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.     

The Role of the Choroid in Stargardt Disease

Stargardt disease is the commonest juvenile macular dystrophy. It is caused by genetic mutations in the ABCA4 gene. Diagnosis is not always straightforward, and various phenocopies exist. Late-onset disease can be misdiagnosed with age-related macular disease. A correct diagnosis is particularly critical because of emergent gene therapies. Stargardt disease is known to affect retinal pigment epithelium and photoreceptors. Many studies have also highlighted the importance of the choroid in the diagnosis, pathophysiology, and progression of the disease. The choroid is in an integral relationship with the retinal pigment epithelium and photoreceptors, and its possible involvement during the disease should be considered. The purpose of this review is to analyze the current diagnostic tools for choroidal evaluation and the extrapolation of useful data for ophthalmologists and researchers studying the disease.     

Anticipating infectious disease re-emergence and elimination: a test of early warning signals using empirically based models

Timely forecasts of the emergence, re-emergence and elimination of human infectious diseases allow for proactive, rather than reactive, decisions that save lives. Recent theory suggests that a generic feature of dynamical systems approaching a tipping point—early warning signals (EWS) due to critical slowing down (CSD)—can anticipate disease emergence and elimination. Empirical studies documenting CSD in observed disease dynamics are scarce, but such demonstration of concept is essential to the further development of model-independent outbreak detection systems. Here, we use fitted, mechanistic models of measles transmission in four cities in Niger to detect CSD through statistical EWS. We find that several EWS accurately anticipate measles re-emergence and elimination, suggesting that CSD should be detectable before disease transmission systems cross key tipping points. These findings support the idea that statistical signals based on CSD, coupled with decision-support algorithms and expert judgement, could provide the basis for early warning systems of disease outbreaks.     

Synchronization of diffusively-coupled limit cycle oscillators

We develop analytical and numerical conditions to determine whether limit cycle oscillations synchronize in diffusively coupled systems. We examine two classes of systems: reaction–diffusion PDEs with Neumann boundary conditions, and compartmental ODEs, where compartments are interconnected through diffusion terms with adjacent compartments. In both cases the uncoupled dynamics are governed by a nonlinear system that admits an asymptotically stable limit cycle. We provide two-time scale averaging methods for certifying stability of spatially homogeneous time-periodic trajectories in the presence of sufficiently small or large diffusion and develop methods using the structured singular value for the case of intermediate diffusion. We highlight cases where diffusion stabilizes or destabilizes such trajectories.     

Computational Photography with Panoramic Sensors that Have Uniform Resolution with Respect to Unwarping Transformations

We address the problem of designing a computational photographic system for panoramic imaging, which employs a rotationally symmetric reflector and yet produces uniform resolution images. Our design is a catadiotpric sensor, whose key component is a rotationally symmetric mirror. Catadioptric sensors have already been designed that are equiresolution with respect to solid angle, but such sensors do not take into account the effect of unwarping transformations that are typically applied to the initially recorded images. The family of catadioptric sensors that we describe may be considered as realizing area preserving/scaling cylindrical projections. We present the derivations of the equations that describe such sensors and demonstrate in simulation their properties with respect to unwarping.     

Integration of Low-Impact Development into the International Stormwater BMP Database

Low impact development (LID) strategies are being encouraged in many communities as an approach to reduce potential adverse impacts of development on receiving streams. Many questions exist regarding how well various LID strategies perform in different settings, just as similar questions have been raised regarding performance of traditional stormwater best management practices (BMPs). Whereas historical focus on BMP performance has been water quality concentrations or loads, characterization of volume reduction benefits for both conventional and LID practices is increasingly an objective of researchers and stormwater managers. More than a decade ago, Urban Water Resources Research Council (UWRRC) members worked to develop a set of standardized monitoring and reporting protocols for traditional BMPs and to establish a master database for the purpose of evaluating BMP performance and the factors affecting performance. This effort culminated in the International Stormwater BMP Database (www.bmpdatabase.org), which contains data for more than 360 BMPs and continues to operate as a clearinghouse for stormwater BMP data and performance analyses. During 2008–2009, the International Stormwater BMP Database project expanded to better integrate LID into the database and develop a set of metrics that can be used to characterize BMP performance with regard to surface runoff volume reduction. This paper provides a condensed overview and progress report on the LID-focused effort, including the following topics: (1)?monitoring guidance for LID at the overall site development level, (2)?an overview of recent changes to the International Stormwater BMP Database to better accommodate LID studies, (3)?a summary of LID studies currently included in the database, and (4)?a proposed approach for evaluating performance of LID studies with regard to reducing surface runoff volumes.     

Absence of a self-induced decay effect in Au

We report the results of an improved experiment aimed at determining whether the half-life (T_1/2) of ¹⁹⁸Au depends on the shape of the source. In this experiment, the half-lives of a gold sphere and a thin gold wire were measured after each had been irradiated in the NIST Center for Neutron Research. In comparison to an earlier version of this experiment, both the specific activities of the samples and their relative surface/volume ratios have been increased, leading to an improved test for the hypothesized self-induced decay (SID) effect. We find T_1/2(sphere)/T_1/2(wire)=(0.9993±0.0002), which is compatible with no SID effect.