bluuebunny/crossref_metadata_2025 huggingface dataset:
The prion hypothesis in Parkinson's disease: Braak to the future
Authors: Visanji Naomi P , Brooks Patricia L , Hazrati Lili-Naz , Lang Anthony E
Published: May 2013

Parkinson’s disease (PD) is a progressive neurodegenerative disorder typified by the presence of intraneuronal inclusions containing aggregated alpha synuclein (αsyn). The progression of parkinsonian pathology and clinical phenotype has been broadly demonstrated to follow a specific pattern, most notably described by Braak and colleagues. In more recent times it has been hypothesized that αsyn itself may be a critical factor in mediating transmission of disease pathology from one brain area to another. Here we investigate the growing body of evidence demonstrating the ability of αsyn to spread transcellularly and induce pathological aggregation affecting neurons by permissive templating and provide a critical analysis of some irregularities in the hypothesis that the progression of PD pathology may be mediated by such a prion-like process. Finally we discuss some key questions that remain unanswered which are vital to determining the potential contribution of a prion-like process to the pathogenesis of PD.
Eco-friendly synthesis and characterization of gold nanoparticles using Klebsiella pneumoniae
Authors: Malarkodi Chelladurai , Rajeshkumar Shanmugam , Vanaja Mahendran , Paulkumar Kanniah , Gnanajobitha Gnanadhas , Annadurai Gurusamy
Published: May 2013

The thrust to develop eco-friendly procedures for the production of nanoparticles arises from the extremely recent nanotechnology research. Extracellular biosynthesis of gold nanoparticles was achieved by an easy biological procedure using Klebsiella pneumoniae as the reducing agent. After exposing the gold ions to K. pneumoniae, rapid reduction of gold ions is observed foremost to the formation of gold nanoparticles in colloidal solution. UV-vis spectrum of the aqueous medium containing gold nanoparticles showed a peak around 560 nm. The crystalline nature of the particles was confirmed from an X-ray diffractometer. Transmission electron microscopy (TEM) micrograph analysis of the gold nanoparticles indicated that they were well dispersed and ranged in sizes 35 to 65 nm. The high crystalline in the FCC phase is evidenced by bright circular spots in a selected-area electron diffraction pattern and clear lattice fringes in the high-resolution TEM image. Fourier transform infrared spectroscopy revealed possible involvement of reductive groups on the surface of nanoparticles. The method exploits a cheap and easily available biomaterial not explored so far for the synthesis of metallic nanoparticles.
The productivity of return migrants: the case of China’s “Sea Turtles”
Authors: Sun Wei
Published: May 2013

This paper explores the productivity differential between return migrants (“Sea Turtles”) and non-migrants through a case study of China’s venture capital (VC) industry. I find that even after correcting for selection bias, return venture capitalists are less productive than comparable non-migrants in targeting promising projects and/or providing value-added services. Given that the VC industry is a useful laboratory in which to look at the performance of return migrants and China’s economic development, I discuss why the presumably better human capital accumulated overseas does not translate into productivity in the Chinese market, and how related policies could reverse this situation in the long run.

JEL Codes

F22, G24, O15
Acute Hypernatremia Exerts an Inhibitory Oxytocinergic Tone That Is Associated With Anxiolytic Mood in Male Rats
Authors: Frazier Charles J. , Pati Dipanwita , Hiller Helmut , Nguyen Dan , Wang Lei , Smith Justin A. , MacFadyen Kaley , de Kloet Annette D. , Krause Eric G.
Published: May 2013

Anxiety disorders are the most common psychiatric illnesses and are associated with heightened stress responsiveness. The neuropeptide oxytocin (OT) has garnered significant attention for its potential as a treatment for anxiety disorders; however, the mechanism mediating its effects on stress responses and anxiety is not well understood. Here we used acute hypernatremia, a stimulus that elevates brain levels of OT, to discern the central oxytocinergic pathways mediating stress responsiveness and anxiety-like behavior. Rats were rendered hypernatremic by acute administration of 2.0 M NaCl and had increased plasma sodium concentration, plasma osmolality, and Fos induction in OT-containing neurons relative to 0.15 M NaCl-treated controls. Acute hypernatremia decreased restraint-induced elevations in corticosterone and created an inhibitory oxytocinergic tone on parvocellular neurosecretory neurons within the paraventricular nucleus of the hypothalamus. In contrast, evaluation of Fos immunohistochemistry determined that acute hypernatremia followed by restraint increased neuronal activation in brain regions receiving OT afferents that are also implicated in the expression of anxiety-like behavior. To determine whether these effects were predictive of altered anxiety-like behavior, rats were subjected to acute hypernatremia and then tested in the elevated plus maze. Relative to controls given 0.15 M NaCl, rats given 2.0 M NaCl spent more time in the open arms of the elevated plus maze, suggesting that acute hypernatremia is anxiolytic. Collectively the results suggest that acute elevations in plasma sodium concentration increase central levels of OT, which decreases anxiety by altering neuronal activity in hypothalamic and limbic nuclei.
Syntheses, Redox Properties, Self-Assembled Structures, and Charge-Transfer Complexes of Imidazole- and Benzimidazole-Annelated Tetrathiafulvalene Derivatives
Authors: Murata Tsuyoshi , Yamamoto Yosuke , Yakiyama Yumi , Nakasuji Kazuhiro , Morita Yasushi
Published: May 2013

