cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.13134656.v1
title: Extracellular microRNA 3’ end modification across diverse body fluids

description: microRNAs (miRNAs) are small non-coding RNAs that play critical roles in gene regulation. The presence of miRNAs in extracellular biofluids is increasingly recognized. However, most previous characterization of extracellular miRNAs focused on their overall expression levels. Alternative sequence isoforms and modifications of miRNAs were rarely considered in the extracellular space. Here, we developed a highly accurate bioinformatic method, called miNTA, to identify 3’ non-templated additions (NTAs) of miRNAs using small RNA-sequencing data. Using miNTA, we conducted an in-depth analysis of miRNA 3’ NTA profiles in 1047 extracellular RNA-sequencing data sets of 4 types of biofluids. This analysis identified hundreds of miRNAs with 3’ uridylation or adenylation, with the former being more prevalent. Among these miRNAs, up to 53% (22%) had an average 3’ uridylation (adenylation) level of at least 10% in a specific biofluid. Strikingly, we found that 3’ uridylation levels enabled segregation of different types of biofluids, more effectively than overall miRNA expression levels. This observation suggests that 3’ NTA levels possess fluid-specific information relatively robust to batch effects. In addition, we observed that extracellular miRNAs with 3’ uridylations are enriched in processes related to angiogenesis, apoptosis, and inflammatory response, and this type of modification may stabilize base-pairing between miRNAs and their target genes. Together, our study provides a comprehensive landscape of miRNA NTAs in human biofluids, which paves way for further biomarker discoveries. The insights generated in our work built a foundation for future functional, mechanistic, and translational discoveries.
DOI: 10.6084/m9.figshare.13207494.v1
title: Identification of HPV16-p16<sup>INK4a</sup> mediated methylation in oral potentially malignant disorder

description: To evaluate the possible involvement of epigenetic modulation by HPV16-p16<sup>INK4a</sup> in oral potentially malignant disorder (OPMD). We generated DNA-methylation profiles, according to p16<sup>INK4a</sup> expression and HPV16 genotype (positive or negative), of OPMD samples and p16<sup>INK4a</sup>-HPV16 negative samples (used as control), using reduced-representation bisulphite sequencing (RRBS-Seq- Illumina) technology. Twelve samples, four for each group, as follows: 1) p16<sup>INK4a</sup>+ HPV16+; 2) p16<sup>INK4a</sup>+ HPV16-; 3) p16<sup>INK4a</sup>- HPV16-, were analysed in triplicate for DNA-methylation profiles. Fifty-four per cent of DMRs were hypermethylated and 46% were hypomethylated. An increase in methylation of loci in OPMD was independent of the presence of HPV. The hypermethylated genes in HPV+ samples were associated with signalling pathways such as NICD traffics to nucleus, signalling by NOTCH1 (p = 0.008), Interferon-gamma (p = 0.008) and Interleukin-6 signalling (p = 0.027). The hypomethylated genes in HPV infection were associated with TRAF3-dependent IRF activation pathway (p = 0.002), RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways (p = 0.005), TRAF6 mediated IRF7 activation (p = 0.009), TRIF-mediated TLR3/TLR4 signalling (p = 0.011) and MyD88-independent cascade release of apoptotic factors (p = 0.011). Protein association analysis of DMRs in OPMD revealed 19 genes involved in the cell cycle regulation, immune system, and focal adhesion. Aberrantly methylated loci in OPMD were observed in p16<sup>INK4a</sup> positive samples which suggests that a shift in global methylation status may be important for cancer progression. The results suggest that HPV infection in OPMD induces modulation of genes related to the immune system and regulation of the cellular cycle.
DOI: 10.6084/m9.figshare.13139392
title: AmpliconDesign – an interactive web server for the design of high-throughput targeted DNA methylation assays

description: Targeted analysis of DNA methylation patterns based on bisulfite-treated genomic DNA (BT-DNA) is considered as a gold-standard for epigenetic biomarker development. Existing software tools facilitate primer design, primer quality control or visualization of primer localization. However, high-throughput design of primers for BT-DNA amplification is hampered by limits in throughput and functionality of existing tools, requiring users to repeatedly perform specific tasks manually. Consequently, the design of PCR primers for BT-DNA remains a tedious and time-consuming process. To bridge this gap, we developed <b><i>AmpliconDesign</i></b>, a webserver providing a scalable and user-friendly platform for the design and analysis of targeted DNA methylation studies based on BT-DNA, e.g. deep amplicon bisulfite sequencing (ampBS-seq) or EpiTYPER MassArray. Core functionality of the web server includes high-throughput primer design and binding site validation based on <i>in silico</i> bisulfite-converted DNA sequences, prediction of fragmentation patterns for EpiTYPER MassArray, an interactive quality control as well as a streamlined analysis workflow for ampBS-seq.
DOI: 10.6084/m9.figshare.13207494
title: Identification of HPV16-p16<sup>INK4a</sup> mediated methylation in oral potentially malignant disorder

