Structure reveals the activation mechanism of the MC4 receptor to initiate satiation signaling

Obesity is a global epidemic causing morbidity and impaired quality of life. The melanocortin receptor 4 (MC4R) is at the crux of appetite, energy homeostasis, and body-weight control in the central nervous system and is a prime target for anti-obesity drugs. Here, we present the cryo-EM structure of the human MC4R-Gs signaling complex bound to the agonist setmelanotide, a cyclic peptide recently approved for the treatment of obesity. The work reveals the mechanism of MC4R activation, highlighting a molecular switch that initiates satiation signaling. In addition, our findings indicate that Ca2+ is required for agonist but not antagonist efficacy. These results fill a gap in understanding MC4R activation and could guide the design of future weight management drugs

Compound effect of EHD and surface roughness in pool boiling and CHF with R-123

This article is a post-print version of the fianl published article which may be accessed at the link below.Saturated pool boiling of R-123 at 1 bar, including the critical heat flux (CHF), was enhanced by modifying the surface characteristics and applying a high intensity electrostatic field, the latter termed electrohydrodynamic (and abbreviated EHD) enhancement. The heat flux was varied from very low values in the natural convection regime up to CHF. Experiments were performed with increasing and decreasing heat flux to study boiling hysteresis without and with EHD. Boiling occurred on the sand blasted surface of a cylindrical copper block with embedded electrical heating elements, with standardized surface parameter Pa = 3.5 μm. The electric field was generated by a potential of 5 kV to 25 kV, applied through a 40 mm diameter circular electrode of ss-304 wire mesh, aperture size 5.1 mm, located at distances of 5 - 60 mm from the surface, with most of the data obtained for 20 mm. The data for the rough surface were compared with earlier data for a smooth surface and indicated a significant increase in the heat transfer rates. EHD produced a further increase in the heat transfer rates, particularly at low heat flux values and near the CHF. Boiling hysteresis was reduced progressively by EHD and eliminated at high field strength.This work was supported by Government of Pakistan under a scholarship programme

Wastewater Reuse in Agriculture: Effects on Soil-Plant System Properties

The use of non-conventional water resources can help to mitigate water stress and can support the agricultural sector. Treated municipal wastewater is one of the most readily available alternative water resources and its use in ag-riculture has been adopted to reduce fresh water usage in several countries, under their respective water quality regulations. This chapter reviews the re-sults of past and current research on the reuse of treated wastewater (munici-pal and agro-industrial) for irrigation and the corresponding effects on soil and plant systems. Particular attention has been given to research efforts high-lighting the effects of chemical-physical wastewater characteristics (e.g., ni-trogen, phosphorus, potassium, sodium, and heavy metals) and the corre-sponding microbiological indicators (e.g., Escherichia coli and Salmonella) on irrigated crops and soils. The selection of irrigation methods is another topic discussed in this chapter. Drip and subsurface irrigation methods are considered the more suitable irrigation techniques to be used with treated wastewater; they minimise toxicity hazards for plants, reduce the contamina-tion of edible crop products, and mitigate human health risks by minimising direct contact between wastewater and plant