G‐quadruplexes form folded structures because of tandem repeats of guanine sequences in DNA or RNA. They adopt a variety of conformations, depending on many factors, including the type of loops and ...cations, the nucleotide strand number, and the main strand polarity of the G‐quadruplex. Meanwhile, the different conformations of G‐quadruplexes have certain influences on their biological functions, such as the inhibition of transcription, translation, and DNA replication. In addition, G‐quadruplex binding proteins also affect the structure and function of G‐quadruplexes. Some chemically synthesized G‐quadruplex sequences have been shown to have biological activities. For example, bimolecular G‐quadruplexes of AS1411 act as targets of exogenous drugs that inhibit the proliferation of malignant tumours. G‐quadruplexes are also used as vehicles to deliver nanoparticles. Thus, it is important to identify the factors that influence G‐quadruplex structures and maintain the stability of G‐quadruplexes. Herein, we mainly discuss the factors influencing G‐quadruplexes and the synthetic G‐quadruplex, AS1411.
Significance of the study
This review summarizes the factors that influence G‐quadruplexes and the functions of the synthetic G‐quadruplex, AS1411. It also discusses the use of G‐quadruplexes for drug delivery in tumour therapy.
Mitogenomes can provide information for phylogenetic analysis and evolutionary biology. The Araneae is one of the largest orders of Arachnida with great economic importance. In order to develop ...mitogenome data for this significant group, we determined the complete mitogenomes of two long jawed spiders Tetragnatha maxillosa and T. nitens and performed the comparative analysis with previously published spider mitogenomes. The circular mitogenomes are 14578 bp long with A+T content of 74.5% in T. maxillosa and 14639 bp long with A+T content of 74.3% in T. nitens, respectively. Both the mitogenomes contain a standard set of 37 genes and an A+T-rich region with the same gene orientation as the other spider mitogenomes, with the exception of the different gene order by the rearrangement of two tRNAs (trnW and trnG). Most of the tRNAs lose TΨC arm stems and have unpaired amino acid acceptor arms. As interesting features, both trnS(AGN) and trnS(UCN) lack the dihydrouracil (DHU) arm and long tandem repeat units are presented in the A+T-rich region of both the spider mitogenomes. The phylogenetic relationships of 23 spider mitogenomes based on the concatenated nucleotides sequences of 13 protein-coding genes indicated that the mitogenome sequences could be useful in resolving higher-level relationship of Araneae. The molecular information acquired from the results of this study should be very useful for future researches on mitogenomic evolution and genetic diversities in spiders.
Introduction: As 'chemical antibodies', aptamers have some advantages, such as lack of immunogenicity, rapid tissue penetration, cell internalization and so on. Consequently, more and more aptamers ...have been screened out by the systematic evolution of ligands through exponential enrichment for the desired cells or membrane receptors. On the basis of the result, researchers use aptamers to guide drug targeting to the desired cells and internalization in vivo.
Areas covered: In this review, we explore the mechanisms of cargo- or aptamer-mediated internalization, and then briefly summarize five strategies for exploring the mechanism of aptamer internalization. Finally, we focus on four types of applications involving aptamer internalization: aptamers as drugs, aptamers as chemical drug-delivery systems, aptamer-based chimeras and aptamer-conjugated nanoparticles or block copolymer micelles.
Expert opinion: Two aptamer-internalization mechanisms are known, namely receptor-mediated endocytosis and macropinocytosis. The latter mechanism, which is has only been verified in the internalization of nucleolin aptamer shuttles between the nucleus and cytoplasm, may be important for nuclear internalization and cargo molecule escape from the endosomal compartment. Thus, it is feasible to use some strategies to further explore the macropinocytosis internalization mechanism and then to screen for aptamers similar to the nucleolin aptamer for use with the desired cell types as a targeted delivery tool.
