CYP1A1, GSTM1 and GSTT1 polymorphisms and lung cancer: a pooled analysis of gene–gene interactions

Gene–environment interactions have been extensively studied in lung cancer. It is likely that several genetic polymorphisms cooperate in increasing the individual risk. Therefore, the study of gene–gene interactions might be important to identify high-susceptibility subgroups. GSEC is an initiative aimed at collecting available data sets on metabolic polymorphisms and the risks of cancer at several sites and performing pooled analyses of the original data. Authors of published papers have provided original data sets. The present paper refers to gene–gene interactions in lung cancer and considers three polymorphisms in three metabolic genes: CYP1A1, GSTM1 and GSTT1. The present analyses compare the gene–gene interactions of the CYP1A1*2A, GSTM1 and GSTT1 polymorphisms from studies on lung cancer conducted in Europe and the USA between 1991 and 2000. Only Caucasians have been included. The data set includes 1466 cases and 1488 controls. The only clear-cut association was found with CYP1A1*2A. This association remained unchanged after stratification by polymorphisms in other genes (with an odds ratio [OR] of approximately 2.5), except when interaction with GSTM1 was considered. When the OR for CYP1A1*2A was stratified according to the GSTM1 genotype, the OR was increased only among the subjects who had the null (homozygous deletion) GSTM1 genotype (OR=2.8, 95% CI=0.9–8.4). The odds ratio for the interactive term (CYP1A1*2A by GSTM1) in logistic regression was 2.7 (95% CI=0.5–15.3). An association between lung cancer and the homozygous CYP1A1*2A genotype is confirmed. An apparent and biologically plausible interaction is suggested between this genotype and GSTM1.     

Asymmetric reduction of (4S)-(+)-carvone catalyzed by baker's yeast: A green method for monitoring the conversion based on liquid–liquid–liquid microextraction with polypropylene hollow fiber membranes

The α,β-unsaturated carbonyl compound (4S)-(+)-carvone was selectively reduced to (1R,2R,4S)-iso-dihydrocarveol using baker's yeasts. The conversion of the bioreduction reaction was monitored using a green hollow-fiber liquid–liquid–liquid microextraction (HF-LLLME) technique. Several parameters which may affect the bioreduction of (4S)-(+)-carvone, such as temperature, time, substrate/enzyme ratio, pH and buffer concentration, were evaluated. The effect of some additives, such as trehalose, DMSO and the ionic liquid [BMIm][PF₆], was also studied. The (1R,2R,4S)-iso-dihydrocarveol was recovered with 52.7% conversion and diastereoisomeric excess >99% after 48 h of reaction at 40 °C in an aqueous monophasic system, with 0.1 mol L^?1 buffer concentration (pH 7.5) and a substrate/yeast cell mass ratio of 8.0 mg g^?1. The HF-LLLME microextraction technique allowed the optimization of the reaction with a reduction of over 99.5% in relation to the use of organic solvents.     

Intraspecific competition replaces interspecific facilitation as abiotic stress decreases: The shifting nature of plant–plant interactions

Plant–plant interactions change depending on environmental conditions, shifting from competition to facilitation when the stress is high. In addition to these changes, the relevance of intraspecific compared to interspecific interactions may also shift as abiotic stress does. We inferred intra- and interspecific plant–plant interactions of the cushion plant Hormathophylla spinosa as related to the dominant shrub Juniperus sabina in two sites with contrasting abiotic conditions (a slope with high-stress conditions vs. a valley bottom with milder conditions) in a Mediterranean high mountain. Specifically, we studied the spatial patterns and several variables related to plant performance (plant size and form, non-structural carbohydrate – NSC – concentrations and radial growth) of H. spinosa.The spatial pattern varied depending on site conditions. H. spinosa plants were positively associated with juniper in the high-stress slope site, probably through higher establishment rates due to the amelioration of soil conditions. In contrast, in the milder valley site H. spinosa establishment occurred mostly in open areas. Age structure, inferred from annual rings, reflected a massive establishment event in the whole study area which occurred 30–50 years ago. Canopy variables and radial growth were density dependent: both were negatively affected by the high density of H. spinosa individuals in the valley, but favoured by junipers on the slope. Interestingly, NSCs showed the opposite pattern, suggesting lower investment in growth by H. spinosa plants in the valley than on the slope.Our results reinforce the strong links existing between intra- and interspecific relationships and the need to include both when studying the influence of abiotic conditions on plant–plant interactions. This approach enabled us to detect that the direction and intensity of plant–plant interactions may shift at different ecological levels. Particularly interesting was the finding that optimal sites at the population level may not necessarily be the sites showing maximum individual performance.     

