Adventitial Tertiary Lymphoid Organs as Potential Source of MicroRNA Biomarkers for Abdominal Aortic Aneurysm

Abdominal aortic aneurysm (AAA) is an inflammatory disease associated with marked changes in the cellular composition of the aortic wall. This study aims to identify microRNA (miRNA) expression in aneurysmal inflammatory cells isolated by laser microdissection from human tissue samples. The distribution of inflammatory cells (neutrophils, B and T lymphocytes, mast cells) was evaluated in human AAA biopsies. We observed in half of the samples that adventitial tertiary lymphoid organs (ATLOs) with a thickness from 0.5 to 2 mm were located exclusively in the adventitia. Out of the 850 miRNA that were screened by microarray in isolated ATLOs (n = 2), 164 miRNAs were detected in ATLOs. The three miRNAs (miR-15a-3p, miR-30a-5p and miR-489-3p) with the highest expression levels were chosen and their expression quantified by RT-PCR in isolated ATLOs (n = 4), M1 (n = 2) and M2 macrophages (n = 2) and entire aneurysmal biopsies (n = 3). Except for the miR-30a-5p, a similar modulation was found in ATLOs and the two subtypes of macrophages. The modulated miRNAs were then evaluated in the plasma of AAA patients for their potential as AAA biomarkers. Our data emphasize the potential of miR-15a-3p and miR-30a-5p as biomarkers of AAA but also as triggers of ATLO evolution. Further investigations will be required to evaluate their targets in order to better understand AAA pathophysiology.     

Conception and Evaluation of Fluorescent Phosphine-Gold Complexes: From Synthesis to in vivo Investigations

A phosphine gold(I) and phosphine-phosphonium gold(I) complexes bearing a fluorescent coumarin moiety were synthesized and characterized. Both complexes displayed interesting photophysical properties: good molar absorption coefficient, good quantum yield of fluorescence, and ability to be tracked in vitro thanks to two-photon imaging. Their in vitro and in vivo biological properties were evaluated onto cancer cell lines both human and murine and into CT26 tumor-bearing BALB/c mice. They displayed moderate to strong antiproliferative properties and the phosphine-phosphonium gold(I) complex induced significant in vivo anti-cancer effect.     

Modulation of Cellular Fate of Vinyl Triarylamines through Structural Fine Tuning: To Stay or Not To Stay in the Mitochondria?

Mitochondria are involved in many cellular pathways and dysfunctional mitochondria are linked to various diseases. Hence efforts have been made to design mitochondria-targeted fluorophores for monitoring the mitochondrial status. However, the factors that govern the mitochondria-targeted potential of dyes are not well-understood. In this context, we synthesized analogues of the TP-2Bzim probe belonging to the vinyltriphenylamine (TPA) class and already described for its capacity to bind nuclear DNA in fixed cells and mitochondria in live cells. These analogues ( TP-1Bzim, TPⁿ-2Bzim, TP¹⁺-2Bzim, TN-2Bzim ) differ in the cationic charge, the number of vinylbenzimidazolium branches and the nature of the triaryl core. Using microscopy, we demonstrated that the cationic derivatives accumulate in mitochondria but do not reach mtDNA. Under depolarisation of the mitochondrial membrane, TP-2Bzim and TP¹⁺-2Bzim translocate to the nucleus in direct correlation with their strong DNA affinity. This reversible phenomenon emphasizes that these probes can be used to monitor ΔΨ_m variations.     

Bacterial spores in spices and dried herbs: The risks for processed food

Production and world consumption of spices are constantly increasing. Although the antimicrobial properties of some spices are well documented, their use in the agri-food industry is also responsible for microbial contamination and spoilage. Bacterial spores introduced by spices can withstand different preparation processes, particularly thermal treatments, leading to food alterations during storage. This review brings together data from the literature about the prevalence and concentrations of spore-forming bacteria in all commercially available spices. The sporeformers found in spices belong mainly to the genera Bacillus and Clostridium. Such contaminations are very common and sometimes reach high levels, as in pepper and turmeric. Bacillus licheniformis and Bacillus cereus are the most frequently detected species. Studying the harvesting, processing, and storage procedures for spices provides elements to explain why high prevalence and concentrations are observed. Spices are mostly produced in developing countries on small farms using traditional production methods. Spices become contaminated by bacterial spores in two main ways: by contact with soil during harvesting or drying, as for pepper, or by cross-contamination during the water-cooking step, as for turmeric. From these observations, we propose some recommendations. Different methods that can be used to eliminate bacterial spores from spices are presented indicating their efficiency and the limitations of their use.     

Template Synthesis of Iminodiacetic Acid Polysiloxane Immobilized Ligand Systems and their Metal Uptake Capacity

Porous solid polysiloxane ligand systems bearing an iminodiacetic acid chelating ligand of the general formula P-IDA (where P- represents [Si-O] _n polysiloxane network and IDA represent an organofunctional group) were achieved in two-step reaction. The first step includes a template synthesis of 3-iodopropylpolysiloxane (P-I) or 3-aminopropylpolysiloxane (P-MA) by hydrolytic polycondensation of TEOS and the corresponding silane agent in the presence of CTAB as a surfactant. The second step includes a modification of 3-iodopropylpolysiloxane with diethyliminodiacetate or 3-aminopropylpolysiloxane with ethylchloroacetate to produce IDA-functionalized polysiloxane ligand systems P-IDA-I & P-IDA-II respectively. It was found that the modified IDA-functionalized polysiloxane ligand systems exhibited higher capacities for uptake of the metal ions (Ni ²⁺, Cu ²⁺ and Pb ²⁺) than those prepared without surfactants.     

