Characterization of the neuronal microtubule regulator SCG10 in transfected cells and " in vivo "

SUMMARY The ability of neuronal processes to find their way along complex paths and to establish appropriate connections depends on continual rearrangements of the cytoskeletal components. The regulation of microtubules plays an important role for morphological changes underlying nevrite outgrowth, axonal elongation, and growth cone steering. SCG10 (superior cervical ganglion clone 10) is a neuronal growthassociated protein developmentally regulated and highly enriched in the neuronal growth cones. SCG10 presents a microtubule destabilizing activity that could participate to the regulation of microtubule dynamics and thus explain microtubule behaviors in the growth cone during axonal elongation and turning. It is here suggested that a tight control of the opposite effects on microtubules of SCG10 and the stabilizing microtubule-associated protein MAP1B allows a fine tuning of cytoskeletal rearrangement and may provide the required microtubule dynamic instability to promote axonal growth. Moreover, antibodyblockade of SCG10 function, that leads to growth cone pauses similar as those triggered by the guidance molecule EphB, and the modulation of SCG10 activity by the Rho GTPase Rnd1 suggest a potential role for SCG10 in the signal transduction pathways of extracellular guidance cues. The identification of the active zone protein Bassoon as a potential interaction partner for the SCG10-related protein NPC2, using atomic force microscopy as well as COS-7 and neuronal cell cultures, also gives new insights for a role of this protein family into the processes of synapse genesis or plasticity. Finally, SCG10 mutant mice generated by gene targeting and expressing a soluble form of the protein have been characterized during early postnatal development and in the adulthood. Due to the deletion of its membrane binding domain, SCG10 specific subcellular targeting to growth cones is compromised and results in impairments of motor and coordination development. Further histological analysis in the sciatic nerve reveal that these symptoms are associated with neurodegenerative signs. RESUME Une navigation correcte des prolongements cellulaires neuronaux leur permettant de former des connections appropriées repose sur de continuels réarrangements des constituants de leur cytosquelette. La régulation des microtubules joue notamment un rôle important dans les changements morphologiques qui accompagnent la croissance axonale et les réorientations du cône de croissance. SCG10 (superior cervical ganglion clone 10) est une protéine étroitement associée à la croissance neuronale, hautement régulée durant le développement et abondante au niveau du cône de croissance. SCG10 présente une activité déstabilisatrice sur les microtubules qui pourrait permettre une régulation des paramètres dynamiques propres aux microtubules et ainsi expliquer leur comportement durant la navigation du cône de croissance. Il est ici proposé qu'un contrôle précis des effets opposés de SCG10 et d'une autre protéine stabilisante associée aux microtubules (MAP1 B) permette un réglage fin des réarrangements du cytosquelette et puisse ainsi produire l'instabilité dynamique nécessaire à la croissance anale. Par ailleurs, le blocage de la fonction de SCG10 par un anticorps spécifique, conduisant à des pauses du cônes de croissance similaires à celles provoquées par la molécule de guidage EphB, ainsi que la modulation de l'activité de SCG10 par la Rho GTPase Rnd1 suggèrent une potentielle implication de SCG10 dans les voies de transduction des signaux provenant de molécules de guidage extracellulaires. L'identification d'une interaction de la protéine synaptique Bassoon avec la protéine NPC2 apparentée à SCG10, au moyen de la microscopie à force atomique et dans des cultures de cellules neuronales et COS-7, ouvre des perspectives concernant ces protéines dans la formation et la plasticité synaptiques. Finalement, des souris mutantes pour SCG10 produites par ciblage de gène et exprimant une forme soluble de la protéine ont été caractérisées durant la phase précoce du développement et à l'âge adulte. La délétion du domaine permettant l'ancrage de SCG10 aux membranes compromet sa sub-localisation au niveau du cône de croissance et résulte en l'apparition de troubles moteurs et de la coordination. Des analyses histologiques complémentaires au niveau du nerf sciatique montrent que ces symptômes sont associés avec des signes neurodégénératifs.

Visuospatial working memory deficits and visual pursuit impairments are not directly related in schizophrenia.

