Concept: Induced demand
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.
Competition induces allelopathy but suppresses growth and anti-herbivore defence in a chemically rich seaweed
- Proceedings. Biological sciences / The Royal Society
- Published almost 4 years ago
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.
Warifteine, a bisbenzylisoquinoline alkaloid, induces relaxation by activating potassium channels in vascular myocytes.
- Clinical and experimental pharmacology & physiology
- Published almost 5 years ago
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.
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.
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.
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.
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.
Basic helix-loop-helix transcription factor Twist1 is a master regulator of Epithelial-Mesenchymal Transition (EMT), a cellular program implicated in different stages of development as well as metastatic dissemination of carcinomas. Here, we show that Twist1 requires TGF-beta type-I receptor (TGFBR1)-activation to bind an enhancer region of downstream effector ZEB1, thereby inducing ZEB1 transcription and EMT. When TGFBR1-phosphorylation is inhibited, Twist1 generates a distinct cell state characterized by collective invasion, simultaneous proliferation and expression of endothelial markers. By contrast, TGFBR1-activation directs Twist1 to induce stable mesenchymal transdifferentiation through EMT, thereby generating cells that display single-cell invasion, but lose their proliferative capacity. In conclusion, preventing Twist1-induced EMT by inhibiting TGFβ-signaling does not generally block acquisition of invasion, but switches mode from single-cell/non-proliferative to collective/proliferative. Together, these data reveal that transient Twist1-activation induces distinct cell states depending on signaling context and caution against the use of TGFβ-inhibitors as a therapeutic strategy to target invasiveness.
Alveolar bone regeneration has aroused worldwide attention and plays an important role in oral clinics. In recent years, the application of biomaterials to induce osteogenic differentiation of periodontal ligament cells has become the hot topic in the field of alveolar bone regeneration. At present, most existing biomaterials lack osteoinductivity, while extrinsic inducers carry the risk of unwanted side effects. The objective of this work was to study the in vitro functionality of a newly developed hydrolyzed tilapia fish collagen (HFC) for periodontal tissue regeneration. HFC was extracted from the scales of tilapia, human periodontal ligament cells (hPDL cells) were cultured with HFC without the addition of any inducing reagent, and the effects of HFC on cell viability and osteogenic differentiation were investigated. The results revealed that HFC promoted the cell viability of hPDL cells. Furthermore, the upregulation of osteogenic markers ALP, COL I, RUNX2, and OCN at the gene level and the production of osteogenic-related proteins (alkaline phosphatase and osteocalcin) proved the success of osteogenic differentiation of hPDL cells treated with HFC. In addition, we revealed that the effect of HFC was mediated by ERK signaling pathways. Taken together, the data presented in this paper suggested for the first time that HFC is a promising bioactive ingredient for biomaterials used in alveolar bone regeneration.
Recent studies revealed that emodin extracted from Chinese herbs exhibits an anti-cancer effect on different cancer types, including colon cancer. However, the mechanism is not well understood by now. In our study, we confirmed that emodin treatment inhibited cell viability and induced apoptosis in colon cancer cells. Further experiments were taken to found that emodin was also able to induce autophagy, which is indispensible for apoptosis induced by it. More interestingly, emodin treatment also results in mitochondrial dysfunction and ROS accumulation in those colon cancer cells. Finally, we stressed that ROS accumulation is essential for autophagy and apoptosis induced by emodin. In conclusion, emodin induces apoptosis in clone cancer cells through induction of autophagy, during which ROS generation is of the essence. Our findings improve understanding of emodin’s effect on colon cancer suppression and provide new theoretical basis for colon cancer therapy.