New tetrathiafulvalene (TTF)-type electron-donor molecules annelated with imidazole or benzimidazole moiety were designed and synthesized by the phosphite-mediated coupling reactions of imidazole- or benzimidazole-annelated 1,3-dithiole-2-thiones. The effect of imidazole-annelation on the redox properties was evaluated by theoretical calculation and electrochemical measurement, and the imidazole-annelation slightly enhances the electron-donating abilities of parent TTF and benzo-TTF skeletons. The substitution of the imidazole ring with an electron-withdrawing cyano group caused a large high potential shift of the oxidation potentials in the cyclic voltammetry and an intense intramolecular charge-transfer absorption band in the electronic spectrum. The self-assembling ability was investigated by crystal structure analysis, where solvent or counter anion mediated one-dimensional hydrogen-bonded arrays of imidazole rings were linked through π-stacks and S···S interactions to construct multidimensional networks. The donor molecules afforded weak charge-transfer complexes with tetracyanoquinodimethane (TCNQ) and fully ionic complexes with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) and 2,3,5,6-tetrafluoro-TCNQ. In the crystal structures of TCNQ complex and iodine salt of a benzimidazole-annelated derivative, π-stacking motifs, donor–acceptor alternating stack, and π-stacking dimer, respectively, were interacted through hydrogen-bonds.
Preparation of Composite Material of Na-P1-Type Zeolite and Magnetite for Cs Decontamination
Authors: Aono Hiromichi , Tamura Kazumasa , Johan Erni , Yamauchi Rie , Yamamoto Toru , Matsue Naoto , Henmi Teruo
Published: May 2013

For the decontamination of radioactive 134Cs and 137Cs using magnetic collection, a new composite material consisting of a Na-P1-type zeolite and magnetite was synthesized from the waste fly-ash from thermal power stations and iron chlorides. The presence of nanosized magnetites in the polycrystalline zeolite (several micrometers) was confirmed by TEM observations. The cation-exchange capacity (CEC) and magnetic properties of these composite materials were characterized.
The Impact of New Product Introduction on Plant Productivity in the North American Automotive Industry
Authors: Gopal Anandasivam , Goyal Manu , Netessine Serguei , Reindorp Matthew
Published: May 2013

Product launch—an event when a new product debuts for production in a plant—is an important phase in product development. But launches disrupt manufacturing operations, resulting in productivity losses. Using data from North American automotive plants from years 1999–2007, we estimate that a product launch entails an average productivity loss of 12%–15% at the plant level. This translates to a monetary loss of $42–$53 million per launch in lost productivity. We identify several ways to mitigate the decrease in productivity. Product (or mix) flexibility in the body shop is critical for reducing the productivity loss. A plant's past experiences with product launches as well as with manufacturing similar products (specifically, on the same platform as the launch product) temper the productivity losses even further. Nevertheless, there are subtle differences in the accrued learning with these two types of experiences: whereas the positive impact of platform experience persists over time, the learning accrued with launching other products in the same plant decays more quickly. Altogether, our results suggest that launching products at a flexible plant with appropriate platform experience could recover approximately $31 million per launch in lost productivity.

This paper was accepted by Kamalini Ramdas, entepreneurship and innovation.
Investors' Heterogeneity and Implied Volatility Smiles
Authors: Li Tao
Published: May 2013

Heterogeneity in beliefs and time preferences among investors make stock volatility stochastic, even though the volatility of the underlying dividend is constant. Prices of the European options written on this stock admit closed-form solutions, hence their hedging deltas. The Black–Scholes implied volatility surface, which depends on wealth distribution, investors' beliefs, and time preferences, exhibits observed patterns that are widely documented in various options markets. Along with benchmark models, the model is calibrated weekly to the S&P 500 index options from January 1996 to April 2006. It shows comparable performance to the stochastic volatility and jump model and outperforms the traders' rules and two no-arbitrage models (stochastic volatility, and stochastic volatility and stochastic interest rate) in terms of out-of-sample pricing errors.

This paper was accepted by Wei Xiong, finance.
ORGANIZAÇÕES DA SOCIEDADE CIVIL NO CIBERESPAÇO: O MODELO DA WIKIPÉDIA LUSÓFONA
Authors: Roveri Pietro Fornitano , Costa André Lucirton
Published: May 2013

