Yttrium-90 delivered via a centering catheter and afterloader, given both before and after stent implantation, inhibits neointima formation in porcine coronary arteries

Background: Intracoronary radiation (IR) studies have shown reduction of neointima formation (NF). Extrapolation of animal studies with beta-radiation to clinical trials have shown variable results, which may be related to dosimetry, centering issues, and/or shielding of beta-rays by the stent metal. We examined the effect of yttrium-90 (90Y), a pure beta-emitter delivered via an automatic afterloader to a centering catheter, on the inhibition of NF in balloon-injured (BI) porcine coronary arteries as well as in arteries receiving 90Y either prior to or following stent implantation (SI).Methods: Twenty-three swine (44 coronary arteries) were studied. In the first study, IR (18 Gy at 1.2 mm from the balloon surface) was administered in 17 arteries following BI, while eight control arteries were subjected to BI only. In the second study, 10 swine (19 coronary arteries) underwent SI. IR (18 Gy) was administered in six arteries before and in eight arteries after SI, while five control arteries received SI only. The animals were sacrificed 2 weeks after BI and 4 weeks after SI. Their coronaries were perfusion fixed and stained, and vessel parameters (intimal area [IA] and medial fracture length [FL]) were analyzed by computer-aided histomorphometry.Results: Arteries subjected to IR following BI had less NF compared to controls (IA/FL=0.14+/-0.2 mm vs. 0.49+/-0.2 mm; P=0.003). IA was reduced significantly in the arteries receiving radiation before and after SI compared to controls (0.92+/-0.98 and 0.00+/-0/00 vs. 2.72+/-1.2 mm(2); P=0.014), despite similar SI in all groups.Conclusions: IR with 90Y delivered via a centering catheter is safe and effective with complete and homogenous inhibition of NF in the context of BI or SI in the porcine coronary model.     

Discovery of new pyridoacridine alkaloids from Lissoclinum cf. badium that inhibit the ubiquitin ligase activity of Hdm2 and stabilize p53

Compounds that stabilize p53 could suppress tumors providing a additional tool to fight cancer. Mdm2, and the human ortholog, Hdm2 serve as ubiquitin E3 ligases and target p53 for ubiquitylation and degradation. Inhibition of Hdm2 stabilizes p53, inhibits cell proliferation and induces apoptosis. Using HTS to discover inhibitors, we identified three new alkaloids, isolissoclinotoxin B, diplamine B, and lissoclinidine B from Lissoclinum cf. badium. Lissoclinidine B inhibited ubiquitylation and degradation of p53, and selectively killed transformed cells harboring wild-type p53, suggesting this compound could be used to develop new treatments.     

Performance of 11 tree species under different management treatments in restoration plantings in a tropical dry forest

Ecological restoration in tropical dry forests urgently needs to incorporate experimental evidence to increase effectiveness. The main barriers for tree establishment are adverse microenvironmental conditions and competition with exotic grasses. Therefore, management should address such barriers in order to enhance tree performance. We evaluated the effect of plastic mulching, grass removal, and no management on survival after 2 months and stem volume and canopy size after 2 years and integrated response index (IRI) in plantings of 11 native tree species with different growth rates in pastures near the tropical dry forest of Chamela, Mexico. Results revealed that: (1) initial seedling mortality was minimal in all treatments (8%) and lowest under no management (2%); (2) plastic mulching, but not grass removal, leads to increased size for most species, irrespective of their growth rank; (3) a trade‐off between initial plant survival and size after 2 years occurred due to plastic mulching; and (4) most species showed similar values of the IRI because of high survival, stem volume, or canopy cover. Grass removal decreased early survival of all species and increased stem volume only for one slow‐growing species. The use of plastic mulching increased stem volume for slow‐growing species, whereas fast‐growing species developed larger canopies with that treatment. Effects of grass removal and mulching seem to be very species‐specific and not dependent in growth rank of species, although overall mulching seems to provide better conditions for seedling performance than grass removal alone.     

