Histamine induces ATP release from human subcutaneous fibroblasts via pannexin-1 hemichannels leading to Ca2+ mobilization and cell proliferation

Changes in the regulation of connective tissue ATP-mediated mechano-transduction and remodeling may be an important link to the pathogenesis of chronic pain. It has been demonstrated that mast cell-derived histamine plays an important role in painful fibrotic diseases. Here we analyzed the involvement of ATP in the response of human subcutaneous fibroblasts to histamine. Acute histamine application caused a rise in intracellular Ca2+ ([Ca2+]i) and ATP release from human subcutaneous fibroblasts via H1 receptor activation. Histamine-induced [Ca2+]i rise was partially attenuated by apyrase, an enzyme that inactivates extracellular ATP, and by blocking P2 purinoceptors with pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) tetrasodium salt and reactive blue 2. [Ca2+]i accumulation caused by histamine was also reduced upon blocking pannexin-1 hemichannels with 10Panx, probenecid, or carbenoxolone but not when connexin hemichannels were inhibited with mefloquine or 2-octanol. Brefeldin A, an inhibitor of vesicular exocytosis, also did not block histamine-induced [Ca2+]i mobilization. Prolonged exposure of human subcutaneous fibroblast cultures to histamine favored cell growth and type I collagen synthesis via the activation of H1 receptor. This effect was mimicked by ATP and its metabolite, ADP, whereas the selective P2Y1 receptor antagonist, MRS2179, partially attenuated histamine-induced cell growth and type I collagen production. Expression of pannexin-1 and ADPsensitive P2Y1 receptor on human subcutaneous fibroblasts was confirmed by immunofluorescence confocal microscopy and Western blot analysis. In conclusion, histamine induces ATP release from human subcutaneous fibroblasts, via pannexin-1 hemichannels, leading to [Ca2+]i mobilization and cell growth through the cooperation of H1 and P2 (probably P2Y1) receptors.

Phenotypic impact of deregulated expression of class I histone deacetylases in urothelial cell carcinoma of the bladder

Deregulated expression of histone deacetylases (HDACs) has been implicated in tumorigenesis. Herein, we investigated class I HDACs expression in bladder urothelial cell carcinoma (BUCC), its prognostic value and biological significance. Significantly increased transcript levels of all HDACs were found in BUCC compared to 20 normal mucosas, and these were higher in lower grade and stage tumors. Increased HDAC3 levels were associated with improved patient survival. SiRNA experiments showed decrease cell viability and motility, and increased apoptosis. We concluded that class I HDACs play an important role in bladder carcinogenesis through deregulation of proliferation, migration and apoptosis, constituting putative therapeutic targets

Enabling inter-domain transactions in bridge-based hybrid wired/wireless PROFIBUS networks

The marriage of emerging information technologies with control technologies is a major driving force that, in the context of the factory-floor, is creating an enormous eagerness for extending the capabilities of currently available fieldbus networks to cover functionalities not considered up to a recent past. Providing wireless capabilities to such type of communication networks is a big share of that effort. The RFieldbus European project is just one example, where PROFIBUS was provided with suitable extensions for implementing hybrid wired/wireless communication systems. In RFieldbus, interoperability between wired and wireless components is achieved by the use specific intermediate networking systems operating as repeaters, thus creating a single logical ring (SLR) network. The main advantage of the SLR approach is that the effort for protocol extensions is not significant. However, a multiple logical ring (MLR) approach provides traffic and error isolation between different network segments. This concept was introduced in, where an approach for a bridge-based architecture was briefly outlined. This paper will focus on the details of the inter-Domain Protocol (IDP), which is responsible for handling transactions between different network domains (wired or wireless) running the PROFIBUS protocol.

