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1.
PLoS One ; 19(3): e0300781, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38512872

RESUMO

The allocation of assets across different markets is a crucial element of investment strategy. In this regard, stocks and bonds are two significant assets that form the backbone of multi-asset allocation. Among publicly offered funds (The publicly offered funds in China correspond to the mutual funds in the United States, with different names and details in terms of legal form and sales channels), the stock-bond hybrid fund gives investors a return while minimizing the risk through capital flow between the stock and bond markets. Our research on China's financial market data from 2006 to 2022 reveals a cross-asset momentum between the stock and bond markets. We find that the momentum in the stock market negatively influences the bond market's return, while the momentum in the bond market positively influences the stock market's return. Portfolios that exploit cross-asset momentum have excess returns that other asset pricing factors cannot explain. Our analysis reveals that hybrid funds play an intermediary role in the transmission mechanism of cross-asset momentum. We observe that the more flexible the asset allocation ratio of the fund, the more crucial the intermediary role played by the fund. Hence, encouraging the development of hybrid funds and relaxing restrictions on asset allocation ratios could improve liquidity and pricing efficiency. These findings have significant implications for investors seeking to optimize their asset allocation across different markets and for policymakers seeking to enhance the efficiency of China's financial market.


Assuntos
Administração Financeira , Estados Unidos , Investimentos em Saúde , Comércio , China , Custos e Análise de Custo
2.
bioRxiv ; 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38260321

RESUMO

Breast cancer progression and metastasis involve the action of multiple transcription factors in tumors and in the cells of the tumor microenvironment (TME) and understanding how these transcription factors are coordinated can guide novel therapeutic strategies. Myocardin related transcription factors A and B (MRTFA/B) are two related transcription factors that redundantly control cancer cell invasion and metastasis in mouse models of breast cancer, but their roles in human cancer are incompletely understood. Here, we used a combination of multiplexed immunofluorescence and bioinformatics analyses to show that MRTFA/B are concurrently activated in tumor cells, but they show distinct patterns of expression across different histological subtypes and in the TME. Importantly, MRTFA expression was elevated in metastatic tumors of African American patients, who disproportionately die from breast cancer. Interestingly, in contrast to publicly available mRNA expression data, MRTFA was similarly expressed across estrogen receptor (ER) positive and negative breast tumors, while MRTFB expression was highest in ER+ breast tumors. Furthermore, MRTFA was specifically expressed in the perivascular antigen presenting cells (APCs) and its expression correlated with the expression of the immune checkpoint protein V-set immunoregulatory receptor (VSIR). These results provide unique insights into how MRTFA and MRTFB can promote metastasis in human cancer, into the racial disparities of their expression patterns, and their function within the complex breast cancer TME.

