Nanoscale Sub-Compartmentalization of the Dendritic Spine Compartment

Compartmentalization of the membrane is essential for cells to perform highly specific tasks and spatially constrained biochemical functions in topographically defined areas. These membrane lateral heterogeneities range from nanoscopic dimensions, often involving only a few molecular constituents, to micron-sized mesoscopic domains resulting from the coalescence of nanodomains. Short-lived domains lasting for a few milliseconds coexist with more stable platforms lasting from minutes to days. This panoply of lateral domains subserves the great variety of demands of cell physiology, particularly high for those implicated in signaling. The dendritic spine, a subcellular structure of neurons at the receiving (postsynaptic) end of central nervous system excitatory synapses, exploits this compartmentalization principle. In its most frequent adult morphology, the mushroom-shaped spine harbors neurotransmitter receptors, enzymes, and scaffolding proteins tightly packed in a volume of a few femtoliters. In addition to constituting a mesoscopic lateral heterogeneity of the dendritic arborization, the dendritic spine postsynaptic membrane is further compartmentalized into spatially delimited nanodomains that execute separate functions in the synapse. This review discusses the functional relevance of compartmentalization and nanodomain organization in synaptic transmission and plasticity and exemplifies the importance of this parcelization in various neurotransmitter signaling systems operating at dendritic spines, using two fast ligand-gated ionotropic receptors, the nicotinic acetylcholine receptor and the glutamatergic receptor, and a second-messenger G-protein coupled receptor, the cannabinoid receptor, as paradigmatic examples.Fil: Valles, Ana Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Barrantes, Francisco Jose. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentin

Gut microbiome and health : mechanistic insights

The gut microbiota is now considered as one of the key elements contributing to the regulation of host health. Virtually all our body sites are colonised by microbes suggesting different types of crosstalk with our organs. Because of the development of molecular tools and techniques (ie, metagenomic, metabolomic, lipidomic, metatranscriptomic), the complex interactions occurring between the host and the different microorganisms are progressively being deciphered. Nowadays, gut microbiota deviations are linked with many diseases including obesity, type 2 diabetes, hepatic steatosis, intestinal bowel diseases (IBDs) and several types of cancer. Thus, suggesting that various pathways involved in immunity, energy, lipid and glucose metabolism are affected. In this review, specific attention is given to provide a critical evaluation of the current understanding in this field. Numerous molecular mechanisms explaining how gut bacteria might be causally linked with the protection or the onset of diseases are discussed. We examine well-established metabolites (ie, short-chain fatty acids, bile acids, trimethylamine N-oxide) and extend this to more recently identified molecular actors (ie, endocannabinoids, bioactive lipids, phenolic-derived compounds, advanced glycation end products and enterosynes) and their specific receptors such as peroxisome proliferator-activated receptor alpha (PPAR alpha) and gamma (PPAR gamma), aryl hydrocarbon receptor (AhR), and G protein-coupled receptors (ie, GPR41, GPR43, GPR119, Takeda G protein-coupled receptor 5). Altogether, understanding the complexity and the molecular aspects linking gut microbes to health will help to set the basis for novel therapies that are already being developed.Peer reviewe

