Genomics and the renaissance of generalism

A meeting report of the sessions on human, eukaryotic and bacterial genome sequencing at the American Society for Microbiology and Institut Pasteur joint conference: Genomes 2000 International Conference on Microbial and Model Genomes, Paris, April 11-15, 2000     

Identification of Small Molecules with Type I Interferon Inducing Properties by High-Throughput Screening

The continuous emergence of virus that are resistant to current anti-viral drugs, combined with the introduction of new viral pathogens for which no therapeutics are available, creates an urgent need for the development of novel broad spectrum antivirals. Type I interferon (IFN) can, by modulating the cellular expression profile, stimulate a non-specific antiviral state. The antiviral and adjuvant properties of IFN have been extensively demonstrated; however, its clinical application has been so far limited. We have developed a human cell-based assay that monitors IFN-β production for use in a high throughput screen. Using this assay we screened 94,398 small molecules and identified 18 compounds with IFN-inducing properties. Among these, 3 small molecules (C3, E51 and L56) showed activity not only in human but also in murine and canine derived cells. We further characterized C3 and showed that this molecule is capable of stimulating an anti-viral state in human-derived lung epithelial cells. Furthermore, the IFN-induction by C3 is not diminished by the presence of influenza A virus NS1 protein or hepatitis C virus NS3/4A protease, which make this molecule an interesting candidate for the development of a new type of broad-spectrum antiviral. In addition, the IFN-inducing properties of C3 also suggest its potential use as vaccine adjuvant.     

Solid cancer risk dependence on the Pasquill–Gifford atmospheric stability classes in a radiological event

In a radiological event, the lack of preliminary information about the site of explosion and the difficulty in predicting the accurate path and distribution of radioactive plumes makes it difficult to predict expected health effects of exposed individuals. So far, in such a health evaluation, radiation-induced stochastic health effects such as cancer are not included. The Pasquill–Gifford atmospheric classes generally allow connecting atmospheric stability with dispersion of radioactive contaminants to the environment. In this work, an environmental release of radioactive Cs-137 was simulated and the resulting relative risk for solid cancer incidence among the affected population calculated. The HotSpot health physics code was used to simulate the radioactive atmospheric dispersion and calculate the Total Effective Dose Equivalent (TEDE), which was then used to estimate the relative risk of cancer incidence. The main results from this work suggest that the relative cancer risk and atmospheric stability classes are linked by differences in the TEDE. Such a finding may support triage, because it adds additional information on the potentially affected population at the early stages of an emergency response.     

Acute administration of the organochalcogen 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one induces biochemical and hematological disorders in male rats

Organochalcogens are extensively produced and employed by industry and agriculture, and the risk of occupational and environmental toxicity to them has been poorly understood. Here, we investigated the acute effect of a new organochalcogen 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on biochemical and hematological parameters in male Wistar rats. The animals were treated with a single intraperitoneal injection of the organochalcogen at doses of 125, 250 or 500 μg·kg(-1). After 60 min, the animals were sacrificed by decapitation, and the trunk blood was collected for determination of glucose, triglycerides, cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase, lactate dehydrogenase, urea, creatinine, C-reactive protein, red blood cells, hematocrit, hemoglobin and white blood cells (WBC). Our results showed a reduction in cholesterol levels in all treated groups, an increase in ALT activity at doses of 250 and 500 μg·kg(-1), a decrease of hemoglobin and an increase in WBC in animals that received 250 and 500 μg·kg(-1) of the organoselenium. In addition, we observed an increase in neutrophil counts at 125 μg·kg(-1) dose and a decrease at 500 μg·kg(-1) dose. We also verified an increase in lymphocyte counts at the dose of 500 μg·kg(-1). Thus, the present study shows that the acute treatment with this new organochalcogen causes biochemical changes and hematological disorders in male rats.     

Climate and geographic distance are more influential than rivers on the beta diversity of passerine birds in Amazonia

Variation in the spatial structure of communities in terms of species composition (beta diversity) is affected by different ecological processes, such as environmental filtering and dispersal limitation. Large rivers are known as barriers for species dispersal (riverine hypothesis) in tropical regions. However, when organisms are not dispersal limited by geographic barriers, other factors, such as climatic conditions and geographic distance per se, may affect species distribution. In order to investigate the relative contribution of major rivers, climate and geographic distance on Passeriformes beta diversity, we divided Amazonia into 549 grid cells (1° of latitude and longitude) and obtained data of species occurrence, climate and geographic position for each cell. Beta diversity was measured using taxonomic, phylogenetic and functional metrics of composition. The influence of climatic variables, geographic distance and rivers on these metrics was tested using regression analyses. Passerine beta diversity is characterized mainly by the change in species taxonomic identity and in phylogenetic lineages across climatic gradients and over geographic distance. However, species with similar traits are found throughout the entire Amazonia. The size of rivers was proportional to their effect on species composition. However, climate and geographic distance are relatively more important than rivers for Amazonian taxonomic and phylogenetic species composition.     

