| 1. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 2. |
- Xin, Yiwei, et al.
(författare)
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Fusobacterium nucleatum- induced exosomal HOTTIP promotes gastric cancer progression through the microRNA-885-3p/EphB2 axis
- 2023
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Ingår i: Cancer Science. - : John Wiley & Sons. - 1347-9032 .- 1349-7006. ; 114:6, s. 2360-2374
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have reported that Fusobacterium nucleatum (Fn) is associated with gastric cancer (GC). Cancer-derived exosomes contain key regulatory noncoding RNAs and are a crucial medium of intercellular communication. However, the function and regulatory mechanism of exosomes (Fn-GCEx) secreted from Fn-infected GC cells remains unclear. In this study, Fn-GCEx enhanced the proliferation, migration, and invasion capacity of GC cells in vitro, as well as tumor growth and metastasis in vivo. HOTTIP was also upregulated in GC cells treated with Fn-GCEx. Moreover, knockdown of HOTTIP weakened the effects of Fn-GCEx in recipient GC cells. Mechanistically, HOTTIP promoted EphB2 expression by sponging microRNA (miR)-885-3p, thus activating the PI3K/AKT pathway in Fn-GCEx treated GC cells. Overall, Fn infection induced the upregulation of exosomal HOTTIP from GC cells that subsequently promoted GC progression through the miR-885-3p/EphB2/PI3K/AKT axis. Herein, we identify a potential molecular pathway and therapeutic target for GC.
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| 3. |
- Du, Mulong, et al.
(författare)
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Cyp2a6 activity and cigarette consumption interact in smoking-related lung cancer susceptibility
- 2024
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Ingår i: Cancer Research. - : American Association For Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 84:4, s. 616-625
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Tidskriftsartikel (refereegranskat)abstract
- Cigarette smoke, containing both nicotine and carcinogens, causes lung cancer. However, not all smokers develop lung cancer, highlighting the importance of the interaction between host susceptibility and environmental exposure in tumorigenesis. Here, we aimed to delineate the interaction between metabolizing ability of tobacco carcinogens and smoking intensity in mediating genetic susceptibility to smoking-related lung tumorigenesis. Single-variant and gene-based associations of 43 tobacco carcinogen–metabolizing genes with lung cancer were analyzed using summary statistics and individual-level genetic data, followed by causal inference of Mendelian randomization, mediation analysis, and structural equation modeling. Cigarette smoke–exposed cell models were used to detect gene expression patterns in relation to specific alleles. Data from the International Lung Cancer Consortium (29,266 cases and 56,450 controls) and UK Biobank (2,155 cases and 376,329 controls) indicated that the genetic variant rs56113850 C>T located in intron 4 of CYP2A6 was significantly associated with decreased lung cancer risk among smokers (OR = 0.88, 95% confidence interval = 0.85–0.91, P = 2.18 X 10-16), which might interact (Pinteraction = 0.028) with and partially be mediated (ORindirect = 0.987) by smoking status. Smoking intensity accounted for 82.3% of the effect of CYP2A6 activity on lung cancer risk but entirely mediated the genetic effect of rs56113850. Mechanistically, the rs56113850 T allele rescued the downregulation of CYP2A6 caused by cigarette smoke exposure, potentially through preferential recruitment of transcription factor helicase-like transcription factor. Together, this study provides additional insights into the interplay between host susceptibility and carcinogen exposure in smoking-related lung tumorigenesis.
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| 4. |
- Euskirchen, Ghia M, et al.
(författare)
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Mapping of transcription factor binding regions in mammalian cells by ChIP : comparison of array- and sequencing-based technologies.
