Bradykinin, but not muscarinic, inhibition of M-current in rat sympathetic ganglion neurons involves phospholipase C-β4

Rat superior cervical ganglion (SCG) neurons express low-threshold noninactivating M-type potassium channels (I-K(M)), which can be inhibited by activation of M-1 muscarinic receptors (M-1 mAChR) and bradykinin (BK) B-2 receptors. Inhibition by the M1 mAChR agonist oxotremorine methiodide (Oxo-M) is mediated, at least in part, by the pertussis toxin-insensitive G-protein G alpha (q) (Caulfield et al., 1994; Haley et al., 1998a), whereas BK inhibition involves G alpha (q) and/or G alpha (11) (Jones et al., 1995). G alpha (q) and G alpha (11) can stimulate phospholipase C-beta (PLC-beta), raising the possibility that PLC is involved in I-K(M) inhibition by Oxo-M and BK. RT-PCR and antibody staining confirmed the presence of PLC-beta1, - beta2, - beta3, and - beta4 in rat SCG. We have tested the role of two PLC isoforms (PLC-beta1 and PLC-beta4) using antisense-expression constructs. Antisense constructs, consisting of the cytomegalovirus promoter driving antisense cRNA corresponding to the 3'-untranslated regions of PLC-beta1 and PLC-beta4, were injected into the nucleus of dissociated SCG neurons. Injected cells showed reduced antibody staining for the relevant PLC-beta isoform when compared to uninjected cells 48 hr later. BK inhibition of I-K(M) was significantly reduced 48 hr after injection of the PLC-beta4, but not the PLC-beta1, antisense-encoding plasmid. Neither PLC-beta antisense altered M-1 mAChR inhibition by Oxo-M. These data support the conclusion of Cruzblanca et al. (1998) that BK, but not M-1 mAChR, inhibition of I-K(M) involves PLC and extends this finding by indicating that PLC-beta4 is involved.

Impaired fast-spiking, suppressed cortical inhibition and increased susceptibility to seizures in mice lacking Kv3.2 K+ channel proteins

Voltage-gated K+ channels of the Kv3 subfamily have unusual electrophysiological properties, including activation at very depolarized voltages (positive to −10 mV) and very fast deactivation rates, suggesting special roles in neuronal excitability. In the brain, Kv3 channels are prominently expressed in select neuronal populations, which include fast-spiking (FS) GABAergic interneurons of the neocortex, hippocampus, and caudate, as well as other high-frequency firing neurons. Although evidence points to a key role in high-frequency firing, a definitive understanding of the function of these channels has been hampered by a lack of selective pharmacological tools. We therefore generated mouse lines in which one of the Kv3 genes, Kv3.2, was disrupted by gene-targeting methods. Whole-cell electrophysiological recording showed that the ability to fire spikes at high frequencies was impaired in immunocytochemically identified FS interneurons of deep cortical layers (5-6) in which Kv3.2 proteins are normally prominent. No such impairment was found for FS neurons of superficial layers (2-4) in which Kv3.2 proteins are normally only weakly expressed. These data directly support the hypothesis that Kv3 channels are necessary for high-frequency firing. Moreover, we found that Kv3.2 −/− mice showed specific alterations in their cortical EEG patterns and an increased susceptibility to epileptic seizures consistent with an impairment of cortical inhibitory mechanisms. This implies that, rather than producing hyperexcitability of the inhibitory interneurons, Kv3.2 channel elimination suppresses their activity. These data suggest that normal cortical operations depend on the ability of inhibitory interneurons to generate high-frequency firing.

