Caffeine and a selective adenosine A2A receptor antagonist induce sensitization and cross-sensitization behavior associated with increased striatal dopamine in mice

<p>Abstract</p> <p>Background</p> <p>Caffeine, a nonselective adenosine A₁and A_2Areceptor antagonist, is the most widely used psychoactive substance in the world. Evidence demonstrates that caffeine and selective adenosine A_2Aantagonists interact with the neuronal systems involved in drug reinforcement, locomotor sensitization, and therapeutic effect in Parkinson's disease (PD). Evidence also indicates that low doses of caffeine and a selective adenosine A_2Aantagonist SCH58261 elicit locomotor stimulation whereas high doses of these drugs exert locomotor inhibition. Since these behavioral and therapeutic effects are mediated by the mesolimbic and nigrostriatal dopaminergic pathways which project to the striatum, we hypothesize that low doses of caffeine and SCH58261 may modulate the functions of dopaminergic neurons in the striatum.</p> <p>Methods</p> <p>In this study, we evaluated the neuroadaptations in the striatum by using reverse-phase high performance liquid chromatography (HPLC) to quantitate the concentrations of striatal dopamine and its metabolites, dihydroxylphenylacetic acid (DOPAC) and homovanilic acid (HVA), and using immunoblotting to measure the level of phosphorylation of tyrosine hydroxylase (TH) at Ser31, following chronic caffeine and SCH58261 sensitization in mice. Moreover, to validate further that the behavior sensitization of caffeine is through antagonism at the adenosine A_2Areceptor, we also evaluate whether chronic pretreatment with a selective adenosine A_2Aantagonist SCH58261 or a selective adenosine A₁antagonist DPCPX can sensitize the locomotor stimulating effects of caffeine.</p> <p>Results</p> <p>Chronic treatments with low dose caffeine (10 mg/kg) or SCH58261 (2 mg/kg) increased the concentrations of dopamine, DOPAC and HVA, concomitant with increased TH phosphorylation at Ser31 and consequently enhanced TH activity in the striatal tissues in both caffeine- and SCH58261-sensitized mice. In addition, chronic caffeine or SCH58261 administration induced locomotor sensitization, and locomotor cross-sensitization to caffeine was observed following chronic treatment of mice with SCH58261 but not with DPCPX.</p> <p>Conclusions</p> <p>Our study demonstrated that low dosages of caffeine and a selective adenosine A_2Aantagonist SCH58261 elicited locomotor sensitization and cross-sensitization, which were associated with elevated dopamine concentration and TH phosphorylation at Ser31 in the striatum. Blockade of adenosine A_2Areceptor may play an important role in the striatal neuroadaptations observed in the caffeine-sensitized and SCH58261-sensitized mice.</p

Emerging Leaderships in an Online Community: A Longitudinal Network Analysis

Online communities have brought great benefits to society; however, relatively few of them are successful in sustaining community activities. It is necessary to have a better understanding of the contextual development of online communities. This study adopts the theory of networked influence to address the research objective. Data is collected from an online community which has been in operation for ten years. We investigate the community’s sustainability on a longitudinal basis, focusing on its dynamic temporal development, with regard to how it was formed, became robust, and either declined or was sustained. Adopting social network analysis with a qualitative approach, we identify several types of emerging leaders and how the relay events between them had a significant impact on communication prolongation. Their influence is found to extend across discussion entities, resulting in communication homogeneity, and leading to significant network effects that are relevant to participants’ interactions

Hydrodynamical Simulations of the Barred Spiral Galaxy NGC 1097

NGC 1097 is a nearby barred spiral galaxy believed to be interacting with the elliptical galaxy NGC 1097A located to its northwest. It hosts a Seyfert 1 nucleus surrounded by a circumnuclear starburst ring. Two straight dust lanes connected to the ring extend almost continuously out to the bar. The other ends of the dust lanes attach to two main spiral arms. To provide a physical understanding of its structural and kinematical properties, two-dimensional hydrodynamical simulations have been carried out. Numerical calculations reveal that many features of the gas morphology and kinematics can be reproduced provided that the gas flow is governed by a gravitational potential associated with a slowly rotating strong bar. By including the self-gravity of the gas disk in our calculation, we have found the starburst ring to be gravitationally unstable which is consistent with the observation in \citet{hsieh11}. Our simulations show that the gas inflow rate is 0.17 M_\sun yr$^{-1}$ into the region within the starburst ring even after its formation, leading to the coexistence of both a nuclear ring and a circumnuclear disk.Comment: 32 pages, 14 figures, 1 table, accepted for publication in the Ap

SENTIMENT ANALYSIS OF CHINESE MICROBLOG MESSAGE USING NEURAL NETWORK-BASED VECTOR REPRESENTATION FOR MEASURING REGIONAL PREJUDICE

