Frankslim3090

Across repeated tests, male rats habituated to the novel food faster than females and by the fourth test ate more of the novel than familiar food. In contrast, females showed sustained, suppressed consumption across habituation tests. These results demonstrated robust differences in feeding behavior depending whether rats were fed at home or in a novel feeding environment, and robust sex differences in habituation to eating in a new environment. These findings suggest that novel context has a greater impact on female consumption than male consumption. This difference may be relevant to sex differences in avoidant behaviors in maladaptive circumstances and the development of psychopathology. Therefore, the behavioral profile outlined in this study for consumption under novelty provides an important starting point for investigation of the underlying neural substrates of novelty processing.Dexamethasone (DXM) is a synthetic adrenal corticosteroid with anti-inflammatory properties used for therapeutic purposes in a wide range of pathologies and of the most common corticosteroids used for anabolic purposes in beef cattle. It is proven that DXM induces histological changes, traceable as increasing fatty infiltration of the thymus associated with a concurrent decrease of the cortex-medulla ratio, so the histological examination of the thymus gland has been established as an indirect morphological biomarker. The aim of the present study is to compare thymus histology and DXM concentrations in biological fluids collected at slaughterhouse after 1 month of DXM treatment. Our findings demonstrate that a low dosage of DXM administered to 12 months-old-Chianina beef cattle induces severe thymic atrophy with concurrent reduction of the cortex/medulla ratio, demonstrable even when DXM residues are not found in serum and urine samples. It is worth to note that, at the slaughterhouse, DXM residues are detectable in bile samples, indicating the ability of this biological fluid to bio-concentrate the administered drug if compared to serum and urine. Therefore, bile could be candidates as new liquid matrix for the screening programs planned to contrast the illegal use of anabolic substances.Prostaglandins (PGs) mediate various physiological processes in insects and other invertebrates, but there is very little information on PG receptors. This study identified a PGE2 receptor (SePGE2R) in the lepidopteran insect, Spodoptera exigua, and addressed its functional association with cellular immunity, development, and reproduction. SePGE2R is expressed in most developmental stages and tissues. After SePGR2R expression knock down by RNA interference (RNAi), larval nodule formation (clears bacterial infections from circulating hemolymph) was severely suppressed coupled with reduced F-actin growth in hemocytes. Treating female adults with RNAi prevented nurse cell dumping in follicles and interfered with oocyte development. SePGE2R was heterologously expressed in Sf9 cells, in which the endogenous S. frugiperda PGE2R was knocked down by small interfering RNA. This transiently expressed SePGE2R responded to PGE2, but not other PGs, with dose-dependent up-regulation of intracellular cAMP concentrations. Treating S. exigua larvae with PGE2 led to activation of a trimeric Gαs subunit, protein kinase A (PKA), and Rho family small intracellular G proteins in hemocytes. A deletion mutant of SePGE2R was generated using CRISPR/Cas9 which exhibited severely retarded larval development and adult reproduction. We infer that PGE2R mediates insect immune and reproductive processes via a PKA signal pathway.Bt protein, produced by Bacillus thuringiensis, can bind receptors to destroy the physiological functions of the insect midgut. It is unknown whether Bt can also target the hindgut and influence its defense against fecal bacteria. Here we show that Crystal protein 1Ab (Cry1Ab), a Bt protein, was detected in the larval hindgut contents of Bombyx mori after ingestion of this toxin protein. The number of fecal bacteria that can be inhibited by the hindgut prophenoloxidase-induced melanization was significantly enhanced after oral ingestion of Cry1Ab. Although the hindgut contents became brown, the activity of hindgut phenoloxidase was decreased. LC-MS/MS analysis of the hindgut lumen contents revealed that many new proteins including several proteases were newly secreted. The enhanced secretion of proteases cleaved prophenoloxidase to decrease its activity, including the corresponding activity to inhibit the fecal bacteria. In addition, after ingestion of Cry1Ab, the pylorus (between the midgut and hindgut) could not autonomously contract due to the physical detachment of the acellular cuticle-like membrane from the epidermal cells, which prevented the movement of food from the midgut to the hindgut. Some cells in the cryptonephry of the hindgut became swollen and degraded, possibly due to the presence of Cry1Ab in the hindgut. These findings demonstrate that the inhibition of feces bacteria by the hindgut prophenoloxidase-induced melanization is out of control after Cry1Ab ingestion.Ketamine, a general anaesthetic and psychotomimetic drug, exerts rapid, potent and long-lasting antidepressant effect, albeit the cellular and molecular mechanisms of this action are yet to be discovered. Besides targeting neuronal NMDARs fundamental for synaptic transmission, ketamine affects the function of astroglia the key homeostatic cells of the central nervous system that contribute to pathophysiology of psychiatric diseases including depression. Here we review studies revealing that (sub)anaesthetic doses of ketamine elevate intracellular cAMP concentration ([cAMP]i) in astrocytes, attenuate stimulus-evoked astrocyte calcium signalling, which regulates exocytotic secretion of gliosignalling molecules, and stabilize the vesicle fusion pore in a narrow configuration possibly hindering cargo discharge or vesicle recycling. Next we discuss how ketamine affects astroglial capacity to control extracellular K+ by reducing cytoplasmic mobility of vesicles delivering the