Adenovirus vectors can induce activation of endothelial cells: CD40-CD40L interactions partly participate in the endothelial cells activation induced by adenovirus vectors in an NF-kappaB-dependent manner

Replication-defective adenovirus vector without both E1 and E3 is one of the most popular tools in transgenic therapies. However, more attention should be paid to adenovirus vectors mediated-gene modified study on endothelial cells (ECs). To verify the possible danger in that process, we explored the effect of adenovirus on ECs in this study. By using western blot analysis, we showed that the level of both CD40 and CD40L on human umbilical vein endothelial cells (HUVECs) were upregraduated by adenovirus vector infection at 100 multiplicity of infection (MOI). The activation of ECs induced by adenovirus vector infection at MOI 100 can be partly inhibited by a blockade of CD40/CD40L interactions by using the recombinant adenovirus Ad-sCD40LIg or an anti-CD40L monoclonal antibody (mAb) in vitro. On ECs, blockade of CD40/CD40L decreased the expression of IL (interleukin)-6, IL-8 and intercellular adhesion molecule (ICAM) in adenovirus vector-induced cells. In electrophoretic mobility shift assay (EMSA), both Ad-sCD40LIg and anti-CD40L mAb can attenuate the activity of NF-kappaB (NF-κB) pathway contributing to the activation of ECs, which indicated that CD40-CD40L interactions played significant role in the activation of ECs induced by adenovirus vectors via an NF-κB pathway. Our study provide evidences for a supplementary mechanism of the ECs activation induced by adenovirus vector infection and suggests that CD40-CD40L interactions partly participate in the ECs activation induced by adenovirus vectors in an NF-κB-dependent manner.Key words: Adenovirus vector, CD40, CD40L, endothelial cells, NF-kappaB

New Terms for the Compact Form of Electroweak Chiral Lagrangian

The compact form of the electroweak chiral Lagrangian is a reformulation of its original form and is expressed in terms of chiral rotated electroweak gauge fields, which is crucial for relating the information of underlying theories to the coefficients of the low-energy effective Lagrangian. However the compact form obtained in previous works is not complete. In this letter we add several new chiral invariant terms to it and discuss the contributions of these terms to the original electroweak chiral Lagrangian.Comment: 3 pages, references adde

Large-scale inference of liver fat with neural networks on UK Biobank body MRI

The UK Biobank Imaging Study has acquired medical scans of more than 40,000 volunteer participants. The resulting wealth of anatomical information has been made available for research, together with extensive metadata including measurements of liver fat. These values play an important role in metabolic disease, but are only available for a minority of imaged subjects as their collection requires the careful work of image analysts on dedicated liver MRI. Another UK Biobank protocol is neck-to-knee body MRI for analysis of body composition. The resulting volumes can also quantify fat fractions, even though they were reconstructed with a two- instead of a three-point Dixon technique. In this work, a novel framework for automated inference of liver fat from UK Biobank neck-to-knee body MRI is proposed. A ResNet50 was trained for regression on two-dimensional slices from these scans and the reference values as target, without any need for ground truth segmentations. Once trained, it performs fast, objective, and fully automated predictions that require no manual intervention. On the given data, it closely emulates the reference method, reaching a level of agreement comparable to different gold standard techniques. The network learned to rectify non-linearities in the fat fraction values and identified several outliers in the reference. It outperformed a multi-atlas segmentation baseline and inferred new estimates for all imaged subjects lacking reference values, expanding the total number of liver fat measurements by factor six

Effect of 1,25-(OH)2D3 on proliferation of fibroblast-like synoviocytes and expressions of pro-inflammatory cytokines through regulating MicroRNA-22 in a rat model of rheumatoid arthritis

