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

Base de dados
Ano de publicação
Tipo de documento
Intervalo de ano de publicação
1.
J Biol Chem ; 300(8): 107590, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39032649

RESUMO

The human tumor suppressor p16INK4a is a small monomeric protein that can form amyloid structures. Formation of p16INK4a amyloid fibrils is induced by oxidation which creates an intermolecular disulfide bond. The conversion into amyloid is associated with a change from an all α-helical structure into ß-sheet fibrils. Currently, structural insights into p16INK4a amyloid fibrils are lacking. Here, we investigate the amyloid-forming regions of this tumor suppressor using isotope-labeling limited-digestion mass spectrometry analysis. We discover two key regions that likely form the structured core of the amyloid. Further investigations using thioflavin-T fluorescence assays, electron microscopy, and solution nuclear magnetic resonance spectroscopy of shorter peptide regions confirm the self-assembly of the identified sequences that include methionine and leucine repeat regions. This work describes a simple approach for studying protein motifs involved in the conversion of monomeric species into aggregated fibril structures. It provides insight into the polypeptide sequence underlying the core structure of amyloid p16INK4a formed after a unique oxidation-driven structural transition.


Assuntos
Amiloide , Inibidor p16 de Quinase Dependente de Ciclina , Proteólise , Humanos , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/química , Inibidor p16 de Quinase Dependente de Ciclina/genética , Amiloide/química , Amiloide/metabolismo , Peptídeos/química , Peptídeos/metabolismo , Sequência de Aminoácidos , Oxirredução , Espectrometria de Massas/métodos
2.
J Cyst Fibros ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38658253

RESUMO

There is an urgent need to develop sensitive, non-invasive biomarkers that can track airway inflammatory activity for patients with cystic fibrosis (CF). Urinary glutathione sulfonamide (GSA) levels correlate well with GSA levels in BAL samples and other markers of neutrophilic inflammation, suggesting that this biomarker may be suitable for tracking disease activity in this population. We recruited 102 children (median 11.5 years-old) and 64 adults (median 32.5 years-old) who were admitted to hospital for management of an acute pulmonary exacerbation and/or eradication of infectious agents such as Pseudomonas aeruginosa or Staphylococcus aureus. Our aim was to explore how urinary GSA levels changed across admission timepoints. Urine samples were collected at admission and discharge, and GSA measured by liquid chromatography with mass spectrometry. Paired admission-discharge results were compared using Wilcoxon signed-rank test. Paired admission-discharge samples were available for 53 children and 60 adults. A statistically significant difference was observed between admission-discharge for children and adults. Spearman's correlation analysis identified a correlation between urinary GSA levels and sex and S. aureus infection for children only. Our preliminary findings suggest that urinary GSA is responsive to the resolution of an acute pulmonary exacerbation and therefore warrants further studies in this population.

3.
Cancer Epidemiol Biomarkers Prev ; 20(10): 2115-9, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21803842

RESUMO

Although it is tacitly recognized that a good coordinating center (CC) is essential to the success of any multisite collaborative project, very little study has been done on what makes a CC successful, why some CCs fail, or how to build a CC that meets the needs of a given project. Moreover, very little published guidance is available, as few CCs outside the clinical trial realm write about their work. The Asia Cohort Consortium (ACC) is a collaborative cancer epidemiology research project that has made strong scientific and organizational progress over the past 3 years by focusing its CC on the following activities: collaboration development; operations management; statistical and data management; and communications infrastructure and tool development. Our hope is that, by sharing our experience building the ACC CC, we can begin a conversation about what it means to run a CC for multi-institutional collaboration in cancer epidemiology, help other collaborative projects solve some of the issues associated with collaborative research, and learn from others.


Assuntos
Pesquisa Biomédica/organização & administração , Pesquisa Biomédica/tendências , Neoplasias/epidemiologia , Neoplasias/prevenção & controle , Ásia/epidemiologia , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA