While alternative splicing (AS) contributes greatly to protein diversities, the relationship between various types of AS and epigenetic factors remains largely unknown.
In this study, we discover ...that a number of epigenetic features, including DNA methylation, nucleosome occupancy, specific histone modifications and protein features, are strongly associated with AS. To further enhance our understanding of the association between these features and AS, we cluster our investigated features based on their association patterns with each AS type into four groups, with H3K36me3, EGR1, GABP, SRF, SIN3A and RNA Pol II grouped together and showing strongest association with AS. In addition, we find that the AS types can be classified into two general classes, namely the exon skipping related process (ESRP), and the alternative splice site selection process (ASSP), based on their association levels with the epigenetic features.
Our analysis thus suggests that epigenetic features are likely to play important roles in regulating AS.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In order to enhance the properties of polymer anion-exchange membranes (AEMs), a class of side-chain-type poly (arylene ether sulfone)s containing tri-imidazole cations in pendant phenoxyphenyl ...spacer (i.e., Im-PES-xx) were designed and prepared by polymer grafting reaction. Based on these imidazole functionalized polymers, a series of new AEMs were successfully prepared by their solution coating and ion exchange. The obtained membranes exhibited good alkaline stability with the retention of ion-exchange capacity in the range of 78.5%–83.3% after immersion in 4 M NaOH solution at 80 °C for 336 h. The membranes also had high hydroxide conductivity with the values of 34.1–70.5 mS cm−1 at 80 °C. Meanwhile, these membranes possessed good dimensional stability, and their swelling ratio was in the range of 2.5%–7.0% at 80 °C. The incorporation of the dense and local imidazole cations in the side chains for AEMs plays an important role for their properties.
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•Side-chain-type AEMs containing dense and local imidazole cations.•Tri-imidazole cations was introduced in pendant phenoxyphenyl spacer.•Enhanced alkaline stability with high retentions of IEC and conductivity.•Good ionic conductivity and low swelling ratio.
Aromatic sulfonated polymers are a class of important proton exchange membranes. With the aim of further enhancing their properties at low levels of ion-exchange capacity (IEC), a class of new ...poly(ether sulfone ketone)s containing multiple sulfonic acids on the side chains of the sulfonated structural units (sPh-PESK-
xx
) were designed and prepared by a convenient and mild post-sulfonation reaction process. The structures of the related monomer and copolymers were confirmed by IR and NMR analysis. The resulting membranes from solution casting of these aromatic sulfonated polymers showed overall good performance at low IEC levels. Their proton conductivities were in the range of 110-154 mS cm
−1
, while their swelling ratios were in the range of 6.2%-16.1% at 80 °C. Meanwhile, they also displayed good thermal and chemical oxidative stabilities. The results confirmed that the incorporation of a high density of pendant sulfonic groups is an effective way to improve the performance of aromatic sulfonated polymers.
A class of new poly(ether sulfone ketone)s containing a high density of pendant sulfonic groups on the sulfonated structural units were designed and the resulting membranes exhibited overall good performance at low IEC levels.
Defining the target genes of distal regulatory elements (DREs), such as enhancer, repressors and insulators, is a challenging task. The recently developed Hi-C technology is designed to capture ...chromosome conformation structure by high-throughput sequencing, and can be potentially used to determine the target genes of DREs. However, Hi-C data are noisy, making it difficult to directly use Hi-C data to identify DRE-target gene relationships. In this study, we show that DREs-gene pairs that are confirmed by Hi-C data are strongly phylogenetic correlated, and have thus developed a method that combines Hi-C read counts with phylogenetic correlation to predict long-range DRE-target gene relationships. Analysis of predicted DRE-target gene pairs shows that genes regulated by large number of DREs tend to have essential functions, and genes regulated by the same DREs tend to be functionally related and co-expressed. In addition, we show with a couple of examples that the predicted target genes of DREs can help explain the causal roles of disease-associated single-nucleotide polymorphisms located in the DREs. As such, these predictions will be of importance not only for our understanding of the function of DREs but also for elucidating the causal roles of disease-associated noncoding single-nucleotide polymorphisms.
The slag resistance of MgO–SiC–C (MSC) refractories should be improved because of the mismatch in the thermal expansion coefficient between the aggregates and matrix, as well as the defects caused by ...the affinity between periclase and slag. In this study, MgO–Mg2SiO4–SiC–C (MMSC) refractories were prepared using porous multiphase MgO–Mg2SiO4 (M-M2S) aggregates to replace dense fused magnesia aggregates. Compared to MSC, the slag penetration index of MMSC decreased by 43.5%. The structure of the porous aggregates increased the surface roughness, and the multiphase composition of the aggregates decreased the mismatch of the thermal expansion coefficient with the matrix, thus reducing debonding between the aggregates and matrix. The aggregates and matrix in the MMSC formed an interlocking structure, which bound them more tightly to improve the slag resistance. The slag viscosity at different depths from the initial slag/refractory interface was calculated using the Ribond model. The M-M2S aggregates increased SixOyz− in the slag, which increased the slag polymerization and slag viscosity. The aggregates and matrix in the MMSC reacted with the slag to form high melting point phases, which reduced the channel of the slag. In addition, the penetration depth and velocity derived from the Washburn Equation were modified for the CaO–SiO2–Al2O3–MgO–FeO slag and magnesia based refractory to accurately evaluate slag penetration.
