Impact of tire debris on in vitro and in vivo systems

Background  

It is estimated that over 80% of respirable particulate matter (PM₁₀) in cities comes from road transport and that tire and brake wear are responsible for the 3–7% emission of it. Data on the indicators of environmental impact of tire debris (TD), originated from the tire abrasion on roads, are extremely scarce, even though TD contains chemicals (zinc and organic compounds) which can be released in the environment.     

Nucleation behavior of blended high‐melting fractions of milk fat as affected by emulsifiers

The effect of highly hydrophobic emulsifiers, the palmitic sucrose ester P‐170 (hydrophilic/lipophilic balance (HLB) = 1.0), the stearic sucrose ester S‐170 (HLB = 1.0), the polyglycerol ester decaglycerol decastearate DAS 7S (HLB = 3.7) and the polyglycerol ester decaglycerol dodecabehenate DDB 750 (HLB = 2.6), on the nucleation of a high melting point milk fat fraction (HMF) and its blends with sunflower oil (SFO) was investigated by polarized laser light turbidimetry, X‐ray diffractometry and polarized light microscopy (PLM). Addition of polyglycerol esters accelerated nucleation, giving shorter induction times for the same supercooling. On the contrary, sucrose esters inhibited nucleation since induction times were elongated in all conditions selected. Addition of emulsifiers modified the polymorphic behavior in the blends with SFO. The β' form was promoted especially with the addition of S‐170. DAS 7S and DDB 750 promoted crystallization. PLM images showed many small crystals that did not appear in HMF images. Addition of P‐170 and S‐170 delayed nucleation and inhibited crystal growth. Crystals were notoriously smaller than the ones that appeared in HMF images. The Fisher–Turnbull model was used to calculate activation free energies of nucleation. In all cases, sucrose esters elevated the energy barrier for nucleation. Polyglycerol esters, however, if they had an effect on the energy barrier, lowered the values.     

Optimization of osmotic dehydration of yacon slices

Osmotic dehydration assisted by ultrasound (ODAU) at low temperatures reduces water activity (a_w) and maintains nutrients. The influence of solution concentration (SC; 20 to 60° Brix, xylitol and sorbitol) and ultrasound application time (t_us, 0 to 40 min) in ODAU of yacon was studied with the aid of a response surface method. The optimum condition with respect to mass transfer parameters, a_w, and fructan retention was SC of 60° Brix for both solutions and t_us of 2.67 min for xylitol samples and 0 min for sorbitol samples. The application of ultrasound improved dehydration but resulted in depolymerization of fructans.     

AICAR Protects Vascular Endothelial Cells from Oxidative Injury Induced by the Long-Term Palmitate Excess

Hyperlipidemia manifested by high blood levels of free fatty acids (FFA) and lipoprotein triglycerides is critical for the progression of type 2 diabetes (T2D) and its cardiovascular complications via vascular endothelial dysfunction. However, attempts to assess high FFA effects in endothelial culture often result in early cell apoptosis that poorly recapitulates a much slower pace of vascular deterioration in vivo and does not provide for the longer-term studies of endothelial lipotoxicity in vitro. Here, we report that palmitate (PA), a typical FFA, does not impair, by itself, endothelial barrier and insulin signaling in human umbilical vein endothelial cells (HUVEC), but increases NO release, reactive oxygen species (ROS) generation, and protein labeling by malondialdehyde (MDA) hallmarking oxidative stress and increased lipid peroxidation. This PA-induced stress eventually resulted in the loss of cell viability coincident with loss of insulin signaling. Supplementation with 5-aminoimidazole-4-carboxamide-riboside (AICAR) increased endothelial AMP-activated protein kinase (AMPK) activity, supported insulin signaling, and prevented the PA-induced increases in NO, ROS, and MDA, thus allowing to maintain HUVEC viability and barrier, and providing the means to study the long-term effects of high FFA levels in endothelial cultures. An upgraded cell-based model reproduces FFA-induced insulin resistance by demonstrating decreased NO production by vascular endothelium.     

Complex of HIV-1 Integrase with Cellular Ku Protein: Interaction Interface and Search for Inhibitors

The interaction of HIV-1 integrase and the cellular Ku70 protein is necessary for HIV replication due to its positive effect on post-integration DNA repair. We have previously described in detail the Ku70 binding site within integrase. However, the integrase binding site in Ku70 remained poorly characterized. Here, using a peptide fishing assay and site-directed mutagenesis, we have identified residues I72, S73, and I76 of Ku70 as key for integrase binding. The molecular dynamics studies have revealed a possible way for IN to bind to Ku70, which is consistent with experimental data. According to this model, residues I72 and I76 of Ku70 form a “leucine zipper” with integrase residues, and, therefore, their concealment by low-molecular-weight compounds should impede the Ku70 interaction with integrase. We have identified such compounds by molecular docking and have confirmed their capacity to inhibit the formation of the integrase complex with Ku70. Our data demonstrate that the site of IN binding within Ku70 identified in the present work may be used for further search for inhibitors of the integrase binding to Ku70.     

Rheokinematics for product development—Formulation screening in rotational rheometers

Product formulations for industrial processes are typically developed at laboratory scale. However, the mixing conditions are not easily mimicked in the laboratory. A rotational device is proposed in this study as a fast laboratory-scale formulation development, which enables mimicking the mixing conditions in the industrial process. The geometrical configurations of the rotational device are from rheometry devices (plate-plate and cone-plate). The main advantages of this method are the small amounts of raw materials and shorter testing times. This methodology is applied to an industrial case study, the reaction injection molding (RIM) process. The mixing length scales evolution in the rotational rheometer were matched to those in RIM machines. The main novelty of this study is the introduction of a protocol that bridges the processing conditions at laboratory using small amounts of raw materials to high throughput continuous flow reactors.     

Structure-Activity Relationships for 5′′ Modifications of 4,5-Aminoglycoside Antibiotics

Modification at the 5’’-position of 4,5-disubstituted aminoglycoside antibiotics (AGAs) to circumvent inactivation by aminoglycoside modifying enzymes (AMEs) is well known. Such modifications, however, unpredictably impact activity and affect target selectivity thereby hindering drug development. A survey of 5’’-modifications of the 4,5-AGAs and the related 5-O-furanosyl apramycin derivatives is presented. In the neomycin and the apralog series, all modifications were well-tolerated, but other 4,5-AGAs require a hydrogen bonding group at the 5’’-position for maintenance of antibacterial activity. The 5’’-amino modification resulted in parent-like activity, but reduced selectivity against the human cytosolic decoding A site rendering this modification unfavorable in paromomycin, propylamycin, and ribostamycin. Installation of a 5’’-formamido group and, to a lesser degree, a 5’’-ureido group resulted in parent-like activity without loss of selectivity. These lessons will aid the design of next-generation AGAs capable of circumventing AME action while maintaining high antibacterial activity and target selectivity.