O objetivo do trabalho é analisar a estruturação e a manutenção da Wikipédia lusófona, em especial os aspectos econômicos e políticos mediados por um arcabouço sócio-técnico, no intuito de identificá-la como um modelo de atuação da sociedade civil no ciberespaço. Benkler (2002) e Lemos (2005) sinalizam para a importância da estrutura tecnológica nos novos processos de colaboração e organização sociais. Nesse sentido, Benkler (2002) observou o surgimento de um novo modelo econômico de produção baseado nas organizações colaborativas. Em suma, são organizações descentralizadas com relações fundamentadas no ciberespaço e que produzem bens não-rivais através do esforço coletivo e voluntário de seus membros, a Wikipédia é um exemplo desse modelo. Todavia, Lévy (1999) propõe que o ciberespaço não é uma infra-estrutura técnica de telecomunicação, mas certa forma de usar as infra-estruturas existentes, assim o indivíduo não pode ser esquecido como problematizador. Para tanto, a metodologia utilizada foi a netnografia, com aplicação de entrevistas, que foram efetuadas de acordo com critérios qualitativos, além da observação participante entre os anos de 2008, 2009 e 2010. Por se tratar de um trabalho qualitativo, se julgou pertinente utilizar os integrantes da lista de maiores contribuidores, com aproximadamente 90 nomes de usuários, como foco de possíveis respondentes da pesquisa, no total foram respondidas 18 entrevistas. As questões foram construídas com o objetivo de identificar as formas de contribuição e as motivações dos contribuintes. Foi detectada a questão dos usuários com mais de um cadastro que podem utilizar esse mecanismo para burlar o sistema político interno. Ainda, foi possível identificar a existência de um tipo wikipédico que se baseia nos sentidos dos fluxos de informação, podendo tipificá-los entre quem lê, quem insere e quem valida. No que concerne à estruturação se observou que há um arcabouço de governo que sustenta as ações do projeto, mantido principalmente pelas diferenciações na liberdade de uso do software. Os wikipedistas se dedicam às atividades de acordo com seu ramo de interesse ou conhecimento técnico da ferramenta wiki e o fazem sem receber qualquer compensação monetária. As atividades dos entrevistados se encaixaram basicamente em três concepções: atividades de gestão como trabalho advindo das liberdades de software, atividades de formatação para enquadrar os artigos nos padrões e atividades de inserção ou pesquisa que seriam as atividades para propor novos artigos ou melhorar os que já existem. Tal fato pode ser corroborado pela teoria da economia de doação proposta por Kollock (1998), uma vez que o autor elencou os fatores (reciprocidade, prestígio, incentivo social e incentivo moral) que seriam tidos como a “moeda” utilizada na Wikipédia. Quanto à manutenção da Wikipédia se verificou que há um norteamento ao consenso em todas as relações e este é norteado pelas políticas gerais do projeto.
Relacionamento na cadeia de abastecimento – Estudo de caso em uma pequena empresa distribuidora
Authors: Torres Jr. Alvair Silveira , RATAO BRUNO PINHEIRO
Published: May 2013

A literatura sobre gerenciamento da cadeia de abastecimento tem considerado fundamentais a eficiência interorganizacional dos processos e a qualidade dos relacionamentos entre os agentes internos e externos à organização, objetivando o alinhamento de esforços e resultados. O presente trabalho objetiva estudar tais aspectos no interior de uma pequena empresa, explorando os elementos que envolvem alcançar resultados na sua cadeia de abastecimento em um ambiente caracterizado pelo contraste entre a informalidade ágil do pequeno negócio, porém em grande parte das vezes desestruturada, diante da formalidade profissional, eficiente, entretanto fria e calculista no seu tecnicismo. Através de uma pesquisa qualitativa de oportunidade sobre uma pequena empresa distribuidora brasileira da cidade de São Paulo, compradora cativa de um produtor de Taiwan, esta pesquisa empreendeu o método do estudo de caso simples, focando em profundidade a cadeia de abastecimento, com o intuito de analisar os relacionamentos entre a empresa, seu fornecedor e seus clientes. Foram coletados dados que apontam para a coexistência de estruturas informais e formais de relacionamento que constituíram a resposta sustentável do negócio à peculiaridade de sua cadeia de abastecimento. A conclusão aponta para uma crítica aos modelos de análise de relacionamento presentes na literatura, que não contemplam os contrastes e as peculiaridades das PME, havendo indícios para propor um processo de transição em que a informalidade deva ser modificada, porém não substituída pelo formalismo. Palavras-chave: cadeia de abastecimento, relacionamento, microempresa, PME.
NAMBISAN, Satish & SAWHNEY, Mohanbir. Cérebro Global – como inovar em um mundo conectado por redes. São Paulo: Évora, 2011. 324p.
Authors: Travassos Marcos da Silva
Published: May 2013

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Inovação no Transporte Público: a Implantação da Bilhetagem Eletrônica na Região Metropolitana de Porto Alegre
Authors: Lübeck Rafael Mendes , Wittmann Milton Luiz , Battistella Luciana Flores , Da Silva Marcia Santos
Published: May 2013

Resumo: Considerando-se o aumento da complexidade no cenário competitivo, a palavra-chave da era pós-industrial é inovação que, para ser alcançada, exige novas estratégias, capacidades e competências. Diante deste cenário, o presente estudo compreendeu a análise das melhorias obtidas com a implementação do sistema de bilhetagem na Região Metropolitana de Porto Alegre no intuito de verificar se as melhorias proporcionadas pela bilhetagem eletrônica possuem características que a definam como uma inovação. Foram coletados dados de natureza qualitativa por entrevistas e análise documental, referentes a fatores circunstanciados em processos eletrônicos de controle de passagens de transporte coletivo urbano nas cidades abrangidas pela pesquisa. A pesquisa baseou-se no modelo teórico sobre inovação de forma a nortear as atividades de investigação descritas. Constatou-se que os efeitos característicos de uma inovação estão em consonância com os resultados da bilhetagem nos casos analisados, fazendo deste sistema uma forma de se alcançar à inovação. Seguindo os preceitos escolhidos para este trabalho, é pertinente reforçar que foram considerados inovadores os efeitos causados pela bilhetagem e não o sistema em si, pois a bilhetagem é um meio para se alcançar a inovação e não uma inovação per se.Palavras-chave: inovação em serviços;bilhetagem eletrônica; transporte público.
Pós-Graduação em Contabilidade - Um Estudo Comparativo Em Cinco Países
Authors: Reina Donizete , Maximiano Reina Diane Rossi , Soares da Silva Harley Almeida , Ensslin Sandra Rolim
Published: May 2013

