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- 2019
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Journal article (peer-reviewed)
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- Wakelam, V., et al.
(author)
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A KINETIC DATABASE FOR ASTROCHEMISTRY (KIDA)
- 2012
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In: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 199:1, s. 21-
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Journal article (peer-reviewed)abstract
- We present a novel chemical database for gas-phase astrochemistry. Named the KInetic Database for Astrochemistry (KIDA), this database consists of gas-phase reactions with rate coefficients and uncertainties that will be vetted to the greatest extent possible. Submissions of measured and calculated rate coefficients are welcome, and will be studied by experts before inclusion into the database. Besides providing kinetic information for the interstellar medium, KIDA is planned to contain such data for planetary atmospheres and for circumstellar envelopes. Each year, a subset of the reactions in the database (kida.uva) will be provided as a network for the simulation of the chemistry of dense interstellar clouds with temperatures between 10 K and 300 K. We also provide a code, named Nahoon, to study the time-dependent gas-phase chemistry of zero-dimensional and one-dimensional interstellar sources.
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- Chandrasekaran, V, et al.
(author)
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AGGREGATED SURVIVIN BINDING AROUND HISTONE H3 EPIGENETIC MODIFICATIONS IN RISK LOCI ASSOCIATED WITH RHEUMATOID ARTHRITIS
- 2021
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In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 428-428
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Conference paper (other academic/artistic)abstract
- Survivin is an integral part of the Chromosomal Passenger Complex (CPC) which plays a vital role in mitosis. Experiments have demonstrated that survivin can physically bind to DNA. Crystallographic studies show that survivin binds to Threonine-3 of histone H3. In patients with autoimmune diseases, increased survivin expression contributes to an aggravated disease phenotype. Thus, functional, and mechanistic data point to a potential chromatin regulatory role for survivin, possibly in combination with the established gene regulatory function carried out by histone epigenetic modifications (EM).Objectives:The objective of the study was to analyse the co-localization of chromatin bound survivin with three histone H3 epigenetic modifications – acetylated lysine 27 (K27ac) and trimethylated lysine 4 (K4me3) and lysine-27 (K27me3). The second objective was to analyse if survivin-bound DNA sequences overlapped with sequences in the vicinity of 106 GWAS SNPs that are associated with a risk of developing rheumatoid arthritis (RA).Methods:Chromatin from CD4 T cells of 14 female subjects was immunoprecipitated with survivin antibodies and each of the histone H3 antibodies, and coupled with sequencing (ChIPseq, Hiseq2000, Illumina). After mapping the annotations of sequenced regions to the human reference genome hg38, enriched peaks were identified through Homer software. The identified survivin ChIP peaks were analysed for colocalization with peaks of the three histone H3 EMs and with RA risk loci, using the Bioconductor package ‘ChIPPeakAnno’ through RStudio.Results:Among the total of ~13,000 individual survivin ChIP-peaks, 33% colocalized with histone H3 EM peaks. The overlapping peaks show a linear increase in average peak size compared with the peaks showing no colocalization with any H3 EM peak. A maximum of 5.5-fold increase in average peak size was observed when survivin bound peaks overlap with peaks of all three H3 EMs. A major proportion (86%) of top RA risk SNPs was associated with either binding of survivin or H3 EMs. In this subset, 63% of RA risk SNPs were found within an area of 100 kilobases from survivin ChIP-peaks, with preferential enrichment of high-scoring peaks when survivin colocalizes with all 3 H3 EMs. Survivin was bound to risk SNPs annotated to, among others, the major immunological genes CD83, IRF4, CD28, ICOS and IL2RAConclusion:This study presents experimental evidence that survivin binding to DNA preferentially occurred in regions with high density of histone EMs. The increased aggregation of survivin around histone H3 EMs point to its potential regulatory function in gene transcription. Since regions around RA risk SNPs overlap with survivin peaks, survivin’s nuclear function could have immunologically important effects in mechanisms of autoimmune diseases.Disclosure of Interests:None declared
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| 6. |
- Chandrasekaran, V, et al.