description: To evaluate the possible involvement of epigenetic modulation by HPV16-p16<sup>INK4a</sup> in oral potentially malignant disorder (OPMD). We generated DNA-methylation profiles, according to p16<sup>INK4a</sup> expression and HPV16 genotype (positive or negative), of OPMD samples and p16<sup>INK4a</sup>-HPV16 negative samples (used as control), using reduced-representation bisulphite sequencing (RRBS-Seq- Illumina) technology. Twelve samples, four for each group, as follows: 1) p16<sup>INK4a</sup>+ HPV16+; 2) p16<sup>INK4a</sup>+ HPV16-; 3) p16<sup>INK4a</sup>- HPV16-, were analysed in triplicate for DNA-methylation profiles. Fifty-four per cent of DMRs were hypermethylated and 46% were hypomethylated. An increase in methylation of loci in OPMD was independent of the presence of HPV. The hypermethylated genes in HPV+ samples were associated with signalling pathways such as NICD traffics to nucleus, signalling by NOTCH1 (p = 0.008), Interferon-gamma (p = 0.008) and Interleukin-6 signalling (p = 0.027). The hypomethylated genes in HPV infection were associated with TRAF3-dependent IRF activation pathway (p = 0.002), RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways (p = 0.005), TRAF6 mediated IRF7 activation (p = 0.009), TRIF-mediated TLR3/TLR4 signalling (p = 0.011) and MyD88-independent cascade release of apoptotic factors (p = 0.011). Protein association analysis of DMRs in OPMD revealed 19 genes involved in the cell cycle regulation, immune system, and focal adhesion. Aberrantly methylated loci in OPMD were observed in p16<sup>INK4a</sup> positive samples which suggests that a shift in global methylation status may be important for cancer progression. The results suggest that HPV infection in OPMD induces modulation of genes related to the immune system and regulation of the cellular cycle.
DOI: 10.6084/m9.figshare.13139392.v1
title: AmpliconDesign – an interactive web server for the design of high-throughput targeted DNA methylation assays

description: Targeted analysis of DNA methylation patterns based on bisulfite-treated genomic DNA (BT-DNA) is considered as a gold-standard for epigenetic biomarker development. Existing software tools facilitate primer design, primer quality control or visualization of primer localization. However, high-throughput design of primers for BT-DNA amplification is hampered by limits in throughput and functionality of existing tools, requiring users to repeatedly perform specific tasks manually. Consequently, the design of PCR primers for BT-DNA remains a tedious and time-consuming process. To bridge this gap, we developed <b><i>AmpliconDesign</i></b>, a webserver providing a scalable and user-friendly platform for the design and analysis of targeted DNA methylation studies based on BT-DNA, e.g. deep amplicon bisulfite sequencing (ampBS-seq) or EpiTYPER MassArray. Core functionality of the web server includes high-throughput primer design and binding site validation based on <i>in silico</i> bisulfite-converted DNA sequences, prediction of fragmentation patterns for EpiTYPER MassArray, an interactive quality control as well as a streamlined analysis workflow for ampBS-seq.
DOI: 10.15151/esrf-es-771243071
title: Belgian BAG

description: The BAG includes groups situated at four Flemish universities: Antwerp, Brussels, Ghent and Leuven. Several of these groups are part of the elite Flemish Institute of Biotechnology (VIB). The proposed projects are highly diverse, including viral, prokaryotic and eukaryotic proteins with a strong focus on targets and processes of biomedical relevance. Many projects deal with membrane proteins, cell surface receptors and protein-protein complexes. Central to the research in the BAG associated groups is the employment of integrative methods in structural biology combining X-ray crystallography, SAXS, and cryo-electron microscopy. Many crystals in the various proposed projects are small in size and radiation sensitive, requiring the use of the high brilliance MX beam lines, preferably with micro-focused X-rays. This is a continuation of a previous Belgian BAG which has resulted in numerous top-tier publications.
DOI: 10.6084/m9.figshare.13312586.v2
title: DNA hypermethylation/boundary control loss identified in retinoblastomas associated with genetic and epigenetic inactivation of the <i>RB1</i> gene promoter

