22 research outputs found
The Seroprevalence and Seroincidence of Enterovirus71 Infection in Infants and Children in Ho Chi Minh City, Viet Nam
Enterovirus 71 (EV71)-associated hand, foot and mouth disease has emerged as a serious public health problem in South East Asia over the last decade. To better understand the prevalence of EV71 infection, we determined EV71 seroprevalence and seroincidence amongst healthy infants and children in Ho Chi Minh City, Viet Nam. In a cohort of 200 newborns, 55% of cord blood samples contained EV71 neutralizing antibodies and these decayed to undetectable levels by 6 months of age in 98% of infants. The EV71 neutralizing antibody seroconversion rate was 5.6% in the first year and 14% in the second year of life. In children 5â15 yrs of age, seroprevalence of EV71 neutralizing antibodies was 84% and in cord blood it was 55%. Taken together, these data suggest EV71 force of infection is high and highlights the need for more research into its epidemiology and pathogenesis in high disease burden countries
Colorectal cancer stages transcriptome analysis
Colorectal cancer (CRC) is the third most common cancer and the second leading cause of
cancer-related deaths in the United States. The purpose of this study was to evaluate the
gene expression differences in different stages of CRC. Gene expression data on 433 CRC
patient samples were obtained from The Cancer Genome Atlas (TCGA). Gene expression
differences were evaluated across CRC stages using linear regression. Genes with
p 0.001 in expression differences were evaluated further in principal component analysis
and genes with p 0.0001 were evaluated further in gene set enrichment analysis. A total of
377 patients with gene expression data in 20,532 genes were included in the final analysis.
The numbers of patients in stage I through IV were 59, 147, 116 and 55, respectively. NEK4
gene, which encodes for NIMA related kinase 4, was differentially expressed across the four
stages of CRC. The stage I patients had the highest expression of NEK4 genes, while the
stage IV patients had the lowest expressions (p = 9*10â6
). Ten other genes (RNF34,
HIST3H2BB, NUDT6, LRCh4, GLB1L, HIST2H4A, TMEM79, AMIGO2, C20orf135 and
SPSB3) had p value of 0.0001 in the differential expression analysis. Principal component
analysis indicated that the patients from the 4 clinical stages do not appear to have distinct
gene expression pattern. Network-based and pathway-based gene set enrichment analyses
showed that these 11 genes map to multiple pathways such as meiotic synapsis and packaging of telomere ends, etc. Ten of these 11 genes were linked to Gene Ontology terms
such as nucleosome, DNA packaging complex and protein-DNA interactions. The protein
complex-based gene set analysis showed that four genes were involved in H2AX complex
II. This study identified a small number of genes that might be associated with clinical stages
of CRC. Our analysis was not able to find a molecular basis for the current clinical staging
for CRC based on the gene expression patterns
k-Nearest neighbor models for microarray gene expression analysis and clinical outcome prediction
In the clinical application of genomic data analysis and modeling, a number of factors contribute to the performance of disease classification and clinical outcome prediction. This study focuses on the k-nearest neighbor (KNN) modeling strategy and its clinical use. Although KNN is simple and clinically appealing, large performance variations were found among experienced data analysis teams in the MicroArray Quality Control Phase II (MAQC-II) project. For clinical end points and controls from breast cancer, neuroblastoma and multiple myeloma, we systematically generated 463â320 KNN models by varying feature ranking method, number of features, distance metric, number of neighbors, vote weighting and decision threshold. We identified factors that contribute to the MAQC-II project performance variation, and validated a KNN data analysis protocol using a newly generated clinical data set with 478 neuroblastoma patients. We interpreted the biological and practical significance of the derived KNN models, and compared their performance with existing clinical factors
Asexual expansion of Toxoplasma gondii merozoites is distinct from tachyzoites and entails expression of non-overlapping gene families to attach, invade, and replicate within feline enterocytes
Common variants near TERC are associated with leukocyte telomere length in the Chinese Han population
A recent genome-wide association study has identified an association between leukocyte telomere length (LTL) and a locus at 3q26 that includes TERC. In order to evaluate the effects of the SNPs rs12696304 and rs16847897 near TERC in the population of mainland China, we conducted an association study of LTL focusing on these two candidate SNPs in a sample of 4016 Chinese Han individuals. Multiple linear regression analyses were performed to evaluate the association of LTL with each SNP adjusted for age, gender and diabetes status. In the study, we confirmed the association of SNP rs12696304 and rs16847897 near TERC with LTL in the Chinese Han population (PâŒ4.5 Ă 10â3 and 9.5 Ă 10â5, respectively). Each copy of the major allele of rs12696304 and rs16847897 was associated with a shorter mean telomere length of 0.024 and 0.031 T/S respectively, which is equivalent to about 3 and 4 years of average age-related telomere attrition. Our short report confirmed the effects of SNPs near TERC on LTL in the Chinese Han population for the first time
RNA-binding IMPs promote cell adhesion and invadopodia formation
Oncofetal RNA-binding IMPs have been implicated in mRNA localization, nuclear export, turnover and translational control. To depict the cellular actions of IMPs, we performed a loss-of-function analysis, which showed that IMPs are necessary for proper cell adhesion, cytoplasmic spreading and invadopodia formation. Loss of IMPs was associated with a coordinate downregulation of mRNAs encoding extracellular matrix and adhesion proteins. The transcripts were present in IMP RNP granules, implying that IMPs were directly involved in the post-transcriptional control of the transcripts. In particular, we show that a 5.0 kb CD44 mRNA contained multiple IMP-binding sites in its 3âČUTR, and following IMP depletion this species became unstable. Direct knockdown of the CD44 transcript mimicked the effect of IMPs on invadopodia, and we infer that CD44 mRNA stabilization may be involved in IMP-mediated invadopodia formation. Taken together, our results indicate that RNA-binding proteins exert profound effects on cellular adhesion and invasion during development and cancer formation
Common variants near TERC are associated with mean telomere length
We conducted genome-wide association analyses of mean leukocyte telomere length in 2,917 individuals, with follow-up replication in 9,492 individuals. We identified an association with telomere length on 3q26 (rs12696304, combined P = 3.72 x 10(-14)) at a locus that includes TERC, which encodes the telomerase RNA component. Each copy of the minor allele of rs12696304 was associated with an similar to 75-base-pair reduction in mean telomere length, equivalent to similar to 3.6 years of age-related telomere-length attrition