3.
BMC Med ; 21(1): 227, 2023 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-37365601

RESUMO

BACKGROUND: Pneumonia is a common disease worldwide in preschool children. Despite its large population size, China has had no comprehensive study of the national prevalence, risk factors, and management of pneumonia among preschool children. We therefore investigated the prevalence of pneumonia among preschool children in Chinese seven representative cities, and explore the possible risk factors of pneumonia on children, with a view to calling the world's attention to childhood pneumonia to reduce the prevalence of childhood pneumonia. METHODS: Two group samples of 63,663 and 52,812 preschool children were recruited from 2011 and 2019 surveys, respectively. Which were derived from the cross-sectional China, Children, Homes, Health (CCHH) study using a multi-stage stratified sampling method. This survey was conducted in kindergartens in seven representative cities. Exclusion criteria were younger than 2 years old or older than 8 years old, non-permanent population, basic information such as gender, date of birth and breast feeding is incomplete. Pneumonia was determined on the basis of parents reported history of clearly diagnosed by the physician. All participants were assessed with a standard questionnaire. Risk factors for pneumonia, and association between pneumonia and other respiratory diseases were examined by multivariable-adjusted analyses done in all participants for whom data on the variables of interest were available. Disease management was evaluated by the parents' reported history of physician diagnosis, longitudinal comparison of risk factors in 2011 and 2019. RESULTS: In 2011 and 2019, 31,277 (16,152 boys and 15,125 girls) and 32,016 (16,621 boys and 15,395 girls) preschool children aged at 2-8 of permanent population completed the questionnaire, respectively, and were thus included in the final analysis. The findings showed that the age-adjusted prevalence of pneumonia in children was 32.7% in 2011 and 26.4% in 2019. In 2011, girls (odds ratio [OR] 0.91, 95%CI [confidence interval]0.87-0.96; p = 0.0002), rural (0.85, 0.73-0.99; p = 0.0387), duration of breastfeeding ≥ 6 months(0.83, 0.79-0.88; p < 0.0001), birth weight (g) ≥ 4000 (0.88, 0.80-0.97; p = 0.0125), frequency of putting bedding to sunshine (Often) (0.82, 0.71-0.94; p = 0.0049), cooking fuel type (electricity) (0.87, 0.80-0.94; p = 0.0005), indoor use air-conditioning (0.85, 0.80-0.90; p < 0.0001) were associated with a reduced risk of childhood pneumonia. Age (4-6) (1.11, 1.03-1.20; p = 0.0052), parental smoking (one) (1.12, 1.07-1.18; p < 0.0001), used antibiotics (2.71, 2.52-2.90; p < 0.0001), history of parental allergy (one and two) (1.21, 1.12-1.32; p < 0.0001 and 1.33, 1.04-1.69; p = 0.0203), indoor dampness (1.24, 1.15-1.33; p < 0.0001), home interior decoration (1.11, 1.04-1.19; p = 0.0013), Wall painting materials (Paint) (1.16, 1.04-1.29; p = 0.0084), flooring materials (Laminate / Composite wood) (1.08, 1.02-1.16; p = 0.0126), indoor heating mode(Central heating)(1.18, 1.07-1.30, p = 0.0090), asthma (2.38, 2.17-2.61; p < 0.0001), allergic rhinitis (1.36, 1.25-1.47; p < 0.0001), wheezing (1.64, 1.55-1.74; p < 0.0001) were associated with an elevated risk of childhood pneumonia; pneumonia was associated with an elevated risk of childhood asthma (2.53, 2.31-2.78; p < 0.0001), allergic rhinitis (1.41, 1.29-1.53; p < 0.0001) and wheezing (1.64, 1.55-1.74; p < 0.0001). In 2019, girls (0.92, 0.87-0.97; p = 0.0019), duration of breastfeeding ≥ 6 months (0.92, 0.87-0.97; p = 0.0031), used antibiotics (0.22, 0.21-0.24; p < 0.0001), cooking fuel type (Other) (0.40, 0.23-0.63; p = 0.0003), indoor use air-conditioning (0.89, 0.83-0.95; p = 0.0009) were associated with a reduced risk of childhood pneumonia. Urbanisation (Suburb) (1.10, 1.02-1.18; p = 0.0093), premature birth (1.29, 1.08-1.55; p = 0.0051), birth weight (g) < 2500 (1.17, 1.02-1.35; p = 0.0284), parental smoking (1.30, 1.23-1.38; p < 0.0001), history of parental asthma (One) (1.23, 1.03-1.46; p = 0.0202), history of parental allergy (one and two) (1.20, 1.13-1.27; p < 0.0001 and 1.22, 1.08-1.37; p = 0.0014), cooking fuel type (Coal) (1.58, 1.02-2.52; p = 0.0356), indoor dampness (1.16, 1.08-1.24; p < 0.0001), asthma (1.88, 1.64-2.15; p < 0.0001), allergic rhinitis (1.57, 1.45-1.69; p < 0.0001), wheezing (2.43, 2.20-2.68; p < 0.0001) were associated with an elevated risk of childhood pneumonia; pneumonia was associated with an elevated risk of childhood asthma (1.96, 1.72-2.25; p < 0.0001), allergic rhinitis (1.60, 1.48-1.73; p < 0.0001) and wheezing (2.49, 2.25-2.75; p < 0.0001). CONCLUSIONS: Pneumonia is prevalent among preschool children in China, and it affects other childhood respiratory diseases. Although the prevalence of pneumonia in Chinese children shows a decreasing trend in 2019 compared to 2011, a well-established management system is still needed to further reduce the prevalence of pneumonia and reduce the burden of disease in children.


