CORAL: Building up QSAR models for the chromosome aberration test

A high level of chromosomal aberrations in peripheral blood lymphocytes may be an early marker of cancer risk, but data on risk of specific cancers and types of chromosomal aberrations are limited. Consequently, the development of predictive models for chromosomal aberrations test is important task. Majority of models for chromosomal aberrations test are so-called knowledge-based rules system. The CORAL software (http://www.insilico.eu/coral, abbreviation of “CORrelation And Logic”) is an alternative for knowledge-based rules system. In contrast to knowledge-based rules system, the CORAL software gives possibility to estimate the influence upon the predictive potential of a model of different molecular alerts as well as different splits into the training set and validation set. This possibility is not available for the approaches based on the knowledge-based rules system. Quantitative Structure–Activity Relationships (QSAR) for chromosome aberration test are established for five random splits into the training, calibration, and validation sets. The QSAR approach is based on representation of the molecular structure by simplified molecular input-line entry system (SMILES) without data on physicochemical and/or biochemical parameters. In spite of this limitation, the statistical quality of these models is quite good.     

Influence of age on the bioaccumulation of heavy metals in Apodemus sylvaticus at Merja Zerga lagoon,Morocco

The influence of age and sex on the bioaccumulation of heavy metals in Apodemus sylvaticus was studied in Merja Zerga lagoon in northern Morocco. Five trace metal elements (Zn, Pb, Cr, Cu and Fe) were quantitatively analyzed by Varian AA 240 atomic absorption spectroscopy with graphite furnace in three organs (Liver, Kidney and Heart) from animals of different age and sex. The maximum metal level of the analyzed samples was recorded in adults and was limited to 46.62 μg/g for Pb and 35.1 μg/g for Cu, while it reached 22.69 μg/g, 7.59 μg/g and 6.78 μg/g for Cr, Zn and Fe, respectively. Highly significant differences were found for bioaccumulation of heavy metals according to animal ages and no significant differences were observed between the two sexes among the studied animals. Our results revealed also the existence of a strong correlation (r > 0.65) between the majority of biometric parameters and the trace element concentrations. In general, we found that age is a critical factor in estimating the level of heavy metal pollution. Other characteristics such as habitat, feeding habits and anti-predator behavior of the species need to be studied.     

Community structure,spatial distribution,diversity and functional characterization of culturable endophytic fungi associated with Glycyrrhiza glabra L.

A total of 266 endophytic fungal isolates were recovered from 1019 tissue segments of Glycyrrhiza glabra collected from four different locations in the North-Western Himalayas. The endophytes grouped into 21 genera and 38 different taxa. The host had strong affinity for the genus Phoma, followed by Fusarium. The species richness was highest at the sub-tropical location, followed by the sub-temperate location and the temperate locations, respectively. The tissue specificity of endophytes was also evident. Some endophytes showed potential antimicrobial activity against phyto-pathogens indicating that they may be helpful to the host in evading pathogens. All the endophytic taxa produced the plant growth promoting hormone, indole acetic acid (IAA), though in varying concentrations. None of these endophytes caused any symptoms of disease in co-cultivation with the tissue cultured plants. Further, all the endophytes had a positive influence on the phenolic and flavonoid content of the host. Three endophytes, Stagonosporopsis cucurbitacearum, Bionectria sp. and Aspergillus terreus also increased the host root (rhizome) and shoot growth visibly. Such endophytes are potential candidates for developing endophyte-based technologies for sustainable cultivation and enhanced productivity of G. glabra. This is the first report of community structure and biological properties of fungal endophytes associated with G. glabra.     

COPD association and repeatability of blood biomarkers in the ECLIPSE cohort

Background

There is a need for biomarkers to better characterise individuals with COPD and to aid with the development of therapeutic interventions. A panel of putative blood biomarkers was assessed in a subgroup of the Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE) cohort.

Methods

Thirty-four blood biomarkers were assessed in 201 subjects with COPD, 37 ex-smoker controls with normal lung function and 37 healthy non-smokers selected from the ECLIPSE cohort. Biomarker repeatability was assessed using baseline and 3-month samples. Intergroup comparisons were made using analysis of variance, repeatability was assessed through Bland-Altman plots, and correlations between biomarkers and clinical characteristics were assessed using Spearman correlation coefficients.

Results

Fifteen biomarkers were significantly different in individuals with COPD when compared to former or non-smoker controls. Some biomarkers, including tumor necrosis factor-α and interferon-γ, were measurable in only a minority of subjects whilst others such as C-reactive protein showed wide variability over the 3-month replication period. Fibrinogen was the most repeatable biomarker and exhibited a weak correlation with 6-minute walk distance, exacerbation rate, BODE index and MRC dyspnoea score in COPD subjects. 33% (66/201) of the COPD subjects reported at least 1 exacerbation over the 3 month study with 18% (36/201) reporting the exacerbation within 30 days of the 3-month visit. CRP, fibrinogen interleukin-6 and surfactant protein-D were significantly elevated in those COPD subjects with exacerbations within 30 days of the 3-month visit compared with those individuals that did not exacerbate or whose exacerbations had resolved.

Conclusions

Only a few of the biomarkers assessed may be useful in diagnosis or management of COPD where the diagnosis is based on airflow obstruction (GOLD). Further analysis of more promising biomarkers may reveal utility in subsets of patients. Fibrinogen in particular has emerged as a potentially useful biomarker from this cohort and requires further investigation.