K(+) channel expression distinguishes subpopulations of parvalbumin- and somatostatin-containing neocortical interneurons

Kv3.1 and Kv3.2 K+ channel proteins form similar voltage-gated K+ channels with unusual properties, including fast activation at voltages positive to −10 mV and very fast deactivation rates. These properties are thought to facilitate sustained high-frequency firing. Kv3.1 subunits are specifically found in fast-spiking, parvalbumin (PV)-containing cortical interneurons, and recent studies have provided support for a crucial role in the generation of the fast-spiking phenotype. Kv3.2 mRNAs are also found in a small subset of neocortical neurons, although the distribution of these neurons is different. We raised antibodies directed against Kv3.2 proteins and used dual-labeling methods to identify the neocortical neurons expressing Kv3.2 proteins and to determine their subcellular localization. Kv3.2 proteins are prominently expressed in patches in somatic and proximal dendritic membrane as well as in axons and presynaptic terminals of GABAergic interneurons. Kv3.2 subunits are found in all PV-containing neurons in deep cortical layers where they probably form heteromultimeric channels with Kv3.1 subunits. In contrast, in superficial layer PV-positive neurons Kv3.2 immunoreactivity is low, but Kv3.1 is still prominently expressed. Because Kv3.1 and Kv3.2 channels are differentially modulated by protein kinases, these results raise the possibility that the fast-spiking properties of superficial- and deep-layer PV neurons are differentially regulated by neuromodulators. Interestingly, Kv3.2 but not Kv3.1 proteins are also prominent in a subset of seemingly non-fast-spiking, somatostatin- and calbindin-containing interneurons, suggesting that the Kv3.1–Kv3.2 current type can have functions other than facilitating high-frequency firing.

From SNPs to pathways: integration of functional effect of sequence variations on models of cell signalling pathways

Background: Single nucleotide polymorphisms (SNPs) are the most frequent type of sequence variation between individuals, and represent a promising tool for finding genetic determinants of complex diseases and understanding the differences in drug response. In this regard, it is of particular interest to study the effect of non-synonymous SNPs in the context of biological networks such as cell signalling pathways. UniProt provides curated information about the functional and phenotypic effects of sequence variation, including SNPs, as well as on mutations of protein sequences. However, no strategy has been developed to integrate this information with biological networks, with the ultimate goal of studying the impact of the functional effect of SNPs in the structure and dynamics of biological networks. Results: First, we identified the different challenges posed by the integration of the phenotypic effect of sequence variants and mutations with biological networks. Second, we developed a strategy for the combination of data extracted from public resources, such as UniProt, NCBI dbSNP, Reactome and BioModels. We generated attribute files containing phenotypic and genotypic annotations to the nodes of biological networks, which can be imported into network visualization tools such as Cytoscape. These resources allow the mapping and visualization of mutations and natural variations of human proteins and their phenotypic effect on biological networks (e.g. signalling pathways, protein-protein interaction networks, dynamic models). Finally, an example on the use of the sequence variation data in the dynamics of a network model is presented. Conclusion: In this paper we present a general strategy for the integration of pathway and sequence variation data for visualization, analysis and modelling purposes, including the study of the functional impact of protein sequence variations on the dynamics of signalling pathways. This is of particular interest when the SNP or mutation is known to be associated to disease. We expect that this approach will help in the study of the functional impact of disease-associated SNPs on the behaviour of cell signalling pathways, which ultimately will lead to a better understanding of the mechanisms underlying complex diseases.

A WiMAX-based implementation of network MIMO for indoor wireless systems

It is well known that multiple-input multiple-output (MIMO) techniques can bring numerous benefits, such as higher spectral efficiency, to point-to-point wireless links. More recently, there has been interest in extending MIMO concepts tomultiuser wireless systems. Our focus in this paper is on network MIMO, a family of techniques whereby each end user in a wireless access network is served through several access points within its range of influence. By tightly coordinating the transmission and reception of signals at multiple access points, network MIMO can transcend the limits on spectral efficiency imposed by cochannel interference. Taking prior information-theoretic analyses of networkMIMO to the next level, we quantify the spectral efficiency gains obtainable under realistic propagation and operational conditions in a typical indoor deployment. Our study relies on detailed simulations and, for specificity, is conducted largely within the physical-layer framework of the IEEE 802.16e Mobile WiMAX system. Furthermore,to facilitate the coordination between access points, we assume that a high-capacity local area network, such as Gigabit Ethernet,connects all the access points. Our results confirm that network MIMO stands to provide a multiple-fold increase in spectralefficiency under these conditions.

