Activation of Notch-1 signaling maintains the neoplastic phenotype in human Ras-transformed cells

Truncated Notch receptors have transforming activity in vitro and in vivo. However, the role of wild-type Notch signaling in neoplastic transformation remains unclear. Ras signaling is deregulated in a large fraction of human malignancies and is a major target for the development of novel cancer treatments. We show that oncogenic Ras activates Notch signaling and that wild-type Notch-1 is necessary to maintain the neoplastic phenotype in Ras-transformed human cells in vitro and in vivo. Oncogenic Ras increases levels and activity of the intracellular form of wild-type Notch-1, and upregulates Notch ligand Delta-1 and also presenilin-1, a protein involved in Notch processing, through a p38-mediated pathway. These observations place Notch signaling among key downstream effectors of oncogenic Ras and suggest that it might be a novel therapeutic target.     

Humans Have Antibodies against a Plant Virus: Evidence from Tobacco Mosaic Virus

Tobacco mosaic virus (TMV), a widespread plant pathogen, is found in tobacco (including cigarettes and smokeless tobacco) as well as in many other plants. Plant viruses do not replicate or cause infection in humans or other mammals. This study was done to determine whether exposure to tobacco products induces an immune response to TMV in humans. Using a sandwich ELISA assay, we detected serum anti-TMV antibodies (IgG, IgG1, IgG3, IgG4, IgA, and IgM) in all subjects enrolled in the study (20 healthy smokers, 20 smokeless-tobacco users, and 20 non-smokers). Smokers had a higher level of serum anti-TMV IgG antibodies than non-smokers, while the serum level of anti-TMV IgA from smokeless tobacco users was lower than smokers and non-smokers. Using bioinformatics, we also found that the human protein TOMM40L (an outer mitochondrial membrane 40 homolog – like translocase) contains a strong homology of six contiguous amino acids to the TMV coat protein, and TOMM40L peptide exhibited cross-reactivity with anti-TMV antibodies. People who smoke cigarettes or other tobacco products experience a lower risk of developing Parkinson’s disease, but the mechanism by which this occurs is unclear. Our results showing molecular mimicry between TMV and human TOMM40L raise the question as to whether TMV has a potential role in smokers against Parkinson’s disease development. The potential mechanisms of molecular mimicry between plant viruses and human disease should be further explored.     

Sputum mediator profiling and relationship to airway wall geometry imaging in severe asthma

Background

Severe asthma is a heterogeneous disease and the relationship between airway inflammation and airway remodelling is poorly understood. We sought to define sputum mediator profiles in severe asthmatics categorised by CT-determined airway geometry and sputum differential cell counts.

Methods

In a single centre cross-sectional observational study we recruited 59 subjects with severe asthma that underwent sputum induction and thoracic CT. Quantitative CT analysis of the apical segment of the right upper lobe (RB1) was performed. Forty-one mediators in sputum samples were measured of which 21 mediators that were assessable in >50% of samples were included in the analyses.

Results

Independent of airway geometry, sputum MMP9 and IL-1β were elevated in those groups with a high sputum neutrophil count while sputum ICAM was elevated in those subjects with a low sputum neutrophil count. In contrast, sputum CCL11, IL-1α and fibrinogen were different in groups stratified by both sputum neutrophil count and airway geometry. Sputum CCL11 concentration was elevated in subjects with a low sputum neutrophil count and high luminal and total RB1 area, whereas sputum IL1α was increased in subjects with a high sputum neutrophil count and low total RB1 area. Sputum fibrinogen was elevated in those subjects with RB1 luminal narrowing and in those subjects with neutrophilic inflammation without luminal narrowing.

Conclusions

We have demonstrated that sputum mediator profiling reveals a number of associations with airway geometry. Whether these findings reflect important biological phenotypes that might inform stratified medicine approaches requires further investigation.     

Prevalence of Myopia and Its Risk Factors in Urban School Children in Delhi: The North India Myopia Study (NIM Study)