Besnoitia besnoiti and Toxoplasma gondii: two apicomplexan strategies to manipulate the host cell centrosome and Golgi apparatus

Besnoitia besnoiti and Toxoplasma gondii are two closely related parasites that interact with the host cell microtubule cytoskeleton during host cell invasion. Here we studied the relationship between the ability of these parasites to invade and to recruit the host cell centrosome and the Golgi apparatus. We observed that T. gondii recruits the host cell centrosome towards the parasitophorous vacuole (PV), whereas B. besnoiti does not. Notably, both parasites recruit the host Golgi apparatus to the PV but its organization is affected in different ways. We also investigated the impact of depleting and over-expressing the host centrosomal protein TBCCD1, involved in centrosome positioning and Golgi apparatus integrity, on the ability of these parasites to invade and replicate. Toxoplasma gondii replication rate decreases in cells over-expressing TBCCD1 but not in TBCCD1-depleted cells; while for B. besnoiti no differences were found. However, B. besnoiti promotes a reorganization of the Golgi ribbon previously fragmented by TBCCD1 depletion. These results suggest that successful establishment of PVs in the host cell requires modulation of the Golgi apparatus which probably involves modifications in microtubule cytoskeleton organization and dynamics. These differences in how T. gondii and B. besnoiti interact with their host cells may indicate different evolutionary paths.

A general overview on hybrid and electric vehicles

The economical and environment impacts of fossil energies increased the interest for hybrid, battery and fuel-cell electric vehicles. Several demanding engineering challenges must be faced, motivated by different physical domains integration. This paper aims to present an overview on hybrid (HEV) and electric vehicles (EV) basic structures and features. In addition, it will try to point out some of the most relevant challenges to overcome for HEV and EV may be a solid option for the mobility issue. New developments in energy storage devices and energy management systems (EMS) are crucial to achieve this goal.

Poster abstract: Smart-HOP: a reliable handoff procedure for supporting mobility in wireless sensor networks

This poster abstract presents smart-HOP, a reliable handoff mechanism for mobility support in Wireless Sensor Networks (WSNs). This technique relies on a fuzzy logic approach applied at two levels: the link quality estimation level and the access point selection level. We present the conceptual design of smart-HOP and then we discuss implementation requirements and challenges.

On the use of code mobility mechanisms in real-time systems

Applications with soft real-time requirements can benefit from code mobility mechanisms, as long as those mechanisms support the timing and Quality of Service requirements of applications. In this paper, a generic model for code mobility mechanisms is presented. The proposed model gives system designers the necessary tools to perform a statistical timing analysis on the execution of the mobility mechanisms that can be used to determine the impact of code mobility in distributed real-time applications.

Inter-application redundancy elimination in sensor networks with compiler-assisted scheduling

Most current-generation Wireless Sensor Network (WSN) nodes are equipped with multiple sensors of various types, and therefore support for multi-tasking and multiple concurrent applications is becoming increasingly common. This trend has been fostering the design of WSNs allowing several concurrent users to deploy applications with dissimilar requirements. In this paper, we extend the advantages of a holistic programming scheme by designing a novel compiler-assisted scheduling approach (called REIS) able to identify and eliminate redundancies across applications. To achieve this useful high-level optimization, we model each user application as a linear sequence of executable instructions. We show how well-known string-matching algorithms such as the Longest Common Subsequence (LCS) and the Shortest Common Super-sequence (SCS) can be used to produce an optimal merged monolithic sequence of the deployed applications that takes into account embedded scheduling information. We show that our approach can help in achieving about 60% average energy savings in processor usage compared to the normal execution of concurrent applications.

On a reliable handoff procedure for supporting mobility in wireless sensor networks

Wireless sensor network (WSN) applications such as patients’ health monitoring in hospitals, location-aware ambient intelligence, industrial monitoring /maintenance or homeland security require the support of mobile nodes or node groups. In many of these applications, the lack of network connectivity is not admissible or should at least be time bounded, i.e. mobile nodes cannot be disconnected from the rest of the WSN for an undefined period of time. In this context, we aim at reliable and real-time mobility support in WSNs, for which appropriate handoff and rerouting decisions are mandatory. This paper1 drafts a mechanism and correspondent heuristics for taking reliable handoff decisions in WSNs. Fuzzy logic is used to incorporate the inherent imprecision and uncertainty of the physical quantities at stake.

Handling mobility on a QoS-Aware servicebased framework for mobile systems

Mobile applications are becoming increasingly more complex and making heavier demands on local system resources. Moreover, mobile systems are nowadays more open, allowing users to add more and more applications, including third-party developed ones. In this perspective, it is increasingly expected that users will want to execute in their devices applications which supersede currently available resources. It is therefore important to provide frameworks which allow applications to benefit from resources available on other nodes, capable of migrating some or all of its services to other nodes, depending on the user needs. These requirements are even more stringent when users want to execute Quality of Service (QoS) aware applications, such as voice or video. The required resources to guarantee the QoS levels demanded by an application can vary with time, and consequently, applications should be able to reconfigure themselves. This paper proposes a QoS-aware service-based framework able to support distributed, migration-capable, QoS-enabled applications on top of the Android Operating system.