Comprehensive evaluation of the IEEE 802.15.4 MAC layer performance with retransmissions

Supported by IEEE 802.15.4 standardization activities, embedded networks have been gaining popularity in recent years. The focus of this paper is to quantify the behavior of key networking metrics of IEEE 802.15.4 beacon-enabled nodes under typical operating conditions, with the inclusion of packet retransmissions. We corrected and extended previous analyses by scrutinizing the assumptions on which the prevalent Markovian modeling is generally based. By means of a comparative study, we singled out which of the assumptions impact each of the performance metrics (throughput, delay, power consumption, collision probability, and packet-discard probability). In particular, we showed that - unlike what is usually assumed - the probability that a node senses the channel busy is not constant for all the stages of the backoff procedure and that these differences have a noticeable impact on backoff delay, packet-discard probability, and power consumption. Similarly, we showed that - again contrary to common assumption - the probability of obtaining transmission access to the channel depends on the number of nodes that is simultaneously sensing it. We evidenced that ignoring this dependence has a significant impact on the calculated values of throughput and collision probability. Circumventing these and other assumptions, we rigorously characterize, through a semianalytical approach, the key metrics in a beacon-enabled IEEE 802.15.4 system with retransmissions.

What can spike train distances tell us about the neural code?

Time scale parametric spike train distances like the Victor and the van Rossum distancesare often applied to study the neural code based on neural stimuli discrimination.Different neural coding hypotheses, such as rate or coincidence coding,can be assessed by combining a time scale parametric spike train distance with aclassifier in order to obtain the optimal discrimination performance. The time scalefor which the responses to different stimuli are distinguished best is assumed to bethe discriminative precision of the neural code. The relevance of temporal codingis evaluated by comparing the optimal discrimination performance with the oneachieved when assuming a rate code.We here characterize the measures quantifying the discrimination performance,the discriminative precision, and the relevance of temporal coding. Furthermore,we evaluate the information these quantities provide about the neural code. Weshow that the discriminative precision is too unspecific to be interpreted in termsof the time scales relevant for encoding. Accordingly, the time scale parametricnature of the distances is mainly an advantage because it allows maximizing thediscrimination performance across a whole set of measures with different sensitivitiesdetermined by the time scale parameter, but not due to the possibility toexamine the temporal properties of the neural code.

Neuronal adaptation effects in decision making

Recently, there has been an increased interest on the neural mechanisms underlying perceptual decision making. However, the effect of neuronal adaptation in this context has not yet been studied. We begin our study by investigating how adaptation can bias perceptual decisions. We considered behavioral data from an experiment on high-level adaptation-related aftereffects in a perceptual decision task with ambiguous stimuli on humans. To understand the driving force behind the perceptual decision process, a biologically inspired cortical network model was used. Two theoretical scenarios arose for explaining the perceptual switch from the category of the adaptor stimulus to the opposite, nonadapted one. One is noise-driven transition due to the probabilistic spike times of neurons and the other is adaptation-driven transition due to afterhyperpolarization currents. With increasing levels of neural adaptation, the system shifts from a noise-driven to an adaptation-driven modus. The behavioral results show that the underlying model is not just a bistable model, as usual in the decision-making modeling literature, but that neuronal adaptation is high and therefore the working point of the model is in the oscillatory regime. Using the same model parameters, we studied the effect of neural adaptation in a perceptual decision-making task where the same ambiguous stimulus was presented with and without a preceding adaptor stimulus. We find that for different levels of sensory evidence favoring one of the two interpretations of the ambiguous stimulus, higher levels of neural adaptation lead to quicker decisions contributing to a speed–accuracy trade off.

The neuronal basis of attention: rate versus synchronization modulation

Extensive theoretical and experimental work on the neuronal correlates of visual attention raises two hypotheses about the underlying mechanisms. The first hypothesis, named biased competition, originates from experimental single-cell recordings that have shown that attention upmodulates the firing rates of the neurons encoding the attended features and downregulates the firing rates of the neurons encoding the unattended features. Furthermore, attentional modulation of firing rates increases along the visual pathway. The other, newer hypothesis assigns synchronization a crucial role in the attentional process. It stems from experiments that have shown that attention modulates gamma-frequency synchronization. In this paper, we study the coexistence of the two phenomena using a theoretical framework. We find that the two effects can vary independently of each other and across layers. Therefore, the two phenomena are not concomitant. However, we show that there is an advantage in the processing of information if rate modulation is accompanied by gamma modulation, namely that reaction times are shorter, implying behavioral relevance for gamma synchronization.