Power battles in ICT standards-setting process : lessons from mobile payments

Standards play an important role in ICT innovation to ensure the interoperability and interconnectivity. However, standardisation is a complex process that involves actors with different interests. Various studies, which are mainly economics, have tried to develop the standards-setting process models. One of the models proposes that standardisation can be distinguished into two main stages, i.e., the pre-standardisation stage and the standardisation stage (Smits, 1993). The distinction is based on the different players involved in each stage. The pre-standardisation stage is the period when the players involved are mostly the firms who have developed a new technological specification or requirement, which they want to become the standard. In this period, they draft proposals or recommendations for submission to a formal standards body. If accepted, the proposal or recommendation becomes a working item within the Technical Committee or Working Group of the standards body. This marks the beginning of the standardisation stage. The outcome of the pre-standardisation stage may, on the other hand, be made publicly available and become the market standard. If this is happens, there is no standardisation stage, and the process becomes de facto standardisation. The early stage of standardisation is considered to be the most important period in the standards-setting process for a number of reasons, the main one being that the dynamics and the interactions among actors during the early period may influence the process and the outcome. Various activities take place in this period, such as information gathering, lobbying, and informal meetings. These initial actions reveal the interactions among involved actors that have a substantial impact on the entire standards-setting process. Power is a factor that shapes the dynamics of these interactions. However, little research has been undertaken to explore this dynamics. This study, thus represents an effort to redress this, by exploring the mechanism of standardisation and the interactions that take place among the parties involved. To be precise, this study explores the power battles among the negotiating parties during the standards-setting process. The main research question of this study can be formulated as: How do the power battles shape the process of standards-setting in ICT industry? Qualitative case study research has been chosen as the research methodology. The qualitative case study consists of case selection and data collection, which includes interviews and documentation from technical report, white papers, news, to company profiles. Prior to the case study activities, literature survey on standardisation and negotiation, which is a part of desk research, has been conducted and serves as the knowledge source and the theoretical framework of this study. In addition, literature survey can also be used as a secondary source of data. Negotiation theory has been used to deliberate the concept of power. For the empirical part, the aspect of the ICT industry that has been chosen is Mobile Payments. The development of Mobile Payments, defined as an activity that occurs between two parties utilising a combination platform Power Battles 222 in ICT Standards-Setting Process between financial and mobile communications, is still in the conceptual and trial period, which means that as yet no standards have been defined. This provides an ideal context in which to track the process of standardisation and all it involves. Moreover, different sectors are involved in this emerging technology, which means a variety of power based negotiations are likely to occur. Therefore, five Mobile Payments developing organisations are revealed as the arena and discussed as the case studies. They are the Mobile Payment Forum, Mobey Forum, Simpay, PayCircle, and ECBS. Mobile Payments can be seen as a result of an innovation in a service industry. By definition, Mobile Payments is an incremental innovation, that is, a new technology that offers improved performance in payment method offered by payment institutions through mobile devices and networks. Mobile Payments is an improved service and a new method of payment, which involves services from the financial and mobile communications industries. Mobile Payments involves the telecommunications and the financial industries. Both industries have several existing standards, supported by powerful parties, and both industries are themselves powerful parties. As a result, standards development for Mobile Payments is being shaped by two powerful parties from different industries. Standards-setting for Mobile Payments thus is an inter-industry battleground, hence the current absence of standards for Mobile Payments. Various actors have made attempts to set standards for Mobile Payments. Mobile Payments is in the beginning and early period of the standards-setting process, in which only related firms are involved. Negotiation and informal meetings between parties occur during this stage, and an agreement among actors about certain solutions would be generated to proceed to the next level. For de facto standardisation, the agreement would be standards launched on the market. In the case of de jure standardisation, the agreement takes the form of a proposal, which must be examined and accepted as the working project by the formal standards body. The two major industry groups involved in Mobile Payments initiated various organisations. Financial industry initiatives resulted in the Mobile Payment Forum, the Mobey Forum and the European Committee for Banking Standards (ECBS). Initiatives from the telecommunications industry resulted in the establishment of what eventually became known as Simpay. In addition to these initiatives from the two major industries, the IT industry group representing manufacturers and vendors – launched PayCircle. Although competing to each other, these groups are inter-related. A number of firms join more than one group, playing a different role in each. For instance, in one group, a firm might be a Board member whilst it might only be an Associate member of another. Grindley (1995) calls these types of alliances cross-membership. It represents a strategic movement, designed to monitor the activities of others in the various fora. In Mobile Payments standardisation, four power types can be identified. These types of power are exercised by the different categories of actors in negotiating standards-setting process; they are legitimate power, expert power, referent power, and informational power. Legitimate power is possessed by the founder of consortia, and reflected from the leadership privilege in decision-making. Expert power is characterised by the expertise in particular area and technological know-how mostly possessed by the manufacturers. The expert power provides them to propose the preferred architecture of Mobile Payments. Referent power is acquired through reputation and influential individual, which is performed well by service oriented organisations. Related Summary 223 information, for instance on the current development on Mobile Payments, provides knowledge to the information possessor, and leads to the informational power. In this case, the typical possessors of informational power are network operators and credit-card companies. The existence of different Mobile Payments developing groups introduces competition at consortium level. The competition between groups affects the power battles among them. Each organisation has different power types, which produce different power dominance. The differences lie in the different membership composition. Mobile Payment Forum is a business and policy oriented consortium, which is reflected in the variety of its membership composition. Mobey Forum is a technically oriented consortium, whose concern is to implement mobile technologies for financial services. Simpay is a commercial and profit oriented group, and is registered as a UK-based company. PayCircle is a technically oriented consortium as exemplified by its membership. And ECBS is a policy-oriented organisation, which is evident from its membership composition and structure. Moreover, ECBS acts as regulator in the banking sector. The power battles among these organisations reveal certain characteristics. Although all Mobile Payments organisations possess expert power, this varies in type depending on the expertise of their members. For instance, although Mobey Forum and PayCirlce are both technically oriented, they have different approaches and different expertise. Although the Mobile Payment Forum and ECBS are both policy-oriented organisations, ECBS has more legitimate power than Mobile Payment Forum because the Mobile Payment Forum is a business-oriented group, which implements its legitimate power within the organisation, while ECBS has legitimate power over external organisations. The result of these power battles is the multiple types of Mobile Payments being developed by the various organisations. The first type is a bank-account-based system, which is also known as wallet-based Mobile Payments. Mobey Forum is the developer of this system, which reflects the expert power of its founders. This payment system is also supported by PayCircle and ECBS, which indicates referent power among these three organisations. The second type is a telco-billing-based system, which is being developed by Simpay. Simpay’s persistence in pursuing this system demonstrates its expert power; its founders are the leading mobile network operators. In addition, this development shows the legitimate power of Simpay’s founder. When developing this system, Simpay demonstrates its informational power in approaching banks to become members. Simpay’s informational power is based on its understanding of the importance of payment systems to banks. However, the commission rate in Simpay’s proposed architecture is too high, which makes it difficult for them to accept the architectures being proposed by the banks. Simpay’s proposed architecture is similarly not supported by other organisations. The third type is credit-card-based, and is being developed by the Mobile Payment Forum. This type of development by the Mobile Payment Forum demonstrates the legitimate power of its founders. Moreover, it also exemplifies the expert power of the founders, which are the leading credit-card institutions. The fact that the Mobile Power Battles 224 in ICT Standards-Setting Process Payment Forum is the most heterogeneous Mobile Payments developing organisation, demonstrates that it has referent power. From the three different types of Mobile Payments being developed, it is obvious that there is a conflict of interests among the involved parties. Each of them would like to gain the maximum outcome by becoming the technological leader through dominant design in the market. As a result, different technologies compete and create the power battles among them. Therefore, one may conclude that the power battles in standardssetting process cause technology variation and lead to the uncertainty of the standards for the technology in question

