Reduction of blood pressure,plasma cholesterol,and atherosclerosis by elevated endothelial nitric oxide

In the vascular system, nitric oxide is generated by endothelial NO synthase (eNOS). NO has pleiotropic effects, most of which are believed to be atheroprotective. Therefore, it has been argued that patients suffering from cardiovascular disease could benefit from an increase in eNOS activity. However, increased NO production can cause oxidative damage, cell toxicity, and apoptosis and hence could be atherogenic rather than beneficial. To study the in vivo effects of increased eNOS activity, we created transgenic mice overexpressing human eNOS. Aortic blood pressure was approximately 20 mm Hg lower in the transgenic mice compared with control mice because of lower systemic vascular resistance. The effects of eNOS overexpression on diet-induced atherosclerosis were studied in apolipoprotein E-deficient mice. Elevation of eNOS activity decreased blood pressure ( approximately 20 mm Hg) and plasma levels of cholesterol ( approximately 17%), resulting in a reduction in atherosclerotic lesions by 40%. We conclude that an increase in eNOS activity is beneficial and provides protection against atherosclerosis.     

Unaltered Nodulation Competitiveness of a Strain of Bradyrhizobium sp. (Lotus) after a Decade in Soil

A Bradyrhizobium sp. (Lotus) strain that formed a soil population that was highly competitive for nodulation of Lotus pedunculatus 11 years after its introduction into a field soil and a culture of the same strain stored lyophilized were compared with an antibiotic-resistant mutant in respect of their nodulation competitiveness. The mutant was less competitive than the wild-type strain it was isolated from and had to be present at a cell ratio of 5.76:1 in mixed inoculum in sand culture to form 50% of the nodules on L. pedunculatus (50% nodulation value, 5.76). The 50% nodulation values for a soil population of the mutant mixed with soil populations of the lyophilized and field soil strain were, respectively, 6.83 and 5.77, indicating that the field soil strain was not significantly different from the lyophilized strain in nodulation competitiveness. A 50% nodulation value of 11.18 obtained when soil containing a recently established mutant population was mixed with the field soil containing the population established 11 years before, indicating that the plant infection technique underestimated cell numbers of the field soil population by 100%. Nodulation competitiveness was unaffected by the size of the strain populations in the range of 100 to 1,000 cells per g of soil; at 10 cells per g a significant correlation between strain ratios in nodules and in soil was still evident. The results indicated that apparently superior nodulation competitiveness of a well-established soil population relative to that of a subsequently introduced strain may not necessarily reflect the intrinsic competitive abilites of the strain(s) involved. The soil strain did not differ from laboratory-maintained cultures in antigenic properties, effectiveness, or whole cell protein electrophoresis profiles.     

Calling on a million minds for community annotation in WikiProteins

WikiProteins enables community annotation in a Wiki-based system. Extracts of major data sources have been fused into an editable environment that links out to the original sources. Data from community edits create automatic copies of the original data. Semantic technology captures concepts co-occurring in one sentence and thus potential factual statements. In addition, indirect associations between concepts have been calculated. We call on a 'million minds' to annotate a 'million concepts' and to collect facts from the literature with the reward of collaborative knowledge discovery. The system is available for beta testing at http://www.wikiprofessional.org.     

Which gene did you mean?

Computational Biology needs computer-readable information records. Increasingly, meta-analysed and pre-digested information is being used in the follow up of high throughput experiments and other investigations that yield massive data sets. Semantic enrichment of plain text is crucial for computer aided analysis. In general people will think about semantic tagging as just another form of text mining, and that term has quite a negative connotation in the minds of some biologists who have been disappointed by classical approaches of text mining. Efforts so far have tried to develop tools and technologies that retrospectively extract the correct information from text, which is usually full of ambiguities. Although remarkable results have been obtained in experimental circumstances, the wide spread use of information mining tools is lagging behind earlier expectations. This commentary proposes to make semantic tagging an integral process to electronic publishing.     

Competitive Abilities of Rhizobium meliloti Strains Considered to Have Potential as Inoculants

Twenty four strains of Rhizobium meliloti considered to have potential for inoculant production were grouped in pairs and tested for their ability to compete for nodulation on Medicago sativa, Medicago truncatula, and Medicago littoralis. At the outset, each pair of strains, which consisted of a wild type and a selected streptomycin-resistant mutant of another strain, was tested in an autoclaved soil. Six strain pairs, each consisting of a good and a poor competitor, reacted consistently when tested in each of five other autoclaved soils; eight pairs consisting of strains with comparable competitive abilities varied in their reactions in some of the soils, or even in the same soil when retested. An effect of soil pH on competitive ability was observed with some of these strains. Not all of the strains identified as good competitors on one or more of the Medicago spp. in the autoclaved soils were able to nodulate these plants satisfactorily in a field soil containing an established population of R. meliloti. Strain RF24, which seemed to be the best competitor on each of the three Medicago spp., grouped among the less effective strains on two of the legumes. Two strains of R. meliloti frequently used for inoculant production differed markedly with regard to competitive ability; this places some doubt on the relevancy of singling out competitive ability for special attention when selecting a strain for inoculant production.     

