Baseline cortisol predicts drunkorexia in female but not male college students.

OBJECTIVE: "Drunkorexia" or compensatory eating behaviors in response to alcohol consumption, resembles a subclinical eating disorder, and is a current public health concern. Eating disorders and alcohol abuse are associated with dysfunction of the hypothalamic-pituitary-adrenal axis (HPA). One index of HPA function is cortisol. As causes of drunkorexia remain elusive, the present study examined cortisol function as it relates to drunkorexia. Participants:n = 73 (49 women) college students. Method: Participants provided daytime saliva samples for cortisol analyses prior to completing an online survey measuring alcohol consumption, drunkorexia, and alcohol problems as measured by the Rutgers Alcohol Problem Index (RAPI). Results: Multiple regressions indicated that baseline cortisol significantly positively correlated with drunkorexia behaviors in women but not men. Higher baseline cortisol and aspects of drunkorexia related to alcohol problems. Conclusion: Programs educating about stress management and health risks of drunkorexia may decrease engagement in drunkorexia behaviors among college students.

Prefrontal control of trace eyeblink conditioning in rabbits (Oryctolagus cuniculus) II: effects of type of unconditioned stimulus (airpuff vs. periorbital shock) and unconditioned stimulus intensity.

Previous research has implicated the medial prefrontal cortex (mPFC) in the control of classically conditioned autonomic and somatomotor responses. In eyeblink (EB) classical conditioning prefrontal involvement appears to be limited to paradigms that are more difficult to learn, in that acquisition is slower. These include trace conditioning and discrimination/reversal. Some of this research suggests that the participation of mPFC in classical EB conditioning is related to the intensity or type of unconditioned stimulus (US) employed. In the present two experiments we thus studied the effects of manipulation of periorbital shock intensity as the US in Experiment 1 and in Experiment 2 the intensity of a corneal airpuff as the US on Pavlovian trace EB conditioning. The results indicate that there are optimal intensities of both airpuff and periorbital shock as the US in the demonstration of mPFC control of trace classical EB conditioning.

Dynamin 3 is a component of the postsynapse, where it interacts with mGluR5 and Homer.

The dynamins comprise a large family of mechanoenzymes known to participate in membrane modeling events. All three conventional dynamin genes (Dyn1, Dyn2, Dyn3) are expressed in mammalian brain and produce more than 27 different dynamin proteins as a result of alternative splicing. Past studies have suggested that Dyn1 participates in specialized neuronal functions such as rapid synaptic vesicle recycling, while Dyn2 may mediate the conventional clathrin-mediated uptake of surface receptors. Currently, the distribution, expression, and function of Dyn3 in neurons, or in any other cell type, are completely undefined. Here, we demonstrate that Dyn1 and Dyn3 localize differentially in the synapse. Dyn1 concentrates within the presynaptic compartment, while Dyn3 localizes to dendritic spine tips. Within the postsynaptic density (PSD), we found Dyn3, but not Dyn1, to be part of a biochemically isolated complex comprised of Homer and metabotropic glutamate receptors. Finally, although dominant-negative Dyn3 did not seem to inhibit receptor endocytosis, overexpression of a specific Dyn3 spliced variant in mature neurons caused a marked remodeling of dendritic spines. These data suggest that Dyn3 is a postsynaptic dynamin and, like its binding partner Homer, plays a significant role in dendritic spine morphogenesis and remodeling.

The mitochondrial protein hFis1 regulates mitochondrial fission in mammalian cells through an interaction with the dynamin-like protein DLP1.

