The function of juvenile-adult transition axis in female sexual receptivity of Drosophila melanogaster.

Female sexual receptivity is essential for reproduction of a species. Neuropeptides play the main role in regulating female receptivity. However, whether neuropeptides regulate female sexual receptivity during the neurodevelopment is unknown. Here, we found the peptide hormone prothoracicotropic hormone (PTTH), which belongs to the insect PG (prothoracic gland) axis, negatively regulated virgin female receptivity through ecdysone during neurodevelopment in Drosophila melanogaster. We identified PTTH neurons as doublesex-positive neurons, they regulated virgin female receptivity before the metamorphosis during the third-instar larval stage. PTTH deletion resulted in the increased EcR-A expression in the whole newly formed prepupae. Furthermore, the ecdysone receptor EcR-A in pC1 neurons positively regulated virgin female receptivity during metamorphosis. The decreased EcR-A in pC1 neurons induced abnormal morphological development of pC1 neurons without changing neural activity. Among all subtypes of pC1 neurons, the function of EcR-A in pC1b neurons was necessary for virgin female copulation rate. These suggested that the changes of synaptic connections between pC1b and other neurons decreased female copulation rate. Moreover, female receptivity significantly decreased when the expression of PTTH receptor Torso was reduced in pC1 neurons. This suggested that PTTH not only regulates female receptivity through ecdysone but also through affecting female receptivity associated neurons directly. The PG axis has similar functional strategy as the hypothalamic-pituitary-gonadal axis in mammals to trigger the juvenile-adult transition. Our work suggests a general mechanism underlying which the neurodevelopment during maturation regulates female sexual receptivity.

Revealing the Combined Effect of Active Sites and Intra-Particle Diffusion on Adsorption Mechanism of Methylene Blue on Activated Red-Pulp Pomelo Peel Biochar.

Phosphoric acid-activated biochar has been proven to be a promising adsorbent for pollutant removal in an aqueous solution. It is urgent to understand how surface adsorption and intra-particle diffusion synergistically contribute to the adsorption kinetic process of dyes. In this work, we prepared a series of PPC adsorbents (PPCs) from red-pulp pomelo peel under different pyrolysis temperatures (150-350 °C), which have a broad specific surface area range from 3.065 m2/g to 1274.577 m2/g. The active sites on the surface of PPCs have shown specific change laws of decreasing hydroxyl groups and increasing phosphate ester groups occurring as the pyrolysis temperature rises. Both reaction models (PFO and PSO models) and diffusion models (intra-particle diffusion models) have been applied to simulate the adsorption experimental data to verify the hypothesis deduced from the Elovich model. PPC-300 exhibits the highest adsorption capacity of MB (423 mg/g) under given conditions. Due to its large quantities of active sites on the external and internal surfaces (1274.577 m2/g), a fast adsorption equilibrium can be achieved within 60 min (with an initial MB concentration of 100 ppm). PPC-300 and PPC-350 also exhibit an intra-particle-diffusion-controlled adsorption kinetic process with a low initial MB concentration (100 ppm) or at the very beginning and final stage of adsorption with a high initial MB concentration (300 ppm) at 40 °C, considering that the diffusion is likely hindered by adsorbate molecules through internal pore channels at the middle stage of adsorption in these cases.

Effects of lithium on aggression in Drosophila.

Lithium is a common medication used to treat mania and bipolar disorder, but the mechanisms by which lithium stabilizes mood and modifies aggression are still not fully understood. Here we found that acute but not chronic lithium significantly suppresses aggression without affecting locomotion in Drosophila melanogaster. Male flies treated with acute lithium are also less competitive than control males in establishing dominance. We also provided evidence that glycogen synthase kinase-3 (GSK-3), a well-known target of lithium, plays an important role in the anti-aggressive effect of lithium in Drosophila. Our genetic data showed that acute knockdown of GSK-3 in neurons can mimic the inhibitory effect of acute lithium on aggression, while specific overexpression of GSK-3 in a subset of P1 neurons profoundly promotes aggression which can be partially rescued by acute lithium application. Thus, these findings revealed the inhibitory effect of lithium on aggression in Drosophila and laid a groundwork for using Drosophila as a powerful model to investigate the mechanisms by which lithium reduces aggression.

