An Iron Refractory Phenotype in Obese Adipose Tissue Macrophages Leads to Adipocyte Iron Overload

Adipocyte iron overload is a maladaptation associated with obesity and insulin resistance. The objective of the current study was to determine whether and how adipose tissue macrophages (ATMs) regulate adipocyte iron concentrations and whether this is impacted by obesity. Using bone marrow-derived macrophages (BMDMs) polarized to M0, M1, M2, or metabolically activated (MMe) phenotypes, we showed that MMe BMDMs and ATMs from obese mice have reduced expression of several iron-related proteins. Furthermore, the bioenergetic response to iron in obese ATMs was hampered. ATMs from iron-injected lean mice increased their glycolytic and respiratory capacities, thus maintaining metabolic flexibility, while ATMs from obese mice did not. Using an isotope-based system, we found that iron exchange between BMDMs and adipocytes was regulated by macrophage phenotype. At the end of the co-culture, MMe macrophages transferred and received more iron from adipocytes than M0, M1, and M2 macrophages. This culminated in a decrease in total iron in MMe macrophages and an increase in total iron in adipocytes compared with M2 macrophages. Taken together, in the MMe condition, the redistribution of iron is biased toward macrophage iron deficiency and simultaneous adipocyte iron overload. These data suggest that obesity changes the communication of iron between adipocytes and macrophages and that rectifying this iron communication channel may be a novel therapeutic target to alleviate insulin resistance.     

Assessing the Morphological and Behavioral Toxicity of Catechol Using Larval Zebrafish

Catechol is a ubiquitous chemical used in the manufacturing of fragrances, pharmaceuticals and flavorants. Environmental exposure occurs in a variety of ways through industrial processes, during pyrolysis and in effluent, yet despite its prevalence, there is limited information regarding its toxicity. While the genotoxicity and gastric carcinogenicity of catechol have been described in depth, toxicological studies have potentially overlooked a number of other effects relevant to humans. Here, we have made use of a general and behavioral larval zebrafish toxicity assay to describe previously unknown catechol-based toxicological phenomena. Behavioral testing revealed catechol-induced hypoactivity at concentrations an order of magnitude lower than observable endpoints. Catechol exposure also resulted in punctate melanocytes with concomitant decreases in the expression of pigment production and regulation markers mitfa, mc1r and tyr. Because catechol is converted into a number of toxic metabolites by tyrosinase, an enzyme found almost exclusively in melanocytes, an evaluation of the effects of catechol on these cells is critical to evaluating the safety of this chemical. This work provides insights into the toxic nature of catechol and highlights the benefits of the zebrafish larval testing platform in being able to dissect multiple aspects of toxicity with one model.     

A Novel Cartesian Plot Analysis for Fixed Monolayers That Relates Cell Phenotype to Transfer of Contents between Fibroblasts and Cancer Cells by Cell-Projection Pumping

We recently described cell-projection pumping as a mechanism transferring cytoplasm between cells. The uptake of fibroblast cytoplasm by co-cultured SAOS-2 osteosarcoma cells changes SAOS-2 morphology and increases cell migration and proliferation, as seen by single-cell tracking and in FACS separated SAOS-2 from co-cultures. Morphological changes in SAOS-2 seen by single cell tracking are consistent with previous observations in fixed monolayers of SAOS-2 co-cultures. Notably, earlier studies with fixed co-cultures were limited by the absence of a quantitative method for identifying sub-populations of co-cultured cells, or for quantitating transfer relative to control populations of SAOS-2 or fibroblasts cultured alone. We now overcome that limitation by a novel Cartesian plot analysis that identifies individual co-cultured cells as belonging to one of five distinct cell populations, and also gives numerical measure of similarity to control cell populations. We verified the utility of the method by first confirming the previously established relationship between SAOS-2 morphology and uptake of fibroblast contents, and also demonstrated similar effects in other cancer cell lines including from melanomas, and cancers of the ovary and colon. The method was extended to examine global DNA methylation, and while there was no clear effect on SAOS-2 DNA methylation, co-cultured fibroblasts had greatly reduced DNA methylation, similar to cancer associated fibroblasts.     