The yeast protein Fis1p has been shown to participate in mitochondrial fission mediated by the dynamin-related protein Dnm1p. In mammalian cells, the dynamin-like protein DLP1/Drp1 functions as a mitochondrial fission protein, but the mechanisms by which DLP1/Drp1 and the mitochondrial membrane interact during the fission process are undefined. In this study, we have tested the role of a mammalian homologue of Fis1p, hFis1, and provided new and mechanistic information about the control of mitochondrial fission in mammalian cells. Through differential tagging and deletion experiments, we demonstrate that the intact C-terminal structure of hFis1 is essential for mitochondrial localization, whereas the N-terminal region of hFis1 is necessary for mitochondrial fission. Remarkably, an increased level of cellular hFis1 strongly promotes mitochondrial fission, resulting in an accumulation of fragmented mitochondria. Conversely, cell microinjection of hFis1 antibodies or treatment with hFis1 antisense oligonucleotides induces an elongated and collapsed mitochondrial morphology. Further, fluorescence resonance energy transfer and coimmunoprecipitation studies demonstrate that hFis1 interacts with DLP1. These results suggest that hFis1 participates in mitochondrial fission through an interaction that recruits DLP1 from the cytosol. We propose that hFis1 is a limiting factor in mitochondrial fission and that the number of hFis1 molecules on the mitochondrial surface determines fission frequency.

Prefrontal control of trace versus delay eyeblink conditioning: role of the unconditioned stimulus in rabbits (Oryctolagus cuniculus).

The conditioned eyeblink (EB) response was studied with trace conditioning procedures in rabbits (Oryctolagus cuniculus) with lesions to the medial prefrontal cortex (mPFC) or sham lesions. Three experiments were performed in which either periorbital shock or a corneal airpuff served as the unconditioned stimulus (US) in separate groups of sham or mPFC-lesioned rabbits. Acquisition of the EB conditioned response (CR) was faster and reached a higher asymptote with the eyeshock US than with the airpuff US. However, mPFC lesion-induced trace conditioning deficits were obtained only in the groups that received the airpuff US. All rabbits showed normal delay conditioning and extinction. These results suggest that mPFC mediates trace EB conditioning when emotional arousal is low. However, in circumstances when emotional arousal may be high (i.e., during exposure to aversive periorbital shock), other structures (such as amygdala) may be activated to permit learning even in the absence of input from mPFC.

Respiration and metabolism of the resting European paper wasp (Polistes dominulus).

The European paper wasp, Polistes dominulus Christ, is an abundant wasp species in South and Central Europe which dispersed to the north in recent times. Polistes dominulus exhibits an energy-extensive mode of life, spending much time resting at the nest, which should be reflected in adaptations regarding gas exchange and standard metabolism. We analysed the resting metabolism (CO2 emission) of Polistes dominulus workers in the ambient temperature range an individual may be exposed to during a breeding season (T a = 2.4-40.6 °C) via flow through respirometry. Behaviour and endothermic activity were assessed by infrared thermography. With rising T a, CO2 release followed an exponential increase from 27 to 149 and 802 nl g(-1) min(-1) at T a = 3, 20 and 35 °C, respectively. Measurements of the thermal regime at the nest showed that resting P. dominulus are most of the time in the lower range of their standard metabolic curve. A comparison with a "highly energetic" wasp like Vespula sp. revealed that Polistes dominulus not only optimises behaviour but also reduces metabolism to save energy. The CO2 emission patterns changed with ambient temperature, from discontinuous (≤ 25 °C) to cyclic (25-36 °C) and continuous gas exchange at higher temperatures. A pronounced break appeared in the data progression regarding cycle frequency and CO2 emission per gas exchange cycle between 15 and 10 °C. This striking change in gas exchange features indicates a physiological adaptation to special respiratory requirements at low temperatures.

Oxymetazoline inhibits and resolves inflammatory reactions in human neutrophils.