A literatura aponta uma carência de professores na área de Contabilidade. E, para alguns autores, essa carência está relacionada ao alto preço a se pagar para realização de uma pós-graduação na área. Assim,este estudo tem como objetivo mapear algumas características de programas de pós-graduação em Contabilidade nas universidades situadas  em países cujo idioma oficial é a língua inglesa. Esta pesquisa é descritiva, teórica-conceitual, qualitativa, e possui lógica indutiva. Principais resultados: nos Estados Unidos, 71% dos programas analisados solicitam de seus candidatos conhecimentos em contabilidade, finanças, economia, tributos, estatística e matemática; 75% das universidades Australiana requerem o TOEFL, 20% requerem o GPA enquanto 10% requerem o GMAT; 88% das instituições que ofertam  mestrados em contabilidade têm como foco melhorar a qualificação profissional dos contadores; na Austrália, 30% dos programas têm a duração de 18 meses, já 66% dos programas no Canadá e 50% da Nova Zelândia possuem período máximo de dois anos para o término; além disso, 82% das universidades exigem uma quantidade entre quatro e nove disciplinas obrigatórias, dentre outros resultados.  Conclui-se que os cursos de mestrado oferecidos nos Estados Unidos e Reino Unido são relativamente mais exigentes em relação aos requisitos de formação do mestre em Contabilidade.Palavras-chave: mestrado em contabilidade; programa de pós-graduação; características dos programas; avaliação de programas.
Perfil e Crescimento dos Temas "Governança Corporativa" e "Estratégia": Uma Análise dos Últimos 11 Anos nos Periódicos da Área de Administração no Brasil
Authors: Ribeiro Henrique César Melo , Muritiba Sérgio Nunes , Muritiba Patricia Morilha
Published: May 2013

O objetivo deste estudo foi investigar o perfil das pesquisas e a evolução dos temas "governança corporativa" e "estratégia" em conjunto nos artigos publicados nas Revistas Qualis B2 a A1, no período de 2000 a 2010. Analisaram-se 79 artigos publicados no referido período. Investigaram-se os seguintes aspectos: o crescimento dos temas e periódicos de destaque; as características de autoria; os autores com maior produção nestes temas; as referências mais citadas; as referências por período e as abordagens metodológicas. Foi um estudo bibliométrico, com abordagem quantitativa,  utilizando a estatística descritiva. Observou-se que os temas "governança corporativa" e "estratégia" estão em constante desenvolvimento teórico e metodológico; verificou-se que ambos os temas são interdisciplinares entre si; constatou-se que as publicações com os temas relacionados estão crescendo em número e em qualidade. Em suma, este estudo mostra que há grandes oportunidades para o crescimento e a consolidação dos temas "governança corporativa" e "estratégia" na literatura acadêmica nacional.Palavras-chave:governança corporativa; estratégia; análise bibliométrica.
O Desenvolvimento de Competências Empreendedoras na Administração Pública: Um Estudo Com Empreendedores Corporativos na Prefeitura de Blumenau, Santa Catarina
Authors: Lenzi Fernando Cesar , Ramos Flavio , Maccari Emerson Antonio , Martens Cristina Dai Pra
Published: May 2013

Esta pesquisa teve como objetivo identificar as competências dos empreendedores corporativos ligados à administração pública. Foi realizada por meio de uma pesquisa com 25 servidores públicos envolvidos no desenvolvimento de projetos inovadores na Prefeitura de Blumenau, em Santa Catarina, cidade que é caracterizada pela excelência em projetos de inovação e desenvolvimento de ações empreendedoras. A pesquisa ressalta que os resultados inovadores têm sua origem em comportamentos manifestos por estes indivíduos a partir do ambiente propício estimulado por um programa de empreendedorismo corporativo. O Programa de Inovação e Melhoria – PIM busca capacitar e desenvolver os servidores públicos para serem empreendedores em suas atividades.  Os resultados apontam as seguintes competências empreendedoras que mais se destacam: a) comprometimento; b) busca de informações; c) persistência; d) planejamento e monitoramento sistemático; e) persuasão; e f) rede de contatos.  Assim, pode-se afirmar que, ao se desenvolver estas competências, os servidores públicos estarão mais preparados para empreender e inovar.Palavras-chave: empreendedor corporativo; competências empreeendedoras; administração pública.
Mensuração da Eficiência Financeira Municipal no Brasil e sua Relação com os Gastos nas Funções de Governo
Authors: Diniz Josedilton Alves , Macedo Marcelo Alvaro da Silva , Corrar Luiz João
Published: May 2013

