Modeling the hydrogeochemical evolution of brine in saline systems: case study of the Sabkha of Oum El Khialate in South East Tunisia

We studied the effects of evaporation and groundwater flow on the formation of salt minerals in the Sabkha of Oum El Khialate in South East Tunisia, which contains large amounts of sulfate sodium mineral deposits. Due to the fact that there are no important surface water bodies present in this sabkha, transport of solutes is dominated by advection rather than mixing in lakes. For our study we used both analytical conservative and numerical reactive transport models. Results showed that salinity varies with distance and may reach very high levels near a watershed where the groundwater flux is zero. As a consequence, reactive transport simulations results showed that more minerals precipitate and water activity decreases values near this watershed. Model results also showed that a sequence of precipitating minerals could be deduced after 140,000 years. From the boundary of the sabkha towards the watershed the mineral sequence was dolomite, gypsum, magnesite, bloedite, halite and mirabilite. It was found that the amounts as well as the mineral precipitation distribution strongly depend on salinity and rates of inflowing water. (C) 2014 Elsevier Ltd. All rights reserved.Peer ReviewedPostprint (author’s final draft

Co-encapsulation of an antigen and CpG oligonucleotides into PLGA microparticles by TROMS technology.

It seems well established that CpG oligonucleotides Th1 biased adjuvant activity can be improved when closely associated with a variety of antigens in, for example, microparticles. In this context, we prepared 1-μm near non-charged PLGA 502 or PLGA 756 microparticles that loaded with high efficiency an antigen (50% ovalbumin (OVA), approximately) into their matrix and CpG-chitosan complexes (near to 20%) onto their surface maintaining OVA and CpG integrity intact. In the intradermal immunization studies, whereas OVA microencapsulated into PLGA 756 alone induced a strong humoral immune response assisted by a very clear Th1 bias (IgG2a/IgG1=0.875) that was decreased by CpG co-delivery (IgG2a/IgG1=0.55), the co-encapsulation of CpG with OVA in PLGA 502 particles significantly improved the antibody response and isotype shifting (IgG2a/IgG1=0.73) in comparison with mice immunized with OVA loaded PLGA 502 (IgG2a/IgG1=0). This improvement was not correlated with the cellular immune response where the effect of co-encapsulated CpG was rather negative (2030.2 pg/mL and 335.3 pg/mL IFN-g for OVA PLGA 502 for OVA CpG PLGA 502, respectively). These results underscore the critical role of polymer nature and microparticle characteristics to show the benefits of coencapsulating CpG motifs in close proximity with an antigen

Novel bioactive hydrophobic gentamicin carriers for the treatment of intracellular bacterial infections.

Gentamicin (GEN) is an aminoglycoside antibiotic with a potent antibacterial activity against a wide variety of bacteria. However, its poor cellular penetration limits its use in the treatment of infections caused by intracellular pathogens. One potential strategy to overcome this problem is the use of particulate carriers that can target the intracellular sites of infection. In this study GEN was ion paired with the anionic AOT surfactant to obtain a hydrophobic complex (GEN-AOT) that was formulated as a particulated material either by the Precipitation with a Compressed Antisolvent (PCA) method, or by encapsulation into poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs). The micronization of GEN-AOT by PCA yielded a particulated material with a higher surface area than the non-precipitated complex, while PLGA NPs within a size range of 250-330 nm and a sustained release of the drug over 70 days were obtained by preparing the NPs using the emulsion solvent evaporation method. For the first time, GEN encapsulation efficiency values around 100% were achieved for the different NP formulations with no signs of interaction between the drug and the polymer. Finally, in vitro studies against the intracellular bacteria Brucella melitensis, used as a model of intracellular pathogen, demonstrated that the bactericidal activity of GEN was unmodified after ion-pairing, precipitation or encapsulation into NPs. These results, encourage their use for treatment for infections caused by GEN sensitive intracellular bacteria

Cellular pharmacokinetics and intracellular activity against Listeria monocytogenes and Staphylococcus aureus of chemically modified and nanoencapsulated gentamicin

