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  • Articles  (66)
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  • 1
    Publication Date: 2014-07-18
    Description: The surface of the cornea consists of a unique type of non-keratinized epithelial cells arranged in an orderly fashion, and this is essential for vision by maintaining transparency for light transmission. Cornea epithelial cells (CECs) undergo continuous renewal from limbal stem or progenitor cells (LSCs), and deficiency in LSCs or corneal epithelium--which turns cornea into a non-transparent, keratinized skin-like epithelium--causes corneal surface disease that leads to blindness in millions of people worldwide. How LSCs are maintained and differentiated into corneal epithelium in healthy individuals and which key molecular events are defective in patients have been largely unknown. Here we report establishment of an in vitro feeder-cell-free LSC expansion and three-dimensional corneal differentiation protocol in which we found that the transcription factors p63 (tumour protein 63) and PAX6 (paired box protein PAX6) act together to specify LSCs, and WNT7A controls corneal epithelium differentiation through PAX6. Loss of WNT7A or PAX6 induces LSCs into skin-like epithelium, a critical defect tightly linked to common human corneal diseases. Notably, transduction of PAX6 in skin epithelial stem cells is sufficient to convert them to LSC-like cells, and upon transplantation onto eyes in a rabbit corneal injury model, these reprogrammed cells are able to replenish CECs and repair damaged corneal surface. These findings suggest a central role of the WNT7A-PAX6 axis in corneal epithelial cell fate determination, and point to a new strategy for treating corneal surface diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4610745/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4610745/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ouyang, Hong -- Xue, Yuanchao -- Lin, Ying -- Zhang, Xiaohui -- Xi, Lei -- Patel, Sherrina -- Cai, Huimin -- Luo, Jing -- Zhang, Meixia -- Zhang, Ming -- Yang, Yang -- Li, Gen -- Li, Hairi -- Jiang, Wei -- Yeh, Emily -- Lin, Jonathan -- Pei, Michelle -- Zhu, Jin -- Cao, Guiqun -- Zhang, Liangfang -- Yu, Benjamin -- Chen, Shaochen -- Fu, Xiang-Dong -- Liu, Yizhi -- Zhang, Kang -- GM049369/GM/NIGMS NIH HHS/ -- R01 EY020846/EY/NEI NIH HHS/ -- R01 EY021374/EY/NEI NIH HHS/ -- England -- Nature. 2014 Jul 17;511(7509):358-61. doi: 10.1038/nature13465. Epub 2014 Jul 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [2] Department of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA. ; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California 92093, USA. ; 1] Department of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing 100730, China (X.Z.); Department of Ophthalmology, Shengjing Hospital of China Medical University, Shenyang 110004, China (Y.Y.). ; Department of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA. ; 1] Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, China [2] Guangzhou KangRui Biological Pharmaceutical Technology Company Ltd., Guangzhou 510005, China. ; Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, China. ; 1] Department of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Department of Nanoengineering, University of California San Diego, La Jolla, California 92093, USA. ; 1] Department of Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Institute for Genomic Medicine, University of California San Diego, La Jolla, California 92093, USA. ; 1] Department of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California 92093, USA [3] Institute for Genomic Medicine, University of California San Diego, La Jolla, California 92093, USA. ; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China. ; 1] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [2] Department of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [3] Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, China [4] Institute for Genomic Medicine, University of California San Diego, La Jolla, California 92093, USA [5] Veterans Administration Healthcare System, San Diego, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25030175" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; Cell Lineage ; Corneal Diseases/*metabolism/*pathology ; Disease Models, Animal ; Epithelium, Corneal/*cytology/*metabolism/pathology ; Eye Proteins/genetics/*metabolism ; Homeodomain Proteins/genetics/*metabolism ; *Homeostasis ; Humans ; Limbus Corneae/cytology/metabolism ; Male ; Paired Box Transcription Factors/genetics/*metabolism ; Rabbits ; Repressor Proteins/genetics/*metabolism ; Signal Transduction ; Skin/cytology/metabolism/pathology ; Stem Cell Transplantation ; Stem Cells/cytology/metabolism ; Transcription Factors/metabolism ; Tumor Suppressor Proteins/metabolism ; Wnt Proteins/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2016-03-10
