Upregulation of Oxytocin Receptor in the Hyperplastic Prostate

Background: The etiology of benign prostatic hyperplasia (BPH) is complex, both age and androgen are thought to be important. However, the failure of androgen blockade treatments suggests other paracrine/autocrine factors involved in BPH. Oxytocin was found to have a paracrine/autocrine role in prostate in recent years. The influence of BPH on prostatic oxytocin receptor (OTR) expression has never been studied.Material and methods: A testosterone-estradiol induced rat model of BPH was employed and human hyperplastic prostate specimens were harvested. Expressions of OTR, α1-adrenoreceptor subtypes and nitric oxide synthase isoforms were determined via real-time RT-PCR. OTR was further analyzed with Western-Blotting and histological examination. Subsequently, rat epithelial cells, human stromal cells and epithelial cells were cultured in vitro and treated with gradient concentrations of OT from 1 to 5 days. Cell proliferation was tested by Cell Counting Kit-8 and Flow Cytometry.Results: The rat BPH model was validated with significant increased prostate weight. H-E stain revealed a different histopathology between human and rat BPH. Masson's trichrome staining demonstrated that smooth muscle (SM) cells, epithelium cells and collagen fibers were simultaneously augmented in this rat BPH model and human BPH samples. OTR mainly localized in epithelium in rat prostate whereas it mainly localized in stroma in human prostate. OTR gene was upregulated 3.3-fold in rat BPH and 3.0-fold in human BPH, along with increased expression of 2.0-fold α1aARs and 3.0-fold eNOS for rat BPH and 5.0-fold α1aARs for human BPH. The expression of OTR protein was upregulated 1.4-fold in rat BPH and 3.9-fold in human BPH, respectively. Increased concentrations of exogenous OT can accelerate proliferation of rat epithelial cells and human stromal cells but has no impact on human epithelial cells in vitro. Flow Cytometry showed oxytocin could significantly increase G2/M period cell number.Conclusions: Our novel data demonstrates a significant and previously undocumented upregulation of OTR in both rat and human BPH. Moreover, exogenous OT accelerates proliferation of rat prostate epithelial cells and human prostate stromal cells. It is suggested OTR is involved in the development of BPH and OT regulatory system could be a potential new target for the BPH treatment

Genome-wide QTL mapping for stripe rust resistance in spring wheat line PI 660122 using the Wheat 15K SNP array

IntroductionStripe rust is a global disease of wheat. Identification of new resistance genes is key to developing and growing resistant varieties for control of the disease. Wheat line PI 660122 has exhibited a high level of stripe rust resistance for over a decade. However, the genetics of stripe rust resistance in this line has not been studied. A set of 239 recombinant inbred lines (RILs) was developed from a cross between PI 660122 and an elite Chinese cultivar Zhengmai 9023.MethodsThe RIL population was phenotyped for stripe rust response in three field environments and genotyped with the Wheat 15K single-nucleotide polymorphism (SNP) array.ResultsA total of nine quantitative trait loci (QTLs) for stripe rust resistance were mapped to chromosomes 1B (one QTL), 2B (one QTL), 4B (two QTLs), 4D (two QTLs), 6A (one QTL), 6D (one QTL), and 7D (one QTL), of which seven QTLs were stable and designated as QYrPI660122.swust-4BS, QYrPI660122.swust-4BL, QYrPI660122.swust-4DS, QYrPI660122.swust-4DL, QYrZM9023.swust-6AS, QYrZM9023.swust-6DS, and QYrPI660122.swust-7DS. QYrPI660122.swust-4DS was a major all-stage resistance QTL explaining the highest percentage (10.67%–20.97%) of the total phenotypic variation and was mapped to a 12.15-cM interval flanked by SNP markers AX-110046962 and AX-111093894 on chromosome 4DS.DiscussionThe QTL and their linked SNP markers in this study can be used in wheat breeding to improve resistance to stripe rust. In addition, 26 lines were selected based on stripe rust resistance and agronomic traits in the field for further selection and release of new cultivars

Phosphoproteomic Profiling of In Vivo Signaling in Liver by the Mammalian Target of Rapamycin Complex 1 (mTORC1)

Our understanding of signal transduction networks in the physiological context of an organism remains limited, partly due to the technical challenge of identifying serine/threonine phosphorylated peptides from complex tissue samples. In the present study, we focused on signaling through the mammalian target of rapamycin (mTOR) complex 1 (mTORC1), which is at the center of a nutrient- and growth factor-responsive cell signaling network. Though studied extensively, the mechanisms involved in many mTORC1 biological functions remain poorly understood.We developed a phosphoproteomic strategy to purify, enrich and identify phosphopeptides from rat liver homogenates. Using the anticancer drug rapamycin, the only known target of which is mTORC1, we characterized signaling in liver from rats in which the complex was maximally activated by refeeding following 48 hr of starvation. Using protein and peptide fractionation methods, TiO(2) affinity purification of phosphopeptides and mass spectrometry, we reproducibly identified and quantified over four thousand phosphopeptides. Along with 5 known rapamycin-sensitive phosphorylation events, we identified 62 new rapamycin-responsive candidate phosphorylation sites. Among these were PRAS40, gephyrin, and AMP kinase 2. We observed similar proportions of increased and reduced phosphorylation in response to rapamycin. Gene ontology analysis revealed over-representation of mTOR pathway components among rapamycin-sensitive phosphopeptide candidates.In addition to identifying potential new mTORC1-mediated phosphorylation events, and providing information relevant to the biology of this signaling network, our experimental and analytical approaches indicate the feasibility of large-scale phosphoproteomic profiling of tissue samples to study physiological signaling events in vivo

