SciCombinator

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Concept: Induced demand

273

Food consumption is thought to induce sleepiness. However, little is known about how postprandial sleep is regulated. Here, we simultaneously measured sleep and food intake of individual flies and found a transient rise in sleep following meals. Depending on the amount consumed, the effect ranged from slightly arousing to strongly sleep inducing. Postprandial sleep was positively correlated with ingested volume, protein, and salt-but not sucrose-revealing meal property-specific regulation. Silencing of leucokinin receptor (Lkr) neurons specifically reduced sleep induced by protein consumption. Thermogenetic stimulation of leucokinin (Lk) neurons decreased whereas Lk downregulation by RNAi increased postprandial sleep, suggestive of an inhibitory connection in the Lk-Lkr circuit. We further identified a subset of non-leucokininergic cells proximal to Lkr neurons that rhythmically increased postprandial sleep when silenced, suggesting that these cells are cyclically gated inhibitory inputs to Lkr neurons. Together, these findings reveal the dynamic nature of postprandial sleep.

Concepts: DNA, Protein, Nutrition, Eating, Ingestion, Food, Induced demand, Meal

165

The reward system is a collection of circuits that reinforce behaviors necessary for survival [1, 2]. Given the importance of reproduction for survival, actions that promote successful mating induce pleasurable feeling and are positively reinforced [3, 4]. This principle is conserved in Drosophila, where successful copulation is naturally rewarding to male flies, induces long-term appetitive memories [5], increases brain levels of neuropeptide F (NPF, the fly homolog of neuropeptide Y), and prevents ethanol, known otherwise as rewarding to flies [6, 7], from being rewarding [5]. It is not clear which of the multiple sensory and motor responses performed during mating induces perception of reward. Sexual interactions with female flies that do not reach copulation are not sufficient to reduce ethanol consumption [5], suggesting that only successful mating encounters are rewarding. Here, we uncoupled the initial steps of mating from its final steps and tested the ability of ejaculation to mimic the rewarding value of full copulation. We induced ejaculation by activating neurons that express the neuropeptide corazonin (CRZ) [8] and subsequently measured different aspects of reward. We show that activating Crz-expressing neurons is rewarding to male flies, as they choose to reside in a zone that triggers optogenetic stimulation of Crz neurons and display conditioned preference for an odor paired with the activation. Reminiscent of successful mating, repeated activation of Crz neurons increases npf levels and reduces ethanol consumption. Our results demonstrate that ejaculation stimulated by Crz/Crz-receptor signaling serves as an essential part of the mating reward mechanism in Drosophila. VIDEO ABSTRACT.

Concepts: Male, Reproduction, Neuropeptide, Female, Insect, Sex, Induced demand, Reinforcement

40

Octacosanol, a component of various food materials, possesses prominent biological activities and functions. It fights against cellular stress by increasing glutathione level and thus scavenging oxygen reactive species. However, its anti-stress activity and role in sleep induction remained elusive. We hypothesize that octacosanol can restore stress-affected sleep by mitigating stress. Cage change strategy was used to induce mild stress and sleep disturbance in mice, and effects of octacosanol administration on amount of sleep and stress were investigated. Results showed that octacosanol did not change rapid eye movement (REM) or non-REM (NREM) sleep compared to vehicle in normal mice. However, in cage change experiment, octacosanol induces significant increase in NREM sleep at doses of 100 and 200 mg/kg (75.7 ± 14.9 and 82.7 ± 9.3 min/5 h) compared to vehicle (21.2 ± 5.1 min/5 h), and decreased sleep latency. Octacosanol induced sleep by increasing number of sleep episodes and decreasing wake episode duration. Plasma corticosterone levels were significantly reduced after octacosanol (200 mg/kg) administration, suggesting a decrease in stress level. Octacosanol-induced changes in sleep-wake parameters in stressed-mice were comparable to the values in normal mice. Together, these data clearly showed that, though octacosanol does not alter normal sleep, it clearly alleviates stress and restore stress-affected sleep.

Concepts: Monotonic function, Convex function, Sleep, Probability theory, Rapid eye movement sleep, Induced demand, Lattice, Non-rapid eye movement sleep

30

Many seaweeds and terrestrial plants induce chemical defences in response to herbivory, but whether they induce chemical defences against competitors (allelopathy) remains poorly understood. We evaluated whether two tropical seaweeds induce allelopathy in response to competition with a reef-building coral. We also assessed the effects of competition on seaweed growth and seaweed chemical defence against herbivores. Following 8 days of competition with the coral Porites cylindrica, the chemically rich seaweed Galaxaura filamentosa induced increased allelochemicals and became nearly twice as damaging to the coral. However, it also experienced significantly reduced growth and increased palatability to herbivores (because of reduced chemical defences). Under the same conditions, the seaweed Sargassum polycystum did not induce allelopathy and did not experience a change in growth or palatability. This is the first demonstration of induced allelopathy in a seaweed, or of competitors reducing seaweed chemical defences against herbivores. Our results suggest that the chemical ecology of coral-seaweed-herbivore interactions can be complex and nuanced, highlighting the need to incorporate greater ecological complexity into the study of chemical defence.