    Description: The repair and regeneration of tissues using endogenous stem cells represents an ultimate goal in regenerative medicine. To our knowledge, human lens regeneration has not yet been demonstrated. Currently, the only treatment for cataracts, the leading cause of blindness worldwide, is to extract the cataractous lens and implant an artificial intraocular lens. However, this procedure poses notable risks of complications. Here we isolate lens epithelial stem/progenitor cells (LECs) in mammals and show that Pax6 and Bmi1 are required for LEC renewal. We design a surgical method of cataract removal that preserves endogenous LECs and achieves functional lens regeneration in rabbits and macaques, as well as in human infants with cataracts. Our method differs conceptually from current practice, as it preserves endogenous LECs and their natural environment maximally, and regenerates lenses with visual function. Our approach demonstrates a novel treatment strategy for cataracts and provides a new paradigm for tissue regeneration using endogenous stem cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lin, Haotian -- Ouyang, Hong -- Zhu, Jie -- Huang, Shan -- Liu, Zhenzhen -- Chen, Shuyi -- Cao, Guiqun -- Li, Gen -- Signer, Robert A J -- Xu, Yanxin -- Chung, Christopher -- Zhang, Ying -- Lin, Danni -- Patel, Sherrina -- Wu, Frances -- Cai, Huimin -- Hou, Jiayi -- Wen, Cindy -- Jafari, Maryam -- Liu, Xialin -- Luo, Lixia -- Zhu, Jin -- Qiu, Austin -- Hou, Rui -- Chen, Baoxin -- Chen, Jiangna -- Granet, David -- Heichel, Christopher -- Shang, Fu -- Li, Xuri -- Krawczyk, Michal -- Skowronska-Krawczyk, Dorota -- Wang, Yujuan -- Shi, William -- Chen, Daniel -- Zhong, Zheng -- Zhong, Sheng -- Zhang, Liangfang -- Chen, Shaochen -- Morrison, Sean J -- Maas, Richard L -- Zhang, Kang -- Liu, Yizhi -- R37 AG024945/AG/NIA NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2016 Mar 17;531(7594):323-8. doi: 10.1038/nature17181. Epub 2016 Mar 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China. ; Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California, San Diego, La Jolla, California 92093, USA. ; Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, China. ; Guangzhou KangRui Biological Pharmaceutical Technology Company, Guangzhou 510005, China. ; Howard Hughes Medical Institute, Children's Research Institute, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. ; Department of Ophthalmology, West China Hospital, Sichuan University, Sichuan 610041, China. ; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. ; Clinical and Translational Research Institute, University of California, San Diego, La Jolla, California 92093, USA. ; Veterans Administration Healthcare System, San Diego, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26958831" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cataract/congenital/pathology/physiopathology/*therapy ; Cataract Extraction ; Epithelial Cells/cytology/metabolism ; Eye Proteins/metabolism ; Homeodomain Proteins/metabolism ; Homeostasis ; Humans ; Lens, Crystalline/*cytology/*physiology ; Macaca ; Paired Box Transcription Factors/metabolism ; Polycomb Repressive Complex 1/metabolism ; Proto-Oncogene Proteins/metabolism ; *Recovery of Function ; Regeneration/*physiology ; Repressor Proteins/metabolism ; Stem Cells/*cytology/metabolism ; Vision, Ocular/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2015-08-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhao, Ling -- Chen, Xiang-Jun -- Zhu, Jie -- Xi, Yi-Bo -- Yang, Xu -- Hu, Li-Dan -- Ouyang, Hong -- Patel, Sherrina H -- Jin, Xin -- Lin, Danni -- Wu, Frances -- Flagg, Ken -- Cai, Huimin -- Li, Gen -- Cao, Guiqun -- Lin, Ying -- Chen, Daniel -- Wen, Cindy -- Chung, Christopher -- Wang, Yandong -- Qiu, Austin -- Yeh, Emily -- Wang, Wenqiu -- Hu, Xun -- Grob, Seanna -- Abagyan, Ruben -- Su, Zhiguang -- Tjondro, Harry Christianto -- Zhao, Xi-Juan -- Luo, Hongrong -- Hou, Rui -- Perry, J Jefferson P -- Gao, Weiwei -- Kozak, Igor -- Granet, David -- Li, Yingrui -- Sun, Xiaodong -- Wang, Jun -- Zhang, Liangfang -- Liu, Yizhi -- Yan, Yong-Bin -- Zhang, Kang -- England -- Nature. 2015 Oct 22;526(7574):595. doi: 10.1038/nature15253. Epub 2015 Aug 26.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26308894" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2015-07-23
    Description: The human lens is comprised largely of crystallin proteins assembled into a highly ordered, interactive macro-structure essential for lens transparency and refractive index. Any disruption of intra- or inter-protein interactions will alter this delicate structure, exposing hydrophobic surfaces, with consequent protein aggregation and cataract formation. Cataracts are the most common cause of blindness worldwide, affecting tens of millions of people, and currently the only treatment is surgical removal of cataractous lenses. The precise mechanisms by which lens proteins both prevent aggregation and maintain lens transparency are largely unknown. Lanosterol is an amphipathic molecule enriched in the lens. It is synthesized by lanosterol synthase (LSS) in a key cyclization reaction of a cholesterol synthesis pathway. Here we identify two distinct homozygous LSS missense mutations (W581R and G588S) in two families with extensive congenital cataracts. Both of these mutations