Effects of Kisspeptin1 on Electrical Activity of an Extrahypothalamic Population of Gonadotropin-Releasing Hormone Neurons in Medaka (Oryzias latipes)

Kisspeptin (product of the kiss1 gene) is the most potent known activator of the hypothalamo-pituitary-gonadal axis. Both kiss1 and the kisspeptin receptor are highly expressed in the hypothalamus of vertebrates, and low doses of kisspeptin have a robust and long-lasting stimulatory effect on the rate of action potential firing of hypophysiotropic gonadotropin releasing hormone-1 (GnRH1) neurons in mice. Fish have multiple populations of GnRH neurons distinguished by their location in the brain and the GnRH gene that they express. GnRH3 neurons located in the terminal nerve (TN) associated with the olfactory bulb are neuromodulatory and do not play a direct role in regulating pituitary-gonadal function. In medaka fish, the electrical activity of TN-GnRH3 neurons is modulated by visual cues from conspecifics, and is thought to act as a transmitter of information from the external environment to the central nervous system. TN-GnRH3 neurons also play a role in sexual motivation and arousal states, making them an important population of neurons to study for understanding coordination of complex behaviors. We investigated the role of kisspeptin in regulating electrical activity of TN-GnRH3 neurons in adult medaka. Using electrophysiology in an intact brain preparation, we show that a relatively brief treatment with 100 nM of kisspeptin had a long-lasting stimulatory effect on the electrical activity of an extrahypothalamic population of GnRH neurons. Dose-response analysis suggests a relatively narrow activational range of this neuropeptide. Further, blocking action potential firing with tetrodotoxin and blocking synaptic transmission with a low Ca2+/high Mg2+ solution inhibited the stimulatory action of kisspeptin on electrical activity, indicating that kisspeptin is acting indirectly through synaptic regulation to excite TN-GnRH3 neurons. Our findings provide a new perspective on kisspeptin's broader functions within the central nervous system, through its regulation of an extrahypothalamic population of GnRH neurons involved in multiple neuromodulatory functions

Aberrant expression of CD133 protein correlates with Ki-67 expression and is a prognostic marker in gastric adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>The relationships between the expression of CD133, Ki-67 and prognosis in gastric adenocarcinoma are unknown and needs exploring.</p> <p>Methods</p> <p>The samples of gastric adenocarcinoma from 336 Chinese patients with follow-up were analyzed for CD133 and Ki-67 protein expressions by immunohistochemical method.</p> <p>Results</p> <p>CD133 was expressed in up to 57.4% (193/336) of this group of gastric carcinoma. The expression of CD133 was significantly higher in carcinoma than in normal (<it>P </it>= 0.0001) and dysplastic mucosas (<it>P </it>= 0.004). CD133 was positive corresponded with the tumour size, grade, infiltrative depth and clinical stage (all <it>P </it>< 0.05). The overall mean survival time of the patients with CD133 positive expression was shorter than that of patients with negative expression (<it>P </it>= 0.0001). The expression of CD133 has a positive correlation with that of Ki-67 (r = 0.188, <it>P </it>= 0.001) in gastric adenocarcinoma. CD133 was an independent prognostic indicator. (<it>P </it>= 0.0001).</p> <p>Conclusions</p> <p>It is suggested that CD133 may play an important role in the evolution of gastric adenocarcinoma and should be considered as a potential marker for the prognosis.</p

Iterative Algorithms for System of Generalized Mixed Equilibrium Problems

Abstract. The purpose of this paper is to present an iterative algorithm for system of generalized mixed equilibrium problems in Banach space. We prove convergence theorems of the iterative algorithm for finding a common element of the fixed point set of relatively nonexpansive mappings and the solution set of system of generalized mixed equilibrium problems in Banach space under some suitable conditions. Our results extend and improve previous result o

