Maximum Gene-Support Tree

Genomes and genes diversify during evolution; however, it is unclear to what extent genes still retain the relationship among species. Model species for molecular phylogenetic studies include yeasts and viruses whose genomes were sequenced as well as plants that have the fossil-supported true phylogenetic trees available. In this study, we generated single gene trees of seven yeast species as well as single gene trees of nine baculovirus species using all the orthologous genes among the species compared. Homologous genes among seven known plants were used for validation of the finding. Four algorithms—maximum parsimony (MP), minimum evolution (ME), maximum likelihood (ML), and neighbor-joining (NJ)—were used. Trees were reconstructed before and after weighting the DNA and protein sequence lengths among genes. Rarely a gene can always generate the “true tree” by all the four algorithms. However, the most frequent gene tree, termed “maximum gene-support tree” (MGS tree, or WMGS tree for the weighted one), in yeasts, baculoviruses, or plants was consistently found to be the “true tree” among the species. The results provide insights into the overall degree of divergence of orthologous genes of the genomes analyzed and suggest the following: 1) The true tree relationship among the species studied is still maintained by the largest group of orthologous genes; 2) There are usually more orthologous genes with higher similarities between genetically closer species than between genetically more distant ones; and 3) The maximum gene-support tree reflects the phylogenetic relationship among species in comparison

Genome-scale approach proves that the lungfish-coelacanth sister group is the closest living relative of tetrapods with the BEST program

The origin of tetrapods has not been resolved for decades. Three principal hypotheses (lungfish-tetrapod, coelacanth-tetrapod, or lungfish-coelacanth sister group) have been proposed. We used the Bayesian method under the coalescence model with the latest program (BEST) to perform a phylogenetic analysis for seven relevant taxa and 43 nuclear genes encoding amino acid residues with the jackknife method for taxon sub-sampling. The results, combined with those of other three genome-scale approaches, successfully prove the hypothesis that lungfishes and coelacanths form a monophyletic sister group and are equally related to tetrapods supported by high Bayesian posterior probabilities of the branch (a lungfish-coelacanth clade) and high taxon jackknife supports

Identification of microRNAs Involved in the Host Response to Enterovirus 71 Infection by a Deep Sequencing Approach

Role of microRNA (miRNA) has been highlighted in pathogen-host interactions recently. To identify cellular miRNAs involved in the host response to enterovirus 71 (EV71) infection, we performed a comprehensive miRNA profiling in EV71-infected Hep2 cells through deep sequencing. 64 miRNAs were found whose expression levels changed for more than 2-fold in response to EV71 infection. Gene ontology analysis revealed that many of these mRNAs play roles in neurological process, immune response, and cell death pathways, which are known to be associated with the extreme virulence of EV71. To our knowledge, this is the first study on host miRNAs expression alteration response to EV71 infection. Our findings supported the hypothesis that certain miRNAs might be essential in the host-pathogen interactions

High-Throughput Sequencing of MicroRNAs in Adenovirus Type 3 Infected Human Laryngeal Epithelial Cells

Adenovirus infection can cause various illnesses depending on the infecting serotype, such as gastroenteritis, conjunctivitis, cystitis, and rash illness, but the infection mechanism is still unknown. MicroRNAs (miRNA) have been reported to play essential roles in cell proliferation, cell differentiation, and pathogenesis of human diseases including viral infections. We analyzed the miRNA expression profiles from adenovirus type 3 (AD3) infected Human laryngeal epithelial (Hep2) cells using a SOLiD deep sequencing. 492 precursor miRNAs were identified in the AD3 infected Hep2 cells, and 540 precursor miRNAs were identified in the control. A total of 44 miRNAs demonstrated high expression and 36 miRNAs showed lower expression in the AD3 infected cells than control. The biogenesis of miRNAs has been analyzed, and some of the SOLiD results were confirmed by Quantitative PCR analysis. The present studies may provide a useful clue for the biological function research into AD3 infection

Obesity-Related Genetic Variants and Hyperuricemia Risk in Chinese Men

Objective: Obesity/metabolic syndrome and hyperuricemia are clinically associated; however, the association of obesity/metabolic syndrome-related genetic variants with hyperuricemia is not clear. Therefore, we assessed this association in Chinese men diagnosed with hyperuricemia in comparison to a non-hyperuricemia group.Methods: We genotyped 47 single nucleotide polymorphisms (SNPs) previously identified to be associated with obesity or metabolic syndrome in 474 adult males (aged ≥ 18 years) using multiplex polymerase chain reaction. Multivariate logistic regression was used to investigate the association between the genetic variations and hyperuricemia. Stratified analyses were applied to further assess the associations.Results: The obesity-related SNP in MSRA rs545854 significantly affected serum uric acid levels. In addition, the G-allele of rs545854 was positively associated with the risk of hyperuricemia [odds ratio (OR) = 2.80, 95% confidence interval (CI) = 1.19–6.64, P = 0.0188]. After adjusting the model for body mass index and central obesity, rs545854 was shown to be an independent factor increasing the risk of hyperuricemia (OR = 2.81, 95%CI = 1.18–6.70, P = 0.0196). Stratified analyses also showed a significant association between rs545854 and hyperuricemia among meat eaters (OR = 2.62, 95%CI = 1.09–6.26, P = 0.0308).Conclusion: The obesity-related SNP rs545854 was correlated with the serum uric acid level and risk of hyperuricemia in a male Chinese population. Therefore, men carrying this SNP could benefit from limiting their meat consumption to prevent hyperuricemia. These findings suggest an underlying genetic link between obesity and hyperuricemia worthy of further exploration

Real-world outcomes of chemotherapy plus immune checkpoint inhibitors versus chemotherapy alone in advanced, unresectable, and recurrent intrahepatic cholangiocarcinoma

BackgroundThere are limited treatment options available to improve the prognosis of patients with advanced or metastatic cholangiocarcinoma particularly intrahepatic cholangiocarcinoma (iCCA). This study aimed to evaluate the efficacy and safety of combining chemotherapy plus anti-PD-1/L1 drugs compared to chemotherapy alone in advanced, unresectable, and recurrent intrahepatic cholangiocarcinoma patients.MethodsPatients with advanced, unresectable, or recurrent iCCA who received chemotherapy combined with PD-1/PD-L1 inhibitors or chemotherapy alone were retrospectively screened and analyzed. The primary outcomes were overall survival (OS) and progression-free survival (PFS). The secondary outcomes were overall response rate (ORR), disease control rate (DCR), and safety.Results81 eligible patients were included in the study (chemotherapy plus anti-PD-1/L1 group n=51, and chemotherapy-alone group n=30). The median OS was 11 months for the chemotherapy plus anti-PD-1/L1 group, significantly longer than the 8 months in the chemotherapy-alone group, with a hazard ratio (HR) of 0.53 (95% CI 0.30–0.94, P = 0.008). The median PFS of 7 months in the chemotherapy plus anti-PD-1/L1 group was significantly longer than the 4 months in the chemotherapy-alone group, with HR of 0.48 (95% CI 0.27–0.87); P = 0.002). Similarly, the combined therapy group showed a higher ORR (29.4%) and DCR (78.4%) compared to 13.3% and 73.3% in the chemotherapy-alone group, respectively. More grade 3–4 treatment-related adverse effects were recorded in the chemotherapy plus anti-PD-1/L1 group (66.7%) compared to the chemotherapy-alone group (23.3%), however, they were manageable and tolerable.ConclusionChemotherapy plus anti-PD-1/L1 represents a more effective and tolerable treatment option for advanced, unresectable, and recurrent iCCA patients compared to chemotherapy alone