Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Dev Cell ; 57(15): 1817-1832.e5, 2022 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-35835116

RESUMO

Stochastic mechanisms diversify cell fates during development. How cells randomly choose between two or more fates remains poorly understood. In the Drosophila eye, the random mosaic of two R7 photoreceptor subtypes is determined by expression of the transcription factor Spineless (Ss). We investigated how cis-regulatory elements and trans factors regulate nascent transcriptional activity and chromatin compaction at the ss gene locus during R7 development. The ss locus is in a compact state in undifferentiated cells. An early enhancer drives transcription in all R7 precursors, and the locus opens. In differentiating cells, transcription ceases and the ss locus stochastically remains open or compacts. In SsON R7s, ss is open and competent for activation by a late enhancer, whereas in SsOFF R7s, ss is compact, and repression prevents expression. Our results suggest that a temporally dynamic antagonism, in which transcription drives large-scale decompaction and then compaction represses transcription, controls stochastic fate specification.


Assuntos
Proteínas de Drosophila , Células Fotorreceptoras de Invertebrados , Animais , Cromatina/genética , Cromatina/metabolismo , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Células Fotorreceptoras de Invertebrados/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
2.
Elife ; 112022 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-35244027

RESUMO

Amino-terminal fragments from proteolytically cleaved gasdermins (GSDMs) form plasma membrane pores that enable the secretion of interleukin-1ß (IL-1ß) and IL-18. Excessive GSDM-mediated pore formation can compromise the integrity of the plasma membrane thereby causing the lytic inflammatory cell death, pyroptosis. We found that GSDMD and GSDME were the only GSDMs that were readily expressed in bone microenvironment. Therefore, we tested the hypothesis that GSDMD and GSDME are implicated in fracture healing owing to their role in the obligatory inflammatory response following injury. We found that bone callus volume and biomechanical properties of injured bones were significantly reduced in mice lacking either GSDM compared with wild-type (WT) mice, indicating that fracture healing was compromised in mutant mice. However, compound loss of GSDMD and GSDME did not exacerbate the outcomes, suggesting shared actions of both GSDMs in fracture healing. Mechanistically, bone injury induced IL-1ß and IL-18 secretion in vivo, a response that was mimicked in vitro by bone debris and ATP, which function as inflammatory danger signals. Importantly, the secretion of these cytokines was attenuated in conditions of GSDMD deficiency. Finally, deletion of IL-1 receptor reproduced the phenotype of Gsdmd or Gsdme deficient mice, implying that inflammatory responses induced by the GSDM-IL-1 axis promote bone healing after fracture.


Assuntos
Inflamassomos , Interleucina-18 , Animais , Consolidação da Fratura , Inflamassomos/metabolismo , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Camundongos , Proteínas de Ligação a Fosfato/genética , Piroptose/genética
3.
Med Oncol ; 31(11): 272, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25301111

RESUMO

Esophageal cancer is the sixth leading cause of cancer-associated death worldwide. In addition to environmental risk factors, genetic factors might play an important role in esophageal cancer carcinogenesis. We conducted a hospital-based case-control study to evaluate the association between functional single nucleotide polymorphisms (SNPs) in uracil-DNA glycosylase (UNG) and the development of esophageal cancer. A total of 380 esophageal squamous cell carcinoma (ESCC) cases and 380 controls were recruited for this study. The UNG rs3219218 A/G and UNG rs246079 G/A genotypes were determined using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). When the UNG rs246079 GG homozygote genotype was used as the reference group, the GA genotype was associated with a significantly decreased risk for ESCC (GA vs. GG: adjusted OR 0.67, 95 % CI 0.49-0.91, P = 0.011); the AA genotype was not associated with the risk of ESCC. In stratification analyses, a significantly decreased risk of ESCC associated with the UNG rs246079 G/A polymorphism was evident among women, younger patients and never-smokers and never-drinkers. The UNG rs3219218 A/G polymorphism was not associated with the risk for ESCC. These findings indicated that UNG rs246079 G/A might contribute to a decreased risk of ESCC in specific populations. Because of the limited sample size, further studies including a larger and more diverse population, as well as tissue-specific biological characterization, are required to confirm the current findings.


Assuntos
Povo Asiático/genética , Neoplasias Esofágicas/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Vigilância da População , Uracila-DNA Glicosidase/genética , Idoso , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/epidemiologia , Feminino , Predisposição Genética para Doença/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...