Sexually Dimorphic Serotonergic Dysfunction in a Mouse Model of Huntington's Disease and Depression

Depression is the most common psychiatric disorder in Huntington's disease (HD) patients. In the general population, women are more prone to develop depression and such susceptibility might be related to serotonergic dysregulation. There is yet to be a study of sexual dimorphism in the development and presentation of depression in HD patients. We investigated whether 8-week-old male and female R6/1 transgenic HD mice display depressive-like endophenotypes associated with serotonergic impairments. We also studied the behavioral effects of acute treatment with sertraline. We found that only female HD mice exhibited a decreased preference for saccharin as well as impaired emotionality-related behaviors when assessed on the novelty-suppressed feeding test (NSFT) and the forced-swimming test (FST). The exaggerated immobility time displayed by female HD in the FST was reduced by acute administration of sertraline. We also report an increased response to the 5-HT1A receptor agonist 8-OH-DPAT in inducing hypothermia and a decreased 5-HT2A receptor function in HD animals. While tissue levels of serotonin were reduced in both male and female HD mice, we found that serotonin concentration and hydroxylase-2 (TPH2) mRNA levels were higher in the hippocampus of males compared to female animals. Finally, the antidepressant-like effects of sertraline in the FST were blunted in male HD animals. This study reveals sex-specific depressive-related behaviors during an early stage of HD prior to any cognitive and motor deficits. Our data suggest a crucial role for disrupted serotonin signaling in mediating the sexually dimorphic depression-like phenotype in HD mice

Shelf life prediction of cereal-based dry foods packed in moisture-sensitive films

A mathematical model able to predict the storage life of cereal-based dry foods is presented. The developed model was, used to assess the influence on the shelf life of cereal-based dry products of both the water barrier properties of the package and the affinity of the packed food with water. Three different cereal-based dry foods and 3 different polyamide films were investigated. It was found that the shelf fife of the investigated food s, as predicted by means of the proposed model, could be overestimated by about 90% if the dependence of water permeability coefficient on water activity inside and outside the package is neglected

Refined crystal structure and absolute configuration of the di-amino acid peptide cyclo(L-aspartyl-L-aspartyl): comparison with the DFT calculated structure

The X-ray crystal structure of the di-amino acid peptide cyclo(l-Asp-l-Asp), C6H10N2O4, has been re-determined at 20 °C using CuKα radiation, λ = 1.54180 Å. The crystals are triclinic P1 with unit cell dimensions a = 5.0829(3), b = 5.0285(4), c = 18.8765(10) Å, α = 88.95(2)°, β = 83.72(2)°, γ = 74.79(2)°, unit cell volume 462.75(5) Å3, and Z = 2 independent molecules A and B per asymmetric unit. Final R indices [I > 2sigma(I)] are R1 = 0.0492, wR2 = 0.1039 for 2,540 independent reflections; R1 = 0.0686 and wR2 = 0.1112 for all 3,193 data; Goodness of Fit, S = 0.979, and the Flack x parameter = 0.1(3). In both molecules the overall shape of the diketopiperazine (DKP) ring displays an almost identical slightly distorted boat conformation with pseudo symmetry C2v (mm2). The two side chains of the cyclic peptide on opposite sides of both molecules differ in their conformations, one side being extended and the other coiled. The coiled chains are located away from the DKP ring plane while the extended chains lie approximately parallel to it. The crystal packing employs two strong hydrogen bonds, which traverse the entire crystal via translational repeats. The geometry of cyclo(l-Asp-l-Asp) derived from Ab initio calculations is compared with those of molecules A and B derived from the X-ray structure reported here. In this calculated model the DKP ring is in a pseudo twist boat conformation; both side chains are extended and lie approximately parallel to the DKP ring face as opposed to molecules A and B in the X-ray structure in each of which one side chain is approximately parallel and the other is folded away from the DKP ring face. Graphical Abstract Cyclic di-amino acid peptides are amongst the “simplest” peptide derivatives commonly found in nature and continue to be of long-standing interdisciplinary scientific interest with respect to potential pharmaceutical applications. Cyclo(l-Asp-l-Asp) is an example of a cyclic di-amino acid peptide, which has a six membered ring, and the amide linkage adopts a cis conformation. In contrast linear (l-Asp-l-Asp) is zwitterionic and has a single amide function which adopts the trans conformation. The synthesis and an X-ray structure of cyclo(l-Asp-l-Asp) have previously been reported, the latter being assigned the wrong absolute configuration. For the purposes of the present study, requiring precise molecular geometry, it was decided to carry out a re-determination of the crystal structure using a more complete measured set of independent intensities (94% against 36%) and correspondingly improved data/parameter ratio (3193/326 against 1215/369)