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.     

Undermining the Corrective Effects of Media‐Based Political Fact Checking? The Role of Contextual Cues and Naïve Theory

Media‐based fact checking contributes to more accurate political knowledge, but its corrective effects are limited. We argue that biographical information included in a corrective message, which is often unrelated to the inaccurate claim itself, can activate misperception‐congruent naïve theories, increasing confidence in a misperception's plausibility and inducing skepticism toward denials. Resistance to corrections occurs regardless of initial belief accuracy, but the effect is strongest among those who find the contextual information objectionable or threatening. We test these claims using an online survey‐embedded experiment (N = 750) conducted in the wake of the controversy over the proposed Islamic cultural center in New York City near the site of the 9/11 attacks, and find support for our predictions. Theoretical and practical implications are discussed.     

ZnO spintronics and nanowire devices

ZnO is a very promising material for spintronics applications, with many groups reporting room-temperature ferromagnetism in films doped with transition metals during growth or by ion implantation. In films doped with Mn during pulsed laser deposition (PLD), we find an inverse correlation between magnetization and electron density as controlled by Sn-doping. The saturation magnetization and coercivity of the implanted single-phase films were both strong functions of the initial anneal temperature, suggesting that carrier concentration alone cannot account for the magnetic properties of ZnO:Mn and factors such as crystalline quality and residual defects play a role. Plausible mechanisms for ferromagnetism include the bound magnetic polaron model or exchange that is mediated by carriers in a spin-split impurity band derived from extended donor orbitals. The progress in ZnO nanowires is also reviewed. The large surface area of nanorods makes them attractive for gas and chemical sensing, and the ability to control their nucleation sites makes them candidates for microlasers or memory arrays. Single ZnO nanowire depletion-mode metal-oxide semiconductor field effect transistors exhibit good saturation behavior, threshold voltage of ∼−3 V, and a maximum transconductance of 0.3 mS/mm. Under ultraviolet (UV) illumination, the drain-source current increased by approximately a factor of 5 and the maximum transconductance was ∼5 mS/mm. The channel mobility is estimated to be ∼3 cm²/Vss, comparable to that for thin film ZnO enhancement mode metal-oxide semiconductor field effect transistors (MOSFETs), and the on/off ratio was ∼25 in the dark and ∼125 under UV illumination. The Pt Schottky diodes exhibit excellent ideality factors of 1.1 at 25°C, very low reverse currents, and a strong photoresponse, with only a minor component with long decay times thought to originate from surface states. In the temperature range from 25°C to 150°C, the resistivity of nanorods treated in H₂ at 400°C prior to measurement showed an activation energy of 0.089 eV and was insensitive to ambient used. By contrast, the conductivity of nanorods not treated in H₂ was sensitive to trace concentrations of gases in the measurement ambient even at room temperature, demonstrating their potential as gas sensors. Sensitive pH sensors using single ZnO nanowires have also been fabricated.     

Providing incentives in providerless networks

This paper explores the extension of a model for the operation of an ad hoc mobile network to more general providerless networks, such as peer-to-peer systems. The model incorporates incentives for users to act as transit nodes on multi-hop paths and to be rewarded with their own ability to send traffic. The paper explores some of the trust questions that arise in this problem space and conjectures that the very structure of a peer organisation may have some hidden benefits for trust re-enforcement, that have not been previously explored (to our knowledge).