affect highly conserved amino acid residues and impair key catalytic functions of LSS. Engineered expression of wild-type, but not mutant, LSS prevents intracellular protein aggregation of various cataract-causing mutant crystallins. Treatment by lanosterol, but not cholesterol, significantly decreased preformed protein aggregates both in vitro and in cell-transfection experiments. We further show that lanosterol treatment could reduce cataract severity and increase transparency in dissected rabbit cataractous lenses in vitro and cataract severity in vivo in dogs. Our study identifies lanosterol as a key molecule in the prevention of lens protein aggregation and points to a novel strategy for cataract prevention and treatment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhao, Ling -- Chen, Xiang-Jun -- Zhu, Jie -- Xi, Yi-Bo -- Yang, Xu -- Hu, Li-Dan -- Ouyang, Hong -- Patel, Sherrina H -- Jin, Xin -- Lin, Danni -- Wu, Frances -- Flagg, Ken -- Cai, Huimin -- Li, Gen -- Cao, Guiqun -- Lin, Ying -- Chen, Daniel -- Wen, Cindy -- Chung, Christopher -- Wang, Yandong -- Qiu, Austin -- Yeh, Emily -- Wang, Wenqiu -- Hu, Xun -- Grob, Seanna -- Abagyan, Ruben -- Su, Zhiguang -- Tjondro, Harry Christianto -- Zhao, Xi-Juan -- Luo, Hongrong -- Hou, Rui -- Perry, J Jefferson P -- Gao, Weiwei -- Kozak, Igor -- Granet, David -- Li, Yingrui -- Sun, Xiaodong -- Wang, Jun -- Zhang, Liangfang -- Liu, Yizhi -- Yan, Yong-Bin -- Zhang, Kang -- England -- Nature. 2015 Jul 30;523(7562):607-11. doi: 10.1038/nature14650. Epub 2015 Jul 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China [2] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [3] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA. ; State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China. ; 1] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. ; BGI-Shenzhen, Shenzhen 518083, China. ; 1] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [2] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA. ; Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA. ; 1] Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China [2] Guangzhou KangRui Biological Pharmaceutical Technology Company, Guangzhou 510005, China. ; Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. ; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China. ; 1] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] CapitalBio Genomics Co., Ltd., Dongguan 523808, China. ; 1] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Department of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai 20080, China. ; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093, USA. ; Guangzhou KangRui Biological Pharmaceutical Technology Company, Guangzhou 510005, China. ; Department of Biochemistry, University of California Riverside, Riverside, California 92521, USA. ; 1] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, USA. ; King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia. ; Department of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai 20080, China. ; Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. ; 1] Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China [2] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [3] Department of Ophthalmology and Biomaterials and Tissue Engineering Center, Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [4] Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, USA [5] Veterans Administration Healthcare System, San Diego, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26200341" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Amino Acid Sequence ; Amyloid/chemistry/drug effects/metabolism/ultrastructure ; Animals ; Base Sequence ; Cataract/congenital/*drug therapy/genetics/*metabolism/pathology ; Cell Line ; Child ; Crystallins/chemistry/genetics/metabolism/ultrastructure ; Dogs ; Female ; Humans ; Lanosterol/administration & dosage/*pharmacology/*therapeutic use ; Lens, Crystalline/drug effects/metabolism/pathology ; Male ; Models, Molecular ; Molecular Sequence Data ; Mutant Proteins/chemistry/genetics/metabolism/ultrastructure ; Pedigree ; Protein Aggregates/*drug effects ; Protein Aggregation, Pathological/*drug therapy/pathology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2018-08-24
    Description: The interaction of N two-level atoms with a single-mode light field is an extensively studied many-body problem in quantum optics, first analyzed by Dicke in the context of superradiance. A characteristic of such systems is the cooperative enhancement of the coupling strength by a factor of N . In this study, we extended this cooperatively enhanced coupling to a solid-state system, demonstrating that it also occurs in a magnetic solid in the form of matter-matter interaction. Specifically, the exchange interaction of N paramagnetic erbium(III) (Er 3+ ) spins with an iron(III) (Fe 3+ ) magnon field in erbium orthoferrite (ErFeO 3 ) exhibits a vacuum Rabi splitting whose magnitude is proportional to N . Our results provide a route for understanding, controlling, and predicting novel phases of condensed matter using concepts and tools available in quantum optics.