Objective: This study aims to investigate the regulatory mechanism of 1,25-(OH)2D3 on the proliferation of fibroblast-like synoviocytes (FLS) and expressions of pro-inflammatory cytokines in rheumatoid arthritis (RA) rats via microRNA-22 (miR-22).Methods: A rat model of RA was established with a subcutaneous injection of type II collagen. After treated with different concentrations of 1,25-(OH)2D3 the proliferation of FLS was estimated by the MTT method, and the optimal concentration of 1,25-(OH)2D3 was selected for further experiments. Cell proliferation was detected by MTT. Cell cycle and apoptosis were analyzed by FCM. The IL-1β, IL-6, IL-8, and PGE2 protein expressions were determined by ELISA, and MMP-3, INOS, and Cox-2 mRNA expressions were measured by qRT-PCR.Results: The rat model of RA was successfully established. Compared with the blank group, the 1,25-(OH)2D3 and miR-22 inhibitors groups exhibited higher proliferation inhibition and apoptosis rates, lower levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and PGE2), and decreased mRNA expressions of MMP-3, INOS, and Cox-2. The miR-22 mimics group had lower proliferation inhibition and apoptosis rates, elevated expressions of pro-inflammatory cytokines and MMP-3, INOS, and Cox-2 than the blank group. In contrast to the 1,25-(OH)2D3 group, the proliferation inhibition and apoptosis rates were down-regulated, and the expressions of pro-inflammatory cytokines and MMP-3, INOS, and Cox-2 were up-regulated in the 1,25-(OH)2D3 + miR-22 mimics group.Conclusion: Our study demonstrated that 1,25-(OH)2D3 inhibits the proliferation of FLS and alleviates inflammatory response in RA rats by down-regulating miR-22

Synonymous Codon Ordering: A Subtle but Prevalent Strategy of Bacteria to Improve Translational Efficiency

Background: In yeast coding sequences, once a particular codon has been used, subsequent occurrence of the same amino acid tends to use codons sharing the same tRNA. Such a phenomenon of co-tRNA codons pairing bias (CTCPB) is also found in some other eukaryotes but it is not known whether it occurs in prokaryotes. Methodology/Principal Findings: In this study, we focused on a total of 773 bacterial genomes to investigate their synonymous codon pairing preferences. After calculating the actual frequencies of synonymous codon pairs and comparing them with their expected values, we detected an obvious pairing bias towards identical codon pairs. This seems consistent with the previously reported CTCPB phenomenon, since identical codons are certainly read by the same tRNA. However, among co-tRNA but non-identical codon pairs, only 22 were often found overrepresented, suggesting that many co-tRNA codons actually do not preferentially pair together in prokaryotes. Therefore, the previously reported co-tRNA codons pairing rule needs to be more rigorously defined. The affinity differences between a tRNA anticodon and its readable codons should be taken into account. Moreover, both within-gene-shuffling tests and phylogenetic analyses support the idea that translational selection played an important role in shaping the observed synonymous codon pairing pattern in prokaryotes. Conclusions: Overall, a high level of synonymous codon pairing bias was detected in 73 % investigated bacterial species

Differential expression of microRNAs during fiber development between fuzzless- lintless mutant and its wild-type allotetraploid cotton

Cotton is one of the most important textile crops but little is known how microRNAs regulate cotton fiber development. Using a well-studied cotton fiberless mutant Xu-142-fl, we compared 54 miRNAs for their expression between fiberless mutant and its wildtype. In wildtype Xu-142, 26 miRNAs are involved in cotton fiber initiation and 48 miRNAs are related to primary wall synthesis and secondary wall thickening. Thirty three miRNAs showed different expression in fiber initiation between Xu-142 and Xu- 142-fl. These miRNAs potentially target 723 protein-coding genes, including transcription factors, such as MYB, ARF, and LRR. ARF18 was newly predicted targets of miR160a, and miR160a was expressed at higher level in −2DPA of Xu-142-fl compared with Xu-142. Furthermore, the result of Gene Ontology- based term classification (GO), EuKaryotic Orthologous Groups (KOG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis shows that miRNA targets were classified to 222 biological processes, 64 cellular component and 42 molecular functions, enriched in 22 KOG groups, and classified into 28 pathways. Together, our study provides evidence for better understanding of miRNA regulatory roles in the process of fiber development, which is helpful to increase fiber yield and improve fiber quality