An artificial neural network based decision support system for solving the buffer allocation problem in reliable production lines

One of the major design problems in the context of manufacturing systems is the well-known Buffer Allocation Problem (BAP). This problem arises from the cost involved in terms of space requirements on the production floor and the need to keep in mind the decoupling impact of buffers in increasing the throughput of the line. Production line designers often need to solve the Buffer Allocation Problem (BAP), but this can be difficult, especially for large production lines, because the task is currently highly time consuming. Designers would be interested in a tool that would rapidly provide the solution to the BAP, even if only a near optimal solution is found, especially when they have to make their decisions at an operational level (e.g. hours). For decisions at a strategic level (e.g. years), such a tool would provide preliminary results that would be useful, before attempting to find the optimal solution with a specific search algorithm.     

Vibrational Energy Transport in Hybrid Ordered/Disordered Nanocomposites: Hybridization and Avoided Crossings of Localized and Delocalized Modes

Vibrational energy transport in disordered media is of fundamental importance to several fields spanning from sustainable energy to biomedicine to thermal management. This work investigates hybrid ordered/disordered nanocomposites that consist of crystalline membranes decorated by regularly patterned disordered regions formed by ion beam irradiation. The presence of the disordered regions results in reduced thermal conductivity, rendering these systems of interest for use as nanostructured thermoelectrics and thermal device components, yet their vibrational properties are not well understood. Here, the mechanism of vibrational transport and the reason underlying the observed reduction is established in detail. The hybrid systems are found to exhibit glass‐crystal duality in vibrational transport. Lattice dynamics reveals substantial hybridization between the localized and delocalized modes, which induces avoided crossings and harmonic broadening in the dispersion. Allen/Feldman theory shows that the hybridization and avoided crossings are the dominant drivers of the reduction. Anharmonic scattering is also enhanced in the patterned nanocomposites, further contributing to the reduction. The systems exhibit features reminiscent of both nanophononic materials and locally resonant nanophononic metamaterials, but operate in a manner distinct to both. These findings indicate that such “patterned disorder” can be a promising strategy to tailor vibrational transport through hybrid nanostructures.     

EFFECT OF HETEROCYCLIC AMINE ADDITIVES ON THE ABSORPTION RATES OF CARBONYL SULFIDE AND CARBON DIOXIDE IN AQUEOUS METHYLDIETHANOLAMINE SOLUTIONS

Absorption rates of carbonyl sulfide and carbon dioxide into aqueous methyldiethanolamine solutions with and without heterocyclic amine additives were measured in a stirred cell apparatus. All of the heterocyclic amine additives catalyzed COS absorption more strongly than that for CO₂. In instances in which absorption rates were improved by the additives, those with the lowest pK_b's were the most effective, although steric factors also apparently influence reaction kinetics.     

Losses of pectic substances during cooking and the effect of water hardness

Differences in the extent of loss of pectic substances from potato (Solanum tuberosum L.) after boiling, steaming and pressure cooking were investigated. Losses were found to be significantly greater (P< 0.001) after boiling than after pressure cooking or steaming. The pectic substance content (g 100 g^?1 dry matter) of potatoes (cv. Pentland Crown) was 2.98 for raw peeled tubers, 0.97 after boiling for 35 min, 1.22 after steaming for 35 min and 1.24 after pressure cooking at 103.4 kPa (15 psi) for 15 min. The roles of cooking time, cooking temperature and heat transfer medium are discussed. The effects of calcium sulphate (at levels typical of ‘hard’ and ‘soft’ water supplies) in the cooking water on losses of pectic substances from potato (Solanum tuberosum L.), carrot (Daucus carota L.), and swede (Brassica napus L. var. napobrassica Peterm.) after boiling and pressure cooking were also investigated. Water hardness did not influence losses during pressure cooking but samples boiled in hard water had decreased losses of pectic substances compared to those boiled in soft water. The increase in retention of pectic substances due to hard water was about 8 % for potatoes (cv. Pentland Dell), about 33 % for sliced carrots (cv. Berlicum, approved maintenance Perfecta) and about 23% for diced swedes (cv. Acme). The interaction of water hardness with cooking method was significant for potato (P< 0.05) and swede (P<0.001) and approaching significance (P=0.055) for carrot.