of the disease. 相似文献
995.
Guiling Ma Yanfang Li Juan Zhang Hao Liu Dongyan Hou Lei Zhu Zhenyu Zhang Lin Zhang 《PloS one》2013,8(3)
Background
Pre-eclampsia is the leading cause of maternal and neonatal morbidity and mortality with incompletely understood etiopathogenesis. The purpose of the current study is to determine whether there is a relationship between the presence of autoantibodies against β1, β2 and α1 adrenoreceptors and severe pre-eclampsia.Methodology/Principal Findings
Synthetic peptides corresponding to amino acid sequences of the second extracellular loops of β1, β2 and α1 adrenoreceptors were synthesized as antigens to test 34 patients with severe pre-eclampsia, 36 normal pregnancy women and 40 non-pregnant controls for the presence of autoantibodies using enzyme-linked immunosorbent assay. The respective frequencies of autoantibodies against β1, β2 and α1 adrenoreceptors were 50.0% (17/34), 52.9% (18/34) and 55.9% (19/34) in patients with severe pre-eclampsia, 19.4% (7/36) (p = 0.011), 19.4% (7/36) (p = 0.006) and 17.6% (6/36) (p = 0.001) in normal pregnancy women and 10% (4/40), 7.5% (3/40) and 10% (4/40) (p<0.001) in non-pregnant controls. Titers of these autoantibodies were also significantly increased in patients with severe pre-eclampsia. By logistic regression analysis, the presence of these three autoantibodies significantly increased the risk of neonatal death (odds ratio, 13.5; 95% confidence interval, 1.3–141.3; p = 0.030) and long-term neonatal hospitalization (odds ratio, 5.0; 95% confidence interval, 1.3–19.1; p = 0.018). The risk of hypertension and fetal distress were also associated with the presence of these three autoantibodies.Conclusions/Significance
This novel pilot study demonstrated for the first time that the presence of autoantibodies against β1, β2 and α1 adrenoreceptors are increased in patients with severe pre-eclampsia. Pregnant women who are positive for the three autoantibodies are at increased risks of neonatal mortality and morbidity. We posit that these autoantibodies may be involved in the pathogenesis of severe pre-eclampsia. 相似文献996.
Christopher Bryant Kelly S. Giovanello Joseph G. Ibrahim Jing Chang Dinggang Shen Bradley S. Peterson Hongtu Zhu for The Alzheimer's Disease Neuroimaging Initiative 《PloS one》2013,8(8)
Typically twin studies are used to investigate the aggregate effects of genetic and environmental influences on brain phenotypic measures. Although some phenotypic measures are highly heritable in twin studies, SNPs (single nucleotide polymorphisms) identified by genome-wide association studies (GWAS) account for only a small fraction of the heritability of these measures. We mapped the genetic variation (the proportion of phenotypic variance explained by variation among SNPs) of volumes of pre-defined regions across the whole brain, as explained by 512,905 SNPs genotyped on 747 adult participants from the Alzheimer''s Disease Neuroimaging Initiative (ADNI). We found that 85% of the variance of intracranial volume (ICV) (p = 0.04) was explained by considering all SNPs simultaneously, and after adjusting for ICV, total grey matter (GM) and white matter (WM) volumes had genetic variation estimates near zero (p = 0.5). We found varying estimates of genetic variation across 93 non-overlapping regions, with asymmetry in estimates between the left and right cerebral hemispheres. Several regions reported in previous studies to be related to Alzheimer''s disease progression were estimated to have a large proportion of volumetric variance explained by the SNPs. 相似文献
997.
998.