Assuntos
Asma , Pneumonia , Rinite Alérgica , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Asma/epidemiologia , Peso ao Nascer , China/epidemiologia , Cidades , Estudos Transversais , População do Leste Asiático , Análise de Séries Temporais Interrompida , Pneumonia/epidemiologia , Prevalência , Sons Respiratórios/etiologia , Rinite Alérgica/complicações , Fatores de Risco , Inquéritos e Questionários
5.
J Environ Public Health ; 2022: 4848738, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35774192

RESUMO

Based on the role separation scenario in which students need parental support, this paper explores the effect of parents' attitude on secondary school students' online learning. Through structural equation model analysis and regression analysis of 745 valid responses to a questionnaire, the data results show that parents' subjective dimension includes perceived gain and perceived loss, and social factor dimension includes teachers' influence and online comments. Perceived value is the key influencing factor of parents' attitude towards secondary school students in online learning platform. Perceived usefulness and platform information influence parents' attitude positively and significantly, while perceived risk influences parents' attitude negatively and significantly. In the dimension of social factors, teachers' influence positively influences parents' attitude, and online comments modulate the influence of perceived value on parents' attitude.


Assuntos
Educação a Distância , Atitude , Humanos , Estudantes , Inquéritos e Questionários
6.
Sustain Prod Consum ; 30: 851-869, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37275511

RESUMO

Past studies related to embodied pollutant accounting reported that free trade has increased the environmental pollution of developing economies, because the developed countries "outsource" their pollutants to developing nations. The COVID-19 pandemic has stimulated the rise of the most serious protectionism after World War II. This study is aimed to discuss whether protectionism improve the environment in developing countries by developing a comprehensive evaluation model, which integrates multi-regional input-output (MRIO), data envelopment analysis (DEA), and scenario analysis. We revealed the role of protectionism from two perspectives: the single impact on pollutant emissions and the comprehensive impact on environmental efficiency. Specifically, the capital inputs, labor inputs, energy consumption, economic output, carbon dioxide, sulfur dioxide and nitrogen oxides emissions related to global trade activities were simulated based on the MRIO. And then, sector-level trade environmental efficiency was computed by intergrading the MRIO and DEA using a non-radial directional distance function. Finally, the environmental efficiency of both developing and developed countries under two scenarios with and without trade were estimated. The results confirmed that trade has increased the CO2, SO2 and NOX emissions of developing economies by 12.9%, 9.8% and 12.3%, and has reduced that of developed economies by 6.0%, 29.4% and 21.2%, respectively. However, the results also uncovered that the environmental efficiency of developing and developed economies was dropped by 3% and 5%, respectively, under no-trade scenario. We contend that protectionism is not conducive to the sustainable development of developing countries because it lowers their environmental efficiency, although it may reduce their territorial pollutant emissions. For developed countries, the single impact of protectionism on pollutant emission reduction and the comprehensive impact on environmental efficiency are both negative.

7.
Environ Sci Pollut Res Int ; 28(28): 37338-37353, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33715115

RESUMO

Achieving equality in water usage is part of the sixth goal of the 2030 Agenda for Sustainable Development. A comprehensive understanding evolution of inequality in water use and the driving factors behind the inequality can facilitate to implement equality in water consumption. In this work, the inequality index was used to measure China's water consumption inequality from 2004 to 2018 and the decomposition technique was used to decompose the status of inequality and the evolution of inequality. The results show the inequality in its water consumption was not reduced obviously despite China's rapid economic growth. There were 38.71% of provinces in China whose per capita water consumption was greater than the national average, mainly in the western region. For the three regions of China, the intraregional inequality was much greater than the interregional inequality. The western index was the largest and the eastern was the smallest. Among the factors that cause the inequality in water consumption, no one factor has been dominant at all times. Moreover, the effects of different factors changed over time. It is almost impossible to reduce inequality in water consumption through policy adjustment to several factors. China's example show that economic development cannot reduce the inequality in water consumption. More targeted policies and more efforts are required to reduce the inequality in water consumption.