Esta pesquisa tem como objetivo avaliar, a partir de uma métrica contábil, a eficiência financeira na gestão dos recursos públicos de municípios brasileiros e mensurar sua relação com os gastos nas funções de governo definidas na estrutura orçamentária brasileira, para municípios que possuíam uma população superior a 200.000 habitantes em 2007. Para tanto, inicialmente, definiram-se dez indicadores da condição financeira de municípios, nos moldes utilizados por Brown (1993). Depois utilizou-se a DEA em dois estágios: o primeiro para definir os escores de eficiência de cada município e num segundo estágio, fez-se uma regressão linear, a partir dos escores (variável dependente), para investigar relações explicativas de variáveis exógenas originarias das 28 funções de governo. Os resultados revelaram, que, dentre as 28 funções de governo dispostas na execução orçamentária, apenas os gastos per capta com saúde, urbanismos e saneamento se correlacionaram como os escores de eficiência financeira dos municípios.
Glycan synthesis, structure, and dynamics: A selection
Authors: Pendrill Robert , Jonsson K. Hanna M. , Widmalm Göran
Published: May 2013

Glycan structural information is a prerequisite for elucidation of carbohydrate function in biological systems. To this end we employ a tripod approach for investigation of carbohydrate 3D structure and dynamics based on organic synthesis; different experimental spectroscopy techniques, NMR being of prime importance; and molecular simulations using, in particular, molecular dynamics (MD) simulations. The synthesis of oligosaccharides in the form of glucosyl fluorides is described, and their use as substrates for the Lam16A E115S glucosyl synthase is exemplified as well as a conformational analysis of a cyclic β-(1→3)-heptaglucan based on molecular simulations. The flexibility of the N-acetyl group of aminosugars is by MD simulations indicated to function as a gatekeeper for transitions of glycosidic torsion angles to other regions of conformational space. A novel approach to visualize glycoprotein (GP) structures is presented in which the protein is shown by, for example, ribbons, but instead of stick or space-filling models for the carbohydrate portion it is visualized by the colored geometrical figures known as CFG representation in a 3D way, which we denote 3D-CFG, thereby effectively highlighting the sugar residues of the glycan part of the GP and the position(s) on the protein.
Estimation of Risk Ratios in Cohort Studies with a Common Outcome: A Simple and Efficient Two-stage Approach
Authors: Tchetgen Tchetgen Eric
Published: May 2013

The risk ratio effect measure is often the main parameter of interest in epidemiologic studies with a binary outcome. In this paper, the author presents a simple and efficient two-stage approach to estimate the risk ratios directly, which does not directly rely on consistency for an estimate of the baseline risk. This latter property is a key advantage of the approach over existing methods, because, unlike these other methods, the proposed approach obviates the need to restrict the predicted risk probabilities to fall below one, in order to recover efficient inferences about risk ratios. An additional appeal of the approach is that it is easy to implement. Finally, when the primary interest is in the effect of a specific binary exposure, a simple doubly robust closed-form estimator is derived, for the multiplicative effect of the exposure. Specifically, we show how one can adjust for confounding by incorporating a working regression model for the propensity score so that the correct inferences about the multiplicative effect of the exposure are recovered if either this model is correct or a working model for the association between confounders and outcome risk is correct, but both do not necessarily hold.
Nanomedicine in diagnostics and therapy of cardiovascular diseases: beyond atherosclerotic plaque imaging
Authors: Cicha Iwona , Lyer Stefan , Alexiou Christoph , Garlichs Christoph D.
Published: May 2013

Atherosclerosis results from the accumulation of the modified lipoproteins within the artery walls, which triggers complex vascular inflammatory processes. Although the pharmacologic agents for the treatment of clinical manifestations of atherosclerosis are available, their systemic delivery has serious disadvantages, such as considerable side effects or low efficacy at tolerated doses. Moreover, the treatment of atherosclerosis using the interventional techniques bears further shortcomings: the implanted stents require a lengthy antiplatelet therapy and carry the risk of in-stent restenosis. In the surgical approach to atherosclerosis, apart from the overall risk of open heart surgery, the lack of adequate venous material for bypasses constitutes a common problem. The nanotechnology has the potential to overcome the disadvantages of the current therapy of atherosclerosis, e.g., by the formation of nanosized assemblies for the earlier detection of atherosclerotic lesions and for cell-specific delivery of therapeutics. Replacing the current systemic pharmacological approach by a locally targeted treatment of plaques can substantially minimize the adverse effects, by lowering the drug cytotoxicity and reducing the required dosage. Moreover, a new generation of nanotechnological approaches to the revascularization procedures is now emerging, e.g., vascular tissue engineering utilizing the magnetic nanoparticles or the design of stents with the reduced risk of thrombosis and restenosis. This review discusses the possible applications of the nanomedical approaches in the treatment of cardiovascular diseases.
Effects of Prefrontal Cortical Inactivation on Neural Activity in the Ventral Tegmental Area
Authors: Jo Yong Sang , Lee Jane , Mizumori Sheri J.Y.
Published: May 2013