description: DNA hypermethylation events occur frequently in human cancers, but less is known of the mechanisms leading to their initiation. Retinoblastoma, an intraocular cancer affecting young children, involves bi-allelic inactivation of the <i>RB1</i> gene (<i>RB<sup>−/-</sup></i>). <i>RB1</i> encodes a tumour suppressing, cell cycle regulating transcription factor (<i>pRB)</i> that binds and regulates the <i>RB1</i> core and other <i>E2F</i> responsive promoters with epigenetic functions that include recruitment of histone deacetylases (<i>HDACs</i>). Evidence suggests that bi-allelic epigenetic inactivation/hypermethylation of the <i>RB1</i> core promoter (<i>Pr<sup>E-/E-</sup></i>), is specific to sporadic retinoblastomas (frequency~10%), whereas heritable <i>RB1</i> promoter variants (<i>Pr<sup>−/+</sup></i>, frequency~1-2%) are not associated with known epigenetic phenomena. We report heritable <i>Pr<sup>−/-</sup></i> retinoblastomas with the expected loss of <i>pRB</i> expression, in which hypermethylation consistent with distal boundary displacement (BD) relative to normal peripheral blood DNAs was detected in 4/4 cases. In contrast, proximal <i>BD</i> was identified in <i>16/16 RB<sup>−/-</sup></i> retinoblastomas while multiple boundaries distal of the core promoter was further identified in <i>Pr<sup>E-/E-</sup></i>and <i>Pr<sup>E-/E+</sup></i> retinoblastomas. However, weak or no DNA hypermethylation/<i>BD</i> in peripheral blood DNA was detected in 8/9 <i>Pr<sup>−/+</sup></i> patients, with the exception, a carrier of a microdeletion encompassing several <i>RB1</i> promoter elements. These findings suggest that loss of boundary control may be a critical step leading to epigenetic inactivation of the <i>RB1</i> gene and that novel DNA methylation boundaries/profiles identified in the <i>RB1</i> promoter of <i>Pr<sup>−/-</sup></i> retinoblastomas, may be the result of epigenetic phenomena associated with epimutation in conjunction with loss of <i>pRB</i> expression/binding and/or <i>RB1</i> promoter interactions with boundary control elements.
DOI: 10.15151/esrf-es-750254485
title: Multi-scale Multi-techniques investigations of Li-ion batteries: towards a European Battery Hub

description: In this science-driven Long-Term proposal, we propose a 3-years multi-beamline program tackling grand challenges for actual, emerging and future battery technologies. We will deploy advanced methodologies for accelerating research by setting new cooperation modes for multi-techniques multi-scale studies. Three chemistry-neutral scientific cases have been identified to fulfil this LTP: bulk-to-surface mechanisms, high energy system and smart sensing. Multiple, time-coordinated, interoperable spectroscopic, imaging & scattering techniques will be implemented. This proposal is the Pilot Phase towards a European Battery Hub aiming at accelerating workflows in battery research by optimizing the exceptional diversity of means available at ESRF. We expect to demonstrate the added value of a new “proposal” mechanism, e.g. science-driven beamtime allocation group, serving the fast growing, highly competitive and rapidly evolving European battery community.
DOI: 10.15151/esrf-es-820923614
title: Refractive micro-lenses tracking to perform fast 3D fluid motion imaging

description: Every sample motion is challenging to characterize in both a fast and 3D fashion. By using perfectly characterized refractive micro-lenses as tracking object, one can determine in one single radiography, their 3D position. Therefore, follow complex motions.
DOI: 10.6084/m9.figshare.13089479.v3
title: Sources of variation of DNA methylation in rainbow trout: combined effects of temperature and genetic background