Assuntos
Ingestão de Líquidos , Desenvolvimento Econômico , China , Desenvolvimento Sustentável , Água
8.
Curr Opin Struct Biol ; 67: 69-77, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33126140

RESUMO

Functional conformational changes of proteins can facilitate numerous biological events in cells. The Markov state model (MSM) built from molecular dynamics simulations provide a powerful approach to study them. We here introduce a protocol that is tailor-made for constructing MSMs to study the functional conformational changes of proteins. In this protocol, one of the important steps is to select proper molecular features that can collectively describe the slowest timescales of conformational changes of interest. We recommend spectral oASIS, the modified version of oASIS, as a promising approach for automatic feature selection. Recently developed deep learning methods could also serve efficient approaches for selecting features and finding collective variables. Using DNA repair enzymes and RNA polymerases as examples, we review recent applications of MSMs to elucidate molecular mechanisms of functional conformational changes. Finally, we discuss remaining challenges and future perspectives for constructing MSMs to study functional conformational changes of proteins.


Assuntos
Simulação de Dinâmica Molecular , Proteínas , RNA Polimerases Dirigidas por DNA , Cadeias de Markov
9.
Financ Res Lett ; 38: 101716, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32837385

RESUMO

We examine the role of ESG performance during market-wide financial crisis, triggered in response to the COVID-19 global pandemic. The unique circumstances create an inimitable opportunity to question if investors interpret ESG performance as a signal of future stock performance and/or risk mitigation. Using a novel dataset covering China's CSI300 constituents, we show (i) high-ESG portfolios generally outperform low-ESG portfolios (ii) ESG performance mitigates financial risk during financial crisis and (iii) the role of ESG performance is attenuated in 'normal' times, confirming its incremental importance during crisis. We phrase the results in the context of ESG investment practices.

10.
Cardiovasc Res ; 116(14): 2197-2206, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33063089

RESUMO

The high mortality rate of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is a critical concern of the coronavirus disease 2019 (COVID-19) pandemic. Strikingly, men account for the majority of COVID-19 deaths, with current figures ranging from 59% to 75% of total mortality. However, despite clear implications in relation to COVID-19 mortality, most research has not considered sex as a critical factor in data analysis. Here, we highlight fundamental biological differences that exist between males and females, and how these may make significant contributions to the male-biased COVID-19 mortality. We present preclinical evidence identifying the influence of biological sex on the expression and regulation of angiotensin-converting enzyme 2 (ACE2), which is the main receptor used by SARS-CoV-2 to enter cells. However, we note that there is a lack of reports showing that sexual dimorphism of ACE2 expression exists and is of functional relevance in humans. In contrast, there is strong evidence, especially in the context of viral infections, that sexual dimorphism plays a central role in the genetic and hormonal regulation of immune responses, both of the innate and the adaptive immune system. We review evidence supporting that ineffective anti-SARS-CoV-2 responses, coupled with a predisposition for inappropriate hyperinflammatory responses, could provide a biological explanation for the male bias in COVID-19 mortality. A prominent finding in COVID-19 is the increased risk of death with pre-existing cardiovascular comorbidities, such as hypertension, obesity, and age. We contextualize how important features of sexual dimorphism and inflammation in COVID-19 may exhibit a reciprocal relationship with comorbidities, and explain their increased mortality risk. Ultimately, we demonstrate that biological sex is a fundamental variable of critical relevance to our mechanistic understanding of SARS-CoV-2 infection and the pursuit of effective COVID-19 preventative and therapeutic strategies.