    Keywords: Physics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
  • 7
    Publication Date: 2018-04-17
    Description: SPAG5 promotes proliferation and suppresses apoptosis in bladder urothelial carcinoma by upregulating Wnt3 via activating the AKT/mTOR pathway and predicts poorer survival SPAG5 promotes proliferation and suppresses apoptosis in bladder urothelial carcinoma by upregulating Wnt3 via activating the AKT/mTOR pathway and predicts poorer survival, Published online: 17 April 2018; doi:10.1038/s41388-018-0223-2 SPAG5 promotes proliferation and suppresses apoptosis in bladder urothelial carcinoma by upregulating Wnt3 via activating the AKT/mTOR pathway and predicts poorer survival
    Print ISSN: 0950-9232
    Topics: Medicine
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  • 8
    Publication Date: 2018-05-09
    Description: Objectives We aimed to characterise the microbial changes associated with histological stages of gastric tumourigenesis. Design We performed 16S rRNA gene analysis of gastric mucosal samples from 81 cases including superficial gastritis (SG), atrophic gastritis (AG), intestinal metaplasia (IM) and gastric cancer (GC) from Xi’an, China, to determine mucosal microbiome dysbiosis across stages of GC. We validated the results in mucosal samples of 126 cases from Inner Mongolia, China. Results We observed significant mucosa microbial dysbiosis in IM and GC subjects, with significant enrichment of 21 and depletion of 10 bacterial taxa in GC compared with SG (q〈0.05). Microbial network analysis showed increasing correlation strengths among them with disease progression (p〈0.001). Five GC-enriched bacterial taxa whose species identifications correspond to Peptostreptococcus stomatis , Streptococcus anginosus , Parvimonas micra , Slackia exigua and Dialister pneumosintes had significant centralities in the GC ecological network (p〈0.05) and classified GC from SG with an area under the receiver-operating curve (AUC) of 0.82. Moreover, stronger interactions among gastric microbes were observed in Helicobacter pylori -negative samples compared with H. pylori -positive samples in SG and IM. The fold changes of selected bacteria, and strengths of their interactions were successfully validated in the Inner Mongolian cohort, in which the five bacterial markers distinguished GC from SG with an AUC of 0.81. Conclusions In addition to microbial compositional changes, we identified differences in bacterial interactions across stages of gastric carcinogenesis. The significant enrichments and network centralities suggest potentially important roles of P. stomatis , D. pneumosintes , S. exigua , P. micra and S. anginosus in GC progression.
    Keywords: Open access, Editor's choice, Gut
    Print ISSN: 0017-5749
    Electronic ISSN: 1468-3288
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 9
    Publication Date: 2018-07-03
    Description: Developing rice varieties adapted to alternate wetting and drying water management is crucial for the sustainability of irrigated rice cropping systems. Here we report the first study exploring the feasibility of breeding rice for adaptation to alternate wetting and drying using genomic prediction methods that account for genotype by environment interactions. Two breeding populations (a reference panel of 284 accessions and a progeny population of 97 advanced lines) were evaluated under alternate wetting and drying and continuous flooding management systems. The predictive ability of genomic prediction for response variables (index of relative performance and the slope of the joint regression) and for multi-environment genomic prediction models were compared. For the three traits considered (days to flowering, panicle weight and nitrogen-balance index), significant genotype by environment interactions were observed in both populations. In cross validation, predictive ability for the index was on average lower (0.31) than that of the slope of the joint regression (0.64) whatever the trait considered. Similar results were found for progeny validation. Both cross-validation and progeny validation experiments showed that the performance of multi-environment models predicting unobserved phenotypes of untested entrees was similar to the performance of single environment models with differences in predictive ability ranging from -6–4% depending on the trait and on the statistical model concerned. The predictive ability of multi-environment models predicting unobserved phenotypes of entrees evaluated under both water management systems outperformed single environment models by an average of 30%. Practical implications for breeding rice for adaptation to alternate wetting and drying system are discussed.
    Electronic ISSN: 2160-1836
    Topics: Biology
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  • 10
    Publication Date: 2018-03-09
    Description: Polymorphisms in C1orf106 are associated with increased risk of inflammatory bowel disease (IBD). However, the function of C1orf106 and the consequences of disease-associated polymorphisms are unknown. Here we demonstrate that C1orf106 regulates adherens junction stability by regulating the degradation of cytohesin-1, a guanine nucleotide exchange factor that controls activation of ARF6. By limiting cytohesin-1–dependent ARF6 activation, C1orf106 stabilizes adherens junctions. Consistent with this model, C1orf106 –/– mice exhibit defects in the intestinal epithelial cell barrier, a phenotype observed in IBD patients that confers increased susceptibility to intestinal pathogens. Furthermore, the IBD risk variant increases C1orf106 ubiquitination and turnover with consequent functional impairments. These findings delineate a mechanism by which a genetic polymorphism fine-tunes intestinal epithelial barrier integrity and elucidate a fundamental mechanism of cellular junctional control.
    Keywords: Cell Biology, Medicine, Diseases
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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