The complete mitogenomes of two orb-weaving spiders Neoscona doenitzi and Neoscona nautica were determined and a comparative mitogenomic analysis was performed to depict evolutionary trends of spider ...mitogenomes. The circular mitogenomes are 14,161bp with A+T content of 74.6% in N. doenitzi and 14,049bp with A+T content of 78.8% in N. nautica, respectively. Both mitogenomes contain a standard set of 37 genes typically presented in metazoans. Gene content and orientation are identical to all previously sequenced spider mitogenomes, while gene order is rearranged by tRNAs translocation when compared with the putative ancestral gene arrangement pattern presented by Limulus polyphemus. A comparative mitogenomic analysis reveals that the nucleotide composition bias is obviously divergent between spiders in suborder Opisthothelae and Mesothelae. The loss of D-arm in the trnSUCN among all of Opisthothelae spiders highly suggested that this common feature is a synapomorphy for entire suborder Opisthothelae. Moreover, the trnSAGN in araneoids preferred to use TCT as an anticodon rather than the typical anticodon GCT. Phylogenetic analysis based on the 13 protein-coding gene sequences consistently yields trees that nest the two Neoscona spiders within Araneidae and recover superfamily Araneoidea as a monophyletic group. The molecular information acquired from the results of this study should be very useful for future research on mitogenomic evolution and genetic diversities in spiders.
•The complete mitogenomes of two Neoscona spiders contain a standard set of 37 genes and a control region.•The nucleotide composition bias is obviously divergent between spiders in suborder Opisthothelae and Mesothelae.•The loss of D-arm in the trnSUCN is a synapomorphy for entire suborder Opisthothelae.•Phylogenetic analysis indicates that mitogenome sequences are useful in resolving higher-level relationship of Araneae
The complete mitogenome of the jumping spider
Carrhotus xanthogramma
was determined and comparative analysis among four salticid mitogenomes was conducted. The circular genome is 14,563 bp in size ...and contains a complete set of genes that usually present in the metazoa. All of the 13 protein-coding genes begin with a typical ATN codon and stop with the canonical stop codons, except for
ND4
and
ND4L
genes with an incomplete stop codon T. All of the tRNAs cannot be formed the fully paired acceptor stems and seven out of them cannot be folded into the typical cloverleaf-shaped secondary structures. The
tRNA
Glu
gene translocates its position as compared to the mitogenomes of other three determined jumping spiders. The A+T content of the majority strand and the A+T-rich region are 75.1 and 80%, respectively. The phylogenetic relationships based on concatenated nucleotide and amino acid sequences of 13 protein-coding genes using Maximum Likelihood and Bayesian Inference methods indicated that mitogenome sequences were useful in resolving higher-level relationship of Araneae.
The complete mitogenomes of Cyrtarachne nagasakiensis and Hypsosinga pygmaea are determined to be 14,402 and 14,193 bp in length, with the A + T content of 75.7% and 76.1%, respectively. All ...protein-coding genes in both spiders start with the initiation codons (ATT, ATA, TTA or TTG) that are usually used in Araneae mitogenomes, and terminate with canonical stop codon TAA or TAG except for ND5 in both spiders and ND4L in H. pygmaea, which end with the incomplete codon TA or T instead. Most of the tRNAs lack the potential to form the typically cloverleaf-shaped secondary structures and none of tandem repeats are present in the control regions of both spider mitogenomes. The phylogenetic analysis based on the Bayesian inference dataset shows a good resolution of relationship of C. nagasakiensis and H. pygmaea in Araneidae.
Hepatic fibrosis is characterized by hepatic stellate cell (HSC) activation and transdifferentiation-mediated extracellular matrix (ECM) deposition, which both contribute to cirrhosis. However, no ...antifibrotic regimen is available in the clinic. microRNA-23b/27b/24-1 cluster inhibition of transforming growth factor-β (TGF-β) signaling during hepatic development prompted us to explore whether this cluster inhibits HSC activation and hepatic fibrosis.
Experimental fibrosis was studied in carbon tetrachloride (CCl4)-treated C57BL/6 mice. After administration of miR-23b/27b/24-1 lentivirus or vehicle, animals were euthanized for liver histology. In primary rat HSC and HSC-T6, the anti-fibrotic effect of miR-23b/27b/24-1 cluster was furtherly investigated by RNA-sequencing, luciferase reporter assay, western blotting and bioinformatic means.
