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Jiaxin Hu

Publications and source records attributed to Jiaxin Hu.

12 recordsLinked to original sources

Small molecule inhibition of CPSF3 may impact R-loop distribution and abundance.

R-loops are three-stranded nucleic acid structures consisting of an RNA/DNA hybrid and a displaced strand of DNA. These structures have been implicated in a variety of regulatory cellular processes. Their untimed or excess accumulation, however, can cause genomic instability and induce DNA damage. Most R-loops form co-transcriptionally when the nascent transcript reanneals to unwound DNA duplex. Changes in transcription rates have the potential to impact R-loop formation, and compounds that modulate R-loop formation would be useful molecular tools and therapeutic leads. Cleavage and Polyadenylation Specific Factor 3 (CPSF3) recognizes the pre-mRNA 3' cleavage site, cleaves the transcript prior to polyadenylation, and has been linked to R-loop formation. Inhibition of CPSF3 has been found to induce transcriptional readthrough and cell proliferation defects. A previous report suggested that inhibition of CPSF3 with a small molecule causes a global increase in R-loop formation. Here, we test the impact of YT-II-100, a novel inhibitor of CPSF3. We find that addition of YT-II-100 increases global R-loop formation but does not change R-loop formation at specific genes that are normally used as positive controls for R-loop formation. We performed parallel assays using a previously reported compound, JTE-607, and observed similar results. Our data emphasize the need for cautious interpretation of experiments using JTE-607 and YT-II-100. There may be different mechanisms of R-loop formation depending on gene loci, where the control of R-loop formation by agonists at certain genes may differ from the trends observed for impacts on global R-loop formation.

R-Loop Structures↗

A spectral framework to map QTLs affecting joint differential networks of gene co-expression.

Studying the mechanisms underlying the genotype-phenotype association is crucial in genetics. Gene expression studies have deepened our understanding of the genotype  →  expression  →  phenotype mechanisms. However, traditional expression quantitative trait loci (eQTL) methods often overlook the critical role of gene co-expression networks in translating genotype into phenotype. This gap highlights the need for more powerful statistical methods to analyze genotype  →  network  →  phenotype mechanism. Here, we develop a network-based method, called spectral network quantitative trait loci analysis (snQTL), to map quantitative trait loci affecting gene co-expression networks. Our approach tests the association between genotypes and joint differential networks of gene co-expression via a tensor-based spectral statistics, thereby overcoming the ubiquitous multiple testing challenges in existing methods. We demonstrate the effectiveness of snQTL in the analysis of three-spined stickleback (Gasterosteus aculeatus) data. Compared to conventional methods, our method snQTL uncovers chromosomal regions affecting gene co-expression networks, including one strong candidate gene that would have been missed by traditional eQTL analyses. Our framework suggests the limitation of current approaches and offers a powerful network-based tool for functional loci discoveries.

Quantitative Trait Loci↗

Comparative analysis of chloroplast genomes in ten holly (Ilex) species: insights into phylogenetics and genome evolution.

In order to clarify the chloroplast genomes and structural features of ten Ilex species and provide insights into the phylogeny and genome evolution of the genus Ilex, we conducted a comparative analysis of chloroplast genomes using bioinformatics methods. The chloroplast genomes of ten Ilex species were obtained, and their structural features and variations were compared. The results indicated that all chloroplast genomes in the genus Ilex exhibit a double-stranded circular structure, with sizes ranging from 157,356 to 158,018 bp, showing minimal differences in size. The chloroplast genomes of the ten Ilex species have a relatively conservative gene count, with a total of 134 to 135 genes, including 88 or 89 protein-coding genes, and a conserved number of 8 rRNA genes. Each chloroplast genome contains 3 to 123 SSR (Simple Sequence Repeat) sites, predominantly composed of mononucleotide and trinucleotide repeats, with no detection of pentanucleotide or hexanucleotide repeats. The variation in dispersed repeat sequences among Ilex species is minimal, with a total repeat sequence number ranging from 1 to 14, concentrated in the length range of 30 to 42 base pairs. The expansion and contraction of chloroplast genome boundaries among Ilex species are relatively stable, with only minor variations observed in individual species. Variations in non-coding regions are more pronounced than those in coding regions, with the variability in the Large Single Copy region (LSC) being the highest, while the variability in the Inverted Repeat region A (IRa) is the lowest. The divergence time among Ilex species was estimated using the MCMC-tree module, revealing the evolutionary relationships among these species, their common ancestors, and their differentiation throughout the evolutionary process. The research findings provide a valuable reference for the systematic study and molecular marker development of Ilex plants.