Assuntos
COVID-19/mortalidade , Doenças Cardiovasculares/mortalidade , Disparidades nos Níveis de Saúde , Inflamação/mortalidade , SARS-CoV-2/imunologia , Animais , COVID-19/diagnóstico , COVID-19/imunologia , COVID-19/virologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/virologia , Comorbidade , Feminino , Interações Hospedeiro-Patógeno , Humanos , Inflamação/diagnóstico , Inflamação/imunologia , Inflamação/virologia , Masculino , Prognóstico , Medição de Risco , Fatores de Risco , Caracteres Sexuais , Fatores Sexuais
11.
Proc Natl Acad Sci U S A ; 117(36): 21889-21895, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32820079

RESUMO

DNA glycosylase is responsible for repairing DNA damage to maintain the genome stability and integrity. However, how glycosylase can efficiently and accurately recognize DNA lesions across the enormous DNA genome remains elusive. It has been hypothesized that glycosylase translocates along the DNA by alternating between a fast but low-accuracy diffusion mode and a slow but high-accuracy mode when searching for DNA lesions. However, the slow mode has not been successfully characterized due to the limitation in the spatial and temporal resolutions of current experimental techniques. Using a newly developed scanning fluorescence resonance energy transfer (FRET)-fluorescence correlation spectroscopy (FCS) platform, we were able to observe both slow and fast modes of glycosylase AlkD translocating on double-stranded DNA (dsDNA), reaching the temporal resolution of microsecond and spatial resolution of subnanometer. The underlying molecular mechanism of the slow mode was further elucidated by Markov state model built from extensive all-atom molecular dynamics simulations. We found that in the slow mode, AlkD follows an asymmetric diffusion pathway, i.e., rotation followed by translation. Furthermore, the essential role of Y27 in AlkD diffusion dynamics was identified both experimentally and computationally. Our results provided mechanistic insights on how conformational dynamics of AlkD-dsDNA complex coordinate different diffusion modes to accomplish the search for DNA lesions with high efficiency and accuracy. We anticipate that the mechanism adopted by AlkD to search for DNA lesions could be a general one utilized by other glycosylases and DNA binding proteins.


Assuntos
Bacillus cereus/genética , Proteínas de Bactérias/química , DNA Glicosilases/química , Bacillus cereus/química , Bacillus cereus/enzimologia , Bacillus cereus/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , DNA Glicosilases/genética , DNA Glicosilases/metabolismo , Reparo do DNA , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Transferência Ressonante de Energia de Fluorescência , Cinética , Cadeias de Markov , Simulação de Dinâmica Molecular , Espectrometria de Fluorescência , Especificidade por Substrato
12.
Sci Total Environ ; 726: 138362, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32481201

RESUMO

Increasing water consumption from various economic activities has posed increasing challenges for the sustainability of developing countries. In particular, China is facing a sharp conflict between rapid economic development and water shortage. Evaluating the decoupling state between economic growth and water consumption and exploring the driving factors behind this could serve to develop strategy to moving to economic growth without water use growth. To this end, this work uses the Tapio decoupling and LMDI decomposition methods to evaluate the decoupling performance between China's water consumption and economic growth at the national and provincial levels, and six driving factors are decomposed, namely water consumption intensity, industrial structure, economic development, water resource utilization rate, water resource endowment and population size. Results show that: (1) Only two decoupling states, strong decoupling and weak decoupling, occurred at national level, and the decoupling index shows a decreasing trend. (2) 31 provinces showed only two states of strong decoupling and weak decoupling. More than 60% of the provinces showed strong decoupling after 2011, and the decoupling effect was significantly better than that of 2004-2011. (3) The effects of water consumption intensity and industrial structure drive the occurrence of decoupling. Economic level and population size have a positive incremental effect on water consumption. Finally, we propose policy recommendations such as developing water-saving technologies and optimizing industrial structure to promote water sustainability. The comprehensive methodology in this paper provides a theoretical reference for research in other countries or other environmental issues. Governments in various regions can formulate effective measures to achieve sustainable use of water resources, responding to the 2030 Agenda for Sustainable Development.

