Quantitative determination of gene strand bias in prokaryotic genomes

Comparative genometrics of microorganisms is a relatively new area, in which genome properties are translated into numerical indexes. Such indexes can be used for a comprehensive and comparative analysis of microbial genomes, contributing to the understanding of their evolution. This work presents a new method for quantitative determination of gene strand bias in prokaryotic chromosomes, in which data transformation of gene position skew leads to a numerical index that can be applied to quantitative comparisons of genome organization. It was applied in the comparative analysis of 49 completely sequenced Firmicutes genomes, allowing the distinction of groups defined according to their patterns of gene strand preference. The resulting groups revealed that, regarding gene strand bias, reduced genomes are, in general, the more disordered among Firmicutes, while genomes of extremophile organisms comprehend those with the highest degree of genome organization in this phylum.     

Viability of phenanthrene biodegradation by an isolated bacterial consortium: optimization and scale-up

In the present work, biodegradation of phenanthrene by a bacterial consortium (LB2), isolated from lab-polluted soils has been investigated. The 16S rRNA gene-based molecular analysis revealed that the bacterial consortium LB2 consisted of two strains showing a very high homology with Staphylococcus warneri and Bacillus pumilus. The optimization of phenanthrene degradation by the consortium LB2, using a central composite face-centered design was carried out taking into account three important parameters such as temperature, pH, and phenanthrene concentration. Near complete phenanthrene degradation was reached by consortium LB2 at the optimal conditions (pH of 7.5 and 37.5 °C) in less than 48 h. Moreover, the efficiency of phenanthrene biodegradation was assessed by using logistic and Luedeking and Piret-type models. Finally, the process was implemented at bench-scale bioreactor and the main degradation routes were identified based on GC-MS data.     

β-Amyloid carrying the Dutch mutation has diverse effects on calpain-mediated toxicity in hippocampal neurons

Hereditary cerebral hemorrhage with amyloidosis-Dutch type is a disorder associated with a missense mutation (E693Q) in the β-amyloid (Aβ)-coding region of the amyloid precursor protein (APP). This familial disease is characterized by cognitive deficits secondary to intracerebral hemorrhage and, in some cases, progressive Alzheimer's disease (AD)-like dementia. Although this mutation was the first ever reported in the human APP gene, little is known about the molecular mechanisms underlying the direct toxic effects of this mutated Aβ on central neurons. In the present study, we assessed the role of calpain-mediated toxicity in such effects using an AD primary culture model system. Our results showed that Dutch mutant Aβ (E22Q) induced calpain-mediated cleavage of dynamin 1 and a significant decrease in synaptic contacts in mature hippocampal cultures. These synaptic deficits were similar to those induced by wild-type (WT) Aβ. In contrast, calpain-mediated tau cleavage leading to the generation of a 17-kDa neurotoxic fragment, as well as neuronal death, were significantly reduced in E22Q Aβ-treated neurons when compared with WT Aβ-treated ones. This complex regulation of the calpain-mediated toxicity pathway by E22Q Aβ could have some bearing in the pathobiology of this familial AD form.     

Corema album Leaves Mediate DNA Damage in Triple-Negative Breast Cancer Cells

Corema (C.) album is a shrub endemic to the Atlantic coast and has been described as yielding beneficial effects for human health. Nevertheless, studies concerning the bioactivity of C. album leaves are scarce. This study aims at investigating the anticancer potential and mode of action, of an hydroethanolic extract of C. album leaves (ECAL) on triple-negative breast cancer. This is a poor survival breast cancer subtype, owing to its high risk of distant reappearance, metastasis rates and the probability of relapse. The ECAL ability to prevent tumor progression through (i) the inhibition of cell proliferation (cell viability); (ii) the induction of apoptosis (morphological changes, TUNEL assay, caspase-3 cleaved) and (iii) the induction of DNA damage (PARP1 and γH2AX) with (iv) the involvement of NF-κB and of ERK1/2 pathways (AlphaScreen assay) was evaluated. ECAL activated the apoptotic pathway (through caspase-3) along with the inhibition of ERK and NF-κB pathways causing DNA damage and cell death. The large polyphenolic content of ECAL was presumed to be accountable for these effects. The extract of C. album leaves can target multiple pathways and, thus, can block more than one possible means of disease progression, evidencing the anticancer therapeutic potential from a plant source.     