Actor perception in business use case modeling

Mainstream literature recognizes the validity and effectiveness of use cases as a technique for gathering and capturing system requirements. Use cases represent the driver of various modern development methods, mainly of object-oriented extraction, such as the Unified Process. Although the adoption of use cases proliferated in the context of software systems development, they are not as extensively employed in business modeling . The concept of business use case is not a novelty, but only recently did it begin to re-circulate in the literature and in case tools. This paper examines the issues involved in adopting business use cases for capturing the functionality of an organization and proposes guidelines for their identification, packaging, and mapping to system use cases. The proposed guidelines are based on the principle of actor perception described in the paper. The application of this principle is exemplified with a worked example aimed at demonstrating the utility of the proposed guidelines and at clarifying the application of the principle of actor perception. The worked example is based on a series of workshops run at a major UK financial institution

Using ATL to define advanced and flexible constraint model transformations

Transforming constraint models is an important task in re- cent constraint programming systems. User-understandable models are defined during the modeling phase but rewriting or tuning them is manda- tory to get solving-efficient models. We propose a new architecture al- lowing to define bridges between any (modeling or solver) languages and to implement model optimizations. This architecture follows a model- driven approach where the constraint modeling process is seen as a set of model transformations. Among others, an interesting feature is the def- inition of transformations as concept-oriented rules, i.e. based on types of model elements where the types are organized into a hierarchy called a metamodel

Defining the organizational structure of dopamine and muscarninic acetylcholine receptors

No abstract available

The evolution of Europe’s financial stability agenda

PhD Thesi