description: Phenotypic plasticity is a key component of the ability of organisms to respond to changing environmental conditions. In this study, we aimed to study the establishment of DNA methylation marks in response to an environmental stress in rainbow trout and to assess whether these marks depend on the genetic background. The environmental stress chosen here was temperature, a known induction factor of epigenetic marks in fish. To disentangle the role of epigenetic mechanisms such as DNA methylation in generating phenotypic variations, nine rainbow trout isogenic lines with no genetic variability within a line were used. For each line, half of the eggs were incubated at standard temperature (11°C) and the other half at high temperature (16°C), from eyed-stage to hatching. In order to gain a first insight into the establishment of DNA methylation marks in response to an early temperature regime (control 11°C vs. heated 16°C), we have studied the expression of 8 <i>dnmt3</i> (DNA methyltransferase) genes, potentially involved in <i>de novo</i> methylation, and analysed global DNA methylation in the different rainbow trout isogenic lines using LUMA (LUminometric Methylation Assay). Finally, finer investigation of genome-wide methylation patterns was performed using EpiRADseq, a reduced-representation library approach based on the ddRADseq (Double Digest Restriction Associated DNA) protocol, for six rainbow trout isogenic lines. We have demonstrated that thermal history during embryonic development alters patterns of DNA methylation, but to a greater or lesser extent depending on the genetic background.
DOI: 10.15151/esrf-es-827543694
title: Pair distribution function analysis of steel

description: Pair distribution function analysis of steel will be carried out.
DOI: 10.15151/esrf-es-750274281
title: Utilizing BCDI to understand finite size effect of AuNP and PdNP on self-organization of gas bubble superlattice

description: This proposal aims to utilize Bragg coherent diffraction imaging (BCDI) at the ID01 beamline to understand the mechanism for self-organization of gas bubbles into superlattices in selected metals. The proposed nanoscale level elucidation of Gas Bubble Superlattice (GBS) formed in model systems such as Au and Pd nano and microcrystals will help elucidate the effect of finite size on GBS formation mechanism. We will use 3D coherent x-ray diffraction patterns to image GBS structures and gain quantitative information on the noble gas bubbles in GBS, such as a change in lattice parameter and strain-induced in gold nanoparticles (AuNP) and palladium nanoparticles (PdNP) of different sizes. In addition, we will compare the effect of radiation flux, fluence, and temperature on the formation mechanism and structure of GBSs within bulk gold with AuNP. Such a systematic study using model systems such as Au and Pd NP will unravel the role of finite size of NPs on the formation mechanism of GBS.
DOI: 10.6084/m9.figshare.13089479.v2
title: Sources of variation of DNA methylation in rainbow trout: combined effects of temperature and genetic background

description: Phenotypic plasticity is a key component of the ability of organisms to respond to changing environmental conditions. In this study, we aimed to study the establishment of DNA methylation marks in response to an environmental stress in rainbow trout and to assess whether these marks depend on the genetic background. The environmental stress chosen here was temperature, a known induction factor of epigenetic marks in fish. To disentangle the role of epigenetic mechanisms such as DNA methylation in generating phenotypic variations, nine rainbow trout isogenic lines with no genetic variability within a line were used. For each line, half of the eggs were incubated at standard temperature (11°C) and the other half at high temperature (16°C), from eyed-stage to hatching. In order to gain a first insight into the establishment of DNA methylation marks in response to an early temperature regime (control 11°C vs. heated 16°C), we have studied the expression of 8 <i>dnmt3</i> (DNA methyltransferase) genes, potentially involved in <i>de novo</i> methylation, and analysed global DNA methylation in the different rainbow trout isogenic lines using LUMA (LUminometric Methylation Assay). Finally, finer investigation of genome-wide methylation patterns was performed using EpiRADseq, a reduced-representation library approach based on the ddRADseq (Double Digest Restriction Associated DNA) protocol, for six rainbow trout isogenic lines. We have demonstrated that thermal history during embryonic development alters patterns of DNA methylation, but to a greater or lesser extent depending on the genetic background.
DOI: 10.15151/esrf-es-780223200
title: Structural studies of SiG anodes for Lithuim-ion Batteries

description: Silicon-graphite (SiG) electrodes are promising anode candidates for next-generation lithium-ion batteries. However, there a still technical challenges to overcome for a successful integration into the battery technology. One of them is the formation of electrochemically less reversible phases, which decreases the overall specific capacity. Another challenge is the optimization of Si/graphite ratio so that the two components participate on the electrochemical (de)-lithiation reactions and that their structures are not affected upon cycling. The proposed analyses will serve to develop improved durable SiG composite anodes and to define operating conditions that minimize the occurrence of undesired side reactions.
DOI: 10.15151/esrf-es-780232662
title: Structural evolution of CO2 sorbents during cyclic operation