OBJECTIVES: The aim of this study was to investigate different hydrophobic gentamicin formulations [gentamicin-bis(2-ethylhexyl) sulfosuccinate (GEN-AOT), microstructured GEN-AOT (PCA GEN-AOT) and GEN-AOT-loaded poly(lactide-co-glycolide) acid (PLGA) nanoparticles (NPs)] in view of improving its therapeutic index against intracellular bacteria. The intracellular accumulation, subcellular distribution and intracellular activity of GEN-AOT and NPs in different monocytic-macrophagic cell lines were studied. METHODS: Human THP-1 and murine J774 phagocytic cells were incubated with GEN-AOT formulations at relevant extracellular concentrations [from 1× MIC to 18 mg/L (human C(max))], and their intracellular accumulation, subcellular distribution and toxicity were evaluated and compared with those of conventional unmodified gentamicin. Intracellular activity of the formulations was determined against bacteria showing different subcellular localizations, namely Staphylococcus aureus (phagolysosomes) and Listeria monocytogenes (cytosol). RESULTS: GEN-AOT formulations accumulated 2-fold (GEN-AOT) to 8-fold (GEN-AOT NPs) more than gentamicin in phagocytic cells, with a predominant subcellular localization in the soluble fraction (cytosol) and with no significant cellular toxicity. NP formulations allowed gentamicin to exert its intracellular activity after shorter incubation times and/or at lower concentrations. With an extracellular concentration of 10× MIC, a 1 log(10) decrease in S. aureus intracellular inoculum was obtained after 12 h instead of 24 h for NPs versus free gentamicin, and a static effect was observed against L. monocytogenes at 24 h with NPs, while free gentamicin was ineffective. CONCLUSIONS: GEN-AOT formulations yielded a high cellular accumulation, especially in the cytosol, which resulted in improved efficacy against both intracellular S. aureus and L. monocytogenes

Brucella abortus Choloylglycine Hydrolase Affects Cell Envelope Composition and Host Cell Internalization

Choloylglycine hydrolase (CGH, E.C. 3.5.1.24) is a conjugated bile salt hydrolase that catalyses the hydrolysis of the amide bond in conjugated bile acids. Bile salt hydrolases are expressed by gastrointestinal bacteria, and they presumably decrease the toxicity of host's conjugated bile salts. Brucella species are the causative agents of brucellosis, a disease affecting livestock and humans. CGH confers Brucella the ability to deconjugate and resist the antimicrobial action of bile salts, contributing to the establishment of a successful infection through the oral route in mice. Additionally, cgh-deletion mutant was also attenuated in intraperitoneally inoculated mice, which suggests that CGH may play a role during systemic infection other than hydrolyzing conjugated bile acids. To understand the role CGH plays in B. abortus virulence, we infected phagocytic and epithelial cells with a cgh-deletion mutant (Δcgh) and found that it is defective in the internalization process. This defect along with the increased resistance of Δcgh to the antimicrobial action of polymyxin B, prompted an analysis of the cell envelope of this mutant. Two-dimensional electrophoretic profiles of Δcgh cell envelope-associated proteins showed an altered expression of Omp2b and different members of the Omp25/31 family. These results were confirmed by Western blot analysis with monoclonal antibodies. Altogether, the results indicate that Brucella CGH not only participates in deconjugation of bile salts but also affects overall membrane composition and host cell internalization

Computational approaches to explainable artificial intelligence: Advances in theory, applications and trends

Deep Learning (DL), a groundbreaking branch of Machine Learning (ML), has emerged as a driving force in both theoretical and applied Artificial Intelligence (AI). DL algorithms, rooted in complex and non-linear artificial neural systems, excel at extracting high-level features from data. DL has demonstrated human-level performance in real-world tasks, including clinical diagnostics, and has unlocked solutions to previously intractable problems in virtual agent design, robotics, genomics, neuroimaging, computer vision, and industrial automation. In this paper, the most relevant advances from the last few years in Artificial Intelligence (AI) and several applications to neuroscience, neuroimaging, computer vision, and robotics are presented, reviewed and discussed. In this way, we summarize the state-of-the-art in AI methods, models and applications within a collection of works presented at the 9th International Conference on the Interplay between Natural and Artificial Computation (IWINAC). The works presented in this paper are excellent examples of new scientific discoveries made in laboratories that have successfully transitioned to real-life applications.MCIU - Nvidia(UMA18-FEDERJA-084

