The GOAT-Ghrelin System Is Not Essential for Hypoglycemia Prevention during Prolonged Calorie Restriction

Ghrelin acylation by ghrelin O-acyltransferase (GOAT) has recently been reported to be essential for the prevention of hypoglycemia during prolonged negative energy balance. Using a unique set of four different genetic loss-of-function models for the GOAT/ghrelin/growth hormone secretagogue receptor (GHSR) system, we thoroughly tested the hypothesis that lack-of-ghrelin activation or signaling would lead to hypoglycemia during caloric deprivation. Male and female knockout (KO) mice for GOAT, ghrelin, GHSR, or both ghrelin and GHSR (dKO) were subjected to prolonged calorie restriction (40% of ad libitum chow intake). Body weight, fat mass, and glucose levels were recorded daily and compared to wildtype (WT) controls. Forty-eight hour blood glucose profiles were generated for each individual mouse when 2% or less body fat mass was reached. Blood samples were obtained for analysis of circulating levels of acyl- and desacyl-ghrelin, IGF-1, and insulin. Chronic calorie restriction progressively decreased body weight and body fat mass in all mice regardless of genotype. When fat mass was depleted to 2% or less of body weight for 2 consecutive days, random hypoglycemic events occurred in some mice across all genotypes. There was no increase in the incidence of hypoglycemia in any of the four loss-of-function models for ghrelin signaling including GOAT KO mice. Furthermore, no differences in insulin or IGF-1 levels were observed between genotypes. The endogenous GOAT-ghrelin-GHSR system is not essential for the maintenance of euglycemia during prolonged calorie restriction

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Structural and function correlation of cone packing utilizing adaptive optics and microperimetry

Aim. To assess the functional aspects of cone mosaic and correlate cone packing with retinal sensitivity utilizing microperimetry in emmetropes at different eccentricities. Methods. Twenty-four healthy volunteers underwent microperimetry (MAIA Centervue, Italy) and assessment of photoreceptors using adaptive optics retinal camera, rtx1 (Imagine Eyes, Orsay, France), at 2 and 3 degrees from the foveal centre in 4 quadrants: superior, inferior, temporal, and nasal. Data was analyzed using SPSS version 17 (IBM). Spearman’s correlation tests were used to establish correlation between mean cone packing density and retinal sensitivity at different quadrants. Results. Thirteen females and 11 males (age range 20–40 years) were included. The cone density was found to be significantly different among all quadrants (temporal = 25786.68/mm2 ± 4367.07/mm2, superior = 23009.35/mm2 ± 5415.81/mm2, nasal = 22838.09/mm2 ± 4166.22/mm2, and inferior = 21097.53/mm2 ± 4235.84/mm2). A statistical significance was found between orthogonal meridians, that is, temporal, nasal superior, inferior (44106.88/mm2). A drop in retinal sensitivity was observed as the eccentricity increased . It was also found that as cone packing density decreased retinal sensitivity also decreased in all quadrants. This was observed at both 2 and 3 degrees. Conclusion. It is of crucial importance to establish normative variations in cone structure-function correlation. This may help in detection of subtle pathology and its early intervention.\u3cbr/\u3e\u3cbr/\u3e1. Introduction\u3cbr/\u3e\u3cbr/\u3eAdaptive optics (AO) is emerging as an objective tool in assessment of the architecture of the photoreceptor layer of retina. It can be used to quantify the cone mosaic including the density and packing arrangements. Studying the cone mosaic shows different reflectance patterns with wide temporal and spatial variations. Multiple AO systems have described this variation in the cone reflectivity to be secondary to differences in the phase of phototransduction, length of the outer segment, disc shedding, wavelength of the light, and so forth [1–3].\u3cbr/\u3e\u3cbr/\u3eBy just studying the cone mosaic, we are unable to assess the functional aspect of a visible cone and correlate whether a visible cone is a functional cone.\u3cbr/\u3e\u3cbr/\u3eOur study aims to assess the functional aspects of the cone mosaic and correlate the cone packing with the retinal sensitivity utilizing microperimetry (MAIA) in emmetropes at different eccentricities

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