Dopamine (DA) cells have been suggested to signal discrepancies between expected and actual rewards in reinforcement learning. DA cells in the ventral tegmental area (VTA) receive direct projections from the medial prefrontal cortex (mPFC), a structure known to be one of the brain areas that represents expected future rewards. To investigate whether the mPFC contributes to generating reward prediction error signals of DA cells, we recorded VTA cells from rats foraging for different amounts of reward in a spatial working memory task. Our results showed that DA cells initially responded after the acquisition of rewards, but over training, they exhibited phasic responses when rats detected sensory cues originating from the rewards before obtaining them. We also observed two separate groups of non-DA cells activated in expectation of upcoming rewards or during reward consumption. Bilateral injections of muscimol, a GABAAagonist, into the mPFC significantly decreased the non-DA activity that encoded reward expectation. By contrast, the same manipulation of the mPFC elevated DA responses to reward-predicting cues. However, neither DA nor non-DA responses elicited after reward acquisition were affected by mPFC inactivation. These results suggest that the mPFC provides information about expected rewards to the VTA, and its functional loss elevates DA responses to reward-predicting cues by altering expectations about forthcoming rewards.
NMDA-Dependent Phase Synchronization between Septal and Temporal CA3 Hippocampal Networks
Authors: Gu Ning , Jackson Jesse , Goutagny Romain , Lowe Germaine , Manseau Frédéric , Williams Sylvain
Published: May 2013

Increasing evidence suggests that synchronization between brain regions is essential for information exchange and memory processes. However, it remains incompletely known which synaptic mechanisms contribute to the process of synchronization. Here, we investigated whether NMDA receptor-mediated synaptic plasticity was an important player in synchronization between septal and temporal CA3 areas of the rat hippocampus. We found that both the septal and temporal CA3 regions intrinsically generate weakly synchronized δ frequency oscillations in the complete hippocampusin vitro. Septal and temporal oscillators differed in frequency, power, and rhythmicity, but both required GABAAand AMPA receptors. NMDA receptor activation, and most particularly the NR2B subunit, contributed considerably more to rhythm generation at the temporal than the septal region. Brief activation of NMDA receptors by application of extracellular calcium dramatically potentiated the septal–temporal coherence for long durations (>40 min), an effect blocked by the NMDA antagonist AP-5. This long-lasting NMDA-receptor-dependent increase in coherence was also associated with an elevated phase locking of spikes locally and across regions. Changes in coherence between oscillators were associated with increases in phase locking between oscillators independent of oscillator amplitude. Finally, although the septal CA3 rhythm preceded the oscillations in temporal regions in control conditions, this was reversed during the NMDA-dependent enhancement in coherence, suggesting that NMDA receptor activation can change the direction of information flow along the septotemporal CA3 axis. These data demonstrate that plastic changes in communication between septal and temporal hippocampal regions can arise from the NMDA-dependent phase locking of neural oscillators.
Small-Molecule Screen in AdultDrosophilaIdentifies VMAT as a Regulator of Sleep
Authors: Nall Aleksandra H. , Sehgal Amita
Published: May 2013

Sleep is an important physiological state, but its function and regulation remain elusive. InDrosophila melanogaster, a useful model organism for studying sleep, forward genetic screens have identified important sleep-modulating genes and pathways; however, the results of such screens may be limited by developmental abnormalities or lethality associated with mutation of certain genes. To circumvent these limitations, we used a small-molecule screen to identify sleep-modulating genes and pathways. We administered 1280 pharmacologically active small molecules to adult flies and monitored their sleep. We found that administration of reserpine, a small-molecule inhibitor of the vesicular monoamine transporter (VMAT) that repackages monoamines into presynaptic vesicles, resulted in an increase in sleep. Supporting the idea that VMAT is the sleep-relevant target of reserpine, we found that VMAT-null mutants have an increased sleep phenotype, as well as an increased arousal threshold and resistance to the effects of reserpine. However, although the VMAT mutants are consistently resistant to reserpine, other aspects of their sleep phenotype are dependent on genetic background. These findings indicate that small-molecule screens can be used effectively to identify sleep-modulating genes whose phenotypes may be suppressed in traditional genetic screens. Mutations affecting single monoamine pathways did not affect reserpine sensitivity, suggesting that effects of VMAT/reserpine on sleep are mediated by multiple monoamines. Overall, we identify VMAT as an important regulator of sleep inDrosophilaand demonstrate that small-molecule screens provide an effective approach to identify genes and pathways that impact adultDrosophilabehavior.
A Substantial and Unexpected Enhancement of Motion Perception in Autism
Authors: Foss-Feig Jennifer H. , Tadin Duje , Schauder Kimberly B. , Cascio Carissa J.
Published: May 2013

Atypical perceptual processing in autism spectrum disorder (ASD) is well documented. In addition, growing evidence supports the hypothesis that an excitatory/inhibitory neurochemical imbalance might underlie ASD. Here we investigated putative behavioral consequences of the excitatory/inhibitory imbalance in the context of visual motion perception. As stimulus size increases, typical observers exhibit marked impairments in perceiving motion of high-contrast stimuli. This result, termed “spatial suppression,” is believed to reflect inhibitory motion-processing mechanisms. Motion processing is also affected by gain control, an inhibitory mechanism that underlies saturation of neural responses at high contrast. Motivated by these behavioral correlates of inhibitory function, we investigated motion perception in human children with ASD (n= 20) and typical development (n= 26). At high contrast, both groups exhibited similar impairments in motion perception with increasing stimulus size, revealing no apparent differences in spatial suppression. However, there was a substantial enhancement of motion perception in ASD: children with ASD exhibited a consistent twofold improvement in perceiving motion. Hypothesizing that this enhancement might indicate abnormal weakening of response gain control, we repeated our measurements at low contrast, where the effects of gain control should be negligible. At low contrast, we indeed found no group differences in motion discrimination thresholds. These low-contrast results, however, revealed weaker spatial suppression in ASD, suggesting the possibility that gain control abnormalities in ASD might have masked spatial suppression differences at high contrast. Overall, we report a pattern of motion perception abnormalities in ASD that includes substantial enhancements at high contrast and is consistent with an underlying excitatory/inhibitory imbalance.
Imbalances in Prefrontal Cortex CC-Homer1 versus CC-Homer2 Expression Promote Cocaine Preference
Authors: Ary Alexis W. , Lominac Kevin D. , Wroten Melissa G. , Williams Amy R. , Campbell Rianne R. , Ben-Shahar Osnat , von Jonquieres Georg , Klugmann Matthias , Szumlinski Karen K.
Published: May 2013