Regional prejudice is prevalent in Chinese cities in which native residents and migrants lack a basic level of trust in the other group. Like Twitter, Sina Weibo is a social media platform where people actively engage in discussions on various social issues. Thus, it provides a good data source for measuring individuals’ regional prejudice on a large scale. We find that a resentful tone dominates in Weibo messages related to migrants. In this paper, we propose a novel approach, named DKV, for recognizing polarity and direction of sentiment for Weibo messages using distributed real-valued vector representation of keywords learned from neural networks. Such a representation can project rich context information (or embedding) into the vector space, and subsequently be used to infer similarity measures among words, sentences, and even documents. We provide a comprehensive performance evaluation to demonstrate that by exploiting the keyword embeddings, DKV paired with support vector machines can effectively recognize a Weibo message into the predefined sentiment and its direction. Results demonstrate that our method can achieve the best performances compared to other approaches

A STUDY OF THE INFLUENCES OF KNOWLEDGE BOUNDARY SPANNING ON PROJECT PERFORMANCE IN INFORMATION SYSTEM DEVELOPMENT PROJECTS

Information system development (ISD) is a knowledge intensive process, and a socialize cross-disciplines collaboration that brings up innovations and creates a competitive advantage for the organization. However, different layers of knowledge boundaries (syntactic, semantic, pragmatic) arise with the knowledge diversity of the ISD project and further lowers the project performance and product quality. To solve the problems, we will follow a construct development methodology to empirically identify the critical knowledge boundary spanning (KBS) processes, roles and objects for different layers of knowledge boundary, examine their influences to the effectiveness of corresponding KBS, and further assess the direct and moderating relationships from KBS effectiveness to project performance and product quality through a questionnaire survey. For academic applications, we not only split up the layers of KBS effectiveness and examine their direct and moderating effects to ISD performance but also offer categorized KBS activities under a formal construct development methodology for future studies. For practical implications, we offer a model for ISD team members to refer to for solving their knowledge boundary issues and increase their project performance and product quality

Initial presentation of mesenteric venous thrombosis mimicking acute duodenitis: A true gastrointestinal vascular emergency

AbstractWe present a patient who had a 3-day history of epigastric pain and acid regurgitation and was found to have gastroesophageal reflux disease and duodenitis by esophagogastroduodenoscopy. His symptoms were refractory to treatment with a proton pump inhibitor. Peritonitis developed subsequently. Enhanced computed tomography (CT) confirmed a diagnosis of mesenteric venous thrombosis (MVT) with jejunum infarction. Emergency exploratory laparotomy with segmental resectioning of the jejunum was performed. We emphasize that emergency department (ED) physicians should always thoroughly re-evaluate patients with abdominal pain using serial physical examinations in accordance with the chronic nature of the disease. There is a need to be highly alert to pain that is out of the proportion to the physical examination results and/or endoscopic findings, the development of peritoneal irritation signs, the presence of fever, and the presence of leukocytosis among patients with nonspecific endoscopic findings. This will help to differentiate MVT as the true etiology of ischemic duodenitis in a timely manner. ED physicians should also be aware that hyperemic edematous duodenitis can be the finding for MVT using endoscopy

Using Rare Earth Elements to Constrain Particulate Organic Carbon Flux in the East China Sea

Fluxes of particulate organic carbon (POC) in the East China Sea (ECS) have been reported to decrease from the inner continental shelf towards the outer continental shelf. Recent research has shown that POC fluxes in the ECS may be overestimated due to active sediment resuspension. To better characterize the effect of sediment resuspension on particle fluxes in the ECS, rare earth elements (REEs) and organic carbon (OC) were used in separate two-member mixing models to evaluate trap-collected POC fluxes. The ratio of resuspended particles from sediments to total trap-collected particles in the ECS ranged from 82-94% using the OC mixing model, and 30-80% using the REEs mixing model, respectively. These results suggest that REEs may be better proxies for sediment resuspension than OC in high turbidity marginal seas because REEs do not appear to undergo degradation during particle sinking as compared to organic carbon. Our results suggest that REEs can be used as tracers to provide quantitative estimates of POC fluxes in marginal sea

Human Tuberculosis Caused by Mycobacterium bovis, Taiwan

Human Tuberculosis Caused by Mycobacterium bovis, Taiwa

Atomically-thin metallic Si and Ge allotropes with high Fermi velocities

Silicon and germanium are the well-known materials used to manufacture electronic devices for the integrated circuits but they themselves are not considered as promising options for interconnecting the devices due to their semiconducting nature. We have discovered that both Si and Ge atoms can form unexpected metallic monolayer structures which are more stable than the extensively studied semimetallic silicene and germanene, respectively. More importantly, the newly discovered two-dimensional allotropes of Si and Ge have Fermi velocities superior to the Dirac fermions in graphene, indicating that the metal wires needed in the silicon-based integrated circuits can be made of Si atom itself without incompatibility, allowing for all-silicon-based integrated circuits.Comment: 10 pages, 3 figures, 1 tabl