Concepts: Algae, Photosynthesis, Plant, Induced demand, Seaweed, Herbivory, Plant defense against herbivory, Sargassum

28

This study employed functional and electrophysiological approaches to investigate the mechanisms by which warifteine, a bisbenzylisoquinoline alkaloid isolated from Cissampelos sympodialis Eichl, causes vasorelaxation in the rat thoracic aorta. Warifteine (1 pM-10 μM) induced a concentration-dependent relaxation (pD(2) =9.40±0.06, n=5) in endothelium-intact aortic rings pre-contracted with noradrenaline (10 - 100 μM). The relaxation effects were not attenuated after endothelium removal. Warifteine also induced relaxations (pD(2) =9.2±0.19,n=8) in rings pre-contracted with PGF2(alfa) (1 - 10 mM). In contrast, the relaxant activity of warifteine was nearly abolished in high-K(+) (80 mM) pre-contracted aortic rings. In preparations incubated with 20 mM KCl or K(+) channel blockers, including: TEA (1, 3 and 5 mM), iberiotoxin (20 nM), 4-aminopyridine (1 mM) or glibenclamide (10 μM), the vasorelaxant activity of warifteine was markedly reduced. Furthermore, BaCl(2) (1 mM) did not affect the relaxant effects of warifteine. In vascular myocytes, warifteine (100 nM) significantly increased whole-cell K(+) currents (at 70 mV). In nominally Ca(2+) -free conditions, warifteine did not reduce extracellular Ca(2+) -induced contractions in high-K(+) or noradrenaline (100 μM) pre-stimulated rings. 4. Taken together, these results indicate that warifteine can induce potent concentration-dependent relaxation in the rat aorta via an endothelium-independent mechanism that involves the activation of K(+) channels. © 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Wiley Publishing Asia Pty Ltd.

Concepts: Heart, Orders of magnitude, Ion channel, Abdominal aorta, Aorta, Descending aorta, Thoracic aorta, Induced demand

28

The mechanism by which cells decide to skip mitosis to become polyploid is largely undefined. Here we used a high-content image-based screen to identify small-molecule probes that induce polyploidization of megakaryocytic leukemia cells and serve as perturbagens to help understand this process. Our study implicates five networks of kinases that regulate the switch to polyploidy. Moreover, we find that dimethylfasudil (diMF, H-1152P) selectively increased polyploidization, mature cell-surface marker expression, and apoptosis of malignant megakaryocytes. An integrated target identification approach employing proteomic and shRNA screening revealed that a major target of diMF is Aurora kinase A (AURKA). We further find that MLN8237 (Alisertib), a selective inhibitor of AURKA, induced polyploidization and expression of mature megakaryocyte markers in acute megakaryocytic leukemia (AMKL) blasts and displayed potent anti-AMKL activity in vivo. Our findings provide a rationale to support clinical trials of MLN8237 and other inducers of polyploidization and differentiation in AMKL.

Concepts: Protein, Cancer, Signal transduction, Leukemia, P53, Aurora kinase, Aurora A kinase, Induced demand

27

Neglect patients show contralesional deficits in egocentric and object-centred visuospatial tasks. The extent to which these different phenomena are modulated by sensory stimulation remains to be clarified. Subliminal galvanic vestibular stimulation (GVS) induces imperceptible, polarity-specific changes in the cortical vestibular systems without the unpleasant side effects (nystagmus, vertigo) induced by caloric vestibular stimulation. While previous studies showed vestibular stimulation effects on egocentric spatial neglect phenomena, such effects were rarely demonstrated in object-centred neglect. Here, we applied bipolar subsensory GVS over the mastoids (mean intensity: 0.7mA) to investigate its influence on egocentric (digit cancellation, text copying), object-centred (copy of symmetrical figures), or both (line bisection) components of visual neglect in 24 patients with unilateral right hemisphere stroke. Patients were assigned to two patient groups (impaired vs. normal in the respective task) on the basis of cut-off scores derived from the literature or from normal controls. Both groups performed all tasks under three experimental conditions carried out on three separate days: (a) sham/baseline GVS where no electric current was applied, (b) left cathodal/right anodal (CL/AR) GVS and © left anodal/right cathodal (AL/CR) GVS, for a period of 20min per session. CL/AR GVS significantly improved line bisection and text copying whereas AL/CR GVS significantly ameliorated figure copying and digit cancellation. These GVS effects were selectively observed in the impaired- but not in the unimpaired patient group. In conclusion, subliminal GVS modulates ego- and object-centred components of visual neglect rapidly. Implications for neurorehabilitation are discussed.