Analysis of the folksonomy of freesound

User generated content shared in online communities is often described using collaborative tagging systems where users assign labels to content resources. As a result, a folksonomy emerges that relates a number of tags with the resources they label and the users that have used them. In this paper we analyze the folksonomy of Freesound, an online audio clip sharing site which contains more than two million users and 150,000 user-contributed sound samplescovering a wide variety of sounds. By following methodologies taken from similar studies, we compute some metrics that characterize the folksonomy both at the globallevel and at the tag level. In this manner, we are able to betterunderstand the behavior of the folksonomy as a whole, and also obtain some indicators that can be used as metadata for describing tags themselves. We expect that such a methodology for characterizing folksonomies can be useful to support processes such as tag recommendation or automatic annotation of online resources.

ClubADSL: When your neighbors are your friends

ADSL is becoming the standard form of residential and small-business broadband Internet access due to, primarily, its low deployment cost. These ADSL residential lines are often deployed with 802.11 Access Points (AP) that providewireless connectivity. Given the density of ADSL deployment, it is often possible for a residential wireless client to be in range of several other APs, belonging to neighbors, with ADSL connectivity. While the ADSL technology has showed evident limits in terms of capacity (with speeds ranging 1-10 Mbps), the short-range wireless communication can guarantee a muchhigher capacity (up to 20 Mbps). Furthermore, the ADSL links in the neighborhood are generally under-utilized, since ADSL subscribers do not connect 100% of the time. Therefore, it is possible for a wireless client to simultaneously connect to several APs in range and effectively aggregate their available ADSL bandwidth.In this paper, we introduce ClubADSL, a wireless client that can simultaneously connect to several APs in range on different frequencies and aggregate both their downlink and uplink capacity. ClubADSL is a software that runs locally on the client-side, and it requires neither modification to the existing Internet infrastructure, nor any hardware/protocol upgradesto the 802.11 local area network. We show the feasibility of ClubADSL in seamlessly transmitting TCP traffic, and validate its implementation both in controlled scenarios and with current applications over real ADSL lines. In particular we show that a ClubADSL client can greatly benefit from the aggregated download bandwidth in the case of server-client applications such as video streaming, but can also take advantage of the increased upload bandwidth greatly reducing download times with incentive-based P2P applications such as BitTorrent.

Identity formation in social networks websites: facebook and the interaction between young individuals in the cases of Slovenia and Catalonia

This paper lays down some theoretical framework for further research to be made on the subject of how identity of young Slovenian and Catalan users is forming within the social networking website Facebook. The author pursues his interest based on observation of how communicationand thus interaction between users is changing and how this is reflected in everyday practices. In so doing he tries to identify the connections between the individual, society and technology, asthese are more and more interwoven, and we cannot think one without the other in thecontemporary globalised world.

Implantació d'una xarxa de telecomunicacions a Catalunya

Aquest projecte està centrat a analitzar els diferents escenaris i tecnologies per a proveir Internet i serveis de connectivitat entre ciutats internacionals (Barcelona, Tarragona, Lleida, Girona i Milà). Així es defineixen tres tipus de xarxes dissenyades per a satisfer els requisits dels nostres clients. Aquests clients són usuaris residencials i petites empreses, hospitals icompanyies d'assegurances internacionals. Tots ells requereixen de diferentample de banda, seguretat i tecnologies, per a cadascun d'ells, s'ha desenvolupat un anàlisi extens que detalla la xarxa lògica i física.Finalment, hem realitzat una simulació per ordinador utilitzant OPNET amb elpropòsit d'avaluar la xarxa física dissenyada prèviament. Els resultats obtinguts van ser presentats i analitzats.

Propuesta de implantación de ITIL en GXI S.A.

Implantamos un sistema de gestion de redes y servicios de una empresa de seguros. Tras analizar la situacion de la empresa, nuestro departamento especifica un servicio de help desk, gestion de incidencias estructurada en 4 niveles con servicio 24/7, gestion de problemas y gestion de cambios; todo ello basado en ITIL.