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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Feng, Ruizhi, et al.
(författare)
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Mutations in TUBB8 and Human Oocyte Meiotic Arrest.
- 2016
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Ingår i: The New England journal of medicine. - 1533-4406. ; 374:3, s. 223-232
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Tidskriftsartikel (refereegranskat)abstract
- Background Human reproduction depends on the fusion of a mature oocyte with a sperm cell to form a fertilized egg. The genetic events that lead to the arrest of human oocyte maturation are unknown. Methods We sequenced the exomes of five members of a four-generation family, three of whom had infertility due to oocyte meiosis I arrest. We performed Sanger sequencing of a candidate gene, TUBB8, in DNA samples from these members, additional family members, and members of 23 other affected families. The expression of TUBB8 and all other β-tubulin isotypes was assessed in human oocytes, early embryos, sperm cells, and several somatic tissues by means of a quantitative reverse-transcriptase-polymerase-chain-reaction assay. We evaluated the effect of the TUBB8 mutations on the assembly of the heterodimer consisting of one α-tubulin polypeptide and one β-tubulin polypeptide (α/β-tubulin heterodimer) in vitro, on microtubule architecture in HeLa cells, on microtubule dynamics in yeast cells, and on spindle assembly in mouse and human oocytes. Results We identified seven mutations in the primate-specific gene TUBB8 that were responsible for oocyte meiosis I arrest in 7 of the 24 families. TUBB8 expression is unique to oocytes and the early embryo, in which this gene accounts for almost all the expressed β-tubulin. The mutations affect chaperone-dependent folding and assembly of the α/β-tubulin heterodimer, disrupt microtubule behavior on expression in cultured cells, alter microtubule dynamics in vivo, and cause catastrophic spindle-assembly defects and maturation arrest on expression in mouse and human oocytes. Conclusions TUBB8 mutations have dominant-negative effects that disrupt microtubule behavior and oocyte meiotic spindle assembly and maturation, causing female infertility. (Funded by the National Basic Research Program of China and others.).
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| 4. |
- Kristan, Matej, et al.
(författare)
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The Sixth Visual Object Tracking VOT2018 Challenge Results
- 2019
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Ingår i: Computer Vision – ECCV 2018 Workshops. - Cham : Springer Publishing Company. - 9783030110086 - 9783030110093 ; , s. 3-53
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Konferensbidrag (refereegranskat)abstract
- The Visual Object Tracking challenge VOT2018 is the sixth annual tracker benchmarking activity organized by the VOT initiative. Results of over eighty trackers are presented; many are state-of-the-art trackers published at major computer vision conferences or in journals in the recent years. The evaluation included the standard VOT and other popular methodologies for short-term tracking analysis and a “real-time” experiment simulating a situation where a tracker processes images as if provided by a continuously running sensor. A long-term tracking subchallenge has been introduced to the set of standard VOT sub-challenges. The new subchallenge focuses on long-term tracking properties, namely coping with target disappearance and reappearance. A new dataset has been compiled and a performance evaluation methodology that focuses on long-term tracking capabilities has been adopted. The VOT toolkit has been updated to support both standard short-term and the new long-term tracking subchallenges. Performance of the tested trackers typically by far exceeds standard baselines. The source code for most of the trackers is publicly available from the VOT page. The dataset, the evaluation kit and the results are publicly available at the challenge website (http://votchallenge.net).
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| 5. |
- Lin, Qing, et al.
(författare)
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Exosome-like nanoplatform modified with targeting ligand improves anti-cancer and anti-inflammation effects of imperialine
- 2019
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Ingår i: Journal of Controlled Release. - : ELSEVIER. - 0168-3659 .- 1873-4995. ; 311, s. 104-116
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Tidskriftsartikel (refereegranskat)abstract
- Currently, most anti-cancer therapies are still haunted by serious and deleterious adverse effects. Here, we report a highly biocompatible tumor cell-targeting delivery systems utilizing exosome-like vesicles (ELVs) that delivers a low-toxicity anti-cancer agent imperialine against non-small cell lung cancer (NSCLC). First, we introduced a novel micelle-aided method to efficiently load imperialine into intact ELVs. Then, integrin alpha 3 beta 1-binding octapeptide cNGQGEQc was modified onto ELV platform for tumor targeting as integrin alpha 3 beta 1 is overexpressed on NSCLC cells. This system not only significantly improved imperialine tumor accumulation and retention, but also had extremely low systemic toxicity both in vitro and in vivo. Our discoveries offer new ways to utilize ELV more efficiently for both drug loading and targeting. The solid pharmacokinetics improvement and extraordinary safety of this system also highlight possibilities of alternative long course cancer therapies using similar strategies.
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| 6. |
- Bai, Ru, et al.