Genome, Chloroplast↗

Mechanism of myocardial microvessel formation in cyanotic congenital heart disease.

BACKGROUND: Patients with cyanotic congenital heart disease (C-CHD) usually have myocardial thickening and fibrosis, both of which can affect the course of surgical management. Hypoxia and ischemia may stimulate microvessel formation in the myocardium, which may accelerate the myocardial thickening and fibrosis. Whether hyperplasia of microvessels occurs in the myocardium of C-CHD was investigated in this report. METHODS AND RESULTS: The patients were divided into 2 groups; the C-CHD group (n = 22), and the acyanotic congenital heart disease (A-CHD) group (n = 24). The microvessels and vascular endothelial growth factor (VEGF) mRNA of the myocardium were detected by immunohistochemical staining assay and real-time quantitative reverse transcriptase polymeric chain reaction, respectively. The serum VEGF levels were measured by using enzyme-linked immunosorbent assay. The results were that: (1) the number of microvessels in the myocardium were more in the C-CHD group than in A-CHD group; (2) the serum VEGF levels in the C-CHD group vs the A-CHD group were higher in the preoperative period (p < 0.001), but there was no difference after operation; and (3) VEGF protein and the expression of VEGF mRNA in the myocardium were higher in the C-CHD group than in the A-CHD group (p < 0.01). CONCLUSIONS: Myocardial microvessels formed in the myocardium of patients with C-CHD, possibly mediated by increasing VEGF levels (for this group of patients).

Adolescent↗

The indole side chain of tryptophan as a versatile pi-donor.

Single-armed, 15- and 18-membered lariat ether receptor systems having indolylethyl side arms bind Na+ and K+ in the ring. The indole residue serves as a pi-donor to the ring-bound cation. Whether the five- or six-membered ring interacts most directly with Na+ or K+ depends on whether the sidearm is attached to indole's 3- or 5-position. This suggests that structural as well as electronic factors are important in pi-complexation of alkali metal cations.

Ethers, Cyclic↗

Probing alkali metal-pi interactions with the side chain residue of tryptophan.

Feeble forces play a significant role in the organization of proteins. These include hydrogen bonding, hydrophobic interactions, salt bridge formation, and steric interactions. The alkali metal cation-pi interaction is a force of potentially profound importance but its consideration in biology has been limited by the lack of experimental evidence. Our previous studies of cation-pi interactions with Na(+) and K(+) involved the side arms of tryptophan (indole), tyrosine (phenol), and phenylalanine (benzene) as the arene donors. The receptor system possesses limiting steric constraints. In this report, we show that direct interactions between alkali metals and arenes occur at or within the van der Waals contact distance.

Benzene↗

Lariat ether receptor systems show experimental evidence for alkali metal cation-pi interactions.

Cation-pi interactions occur between cations and electron-rich species such as double bonds, triple bonds, and arenes. The pi-electron system may be neutral or anionic, but the latter are less relevant to biology, at least so far as is currently known. Among the 20 essential amino acids, there are four aromatic residues. These are benzene, phenol, indole, and imidazole, on the side chains of phenylalanine, tyrosine, tryptophan, and histidine, respectively. Of these, imidazole is expected to be a sigma-donor, and benzene, phenol, and indole are antipicated to serve as pi-donors. Sodium and potassium are the most abundant cations in living systems. This Account describes an experimental system that has been developed to probe, especially by X-ray crystallography, the interactions that occur between Na(+) or K(+) and the neutral arenes of particular biological significance.

Amino Acids↗