Ordering policy and coordination of a supply chain with two-period demand uncertainty

We develop a two-period game model of a one-manufacturer and one-retailer supply chain to investigate the optimal decisions of the players, where stock-out and holding costs are incorporated into the model. The demand at each period is stochastic and price sharply drops in mid-life. We assume the retailer has a single order opportunity, and decides how much inventory to keep in the middle of selling season. We show that both the price-protection mid-life and end-of-life returns (PME) scheme and the only mid-life and end-of-life returns (ME) scheme may achieve channel coordination and access a 'win-win' situation under some conditions. The larger the lowest expected profit of the retailer, the lower the possibility of 'win-win' situation will be. Combined with the analysis of feasible regions for coordination policies, we find that PME scheme is not always better than ME scheme from the perspective of implementable mechanism. Finally, we find that adopting the dispose-down-to (DDT) policy can bring a larger improvement of the expected channel profit in the centralized setting, and it is interesting that by using DDT policy, double marginalization occurs only at Period 1, and however, does not plague the retailer in Period 2.Supply chain management Channel coordination Game theory Buyback contract

Demand disruption and coordination of the supply chain with a dominant retailer

This paper develops two coordination models of a supply chain consisting of one manufacturer, one dominant retailer and multiple fringe retailers to investigate how to coordinate the supply chain after demand disruption. We consider two coordination schedules, linear quantity discount schedule and Groves wholesale price schedule. We find that, under the linear quantity discount schedule, the manufacturer only needs to adjust the maximum variable wholesale price after demand disruption. For each case of the disrupted amount of demand, the higher the market share of the dominant retailer, the lower its average wholesale price and the subsidy will be under the linear quantity discount schedule, while the higher its fraction of the supply chain's profit will be under Groves wholesale price schedule. When the increased amount of demand is very large and production cost is sufficiently low, linear quantity discount schedule is better for the manufacturer. However, when the production cost is sufficiently large, Groves wholesale price schedule is always better. We also find that the disrupted amount of demand largely affects the allocation of the supply chain's profit.Coordination mechanism Disruption management Supply chain management Game theory

Game Models on Optimal Strategies in a Tourism Dual-Channel Supply Chain

This paper explores a two-echelon tourism supply chain consisting of a hotel and an online travel agency. The upside hotel rooms can be sold through the downside hotel alliance and online travel agency. The hotel alliance, selling rooms at a lower price, is a direct sale platform with a negligible entry fee. Notwithstanding, the online travel agency sells the room at a higher price with related personalized service. Customers will be refunded partially in case of their cancellation or no-show. An integrated model and two decentralized models based on Bertrand and Stackelberg games are developed, respectively. The results show that when the wholesale price is lower than a certain value, both the hotel and the online travel agency can gain more profit from the Stackelberg game than that from the Bertrand game. In the case that the hotel allows overbooking, the optimal overbooking quantity is obtained. If the overbooking proportion is too high, overbooking is profitable for the hotel only when the overbooking cost is lower than a certain value. At the end of the study, some experiments are conducted to analyze the sensitivity of the optimal prices and profits in the light of certain parameters

An analysis of supply chain decisions with asymmetrical retailers : effects of disruptions and static service cost on coordination mechanism

The risk of demand or production cost disruption is one of the challenging problems in the supply chain management. This paper explores a generalized supply chain game model incorporating the possible disruptions. We find that a nonlinear Grove wholesale price scheme can fully coordinate such a supply chain even when both market demand and production cost are disrupted. The nonlinear Grove wholesale price scheme has three sides to coordinate the decision behavior of the players. One is that the mechanism can induce the retail pricing decided by the dominant retailer to be equal with that of the channel; the second is that the mechanism can induce fringe retailers to be not priced out of the market; the third is that the mechanism can ensure that the manufacturer uses minimum incentives to induce the dominant retailer to sell its product as well as providing the demand-stimulating service. Disruptions from both demand side and production cost side may also affect the wholesale price, order quantity as well as retail price, and the share of the dominant retailer and the subsidy rate provided by the manufacturer are unity of opposites. We also find that it is optimal for the manufacturer to keep the original production plan when the joint-disruption amount is sufficiently small

Information sharing for competing supply chains with demand disruption

We investigate pricing decisions and information value in two competing supply chains, each consisting of one manufacturer and one retailer. Both retailers are engaged in Bertrand retail competition and are endowed with the private information on the disrupted demand. Three information sharing scenarios have been considered, i.e., information sharing in both chains, information sharing in only one chain, and information sharing in neither chain. For each information scenario, there always exists robustness for each manufacturer’s production plan. That is, when the disrupted amount of the market demand is sufficiently small, the manufacturer’s production plan or the retailer’s order quantity will be unchanged. Meanwhile, we also study the information value by comparing these three information scenarios, and find that the information value not only works in one chain directly, but also does in the competing chain indirectly. Through comparative analysis, we find that the retailer is reluctant to share his private information on the disrupted demand with his partner because of the fear of information leakage. Meanwhile, the performance of the whole chain may become worse off if the information of disrupted demand is shared in this chain