Trial Registration

SCO104960, clinicaltrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT00292552","term_id":"NCT00292552"}}NCT00292552     

Ultrasound-Targeted Microbubble Destruction (UTMD) for Localized Drug Delivery into Tumor Tissue

Background

Ultrasound-targeted microbubble destruction (UTMD) is a type of ultrasound therapy, in which low frequency moderate power ultrasound is combined with microbubbles to trigger cavitation. Cavitation is the process of oscillation of gas bubbles causing biophysical effects such as pushing and pulling or shock waves that permeabilize biological barriers. In vivo, cavitation results in tissue permeabilization and is used to enable local delivery of nanomedicine. While cavitation can occur in biological liquids when high pressure ultrasound is applied, the use of microbubbles as cavitation nuclei in UTMD largely facilitates the induction of cavitation. UTMD is intensively studied for drug delivery into tumor tissue, but also for the activation of anti-tumor immune responses. The first clinical studies of UTMD-mediated chemotherapy delivery confirmed safety and efficacy of this approach.

Secondary structure of mouse and rabbit α- and β-globin mRNAs: Differential accessibility of α and β initiator AUG codons towards nucleases

The nucleotide sequence from the 5′ terminus inward of one third of mouse α- and β^maj-globin messenger RNAs has been established. In addition, using 5′ ³²P end-labeled mRNAs as substrates and S1 and T1 nucleases as probes for single-stranded regions, the secondary structures of mouse and rabbit α- and β-globin mRNAs have been analyzed. Our results indicate that the AUG initiator codon in both mouse and rabbit β-globin mRNA is quite susceptible to cleavage with S1 and T1 nucleases, suggesting that it resides in a single-stranded exposed region. In contrast, the initiator AUG in the α-globin mRNA of both species is inaccessible to cleavage, indicating that it is either buried by tertiary structure or is base-paired. Since the rate of initiation of protein synthesis with β-globin mRNA in rabbit reticulocyte is 30–40% faster than for α-globin mRNA, these results imply a possible correlation between the differential rates of initiation with these two mRNAs and the accessibility of the respective AUG initiator codons.     

Effects of taurine and γ-aminobutyric acid on akinesia and analgesia induced by D-Ala2-Met-enkephalinamide in rats

Effects of taurine or γ-aminobutyric acid (GABA) on akinesia and analgesia induced by D-Ala²-Met-enkephalinamide were investigated in rats. Administration of taurine (dose range: 2.375×10^?2 M–9.5×10^?2 M/10 μl) into the left lateral ventricle 10 min prior to the injection of D-Ala²-Met-enkephalinamide (50 μg/10 μl) produced a dose-dependent reduction in the duration of akinesia and to some extent of analgesia, as estimated at 30 min and 60 min following the enkephalinamide injection; at the first estimation-time (10 min), taurine did not alter the duration of akinesia or that of analgesia. The median effective dose (ED₅₀) for akinesia determined at 60 min after D-Ala²-Met-enkephalinamide was 5 times greater and that for analgesia assessed at the same time was 1.7 times greater in taurine-treated rats than the respective doses in control animals. Administration of GABA under similar experimental conditions produced a dose-dependent reduction in the duration of analgesia from the initial estimation time (10 min) following the injection of D-Ala²-Met-enkephalinamide. The ED₅₀ for analgesia determined at 30 min after D-Ala²-Met-enkephalinamide was 3 times greater in GABA-treated rats than in control animals. Unlike the effects of taurine, GABA did not alter the duration of akinesia. Neither the duration of akinesia nor that of analgesia was modified by taurine or GABA alone in rats tested 9 min after the injection of each amino acid. These findings suggest that taurine may promote a recovery from both akinesia and analgesia, while GABA decreases only the analgesia induced by D-Ala²-Met-enkephalinamide.     

N-demethylation of p-chloro-N-methylaniline catalyzed by subcellular fractions from the avocado pear (Persea americana)

Subcellular fractions from the avocado pear ( Persea americana) catalyzed formation of p-chloroaniline from p-chloro-N-methylaniline. Fractions prepared by centrifugation of avocado homogenates at 20, 000g for 20 min formed p-chloroaniline (2900 +/- 500 pmol min-1 mg protein-1) with an NADPH-generating system. p-Chloroaniline formation required reduced pyridine nucleotide (NADPH was 6-7 times more effective than NADH) and O2. N-Demethylation was inhibited by CO (55% inhibition at CO:O2 = 1) and was not inhibited by CN. Cytochrome P-450 was detected in the 20, 000g pellet at levels of 300-380 pmol/mg protein. This particulate preparation was also active in catalyzing the NADPH-dependent epoxidation of the chlorinated cyclodiene aldrin. Improvements to a colorimetric procedure for measuring p-chloroaniline increased the sensitivity of the procedure fourfold, and allowed use of samples containing high amounts of lipid. Avocado pear is suitable tissue for further studies on the oxidation of foreign compounds by higher plants.     

Isolation and characterization of the rabbit prt gene product

The product of the rabbit prt gene (PRT), a gene linked to the immunoglobulin κ-light chain gene ab, was purified from rabbit serum by precipitation with ammonium sulfate and by chromotography on DEAE-Sephadex and Sephacryl S300. Analysis of PRT indicated that it was associated rabbit hemopexin; the molecular weight of PRT (i.e., 68,000), as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was similar to the reported molecular weight of rabbit hemopexin; the PRT phenotypes correlated with the phenotypes of a hematin binding protein; PRT itself bound hematin; and the amino acid composition of PRT was similar to the amino acid composition of rabbit hemopexin. The prt gene, however, need not be the structural gene for hemopexin; it may encode a glycosyl transferase responsible in part for the carbohydrate associated with the protein.