Neural Crest-Derived Stem Cells (NCSCs) Obtained from Dental-Related Stem Cells (DRSCs): A Literature Review on Current Knowledge and Directions toward Translational Applications

Evidence from dental-related stem cells (DRSCs) suggests an enhanced potential for ectodermal lineage differentiation due to their neural crest origin. Growing evidence that DRSC cultures can produce cells with a neural crest-derived stem cell (NCSC)-like phenotype supports their potential for future therapeutic approaches for neurodegenerative diseases and nerve injuries. However, most of the evidence is limited to the characterization of DRSCs as NCSCs by detecting the expression of neural crest markers. Only a few studies have provided proof of concept of an improved neuro-glial differentiation or direct applicability in relevant models. In addition, a current problem is that several of the existing protocols do not meet manufacturing standards for transferability to a clinical scenario. This review describes the current protocols to obtain NCSCs from DRSCs and their characterization. Also, it provides important considerations from previous work where DRSCs were established and characterized as mesenchymal stromal cells but studied for their neuro-glial differentiation potential. The therapeutic advancement of DRSCs would depend on establishing protocols that can yield a neural crest-like phenotype efficiently, using appropriate manufacturing standards and testing them in relevant models of disease or injury. Achieving these conditions could then facilitate and validate the therapeutic potential of DRSC-NCSCs in regenerative therapies.     

Assessment of Mineralogical,Textural, and Water Chemistry Changes During Long-Distance Tailings-Slurry Transport

An exploratory study demonstrated that subtle changes in solids and process water were caused by long-distance turbulent transport of tailings from the concentrator to the impoundment of a Cu (Mo) porphyry copper deposit. Slurry water chemical analysis was complemented by modelling potential phase precipitation or dissolution and speciation of dissolved metals. It was found that transport did not affect major insoluble mineral phases. However, the degrees of liberation of several phyllosilicates, as determined by automated mineralogy, were reduced close to the impoundment, which points to separation of clay particles from tectosilicate surfaces by the turbulence; this also was observed by SEM examination of micro-aggregate specimens. Reduction of maximum particle sizes, increased N2 monolayer adsorption, and resultant specific surface areas indicate that transport modified the micro-aggregates. Major element water chemistry is controlled by the presence of soluble mineral phases, such as gypsum, and reagents, such as lime, in the flotation process. Changes in the dissolved concentrations of some elements could potentially affect tailings deportment in the impoundment. Increased concentrations of Al may affect the clay settling behaviour, while Mo and As levels will require treatment prior to the discharge of water from the tailings impoundment. This study demonstrated that systematic scrutiny of tailings slurries leaving the concentrator and before entering the impoundment can be potentially useful, though care will have to be exercised to replicate sample handling and analytical conditions, during any long-term monitoring.     

A review of adaptive online learning for artificial neural networks

In real applications learning algorithms have to address several issues such as, huge amount of data, samples which arrive continuously and underlying data generation processes that evolve over time. Classical learning is not always appropriate to work in these environments since independent and indentically distributed data are assumed. Taking into account the requirements of the learning process, systems should be able to modify both their structures and their parameters. In this survey, our aim is to review the developed methodologies for adaptive learning with artificial neural networks, analyzing the strategies that have been traditionally applied over the years. We focus on sequential learning, the handling of the concept drift problem and the determination of the network structure. Despite the research in this field, there are currently no standard methods to deal with these environments and diverse issues remain an open problem.     

