CX3CL1 Action on Microglia Protects from Diet-Induced Obesity by Restoring POMC Neuronal Excitability and Melanocortin System Activity Impaired by High-Fat Diet Feeding

Both hypothalamic microglial inflammation and melanocortin pathway dysfunction contribute to diet-induced obesity (DIO) pathogenesis. Previous studies involving models of altered microglial signaling demonstrate altered DIO susceptibility with corresponding POMC neuron cytological changes, suggesting a link between microglia and the melanocortin system. We addressed this hypothesis using the specific microglial silencing molecule, CX3CL1 (fractalkine), to determine whether reducing hypothalamic microglial activation can restore POMC/melanocortin signaling to protect against DIO. We performed metabolic analyses in high fat diet (HFD)-fed mice with targeted viral overexpression of CX3CL1 in the hypothalamus. Electrophysiologic recording in hypothalamic slices from POMC-MAPT-GFP mice was used to determine the effects of HFD feeding and microglial silencing via minocycline or CX3CL1 on GFP-labeled POMC neurons. Finally, mice with hypothalamic overexpression of CX3CL1 received central treatment with the melanocortin receptor antagonist SHU9119 to determine whether melanocortin signaling is required for the metabolic benefits of CX3CL1. Hypothalamic overexpression of CX3CL1 increased leptin sensitivity and POMC gene expression, while reducing weight gain in animals fed an HFD. In electrophysiological recordings from hypothalamic slice preparations, HFD feeding was associated with reduced POMC neuron excitability and increased amplitude of inhibitory postsynaptic currents. Microglial silencing using minocycline or CX3CL1 treatment reversed these HFD-induced changes in POMC neuron electrophysiologic properties. Correspondingly, blockade of melanocortin receptor signaling in vivo prevented both the acute and chronic reduction in food intake and body weight mediated by CX3CL1. Our results show that suppressing microglial activation during HFD feeding reduces DIO susceptibility via a mechanism involving increased POMC neuron excitability and melanocortin signaling.     

Conversational Collaborative Recommendation – An Experimental Analysis

Traditionally, collaborative recommender systems have been based on a single-shot model of recommendation where a single set of recommendations is generated based on a user’s (past) stored preferences. However, content-based recommender system research has begun to look towards more conversational models of recommendation, where the user is actively engaged in directing search at recommendation time. Such interactions can range from high-level dialogues with the user, possibly in natural language, to more simple interactions where the user is, for example, asked to indicate a preference for one of k suggested items. Importantly, the feedback attained from these interactions can help to differentiate between the user’s long-term stored preferences, and her current (short-term) requirements, which may be quite different. We argue that such interactions can also be beneficial to collaborative recommendation and provide experimental evidence to support this claim.     

Experimental Perspectives on Direct Visualization of Endosomal Rupture

Endosomal escape continues to be a limiting factor in the therapeutic use of nanomaterials. Assays to visualize endosomal escape often do not decouple the endosomal/lysosomal disruption from the release of payload into the cytosol. Here, we discuss three approaches to directly probe endosomal/lysosomal rupture: calcein dye dilution, lysosome size quantification and endosome/lysosome membrane integrity visualized with a genetically engineered cell line. We apply the three assays to endosomes/lysosomes ruptured via osmotic pressure and photochemical internalization.     

A dual-polarization InSb receiver for 461/492 GHz

A dual-polarization InSb hot-electron bolometer-mixer receiver has been built for the James Clerk Maxwell Telescope, for operation at 461 and 492 GHz (the frequencies of theJ=4→3 rotational transition of CO and of the³ P ₁→³ P ₀ transition of neutral carbon). Receiver noise temperatures of 500K have been obtained at 461 GHz, in observing bandwidths of 3 MHz. The receiver was designed as a “common-user” or facility instrument. Here we describe those aspects of the design and construction which enabled this goal to be realized.     

Effects of processing and storage on chlorophyll derivatives in commercially extracted canola oil

This study characterizes the chlorophyll pigments present in canola oil immediately after commercial extraction and following oil storage to determine the best storage conditions for analytical samples and to examine the changes that chlorophyll derivatives undergo during oil processing and storage. Samples of pressed, solvent-extracted, crude and degummed canola oils, obtained from a commercial crushing plant, were stored for one month under four different conditions—in the freezer, in a refrigerator and at room temperature both in the light and in the dark. Chlorophyll derivatives (chlorophylls, pheophytins, pyropheophytins) were measured by high-performance liquid chromatography immediately after sampling and then on a weekly basis. The main pigments present in commercially extracted canola oil were pheophytin a, pyropheophytin a, chlorophyll a and chlorophyll b. The “a” derivatives comprised 81 to 100% of total chlorophyll pigments in the fresh oil samples. During degumming, the remaining chlorophylls were converted to pheophytins and pyropheophytins. During oil storage, exposure to light at room temperature affected the composition of chlorophyll derivatives as chlorophyll b was converted to pheophytin b and chlorophyll a was converted first to pheophytin a, then to pyropheophytin a.     

Saving the neighbourhood: understanding tenant activism in middle-class Manhattan

Abstract

Recent debates question whether assemblage urbanism provides an appropriate framework for addressing the housing question under late capitalism. On one side, proponents note the capacity of assemblage to reveal the complex emergence of events, places and processes, whereas critics argue assemblage accounts provide deep empirical detail but avoid engaging with political economy. This paper addresses such criticism through an assemblage account of local activism in the context of ownership changes that threatened the rent-regulated Stuyvesant Town neighbourhood in Manhattan. We adopt an assemblage methodology to examine this case of privileged tenant activism and find that it provides an additive lens for understanding the networks of relations that influenced the community during the mid-2000s. Noting that assemblage and the financial ecologies approach are similar in their attendance to relational thinking, we describe how these approaches can be used in conjunction to better understand the linkages between housing and financialization.     

The feasibility of membrane separations in the HIx processing section of the sulphur iodine thermochemical cycle

One of the most promising routes currently under development for sustainable hydrogen production is the sulphur iodine thermochemical water splitting cycle. The most important stage in determining overall process efficiency and feasibility of the cycle is the separation of HI_x, a mixture of HI, H₂O and I₂. This paper investigates the scope for applying membrane separations to the HI_x processing section, with the aim of improving the overall efficiency of the process. Simulations using ProSimPlus indicate that this efficiency can be increased from a base value of 36.9% to over 39% by applying a membrane separation unit which achieves 8.25% dewatering to the feed of the reactive distillation column. Comparison with experimental flux and separation data for both pervaporation and membrane distillation membranes gives design limits for the cost and feasibility of such a membrane system.