inward rectifying potassium channel (Kir4.1) to the plasmalemma. Modified astroglial K+ buffering impacts upon neuronal excitability as demonstrated in the lateral habenula rat model of depression. Finally, we highlight the recent discovery that ketamine rapidly redistributes cholesterol in the plasmalemma of astrocytes, but not in fibroblasts nor in neuronal cells. This alteration of membrane structure may modulate a host of processes that synergistically contribute to ketamine's rapid and prominent antidepressant action.Intramembrane proteases catalyze the unusual cleavage of peptide bonds in the plane of biological membranes. They are categorized according to their active site. The GxGD aspartyl proteases comprise presenilin, the signal peptide peptidase (SPP), and SPP-like (SPPL) proteases. Here we focus on the functionally related SPP and SPPL proteases, and review the current understanding of their substrate specificity and summarize known physiological functions in mammalian cells. We discuss how on the one hand regulated intramembrane proteolysis generates signaling molecules, and on the other hand how processes such as endoplasmic reticulum-associated degradation controls the quantity and activity of central regulators. While the enzymatic core of GxGD intramembrane proteases is conserved, association with regulatory factors and substrate adaptors may have tailored enzymes for various specific functions.Fipronil is a widely used commercial insecticide whose action mechanism consists in blocking the influx of chloride ions through the γ-aminobutyric acid type A receptor (GABAA-R), an integral membrane protein. The present study investigates the interaction of fipronil with phospholipid Langmuir monolayers, in order to characterize the effects that its partition could exert on the physical properties of these model membranes. A combined experimental and molecular dynamics (MD) simulations approach was performed. MD simulations were conducted in such a way that they resemble an experimental compression isotherm of DPPC in the presence of fipronil in the aqueous subphase. Both the experimental and the simulated compression isotherm showed that the partition of fipronil between DPPC molecules induces an expansion of the monolayer. Experimental results also showed that fipronil can penetrate lipid monolayers even in condensed packing states. MD simulations showed that fipronil induces an ordering effect in the acyl chains of DPPC in the liquid-condensed phase. In addition, the simulations indicate that fipronil orients parallel to the plane of the monolayer and that it establishes hydrogen bonds with the glycerol region of DPPC. Free energy profiles of the partition of fipronil into the monolayers, obtained by means of umbrella sampling, indicated that its penetration is thermodynamically favorable, being the interphase between the glycerol region and the acyl chains of DPPC its most favorable location. Our results suggest that fipronil could modulate the supramolecular organization of biological membranes surrounding GABAA-R, contributing, at least in part, to its action mechanism.Photopolymerizable lipids, such as diacetylene lipids have attracted much attention for their ability to stabilize lipid bilayer structure. In this study, we investigated the phase separation behavior of a lipid bilayer containing 1,2‑bis(10,12‑tricosadiynoyl)‑sn‑glycero‑3‑phosphocholine (DiynePC). click here The phase separation behavior of liposomes composed of DiynePC and the non-polymerizable lipid, 1,2‑dioleoyl‑sn‑glycero‑3‑phosphocholine (DOPC) was evaluated using a fluorescence resonance energy transfer (FRET) assay during both the cooling and heating processes. The polymerization behavior and orientation of DiynePC was evaluated by measuring the absorbance contributed by polymerized diacetylene groups. The main phase transition temperature (Tm) and orientation temperature (To) of DiynePC were determined from differential scanning calorimetry (DSC) and absorbance measurements. As a comparison, liposomes composed of 1,2‑dipalmitoyl‑sn‑glycero‑3‑phosphocholine (DPPC), which has a similar Tm as DiynePC, but a dissimilar To, were evaluated as well as, DiynePC-containing liposomes. The DPPC/DOPC liposomes showed phase separation at the Tm of DPPC during both the cooling and heating processes. link2 On the other hand, the phase separation of the DiynePC/DOPC liposomes occurred near To of DiynePC but slightly increased during the cooling process. Interestingly, once the liposomes were cooled to a much lower temperature than the To, the phase separation was promoted by the subsequent heating process, and reached a maximum state of the phase separation near the To. link3 These results indicated that the phase separation of DiynePC is affected by both the orientation state and thermal molecular motion.Objective Early detection and treatment can prevent irreversible blindness from diabetic retinopathy (DR), which is the leading cause of visual impairment among working-aged adults worldwide. 80% of affected persons live in low- and middle-income countries, yet, lack of resources has largely prevented DR screening implementation in these world regions. Smartphone-based fundus imaging (SBFI) allows for low-cost mobile fundus examination using an adapter on a smartphone, however, key aspects such as image quality, diagnostic accuracy and comparability of different approaches have not been systematically assessed to date. Design Evaluation of diagnostic technology PARTICIPANTS Three hundred and eighty one eyes of 193 patients with diabetes were recruited at outreach eye clinics in South-India. Methods We compared four technically different approaches of SBFI (three approaches based on direct and one approach based on indirect ophthalmoscopy) in terms of image quality and diagnostic accuracy for DR screening. Main outcome measures Image quality (sharpness, reflex artifacts, contrast and illumination), field-of-view, examination time, and diagnostic accuracy for DR screening were analyzed against conventional fundus photography and clinical examination.