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1.
Mol Biol Cell ; 29(15): 1786-1797, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29897835

RESUMO

FUS (fused in sarcoma) is an abundant, predominantly nuclear protein involved in RNA processing. Under various conditions, FUS functionally associates with RNA and other macromolecules to form distinct, reversible phase-separated liquid structures. Persistence of the phase-separated state and increased cytoplasmic localization are both hypothesized to predispose FUS to irreversible aggregation, which is a pathological hallmark of subtypes of amyotrophic lateral sclerosis and frontotemporal dementia. We previously showed that phosphorylation of FUS's prionlike domain suppressed phase separation and toxic aggregation, proportionally to the number of added phosphates. However, phosphorylation of FUS's prionlike domain was previously reported to promote its cytoplasmic localization, potentially favoring pathological behavior. Here we used mass spectrometry and human cell models to further identify phosphorylation sites within FUS's prionlike domain, specifically following DNA-damaging stress. In total, 28 putative sites have been identified, about half of which are DNA-dependent protein kinase (DNA-PK) consensus sites. Custom antibodies were developed to confirm the phosphorylation of two of these sites (Ser-26 and Ser-30). Both sites were usually phosphorylated in a subpopulation of cellular FUS following a variety of DNA-damaging stresses but not necessarily equally or simultaneously. Importantly, we found DNA-PK-dependent multiphosphorylation of FUS's prionlike domain does not cause cytoplasmic localization.


Assuntos
Núcleo Celular/metabolismo , Dano ao DNA , Príons/química , Proteína FUS de Ligação a RNA/química , Proteína FUS de Ligação a RNA/metabolismo , Sequência de Aminoácidos , Aminoglicosídeos/farmacologia , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Proteína Quinase Ativada por DNA/metabolismo , Humanos , Fosforilação/efeitos dos fármacos , Domínios Proteicos , Transporte Proteico/efeitos dos fármacos
2.
J Neurointerv Surg ; 9(11): 1118-1124, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29030464

RESUMO

BACKGROUND: The severity of aneurysmal subarachnoid hemorrhage (SAH) is often assessed by the clinical state of the patient on presentation, but radiological evaluation of the extent of hemorrhage has rarely been examined in the literature. Several CT scan based grading systems exist yet only a few studies have investigated interobserver agreement. We evaluated five radiological grading systems and assessed their clinical value for early prognostication. METHODOLOGY: This was a retrospective study of patients diagnosed with aneurysmal SAH with a CT scan performed within 72 hours of symptom onset. Four independent observers, blinded to patient outcome, evaluated each scan using the five grading systems. A separate assessor determined 6 month outcome from clinical records. The primary outcome was interobserver agreement for each grading system using the Fleiss κ statistic. The secondary endpoint was the 6 month modified Rankin Scale score, with poor outcome defined as a score of 4-6. RESULTS: 165 patients with a mean age of 59 years were assessed. Interobserver agreement for the Fisher, modified Fisher, Claassen, Barrow Neurological Institute, and Hijdra grading systems were as follows: k=0.53 (moderate), k=0.42 (moderate), k=0.38 (mild), k=0.20 (poor), and k=0.66 (good), respectively. The only independent clinical risk factor for poor outcome was a World Federation of Neurological Surgeons (WFNS) grade of 4 or 5 (adjusted OR 6.55; p<0.05). After adjusting for confounders, Fisher grade 4 (adjusted OR 17.84), modified Fisher grade 4 (adjusted OR 5.65), and Hijdra grade 3 (adjusted OR 3.34) were associated with poor outcome. Receiver operator characteristic analysis revealed that the Hijdra grading system (area under the curve=0.76) was more predictive of outcome compared with the Fisher and modified Fisher systems. A Hijdra cut-off score of 22 was associated with poor outcome (adjusted OR 5.92). CONCLUSIONS: The Hijdra grading system had the best interobserver agreement and was a better independent early predictor for 6 month clinical outcome than the other systems. A Hijdra score ≥22 was associated with poor outcome.


