Sweet Taste Signaling Functions as a Hypothalamic Glucose Sensor

Brain glucosensing is essential for normal body glucose homeostasis and neuronal function. However, the exact signaling mechanisms involved in the neuronal sensing of extracellular glucose levels remain poorly understood. Of particular interest is the identification of candidate membrane molecular sensors that would allow neurons to change firing rates independently of intracellular glucose metabolism. Here we describe for the first time the expression of the taste receptor genes Tas1r1, Tas1r2 and Tas1r3, and their associated G-protein genes, in the mammalian brain. Neuronal expression of taste genes was detected in different nutrient-sensing forebrain regions, including the paraventricular and arcuate nuclei of the hypothalamus, the CA fields and dentate gyrus of the hippocampus, the habenula, and cortex. Expression was also observed in the intra-ventricular epithelial cells of the choroid plexus. These same regions were found to express the corresponding gene products that form the heterodimeric T1R2/T1R3 and T1R1/T1R3 sweet and l-amino acid taste G-protein coupled receptors, respectively, along with the taste G-protein α-gustducin. Moreover, in vivo studies in mice demonstrated that the hypothalamic expression of taste-related genes is regulated by the nutritional state of the animal, with food deprivation significantly increasing expression levels of Tas1r1 and Tas1r2 in hypothalamus, but not in cortex. Furthermore, exposing mouse hypothalamic cells to a low-glucose medium, while maintaining normal l-amino acid concentrations, specifically resulted in higher expression levels of the sweet-associated gene Tas1r2. This latter effect was reversed by adding the non-metabolizable artificial sweetener sucralose to the low-glucose medium, indicating that taste-like signaling in hypothalamic neurons does not require intracellular glucose oxidation. Taken together, our findings suggest that the heterodimeric G-protein coupled sweet receptor T1R2/T1R3 is a candidate membrane-bound brain glucosensor

Length to diameter ratio effect on heat transfer performance of simple and compound angle holes in thin-wall airfoil cooling

Heat transfer coefficients on a flat plate surface downstream a row of simple and compound angle cylindrical holes are investigated using high-resolution thermographic liquid crystal technique. A variation of flow parameters including blowing ratio, and geometry parameters including compound angle and length-to-diameter ratio are examined. Blowing ratios (M) ranging from 0.3 to 2, length to diameter ratios (L/D) from 0.5 to 5, and two compound angle (β: 0°, 45°) are employed composing a test matrix of 70 test cases. Detailed local, spanwise averaged, and area averaged heat transfer coefficients hf/h0 are presented to illustrate the effect of length-to-diameter ratio and compound angle. The film cooling performance is also evaluated using NHFR method and Δφ method by combining adiabatic film effectiveness and heat transfer coefficient data. Results indicate that Δφ method has superiority in evaluating film cooling performance due to its direct reflection of temperature reduction by film protection

Experimental investigation of wall thickness and hole shape variation effects on full-coverage film cooling performance for a gas turbine vane

The effects of wall thickness and hole shape variation on a full-coverage film cooled turbine vane are investigated in a stationary and linear cascade utilizing the pressure sensitive paint technique. The varied wall thickness produces hole length-to-diameter ratio (L/D) in a range from L/D = 2 to 5, and holes tested include simple angle hole, compound angle hole, and fan-shaped hole. Five rows of holes are provided on the pressure side while three rows of holes are provided on the suction side, with six rows of cylindrical holes drilled on the leading edge to construct showerhead film cooling. The tested blowing ratios for the showerhead, pressure side, and suction side range from 0.25 to 1.5, with a density ratio of 1.5. The freestream Reynolds number is 1.35 × 105, based on the axial chord length and the inlet velocity, with a freestream turbulence intensity level of 3.5% at the cascade inlet. The results indicate that the wall thickness variation produces significant influence on the pressure side film cooling effectiveness, while only marginal effect on the showerhead and suction side film cooling. Also observed is that the fan-shaped hole generates the highest film cooling effectiveness on pressure or suction side. Also discussed is the surface curvature effect, combining with effects of wall thickness and hole shape variations, on the film cooling effectiveness in comparison to the flat-plate data

Identification of phase relative genes in tetrasporophytes and female gametophytes of Gracilaria/Gracilariopsis lemaneiformis (Gracilariales, Rhodophyta)

