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661.
K Gianesin R Freguja F Carmona M Zanchetta P Del Bianco S Malacrida M Montagna O Rampon C Giaquinto A De Rossi 《PloS one》2012,7(9):e44460
Stromal cell-Derived Factor 1 (SDF1) is the natural ligand of CXCR4, the coreceptor of HIV-1 X4 viruses. This study investigated the role of the single nucleotide polymorphism (SNP) rs1801157 (:c.*519G>A) of the SDF1 gene in the natural history of mother-to-child transmission of HIV-1 and disease progression of HIV-1-infected children. The study was conducted in 428 children born to HIV-1-seropositive mothers, who had not undergone antiretroviral therapy (ART) during pregnancy, and in 120 HIV-1-infected children for whom the end-point was the onset of AIDS or the initiation of ART; 16 children developed early AIDS (<24 months of life), 13 from 24 to 84 months of age, and 14 had late AIDS (>84 months). The rs1801157 SNP was not associated with risk of perinatal infection in any genetic models tested. By contrast, this SNP influenced disease progression in a time-dependent manner. rs1801157 GA heterozygous children had a higher risk of late AIDS (HR = 6.3, 95%CI 1.9–20.7, p = 0.002) than children with the rs1801157 GG genotype. Children were studied for viral coreceptor usage at birth, after 84 months of age and/or at AIDS onset. While R5 viruses using CCR5 coreceptor were predominant at birth (94%) and at early AIDS (85%), viruses using CXCR4 coreceptor emerged during the course of infection and were detected in 49% of children older than 84 months and in 62% of late AIDS. The rs1801157 SNP did not influence the emergence of R5X4 viruses, but children with the rs1801157 GA genotype and R5X4 viruses were at significantly higher risk of late AIDS than children with rs1801157 GG genotype (OR = 8.0, 95% CI 1.2–52.2, p = 0.029). Our results indicate that the rs1801157 SNP does not influence perinatal infection, but impacts disease progression. This effect is time-dependent and linked to the coreceptor-usage of viral variants that undergo evolution during the course of HIV-1 infection. NM_000609.5相似文献
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Tissières P Ochoda A Dunn-Siegrist I Drifte G Morales M Pfister R Berner M Pugin J 《PloS one》2012,7(3):e32863
Background
Bacterial sepsis is a major threat in neonates born prematurely, and is associated with elevated morbidity and mortality. Little is known on the innate immune response to bacteria among extremely premature infants.Methodology/Principal Findings
We compared innate immune functions to bacteria commonly causing sepsis in 21 infants of less than 28 wks of gestational age, 24 infants born between 28 and 32 wks of gestational age, 25 term newborns and 20 healthy adults. Levels of surface expression of innate immune receptors (CD14, TLR2, TLR4, and MD-2) for Gram-positive and Gram-negative bacteria were measured in cord blood leukocytes at the time of birth. The cytokine response to bacteria of those leukocytes as well as plasma-dependent opsonophagocytosis of bacteria by target leukocytes was also measured in the presence or absence of interferon-γ. Leukocytes from extremely premature infants expressed very low levels of receptors important for bacterial recognition. Leukocyte inflammatory responses to bacteria and opsonophagocytic activity of plasma from premature infants were also severely impaired compared to term newborns or adults. These innate immune defects could be corrected when blood from premature infants was incubated ex vivo 12 hrs with interferon-γ.Conclusion/Significance
Premature infants display markedly impaired innate immune functions, which likely account for their propensity to develop bacterial sepsis during the neonatal period. The fetal innate immune response progressively matures in the last three months in utero. Ex vivo treatment of leukocytes from premature neonates with interferon-γ reversed their innate immune responses deficiency to bacteria. These data represent a promising proof-of-concept to treat premature newborns at the time of delivery with pharmacological agents aimed at maturing innate immune responses in order to prevent neonatal sepsis. 相似文献664.