Assuntos
Angiografia Cerebral/normas , Hemorragia Subaracnóidea/diagnóstico por imagem , Tomografia Computadorizada por Raios X/normas , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Método Simples-Cego , Hemorragia Subaracnóidea/cirurgia , Resultado do Tratamento
3.
Chemosphere ; 52(9): 1405-10, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12867170

RESUMO

As far as the impact of air pollutants on human health being concerned, ozone is one of the main pollutants in atmosphere. In particular, the ground level ozone is responsible for a variety of adverse effects on both human being and plant life. To protect the humankind from such adverse health effects, early information and precautions of high ozone level need to be supplied in times. In this study, statistical characteristics of ground level ozone is analyzed according to the field monitoring data in mixed residential, commercial and industrial areas, e.g., Tsuen Wan area in Hong Kong. The study deals with the characteristics of hourly and daily mean ozone levels under different climatic conditions such as temperature, solar radiation, wind speed, and other pollutant concentration levels. The study aims to investigate the importance of meteorological factors and their impact on relevant pollutant concentration levels from chemical aspect. Further, reasons causing the spatial and temporal variations of ozone levels are discussed. All these results will provide a physical basis for accurately predicting ozone concentration in extensive, future research.


Assuntos
Poluentes Atmosféricos/análise , Ozônio/análise , Cidades , Monitoramento Ambiental/métodos , Hong Kong , Humanos , Conceitos Meteorológicos , Oxidantes Fotoquímicos/análise , Saúde Pública/métodos , Estatística como Assunto
4.
Chemosphere ; 52(9): 1451-9, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12867175

RESUMO

With the ever-increasing urban population and economic activities, water usage and demand are continuously increasing. Hence, finding/re-creating adequate water supply and fully utilizing wastewater become important issues in sustainable urban development and environmental benign aspect. Considering Hong Kong's situation, e.g., lack of natural fresh water, domination of municipal wastewater, etc., developing wastewater reclamation and reuse system is of specific significance to exploit new water resource and save natural fresh water supplied from Mainland China. We propose and have carried out some preliminary studies on the potential of categorizing municipal wastewater, developing grey and storm water recycling system in public housing estate, investigating the feasibility and potential of using reclaimed grey water, etc. Since there is very limited experience in grey water recycling, such initial studies can help to understand and increase knowledge in utilizing grey water, to foresee the feasibility of developing new water resource, to estimate the cost-effectiveness of reclaiming grey water in metropolitan city.


Assuntos
Eliminação de Resíduos Líquidos , Purificação da Água/métodos , Abastecimento de Água , Lavanderia , Purificação da Água/economia , Purificação da Água/instrumentação
5.
Environ Int ; 29(5): 555-62, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12742398

RESUMO

Analysis and forecasting of air quality parameters are important topics of atmospheric and environmental research today due to the health impact caused by air pollution. As one of major pollutants, ozone, especially ground level ozone, is responsible for various adverse effects on both human being and foliage. Therefore, prediction of ambient ozone levels in certain environment, especially the ground ozone level in densely urban areas, is of great importance to urban air quality and city image. To date, though several ozone prediction models have been established, there is still a need for more accurate models to develop effective warning strategies. The development of such models is difficult because the meteorological variables and the photochemical reactions involved in ozone formation are very complex. The present work aims to develop an improved neural network model, which combines the adaptive radial basis function (ARBF) network with statistical characteristics of ozone in selected specific areas, and is used to predict the daily maximum ozone concentration level. The improved method is trained and testified by hourly time series data collected at three air pollutant-monitoring stations in Hong Kong during 1999 and 2000. The simulation results demonstrate the effectiveness and the reliability of the proposed method.


Assuntos
Poluentes Atmosféricos/análise , Modelos Teóricos , Redes Neurais de Computação , Oxidantes Fotoquímicos/análise , Ozônio/análise , Previsões , Hong Kong , Sensibilidade e Especificidade
6.
Environ Int ; 28(6): 503-12, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12503916

RESUMO

As far as the impact of air pollutants on human health being is concerned, ozone (O3) is one of the most pollutant sources, and, in particular, the ground level ozone is responsible for a variety of adverse effects on both human being and plant life. To protect the population from such adverse health effects, early information and precautions about the high ozone level need to be ascertained. In this study, statistical characteristics of ground level ozone is analyzed according to field monitoring data in mixed residential, commercial and industrial areas, e.g., Tsuen Wan area in Hong Kong. The study deals with the characteristics of hourly and daily mean ozone levels under different climatic conditions such as temperature, solar radiation (SR), wind speed (WS), and other pollutant concentration levels. The study aims to investigate the importance of meteorological factors and their impact on relevant pollutant concentration levels from a chemical aspect. Further, reasons for the spatial and temporal variation of ozone levels are discussed. All these results will provide a physical basis for accurately predicting ozone concentration in similar research.


Assuntos
Oxidantes Fotoquímicos/análise , Ozônio/análise , Monitoramento Ambiental , Hong Kong , Humanos , Conceitos Meteorológicos , Oxidantes Fotoquímicos/efeitos adversos , Ozônio/efeitos adversos , Saúde Pública , Medição de Risco , População Urbana
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