Genes differentially expressed between tetrasporophytes and female gametophytes of Gracilaria/Gracilariopsis lemaneiformis were isolated by suppression subtractive hybridization (SSH) and screened by dot-blot macro-arrays. Different expression profiles of selected clones based on the results of dot-blot macro-arrays were verified using virtual Northern blots. Totally, 14 phase relative cDNAs had been isolated and sequence identified. Among them, seven cDNAs were respectively homologous to crucial metabolic enzymes, Rab GTPase, RP42 homolog, and two hypothetical proteins, while the rest did not have significant hits in the databases examined. The results of virtual Northern blots revealed that 11 cDNAs were differentially expressed between the two samples, including 7 genes up-regulated in tetrasporophytes, 1 expressed exclusively in tetrasporophytes and 3 up-regulated in female gametophytes. By densitometric analysis relative to GAPDH, 8 cDNAs increased 1.3-4.2 fold and 3 decreased about 0.4-0.7 fold in tetrasporophytes compared to female gametophytes. The present study provides the first insight into genes that may involve in phase differentiation in G. lemaneiformis

Leptin regulates the reward value of nutrient

We developed an assay for quantifying the reward value of nutrient and used it to analyze the effects of metabolic state and leptin. In this assay, mice chose between two sippers, one of which dispensed water and was coupled to optogenetic activation of dopaminergic (DA) neurons and the other of which dispensed natural or artificial sweeteners. This assay measured the reward value of sweeteners relative to lick-induced optogenetic activation of DA neurons. Mice preferred optogenetic stimulation of DA neurons to sucralose, but not to sucrose. However, the mice preferred sucralose plus optogenetic stimulation versus sucrose. We found that food restriction increased the value of sucrose relative to sucralose plus optogenetic stimulation, and that leptin decreased it. Our data suggest that leptin suppresses the ability of sucrose to drive taste-independent DA neuronal activation and provide new insights into the mechanism of leptin's effects on food intake

Comparative transcriptomic analysis reveals the molecular mechanism underlying seedling heterosis and its relationship with hybrid contemporary seeds DNA methylation in soybean

Heterosis is widely used in crop production, but phenotypic dominance and its underlying causes in soybeans, a significant grain and oil crop, remain a crucial yet unexplored issue. Here, the phenotypes and transcriptome profiles of three inbred lines and their resulting F1 seedlings were analyzed. The results suggest that F1 seedlings with superior heterosis in leaf size and biomass exhibited a more extensive recompilation in their transcriptional network and activated a greater number of genes compared to the parental lines. Furthermore, the transcriptional reprogramming observed in the four hybrid combinations was primarily non-additive, with dominant effects being more prevalent. Enrichment analysis of sets of differentially expressed genes, coupled with a weighted gene co-expression network analysis, has shown that the emergence of heterosis in seedlings can be attributed to genes related to circadian rhythms, photosynthesis, and starch synthesis. In addition, we combined DNA methylation data from previous immature seeds and observed similar recompilation patterns between DNA methylation and gene expression. We also found significant correlations between methylation levels of gene region and gene expression levels, as well as the discovery of 12 hub genes that shared or conflicted with their remodeling patterns. This suggests that DNA methylation in contemporary hybrid seeds have an impact on both the F1 seedling phenotype and gene expression to some extent. In conclusion, our study provides valuable insights into the molecular mechanisms of heterosis in soybean seedlings and its practical implications for selecting superior soybean varieties

Dominant role of GABAB2 and Gbetagamma for GABAB receptor-mediated-ERK1/2/CREB pathway in cerebellar neurons

gamma-aminobutyric acid type B (GABA(B)) receptor is an allosteric complex made of two subunits, GABA(B1) and GABA(B2). GABA(B2) plays a major role in the coupling to G protein whereas GABA(B1) binds GABA. It has been shown that GABA(B) receptor activates ERK(1/2) in neurons of the central nervous system, but the molecular mechanisms underlying this event are poorly characterized. Here, we demonstrate that activation of GABA(B) receptor by either GABA or the selective agonist baclofen induces ERK(1/2) phosphorylation in cultured cerebellar granule neurons. We also show that CGP7930, a positive allosteric regulator specific of GABA(B2), alone can induce the phosphorylation of ERK(1/2). PTX, a G(i/o) inhibitor, abolishes both baclofen and CGP7930-mediated-ERK(1/2) phosphorylation. Moreover, both baclofen and CGP7930 induce ERK-dependent CREB phosphorylation. Furthermore, by using LY294002, a PI-3 kinase inhibitor, and a C-term of GRK-2 that has been reported to sequester Gbetagamma subunits, we demonstrate the role of Gbetagamma in GABA(B) receptor-mediated-ERK(1/2) phosphorylation. In conclusion, the activation of GABA(B) receptor leads to ERK(1/2) phosphorylation via the coupling of GABA(B2) to G(i/o) and by releasing Gbetagamma subunits which in turn induce the activation of CREB. These findings suggest a role of GABA(B) receptor in long-term change in the central nervous system