ESR spectra of copper complexes of cellulose

The ESR spectra of complexes of fibrous cotton cellulose and cupriammonia dihydroxide or cupriethylene diamine dihydroxide under various experimental conditions were determined. The spectra of both complexes with cotton cellulose were almost identical at ?100 and 25°C. The spectrum of the complex of cupriethylene diamine dihydroxide with cellulose was stable to temperatures as high as 100°C. The sum of the linewidths of the hyperfine components of the spectra for each complex was about 180 gauss. Cotton fibers were combed and aligned with their axes (lengths) parallel to the magnetic field (B_∥); after formation of either of the complexes with cellulose a minumum of hyperfine structure of components centered at H_∥ was observed. A maximum of hyperfine structure of these components was observed when the complexed fibers were aligned with their axes perpendicular to the magnetic field (B_⊥). The opposite was true of components centered at H_⊥. For a complex of cupriethylene diamine dihydroxide and cellulose at 25°C. and at high pH the g_∥ was 2.2127 and the g_∥ was 2.0476. It was suggested that the alignment of most of the complex was its axis of symmetry at a maximum angle to the axes of the cotton fiber, when the axes of the fibers were in the parallel alignment with the magnetic field. At high pH these observations were even more marked. When ramie was used with cupriethylene diamine dihydroxide at high pH, the contribution of components centered at H_∥ to the spectra was zero. Spectra for the copper compounds alone and complexed with cellobiose are also reported.     

Serendipitous Identification of a Covalent Activator of Liver Pyruvate Kinase

Enzymes are effective biological catalysts that accelerate almost all metabolic reactions in living organisms. Synthetic modulators of enzymes are useful tools for the study of enzymatic reactions and can provide starting points for the design of new drugs. Here, we report on the discovery of a class of biologically active compounds that covalently modifies lysine residues in human liver pyruvate kinase (PKL), leading to allosteric activation of the enzyme (EC₅₀=0.29 μM). Surprisingly, the allosteric activation control point resides on the lysine residue K282 present in the catalytic site of PKL. These findings were confirmed by structural data, MS/MS experiments, and molecular modelling studies. Altogether, our study provides a molecular basis for the activation mechanism and establishes a framework for further development of human liver pyruvate kinase covalent activators.     

Residual stress versus microstructural effects on the strength and toughness of phase-separated PbO–B2O3–Al2O3 glasses

A few authors have reasonably proposed that liquid–liquid phase-separated (LLPS) glasses could show improved fracture strength, S_f, and toughness, K_Ic, as the second phase could provide a barrier to crack propagation via deflection, bowing, trapping, or bridging. Due to the associated tensile or compressive residual stresses, the second phase could also act as a toughening or a weakening mechanism. In this work, we investigated five glasses of the PbO–B₂O₃–Al₂O₃ system spanning across the miscibility gap: Four of them undergo LLPS—three are binodal (two B₂O₃-rich and one PbO-rich) and one is spinodal—and one does not show LLPS (composition outside the miscibility gap). Their compositions were designed in such a way that the amorphous particles are under compressive residual stresses in some and under tensile residual stresses in others. The following mechanical properties were determined: the Vickers hardness, ball on three balls (B3B) strength, and toughness, K_Ic-SEVNB (single-edge V-notch beam [SEVNB]). The microstructures and compositions were analyzed using scanning electron microscopy with energy-dispersive X-ray spectrometry. The spinodal glass showed, by far, the best mechanical properties. Its K_Ic-SEVNB = 1.6 ± 0.1 MPa m^1/2, which embodies an increase of almost 50% over the B₂O₃-rich binodal composition, and 90% considering the PbO-rich binodal composition. Moreover, its fracture strength, S_f = 166 ± 7 MPa, is one of the highest ones ever reported for an LLPS glass. Fracture analyses evidenced that the spinodal composition exhibited the lowest net stress at the fracture point. Moreover, calculations indicate that the internal residual stress level is the lowest in the spinodal glass. The overall results indicate that the microstructural effect of the spinodal glass is the most significant factor for its superior mechanical properties. This work corroborates the idea that LLPS provides a feasible and stimulating solution to improve the mechanical properties of glasses.     