(author)
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FUNCTIONAL ROLE OF SURVIVIN IN ORGANIZATION OF BIVALENT CHROMATIN REGIONS AND CONSEQUENCE FOR ARTHRITIS-RELEVANT GENE EXPRESSION
- 2022
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In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 231-231
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Conference paper (other academic/artistic)abstract
- Bivalent chromatin (BvCR) is characterized by the presence of simultaneous active and repressive modifications on histone H3 proteins. Influencing expression of the genes, BvCR determine cell fate and direct differentiation and lineage commitment in primary T cells and contribute to autoimmunity. Survivin is highly expressed during cell division and in effector Th1 cells contributing to aggravation of autoimmune inflammation. Survivin can physically bind to DNA, specifically to Threonine-3 of histone H3 (1). Thus, functional, and mechanistic data point to a potential chromatin regulatory role for survivin, potentially acting in combination with histone epigenetic modifications (EMs).ObjectivesThe goal of our study is to establish the colocalization of survivin with BvCRs and to deduce functional effects of this collaboration on chromatin organization and gene expression.MethodsChromatin from CD4+ T cells of 14 female subjects was immunoprecipitated with survivin antibodies and histone H3K27ac, H3K27me3, H3K4me3 antibodies, and coupled with DNA sequencing (ChIPseq, Hiseq2000, Illumina). BvCR were identified as exact overlaps of the three histone EM peaks and the overlapping regions were searched for co-localization with survivin using the ‘ChIPPeakAnno’ Bioconductor package. Tag counts K27me3>K27ac were defined as inactive/poised BvCR, while tag count K27me3<K27ac were identified asactive BvCR. Motif search was done through the MEME tool, and high/moderate complexity motifs with E-value >10e-5 were selected and scanned through the HOCOMOCO database to identify consensus transcription factor (TF) motifs. TFs co-localized with the BvCD were identified through ReMap database. To identify survivin sensitive genes, CD4+ T cells were treated with survivin inhibitor YM155 and a list of reproducible DEG (log2FC>[0.4], >1 experiment) was mapped and analysed for clustering with BvCR.ResultsCo-localization of survivin ChIP peaks with individual H3-peaks was significantly less frequent compared to overlap with all three (a3)-H3 BvCR (7.1 vs 29.8%, p=8.9e-13). Overlap of a3-H3 peaks not containing survivin was less frequent (34%) compared to those which contained survivin (66%). Notably, survivin peak size was 5.5-fold higher when colocalized with a3-H3 peaks, compared to no, or any single H3 (p<2.2e-16). In contrast, no size difference for any of the H3 EM peaks was found.Further analysis of two non-redundant groups of BvCR that contain (survivin-a3H3, n=4085), and not containing survivin (a3H3noSurv, n = 2131) demonstrated that survivin was mostly associated with inactive BvCR (OR1.29, p=6.6e-6), while no such specificity was found for BvCR with no survivin. Additionally, survivin containing BvCR contained abundant binding sites matching known consensus TF motifs. No sequence-specific motifs were identified in BvCR with no survivin. Comparison of results obtained through HOCOMOCO and ReMap databases resulted in a list of 68 unique TFs. Many of those are key regulators of adaptive immune responses, cellular metabolism, and pluripotency. Differentially expressed genes mapped to BvCR demonstrated enrichment for cellular hormone metabolic processes, regeneration and DNA biosynthesis.ConclusionThis study provides experimental evidence that survivin defines binding specificity in bivalent chromatin regions being associated with regulation of cellular metabolism and renewal of CD4+ T cells that are functionally important to resist autoimmunity.References[1]Kelly AE, Ghenoiu C, Xue JZ, Zierhut C, Kimura H, Funabiki H. Survivin reads phosphorylated histone H3 threonine 3 to activate the mitotic kinase Aurora B Science. 2010 Oct 8; 330(6001): 235–239.Disclosure of InterestsNone declared
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- Hayagrivan, Vishal, et al.
(author)
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Optimization of process parameters for fused filament fabrication using tool path reversing
- 2019
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In: ICCM International Conferences on Composite Materials. - : International Committee on Composite Materials.