Parrino C Rossetti P Baratta R La Spina N La Delfa L Squatrito S Vigneri R Frittitta L 《PloS one》2012,7(4):e34551
The present study evaluates trends in the prevalence of overweight and obesity in relation to gender and area of residence between two cohorts of students aged 11–13 years in Sicily. The analysis was performed on 1,839 schoolchildren, with 924 and 915 children being studied in 1999–2001 and 2009–2010, respectively. The children who were enrolled during 2009–2010 had significantly higher body mass indexes (BMI), BMI z-scores, and waist circumferences than the children who were studied during 1999–2001 (p<0.0001 for all); these differences was also observed when the cohort was subdivided according to gender or residence area The prevalence of obesity increased significantly from 7.9% in 1999–2001 to 13.7% in 2009–2010 (p<0.0001), whereas thinness decreased significantly from 10.1% to 2.3% (p<0.0001) in the same periods. The increase of trends in the prevalence of obesity was significantly higher in males (9.7% vs. 17.6%, p = 0.0006) than in females (6.3% vs. 9.8%, p = 0.04) and was slightly higher in urban areas (8.8% vs. 14.3%, p = 0.002) than in rural areas (7.8% vs. 13.0%, p = 0.012). The male gender was associated with a higher risk of being overweight or obese (odds ratio: 1.63; 95% confidence intervals: 1.24–2.15; p = 0.0005) in 2009–2010 than in 1999–2001, after adjusting for age and the residence area. In conclusion, this study showed an increasing trend in the prevalence of overweight and obesity in Sicilian schoolchildren during the last decade and that this trend was related to gender, age and the area of residence. More specifically, our data indicated that the prevalence of obesity increased by 5.8%, the prevalence of thinness decreased by 7.8% and the prevalence of normal-weight children did not change over the course of a decade. These results suggest a shift in the body weights of Sicilian children toward the upper percentiles. 相似文献
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Hyperargininemia (HA) is an autosomal recessive disease that typically has a clinical presentation that is distinct from other urea cycle disorders. It is caused by the deficient activity of the enzyme arginase I, encoded by the gene ARG1. We screened for ARG1 mutations and measured erythrocyte enzyme activity in a series of 16 Brazilian HA patients. Novel mutations, in addition to previously described missense mutations, were analysed for their effect on the structure, stability and/or function of arginase I (ARG1) using bioinformatics tools. Three previously reported mutations were found (p.R21X; p.I11T and p.W122X), and five novel mutations were identified (p.G27D; p.G74V; p.T134I; p.R308Q; p.I174fs179). The p.T134I mutation was the most frequent in the Brazilian population. Patients carrying the p.R308Q mutation had higher residual ARG1 decreased activity, but presented no distinguishable phenotype compared to the other patients. Bioinformatics analyses revealed that missense mutations (1) affect the ARG1 active site, (2) interfere with the stability of the ARG1 folded conformation or (3) alter the quaternary structure of the ARG1. Our study reinforced the role of Arg308 residue for assembly of the ARG1 homotrimer. The panel of heterogeneous ARG1 mutations that cause HA was expanded, nevertheless a clear genotype-phenotype correlation was not observed in our series. 相似文献
669.
Herbert Marini Monica Currò Elena B. Adamo Francesca Polito Nadia Ferlazzo Alessandra Bitto Marco Atteritano Rosario D'Anna Angela Alibrandi Domenica Altavilla Francesco Squadrito Riccardo Ientile Daniela Caccamo 《Gene》2012
The incidence of cardiovascular disease (CVD) and resultant morbidity and mortality are highly increased in postmenopausal women. Recent observations indicate the involvement of estrogen receptor beta in the pathogenesis of CVD, and the potential role of ESR2 gene polymorphisms as independent risk factors for CVD. We aimed to investigate the possible association between the ESR2 AluI 1730G>A gene polymorphism (rs4986938) with different CVD risk markers, such as body mass index (BMI), blood fibrinogen, glucose and insulin, homeostasis model assessment of insulin resistance and urinary F2-isoprostanes, in 89 postmenopausal women. Genotyping for ESR2 1730G>A polymorphism showed the higher prevalence of heterozygous GA1730 genotype than either wild-type GG1730 or homozygously mutated AA1730 genotype (50.6 vs 34.8 or 14.6%, respectively). Statistical analysis of between-group variability revealed that mean levels of the examined CVD risk markers, except BMI and fibrinogen, were within the normal range in all subjects grouped to different ESR2 1730G>A genotypes. Interestingly, only fibrinogen levels were statistically different in AA1730 carriers compared with other genotypes. The analysis of genotype relative risk showed a significant elevation of plasma fibrinogen in AA1730 carriers compared with GG + GA ones. The present data strongly indicate that genotyping for the ESR2 AluI 1730G>A gene variant should be included in a screening panel for assessment of cardiovascular risk in menopausal women. 相似文献
670.
Fabrias G Muñoz-Olaya J Cingolani F Signorelli P Casas J Gagliostro V Ghidoni R 《Progress in lipid research》2012,51(2):82-94
Sphingolipids are a wide family of lipids that share common sphingoid backbones, including (2S,3R)-2-amino-4-octadecane-1,3-diol (dihydrosphingosine) and (2S,3R,4E)-2-amino-4-octadecene-1,3-diol (sphingosine). The metabolism and biological functions of sphingolipids derived from sphingosine have been the subject of many reviews. In contrast, dihydrosphingolipids have received poor attention, mainly due to their supposed lack of biological activity. However, the reported biological effects of active site directed dihydroceramide desaturase inhibitors and the involvement of dihydrosphingolipids in the response of cells to known therapeutic agents support that dihydrosphingolipids are not inert but are in fact biologically active and underscore the importance of elucidating further the metabolic pathways and cell signaling networks involved in the biological activities of dihydrosphingolipids. Dihydroceramide desaturase is the enzyme involved in the conversion of dihydroceramide into ceramide and it is crucial in the regulation of the balance between sphingolipids and dihydrosphingolipids. Furthermore, given the enzyme requirement for O? and the NAD(P)H cofactor, the cellular redox balance and dihydroceramide desaturase activity may reciprocally influence each other. In this review both dihydroceramide desaturase and the biological functions of dihydrosphingolipids are addressed and perspectives on this field are discussed. 相似文献