The effects of juvenile stress on anxiety, cognitive bias and decision making in adulthood:a rat model

Stress experienced in childhood is associated with an increased risk of developing psychiatric disorders in adulthood. These disorders are particularly characterized by disturbances to emotional and cognitive processes, which are not currently fully modeled in animals. Assays of cognitive bias have recently been used with animals to give an indication of their emotional/cognitive state. We used a cognitive bias test, alongside a traditional measure of anxiety (elevated plus maze), to investigate the effects of juvenile stress (JS) on adulthood behaviour using a rodent model. During the cognitive bias test, animals were trained to discriminate between two reward bowls based on a stimulus (rough/smooth sandpaper) encountered before they reached the bowls. One stimulus (e.g. rough) was associated with a lower value reward than the other (e.g. smooth). Once rats were trained, their cognitive bias was explored through the presentation of an ambiguous stimulus (intermediate grade sandpaper): a rat was classed as optimistic if it chose the bowl ordinarily associated with the high value reward. JS animals were lighter than controls, exhibited increased anxiety-like behaviour in the elevated plus maze and were more optimistic in the cognitive bias test. This increased optimism may represent an optimal foraging strategy for these underweight animals. JS animals were also faster than controls to make a decision when presented with an ambiguous stimulus, suggesting altered decision making. These results demonstrate that stress in the juvenile phase can increase anxiety-like behaviour and alter cognitive bias and decision making in adulthood in a rat model

Bitter Taste Receptors Influence Glucose Homeostasis

TAS1R- and TAS2R-type taste receptors are expressed in the gustatory system, where they detect sweet- and bitter-tasting stimuli, respectively. These receptors are also expressed in subsets of cells within the mammalian gastrointestinal tract, where they mediate nutrient assimilation and endocrine responses. For example, sweeteners stimulate taste receptors on the surface of gut enteroendocrine L cells to elicit an increase in intracellular Ca2+ and secretion of the incretin hormone glucagon-like peptide-1 (GLP-1), an important modulator of insulin biosynthesis and secretion. Because of the importance of taste receptors in the regulation of food intake and the alimentary responses to chemostimuli, we hypothesized that differences in taste receptor efficacy may impact glucose homeostasis. To address this issue, we initiated a candidate gene study within the Amish Family Diabetes Study and assessed the association of taste receptor variants with indicators of glucose dysregulation, including a diagnosis of type 2 diabetes mellitus and high levels of blood glucose and insulin during an oral glucose tolerance test. We report that a TAS2R haplotype is associated with altered glucose and insulin homeostasis. We also found that one SNP within this haplotype disrupts normal responses of a single receptor, TAS2R9, to its cognate ligands ofloxacin, procainamide and pirenzapine. Together, these findings suggest that a functionally compromised TAS2R receptor negatively impacts glucose homeostasis, providing an important link between alimentary chemosensation and metabolic disease

Immunological characterization of trichocyst proteins in the ciliate Pseudomicrothorax dubius

Ejectable trichocysts were isolated from the ciliate Pseudomicrothorax dubius. Polyclonal antibodies were raised against three groups of trichocyst proteins: G1 (30-31 kDa), G2 (26-27 kDa) and G3 (15-20 kDa). By indirect immunofluorescence, the three antisera strongly label the shafts of ejected trichocysts and the proximal ends of condensed trichocysts within the cells. By immunogold labeling for electron microscopy, the three sera specifically recognize the shafts of both extended and condensed trichocysts and shaft precursors in pretrichocysts as well. On one-dimensional immunoblots of isolated trichocysts, anti-G1 serum recognizes the G1 proteins, anti-G2 serum detects G2 proteins and some G1 proteins, and anti-G3 serum reacts with 15 bands, mainly the G3 and (30-41)-kDa proteins. In cells with and without trichocysts, the sera recognize non-ejectable trichocyst proteins at 41-42 kDa and 47 kDa. On two-dimensional immunoblots of isolated trichocysts, anti-G1 serum labels proteins with a pI of 4.75-5.7, anti-G2 serum labels proteins with a pI of 4.75-6.25 and anti-G3 serum labels proteins with a pI of 4.7-6.6. Analyses of cells with and without trichocysts allow identification of possible precursors between 41 and 47 kDa. Some are in the same pI range as their putative products, but others, labeled by anti-G3 serum, are less acidic than most of their mature products

Rat brain vascular distribution of interleukin-1 type-1 receptor immunoreactivity : relationship to patterns of inducible cyclooxygenase expression by peripheral inflammatory stimuli

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Reduced Sweetness of a Monellin (MNEI) Mutant Results from Increased Protein Flexibility and Disruption of a Distant Poly-(L-Proline) II Helix

Monellin is a highly potent sweet-tasting protein but relatively little is known about how it interacts with the sweet taste receptor. We determined X-ray crystal structures of 3 single-chain monellin (MNEI) proteins with alterations at 2 core residues (G16A, V37A, and G16A/V37A) that induce 2- to 10-fold reductions in sweetness relative to the wild-type protein. Surprisingly, no changes were observed in the global protein fold or the positions of surface amino acids important for MNEI sweetness that could explain these differences in protein activity. Differential scanning calorimetry showed that while the thermal stability of each mutant MNEI was reduced, the least sweet mutant, G16A-MNEI, was not the least stable protein. In contrast, solution spectroscopic measurements revealed that changes in protein flexibility and the C-terminal structure correlate directly with protein activity. G16A mutation-induced disorder in the protein core is propagated via changes to hydrophobic interactions that disrupt the formation and/or position of a critical C-terminal poly-(L-proline) II helix. These findings suggest that MNEI interaction with the sweet taste receptor is highly sensitive to the relative positions of key residues across its protein surface and that loss of sweetness in G16A-MNEI may result from an increased entropic cost of binding