G-quadruplexes (G4s) are noncanonical DNA secondary structures formed through the self-association of guanines, and G4s are distributed widely across the genome. G4 participates in multiple biological processes including gene transcription, and G4-targeted ligands serve as potential therapeutic agents for DNA-targeted therapies. However, genome-wide studies of the exact roles of G4s in transcriptional regulation are still lacking. Here, we establish a sensitive G4-CUT&Tag method for genome-wide profiling of native G4s with high resolution and specificity. We find that native G4 signals are cell type–specific and are associated with transcriptional regulatory elements carrying active epigenetic modifications. Drug-induced promoter-proximal RNA polymerase II pausing promotes nearby G4 formation. In contrast, G4 stabilization by G4-targeted ligands globally reduces RNA polymerase II occupancy at gene promoters as well as nascent RNA synthesis. Moreover, ligand-induced G4 stabilization modulates chromatin states and impedes transcription initiation via inhibition of general transcription factors loading to promoters. Together, our study reveals a reciprocal genome-wide regulation between native G4 dynamics and gene transcription, which will deepen our understanding of G4 biology toward therapeutically targeting G4s in human diseases.
Constructing a reversible supramolecular network cross-linked by noncovalent bonds is an effective approach to realize self-healing as well as reprocessing and recycling for rubbers. Unfortunately, in most case the resultant noncovalent cross-linked rubbers cannot hold enough forces to meet the routine applications. In this paper, our strategy was based on a simple reaction between carboxy groups in carboxylated styrene butadiene rubber (XSBR) and zinc oxide (ZnO), where the formed Zn2+ salt bondings connect separate XSBR molecules. The further self-aggregation of ion pairs of Zn2+ salts resulted in an ionic cross-linked network, whose rearrangements brought XSBR excellent reprocessing/recycling ability. Additionally, the reclaimed XSBR exhibited valuable mechanical properties due to the compensation of additional formed new Zn2+ salt bondings during recycling. The fresh XSBR with 5 wt % zinc oxide showed a tensile strength of 6.7 MPa, and it was further increased to 10.3 MPa after 3 recycles, which was far higher than most reported noncovalent supramolecular rubbers. This study thus opens up an avenue to further extending the recyclable cross-linked XSBR with considerable mechanical properties to various engineering applications.
ObjectiveTo investigate warning effect of serum miRNA for intracranial aneurysm rupture through microarray hybridization.Methods24 were selected from 560 patients in our department and divided into group A, B, C and D. They are aneurysms with daughter aneurysms group, aneurysm without daughter aneurysms group, ruptured aneurysms group and angiography negative group. Then a microarray study was carried out using serum miRNA. Differentially expressed miRNAs were identified. Cluster analysis was performed in order to make the results looks more intuitive and potential gene targets were retrieved from miRNA target prediction databases.ResultsMicroarray study identified 86 miRNAs with significantly different (p < 0.05) expression levels between three experimental groups and control group. Among them 69 are up-regulated and 17 are down-regulated. All miRNAs in group A are up-regulated, while there are up and down-regulated in group B and C. A total of 8291 predicted target genes are related to these miRNAs. Bioinformatic analysis revealed that several target genes are involved in apoptosis and activation of cells associated with function of vascular wall.ConclusionOur gene level approach reveals several different serum miRNAs between normal people and aneurysm patients, as well as among different phases of aneurysm, suggesting that miRNA may participate in the regulation of the occurrence and development of intracranial aneurysm, and also have warning effect for intracranial aneurysm rupture. All differently expressed miRNA in group A are up-regulated, which may suggesting protective function of miRNA for intracranial vascular wall.
An R loop is a unique triple-stranded structure that participates in multiple key biological processes and is relevant to human diseases. Accurate and comprehensive R loop profiling is a prerequisite for R loops studies. However, current R loop mapping methods generate large discrepancies, therefore an independent method is in urgent need. Here, we establish an independent R loop CUT&Tag (Tn5-based cleavage under targets and tagmentation) method by combining CUT&Tag and GST-His6-2×HBD (glutathione S-transferase–hexahistidine–2× hybrid-binding domain), an artificial DNA-RNA hybrid sensor that specifically recognizes the DNA-RNA hybrids. We demonstrate that the R loop CUT&Tag is sensitive, reproducible, and convenient for native R loop mapping with high resolution, and find that the capture strategies, instead of the specificity of sensors, largely contribute to the disparities among different methods. Together, we provide an independent strategy for genomic profiling of native R loops and help resolve discrepancies among multiple R loop mapping methods.
