Evolutionary Expansion of Nematode-Specific Glycine-Rich Secreted Peptides

A genome‐wide survey across 10 species from algae Guillardia theta to mammals revealed that Caenorhabditis elegans and Caenorhabditis briggsae acquired a large number of glycine‐rich secreted peptides (GRSPs, 110 GRSPs in C. elegans and 93 in C. briggsae) during evolution in this study. Chromosomal mapping indicated that most GRSPs were clustered on their genomes [103 (93.64%) in C. elegans and 82 (88.17%) in C. briggsae]. Totally, there are 18 GRSPs cluster units in C. elegans and 13 in C. briggsae. Except for four C. elegans where GRSP clusters lacking matching clusters in C. briggsae, all other GRSP clusters had its corresponding orthologous clusters between the two nematodes. Using eight transcriptomic datasets of Affmyetrix microarray, genome‐wide association studies identified many co‐expressed GRSPs clusters after C. elegans infections. Highly homologous coding sequences and conserved exon‐intron organizations indicated that GRSP tight clusters might have originated from local DNA duplications. The conserved synteny blocks of GRSP clusters between their genomes, the co‐expressed GRSPs clusters after C. elegans infections, and a strong purifying selection of protein‐coding sequences suggested evolutionary constraint acting on C. elegans to ensure that C. elegans could rapidly launch and fulfill systematic responses against infections by co‐expression, co‐regulation, and co‐functionality of GRSP clusters

Comprehensively Surveying Structure and Function of RING Domains from Drosophila melanogaster

Using a complete set of RING domains from Drosophila melanogaster, all the solved RING domains and cocrystal structures of RING-containing ubiquitin-ligases (RING-E3) and ubiquitin-conjugating enzyme (E2) pairs, we analyzed RING domains structures from their primary to quarternary structures. The results showed that: i) putative orthologs of RING domains between Drosophila melanogaster and the human largely occur (118/139, 84.9%); ii) of the 118 orthologous pairs from Drosophila melanogaster and the human, 117 pairs (117/118, 99.2%) were found to retain entirely uniform domain architectures, only Iap2/Diap2 experienced evolutionary expansion of domain architecture; iii) 4 evolutionary structurally conserved regions (SCRs) are responsible for homologous folding of RING domains at the superfamily level; iv) besides the conserved Cys/His chelating zinc ions, 6 equivalent residues (4 hydrophobic and 2 polar residues) in the SCRs possess good-consensus and conservation- these 4 SCRs function in the structural positioning of 6 equivalent residues as determinants for RING-E3 catalysis; v) members of these RING proteins located nucleus, multiple subcellular compartments, membrane protein and mitochondrion are respectively 42 (42/139, 30.2%), 71 (71/139, 51.1%), 22 (22/139, 15.8%) and 4 (4/139, 2.9%); vi) CG15104 (Topors) and CG1134 (Mul1) in C3HC4, and CG3929 (Deltex) in C3H2C3 seem to display broader E2s binding profiles than other RING-E3s; vii) analyzing intermolecular interfaces of E2/RING-E3 complexes indicate that residues directly interacting with E2s are all from the SCRs in RING domains. Of the 6 residues, 2 hydrophobic ones contribute to constructing the conserved hydrophobic core, while the 2 hydrophobic and 2 polar residues directly participate in E2/RING-E3 interactions. Based on sequence and structural data, SCRs, conserved equivalent residues and features of intermolecular interfaces were extracted, highlighting the presence of a nucleus for RING domain fold and formation of catalytic core in which related residues and regions exhibit preferential evolutionary conservation