Homer postsynaptic scaffolding proteins regulate forebrain glutamate transmission and thus, are likely molecular candidates mediating hypofrontality in addiction. Protracted withdrawal from cocaine experience increases the relative expression of Homer2 versus Homer1 isoforms within medial prefrontal cortex (mPFC). Thus, this study used virus-mediated gene transfer strategies to investigate the functional relevance of an imbalance in mPFC Homer1/2 expression as it relates to various measures of sensorimotor, cognitive, emotional and motivational processing, as well as accompanying alterations in extracellular glutamate in C57BL/6J mice. mPFC Homer2b overexpression elevated basal glutamate content and blunted cocaine-induced glutamate release within the mPFC, whereas Homer2b knockdown produced the opposite effects. Despite altering mPFC glutamate, Homer2b knockdown failed to influence cocaine-elicited conditioned place preferences, nor did it produce consistent effects on any other behavioral measures. In contrast, elevating the relative expression of Homer2b versus Homer1 within mPFC, by overexpressing Homer2b or knocking down Homer1c, shifted the dose-response function for cocaine-conditioned reward to the left, without affecting cocaine locomotion or sensitization. Intriguingly, both these transgenic manipulations produced glutamate anomalies within the nucleus accumbens (NAC) of cocaine-naive animals that are reminiscent of those observed in cocaine experienced animals, including reduced basal extracellular glutamate content, reduced Homer1/2 and glutamate receptor expression, and augmented cocaine-elicited glutamate release. Together, these data provide novel evidence in support of opposing roles for constitutively expressed Homer1 and Homer2 isoforms in regulating mPFC glutamate transmissionin vivoand support the hypothesis that cocaine-elicited increases in the relative amount of mPFC Homer2 versus Homer1 signaling produces abnormalities in NAC glutamate transmission that enhance vulnerability to cocaine reward.
Representations of Facial Identity Information in the Ventral Visual Stream Investigated with Multivoxel Pattern Analyses
Authors: Goesaert Elfi , Op de Beeck Hans P.
Published: May 2013

The neural basis of face recognition has been investigated extensively. Using fMRI, several regions have been identified in the human ventral visual stream that seem to be involved in processing and identifying faces, but the nature of the face representations in these regions is not well known. In particular, multivoxel pattern analyses have revealed distributed maps within these regions, but did not reveal the organizing principles of these maps. Here we isolated different types of perceptual and conceptual face properties to determine which properties are mapped in which regions. A set of faces was created with systematic manipulations of featural and configural visual characteristics. In a second part of the study, personal and spatial context information was added to all faces except one. The perceptual properties of faces were represented in face regions and in other regions of interest such as early visual and object-selective cortex. Only representations in early visual cortex were correlated with pixel-based similarities between the stimuli. The representation of nonperceptual properties was less distributed. In particular, the spatial location associated with a face was only represented in the parahippocampal place area. These findings demonstrate a relatively distributed representation of perceptual and conceptual face properties that involves both face-selective/sensitive and non-face-selective cortical regions.
Initiation, Labile, and Stabilization Phases of Experience-Dependent Plasticity at Neocortical Synapses
Authors: Wen Jing A. , DeBlois Mark C. , Barth Alison L.
Published: May 2013

Alteration of sensory input can change the strength of neocortical synapses. Selective activation of a subset of whiskers is sufficient to potentiate layer 4-layer 2/3 excitatory synapses in the mouse somatosensory (barrel) cortex, a process that is NMDAR dependent. By analyzing the time course of sensory-induced synaptic change, we have identified three distinct phases for synaptic strengtheningin vivo. After an early, NMDAR-dependent phase where selective whisker activation is rapidly translated into increased synaptic strength, we identify a second phase where this potentiation is profoundly reduced by an input-specific, NMDAR-dependent depression. This labile phase is transient, lasting only a few hours, and may require ongoing sensory input for synaptic weakening. Residual synaptic strength is maintained in a third phase, the stabilization phase, which requires mGluR5 signaling. Identification of these three phases will facilitate a molecular dissection of the pathways that regulate synaptic lability and stabilization, and suggest potential approaches to modulate learning.
The Novel Genetank, a Tumor Suppressor Homolog, Regulates Ethanol Sensitivity inDrosophila
Authors: Devineni Anita V. , Eddison Mark , Heberlein Ulrike
Published: May 2013