To improve the service life of periclase-forsterite refractories, it is important to develop aggregates with high thermal shock resistance. In this study, periclase-forsterite aggregates with good ...resistance to thermal shock and micro-nanopores were prepared using high-silicon magnesite, silica, and silica sol. Microcracks were generated in the multiphase aggregates, which inhibited the continuous propagation of cracks during thermal shock through mismatched thermal expansion coefficients. Based on Hasselman's thermal shock stability factor, the reduction in the average thermal expansion coefficient and improved mechanical characteristics were critical factors in improving the thermal shock resistance of the multiphase aggregates. As a binder, silica sol provided nano-SiO2 and superplasticity, which facilitated the formation of micro-nanopores and strengthened the combination of the various phases in the aggregates.
Automated annotation of protein function is challenging. As the number of sequenced genomes rapidly grows, the overwhelming majority of protein products can only be annotated computationally. If ...computational predictions are to be relied upon, it is crucial that the accuracy of these methods be high. Here we report the results from the first large-scale community-based critical assessment of protein function annotation (CAFA) experiment. Fifty-four methods representing the state of the art for protein function prediction were evaluated on a target set of 866 proteins from 11 organisms. Two findings stand out: (i) today's best protein function prediction algorithms substantially outperform widely used first-generation methods, with large gains on all types of targets; and (ii) although the top methods perform well enough to guide experiments, there is considerable need for improvement of currently available tools.
Increasing the local charge density of flexible side-chain cations in the hydrophilic segments of anion exchange membranes (AEMs) is helpful for improving their properties. However, due to ...limitations of structural design strategies and available synthetic methods, very few AEMs with more than four flexible side-chain cationic groups in hydrophilic segments have been reported. In order to further improve the hydroxide conductivity, alkaline stability and dimensional stability, herein we report a series of AEMs containing eight flexible side-chain cations in hydrophilic segments, based on poly(aryl ether sulfone)s (PAES). The synthesis, ion exchange capacity (IEC), water absorption, dimensional swelling, alkaline stability and hydroxide conductivity of the obtained membranes (PAES-8TMA-x) were examined and the relationships between structures and properties of different types of AEMs were also systematically compared. The resulting AEMs with IEC values of 1.76–2.76 mmol g
−1
displayed comprehensively desirable properties, with hydroxide conductivities of 62.7–92.8 mS cm
−1
and dimensional swelling in the range of 8.3% to 15.8% at 60°C. The IEC and hydroxide conductivity for a representative sample, PAES-8TMA-0.35, maintained 82.2% and 79.6% of the initial values after being immersed in 2 mol L
−1
NaOH at 90°C for 480 h, respectively. This study expands the design and preparation of AEMs containing high local densities of flexible side chain cations, and provides a new strategy for new AEM materials.
Objective. To investigate the joint effects of the single nucleotide polymorphisms (SNPs) of genes in the folic acid pathway on homocysteine (Hcy) metabolism. Methods. Four hundred women with normal ...pregnancies were enrolled in this study. SNPs were identified by MassARRAY. Serum folic acid and Hcy concentration were measured. Analysis of variance (ANOVA) and support vector machine (SVM) regressions were used to analyze the joint effects of SNPs on the Hcy level. Results. SNPs of MTHFR (rs1801133 and rs3733965) were significantly associated with maternal serum Hcy level. In the different genotypes of MTHFR (rs1801133), SNPs of RFC1 (rs1051266), TCN2 (rs9606756), BHMT (rs3733890), and CBS (rs234713 and rs2851391) were linked with the Hcy level adjusted for folic acid concentration. The integrated SNPs scores were significantly associated with the residual Hcy concentration (RHC) (r=0.247). The Hcy level was significantly higher in the group with high SNP scores than that in other groups with SNP scores of less than 0.2 (P=0.000). Moreover, this difference was even more significant in moderate and high levels of folic acid. Conclusion. SNPs of genes in the folic acid pathway possibly affect the Hcy metabolism in the presence of moderate and high levels of folic acid.
The toxicity of the water-soluble extract of
Rhizoma Polygonati Odorati was studied in the present investigation, which included its acute toxicity, chronic toxicity, and genetic toxicity. The ...aqueous extract of
Rhizoma Polygonati Odorati did not cause seriously abnormal signs or death to animals in the acute toxicity test and in the 6-month chronic toxicity test. Neither was genetic toxicity found in the Ames test, the micronucleus test of bone marrow and the sperm malformation test in mice.
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