Molecular mobility of n-ethylene glycol dimethacrylate glass formers upon free radical polymerization

Quando um líquido evita a cristalização durante o arrefecimento, diz-se que entra no estado sobrearrefecido. Se a temperatura continuar a diminuir, o consequente aumento da viscosidade reflecte-se na mobilidade molecular de tal maneira que os tempos característicos se tornam da mesma ordem de grandeza que os tempos acessíveis experimentalmente. Se o arrefecimento continuar, o líquido altamente viscoso acaba por vitrificar, i.e. entra no estado vítreo onde apenas os movimentos locais são permitidos. Os monómeros da família n -etileno glicol dimetacrilato ( n -EGDMA, para n = 1 até 4, que constituem o objecto deste estudo, facilmente evitam a cristalização, sendo pois bons candidatos para estudar a mobilidade molecular nos estados sobrearrefecido e vítreo. A Espectroscopia de Relaxação Dieléctrica (DRS) foi a técnica escolhida para obter informação detalhada sobre a sua dinâmica molecular (Capítulos 1 e 2). A primeira parte deste trabalho consistiu na caracterização dieléctrica dos processos de relaxação existentes acima e abaixo da temperatura de transição vítrea (g T ), a qual aumenta com o aumento do peso molecular (w M ), sendo este resultado confirmado por Calorimetria Diferencial de Varrimento (DSC). No que respeita ao processo cooperativo a , associado à transição vítrea, e ao processo secundário b, observa-se uma dependência com w M , enquanto que o outro processo secundário, g , aparenta ser independente deste factor (Capítulo 3). Nos capítulos seguintes, foram levadas a cabo diferentes estratégias com o objectivo de clarificar os mecanismos que estão na origem destas duas relaxações secundárias (b e g ), assim como conhecer a sua respectiva relação com a relaxação principal (a ). Do estudo, em tempo real, da polimerização isotérmica via radicais livres do TrEGDMA por Calorimetria de Varrimento Diferencial com Modulação de Temperatura (TMDSC), levado a cabo a temperaturas abaixo da g T do polímero final, concluem-se entre outros, dois importantes aspectos: i) que a vitrificação do polímero em formação conduz a graus de conversão relativamente baixos, e ii) que o monómero que está por reagir é expulso da rede polimérica que se forma, dando lugar a uma clara separação de fases (Capítulo 4). Com base nesta informação, o passo seguinte foi estudar separadamente a polimerização isotérmica do di-, tri- e tetra-EGDMA, dando especial atenção às alterações de mobilidade do monómero ainda por reagir. Com as restrições impostas pela formação de ligações químicas, as relaxações a e b detectadas no monómero tendem a desaparecer no novo polímero formado, enquanto que a relaxação g se mantém quase inalterada. Os diferentes comportamentos que aparecem durante a polimerização permitiram a atribuição da origem molecular dos processos secundários: o processo g foi associado ao movimento twisting das unidades etileno glicol, enquanto que a rotação dos grupos carboxilo foi relacionada com a relaxação b (Capítulo 5). No que respeita ao próprio polímero, um processo de relaxação adicional foi detectado, pol b , no poly-DEGDMA, poly-TrEGDMA e poly-TeEGDMA, com características similares ao encontrado nos poli(metacrilato de n -alquilo). Este processo foi confirmado e bem caracterizado aquando do estudo da copolimerização do TrEGDMA com acrilato de metilo (MA) para diferentes composições (Capítulo 6). Para finalizar, o EGDMA, o elemento mais pequeno da família de monómeros estudada, além de vitrificar apresenta uma marcada tendência para cristalizar quer a partir do estado líquido ou do estado vítreo. Durante a cristalização, a formação de uma fase rígida afecta principalmente o processo a , cuja intensidade diminui sem no entanto se observarem modificações significativas na dependência do tempo de relaxação característico com a temperatura. Por outro lado, o processo secundário b torna-se melhor definido e mais estreito, o que pode ser interpretado em termos de uma maior homogeneidade dos micro-ambientes associados aos movimentos locais(Capítulo 7).