OBJECTIVE: Patients with schizophrenia show deficits in visuospatial working memory and visual pursuit processes. It is currently unclear, however, whether both impairments are related to a common neuropathological origin. The purpose of the present study was therefore to examine the possible relations between the encoding and the discrimination of dynamic visuospatial stimuli in schizophrenia. METHOD: Sixteen outpatients with schizophrenia and 16 control subjects were asked to encode complex disc displacements presented on a screen. After a delay, participants had to identify the previously presented disc trajectory from a choice of six static linear paths, among which were five incorrect paths. The precision of visual pursuit eye movements during the initial presentation of the dynamic stimulus was assessed. The fixations and scanning time in definite regions of the six paths presented during the discrimination phase were investigated. RESULTS: In comparison with controls, patients showed poorer task performance, reduced pursuit accuracy during incorrect trials and less time scanning the correct stimulus or the incorrect paths approximating its global structure. Patients also spent less time scanning the leftmost portion of the correct path even when making a correct choice. The accuracy of visual pursuit and head movements, however, was not correlated with task performance. CONCLUSIONS: The present study provides direct support for the hypothesis that active integration of visuospatial information within working memory is deficient in schizophrenia. In contrast, a general impairment of oculomotor mechanisms involved in smooth pursuit did not appear to be directly related to lower visuospatial working memory performance in schizophrenia.

The geometric structure of the brain fiber pathways.

The structure of the brain as a product of morphogenesis is difficult to reconcile with the observed complexity of cerebral connectivity. We therefore analyzed relationships of adjacency and crossing between cerebral fiber pathways in four nonhuman primate species and in humans by using diffusion magnetic resonance imaging. The cerebral fiber pathways formed a rectilinear three-dimensional grid continuous with the three principal axes of development. Cortico-cortical pathways formed parallel sheets of interwoven paths in the longitudinal and medio-lateral axes, in which major pathways were local condensations. Cross-species homology was strong and showed emergence of complex gyral connectivity by continuous elaboration of this grid structure. This architecture naturally supports functional spatio-temporal coherence, developmental path-finding, and incremental rewiring with correlated adaptation of structure and function in cerebral plasticity and evolution.

1010-005 Bloody Run Creek Watershed Final Report

The City of Marquette lies in the 65,000 acre Mississippi River watershed, and is surrounded by steep bluffs. Though scenic, controlling water runoff during storm events presents significant challenges. Flash-flooding from the local watershed has plagued the city for decades. The people of Marquette have committed to preserve the water quality of key natural resources in the area including the Bloody Run Creek and associated wetlands by undertaking projects to control the spread of debris and sediment caused by excess runoff during area storm events. Following a July 2007 storm (over 8” of rain in 24 hours) which caused unprecedented flood damage, the City retained an engineering firm to study the area and provide recommendations to eliminate or greatly reduce uncontrolled runoff into the Bloody Run Creek wetland, infrastructure damage and personal property loss. Marquette has received Iowa Great Places designation, and has demonstrated its commitment to wetland preservation with the construction of Phase I of this water quality project. The Bench Area Storm Water Management Plan prepared by the City in 2008 made a number of recommendations to mitigate flash flooding by improving storm water conveyance paths, detention, and infrastructure within the Bench area. Due to steep slopes and rocky geography, infiltration based systems, though desirable, would not be an option over surface based systems. Runoff from the 240 acre watershed comes primarily from large, steep drainage areas to the south and west, flowing to the Bench area down three hillside routes; designated as South East, South Central and South West. Completion of Phase I, which included an increased storage capacity of the upper pond, addressed the South East and South Central areas. The increased upper pond capacity will now allow Phase II to proceed. Phase II will address runoff from the South West drainage area; which engineers have estimated to produce as much water volume as the South Central and South East areas combined. Total costs for Phase I are $1.45 million, of which Marquette has invested $775,000, and IJOBS funding contributed $677,000. Phase II costs are estimated at $617,000. WIRB funding support of $200,000 would expedite project completion, lessen the long term debt impact to the community and aid in the preservation of the Bloody Run Creek and adjoining wetlands more quickly than Marquette could accomplish on its own.