13.
Sci Total Environ ; 714: 136689, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-31978772

RESUMO

Residual chemicals discharged from wastewater treatment plants (WWTPs) and subsequent ecological risk are important in production safety when reuse of the effluent water occurs. Thus, this work provides an investigation of the occurrence and removal of dissolved Endocrine-disrupting chemicals (EDCs) in 38 WWTPs in Guangdong Province, China. The results indicate that EDCs are widely distributed in the investigated WWTPs, while nonylphenols (NPs) are the predominant chemical among the target EDCs, accounting for >98% of the concentration in the influent and >97% of the concentration in the effluent. Moreover, 4 main types of wastewater treatment processes (oxidation ditch, A2/O, conventional activated sludge and microaeration oxidation ditch followed by A2/O) were found to be inefficient for removing dissolved EDCs, with a mean removal rate of approximately 25%. The potential environmental risk was predicted for residual EDCs. Specifically, 17α-ethynylestradiol (EE2) was considered to be the most hazardous chemical among the target EDCs, with a median risk quotient (RQ) of 8.94. In addition, ß-estradiol (E2) and estrone (E1) have median RQs of 1.14 and 0.27, and NPs have median RQs of 0.61 (algae), 0.37 (inverberate) and 0.25 (fish), respectively.


Assuntos
Águas Residuárias/química , China , Disruptores Endócrinos , Monitoramento Ambiental , Medição de Risco , Eliminação de Resíduos Líquidos , Poluentes Químicos da Água
15.
J Arthroplasty ; 34(6): 1287-1296, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30852065

RESUMO

BACKGROUND: Hip fracture is a significant health risk for older adults and malnutrition indicates hip fracture risk. METHODS: We evaluated whether nutrition status could predict clinical outcomes and mortality after hip fracture surgery in older adults. MEDLINE, Cochrane, EMBASE, and Google Scholar databases were searched for studies published until July 1, 2018, in patients with serum albumin or total lymphocyte count (TLC) at admission, nutritional status by Mini Nutritional Assessment (MNA), and in-hospital follow-up. Data extracted were analyzed using random-effects or fixed-effects models. RESULTS: Nineteen studies with 34,363 adults aged 74-85 years receiving hip fracture surgery were eligible for inclusion. Among these studies, 13 were screened for low albumin, 4 were evaluated for TLC, and 4 for nutritional status by MNA. Hypoalbuminemia was significantly associated with higher total mortality and higher risk of in-hospital death (both P < .001). Low TLC and MNA results "at risk of malnutrition" (hazard ratio, 1.67; 95% confidence interval = 1.28-2.18) and "malnourished" nutritional status (hazard ratio, 2.65; 95% CI = 1.81-3.88) also were significantly associated with higher total mortality (all P < .001). CONCLUSION: Low serum albumin level is a sole indicator for increased risk of in-hospital death, postoperative complications, and total mortality after hip fracture surgery in older adults. Low TLC and malnutrition classified by MNA predict increased mortality. These indicators provide valuable prognostic information and routine use may be prudent.


Assuntos
Artroplastia de Quadril/efeitos adversos , Avaliação Geriátrica , Fraturas do Quadril/cirurgia , Contagem de Linfócitos , Avaliação Nutricional , Albumina Sérica/análise , Idoso , Idoso de 80 Anos ou mais , Feminino , Consolidação da Fratura , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/mortalidade , Mortalidade Hospitalar , Hospitalização , Humanos , Masculino , Desnutrição/complicações , Estado Nutricional , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/mortalidade , Prognóstico , Modelos de Riscos Proporcionais
17.
PLoS Negl Trop Dis ; 8(9): e3124, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25254513