Optimising and adapting the QoS of a dynamic set of inter-dependent tasks

Due to the growing complexity and adaptability requirements of real-time systems, which often exhibit unrestricted Quality of Service (QoS) inter-dependencies among supported services and user-imposed quality constraints, it is increasingly difficult to optimise the level of service of a dynamic task set within an useful and bounded time. This is even more difficult when intending to benefit from the full potential of an open distributed cooperating environment, where service characteristics are not known beforehand and tasks may be inter-dependent. This paper focuses on optimising a dynamic local set of inter-dependent tasks that can be executed at varying levels of QoS to achieve an efficient resource usage that is constantly adapted to the specific constraints of devices and users, nature of executing tasks and dynamically changing system conditions. Extensive simulations demonstrate that the proposed anytime algorithms are able to quickly find a good initial solution and effectively optimise the rate at which the quality of the current solution improves as the algorithms are given more time to run, with a minimum overhead when compared against their traditional versions.

Bilirubin directly disrupts membrane lipid polarity and fluidity, protein order, and redox status in rat mitochondria

Background/Aims: Unconjugated bilirubin (UCB) impairs crucial aspects of cell function and induces apoptosis in primary cultured neurones. While mechanisms of cytotoxicity begin to unfold, mitochondria appear as potential primary targets. Methods: We used electron paramagnetic resonance spectroscopy analysis of isolated rat mitochondria to test the hypothesis that UCB physically interacts with mitochondria to induce structural membrane perturbation, leading to increased permeability, and subsequent release of apoptotic factors. Results: Our data demonstrate profound changes on mitochondrial membrane properties during incubation with UCB, including modified membrane lipid polarity and fluidity (P , 0:01), as well as disrupted protein mobility(P , 0:001). Consistent with increased permeability, cytochrome c was released from the intermembrane space(P , 0:01), perhaps uncoupling the respiratory chain and further increasing oxidative stress (P , 0:01). Both ursodeoxycholate, a mitochondrial-membrane stabilising agent, and cyclosporine A, an inhibitor of the permeability transition, almost completely abrogated UCB-induced perturbation. Conclusions: UCB directly interacts with mitochondria influencing membrane lipid and protein properties, redox status, and cytochrome c content. Thus, apoptosis induced by UCB may be mediated, at least in part, by physical perturbation of the mitochondrial membrane. These novel findings should ultimately prove useful to our evolving understanding of UCB cytotoxicity.

Professions and inter-disciplinary teamwork in socially embedded bureaucracies: Synthesis and hypotheses on the impact of informal and formal organization

In order to maximize their productivity, inter-disciplinary multi-occupation teams of professionals need to maximize inter-occupational cooperation in team decision making. Cooperation, however, is challenged by status anxiety over organizational careers and identity politics among team members who differ by ethnicity-race, gender, religion, nativity, citizenship status, etc. The purpose of this paper is to develop hypotheses about how informal and formal features of bureaucracy influence the level of inter-occupation cooperation achieved by socially diverse, multi-occupation work teams of professionals in bureaucratic work organizations. The 18 hypotheses, which are developed with the heuristic empirical case of National Science Foundation-sponsored university school partnerships in math and science curriculum innovation in the United States, culminate in the argument that cooperation can be realized as a synthesis of tensions between informal and formal features of bureaucracy in the form of participatory, high performance work systems.

Dynamic QoS adaptation of inter- dependent task sets in cooperative embedded systems

Due to the growing complexity and dynamism of many embedded application domains (including consumer electronics, robotics, automotive and telecommunications), it is increasingly difficult to react to load variations and adapt the system's performance in a controlled fashion within an useful and bounded time. This is particularly noticeable when intending to benefit from the full potential of an open distributed cooperating environment, where service characteristics are not known beforehand and tasks may exhibit unrestricted QoS inter-dependencies. This paper proposes a novel anytime adaptive QoS control policy in which the online search for the best set of QoS levels is combined with each user's personal preferences on their services' adaptation behaviour. Extensive simulations demonstrate that the proposed anytime algorithms are able to quickly find a good initial solution and effectively optimise the rate at which the quality of the current solution improves as the algorithms are given more time to run, with a minimum overhead when compared against their traditional versions.