Ligand Binding Promiscuity of Human Liver Fatty Acid Binding Protein: Structural and Dynamic Insights from an Interaction Study with Glycocholate and Oleate

Human liver fatty acid binding protein (hL‐FABP) has been reported to act as an intracellular shuttle of lipid molecules, thus playing a central role in systemic metabolic homeostasis. The involvement of hL‐FABP in the transport of bile salts has been postulated but scarcely investigated. Here we describe a thorough NMR investigation of glycocholate (GCA) binding to hL‐FABP. The protein molecule bound a single molecule of GCA, in contrast to the 1:2 stoichiometry observed with fatty acids. GCA was found to occupy the large internal cavity of hL‐FABP, without requiring major conformational rearrangement of the protein backbone; rather, this led to increased stability, similar to that estimated for the hL‐FABP:oleate complex. Fast‐timescale dynamics appeared not to be significantly perturbed in the presence of ligands. Slow motions (unlike for other proteins of the family) were retained or enhanced upon binding, consistent with a requirement for structural plasticity for promiscuous recognition.     

A COMPARATIVE STUDY OF KINETIC MODELS FOR ION-EXCHANGE USING MACROPOROUS RESINS AND CONCENTRATED SOLUTIONS

ABSTRACT

A “shallow bed” technique was employed for the study of the kinetics of K⁺ ? H⁺ exchange in concentrated solutions with a macroporous ion-exchange resin. Six kinetic models were applied to the experimental data. The fitting of the mathematical models and the behaviour of the kinetic curves when some variables change, show that there does not exist any model based on the Donnan exclusion principle suitable for explaining the experimental data. The best model in these extreme conditions is a modification of the Progressive Conversion mechanism. It can be easily applied to the design of industrial operations.     

The Efficacy of the Quorum Sensing Inhibitor FS8 and Tigecycline in Preventing Prosthesis Biofilm in an Animal Model of Staphylococcal Infection

We investigated the efficacy of tigecycline and FS8, alone or combined, in preventing prosthesis biofilm in a rat model of staphylococcal vascular graft infection. Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with 2 × 10⁷ colony-forming units of Staphylococcus aureus, strain Smith diffuse. The study included a control group, a contaminated group that did not receive any antibiotic prophylaxis, and three contaminated groups that received: (i) intraperitoneal tigecycline, (ii) FS8-soaked graft, and (iii) tigecycline plus FS8-soaked graft, respectively. Each group included 15 animals. The infection burden was evaluated by using sonication and quantitative agar culture. Moreover, an in vitro binding-study was performed to quantify the how much FS8 was coated to the surface of the prosthesis. Tigecycline, combined with FS8, against the adherent bacteria showed MICs (2.00 mg/L) and MBCs (4.00 mg/L) four-fold lower with respect to tigecycline alone in in vitro studies. The rat groups treated with tigecycline showed the lowest bacterial numbers (4.4 × 10⁴ ± 1.2 × 10⁴ CFU/mL). The FS8-treated group showed a good activity and significant differences compared to control group with bacterial numbers of 6.8 × 10⁴ ± 2.0 × 10⁴ CFU/mL. A stronger inhibition of bacterial growth was observed in rats treated with a combined FS8 and tigecycline therapy than in those that were singly treated with bacterial numbers of 10¹ CFU/mL graft. In conclusion, the ability to affect biofilm formation as well, its property to be an antibiotic enhancer suggests FS8 as alternative or additional agent to use in conjunction with conventional antimicrobial for prevention of staphylococcal biofilm related infection.     

Modification of the optical and structural properties of ZnO nanowires by low-energy Ar+ ion sputtering

The effects of low-energy (≤2 kV) Ar⁺ irradiation on the optical and structural properties of zinc oxide (ZnO) nanowires (NWs) grown by a simple and cost-effective low-temperature technique were investigated. Both photoluminescence spectra from ZnO NW-coated films and cathodoluminescence analysis of individual ZnO NWs demonstrated obvious evidences of ultraviolet/visible luminescent enhancement with respect to irradiation fluence. Annihilation of the thinner ZnO NWs after the ion bombardment was appreciated by means of high-resolution scanning electron microscopy and transmission electron microscopy (TEM), which results in an increasing NW mean diameter for increasing irradiation fluences. Corresponding structural analysis by TEM pointed out not only significant changes in the morphology but also in the microstructure of these NWs, revealing certain radiation-sensitive behavior. The possible mechanisms accounting for the decrease of the deep-level emissions in the NWs with the increasing irradiation fluences are discussed according to their structural modifications.