The slow transformation of Swiss federal administrative elites

This article sets out to study the profile of Swiss administrative elites at federal level by showing how their profile has evolved in the light of what has come to be known as the wave of New Public Management (NPM), which has benefited from a very fertile ground in Switzerland. These elites correspond to a specific institutional order, in relation to specific organizational structures and workings, and have specific characteristics in terms of career paths and academic background. However, the administrative reforms that have been rolled out since the 1980s have transformed the institutional order within which executives of the federal administration evolve. This article analyses the extent to which these transformations have had an impact on the characteristics of these elites, through indicators such as academic capital, social capital, and career path within and outside the administration. The results show a slow but significant transformation in the profiles of these elites towards an increasing managerialization, reflecting that of the context in which they evolve.Points for practitioners The relationship between politics and the administration is naturally shaped by individuals but is closely dependent on the profiles of the players. They are currently undergoing a transformation in the wake of administrative reforms, and also of the changing profiles of both the political and administrative players. Gaining an insight into the slow transformation of the profiles of administrative elites therefore sheds light on the political-administrative nexus. The gradual managerialization of the administrative elite highlighted in this article also allows for a better understanding of which professional experiences, qualifications and skills are valued today within the senior civil service in Switzerland.

Seismic Wave Velocity as a Means of In-Place Density Measurement, Part 1, HR-114

Velocity-density tests conducted in the laboratory involved small 4-inch diameter by 4.58-inch-long compacted soil cylinders made up of 3 differing soil types and for varying degrees of density and moisture content, the latter being varied well beyond optimum moisture values. Seventeen specimens were tested, 9 with velocity determinations made along two elements of the cylinder, 180 degrees apart, and 8 along three elements, 120 degrees apart. Seismic energy was developed by blows of a small tack hammer on a 5/8-inch diameter steel ball placed at the center of the top of the cylinder, with the detector placed successively at four points spaced 1/2-inch apart on the side of the specimen involving wave travel paths varying from 3.36 inches to 4.66 inches in length. Time intervals were measured using a model 217 micro-seismic timer in both laboratory and field measurements. Forty blows of the hammer were required for each velocity determination, which amounted to 80 blows on 9 laboratory specimens and 120 blows on the remaining 8 cylinders. Thirty-five field tests were made over the three selected soil types, all fine-grained, using a 2-foot seismic line with hammer-impact points at 6-inch intervals. The small tack hammer and 5/8-inch steel ball was, again, used to develop seismic wave energy. Generally, the densities obtained from the velocity measurements were lower than those measured in the conventional field testing. Conclusions were reached that: (1) the method does not appear to be usable for measurement of density of essentially fine-grained soils when the moisture content greatly exceeds the optimum for compaction, and (2) due to a gradual reduction in velocity upon aging, apparently because of gradual absorption of pore water into the expandable interlayer region of the clay, the seismic test should be conducted immediately after soil compaction to obtain a meaningful velocity value.

Ibotenate Lesions of Hippocampus and/or Subiculum: Dissociating Components of Allocentric Spatial Learning

This study examined the effects of ibotenic acid-induced lesions of the hippocampus, subiculum and hippocampus +/- subiculum upon the capacity of rats to learn and perform a series of allocentric spatial learning tasks in an open-field water maze. The lesions were made by infusing small volumes of the neurotoxin at a total of 26 (hippocampus) or 20 (subiculum) sites intended to achieve complete target cell loss but minimal extratarget damage. The regional extent and axon-sparing nature of these lesions was evaluated using both cresyl violet and Fink - Heimer stained sections. The behavioural findings indicated that both the hippocampus and subiculum lesions caused impairment to the initial postoperative acquisition of place navigation but did not prevent eventual learning to levels of performance almost as effective as those of controls. However, overtraining of the hippocampus + subiculum lesioned rats did not result in significant place learning. Qualitative observations of the paths taken to find a hidden escape platform indicated that different strategies were deployed by hippocampal and subiculum lesioned groups. Subsequent training on a delayed matching to place task revealed a deficit in all lesioned groups across a range of sample choice intervals, but the subiculum lesioned group was less impaired than the group with the hippocampal lesion. Finally, unoperated control rats given both the initial training and overtraining were later given either a hippocampal lesion or sham surgery. The hippocampal lesioned rats were impaired during a subsequent retention/relearning phase. Together, these findings suggest that total hippocampal cell loss may cause a dual deficit: a slower rate of place learning and a separate navigational impairment. The prospect of unravelling dissociable components of allocentric spatial learning is discussed.