Drosophila PRL-1 Is a Growth Inhibitor That Counteracts the Function of the Src Oncogene

Phosphatase of Regenerating Liver (PRL) family members have emerged as molecular markers that significantly correlate to the ability of many cancers to metastasize. However, contradictory cellular responses to PRL expression have been reported, including the inhibition of cell cycle progression. An obvious culprit for the discrepancy is the use of dozens of different cell lines, including many isolated from tumors or cultured cells selected for immortalization which may have missing or mutated modulators of PRL function. We created transgenic Drosophila to study the effects of PRL overexpression in a genetically controlled, organismal model. Our data support the paradigm that the normal cellular response to high levels of PRL is growth suppression and furthermore, that PRL can counter oncogenic activity of Src. The ability of PRL to inhibit growth under normal conditions is dependent on a CAAX motif that is required to localize PRL to the apical edge of the lateral membrane. However, PRL lacking the CAAX motif can still associate indiscriminately with the plasma membrane and retains its ability to inhibit Src function. We propose that PRL binds to other membrane-localized proteins that are effectors of Src or to Src itself. This first examination of PRL in a model organism demonstrates that PRL performs as a tumor suppressor and underscores the necessity of identifying the conditions that enable it to transform into an oncogene in cancer.     

Effect of gelation temperature and gel-dissolving solution on cell viability and recovery of two Pseudomonas putida strains co-immobilized within calcium alginate or κ-carrageenan gel beads

Summary Since a lethal effect of an increased temperature (42°C) on Pseudomonas putida strains PaW8 and PaW130 was demonstrated, strictly ionotropic gels such as calcium alginate or -carrageenan type X 0909 were used for cell co-immobilization, rather than a thermoionotropic -carrageenan gel. Among the variety of gel-dissolving solutions tested, only a 0.05M Na₂CO₃/0.02M citric acid solution was able to preserve around 100 % of the cell viability. A complete cell recovery was obtained from calcium alginate gel beads, while only 6 % of viable cells was recovered from the ionotropic -carrageenan gel.     

Experimental optimization of a real time fed-batch fermentation process using Markov decision process

This article describes a methodology that implements a Markov decision process (MDP) optimization technique in a real time fed-batch experiment. Biological systems can be better modeled under the stochastic framework and MDP is shown to be a suitable technique for their optimization. A nonlinear input/output model is used to calculate the probability transitions. All elements of the MDP are identified according to physical parameters. Finally, this study compares the results obtained when optimizing ethanol production using the infinite horizon problem, with total expected discount policy, to previous experimental results aimed at optimizing ethanol production using a recombinant Escherichia coli fed-batch cultivation. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 317-327, 1997.     

Analysis of different methods to estimate fecundity in bivalve molluscs

Abstract

We analyzed the advantages and disadvantages of three methods to estimate potential fecundity in the bivalve molluscs Pinctada mazatlanica and Atrina maura, both species having commercial value in northwestern Mexico. Data of gonad samples collected during the breeding season in March 1999 (P. mazatlanica) and March 2003 (A. maura) were processed with histological techniques combined with Cavalieri’s Principle; stereological analysis of the gonad with the caliper method; and estimation of the theoretical radius of oocytes. These estimates were compared to a reference value obtained from direct counts of the number of oocytes stripped from the gonad. Compared to other methods, potential fecundity determined with the caliper method was more accurate in both species: A. maura (9.8–15 × 10⁶ cells ind^?1 and P. mazatlanica (10.8–17 × 10⁶ cells ind^?1). The potential of the caliper method, combined with image analysis software may offer accurate estimates of aspects of reproduction in different bivalve species, which has direct applications in hatcheries and conservation programs.     

Differential Inhibitory Effects of Cyanovirin-N,Griffithsin, and Scytovirin on Entry Mediated by Envelopes of Gammaretroviruses and Deltaretroviruses

The antiviral lectins griffithsin (GRFT), cyanovirin-N (CV-N), and scytovirin (SVN), which inhibit several enveloped viruses, including lentiviruses, were examined for their ability to inhibit entry mediated by Env proteins of delta- and gammaretroviruses. The glycoproteins from human T-cell leukemia virus type 1 (HTLV-1) were resistant to the antiviral effects of all three lectins. For gammaretroviruses, CV-N inhibited entry mediated by some but not all of the envelopes examined, whereas GRFT and SVN displayed only little or no effect.     

High resolution HPLC method with reverse phase C18 symmetry™ column for the analysis of tetracyclines produced by Streptomyces aureofaciens immobilized in Ca-alginate gel

Summary To analyse the effect of immobilization of Streptomyces aureofaciens in Ca-alginate on tetracycline production, an HPLC technique for direct injection of the culture medium has been developed. The high resolution obtained with this method is achieved by using a Symmetry C18^TM reverse phase HPLC column. The comparison of our results with those previously described by different authors, shows that highest performances are obtained without using relatively drastic conditions such as 0.2 M oxalic acid at pH 2. Thus, our method, which has shown a very good reproducibility for hundreds of injections, is also better for life-time column preservation.