The cross-sectional study of hepatic lipase SNPs and plasma lipid levels

By the combination of meta-analysis, the data of the 1,000 Genomes Project Phase 3, and the promoter sequence of hepatic lipase (LIPC), we performed the cross-sectional study to explore the associations of four variants (rs1077835; rs1077834; rs1800588 [C-514T], and rs2070895 [G-250A]) in LIPC promoter with plasma lipid levels. Our results indicate that the first and the next three of the four SNPs are, respectively, reported to be associated with the decreased and increased HDL-c level. Meta-analysis of 87 studies with 101,988 participants indicates that HDL-c level in rs1800588 (C-514T) (pooled mean difference = 0.03, 95%CI (0.03, 0.04), p < .001) and rs2070895 (G-250A) (pooled mean difference = 0.07, 95%CI (0.05, 0.09), p < .001) is higher in allele T or A carriers. Similarly, LDL-c, TC, TG, and BMI levels are generally increased in T or A alleles carriers. We failed to conduct the meta-analysis of rs1077835 and rs1077834 due to the limited previous reports. Data from the 1,000 Genomes indicate that the allele frequencies of the four SNPs in total or subpopulations are almost equal to each other. The paired value r2 and D' of the four SNPs are larger than 0.8, which indicate the linkage disequilibrium of the four variants. The analysis of LIPC promoter indicate that C-514T and G-250A are, respectively, located in transcriptional factor binding sites of USF1and Pbx1b, which may partly explain the effect of the two SNPs on the decreased LIPC activity in the alleles carriers and the corresponding increased plasma lipids hydrolyzed by LIPC. These results may help us to better understand the different effects of the four SNPs on the plasma lipid levels among subpopulations and offer clues for future clinical treatment of dyslipidemia-related diseases

Correction to: The imbalance in the complement system and its possible physiological mechanisms in patients with lung cancer

Following publication of the original article [1], it was noticed that Fig. 3c was omitted from the final published article

The imbalance in the complement system and its possible physiological mechanisms in patients with lung cancer

Abstract Background The clinical and experimental evidences for complement-cancer relationships are solid, whereas an epidemiological study reporting the imbalance of complement system in patients is still lacking. Methods Using publicly available databases, we jointly compared the levels of complement components in plasma and lung cancer tissues. With iTRAQ proteomics, quantitative RT-PCR and western blotting, we analysed the differences in complement levels in lung cancer tissues and normal control tissues. Complement components are mainly synthesized by the liver and secreted into the blood. Using paired co-cultures of human normal QSG-7701 hepatocytes with lung cancer cells (A549, LTEP-α-2 or NCI-H1703) or human normal bronchial epithelial (HBE) cells, we examined the effects of lung cancer cells on complement synthesis and secretion in QSG-7701 hepatocytes. Results An integrated analysis of transcriptome and proteome datasets from 43 previous studies revealed lower mRNA and protein levels of 25 complement and complement-related components in lung cancer tissues than those in normal control tissues; conversely, higher levels of complement proteins were detected in plasma from patients than those in healthy subjects. Our iTRAQ proteome study identified decreased and increased levels of 31 and 2 complement and complement-related proteins, respectively, in lung cancer tissues, of which the reduced levels of 10 components were further confirmed using quantitative RT-PCR and western blotting. Paired co-cultures of QSG-7701 hepatocytes with A549, LTEP-α-2, NCI-H1703 or HBE cells indicated that lung cancer cells increased complement synthesis and secretion in QSG-7701 cells compared to HBE cells. Conclusions The opposite associations between the levels of complement and complement-related components in lung cancer tissues and plasma from patients that have been repeatedly reported by independent publications may indicate the prevalence of an imbalance in the complement system of lung cancer patients. The possible mechanism of the imbalance may be associated not only with the decreased complement levels in lung cancer tissues but also the concurrent lung cancer tissue-induced increase in hepatocyte complement synthesis and plasma secretion in patients. And the imbalance should be accompanied by a suppression of complement-dependent immunity in lung cancer tissues coupled with a burden of complement immunity in the circulation of patients

Enhanced Electrochemical Performance of LiNi_0.5Mn_1.5O₄ Cathode Material by YPO₄ Surface Modification

Cathode material LiNi_0.5Mn_1.5O₄ (LNMO) for lithium-ion batteries is successfully synthesized by a sol–gel method and is further modified by a thin layer of YPO₄ (1, 3, and 5 wt %) through a simple wet chemical strategy. Physical characterizations indicate that the YPO₄ nanolayer has a little impact on the cathode structure. Electrochemical optimization reveals that the 3 wt % YPO₄-coated LNMO could still deliver a high specific capacity of 107 mAh g^–1 after 240 cycles, with a capacity retention of 77.5%, much higher than that of the pristine electrode. Electrochemical impedance spectroscopy (EIS) analysis proves that the rapid increase of surface impedance could be suppressed by the YPO₄ coating layer and thus facilitates the surface kinetics behavior in repeated cycling. Through further material aging experiments, the improvement of electrochemical performances could be attributed to the formation of Lewis acid YF₃, converted from the YPO₄ coating layer in the LiPF₆-based electrolyte, which not only scavenges the surface insulating alkaline species with a high acidity but also accelerates ion exchange on the material surface and thus helps to generate the solid solution Li–Ni–Mn–Y–O on the surface of YPO₄-coated LNMO