MicroRNA Profiling of B Cell Subsets from Systemic Lupus Erythematosus Patients Reveals Promising Novel Biomarkers

MicroRNAs control the differentiation and function of B cells, which are considered key elements in the pathogenesis of systemic lupus erythematosus (SLE). However, a common micro(mi)RNA signature has not emerged since published data includes patients of variable ethnic background, type of disease, and organ involvement, as well as heterogeneous cell populations. Here, we aimed at identifying a miRNA signature of purified B cells from renal and non-renal severe SLE patients of Latin American background, a population known to express severe disease. Genome-wide miRNA expression analyses were performed on naive and memory B cells and revealed two categories of miRNA signatures. The first signature represents B cell subset-specific miRNAs deregulated in SLE: 11 and six miRNAs discriminating naive and memory B cells of SLE patients from healthy controls (HC), respectively. Whether the miRNA was up or down-regulated in memory B cells as compared with naive B cells in HC, this difference was abolished in SLE patients, and vice versa. The second signature identifies six miRNAs associated with specific pathologic features affecting renal outcome, providing a further understanding for SLE pathogenesis. Overall, the present work provided promising biomarkers in molecular diagnostics for disease severity as well as potential new targets for therapeutic intervention in SLE.     

Personalization of cardiac motion and contractility from images using variational data assimilation

Personalization is a key aspect of biophysical models in order to impact clinical practice. In this paper, we propose a personalization method of electromechanical models of the heart from cine-MR images based on the adjoint method. After estimation of electrophysiological parameters, the cardiac motion is estimated based on a proactive electromechanical model. Then cardiac contractilities on two or three regions are estimated by minimizing the discrepancy between measured and simulation motion. Evaluation of the method on three patients with infarcted or dilated myocardium is provided.     

Intracellular Fate of Hydrophobic Nanocrystal Self‐Assemblies in Tumor Cells

Control of interactions between nanomaterials and cells remains a biomedical challenge. A strategy is proposed to modulate the intralysosomal distribution of nanoparticles through the design of 3D suprastructures built by hydrophilic nanocrystals (NCs) coated with alkyl chains. The intracellular fate of two water‐dispersible architectures of self‐assembled hydrophobic magnetic NCs: hollow deformable shells (colloidosomes) or solid fcc particles (supraballs) is compared. These two self‐assemblies display increased cellular uptake by tumor cells compared to dispersions of the water‐soluble NC building blocks. Moreover, the self‐assembly structures increase the NCs density in lysosomes and close to the lysosome membrane. Importantly, the structural organization of NCs in colloidosomes and supraballs are maintained in lysosomes up to 8 days after internalization, whereas initially dispersed hydrophilic NCs are randomly aggregated. Supraballs and colloidosomes are differently sensed by cells due to their different architectures and mechanical properties. Flexible and soft colloidosomes deform and spread along the biological membranes. In contrast, the more rigid supraballs remain spherical. By subjecting the internalized suprastructures to a magnetic field, they both align and form long chains. Overall, it is highlighted that the mechanical and topological properties of the self‐assemblies direct their intracellular fate allowing the control intralysosomal density, ordering, and localization of NCs.     

Studies of the pulse charge of lead-acid batteries for photovoltaic applications: Part IV. Pulse charge of the negative plate

The paper discusses the influence of the state of charge and pulse charge frequency on the mechanism of the lead-acid battery recharge with pulse current. The data from the pulse charge transients of the negative plate potential at various frequencies show that a decrease of the pulse charge frequency keeping constant average pulse current can impede the charge reaction leading to earlier start of the hydrogen evolution reaction. The dependence of the electrochemical double layer (EDL) capacitance on the state of charge was estimated both during the charge and the discharge using electrochemical impedance spectroscopy measurements at open circuit, followed by equivalent circuit modelling. These data were used to derive the dependence of the average double layer current on SOC and pulse charge frequency. The results show that in the end of the charge almost all of the charge proceeds with the participation of EDL in a certain pulse frequency domain. Using the data from the impedance measurements the optimal pulse charge frequencies were predicted, considering the existence of “electrochemical resonance”. The latter appears when the pulse charge frequency approaches the characteristic frequency of the Pb electrodeposition process, given by the product between EDL capacitance and the charge transfer resistance.     

Binary integer programming formulations for scheduling in market-driven foundries

This paper describes the development and solution of binary integer formulations for production scheduling problems in market-driven foundries. This industrial sector is comprised of small and mid-sized companies with little or no automation, working with diversified production, involving several different metal alloy specifications in small tailor-made product lots. The characteristics and constraints involved in a typical production environment at these industries challenge the formulation of mathematical programming models that can be computationally solved when considering real applications. However, despite the interest on the part of these industries in counting on effective methods for production scheduling, there are few studies available on the subject. The computational tests prove the robustness and feasibility of proposed models in situations analogous to those found in production scheduling at the analyzed industrial sector.