Serotonin Signaling Modulates Sexual Receptivity of Virgin Female Drosophila.

The choice of females to accept or reject male courtship is a critical decision for animal reproduction. Serotonin (5-hydroxytryptamine; 5-HT) has been found to regulate sexual behavior in many species, but it is unclear how 5-HT and its receptors function to regulate different aspects of sexual behavior. Here we used Drosophila melanogaster as the model animal to investigate how 5-HT and its receptors modulate female sexual receptivity. We found that knockout of tryptophan hydroxylase (Trh), which is involved in the biosynthesis of 5-HT, severely reduced virgin female receptivity without affecting post-mating behaviors. We identified a subset of sexually dimorphic Trh neurons that co-expressed fruitless (fru), in which the activity was correlated with sexual receptivity in females. We also found that 5-HT1A and 5-HT7 receptors regulate virgin female receptivity. Our findings demonstrate how 5-HT functions in sexually dimorphic neurons to promote virgin female receptivity through two of its receptors.

A neuropeptide regulates fighting behavior in Drosophila melanogaster.

Aggressive behavior is regulated by various neuromodulators such as neuropeptides and biogenic amines. Here we found that the neuropeptide Drosulfakinin (Dsk) modulates aggression in Drosophila melanogaster. Knock-out of Dsk or Dsk receptor CCKLR-17D1 reduced aggression. Activation and inactivation of Dsk-expressing neurons increased and decreased male aggressive behavior, respectively. Moreover, data from transsynaptic tracing, electrophysiology and behavioral epistasis reveal that Dsk-expressing neurons function downstream of a subset of P1 neurons (P1a-splitGAL4) to control fighting behavior. In addition, winners show increased calcium activity in Dsk-expressing neurons. Conditional overexpression of Dsk promotes social dominance, suggesting a positive correlation between Dsk signaling and winning effects. The mammalian ortholog CCK has been implicated in mammal aggression, thus our work suggests a conserved neuromodulatory system for the modulation of aggressive behavior.

MiR-154 Functions as a Tumor Suppressor in Glioblastoma by Targeting Wnt5a.

Recently, deregulated microRNA (miRNA) expression contributes to the development and progression of human glioblastoma. The aim of the present study was to evaluate the level of miR-154 and Wnt5a in glioblastoma tissues and cells. We further investigated the molecular mechanisms of miR-154 and Wnt5a in glioblastoma cell lines. In the present study, we found that miR-154 expression was downregulated in glioblastoma tissues and U87, U251, and A172 cells (all p < 0.001). By contrast, Wnt5a was upregulated. Furthermore, we found that overexpression of miR-154 suppressed cell migration and invasion of U87 and U251 cells. Mechanically, overexpression of miR-154 inhibited epithelial-to-mesenchymal transition (EMT) of U87 and U251 cells. Importantly, we identified that the 3' untranslated region (3'-UTR) of Wnt5a was a direct target of miR-154. Luciferase reporter assays confirmed that miR-154 binding to the 3'-UTR regions of Wnt5a inhibited the expression of Wnt5a in U87 and U251 cells. At the same time, overexpressed Wnt5a also reversed EMT inhibited by miR-154. In conclusion, this study suggested that high miR-154 expression suppressed glioblastoma cell migration, invasion, and EMT development through targeting Wnt5a, which may be recommended as a therapeutic target for glioblastoma.

Low-Dose Versus Standard-Dose Tissue Plasminogen Activator in Acute Ischemic Stroke in Asian Populations: A Meta-Analysis.