(författare)
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The NF-κB-modulated miR-19a-3p enhances malignancy of human ovarian cancer cells through inhibition of IGFBP-3 expression
- 2019
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Ingår i: Molecular Carcinogenesis. - : Wiley. - 0899-1987 .- 1098-2744. ; 58:12, s. 2254-2265
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Tidskriftsartikel (refereegranskat)abstract
- Ovarian cancer is the most lethal gynecologic malignancy due to the lack of symptoms until advanced stages, and new diagnosis and treatment strategy is in urgent need. In this study, we found higher expression of miR-19a-3p in ovarian cancer tissues compared with that in the adjacent normal tissues. By chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA) analysis, we showed that nuclear factor-kappaB (NF-κB) binds to the promoter of miR-19a-3p, leading to reduced expression in ovarian cancer cells. Further study indicated that miR-19a-3p inhibits the expression of insulin-like growth factor binding protein-3 (IGFBP-3), resulting in enhanced growth and migration of ovarian cancer cells in vitro and tumor growth in vivo. These results showed that miR-19a-3p enhances the oncogenesis of ovarian cancer through inhibition of IGFBP-3 expression, and which can be inhibited by NF-κB, suggesting an NF-κB/miR-19a-3p/IGFBP-3 pathway in the oncogenesis of ovarian cancer, which expands our understanding of ovarian cancer and they may contribute to the development of new diagnosis and treatment of ovarian cancer.
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| 7. |
- Feng, Ruizhi, et al.
(författare)
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MiRNA-320 in the human follicular fluid is associated with embryo quality in vivo and affects mouse embryonic development in vitro.
- 2015
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Previous work from our laboratory demonstrated the existence of miRNAs in human follicular fluid. In the current study, we have sought to identify miRNAs that might affect oocyte/embryo quality in patients undergoing intracytoplasmic sperm injection and to investigate their roles in in vitro fertilization outcomes in mouse oocytes. 53 samples were classified as Group 1 (high quality) if the day-3 embryos had seven and more cells or as Group 2 (low quality) if the embryos had six and fewer cells. TaqMan Human microRNAs cards and qRT-PCR were performed to verify differently expressed miRNAs. The function of the corresponding miRNA was investigated in mouse oocytes by injecting them with miRNA-inhibitor oligonucleotides. We found that hsa-miR-320a and hsa-miR-197 had significantly higher expression levels in the Group 1 follicular fluids than in Group 2 (p = 0.0073 and p = 0.008, respectively). Knockdown of mmu-miR-320 in mouse oocytes strongly decreased the proportions of MII oocytes that developed into two-cell and blastocyst stage embryos (p = 0.0048 and p = 0.0069, respectively). Wnt signaling pathway components had abnormal expression level in miR-320 inhibitor-injected oocytes. This study provides the first evidence that miRNAs in human follicular fluid are indicative of and can influence embryo quality.
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| 8. |
- Horvatovich, Peter, et al.
(författare)
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Quest for Missing Proteins : Update 2015 on Chromosome-Centric Human Proteome Project
- 2015
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 14:9, s. 3415-3431
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- This paper summarizes the recent activities of the Chromosome-Centric Human Proteome Project (C-HPP) consortium, which develops new technologies to identify yet-to-be annotated proteins (termed "missing proteins") in biological samples that lack sufficient experimental evidence at the protein level for confident protein identification. The C-HPP also aims to identify new protein forms that may be caused by genetic variability, post-translational modifications, and alternative splicing. Proteogenomic data integration forms the basis of the C-HPP's activities; therefore, we have summarized some of the key approaches and their roles in the project. We present new analytical technologies that improve the chemical space and lower detection limits coupled to bioinformatics tools and some publicly available resources that can be used to improve data analysis or support the development of analytical assays. Most of this paper's content has been compiled from posters, slides, and discussions presented in the series of C-HPP workshops held during 2014. All data (posters, presentations) used are available at the C-HPP Wild (http://c-hpp.webhosting.rug.nl/) and in the Supporting Information.
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| 9. |
- Hu, Xian-Ge, et al.
(författare)
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Global transcriptome analysis of Sabina chinensis (Cupressaceae), a valuable reforestation conifer
- 2016
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Ingår i: Molecular breeding. - : Springer Science and Business Media LLC. - 1380-3743 .- 1572-9788. ; 36:7
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Tidskriftsartikel (refereegranskat)abstract
- Sabina chinensis has broad distribution in China and is widely used in the reforestation and as an urban tree. The species is frost resistant and grows well on contaminated soils and is becoming valuable for soil remediation and protection against air pollution. Breeding programs aimed at exploiting the species' unique properties were handicapped by the lack of basic genetic information. Here, we established a transcriptomic profiling study from five different tissues using RNA-Seq to gain insight on the functional genes and the development of molecular markers for breeding and conservation purposes. In total 90,382,108 high-quality sequence reads (similar to 9.0 bp) were obtained, and 116,814 unigenes (>= 200 nt) were assembled. Of which, 45,026 and 15,589 unigenes were mapped to the Nr and KOG databases, 31,288 (26.78 %) and 17,596 (15.06 %) were annotated to GO and KEGG database, respectively. Additionally, 28,843 (24.68 %) and 43,033 (36.84 %) S. chinensis unigenes were aligned to the Pinus taeda draft genome and PLAZA2.5 database, respectively. A total of 4570 simple sequence repeat (SSR) motifs were identified in the unigenes. Furthermore, we obtained 6 (12.5 %) polymorphic and 21 (43.75 %) monomorphic loci in the verification of 48 randomly selected SSR loci. This study represents the first transcriptome data of S. chinensis and confirms that the transcriptome assembly data of S. chinensis are a useful resource for EST-SSR loci development. The substantial number of transcripts obtained will aid our understanding of the species adaptation mechanisms and provide valuable genomic information for conservation and breeding applications.
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| 10. |
- Huyghe, Jeroen R., et al.
(författare)
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Discovery of common and rare genetic risk variants for colorectal cancer
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:1, s. 76-
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Tidskriftsartikel (refereegranskat)abstract
- To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
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