RESUMO

BACKGROUND: Parasite-specific IgE is thought to correlate with protection against Schistosoma mansoni infection or re-infection. Only a few molecular targets of the IgE response in S. mansoni infection have been characterised. A better insight into the basic mechanisms of anti-parasite immunity could be gained from a genome-wide characterisation of such S. mansoni allergens. This would have repercussions on our understanding of allergy and the development of safe and efficacious vaccinations against helminthic parasites. METHODOLOGY/PRINCIPAL FINDINGS: A complete medium- to high-throughput amenable workflow, including important quality controls, is described, which enables the rapid translation of S. mansoni proteins using wheat germ lysate and subsequent assessment of potential allergenicity with a humanised Rat Basophilic Leukemia (RBL) reporter cell line. Cell-free translation is completed within 90 minutes, generating sufficient amounts of parasitic protein for rapid screening of allergenicity without any need for purification. Antigenic integrity is demonstrated using Western Blotting. After overnight incubation with infected individuals' serum, the RS-ATL8 reporter cell line is challenged with the complete wheat germ translation mixture and Luciferase activity measured, reporting cellular activation by the suspected allergen. The suitability of this system for characterization of novel S. mansoni allergens is demonstrated using well characterised plant and parasitic allergens such as Par j 2, SmTAL-1 and the IgE binding factor IPSE/alpha-1, expressed in wheat germ lysates and/or E. coli. SmTAL-1, but not SmTAL2 (used as a negative control), was able to activate the basophil reporter cell line. CONCLUSION/SIGNIFICANCE: This method offers an accessible way for assessment of potential allergenicity of anti-helminthic vaccine candidates and is suitable for medium- to high-throughput studies using infected individual sera. It is also suitable for the study of the basis of allergenicity of helminthic proteins.


Assuntos
Alérgenos/imunologia , Antígenos de Helmintos/imunologia , Proteínas de Helminto/imunologia , Vacinas Protozoárias/imunologia , Schistosoma mansoni/imunologia , Adolescente , Adulto , Animais , Linhagem Celular Tumoral , Criança , Humanos , Masculino , Ratos , Adulto Jovem
18.
Neurosurgery ; 75(1): 51-60, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24594926

RESUMO

BACKGROUND: Neuronal Nogo-66 receptor 1 (NgR1) has attracted attention as a converging point for mediating the effects of myelin-associate inhibitory ligands in the central nervous system, establishing the growth-restrictive environment, and limiting axon regeneration after traumatic injury. OBJECTIVE: To investigate the factors that may be contributing to the discrepancy in the importance of NgR1, which has been undermined by several studies that have shown the lack of substantial axon regeneration after spinal cord injury (SCI) in NgR1-knockout or -knockdown animal models. METHODS: We used mice carrying either a homozygous or heterozygous null mutation in the NgR1 gene and subjected them to either a moderate or severe SCI. RESULTS: Locomotor function assessments revealed that the level of functional recovery is affected by the degree of injury suffered. NgR1 ablation enhanced local collateral sprouting in the mutant mice. Reactive astrocytes and chondroitin sulfate proteoglycans (CSPGs) are upregulated surrounding the injury site. Matrix metalloproteinase-9, which has been shown to degrade CSPGs, was significantly upregulated in the homozygous mutant mice compared with the heterozygous or wild-type mice. However, CSPG levels remained higher in the homozygous compared with the heterozygous mice, suggesting that CSPG-degrading activity of matrix metalloproteinase-9 may require the presence of NgR1. CONCLUSION: Genetic ablation of NgR1 may lead to significant recovery in locomotor function after SCI. The difference in locomotor recovery we observed between the groups that suffered various degrees of injury suggests that injury severity may be a confounding factor in functional recovery after SCI.


Assuntos
Proteínas da Mielina/genética , Regeneração Nervosa/genética , Receptores de Superfície Celular/genética , Recuperação de Função Fisiológica/genética , Traumatismos da Medula Espinal/genética , Animais , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Modelos Animais de Doenças , Proteínas Ligadas por GPI/genética , Immunoblotting , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Knockout , Receptor Nogo 1 , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/fisiopatologia
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