Francesca D’Addio Takuya Ueno Michael Clarkson Baogong Zhu Andrea Vergani Gordon J. Freeman Mohamed H. Sayegh Mohammed Javeed I. Ansari Paolo Fiorina Antje Habicht 《PloS one》2013,8(4)
CD160 is a cell surface molecule expressed by most NK cells and approximately 50% of CD8+ cytotoxic T lymphocytes. Engagement of CD160 by MHC class-I directly triggers a costimulatory signal to TCR-induced proliferation, cytokine production and cytotoxic effector functions. The role of CD160 in alloimmunity is unknown. Using a newly generated CD160 fusion protein (CD160Ig) we examined the role of the novel costimulatory molecule CD160 in mediating CD4+ or CD8+ T cell driven allograft rejection. CD160Ig inhibits alloreactive CD8+ T cell proliferation and IFN-γ production in vitro, in particular in the absence of CD28 costimulation. Consequently CD160Ig prolongs fully mismatched cardiac allograft survival in CD4−/−, CD28−/− knockout and CTLA4Ig treated WT recipients, but not in WT or CD8−/− knockout recipients. The prolonged cardiac allograft survival is associated with reduced alloreactive CD8+ T cell proliferation, effector/memory responses and alloreactive IFN-γ production. Thus, CD160 signaling is particularly important in CD28-independent effector/memory CD8+ alloreactive T cell activation in vivo and therefore may serve as a novel target for prevention of allograft rejection. 相似文献
999.
Yan Wang Yajuan Wang Yuesheng Qain Jin Zhang Xiaofeng Tang Junlei Sun Dingliang Zhu 《PloS one》2013,8(8)
Background
Most studies have suggested that elevated body mass index (BMI) was associated with the risk of death from all cause and from specific causes. However, there was little evidence illustrating the effect of BMI on the mortality in elderly hypertensive patients in Chinese population.Methods
The information of 10,957 hypertensive patients at baseline not less than 60 years were from Xinzhuang, a town in Minhang district of Shanghai, was extracted from the Electronic Health Record (EHR) system. All study participants were divided into eight categories of baseline BMI (with cut-points at 18, 20, 22, 24, 26, 28 and 30 kg/m2). Relative hazard ratio of death from all cause, cardiovascular and non-cardiovascular cause by baseline BMI groups were calculated, standardized for sex, age, smoking, drinking, physical activity, systolic blood pressure, history of cardiovascular disorders, serum lipid disturbance, diabetes mellitus and antihypertensive drug treatment.Results
During follow up (median: 3.7 years), 561 deaths occurred. Underweight (BMI<18 kg/m2) was associated with significantly increased mortality from all cause mortality (OR: 2.00; 95% CI: 1.43–2.79) and non cardiovascular mortality (OR: 2.76; 95% CI: 1.87–4.07), but not with cardiovascular mortality. For the cause specific analysis, the underweight was associated significantly with neoplasms (OR: 2.15; 95% CI: 1.16–4.00) and respiratory disorders (OR: 3.41; 95% CI: 1.64–7.06). The results for total mortality and specific cause mortality were not influenced by sex, age and smoking status.Conclusion
Our study revealed an association between underweight and increased mortality from non-cardiovascular disorders in elderly hypertensive patients in Chinese community. Overweight and obesity were not associated with all cause or cause specific death. 相似文献1000.
Mi Kyung Kwak Daniel T. Johnson Chunfang Zhu Suk Hyung Lee Ding-Wei Ye Richard Luong Zijie Sun 《PloS one》2013,8(1)
The PTEN tumor suppressor gene is frequently inactivated in human prostate cancer. Using Osr1 (odd skipped related 1)-Cre mice, we generated a novel conditional Pten knockout mouse strain, PtenLoxP:Osr1-Cre. Conditional biallelic and monoallelic Pten knockout mice were viable. Deletion of Pten expression was detected in the prostate of PtenLoxP/LoxP:Osr1-Cre mice as early as 2 weeks of age. Intriguingly, PtenLoxP/LoxP:Osr1-Cre mice develop high-grade prostatic intraepithelial neoplasms (PINs) with high penetrance as early as one-month of age, and locally invasive prostatic tumors after 12-months of age. PtenLoxP/+:Osr1-Cre mice show only mild oncogenic changes after 8-weeks of age. Castration of PtenLoxP/LoxP:Osr1-Cre mice shows no significant regression of prostate tumors, although a shift of androgen receptor (AR) staining from the nuclei to cytoplasm is observed in Pten null tumor cells of castrated mice. Enhanced Akt activity is observed in Pten null tumor cells of castrated PtenLoxP/LoxP:Osr1-Cre. This study provides a novel mouse model that can be used to investigate a primary role of Pten in initiating oncogenic transformation in the prostate and to examine other genetic and epigenetic changes that are required for tumor progression in the mouse prostate. 相似文献