Concepts: Patient, Vestibular system, Sensory system, Task, Induced demand, Hemispatial neglect, Galvanic Vestibular Stimulation

27

The effect of recovery mode (Active [AR] vs. Passive [PR]) on plasma catecholamine (Adrenaline [A] and Noradrenaline [NA]) responses to maximal exercise (Exemax) was studied during interval training (IT). 24 male subjects (21.1±1.1 years) were randomly assigned to a control group (CG, n=6), AR training group (ARG, n=9) or PR group (PRG, n=9). ARG and PRG participated in an IT program 3 times a week for 7 weeks. Before and after training, maximal oxygen uptake (VO2max) and maximal aerobic velocity (MAV) were measured. Plasma A and NA were determined at rest, at the end of Exemax and after 10 and 30 min of recovery. Training induced significant changes only in ARG: an increase of VO2max and MAV along with a significant increase of A and NA at the end of Exemax (2.82±0.15 vs. 1.03±0.15 nmol/l and 7.22±0.36 vs. 6.65±0.57 nmol/l, respectively p<0.05). The ratio A/NA measured at the end of Exemax also increased significantly after training (0.41±0.11 vs. 0.16±0.08, P>0.05). The present results show that IT with AR induces a significant increase of A and NA concentrations in response to maximal exercise. The study furthermore shows that IT program with AR may induce more stress than the same program with PR.

Concepts: Epinephrine, Dopamine, Norepinephrine, Exercise physiology, Induced demand, Cooper test, VO2 max, Physical fitness

26

Background: Endoplasmic reticulum (ER) stress has been implicated in inducing epithelial-mesenchymal transition (EMT). ER stress is also known to induce autophagy. However, it is unclear whether ER stress-induced autophagy contributes to EMT. We hypothesized that ER stress might induce EMT through autophagy via activation of c-Src kinase in tubular epithelial cells. Method: All experiments were performed using HK-2 cells. Protein expression was measured by Western blot analysis. Immunofluorescence and small interfering RNA (siRNA) experiments were performed. Results: Chemical ER stress inducers such as tunicamycin (TM, 0.2 μM) and thapsigargin (TG, 0.2 μM) induced EMT, as shown by upregulation of α-smooth muscle actin and downregulation of E-cadherin. ER stress inhibitors such as 4-PBA and salubrinal suppressed both TM- and TG-induced EMT. TM and TG also induced autophagy, as evidenced by upregulation of LC3-II and beclin-1, which were abolished by pretreatment with ER stress inhibitors. Transfection with siRNA targeting ER stress protein (IRE-1) blocked the TM- or TG-induced EMT and autophagy. Autophagy inhibitors such as 3-methyladenine and bafilomycin inhibited the TM- or TG-induced EMT. Transfection with siRNA targeting autophagy protein (beclin-1) also blocked the TM- or TG-induced EMT. Both TM and TG induced activation of c-Src kinase. Inhibitor of c-Src kinase (PP2) suppressed the TM- or TG-induced autophagy and EMT. Conclusion: ER stress by TM or TG induced EMT through autophagy via activation of c-Src kinase in tubular epithelial cells. © 2014 S. Karger AG, Basel.

Concepts: Protein, Gene expression, Molecular biology, RNA, Endoplasmic reticulum, Messenger RNA, Actin, Induced demand

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Eosinophilic folliculitis (EF) is an idiopathic dermatitis included in the spectrum of eosinophilic pustular follicular reactions. Demodex folliculorum has been implicated as contributing to the pathogenesis of human immunodeficiency virus-associated EF, but it has not been described outside this context. We present an immunocompetent 65-year-old white man with a 5-year history of recurrent pruritic erythematous and oedematous lesions on his face, neck and scalp. Histopathologically, an eosinophilic microabcess with Demodex folliculorum mite within a pilosebaceous follicle was seen, and considered the causal agent. There were also accumulations of eosinophil granules on collagen bundles, and flame figure formations in the dermis. We believe that ‘eosinophilic follicular reaction’ is an appropriate term to describe this case of EF induced by D. folliculorum and thus distinguish it from the idiopathic form of EF. Moreover, this case suggests that D. folliculorum can sometimes induce an eosinophilic immune reaction.

Concepts: Immune system, Inflammation, Chemical reaction, Anatomical pathology, Induced demand, Demodex, Demodex folliculorum, Demodex brevis