Personalized Modeling for Prediction with Decision-Path Models

Deriving predictive models in medicine typically relies on a population approach where a single model is developed from a dataset of individuals. In this paper we describe and evaluate a personalized approach in which we construct a new type of decision tree model called decision-path model that takes advantage of the particular features of a given person of interest. We introduce three personalized methods that derive personalized decision-path models. We compared the performance of these methods to that of Classification And Regression Tree (CART) that is a population decision tree to predict seven different outcomes in five medical datasets. Two of the three personalized methods performed statistically significantly better on area under the ROC curve (AUC) and Brier skill score compared to CART. The personalized approach of learning decision path models is a new approach for predictive modeling that can perform better than a population approach.     

Recombinant Escherichia coli heat-labile enterotoxin B subunit humoral adjuvant effect depends on dose and administration route

Information on the use of Escherichia coli heat-labile enterotoxin B subunit (LTB) as a parenteral adjuvant is scarce. We evaluate the adjuvant effect of different concentrations of recombinant LTB (rLTB), as well as the influence of administration route (intramuscular and subcutaneous) on mice immune response. The use of 10 μg/dose of rLTB as adjuvant of an inactivated vaccine composed by Suid herpesvirus type 1 (SuHV-1), used to immunize mice intramuscularly, induced the highest average titers of anti-SuHV-1 antibodies (P < 0.05). The same vaccines used subcutaneously induced lower titers of antibodies. The lower the anti-rLTB humoral response determined by ELISA, the higher was its adjuvant activity. In the challenge experiment with SuHV-1, 56% (14/25) (P < 0.05) of the animals inoculated intramuscularly and 32% (8/25) inoculated subcutaneously survived, highlighting the influence of the concentration and the route of administration of rLTB on its performance as an adjuvant. Therefore, rLTB can significantly help in the induction of immunity against SuHV-1 in mice, especially if used intramuscularly in the concentration of 10 μg/dose, representing the best cost-benefit ratio.     

Lipid-Free Antigen B Subunits from Echinococcus granulosus: Oligomerization,Ligand Binding,and Membrane Interaction Properties

BackgroundThe hydatid disease parasite Echinococcus granulosus has a restricted lipid metabolism, and needs to harvest essential lipids from the host. Antigen B (EgAgB), an abundant lipoprotein of the larval stage (hydatid cyst), is thought to be important in lipid storage and transport. It contains a wide variety of lipid classes, from highly hydrophobic compounds to phospholipids. Its protein component belongs to the cestode-specific Hydrophobic Ligand Binding Protein family, which includes five 8-kDa isoforms encoded by a multigene family (EgAgB1-EgAgB5). How lipid and protein components are assembled into EgAgB particles remains unknown. EgAgB apolipoproteins self-associate into large oligomers, but the functional contribution of lipids to oligomerization is uncertain. Furthermore, binding of fatty acids to some EgAgB subunits has been reported, but their ability to bind other lipids and transfer them to acceptor membranes has not been studied.Conclusions/SignificanceWe show that EgAgB apolipoproteins can oligomerize in the absence of lipids, and can bind and transfer fatty acids to phospholipid membranes. Since imported fatty acids are essential for Echinococcus granulosus, these findings provide a mechanism whereby EgAgB could engage in lipid acquisition and/or transport between parasite tissues. These results may therefore indicate vulnerabilities open to targeting by new types of drugs for hydatidosis therapy.