240 research outputs found

    Graph tilings in incompatibility systems

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    Given two graphs HH and GG, an \emph{HH-tiling} of GG is a collection of vertex-disjoint copies of HH in GG and an \emph{HH-factor} is an HH-tiling that covers all vertices of GG. K\"{u}hn and Osthus managed to characterize, up to an additive constant, the minimum degree threshold which forces an HH-factor in a host graph GG. In this paper we study a similar tiling problem in a system that is locally bounded. An \emph{incompatibility system} F\mathcal{F} over GG is a family F={Fv}v∈V(G)\mathcal{F}=\{F_v\}_{v\in V(G)} with Fv⊆{{e,e′}∈(E(G)2):e∩e′={v}}F_v\subseteq \{\{e,e'\}\in {E(G)\choose 2}: e\cap e'=\{v\}\}. We say that two edges e,e′∈E(G)e,e'\in E(G) are \emph{incompatible} if {e,e′}∈Fv\{e,e'\}\in F_v for some v∈V(G)v\in V(G), and otherwise \emph{compatible}. A subgraph HH of GG is \emph{compatible} if every pair of edges in HH are compatible. An incompatibility system F\mathcal{F} is \emph{Δ\Delta-bounded} if for any vertex vv and any edge ee incident with vv, there are at most Δ\Delta two-subsets in FvF_v containing ee. This notion was partly motivated by a concept of transition system introduced by Kotzig in 1968, and first formulated by Krivelevich, Lee and Sudakov to study the robustness of Hamiltonicity of Dirac graphs. We prove that for any α>0\alpha>0 and any graph HH with hh vertices, there exists a constant μ>0\mu>0 such that for any sufficiently large nn with n∈hNn\in h\mathbb{N}, if GG is an nn-vertex graph with δ(G)≥(1−1χ∗(H)+α)n\delta(G)\ge(1-\frac{1}{\chi^*(H)}+\alpha)n and F\mathcal{F} is a μn\mu n-bounded incompatibility system over GG, then there exists a compatible HH-factor in GG, where the value χ∗(H)\chi^*(H) is either the chromatic number χ(H)\chi(H) or the critical chromatic number χcr(H)\chi_{cr}(H) and we provide a dichotomy. Moreover, the error term αn\alpha n is inevitable in general case

    Mechanism of action and resistant profile of anti-HIV-1 coumarin derivatives

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    Dicamphanoyl khellactone (DCK) is a coumarin derivative that can potently inhibit HIV-1 replication. DCK does not inhibit RNA-dependent DNA synthesis. However, an HIV reverse transcriptase (RT) inhibitor-resistant strain, HIV-1/RTMDR1, is resistant to DCK. Thus, it is possible that HIV-1 RT is the target of DCK. To test this possibility, DCK-resistant viruses were selected in the presence of DCK. Our results indicate that a single amino acid mutation, E138K in HIV-1 RT, is sufficient to confer DCK resistance. Interestingly, a DCK derivative, 3'R,4'R-Di-O-(-)-camphanoyl-2-ethyl-2',2'-dimethyldihydropyrano[2,3-f]chromo ne (DCP8), is effective against HIV-1/RTMDR1. However, the DCK-escape virus carrying the E138K mutation remains resistant to DCP8. Since DCK did not inhibit the RNA-dependent DNA polymerase activity of HIV-1 RT when using poly-rA or poly-rC as template, we evaluated the effect of DCK on the DNA-dependent DNA polymerase activity of HIV-1 RT. Our results indicate that DCK can inhibit the DNA-dependent DNA polymerase activity of HIV-1 RT. In conclusion, DCK is a unique HIV-1 RT inhibitor that inhibits the DNA-dependent DNA polymerase activity. In contrast, DCK did not significantly affect the RNA-dependent DNA polymerase activity when poly-rA or poly-rC was used as templates. An E138K mutation in the non-nucleoside RT inhibitors (NNRTIs) binding pocket of HIV-1 RT confers resistance to DCK and its chromone derivative, DCP8

    Photoactivatable senolysis with single-cell resolution delays aging

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    Strategies that can selectively eliminate senescent cells (SnCs), namely senolytics, have been shown to promote healthy lifespan. However, it is challenging to achieve precise, broad-spectrum and tractable senolysis. Here, we integrate multiple technologies that combine the enzyme substrate of senescence-associated β-galactosidase (SA-β-gal) with fluorescence tag for the precise tracking of SnCs, construction of a bioorthogonal receptor triggered by SA-β-gal to target and anchor SnCs with single-cell resolution and incorporation of a selenium atom to generate singlet oxygen and achieve precise senolysis through controllable photodynamic therapy (PDT). We generate KSL0608-Se, a photosensitive senolytic prodrug, which is selectively activated by SA-β-gal. In naturally-aged mice, KSL0608-Se-mediated PDT prevented upregulation of age-related SnCs markers and senescence-associated secretory phenotype factors. This treatment also countered age-induced losses in liver and renal function and inhibited the age-associated physical dysfunction in mice. We therefore provide a strategy to monitor and selectively eliminate SnCs to regulate aging