Essential fatty acids in erythrocyte phospholipids during pregnancy and at delivery in mothers and their neonates: comparison with plasma phospholipids

Evidence that the essential fatty acid (EFA) status during pregnancy and at birth may not be optimal is mainly based on fatty acid profiles of maternal and neonatal plasma phospholipids. However, erythrocyte phospholipids may be more reliable than plasma phospholipids to reflect the EFA status of an individual. Therefore, the present study compares the levels of EFA and of their derivatives (LCPUFA) in erythrocyte and plasma phospholipids collected during pregnancy and at delivery of 184 women and of their infants at birth. In general, the relative concentrations of erythrocyte and plasma phospholipid fatty acids (% of total fatty acids) were strongly correlated, but not at early pregnancy. The overall changes in fatty acid concentrations during pregnancy were qualitatively comparable between erythrocytes and plasma, although the comparability became less towards the end of pregnancy. The changes in absolute amounts (mg/l) of fatty acids in erythrocyte and plasma phospholipids also compare quite well till 32 weeks of gestation, but not thereafter. Most maternal-neonatal differences in relative fatty acid concentrations are qualitatively comparable for erythrocyte and plasma phospholipids. However, significant differences were observed for the absolute amounts of arachidonic and docosahexaenoic acids. No matter these differences, plasma and erythrocyte phospholipids seem equally suitable to reliably quantify the more functional EFA and LCPUFA status based on fatty acid ratios. Correlations between neonatal and maternal fatty acid values at delivery/birth are highly significant in erythrocyte as well as plasma phospholipids. Neonatal erythrocyte (but not plasma) values also correlated strongly with maternal values at early pregnancy. Therefore, the neonatal EFA and LCPUFA status might be predicted on the basis of EFA and LCPUFA concentrations of maternal erythrocyte phospholipids at early pregnancy.     

Phosphatidylinositol transfer protein alpha regulates growth and apoptosis of NIH3T3 cells: involvement of a cannabinoid 1-like receptor

Mouse fibroblast cells overexpressing phosphatidylinositol transfer protein alpha [PI-TPalpha; sense PI-TPalpha (SPIalpha) cells] show a significantly increased rate of proliferation and an extreme resistance toward ultraviolet- or tumor necrosis factor-alpha-induced apoptosis. The conditioned medium (CM) from SPIalpha cells or the neutral lipid extract from CM stimulated the proliferation of quiescent wild-type NIH3T3 cells. CM was also highly effective in increasing resistance toward induced apoptosis in both wild-type cells and the highly apoptosis-sensitive SPIbeta cells (i.e., wild-type cells overexpressing PI-TPbeta). CM from SPIalpha cells grown in the presence of NS398, a specific cyclooxygenase-2 (COX-2) inhibitor, expressed a diminished mitogenic and antiapoptotic activity. This strongly suggests that at least one of the bioactive factor(s) is an eicosanoid. In accordance, SPIalpha cells express enhanced levels of COX-1 and COX-2. The antiapoptotic activity of CM from SPIalpha cells tested on SPIbeta cells was inhibited by approximately 50% by pertussis toxin and suramin as well as by SR141716A, a specific antagonist of the cannabinoid 1 receptor. These inhibitors had virtually no effect on the COX-2-independent antiapoptotic activity of CM from SPIalpha cells. The latter results imply that PI-TPalpha mediates the production of a COX-2-dependent eicosanoid that activates a G-protein-coupled receptor, most probably a cannabinoid 1-like receptor.     

Online tools to support literature-based discovery in the life sciences

In biomedical research, the amount of experimental data and published scientific information is overwhelming and ever increasing, which may inhibit rather than stimulate scientific progress. Not only are text-mining and information extraction tools needed to render the biomedical literature accessible but the results of these tools can also assist researchers in the formulation and evaluation of novel hypotheses. This requires an additional set of technological approaches that are defined here as literature-based discovery (LBD) tools. Recently, several LBD tools have been developed for this purpose and a few well-motivated, specific and directly testable hypotheses have been published, some of which have even been validated experimentally. This paper presents an overview of recent LBD research and discusses methodology, results and online tools that are available to the scientific community.     

The mannose receptor mediates dengue virus infection of macrophages

Macrophages (MØ) and mononuclear phagocytes are major targets of infection by dengue virus (DV), a mosquito-borne flavivirus that can cause haemorrhagic fever in humans. To our knowledge, we show for the first time that the MØ mannose receptor (MR) binds to all four serotypes of DV and specifically to the envelope glycoprotein. Glycan analysis, ELISA, and blot overlay assays demonstrate that MR binds via its carbohydrate recognition domains to mosquito and human cell–produced DV antigen. This binding is abrogated by deglycosylation of the DV envelope glycoprotein. Surface expression of recombinant MR on NIH3T3 cells confers DV binding. Furthermore, DV infection of primary human MØ can be blocked by anti-MR antibodies. MR is a prototypic marker of alternatively activated MØ, and pre-treatment of human monocytes or MØ with type 2 cytokines (IL-4 or IL-13) enhances their susceptibility to productive DV infection. Our findings indicate a new functional role for the MR in DV infection.