In this study, we showed that increasing the miR-23b/27b/24-1 level through intravenous delivery of miR-23b/27b/24-1 lentivirus ameliorated mouse hepatic fibrosis. Mechanistically, the miR-23b/27b/24-1 cluster directly targeted messenger RNAs, which reduced the protein expression of 5 secretory profibrotic genes (TGF-β2, Gremlin1, LOX, Itgα2, and Itgα5) in HSCs. Suppression of the TGF-β signaling pathway by down-regulation of TGF-β2, Itgα2, and Itgα5, and activation of the bone morphogenetic protein signaling pathway by inhibition of Gremlin1, decreased extracellular matrix secretion of HSCs. Furthermore, down-regulation of LOX expression softened the ECM. Moreover, a reduction in tissue inhibitors of metalloproteinase 1 expression owing to weakened TGF-β signaling increased ECM degradation.
Hepatic overexpression of the miR-23b/27b/24-1 cluster blocked hepatic fibrosis and may be a novel therapeutic regimen for patients with hepatic fibrosis.
The complete mitochondrial genome of an orb-weaver spider Cyclosa argenteoalba is determined in this article. The genome encodes the same 37 genes with a length of 14,575 bp as all other metazoan ...mitogenomes. The A + T content of the majority strand is 73.1%. Among the protein-coding genes, one gene (COI) begins with TTA, three (COII, COIII and ND6) start with ATT, three (ATP6, ND3 and ND4) begin with ATA and other six genes use ATT as initiation codon. All the protein-coding genes end with the canonical termination codons (TAA or TAG), except for ND3 and ND4L, which use an incomplete stop codon (T). Thirteen transfer RNAs genes lack the potential to form the cloverleaf-shaped secondary structure. The A + T-rich region is 1052 bp in length with an A + T content of 68.9%. In the phylogenetic analyses, C. argenteoalba was nested within Araneidae and the species from the superfamily Araneoidea form a momophyletic group.
The complete mitochondrial genome of an orb-weaving spider Neoscona theisi (Walckenaer) is determined in this article. It is a typical circular duplex DNA molecule with a length of 14,156 bp, which ...encodes the same 37 genes as all metazoan mitogenomes and an A + T-rich region (D-loop). The overall A + T content is 75.2% (A: 35.5%; T: 39.8%; G: 15.6%; C: 9.3%). All of the protein-coding genes were initiated by ATN, with the exceptions in three genes. COI has a TTA start codon, COII, COIII and ND6 use TTG as initiation codon. Three genes (ND3, COII and ND5) end with incomplete stop codons (T or TA), while all other genes terminated with canonical stop codons (TAA or TAG). Among 22 transfer RNAs genes, six of them (tRNA
Ala
, tRNA
Ser(AGN)
, tRNA
Ser(UCN)
, tRNA
Gly
, tRNA
Arg
and tRNA
His
) lack the potential to form the cloverleaf-shaped secondary structure. The A + T-rich region is 559 bp with an A + T content of 79.6%.
The complete mitochondrial genome of the wolf spider Wadicosa fidelis was determined. It is a circular molecule of 14,741 bp in length and contains a standard set of 13 protein-coding genes, 2 ...ribosomal RNAs, 22 transfer RNAs and a control region. The A + T content of the overall base composition of majority strand (J-strand) is 76.1% (T: 43.0%; C: 8.2%; A:33.1%; G: 15.7%). Start codons in all 13 protein-coding genes (PCGs) follow the ATN rule, except of four genes (COII, COII, ND4 and ND6), which have TTG start codon. The usual termination codons (TAA and TAG) are found from nine PCGs. However, COI, ND1, ND4L, ND5 had an incomplete termination codon (T). The control region (D-loop) is 1071 bp long with 67.9% A + T content, and contains a long tandem repeat region, which is comprising three full 215 bp copies and a partial fourth (87 bp) copy.
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