- 2007
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 17:6, s. 898-909
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Tidskriftsartikel (refereegranskat)abstract
- Recent progress in mapping transcription factor (TF) binding regions can largely be credited to chromatin immunoprecipitation (ChIP) technologies. We compared strategies for mapping TF binding regions in mammalian cells using two different ChIP schemes: ChIP with DNA microarray analysis (ChIP-chip) and ChIP with DNA sequencing (ChIP-PET). We first investigated parameters central to obtaining robust ChIP-chip data sets by analyzing STAT1 targets in the ENCODE regions of the human genome, and then compared ChIP-chip to ChIP-PET. We devised methods for scoring and comparing results among various tiling arrays and examined parameters such as DNA microarray format, oligonucleotide length, hybridization conditions, and the use of competitor Cot-1 DNA. The best performance was achieved with high-density oligonucleotide arrays, oligonucleotides >/=50 bases (b), the presence of competitor Cot-1 DNA and hybridizations conducted in microfluidics stations. When target identification was evaluated as a function of array number, 80%-86% of targets were identified with three or more arrays. Comparison of ChIP-chip with ChIP-PET revealed strong agreement for the highest ranked targets with less overlap for the low ranked targets. With advantages and disadvantages unique to each approach, we found that ChIP-chip and ChIP-PET are frequently complementary in their relative abilities to detect STAT1 targets for the lower ranked targets; each method detected validated targets that were missed by the other method. The most comprehensive list of STAT1 binding regions is obtained by merging results from ChIP-chip and ChIP-sequencing. Overall, this study provides information for robust identification, scoring, and validation of TF targets using ChIP-based technologies.
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| 5. |
- Gerstein, Mark B, et al.
(författare)
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What is a gene, post-ENCODE? : History and updated definition
- 2007
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 17:6, s. 669-681
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Tidskriftsartikel (refereegranskat)abstract
- While sequencing of the human genome surprised us with how many protein-coding genes there are, it did not fundamentally change our perspective on what a gene is. In contrast, the complex patterns of dispersed regulation and pervasive transcription uncovered by the ENCODE project, together with non-genic conservation and the abundance of noncoding RNA genes, have challenged the notion of the gene. To illustrate this, we review the evolution of operational definitions of a gene over the past century--from the abstract elements of heredity of Mendel and Morgan to the present-day ORFs enumerated in the sequence databanks. We then summarize the current ENCODE findings and provide a computational metaphor for the complexity. Finally, we propose a tentative update to the definition of a gene: A gene is a union of genomic sequences encoding a coherent set of potentially overlapping functional products. Our definition side-steps the complexities of regulation and transcription by removing the former altogether from the definition and arguing that final, functional gene products (rather than intermediate transcripts) should be used to group together entities associated with a single gene. It also manifests how integral the concept of biological function is in defining genes.
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| 6. |
- Liu, Jun, et al.
(författare)
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Resource utilization of municipal solid waste incineration fly ash - cement and alkali-activated cementitious materials: A review
- 2022
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 852
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Forskningsöversikt (refereegranskat)abstract
- The increase in municipal solid waste (MSW) production has led to an increase in MSW incineration fly ash (MSWIFA) production. MSWIFA contains toxic and harmful substances such as heavy metals and dioxins, which can cause harm to the environment if not treated properly. Only a few MSWIFAs will be landfilled directly, and the rest will need to be treated by other methods. The treatment of MSWIFA can be divided into three types: separation, stabilization/solidification (S/S), and thermal treatment, which are either not fully developed or too costly. Resource utilization is a sustainable means of treating MSWIFA. MSWIFA is used in the production of cement and alkali-activated cementitious materials as a means of resource utilization with significant advantages. This can alleviate the consumption of nature and reduce greenhouse gas emissions in conventional cement production. Compared with MSWIFA cement, MSWIFA alkali-activated cementitious material can be achieved with almost no consumption of natural resources, which is worthy of further research to realize the large-scale application of MSWIFA. At the end of the paper, the perspective of separation of dioxins from MSWIFA, co-processing of MSWI ash, and production of “MSWIFA green materials” is presented.
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| 7. |
- Liu, Jun, et al.