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Conference paper (peer-reviewed)abstract
- Fused filament fabrication (FFF) is one of the most economical additive manufacturing techniques. The difficulty in estimating the effects of process parameters on the mechanical properties of the manufactured part, hinders the wide spread industrial adaptation of FFF. The quality of a part manufactured by FFF highly depends on the process parameters so, it is imperative to develop a technique to fine tune the process parameters. The large number of process parameters and complex relationship between the geometry, parameters and mechanical properties makes it impractical to derive an analytical or an empirical relationship and calls for the use of a finite element (FE) model. A few commercially available FE packages support the simulation of a select types of additive manufacturing techniques - such packages primarily focus on metal additive manufacturing. A novel method to automatically build a FE model from a geometry and given process parameters is developed in this paper. Image recognition techniques are used to analyse the GCode instructions to build a FE model. As the FE model is built by using the same instruction set a FFF machine uses to manufacture the part, the generated FE model will encompass the effects of all parameters which affect the mechanical behaviour of the manufactured part. The automatic generation of a FE model enables the optimization of the FFF parameters.
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| 9. |
- Oparina, N, et al.
(author)
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COMPLEX LANDSCAPE OF BIRC5/SURVIVIN GENOME BINDING IN HUMAN CD4+T CELLS
- 2021
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In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 410-410
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Conference paper (other academic/artistic)abstract
- Survivin, coded by BIRC5 gene, is a multitasking protein essential for cell renewal and homeostasis. In autoimmune conditions as rheumatoid and psoriasis arthritis, survivin was associated with inflammation severity and joint damage. Importantly, inhibition of survivin alleviated experimental arthritis in mice. We have recently shown survivin to be essential for T cell differentiation and micro-RNA processing. The known anti-apoptotic and proliferation facilitating functions of survivin does not explain the nuclear localization of survivin in interphase.Objectives:We aimed to uncover nuclear functions of BIRC5/survivin in CD4 cell of RA patients and healthy.Methods:CD4 T cells were isolated from the peripheral blood using positive selection on magnetic beads (EasySep) and activated for 48h with ConA+LPS. Chromatin immunoprecipitation (ChIP) with polyclonal anti-survivin antibodies was done in four independent samples of healthy donors (n=5), healthy smokers (n=3), rheumatoid arthritis (n=3) and breast cancer (n=2). Pooled libraries were constructed for each group and ChIPseq was carried out (Illumina). For comparative RNAseq analysis, activated CD4 T cells were incubated with or without survivin inhibitor (YM155) for 24h. State-of-the-art bioinformatics pipelines were applied for NGS data and the survivin-binding peaks were used for comparison with genes, chromatin state annotation and functional gene- and regulatory regions-based functional analysis. Co-localization of peaks in the whole genome and in vicinity of the differentially expressed genes (DEG) was done using ReMap integrated ChIPseq datasets for all human cells and tissues.Results:We identified 13 thousands non-overlapping survivin ChIP-peaks (>3000 peaks were present in at least 3 samples). Survivin-bound regions were enriched near the genes and promoters (p=e-30 and p=e-8), which implied that survivin role in transcription could be mediated by known transcription factors. Thus, we analyzed survivin peaks vs binding regions of 1135 transcription regulators (TR) available in ReMap.Potential partner proteins of survivin were selected based on the enrichment of the overlapping peaks in the whole genome and in CD4-active regulatory areas. Both, strict overlaps and location within 10 and 100kb survivin peak vicinity were analyzed. This approach allowed us to select >150 TRs enriched in all tests. The enriched TRs were involved in immunity and RA-relevant pathways including cytokine response and production, JAK-STAT signaling, etc. Among the TRs co-localized with survivin were CHD8, MAX, EP300, BRD2, CTCF and RAD21, all responsible for chromatin architecture. Several TRs were massively enriched in the vicinity of DEGs after survivin depletion including MAX, AR, CTCF, MYC and IRF1. Search for TR binding motifs in survivin peaks supported over-representation of binding sites for IRFs (p=e-5) and several proteins of the bZIP-family (p=e-5).Conclusion:Analysis of the survivin bound DNA in CD4 cells demonstrated the nonrandom distribution with specific enrichment within the regulatory elements of the genes and co-localizeation with protein partners to regulate their transcription.Disclosure of Interests:None declared
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