Sensing the fuels: glucose and lipid signaling in the CNS controlling energy homeostasis

The central nervous system (CNS) is capable of gathering information on the body’s nutritional state and it implements appropriate behavioral and metabolic responses to changes in fuel availability. This feedback signaling of peripheral tissues ensures the maintenance of energy homeostasis. The hypothalamus is a primary site of convergence and integration for these nutrient-related feedback signals, which include central and peripheral neuronal inputs as well as hormonal signals. Increasing evidence indicates that glucose and lipids are detected by specialized fuel-sensing neurons that are integrated in these hypothalamic neuronal circuits. The purpose of this review is to outline the current understanding of fuel-sensing mechanisms in the hypothalamus, to integrate the recent findings in this field, and to address the potential role of dysregulation in these pathways in the development of obesity and type 2 diabetes mellitus

Subchondral pressures and perfusion during weight bearing

Background: Joints withstand huge forces, but little is known about subchondral pressures and perfusion during loading. We developed an in vitro calf foot model to explore intraosseous pressure (IOP) and subchondral perfusion during weight bearing. Methods: Freshly culled calf forefeet were perfused with serum. IOP was measured at three sites in the foot using intraosseous needles, pressure transducers, and digital recorders. IOP was measured during perfusion, with and without a tourniquet and with differing weights, including static loading and dynamic loading to resemble walking. Results: IOP varied with perfusion pressure. Static loading increased subchondral IOP whether the bone was non-perfused, perfused, or perfused with a proximal venous tourniquet (p Conclusion: Superimposed on a variable background IOP, increased perfusion and physiological loading caused a significant increase in subchondral IOP. Force was thereby transmitted through subchondral bone partly by hydraulic pressure. A falling IOP with repeat loading suggests that there is an intraosseous one-way valve. This offers a new understanding of subchondral perfusion physiology.</br

Collaborative Assessment of a Novel MOF Material for Efficient Removal of Indoor Formaldehyde

Formaldehyde (FA) is a significant indoor pollutant due to its widespread presence in construc-tion materials and its harmful health effects. Recently, a porous MOF (Metal-Organic Frame-work) material designated as Al-3,5-PDA (pyrazole dicarboxylate) has been developed for ef-ficient removal of FA. Once shaped as a MOF paper sheet, under the Energy in Buildings and Communities (EBC) Program Annex 86, the material is undergoing evaluation in diverse indoor conditions across multiple institutions. Tests in 50-L chambers showed that the MOF paper exhibits 49 - 90% removal efficiency of FA over 7 – 28 days. The high removal efficiency was maintained at different concentrations (50 – 500 μg/m3) and relative humidity (10 – 70%). The observations imply adaptability and potential of Al-3,5-PDA for use in addressing FA pollution in diverse indoor environments. However, re-emission of FA was observed at the end of 7-day and 28-day adsorption tests. This is likely due to the desorption from the cellulose in the paper sheet. Further research is planned to determine the process of desorption within the membrane and impact of temperatures and other indoor pollutants

Neisseria meningitidis recruits factor H using protein mimicry of host carbohydrates

The complement system is an essential component of the innate and acquired immune system, and consists of a series of proteolytic cascades that are initiated by the presence of microorganisms. In health, activation of complement is precisely controlled through membrane-bound and soluble plasma-regulatory proteins including complement factor H (fH; ref. 2), a 155 kDa protein composed of 20 domains (termed complement control protein repeats). Many pathogens have evolved the ability to avoid immune-killing by recruiting host complement regulators and several pathogens have adapted to avoid complement-mediated killing by sequestering fH to their surface. Here we present the structure of a complement regulator in complex with its pathogen surface-protein ligand. This reveals how the important human pathogen Neisseria meningitidis subverts immune responses by mimicking the host, using protein instead of charged-carbohydrate chemistry to recruit the host complement regulator, fH. The structure also indicates the molecular basis of the host-specificity of the interaction between fH and the meningococcus, and informs attempts to develop novel therapeutics and vaccines