(författare)
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Synthesis of geopolymer using municipal solid waste incineration fly ash and steel slag: Hydration properties and immobilization of heavy metals
- 2023
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Ingår i: Journal of Environmental Management. - 0301-4797 .- 1095-8630. ; 341
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Tidskriftsartikel (refereegranskat)abstract
- In this study, a novel method for the disposal of municipal solid waste incineration fly ash (MSWIFA) was proposed. By applying geopolymer technology, steel slag (SS) and MSWIFA were used together as precursors to synthesize a cementitious material with sufficient strength that is useable in construction. The effects of the dosages of SS and alkaline activator on the properties of the geopolymer were investigated. Compressive testing was used to characterize the mechanical properties of the geopolymer. X-ray diffraction (XRD), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) were used for microscopic analysis. Leaching tests were performed to assess the immobilization effect of the geopolymer on heavy metals. The results showed that the compressive strength of the geopolymer reached 23.03 MPa at 56 d with 20% SS and 11% Na2O admixture. Highly polymerized hydration products, such as C-(A)-S-H gels and N-A-S-H gels, contributed to the compact microstructure, which provided mechanical strength and limited the migration and leaching of heavy metals in the geopolymer matrix. In terms of the results, this work is significant for the development of MSWIFA management.
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| 8. |
- Song, Han Hee, et al.
(författare)
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Clustered Embedding of Massive Social Networks
- 2012
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Ingår i: Proceedings of the 12th ACM SIGMETRICS/PERFORMANCE joint international conference on Measurement and Modeling of Computer Systems. - New York, NY, USA : Association for Computing Machinery (ACM). - 9781450310970 ; , s. 331-342
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The explosive growth of social networks has created numerous exciting research opportunities. A central concept in the analysis of social networks is a proximity measure, which captures the closeness or similarity between nodes in a social network. Despite much research on proximity measures, there is a lack of techniques to eciently and accurately compute proximity measures for large-scale social networks. In this paper, we develop a novel dimensionality reduction technique, called clustered spectral graph embedding, to embed the graphs adjacency matrix into a much smaller matrix. The embedded matrix together with the embedding subspaces capture the essential clustering and spectral structure of the original graph and allows a wide range of analysis tasks to be performed in an ecient and accurate fashion. To evaluate our technique, we use three large real-world social network datasets: Flickr, LiveJournal and MySpace, with up to 2 million nodes and 90 million links. Our results clearly demonstrate the accuracy, scalability and exibility of our approach in the context of three importantsocial network analysis tasks: proximity estimation, missing link inference, and link prediction.
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| 9. |
- Yong, Zhengdong, et al.
(författare)
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Broadband Nanoantennas for Plasmon Enhanced Fluorescence and Raman Spectroscopies
- 2015
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Ingår i: Progress In Electromagnetics Research. - : EMW Publishing. - 1070-4698 .- 1559-8985. ; 153, s. 123-131
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Tidskriftsartikel (refereegranskat)abstract
- We propose a novel design of broadband plasmonic nanoantenna that is suitable for fluorescence and Raman enhancement. The structure consists of a gold nanoring and bowties at the center. We numerically investigate the near field and far field performance by employing the finite-difference time-domain method. High Purcell enhancement and large SERS are demonstrated in a record wide spectral bandwidth of 700 nm based on a single emitter-antenna configuration. Moreover, unlike a traditional antenna design, the proposed nanoantenna has low heat generation and high field enhancement at the gap simultaneously when operating off resonance.
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| 10. |
- Yong, Zhengdong, et al.
(författare)
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Narrow band perfect absorber for maximum localized magnetic and electric field enhancement and sensing applications
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Plasmonics offer an exciting way to mediate the interaction between light and matter, allowing strong field enhancement and confinement, large absorption and scattering at resonance. However, simultaneous realization of ultra-narrow band perfect absorption and electromagnetic field enhancement is challenging due to the intrinsic high optical losses and radiative damping in metals. Here, we propose an all-metal plasmonic absorber with an absorption bandwidth less than 8 nm and polarization insensitive absorptivity exceeding 99%. Unlike traditional Metal-Dielectric-Metal configurations, we demonstrate that the narrowband perfect absorption and field enhancement are ascribed to the vertical gap plasmonic mode in the deep subwavelength scale, which has a high quality factor of 120 and mode volume of about 10(-4) x (lambda(res)/n)(3). Based on the coupled mode theory, we verify that the diluted field enhancement is proportional to the absorption, and thus perfect absorption is critical to maximum field enhancement. In addition, the proposed perfect absorber can be operated as a refractive index sensor with a sensitivity of 885 nm/RIU and figure of merit as high as 110. It provides a new design strategy for narrow band perfect absorption and local field enhancement, and has potential applications in biosensors, filters and nonlinear optics.
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