A mutation in an ontogene acts as a conditional dominant lethal: it is lethal in a certain genotype but not lethal in another. In total, 30 mutations of this type residing in the Drosophila melanogaster X chromosome h...A mutation in an ontogene acts as a conditional dominant lethal: it is lethal in a certain genotype but not lethal in another. In total, 30 mutations of this type residing in the Drosophila melanogaster X chromosome have been assayed for their ability to cause meiotic nondisjunction. The level of X nondisjunction in the females heterozygous for the mutation in ontogene appears to be very high. The share of matroclinous daughters reaches 24.7% of the overall offspring and of patroclinous males, 24.9%. Neither inversion in the opposite X chromosome nor additional Y chromosome has any effect on the X nondisjunction. The balance of the XX and X0 egg cells is disturbed: exceptional daughters are prevalent in the offspring of the females with a normal opposite X chromosome and exceptional sons, in the offspring of the females with an inverted X chromosome. In addition, 12% of the matroclinous daughters of the females with a normal opposite X chromosome are homozygous for the marker of one of the maternal X chromosomes (“equational” nondisjunction). A “fading” parental effect of the mutation in ontogene on the X chromosome nondisjunction is also observed. Under experimental conditions, the mutant ontogenes reside in meiotic densely compacted X chromosomes. We infer that the ontogenes are DNA regions with controlled compaction. It is postulated that the genetic activity of ontogenes is determined by this compaction and has a biophysical (electromagnetic) nature. In a meiotic cell, ontogenes induce physical fields providing the operation of meiotic proteins. The structure of these fields is distorted in the mutants for ontogenes, thereby decreasing the efficiency of proteins and, as a consequence, causing meiotic defects.展开更多
Background:Considering the increase in the proportion of lung adenocarcinoma(LUAD)cases among all lung cancers and its considerable contribution to cancer-related deaths worldwide,we sought to identify novel oncogenes...Background:Considering the increase in the proportion of lung adenocarcinoma(LUAD)cases among all lung cancers and its considerable contribution to cancer-related deaths worldwide,we sought to identify novel oncogenes to provide potential targets and facilitate a better understanding of the malignant progression of LUAD.Methods:The results from the screening of transcriptome and survival analyses according to the integrated Gene Expression Omnibus(GEO)datasets and The Cancer Genome Atlas(TCGA)data were combined,and a promising risk biomarker called meiotic nuclear divisions 1(MND1)was selectively acquired.Cell viability assays and subcutaneous xenograftmodelswere used to validate the oncogenic role ofMND1 in LUADcell proliferation and tumor growth.Aseries of assays,including mass spectrometry,co-immunoprecipitation(Co-IP),and chromatin immunoprecipitation(ChIP),were performed to explore the underlying mechanism.Results:MND1 up-regulation was identified to be an independent risk factor for overall survival in LUAD patients evaluated by both tissue microarray staining and third party data analysis.In vivo and in vitro assays showed that MND1 promoted LUAD cell proliferation by regulating cell cycle.The results of the Co-IP,ChIP and dual-luciferase reporter assays validated that MND1 competitively bound to tumor suppressor Kruppel-like factor 6(KLF6),and thereby protecting E2F transcription factor 1(E2F1)from KLF6-induced transcriptional repression.Luciferase reporter and ChIP assays found that E2F1 activated MND1 transcription by binding to its promoter in a feedback manner.Conclusions:MND1,KLF6,and E2F1 form a positive feedback loop to regulate cell cycle and confer DDP resistance in LUAD.MND1 is crucial for malignant progression and may be a potential therapeutic target in LUAD patients.展开更多
文摘A mutation in an ontogene acts as a conditional dominant lethal: it is lethal in a certain genotype but not lethal in another. In total, 30 mutations of this type residing in the Drosophila melanogaster X chromosome have been assayed for their ability to cause meiotic nondisjunction. The level of X nondisjunction in the females heterozygous for the mutation in ontogene appears to be very high. The share of matroclinous daughters reaches 24.7% of the overall offspring and of patroclinous males, 24.9%. Neither inversion in the opposite X chromosome nor additional Y chromosome has any effect on the X nondisjunction. The balance of the XX and X0 egg cells is disturbed: exceptional daughters are prevalent in the offspring of the females with a normal opposite X chromosome and exceptional sons, in the offspring of the females with an inverted X chromosome. In addition, 12% of the matroclinous daughters of the females with a normal opposite X chromosome are homozygous for the marker of one of the maternal X chromosomes (“equational” nondisjunction). A “fading” parental effect of the mutation in ontogene on the X chromosome nondisjunction is also observed. Under experimental conditions, the mutant ontogenes reside in meiotic densely compacted X chromosomes. We infer that the ontogenes are DNA regions with controlled compaction. It is postulated that the genetic activity of ontogenes is determined by this compaction and has a biophysical (electromagnetic) nature. In a meiotic cell, ontogenes induce physical fields providing the operation of meiotic proteins. The structure of these fields is distorted in the mutants for ontogenes, thereby decreasing the efficiency of proteins and, as a consequence, causing meiotic defects.
基金Project of Jiangsu Provincial Medical Talent,Grant/Award Number:ZDRCA2016033China Postdoctoral Science Foundation,Grant/Award Number:2018M640465+2 种基金National Natural Science Foundation of China,Grant/Award Numbers:81672295,81702265,81802277,81872378Research Program of Jiangsu Health Department,Grant/Award Number:LGY2016025Social Development Project of Jiangsu Province,Grant/Award Number:BE2019758。
文摘Background:Considering the increase in the proportion of lung adenocarcinoma(LUAD)cases among all lung cancers and its considerable contribution to cancer-related deaths worldwide,we sought to identify novel oncogenes to provide potential targets and facilitate a better understanding of the malignant progression of LUAD.Methods:The results from the screening of transcriptome and survival analyses according to the integrated Gene Expression Omnibus(GEO)datasets and The Cancer Genome Atlas(TCGA)data were combined,and a promising risk biomarker called meiotic nuclear divisions 1(MND1)was selectively acquired.Cell viability assays and subcutaneous xenograftmodelswere used to validate the oncogenic role ofMND1 in LUADcell proliferation and tumor growth.Aseries of assays,including mass spectrometry,co-immunoprecipitation(Co-IP),and chromatin immunoprecipitation(ChIP),were performed to explore the underlying mechanism.Results:MND1 up-regulation was identified to be an independent risk factor for overall survival in LUAD patients evaluated by both tissue microarray staining and third party data analysis.In vivo and in vitro assays showed that MND1 promoted LUAD cell proliferation by regulating cell cycle.The results of the Co-IP,ChIP and dual-luciferase reporter assays validated that MND1 competitively bound to tumor suppressor Kruppel-like factor 6(KLF6),and thereby protecting E2F transcription factor 1(E2F1)from KLF6-induced transcriptional repression.Luciferase reporter and ChIP assays found that E2F1 activated MND1 transcription by binding to its promoter in a feedback manner.Conclusions:MND1,KLF6,and E2F1 form a positive feedback loop to regulate cell cycle and confer DDP resistance in LUAD.MND1 is crucial for malignant progression and may be a potential therapeutic target in LUAD patients.