The nasal decongestant oxymetazoline (OMZ) exhibits anti-oxidative and anti-inflammatory properties (I. Beck-Speier et al., J Pharmacol Exp Ther. 2006;316:842-851). In a follow up study, we hypothesized that OMZ generates pro-resolving lipoxins being paralleled by production of immune-modulating prostaglandin E(2) (PGE(2)) and anti-inflammatory 15(S)-hydroxy-eicosatetraenoic acid [15(S)-HETE] and depletion of pro-inflammatory leukotriene B(4) (LTB(4)). Human neutrophils (PMN) were chosen as the cellular system. The effect of OMZ on these parameters as well as on respiratory burst activity and oxidative stress marker 8-isprostane was analyzed in unstimulated and co-stimulated PMN by ultrafine carbon particles (UCP) or opsonized zymosan (OZ), respectively. In unstimulated cells, OMZ induced formation of PGE(2), 15(S)-HETE, and LXA(4). The levels of LTB(4) and 8-isoprostane were not affected, whereas respiratory burst activity was drastically inhibited. In UCP- and OZ-stimulated control cells, all parameters were elevated. Here, OMZ maintained the increased levels of PGE(2), 15(S)-HETE, and LXA(4), but substantially suppressed levels of LTB(4) and 8-isoprostane and inhibited the respiratory burst activity. These findings suggest a switch from the pro-inflammatory eicosanoid class LTB(4) to the pro-resolving LXA(4). Since LXA(4) is most relevant in returning inflamed tissue to homeostasis, OMZ is postulated to terminate rhinitis-related inflammation, thus contributing to shortening of disease duration.

Impairments in trace EB conditioning by knife-cut lesions to the fornix in rabbits: reversal by galantamine.

Previous work in our laboratory demonstrated that galantamine, a cholinesterase inhibitor and weak cholinergic agonist, facilitated classical trace eyeblink conditioning in healthy, young rabbits [Simon, B. B., Knuckley, B., & Powell, D. A. (2004). Galantamine facilitates acquisition of a trace-conditioned eyeblink response in healthy, young rabbits. Learning & Memory, 11(1), 116-122.]. The current study investigated the effects of galantamine (0.0 or 3.0mg/kg) in rabbits sustaining knife-cut lesions to the fimbria-fornix, a major projection pathway connecting the hippocampus to cortical and subcortical brain structures involved in the formation of long-term memories. Two experiments were conducted. Experiment one assessed the effects of knife-cut lesions to the fornix or sham surgeries on trace eyeblink (EB) conditioning. Results indicate that fornix lesions significantly retarded EB conditioning when trace parameters were employed. Experiment 2 assessed whether treatment with galantamine would reverse the deficits caused by fornix damage. Results indicate that 3.0mg/kg GAL reversed trace EB conditioning deficits in animals with fornix knife-cut lesions. These findings suggest that galantamine may provide benefit in the reversal of cognitive dysfunction following certain types of brain damage, especially damage involving hippocampal structures.

H(2)O(2)-induced kinetic and chemical modifications of smooth muscle myosin: correlation to effects of H(2)O(2) on airway smooth muscle.

The effect of H(2)O(2) on smooth muscle heavy meromyosin (HMM) and subfragment 1 (S1) was examined. The number of molecules that retained the ability to bind ATP and the actinactivated rate of P(i) release were measured by single-turnover kinetics. H(2)O(2) treatment caused a decrease in HMM regulation from 800- to 27-fold. For unphosphorylated and phosphorylated heavy meromyosin and for S1, approximately 50% of the molecules lost the ability to bind to ATP. H(2)O(2) treatment in the presence of EDTA protected against ATPase inactivation and against the loss of total ATP binding. Inactivation of S1 versus time correlated to a loss of reactive thiols. Treatment of H(2)O(2)-inactivated phosphorylated HMM or S1 with dithiothreitol partially reactivated the ATPase but had no effect on total ATP binding. H(2)O(2)-inactivated S1 contained a prominent cross-link between the N-terminal 65-kDa and C-terminal 26-kDa heavy chain regions. Mass spectral studies revealed that at least seven thiols in the heavy chain and the essential light chain were oxidized to cysteic acid. In thiophosphorylated porcine tracheal muscle strips at pCa 9 + 2.1 mM ATP, H(2)O(2) caused a approximately 50% decrease in the amplitude but did not alter the rate of force generation, suggesting that H(2)O(2) directly affects the force generating complex. Dithiothreitol treatment reversed the H(2)O(2) inhibition of the maximal force by approximately 50%. These data, when compared with the in vitro kinetic data, are consistent with a H(2)O(2)-induced loss of functional myosin heads in the muscle.