Proteomics of human prostate cancer biospecimens: the global,systems-wide perspective for Protein markers with potential clinical utility

Despite intense global efforts, no new clinical and/or viable biomarkers have been established to overcome the limitation of the prostate specific antigen in the early diagnosis and prognosis of prostate cancer (PCa). The current proteomic approaches to PCa biomarker discovery, each have distinct advantages and disadvantages, yet when combined hold real promise in the coming years. One key approach to this effort is the development of non-targeted, depletion-free and quantitative liquid chromatography–ultra high resolution tandem mass spectrometry (LC–MS) pipelines for the systems-wide interrogation of the diverse proteomes encompassed in whole tissue and blood serum or plasma. Derived quantitative proteomes can be decoded for their biomedical relevance with advanced bioinformatics and bibliographic mining to yield promising ‘molecular portraits’ that can gauge prostatic disease at the serological level. Their functional annotation, although potentially useful, is beyond our current level of biological understanding and should not be requisite for their effective use in the clinical monitoring of prostatic disease.     

The shaping of invasive glioma phenotype by the ubiquitin–proteasome system

Abstract

Protein degradation is an indispensable process for cells which is often deregulated in various diseases, including malignant conditions. Depending on the specific cell type and functions of expressed proteins, this aberration may have different effects on the determination of malignant phenotypes. A discrete, inherent feature of malignant glioma is its profound invasive and migratory potential, regulated by the expression of signaling and effector proteins, many of which are also subjected to post-translational regulation by the ubiquitin–proteasome system (UPS). Here we provide an overview of this connection, focusing on important pro-invasive protein signals targeted by the UPS.     

Ras guanyl nucleotide releasing protein 2 affects cell viability and cell–matrix adhesion in ECV304 endothelial cells

Ras guanyl nucleotide releasing proteins (RasGRPs) are guanine nucleotide exchange factors that activate Ras and Rap. We recently reported that xrasgrp2, which is a homolog of the human rasgrp2, plays a role in vasculogenesis and/or angiogenesis during early development of Xenopus embryos. However, the function of RasGRP2 in human vascular endothelium remains unknown. Therefore we aimed to analyze the function of human RasGRP2 in vascular endothelial cells. RasGRP2 overexpression did not increase Ras activation. However, it slightly increased Ras expression and increased proliferation in ECV304 cells. Furthermore, RasGRP2 overexpression increased Rap1 activation and cell–matrix adhesion in ECV304 cells. These data demonstrate that RasGRP2 increases cell viability and cell–matrix adhesion through increased Ras expression and Rap1 activation, respectively, in endothelial cells.     

Quantitative aspects of oxygen and carbon dioxide exchange through the lungs in Ocypode ceratophthalmus (Crustacea: Decapoda) during rest and exercise in water and air

