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.     

Hot-Water Extraction Optimization of Sugar Maple (Acer saccharum Marsh.) and Red Maple (Acer rubrum L.) Bark Applying Principal Component Analysis

In the forest industry, bark is an abundant residue, predominantly converted into calorific energy. As the antioxidant potential of phenolic compounds from sugar maple (Acer saccharum Marsh.) and red maple (Acer rubrum L.) bark has previously been established, the present study focused on the hot-water extraction optimization of these barks. Several process parameters (maple species, temperature, duration, ratio bark/water, particle size) were thus studied and large disparities were found between the two species. Extraction yield, phenolic content, and antioxidant capacity of red maple extracts were several times higher than those of sugar maple extracts. Principal component analysis, applied to the selected best extraction conditions, identified 3–4 clusters depending on the maple species. These groups were sorted from the highest extraction yield and energy consumption combined with the lowest phenolic content and antioxidant capacity, to moderate extraction yield and energy consumption with the highest phenolic content and antioxidant capacity.     

Modeling the dynamics of tamponade multicomponent gases during retina reattachment surgery

Vitrectomy and pneumatic retinopexy are common surgical procedures used to treat retinal detachment. To reattach the retina, gases are used to inflate the vitreous space allowing the retina to attach by surface tension and buoyancy forces that are superior to the location of the bubble. These procedures require the injection of either a pure tamponade gas, such as C₃F₈ or SF₆, or mixtures of these gases with air. The location of the retinal detachment, the anatomical spread of the retinal defect, and the length of time the defect has persisted, will determine the suggested volume and duration of the gas bubble to allow reattachment. After inflation, the gases are slowly absorbed by the blood allowing the vitreous to be refilled by aqueous. We have developed a model of the mass transfer dynamics of tamponade gases during pneumatic retinopexy or pars plana vitrectomy procedures. The model predicts the expansion and persistence of intraocular gases (C₃F₈, SF₆), oxygen, nitrogen, and carbon dioxide, as well as the intraocular pressure. The model was validated using published literature in rabbits and humans. In addition to correlating the mass transfer dynamics by surface area, permeability, and partial pressure driving forces, the mass transfer dynamics are affected by the percentage of the tamponade gases. Rates were also correlated with the physical properties of the tamponade and blood gases. The model gave accurate predictions in humans. © 2017 American Institute of Chemical Engineers AIChE J, 63: 3651–3662, 2017     

MODELING VACUUM-CONTACT DRYING OF WOOD: THE WATER POTENTIAL APPROACH

ABSTRACT

A two-dimensional mathematical model for vacuum-contact drying of wood is presented. The moisture and heat equations are based on the water potential concept whereas the pressure equation is formulated considering unsteady state conservation equation of dry air. Most of the model parameters were determined during independent experiments. The set of equations is then solved in a coupled form using the finite element method. The validation of the model is performed using experimental results obtained during vacuum-contact drying of sugar maple sapwood. The experimental and calculated data are in good agreement. Nevertheless, some discrepancies are observed which can be attributed to the boundary conditions used and to the fact that heat transfer by convection was neglected.     

Discovery of an Acyclic Nucleoside Phosphonate that Inhibits Mycobacterium tuberculosis ThyX Based on the Binding Mode of a 5‐Alkynyl Substrate Analogue

The urgent need for new antibiotics poses a challenge to target un(der)exploited vital cellular processes. Thymidylate biosynthesis is one such process due to its crucial role in DNA replication and repair. Thymidylate synthases (TS) catalyze a crucial step in the biosynthesis of thymidine 5‐triphosphate (TTP), an elementary building block required for DNA synthesis and repair. To date, TS inhibitors have only been successfully applied in anticancer therapy due to their lack of specificity for antimicrobial versus human enzymes. However, the discovery of a new family of TS enzymes (ThyX) in a range of pathogenic bacteria that is structurally and biochemically different from the “classic” TS (ThyA) has opened the possibility to develop selective ThyX inhibitors as potent antimicrobial drugs. Here, the interaction of the known inhibitor 5‐(3‐octanamidoprop‐1yn‐1yl)‐2′‐deoxyuridine‐5′‐monophosphate ( 1 ) with Mycobacterium tuberculosis ThyX enzyme is explored using molecular modeling starting from published crystal structures, with further confirmation through NMR experiments. While the deoxyuridylate (dUMP) moiety of compound 1 occupies the cavity of the natural substrate in ThyX, the rest of the ligand (the “5‐alkynyl tail”) extends to the outside of the enzyme between two of its four subunits. The hydrophobic pocket that accommodates the alkyl part of the tail is formed by displacement of Tyr 44.C, Tyr 108.A and Lys 165.A. Changes to the resonance of the Lys 165 NH₃ group upon ligand binding were monitored in a titration experiment by 2D HISQC NMR. Guided by the results of the modeling and NMR studies, and inspired by the success of acyclic antiviral nucleosides, compounds where a 5‐alkynyl uracyl moiety is coupled to an acyclic nucleoside phosphonate (ANP) were synthesized and evaluated. Of the compounds evaluated, sodium (6‐(5‐(3‐octanamidoprop‐1‐yn‐1‐yl)‐2,4‐dioxo‐3,4‐dihydropyrimidin‐1(2H)‐yl)hexyl)phosphonate ( 3 e ) exhibited 43 % of inhibitory effect on ThyX at 50 μM . While only modest activity was achieved, this is the first example of an ANP inhibiting ThyX, and these results can be used to further guide structural modifications to this class to develop more potent compounds with potential application as antibacterial agents acting through a novel mechanism of action.     

Nanocomposite piezoelectric films of P(VDF‐TrFE)/LiNbO3

Piezoelectric films were prepared by incorporation of lithium niobate (LiNbO₃) nanoparticles into copolymer of vinylidene difluoride and trifluoroethylene. Nanoparticles of LiNbO₃ with ferroelectric phase were successfully synthesized and dispersed homogenously by ultrasonication in the copolymer matrix without any surfactant or surface functionalization. The nanocomposites were fully characterized by electronic microscopy, X‐ray diffraction, differential scanning calorimetry, dynamical mechanical analysis, and piezometer. Surprisingly, the copolymer matrix crystallinity and morphology were not affected by the incorporation of nanoparticles. Therefore the nanocomposites remained good mechanicals properties and high ferroelectricity coupled to nonlinear optical activity thanks to the noncentro symmetric space group of lithium niobate. This could be a novel approach to develop new multifunctional materials. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Design of poly(N‐acryloylglycine) materials for incorporation of microorganisms

To incorporate microorganisms and to preserve their integrity, new matrices of poly(N‐acryloylglycine) have been designed under appropriate conditions. To understand the interactions between the microorganisms and the organic part of the matrices, different conetworks of poly(N‐acryloylglycine) have been synthesized and characterized. Copolymerization with two crosslinkers was performed with different compositions. The thermal and swelling properties of conetworks are specifically controlled and compared. These investigations show that the swelling ratio of these materials is compatible with the incorporation of biomolecules in these matrices. They successfully permit Pseudomonasspecies 1625 bacteria incorporation. The biological activity of bacteria is also preserved, allowing the use of these materials for innovative biological applications. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 835‐841, 2013