description: In order to mitigate climate change and suppress ever-increasing atmospheric CO2 emission, capture and storage technologies have been proposed. The development of efficient and stable CO2 sorbents is a crucial step towards carbon dioxide neutrality. Solid CaO- and MgO-based sorbents are highly promising materials for CO2 capture, owning to their high theoretical CO2 uptake and intermediate operational temperatures and natural abundance. However, bare MgO has a very low CO2 uptake that can be accelerated appreciably through the addition of alkali metal salts (e.g., NaNO3, KNO3, LiNO3, and their eutectic mixtures). Our research is focused on resolving the structural mechanism of CO2 uptake by a combination of complementary in situ methods including in situ environmental SEM, in situ TEM and in situ XRD techniques.
DOI: 10.15151/esrf-es-780223803
title: Quantifying accessible Cu(I) ions in Cu-zeolites by CO titration

description: Cu-exchanged zeolites are the most studied materials for the direct conversion of methane to methanol (DMTM), a “dream reaction” with important consequences in the fields of environment, energy and resource management. Although the mechanism of DMTM is debated, Cu(I)/(II) redox speciation, and especially Cu reducibility, plays a key role in this reaction. Currently, the main technique used to quantitatively assess Cu oxidation state in these materials is XANES spectroscopy. We have been currently developing a new technique to titrate Cu(I) on such systems, based on the specific interaction of CO with this species, that exploits isothermal volumetric adsorption as a quantitative tool. This methodology, however, could be affected by the lack of accessibility of Cu(I) ions by CO within the zeolitic framework. A comparison with a well-affirmed technique for the same quantification, as Cu K-edge XAS, is thus desirable.
DOI: 10.15151/esrf-es-749924096
title: XRF anlayses to unravel the role of iron and other metals in endometriosis

description: Endometriosis is an inflammatory disease affecting about 10% of women of reproductive age, which is still poorly understood. A role of iron has been proposed. In endometriosis, iron accumulation can occur within endometrial lesions and peritoneal macrophages. This project aimed at investigating by XRF microscopy and XANES the iron migration and its chemical state in the invading endometrium, as well as to monitor the possible appearance of environmental chemical elements. The analyses will expand actual knowledge and could suggest therapeutic interventions.
DOI: 10.15151/esrf-es-750919007
title: Bridging the gap between cellular and whole body imaging using Hierarchical Phase-Contrast Tomography: HiP-CT

description: Humans and other large organisms are three-dimensional multiscale biological systems where large scale function and structure are dependent on the macrostructure’s interconnectivity down to the cellular and subcellular level. Using the exceptional coherence provided by the ESRF-EBS, we have demonstrated that propagation-based phase-contrast can effectively decouple resolution from specimen size in soft tissue, obtaining 1.4 micron voxel resolution in 150 mm diameter human organs. Through this Long Term Proposal (LTP) we will develop the techniques required to image whole human and animal bodies ex vivo at 25 micron resolution, zooming to sub-micron voxels (0.7micron) locally, resolving sub-cellular structures through hard- and soft-tissue. Resolving how the micro (sub-cellular) interacts with the macro (whole organism) across length scales will provide all new insights into biological and biomedical function. This is true for both healthy and pathological system level behaviour.
DOI: 10.15151/esrf-es-779299765
title: Grazing incidence small angle X-ray scattering and asymmetric X-ray diffraction on Ga droplets on Si substrates and on top of GaAs nanowires

description: GaAs nanowires (NWs) are often fabricated by molecular beam epitaxy using the self-catalyzed vapour-liquid-solid mode, where a liquid Ga catalyst droplet at the apex of the NW drives the axial crystal growth. The wetting angle of the droplet determines the crystal structure of the NWs which mainly consists of the zinc blende (ZB) and wurtzite (WZ) crystal phases when grown along the [111] crystallographic direction. Regardless of the achieved high degree of control over the crystal phase of GaAs NWs during latter growth stages, it is challenging to control the polytypism at the beginning of the NW growth due to transients in the droplet contact angle. Here, we aim to correlate the crystal structure of as-grown GaAs NWs with the wetting angle of their catalyst liquid Ga droplets at the nucleation phase, by performing (1) grazing incidence small angle X-ray scattering on the Ga droplets, and (2) asymmetric X-ray diffraction of polytype sensitive reflections on the NWs underneath.