New Generation University College

About: New Generation University College is a education organization based out in Addis Ababa, Ethiopia. It is known for research contribution in the topics: Population & Cancer. The organization has 17440 authors who have published 28460 publications receiving 667288 citations. The organization is also known as: National University College.

Epstein-barr virus-positive gastric carcinoma demonstrates frequent aberrant methylation of multiple genes and constitutes CpG island methylator phenotype-positive gastric carcinoma

Abstract: CpG island methylation is an important mechanism for inactivating the genes involved in tumorigenesis. Gastric carcinoma (GC) is one of the tumors that exhibits a high frequency of aberrant CpG island methylation. There have been many reports suggesting a close link between Epstein-Barr virus (EBV) and the development of GC. However, little is known about the oncogenic mechanism of EBV in gastric carcinogenesis. Twenty-one cases of EBV-positive GC and 56 cases of EBV-negative GC were examined for aberrant DNA methylation of the CpG islands of 19 genes or loci and the differences in the methylation frequency between EBV-positive and -negative GCs were investigated to determine a role of aberrant methylation in EBV-related gastric carcinogenesis. The average number of methylated genes or loci was higher in EBV-positive GCs than in EBV-negative GCs (13.4 versus 7.8, respectively, P 90% in EBV-positive GCs. The methylation frequency difference in the respective CpG islands between EBV-positive and -negative GCs was statistically significant (P < 0.05). Among these genes or loci, the methylation frequency of p16 in the EBV-positive GCs was more than three times higher than in the EBV-negative GCs. The PTEN, RASSF1A, GSTP1, MGMT, and MINT2 were methylated in EBV-positive GCs at a frequency of more than three times that of the EBV-negative GCs. These results demonstrate a relationship between EBV and aberrant methylation in GC and suggest that aberrant methylation may be an important mechanism of EBV-related gastric carcinogenesis.

De novo assembly and phasing of a Korean human genome

Abstract: De novo assembly and phasing of the genome of an individual from Korea using a combination of different sequencing approaches provides a useful population-specific reference genome and represents the most contiguous human genome assembly so far. Jeong-Sun Seo and colleagues report de novo assembly and phasing of the genome of an individual from Korea using a combination of PacBio long-read sequencing, Illumina short-read sequencing, 10X Genomics linked reads, bacterial artificial chromosome (BAC) sequencing and BioNano Genomics optical mapping. This provides a useful population-specific reference genome and represents the most contiguous human genome assembly to date. The authors use this to close gaps in the human reference genome and map structural variation. Advances in genome assembly and phasing provide an opportunity to investigate the diploid architecture of the human genome and reveal the full range of structural variation across population groups. Here we report the de novo assembly and haplotype phasing of the Korean individual AK1 (ref. 1) using single-molecule real-time sequencing2, next-generation mapping3, microfluidics-based linked reads4, and bacterial artificial chromosome (BAC) sequencing approaches. Single-molecule sequencing coupled with next-generation mapping generated a highly contiguous assembly, with a contig N50 size of 17.9 Mb and a scaffold N50 size of 44.8 Mb, resolving 8 chromosomal arms into single scaffolds. The de novo assembly, along with local assemblies and spanning long reads, closes 105 and extends into 72 out of 190 euchromatic gaps in the reference genome, adding 1.03 Mb of previously intractable sequence. High concordance between the assembly and paired-end sequences from 62,758 BAC clones provides strong support for the robustness of the assembly. We identify 18,210 structural variants by direct comparison of the assembly with the human reference, identifying thousands of breakpoints that, to our knowledge, have not been reported before. Many of the insertions are reflected in the transcriptome and are shared across the Asian population. We performed haplotype phasing of the assembly with short reads, long reads and linked reads from whole-genome sequencing and with short reads from 31,719 BAC clones, thereby achieving phased blocks with an N50 size of 11.6 Mb. Haplotigs assembled from single-molecule real-time reads assigned to haplotypes on phased blocks covered 89% of genes. The haplotigs accurately characterized the hypervariable major histocompatability complex region as well as demonstrating allele configuration in clinically relevant genes such as CYP2D6. This work presents the most contiguous diploid human genome assembly so far, with extensive investigation of unreported and Asian-specific structural variants, and high-quality haplotyping of clinically relevant alleles for precision medicine.

Decline in miR-181a expression with age impairs T cell receptor sensitivity by increasing DUSP6 activity

Abstract: The ability of the human immune system to respond to vaccination declines with age. We identified an age-associated defect in T cell receptor (TCR)-induced ERK phosphorylation in naive CD4+ T cells (P<0.0001) while other signals, such as ZAP70 and PLC-γ1 phosphorylation were not impaired. The defective ERK signaling was caused by the dual specific phosphatase (DUSP) 6 whose protein levels increased with age (r = 0.68, P < 0.0001) due to a decline in repression by miR-181a (r = −0.59, P < 0.0001). Reconstitution of miR-181a lowered DUSP6 levels in naive CD4+ T cells in elderly individuals. DUSP6 repression with miR-181a or specific siRNA, and DUSP6 inhibition with the allosteric inhibitor (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one improved CD4+ T cell responses as seen by increased expression of activation markers, improved proliferation and supported preferential TH1 differentiation. DUSP6 is a potential intervention target for restoring T cell responses in the elderly, which may augment the effectiveness of vaccination.

Comparative absorption, distribution, and excretion of titanium dioxide and zinc oxide nanoparticles after repeated oral administration

Abstract: Background: The in vivo kinetics of nanoparticles is an essential to understand the hazard of nanoparticles. Here, the absorption, distribution, and excretion patterns of titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles following oral administration were evaluated. Methods: Nanoparticles were orally administered to rats for 13 weeks (7 days/week). Samples of blood, tissues (liver, kidneys, spleen, and brain), urine, and feces were obtained at necropsy. The level of Ti or Zn in each sample was measured using inductively coupled plasma-mass spectrometry. Results: TiO2 nanoparticles had extremely low absorption, while ZnO nanoparticles had higher absorption and a clear dose-response curve. Tissue distribution data showed that TiO2 nanoparticles were not significantly increased in sampled organs, even in the group receiving the highest dose (1041.5 mg/kg body weight). In contrast, Zn concentrations in the liver and kidney were significantly increased compared with the vehicle control. ZnO nanoparticles in the spleen and brain were minimally increased. Ti concentrations were not significantly increased in the urine, while Zn levels were significantly increased in the urine, again with a clear dose-response curve. Very high concentrations of Ti were detected in the feces, while much less Zn was detected in the feces. Conclusions: Compared with TiO2 nanoparticles, ZnO nanoparticles demonstrated higher absorption and more extensive organ distribution when administered orally. The higher absorption of ZnO than TiO2 nanoparticles might be due to the higher dissolution rate in acidic gastric fluid, although more thorough studies are needed.