Ghost crabs Ocypode ceratophthalmus were exercised in air and water to measure CO₂ and O₂ exchange rates using the method of instantaneous measurements of oxygen consumption rate (MO₂) where applicable. Average heart rate increased from 100 to nearly 400 pulses per minute after five minutes of exercise on a treadmill at a run rate of 0.133 m s^?1. It took less than a minute for oxygen taken up through the lung epithelium from the air inside the branchial cavity to reach the maximal oxygen consumption rate of 26.1 mmol O₂ kg^?1 h^?1. Resting MO₂ was 4.06 mmol O₂ kg^?1 h^?1 in air, but decreased to 3.37 mmol O₂ kg^?1 h^?1 in seawater. Radioactive CO₂ from injected l-lactate is released linearly by the lung. The percent accumulated 14-CO₂ in exhaled air, plotted against time, intersects zero time on the x -axis, indicating rapid gas exchange at the lung surface. The P ₅₀ values for native haemocyanin of 4.89 mm Hg before exercise, and 8.99 mm Hg after exercise, are typical of a high-affinity haemocyanin usually associated with terrestrial crabs. The current notion that Ocypode ceratophthalmus drown when submerged in seawater was not substantiated by our experiments. MO₂ in seawater increased from 3.37 mmol O₂ kg^?1 h^?1 for resting crabs to 5.72 mmol O₂ kg^?1 h^?1 during exercise. When submerged by wave-seawater in the natural environment and during exercise in respirometer-seawater O. ceratophthalmus do not swim but, having a specific density of 1.044, float nearly weightless with a minimum of body movements.     

A tethering coherent protein in autophagosome maturation

Autophagy is a cellular pathway that degrades damaged organelles, cytosol and microorganisms, thereby maintaining human health by preventing various diseases including cancers, neurodegenerative disorders and diabetes. In autophagy, autophagosomes carrying cellular cargoes fuse with lysosomes for degradation. The proper autophagosome-lysosome fusion is pivotal for efficient autophagy activity. However, the molecular mechanism that specifically directs the fusion process is not clear. Our study reported that lysosome-localized TECPR1 (TECtonin β-Propeller Repeat containing 1) binds the autophagosome-localized ATG12–ATG5 conjugate and recruits it to autolysosomes. TECPR1 also binds PtdIns3P in an ATG12–ATG5-dependent manner. Consequently, depletion of TECPR1 leads to a severe defect in autophagosome maturation. We propose that the interaction between TECPR1 and ATG12–ATG5 initiates the fusion between the autophagosome and lysosome, and TECPR1 is a TEthering Coherent PRotein in autophagosome maturation.     

The effects of different vegetation restoration patterns on soil bacterial diversity for sandy land in Hulunbeier

Grassland desertification seriously threatens sustainable economic and social development. Much attention has been paid to the control of grassland desertification, and even to the restoration and reconstruction of the grassland. Vegetation restoration is considered to be a very effective solution. Soil sustains an immense diversity of microbes, and the characteristics of soil microbial communities are sensitive indicators of soil. It is important to understand the relationship between vegetation and soil microbial diversity during the restoration process. Soil microbial, which is the main index to evaluate soil quality, plays a significant role in ecosystem and soil microbial diversity is the important one of global diversity. Exploring the effects of different vegetation patterns on soil microbial diversity can provide scientific bases and technical support for systemic and impersonal assessment of the best vegetation restoration patterns, as well as the vegetation restoration and reconstruction of Hulunbeier sandy land. Based on PCR–DGGE technology, a case study was carried out to investigate the effects of five different vegetation restoration patterns on soil microbial functional diversity after 4 years in sandy land in Hulunbeier, China. The five vegetation restoration patterns included mono-cultivar planting of Agropyron cristatum (UA), mono-cultivar planting of Hedysarum fruticosum (UH), mono-cultivar planting of Caragana korshinskii (UC), mixed-cultivar planting of Agropyron cristatum and Hedysarum fruticosum (AC) and mixed-cultivar planting of Agropyron cristatum, Hedysarum fruticosum, Caragana korshinskii and Elymus nutans (ACHE). Completely degraded sandy land was used as control.The results indicated that the vegetation restoration increased the genetic diversity of soil bacterial community obviously, and the structure of soil bacterial community was changed. The results of phylogenetic analysis suggested that the bacterial community in Hulunbeier sandy land mainly attributed to Proteobacteria, Bacteroidetes, Firmicutes, Actinobacteria, and Acidobacteria. The dominant groups were Proteobacteria and Bacteroidetes. The effects of different vegetation type on soil bacterial community structures were different.