Abstract Background A major goal of post-genomics research is the integrated analysis of genes, regulatory elements and the chromatin architecture on a genome-wide scale. Mapping DNase I hypersensitive sites within the nuclear chromatin is a powerful and well-established method of identifying regulatory element candidates. Results Here, we report the first genome-wide analysis of DNase I hypersensitive sites (DHSs) in Caenorhabditis elegans . The data was obtained by hybridizing DNase I-treated and end-captured material from young adult worms to a high-resolution tiling microarray. The data show that C. elegans DHSs were significantly enriched within intergenic regions located 2 kb upstream and downstream of coding genes, and also that a considerable fraction of all DHSs mapped to intergenic positions distant to annotated coding genes. Annotated transcribed loci were generally depleted in DHSs relative to intergenic regions, but DHSs were nonetheless enriched in coding exons and UTRs, whereas introns were significantly depleted in DHSs. Many DHSs appeared to be associated with annotated non-coding RNAs and recently detected transcripts of unknown function. It has been reported that nematode highly conserved non-coding elements were associated with cis-regulatory elements, and we also found that DHSs, particularly distal intergenic DHSs, were significantly enriched in regions that were conserved between the C. elegans and C. briggsae genomes. Conclusion We describe the first genome-wide analysis of C. elegans DHSs, and show that the distribution of DHSs is strongly associated with functional elements in the genome.
Let F q OEx be the polynomial ring over the finite field F q containing q elements.We compute the probability that n polynomials in F q OEx are k-wise relatively coprime, using the concept of natural density.As a special case, we get the probability that n polynomials in F q OEx are pairwise coprime.
Leiomyosarcoma is a malignant neoplasm with smooth muscle differentiation. Little is known about its molecular heterogeneity and no targeted therapy currently exists for leiomyosarcoma. Recognition of different molecular subtypes is necessary to evaluate novel therapeutic options. In a previous study on 51 leiomyosarcomas, we identified three molecular subtypes in leiomyosarcoma. The current study was performed to determine whether the existence of these subtypes could be confirmed in independent cohorts.Ninety-nine cases of leiomyosarcoma were expression profiled with 3'end RNA-Sequencing (3SEQ). Consensus clustering was conducted to determine the optimal number of subtypes.We identified 3 leiomyosarcoma molecular subtypes and confirmed this finding by analyzing publically available data on 82 leiomyosarcoma from The Cancer Genome Atlas (TCGA). We identified two new formalin-fixed, paraffin-embedded tissue-compatible diagnostic immunohistochemical markers; LMOD1 for subtype I leiomyosarcoma and ARL4C for subtype II leiomyosarcoma. A leiomyosarcoma tissue microarray with known clinical outcome was used to show that subtype I leiomyosarcoma is associated with good outcome in extrauterine leiomyosarcoma while subtype II leiomyosarcoma is associated with poor prognosis in both uterine and extrauterine leiomyosarcoma. The leiomyosarcoma subtypes showed significant differences in expression levels for genes for which novel targeted therapies are being developed, suggesting that leiomyosarcoma subtypes may respond differentially to these targeted therapies.We confirm the existence of 3 molecular subtypes in leiomyosarcoma using two independent datasets and show that the different molecular subtypes are associated with distinct clinical outcomes. The findings offer an opportunity for treating leiomyosarcoma in a subtype-specific targeted approach.
Let $R := R_{2}(p)=\mathbb{C}[t^{\pm 1}, u : u^2 = t(t-\alpha_1)\cdots (t-\alpha_{2n})] $ be the coordinate ring of a nonsingular hyperelliptic curve and let $\mathfrak{g}\otimes R$ be the corresponding current Lie algebra. \color{black} Here $\mathfrak g$ is a finite dimensional simple Lie algebra defined over $\mathbb C$ and \begin{equation*} p(t)= t(t-\alpha_1)\cdots (t-\alpha_{2n})=\sum_{k=1}^{2n+1}a_kt^k. \end{equation*} In earlier work, Cox and Im gave a generator and relations description of the universal central extension of $\mathfrak{g}\otimes R$ in terms of certain families of polynomials $P_{k,i}$ and $Q_{k,i}$ and they described how the center $\Omega_R/dR$ of this universal central extension decomposes into a direct sum of irreducible representations when the automorphism group was the cyclic group $C_{2k}$ or the dihedral group $D_{2k}$. We give examples of $2n$-tuples $(\alpha_1,\dots,\alpha_{2n})$, which are the automorphism groups $\mathbb G_n=\text{Dic}_{n}$, $\mathbb U_n\cong D_n$ ($n$ odd), or $\mathbb U_n$ ($n$ even) of the hyperelliptic curves \begin{equation} S=\mathbb{C}[t, u: u^2 = t(t-\alpha_1)\cdots (t-\alpha_{2n})] \end{equation} given in [CGLZ17]. In the work below, we describe this decomposition when the automorphism group is $\mathbb U_n=D_n$, where $n$ is odd.