Nitrogen Use Efficiency in Rice

Food security is a major global issue because of the growing population and decreasing land area. Rice (Oryza sativa L.) is the most important staple cereal crop in the world. Application of nitrogen (N) fertilizer has improved crop yield in the world during the past five decades but with considerable negative impacts on the environment. New solutions are therefore urgently needed to simultaneously increase yields while maintaining or preferably decreasing applied N to maximize the nitrogen use efficiency (NUE) of crops. Plant NUE is inherently complex with each step (including N uptake, translocation, assimilation, and remobilization) governed by multiple interacting genetic and environmental factors. Based on the current knowledge, we propose some possible approaches enhancing NUE, by molecular manipulation selecting candidate genes and agricultural integrated management practices for NUE improvement. Developing an integrated research program combining approaches, mainly based on whole-plant physiology, quantitative genetics, forward and reverse genetics, and agronomy approaches to improve NUE, is a major objective in the future

Optimizing Gear Shifting Strategy for Off-Road Vehicle with Dynamic Programming

Gear shifting strategy of vehicle is important aid for the acquisition of dynamic performance and high economy. A dynamic programming (DP) algorithm is used to optimize the gear shifting schedule for off-road vehicle by using an objective function that weighs fuel use and trip time. The optimization is accomplished through discrete dynamic programming and a trade-off between trip time and fuel consumption is analyzed. By using concave and convex surface road as road profile, an optimal gear shifting strategy is used to control the longitudinal behavior of the vehicle. Simulation results show that the trip time can be reduced by powerful gear shifting strategy and fuel consumption can achieve high economy with economical gear shifting strategy in different initial conditions and route cases

The effect of Shenmai injection on the proliferation of Rat airway smooth muscle cells in asthma and underlying mechanism

BACKGROUND: Over-proliferation of airway smooth muscle cell (ASMC) is one of the important contributors to airway remodeling in asthma. The aim of this study was to investigate the effect of Shenmai injection (SMI) on the proliferation of the rat ASMC in asthma. METHODS: Rats were randomly divided into three groups: the control group, the asthma group, and the SMI treatment group. Reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry staining were used to detect the mRNA and protein expression of transient receptor potential vanilloid 1 (TRPV1) and proliferating cell nuclear antigen (PCNA) in rat ASMC respectively. Intracellular Ca(2+) concentration ( [Ca(2+)]i ) in rat ASMC were measured with Fluo-3/AM by confocal microscopy. The proliferation was detected by MTT assay. RESULTS: Compared with the control group, the asthma group showed an increased expression of TRPV1 and [Ca(2+)]i in rat ASMC. The expression of PCNA and absorbance of MTT assay in asthma rat ASMC was also significantly increased. SMI could significantly decrease the expression of TRPV1 channel and [Ca(2+)]i in the asthmatic rat ASMC. Furthermore, the expression of PCNA and absorbance of MTT assay in asthmatic rat ASMC was significantly reduced after SMI treatment. CONCLUSIONS: SMI may prevent asthma-induced ASMC over-proliferation probably by inhibiting the expression of TRPV1 channel, which regulates the intracellular calcium concentration

Transcriptome Analysis and Ultrastructure Observation Reveal that Hawthorn Fruit Softening Is due to Cellulose/Hemicellulose Degradation