In both mammalian and insect models of ethanol intoxication, high doses of ethanol induce motor impairment and eventually sedation. Sensitivity to the sedative effects of ethanol is inversely correlated with risk for alcoholism. However, the genes regulating ethanol sensitivity are largely unknown. Based on a previous genetic screen inDrosophilafor ethanol sedation mutants, we identified a novel gene,tank(CG15626), the homolog of the mammalian tumor suppressorEI24/PIG8, which has a strong role in regulating ethanol sedation sensitivity. Genetic and behavioral analyses revealed thattankacts in the adult nervous system to promote ethanol sensitivity. We localized the function oftankin regulating ethanol sensitivity to neurons within the pars intercerebralis that have not been implicated previously in ethanol responses. We show that acutely manipulating the activity of alltank-expressing neurons, or of pars intercerebralis neurons in particular, alters ethanol sensitivity in a sexually dimorphic manner, since neuronal activation enhanced ethanol sedation in males, but not females. Finally, we provide anatomical evidence thattank-expressing neurons form likely synaptic connections with neurons expressing the neural sex determination factorfruitless(fru), which have been implicated recently in the regulation of ethanol sensitivity. We suggest that a functional interaction withfruneurons, many of which are sexually dimorphic, may account for the sex-specific effect induced by activatingtankneurons. Overall, we have characterized a novel gene and corresponding set of neurons that regulate ethanol sensitivity inDrosophila.
Amperometric Resolution of a Prespike Stammer and Evoked Phases of Fast Release from Retinal Bipolar Cells
Authors: Grabner Chad P. , Zenisek David
Published: May 2013

The neurotransmitter glutamate is used by most neurons in the brain to activate a multitude of different types of glutamate receptors and transporters involved in fast and relatively slower signaling. Synaptic ribbons are large presynaptic structures found in neurons involved in vision, balance, and hearing, which use a large number of glutamate-filled synaptic vesicles to meet their signaling demands. To directly measure synaptic vesicle release events, the ribbon-type presynaptic terminals of goldfish retinal bipolar cells were coaxed to release a false transmitter that could be monitored with amperometry by placing the carbon fiber directly on the larger synaptic terminal. Spontaneous secretion events formed a unimodal charge distribution, but single spike properties were heterogeneous. Larger events rose exponentially without interruption (τ ∼ 30 μs), and smaller events exhibited a stammer in their rising phase that is interpreted as a brief pause in pore dilation, a characteristic commonly associated with large dense core granule fusion pores. These events were entirely Ca2+-dependent. Holding the cells at −60 mV halted spontaneous release; and when the voltage was stepped to >−40 mV, secretion ensued. When stepping the voltage to 0 mV, novel kinetic phases of vesicle recruitment were revealed. Approximately 14 vesicles were released per ribbon in two kinetic phases with time constants of 1.5 and 16 ms, which are proposed to represent different primed states within the population of docked vesicles.
Frontal Theta Overrides Pavlovian Learning Biases
Authors: Cavanagh James F. , Eisenberg Ian , Guitart-Masip Marc , Huys Quentin , Frank Michael J.
Published: May 2013

Pavlovian biases influence learning and decision making by intricately coupling reward seeking with action invigoration and punishment avoidance with action suppression. This bias is not always adaptive—it can often interfere with instrumental requirements. The prefrontal cortex is thought to help resolve such conflict between motivational systems, but the nature of this control process remains unknown. EEG recordings of midfrontal theta band power are sensitive to conflict and predictive of adaptive control over behavior, but it is not clear whether this signal reflects control over conflict between motivational systems. Here we used a task that orthogonalized action requirements and outcome valence while recording concurrent EEG in human participants. By applying a computational model of task performance, we derived parameters reflective of the latent influence of Pavlovian bias and how it was modulated by midfrontal theta power during motivational conflict. Between subjects, those who performed better under Pavlovian conflict exhibited higher midfrontal theta power. Within subjects, trial-to-trial variance in theta power was predictive of ability to overcome the influence of the Pavlovian bias, and this effect was most pronounced in subjects with higher midfrontal theta to conflict. These findings demonstrate that midfrontal theta is not only a sensitive index of prefrontal control, but it can also reflect the application of top-down control over instrumental processes.
Thalamic Control of Neocortical Area Formation in Mice
Authors: Vue Tou Yia , Lee Melody , Tan Yew Ei , Werkhoven Zachary , Wang Lynn , Nakagawa Yasushi
Published: May 2013

The mammalian neocortex undergoes dramatic transformation during development, from a seemingly homogenous sheet of neuroepithelial cells into a complex structure that is tangentially divided into discrete areas. This process is thought to be controlled by a combination of intrinsic patterning mechanisms within the cortex and afferent axonal projections from the thalamus. However, roles of thalamic afferents in the formation of areas are still poorly understood. In this study, we show that genetically increasing or decreasing the size of the lateral geniculate nucleus of the mouse thalamus resulted in a corresponding change in the size of the primary visual area. Furthermore, elimination of most thalamocortical projections from the outset of their development resulted in altered areal gene expression patterns, particularly in the primary visual and somatosensory areas, where they lost sharp boundaries with adjacent areas. Together, these results demonstrate the critical roles of thalamic afferents in the establishment of neocortical areas.