The longstanding Alperin weight conjecture and its blockwise version have been reduced to simple groups recently by Navarro, Tiep, Späth and Koshitani. Thus, to prove this conjecture, it suffices to verify the corresponding inductive condition for all finite simple groups. The first is to establish an equivariant bijection between irreducible Brauer characters and weights for the universal covering groups of simple groups. Assume q is a power of some odd prime p. We first prove the blockwise Alperin weight conjecture for Sp 2n (q) and odd non-defining characteristics. If the decomposition matrix of Sp 2n (q) is unitriangular with respect to an Aut(Sp 2n (q))-stable basic set (this assumption holds for linear primes), we can establish an equivariant bijection between the irreducible Brauer characters and weights. , then (R, ϕ) is called a B-weight. Denote the set of all G-conjugacy classes of B-weights by W(B). In the sequel, the term "weight" will mean a single weight or a conjugacy class of weights depending on the context. J. L. Alperin gives the following conjecture in [1] called blockwise Alperin weight (BAW) conjecture.Conjecture (Alperin). Let G be a finite group, ℓ a prime and B an ℓ-block of G,This conjecture has been reduced to the simple groups, which means that the BAW conjecture holds for a finite group G if all non-abelian simple groups involved in G satisfy the inductive blockwise Alperin weight (iBAW) condition. See [31] for a definition of the iBAW condition and see [19] for another version. Basically speaking, the iBAW condition consists of two parts: the first one requires to establish an equivariant bijection between irreducible Brauer characters and weights; the second one (normally embedded conditions) requires to consider the extension of irreducible Brauer characters and weight characters. This inductive condition has been verified for several cases, such as: simple alternate groups, many sporadic simple groups, simple groups of Lie type and the defining characteristic, some few cases of simple groups of Lie type and primes different from the defining characteristic; see [7], [10], [13], [19], [21], [24], [28], [29], [31], etc.The purpose of this paper is to start the consideration of the iBAW condition for PSp 2n (q) with q a power of an odd prime p and an odd prime ℓ p. To do this, we first need to establish a blockwise bijection between the irreducible Brauer characters and weights of the universal covering group Sp 2n (q) of PSp 2n (q).Theorem 1. Let p be an odd prime, q = p f and ℓ an odd prime different from p, then the blockwise Alperin weight conjecture holds for Sp 2n (q) for ℓ.In [15], the classification of blocks and the partition of irreducible ordinary characters into blocks for CSp 2n (q) are obtained. Using the results of Fong and Srinivasan in [15] and the results of Lusztig in [20], we can classify the blocks of Sp 2n (q) and partition irreducible ordinary characters into blocks. To give a parametrization of irreducible Brauer characters, we use the basic set E(Sp 2n (q), ℓ...
To discuss the coupling coordination relationship among tourism carbon emissions, economic development and regional innovation it is not only necessary to realize the green development of tourism economy, but also great significance for the tourism industry to take a low-carbon path. Taking the 30 provinces of China for example, this paper calculated the tourism carbon emission efficiency based on the super-efficiency Slacks based measure and Data envelope analyse (SBM-DEA) model from 2007 to 2017, and on this basis, defined a compound system that consists of tourism carbon emissions, tourism economic development and tourism regional innovation. Further, the coupling coordination degree model and dynamic degree model were used to explore its spatiotemporal evolution characteristics of balanced development, and this paper distinguished the core influencing factors by Geodetector model. The results showed that (1) during the study period, the tourism carbon emission efficiency showed a reciprocating trend of first rising and then falling, mainly due to the change of pure technical efficiency. (2) The coupling coordination degree developed towards a good trend, while there were significant differences among provinces, showing a gradient distribution pattern of decreasing from east to west. Additionally, (3) the core driving factors varied over time, however, in general, the influence from high to low were as follows: technological innovation, economic development, urbanization, environmental pollution control, and industrial structure. Finally, some policy recommendations were put forward to further promote the coupling coordination degree.
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