Softening, a common phenomenon in many fruits, is a well coordinated and genetically determined process. However, the process of flesh softening during ripening has rarely been described in hawthorn. In this study, we found that ‘Ruanrou Shanlihong 3 Hao’ fruits became softer during ripening, whereas ‘Qiu JinXing’ fruits remained hard. At late developmental stages, the firmness of ‘Ruanrou Shanlihong 3 Hao’ fruits rapidly declined, and that of ‘Qiu JinXing’ fruits remained essentially unchanged. According to transmission electron microscopy (TEM), the middle lamella of ‘Qiu JinXing’ and ‘Ruanrou Shanlihong 3 Hao’ fruit flesh was largely degraded as the fruits matured. Microfilaments in ‘Qiu JinXing’ flesh were arranged close together and were deep in color, whereas those in ‘Ruanrou Shanlihong 3 Hao’ fruit flesh were arranged loosely, partially degraded and light in color. RNA-Seq analysis yielded approximately 46.72 Gb of clean data and 72,837 unigenes. Galactose metabolism and pentose and glucuronate interconversions are involved in cell wall metabolism, play an important role in hawthorn texture. We identified 85 unigenes related to the cell wall between hard- and soft-fleshed hawthorn fruits. Based on data analysis and real-time PCR, we suggest that β-GAL and PE4 have important functions in early fruit softening. The genes Ffase, Gns, α-GAL, PE63, XTH and CWP, which are involved in cell wall degradation, are responsible for the different textures of hawthorn fruits. Thus, we hypothesize that the different textures of ‘Qiu JinXing’ and ‘Ruanrou Shanlihong 3 Hao’ fruits at maturity mainly result from cellulose/hemicelluloses degradation rather than from lamella degradation. Overall, we propose that different types of hydrolytic enzymes in cells interact to degrade the cell wall, resulting in ultramicroscopic Structure changes in the cell wall and, consequently, fruit softening. These results provide fundamental insight regarding the mechanisms by which hawthorn fruits acquire different textures and also lay a solid foundation for further research

Id2 promotes the invasive growth of MCF-7 and SKOV-3 cells by a novel mechanism independent of dimerization to basic helix-loop-helix factors

<p>Abstract</p> <p>Background</p> <p>Inhibitor of differentiation 2 (<it>Id2</it>) is a critical factor for cell proliferation and differentiation in normal vertebrate development. Most of the biological function of Id2 has been ascribed to its helix-loop-helix motif. Overexpression of Id2 is frequently observed in various human tumors, but its role for invasion potential in tumor cells is dispute. We aimed to reveal the role of Id2 in invasion potential in poorly invasive and estrogen receptor α (ERα)-positive MCF-7 and SKOV-3 cancer cells.</p> <p>Methods</p> <p>MCF-7 and SKOV-3 cells were stably transfected with the wild-type, degradation-resistant full-length or helix-loop-helix (HLH)-deleted Id2, respectively. Protein levels of Id2 and its mutants and E-cadherin were determined by western blot analysis and mRNA levels of Id2 and its mutants were determined by RT-PCR. The effects of Id2 and its mutants on cell proliferation were determined by [³H]-thymidine incorporation assay and the 3- [4, 5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) dye method. The <it>in vitro </it>invasion potential of cells was evaluated by Transwell assay. Cell motility was assessed by scratch wound assay. The promoter activity of <it>E-cadherin </it>was determined by cotransfection and luciferase assays.</p> <p>Results</p> <p>Ectopic transfection of the wild-type Id2 markedly increased the protein and mRNA expression of <it>Id2 </it>in MCF-7 and SKOV-3 cells; the protein level but not mRNA level was further increased by transfection with the degradation-resistant Id2 form. The ectopic expression of Id2 or its mutants did not alter proliferation of either MCF-7 or SKOV-3 cells. Transfection of the wild-type Id2 significantly induced the invasion potential and migratory capacity of cells, which was further augmented by transfection with the degradation-resistant full-length or HLH-deleted Id2. E-cadherin protein expression and transactivation of the proximal E-cadherin promoter were markedly suppressed by the degradation-resistant full-length or HLH-deleted Id2 but not wild-type Id2. Ectopic expression of E-cadherin in MCF-7 and SKOV-3 cells only partially blunted the invasion potential induced by the degradation-resistant HLH-deleted Id2.</p> <p>Conclusion</p> <p>Overexpression of Id2 in ERα-positive epithelial tumor cells indeed increases the cells' invasive potential through a novel mechanism independent of dimerization to basic helix-loop-helix factors. E-cadherin contributes only in part to Id2-induced cell invasion when Id2 is accumulated to a higher level in some specific cell types.</p