Brucella abortus Uses a Stealthy Strategy to Avoid Activation of the Innate Immune System during the Onset of Infection

To unravel the strategy by which Brucella abortus establishes chronic infections, we explored its early interaction with innate immunity. Methodology/Principal Findings Brucella did not induce proinflammatory responses as demonstrated by the absence of leukocyte recruitment, humoral or cellular blood changes in mice. Brucella hampered neutrophil (PMN) function and PMN depletion did not influence the course of infection. Brucella barely induced proinflammatory cytokines and consumed complement, and was strongly resistant to bactericidal peptides, PMN extracts and serum. Brucella LPS (BrLPS), NH-polysaccharides, cyclic glucans, outer membrane fragments or disrupted bacterial cells displayed low biological activity in mice and cells. The lack of proinflammatory responses was not due to conspicuous inhibitory mechanisms mediated by the invading Brucella or its products. When activated 24 h post-infection macrophages did not kill Brucella, indicating that the replication niche was not fusiogenic with lysosomes. Brucella intracellular replication did not interrupt the cell cycle or caused cytotoxicity in WT, TLR4 and TLR2 knockout cells. TNF-α-induction was TLR4- and TLR2-dependent for live but not for killed B. abortus. However, intracellular replication in TLR4, TLR2 and TLR4/2 knockout cells was not altered and the infection course and anti-Brucella immunity development upon BrLPS injection was unaffected in TLR4 mutant mice. Conclusion/Significance We propose that Brucella has developed a stealth strategy through PAMPs reduction, modification and hiding, ensuring by this manner low stimulatory activity and toxicity for cells. This strategy allows Brucella to reach its replication niche before activation of antimicrobial mechanisms by adaptive immunity. This model is consistent with clinical profiles observed in humans and natural hosts at the onset of infection and could be valid for those intracellular pathogens phylogenetically related to Brucella that also cause long lasting infections

Computational Approaches to Explainable Artificial Intelligence:Advances in Theory, Applications and Trends

Deep Learning (DL), a groundbreaking branch of Machine Learning (ML), has emerged as a driving force in both theoretical and applied Artificial Intelligence (AI). DL algorithms, rooted in complex and non-linear artificial neural systems, excel at extracting high-level features from data. DL has demonstrated human-level performance in real-world tasks, including clinical diagnostics, and has unlocked solutions to previously intractable problems in virtual agent design, robotics, genomics, neuroimaging, computer vision, and industrial automation. In this paper, the most relevant advances from the last few years in Artificial Intelligence (AI) and several applications to neuroscience, neuroimaging, computer vision, and robotics are presented, reviewed and discussed. In this way, we summarize the state-of-the-art in AI methods, models and applications within a collection of works presented at the 9 International Conference on the Interplay between Natural and Artificial Computation (IWINAC). The works presented in this paper are excellent examples of new scientific discoveries made in laboratories that have successfully transitioned to real-life applications

Computational approaches to Explainable Artificial Intelligence:Advances in theory, applications and trends

Deep Learning (DL), a groundbreaking branch of Machine Learning (ML), has emerged as a driving force in both theoretical and applied Artificial Intelligence (AI). DL algorithms, rooted in complex and non-linear artificial neural systems, excel at extracting high-level features from data. DL has demonstrated human-level performance in real-world tasks, including clinical diagnostics, and has unlocked solutions to previously intractable problems in virtual agent design, robotics, genomics, neuroimaging, computer vision, and industrial automation. In this paper, the most relevant advances from the last few years in Artificial Intelligence (AI) and several applications to neuroscience, neuroimaging, computer vision, and robotics are presented, reviewed and discussed. In this way, we summarize the state-of-the-art in AI methods, models and applications within a collection of works presented at the 9th International Conference on the Interplay between Natural and Artificial Computation (IWINAC). The works presented in this paper are excellent examples of new scientific discoveries made in laboratories that have successfully transitioned to real-life applications.</p