Fetal calf serum enhances in vitro production of Bos taurus indicus embryos

The objective of this study was to determine the effect of fetal calf serum (FCS) on the quality of in vitro produced bovine embryos. Cumulus oocyte-complexes (COCs, n = 2 449) recovered by ovum pick-up from Bos taurus indicus donors were randomly assigned to experimental groups. Sperm selected by Percoll gradient was used for in vitro fertilization (insemination = Day 0). In Experiment 1 (n = 1 745 COCs), zygotes were cultured in vitro in Synthetic Oviduct Fluid + 4 mg/mL of bovine serum albumin (BSA), or BSA + 2% FCS (BSA+FCS). In Experiment 2 (n = 704 COCs), the COCs were cultured in SOF + BSA, BSA + 2% FCS, or BSA + 2% FCS on D4 (BSA + FCSD4). In Experiment 1, blastocyst yield (51%) and Quality I blastocysts (41%) at Day 7 were higher (P < 0.05) in the BSA + FCS treatment than in BSA (42 and 30%, respectively). In Experiment 2, blastocyst yield was higher (P < 0.05) in the BSA+FCS (47%) treatment. Quality I blastocyst yield was higher (P < 0.05) for BSA + FCS (34%) and BSA+FCSD4 (32%) compared to the BSA treatment (20%). A total of 820 embryos were transferred, with no significant differences among groups in pregnancy rates. In conclusion, in vitro culture in SOFaaci + BSA + FCS enhanced blastocyst yield and Quality I blastocysts; adding FCS to the culture medium increased the efficiency of IVP of bovine embryos.     

The organochalcogen 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one induces oxidative stress in heart, liver, and kidney of rats

The objective of this study was to investigate the in vitro effects of the organochalcogen 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on some parameters of oxidative stress in liver, kidney, and heart of 10-day-old rats. The homogenates of liver, kidney, and heart were incubated for 1 h in the absence (control) or in the presence of 1, 10, or 30 μM of the organoselenium and thiobarbituric acid reactive substances, carbonyl, and the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) were measured. First, we tested the influence of the compound on 1,1-diphenyl-2-picrylhydrazyl (DPPH(?)) radical scavenging and verified that the organochalcogen did not have any antioxidant properties. We observed an increase of lipid peroxidation in all concentrations tested in heart and kidney, while in liver only in the concentrations of 10 and 30 μM. Moreover, we also verified an enhance of protein oxidation in the concentrations of 10 and 30 μM in kidney. On the other hand, the compound caused a reduction on the activity of CAT in heart (10 and 30 μM), liver (30 μM), and kidney (30 μM). The activity of SOD was increased in heart (10 and 30 μM), while in liver (30 μM) and in kidney (10 and 30 μM) the activity was reduced. Our findings indicate that this organoselenium compound induces oxidative stress in liver, heart, and kidney of immature rats, collaborating to the fact that these tissues are potential targets for the organochalcogen action.     

Efficient hydrogen production from ethanol and glycerol by vapour-phase reforming processes with new cobalt-based catalysts

The aim of this study was to investigate biohydrogen production from biofuel-reforming processes using new multi-component bulk-type cobalt-based catalysts. The addition of different components to improve the catalytic performance was studied. Monometallic cobalt catalyst and catalysts containing Ru (ca. 1%) and/or Na (ca. 0.5%) were characterized and tested in the 623-673 K temperature range in ethanol steam reforming (ESR) with a steam/carbon ratio (S/C) of 3. The catalysts showed a high performance for hydrogen production and, except for H(2) and CO(2), only small amounts of by-products were obtained, depending on the temperature and the catalyst used. The catalyst containing both Ru and Na (Co-Ru(Na)) showed the best catalytic behavior in ESR. It operated stably for at least 12 days under cycles of oxidative steam reforming of glycerol/ethanol mixtures (S/C=2) and activation under O(2).