Cross-talk between competitive endogenous RNAs (ceRNAs) may play a critical role in revealing potential mechanism of bovine follicular cysts. Ovarian cyst has always been an intractable scientific problem and has led to considerable economic losses to bovine breeding industry. However, its pathogenesis and molecular mechanisms are still not well understood. Here, this study aimed to investigate the role of non-coding RNAs (ncRNAs) and the ceRNA networks in bovine follicular cyst. Whole transcriptome sequencing of bovine follicular granulosa cells (GCs) was conducted to obtain the expression profiles of mRNAs, lncRNAs and miRNAs. The results for the identified expressions of 8,003 mRNAs, 579 lncRNAs and 205 miRNAs were often altered between cystic and normal follicular GCs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed on these differentially expressed mRNAs. Furthermore, the ceRNA network combining mRNAs, miRNAs, and lncRNAs using several bioinformatics methods based on co-expression analysis between the differentially expressed RNAs was conducted. Finally, the lncRNA NONBTAT027373.1-miR-664b-HSD17B7 pathway was verified by dual-luciferase reporting assay and RNA binding protein immunoprecipitation (RIP) assay. LncRNA NONBTAT027373.1 sponged miR-664b in GCs and prevented miR-664b from binding to the HSD17B7 3'-UTR. These results indicated that genes and lncRNAs related to steroid hormone synthesis and energy metabolism could play important roles in the formation of bovine cystic follicles through the ceRNA mechanism and represent candidate targets for further research. This can be used as a practical guideline for promoting healthy and highly efficient development in the bovine industry.
Aim: To reveal the prognostic significance of serum albumin (ALB) concentration in endometrial cancer (EC) patients in China. Patients & methods: 345 EC patients were enrolled in a single center, and the preoperative serum ALB concentration were measured. Kaplan-Meier curve analysis and Cox proportional hazards regression model were performed to evaluate the associations between ALB concentration and overall survival (OS) of EC patients. Results: The EC patients with lower preoperative serum ALB concentration exhibited a significantly poorer OS (p < 0.05). Univariate analysis and multivariate analysis indicated that serum ALB concentration was an independent prognostic factor of unfavorable OS for EC patients. Conclusion: Our results showing that ALB concentration may serve as an independent prognostic factor for EC patients.
Affinity labeling of biomacromolecules is vital for bioimaging and functional studies. However, affinity probes recognizing glycans with high specificity remain scarce. Here we report the development of glycan recombinant affinity binders (GRABs) based on mutant bacterial sialidases, which are enzymatically inactive but preserve stringent specificity for sialoglycan substrates. By mutating a key catalytic residue of Streptococcus pneumoniae neuraminidase A (SpNanA) and Ruminococcus gnavus neuraminidase H (RgNanH), we develop GRAB-Sia and GRAB-Sia3 recognizing total sialoglycans and α2,3-sialosides, respectively. The GRABs exhibit strict substrate and linkage specificity, and tetramerization with streptavidin substantially increases their avidity. The GRABs and tetrameric GRABs (tetra-GRABs) are effective tools for probing sialoglycans in immunoblotting, flow cytometry, immunoprecipitation, and fluorescence imaging. Furthermore, multiplex analysis with tetra-GRABs uncovers spatially distinct sialoglycans in the various mouse organs. This work provides a versatile toolkit for labeling and analyzing sialoglycans with high specificity, sensitivity, and convenience. Highly specific glycan labels remain scarce, limiting their use in many applications. Here, authors report recombinant glycan affinity binders based on sialidase mutants, which are enzymatically inactive but preserve specificity for sialoglycans.
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