    Photoactivatable senolysis with single-cell resolution delays aging

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    Strategies that can selectively eliminate senescent cells (SnCs), namely senolytics, have been shown to promote healthy lifespan. However, it is challenging to achieve precise, broad-spectrum and tractable senolysis. Here, we integrate multiple technologies that combine the enzyme substrate of senescence-associated β-galactosidase (SA-β-gal) with fluorescence tag for the precise tracking of SnCs, construction of a bioorthogonal receptor triggered by SA-β-gal to target and anchor SnCs with single-cell resolution and incorporation of a selenium atom to generate singlet oxygen and achieve precise senolysis through controllable photodynamic therapy (PDT). We generate KSL0608-Se, a photosensitive senolytic prodrug, which is selectively activated by SA-β-gal. In naturally-aged mice, KSL0608-Se-mediated PDT prevented upregulation of age-related SnCs markers and senescence-associated secretory phenotype factors. This treatment also countered age-induced losses in liver and renal function and inhibited the age-associated physical dysfunction in mice. We therefore provide a strategy to monitor and selectively eliminate SnCs to regulate aging

    Conservation and implications of eukaryote transcriptional regulatory regions across multiple species

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    <p>Abstract</p> <p>Background</p> <p>Increasing evidence shows that whole genomes of eukaryotes are almost entirely transcribed into both protein coding genes and an enormous number of non-protein-coding RNAs (ncRNAs). Therefore, revealing the underlying regulatory mechanisms of transcripts becomes imperative. However, for a complete understanding of transcriptional regulatory mechanisms, we need to identify the regions in which they are found. We will call these transcriptional regulation regions, or TRRs, which can be considered functional regions containing a cluster of regulatory elements that cooperatively recruit transcriptional factors for binding and then regulating the expression of transcripts.</p> <p>Results</p> <p>We constructed a hierarchical stochastic language (HSL) model for the identification of core TRRs in yeast based on regulatory cooperation among TRR elements. The HSL model trained based on yeast achieved comparable accuracy in predicting TRRs in other species, e.g., fruit fly, human, and rice, thus demonstrating the conservation of TRRs across species. The HSL model was also used to identify the TRRs of genes, such as p53 or <it>OsALYL1</it>, as well as microRNAs. In addition, the ENCODE regions were examined by HSL, and TRRs were found to pervasively locate in the genomes.</p> <p>Conclusion</p> <p>Our findings indicate that 1) the HSL model can be used to accurately predict core TRRs of transcripts across species and 2) identified core TRRs by HSL are proper candidates for the further scrutiny of specific regulatory elements and mechanisms. Meanwhile, the regulatory activity taking place in the abundant numbers of ncRNAs might account for the ubiquitous presence of TRRs across the genome. In addition, we also found that the TRRs of protein coding genes and ncRNAs are similar in structure, with the latter being more conserved than the former.</p

    Slower-decaying tropical cyclones produce heavier precipitation over China

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    The post-landfall decay of tropical cyclones (TC) is often closely linked to the magnitude of damage to the environment, properties, and the loss of human lives. Despite growing interest in how climate change affects TC decay, data uncertainties still prevent a consensus on changes in TC decay rates and related precipitation. Here, after strict data-quality control, we show that the rate of decay of TCs after making landfall in China has significantly slowed down by 45% from 1967 to 2018. We find that, except the warmer sea surface temperature, the eastward shift of TC landfall locations also contributes to the slowdown of TC decay over China. That is TCs making landfall in eastern mainland China (EC) decay slower than that in southern mainland China (SC), and the eastward shift of TCs landfall locations causes more TCs landfalling in EC with slower decay rate. TCs making landfall in EC last longer at sea, carry more moisture upon landfall, and have more favorable dynamic and thermodynamic conditions sustaining them after landfall. Observational evidence shows that the decay of TC-induced precipitation amount and intensity within 48 h of landfall is positively related to the decay rate of landfalling TCs. The significant increase in TC-induced precipitation over the long term, due to the slower decay of landfalling TCs, increases flood risks in China’s coastal areas. Our results highlight evidence of a slowdown in TC decay rates at the regional scale. These findings provide scientific support for the need for better flood management and adaptation strategies in coastal areas under the threat of greater TC-induced precipitation

    Production of human blood group B antigen epitope conjugated protein in Escherichia coli and utilization of the adsorption blood group B antibody

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    Additional file 1: Table S1. List of constructed plasmids, strains and primers used in the study. Figure S1. MALDI-TOF detection of MBPmut (a) and MBPmut-OPS (b)
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