Recent studies have investigated the most efficacious dose of intravenous tissue plasminogen activator (IV-tPA) for acute ischemic stroke (AIS) patients. There remains no definitive consensus concerning the superior efficacious IV-tPA dose (standard- vs. low-dose), prompting us to perform a meta-analysis comparing the efficacy and safety profile of standard- versus low-dose IV-tPA.We identified relevant studies pertaining to the specific aim of our meta-analysis by searching PubMed and EMBASE (January 1990-September 2015) Either a fixed- or random-effects model was employed (dependent upon data heterogeneity) to analyze the efficacy and safety outcome.Ten cohort studies involving 4389 sum patients were included in the meta-analysis. By using the random-effects model, the meta-analysis indicated no statistically significant difference in favorable functional outcome (modified Rankin scale 0-1) at 3 months (heterogeneity: χ = 17.45, P = 0.04, I = 48%; OR: 0.88 [95% CI: 0.71-1.11]; P = 0.28) and incidence of symptomatic intracranial hemorrhage (SICH) (heterogeneity: χ = 14.41, P = 0.11, I = 38%; OR: 1.19 [95% CI: 0.76 to 1.87]; P = 0.45) between the standard- and low-dose groups. The fixed-effects model demonstrated no significant difference in mortality within 3 months (heterogeneity: χ = 6.73, P = 0.57, I = 0%; OR: 0.91 [95% CI: 0.73-1.12]; P = 0.37) between the standard- and low-dose groups.Low-dose IV-tPA is comparable to standard-dose IV-tPA in both efficacy (favorable functional outcome) and safety (SICH and mortality). Confirmation of these findings through randomized trials is warranted.

Intraperitoneal administration of thioredoxin decreases brain damage from ischemic stroke.

Recent studies demonstrate that Thioredixin (Trx) possesses a neuronal protective effect and closely relates to oxidative stress and apoptosis of cerebral ischemia injury. The present study was conducted to validate the neuroprotective effect of recombinant human Trx-1 (rhTrx-1) and its potential mechanisms against ischemia injury at middle cerebral artery occlusion (MCAO) in mice. rhTrx-1 was administrated intraperitoneally at a dose of 5, 10 and 20mg/kg 30 min before MCAO in mice, and its neuronal protective effect was evaluated by neurological deficit score, brain dry-wet weight, 2,3,5-triphenyltetrazolium chloride (TTC) staining. The protein carbonyl content and HO-1 were detected to investigate its potential anti-oxidative and anti-inflammatory property, and the anti-apoptotic ability of rhTrx-1 was assessed by casepase-3 and TUNEL staining. The results demonstrated that rhTrx-1 significantly improved neurological functions and reduced cerebral infarction and apoptotic cell death at 24h after MCAO. Moreover, rhTrx-1 resulted in a significant decrease in carbonyl contents and HO-1 against oxidative stress, which turned to be fast reduction during the first 24h and tended to be stable from 24h to 72h after MCAO. The study shows that rhTrx-1 exerts an neuroprotective effect in cerebral ischemia injury. The anti-oxidative, anti-apoptotic and anti-inflammatory properties of rhTrx-1 are more likely to succeed as a therapeutic approach to diminish oxidative stress-induced neuronal apoptotic cell death in acute ischemic stroke.

Activation of peroxisome proliferator-activated receptor ß/δ attenuates acute ischemic stroke on middle cerebral ischemia occlusion in rats.

BACKGROUND: Peroxisome proliferator-activated receptor (PPAR)-ß/δ is a transcription factor that belongs to the nuclear hormone receptor family. There is little information about the effects of the immediate administration of specific ligands of PPAR-ß/δ (GW0742) in animal models of acute ischemic stroke. Using a rat model of middle cerebral ischemia occlusion (MCAO) in vivo, we have investigated the effect of pretreatment with GW0742 before MCAO. METHODS: The neuroprotective effect of GW0742 against acute ischemic stroke was evaluated by the neurologic deficit score (NDS), dry-wet weight, and 2,3,5-triphenyltetrazolium chloride staining. The levels of interleukin (IL)-1ß, nuclear factor (NF)-κB, and tumor necrosis factor (TNF)-α were detected by an enzyme-linked immunosorbent assay. The expressions of inducible nitric oxide synthase (iNOS), Bax, and Bcl-2 were detected by Western blot. The apoptotic cells were counted by in situ terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay. RESULTS: The pretreatment with GW0742 significantly increased the expression of Bcl-2, and significantly decreased in the volume of infarction, NDS, edema, expressions of IL-1ß, NF-κB, TNFα, and Bax, contents of iNOS and the apoptotic cells in infarct cerebral hemisphere compared with rats in the vehicle group at 24 hours after MCAO. CONCLUSIONS: The study suggests the neuroprotective effect of the PPAR-ß/δ ligand GW0742 in acute ischemic stroke by a mechanism that may involve its anti-inflammatory and antiapoptotic action.