PurposeAssess prevalence of myopia and identify associated risk factors in urban school children.MethodsThis was a cross-sectional study screening children for sub-normal vision and refractive errors in Delhi. Vision was tested by trained health workers using ETDRS charts. Risk factor questionnaire was filled for children with vision <6/9.5, wearing spectacles and for a subset (10%) of randomly selected children with normal vision. All children with vision <6/9.5 underwent cycloplegic refraction. The prevalence of myopia <-0.5 diopters was assessed. Association of risk factors and prevalence of myopia was analyzed for children with myopia and randomly selected non myopic children and adjusted odds ratio values for all risk factors were estimated.ResultsA total number of 9884 children were screened with mean age of 11.6 + 2.2 years and 66.8% boys. Prevalence of myopia was 13.1% with only 320 children (24.7%) wearing appropriate spectacles. Mean myopic spherical error was -1.86 + 1.4 diopters. Prevalence of myopia was higher in private schools compared to government schools (p<0.001), in girls vs. boys (p = 0.004) and among older (> 11 years) children (p<0.001). There was a positive association of myopia with studying in private schools vs. government schools (p<0.001), positive family history (p< 0.001) and higher socio-economic status (p = 0.037). Positive association of presence of myopia was observed with children studying/reading > 5 hours per day (p < 0.001), watching television > 2 hours / day (p < 0.001) and with playing computer/video/mobile games (p < 0.001). An inverse association with outdoor activities/playing was observed with children playing > 2 hours in a day.ConclusionMyopia is a major health problem in Indian school children. It is important to identify modifiable risk factors associated with its development and try to develop cost effective intervention strategies.     

市售长叶松油和锡兰肉桂油对登革热媒蚊埃及伊蚊的灭幼效果(英文)

松油和桂皮油由于具有芳香性气味, 因而成为良好的成虫驱避剂, 但是关于它们对蚊虫的杀幼虫作用研究不多。为揭示市售的长叶松Pinus longifolia油和锡兰肉桂Cinnamomum zeylanicum油对来源于印度德里的埃及伊蚊Aedes aegypti 4龄幼虫的毒杀潜力, 我们进行了室内研究, 以幼虫死亡率及行为改变和形态改变等指标评估其杀幼虫潜力。结果表明： 两种油对埃及伊蚊4龄幼虫均具有毒杀作用, 且松油的灭幼效果优于桂皮油。松油的LC₅₀和LC₇₀ 值分别为0.33093 mg/L 和0.54476 mg/L, 而桂皮油的LC₅₀和LC₇₀ 值分别为0.63159 mg/L和0.77736。进一步观察发现, LC₉₀剂量下桂皮油的杀幼虫潜力强于松油, 其LC₉₀为1.11879 mg/L, 而松油的LC₉₀为 1.04915 mg/L。在处理的幼虫中观察到行为改变, 如兴奋、 坐立不安、 颤抖、 痉挛然后瘫痪, 说明这两种油可能对其神经肌肉系统产生了影响。显微观察处理幼虫的形态改变发现, 与对照相比, 大多数器官的外观正常, 只是肛鳃略为内收缩而引起结构畸形, 提示肛腮可能是这两种油的作用位点, 腮的功能异常引起了幼虫死亡。这两种油品可开发用作防治蚊虫的新型杀幼虫药剂。     

Biological control of onion leaf blight disease by bulb and foliar application of powder formulation of antagonist mixture

Abstract

Three antagonists: Pseudomonas fluorescens (Pf1), Bacillus subtilis and Trichoderma viride, were tested alone and in combination for suppression of onion leaf blight (Alternaria palandui) disease under glasshouse and field conditions. The average mean of disease reduction was 24.81% for single strains and 42.44% for mixtures. In addition to disease suppression, treatment with a mixture of antagonists promoted plant growth in terms of increased plant height and ultimately bulb yield. Though seed treatment of either single strain or strain mixtures alone could reduce the disease, subsequent application to root, leaves or soil further reduced the disease and enhanced the plant growth. The mixture consisting of Pseudomonas fluorescens Pf1 plus Bacillus subtilis plus Trichoderma viride was the most effective in reducing the disease and in promoting plant growth and bulb yield in greenhouse and field tests.     

5Alpha-reductase inhibition activity of steroids isolated from marine soft corals

The aim of this study is to determine the 5alpha-reductase inhibitory activity of several new steroidal compounds PR-01-PR-07 by measuring the conversion of [3H]T to[3H]DHT in Penicillium crustosum broths. These compounds were obtained from marine soft corals collected on the coasts of Andaman and Nicobar at Hori, Natkal and Kalipur (Diglipur) Islands and identified as Sinularia grandilobata Verseveldt, Sinularia crassa Tixier- Durivault, Sinularia gravis Tixier- Durivault, Sinularia sp., Lobophytum sp., Lobophytum crassum and Cladiella sp. PR-01-PR-04 significantly inhibited the conversion of [3H]T to [3H]DHT (P < 0.05) whereas PR-05 and PR-06 did not show an appreciable difference (P > 0.05) in this model. On the other hand PR-07 stimulated (P < 0.05) the enzymatic reaction.