3D crosshole ERT for aquifer characterization and monitoring of infiltrating river water

The hydrogeological properties and responses of a productive aquifer in northeastern Switzerland are investigated. For this purpose, 3D crosshole electrical resistivity tomography (ERT) is used to define the main lithological structures within the aquifer (through static inversion) and to monitor the water infiltration from an adjacent river. During precipitation events and subsequent river flooding, the river water resistivity increases. As a consequence, the electrical characteristics of the infiltrating water can be used as a natural tracer to delineate preferential flow paths and flow velocities. The focus is primarily on the experiment installation, data collection strategy, and the structural characterization of the site and a brief overview of the ERT monitoring results. The monitoring system comprises 18 boreholes each equipped with 10 electrodes straddling the entire thickness of the gravel aquifer. A multi-channel resistivity system programmed to cycle through various four-point electrode configurations of the 180 electrodes in a rolling sequence allows for the measurement of approximately 15,500 apparent resistivity values every 7 h on a continuous basis. The 3D static ERT inversion of data acquired under stable hydrological conditions provides a base model for future time-lapse inversion studies and the means to investigate the resolving capability of our acquisition scheme. In particular, it enables definition of the main lithological structures within the aquifer. The final ERT static model delineates a relatively high-resistivity, low-porosity, intermediate-depth layer throughout the investigated aquifer volume that is consistent with results from well logging and seismic and radar tomography models. The next step will be to define and implement an appropriate time-lapse ERT inversion scheme using the river water as a natural tracer. The main challenge will be to separate the superposed time-varying effects of water table height, temperature, and salinity variations associated with the infiltrating water.

Extending Learning Objects by Means of Social Networking

Learning objects have been the promise of providing people with high quality learning resources. Initiatives such as MIT Open-CourseWare, MERLOT and others have shown the real possibilities of creating and sharing knowledge through Internet. Thousands of educational resources are available through learning object repositories. We indeed live in an age of content abundance, and content can be considered as infrastructure for building adaptive and personalized learning paths, promoting both formal and informal learning. Nevertheless, although most educational institutions are adopting a more open approach, publishing huge amounts of educational resources, the reality is that these resources are barely used in other educational contexts. This paradox can be partly explained by the dificulties in adapting such resources with respect to language, e-learning standards and specifications and, finally, granularity. Furthermore, if we want our learners to use and take advantage of learning object repositories, we need to provide them with additional services than just browsing and searching for resources. Social networks can be a first step towards creating an open social community of learning around a topic or a subject. In this paper we discuss and analyze the process of using a learning object repository and building a social network on the top of it, with respect to the information architecture needed to capture and store the interaction between learners and resources in form of learning object metadata.

Gestió dels recursos docents en el marc de l'EEES

L'Espai Europeu d'Educació Superior comporta un canvi de paradigma molt important, com ésl'adopció d'un procés d'aprenentatge basat en l'adquisició i desenvolupament de competències mitjançant activitats, relegant els continguts a un segon terme. El propi concepte d'activitat inclou i combina elements molt diversos que involucren recursos docents de tota mena, tot abastant un ventall més ampli del que s'entén estrictament per contingut en el sentit tradicional. És necessari, doncs, plantejar-se una gestió dels recursos docents orientada a facilitar la creació d'itineraris formatius que permetin als estudiants assolir les competències desitjades, així com complementar la seva formació. En lloc de proporcionar els continguts directament als estudiants, l'objectiu és aconseguir un procés d'aprenentatge centrat en l'usuari mitjançant la formació que els permeti ser autònoms en la localització, l'ús i fins i tot la generació de continguts necessaris en cada activitat.

Promoting the Creation, Share and Use of OERs through Open Repositories and Social Networks

In this paper we discuss and analyze the process of using a learning object repository and building a social network on the top of it, including aspects related to open source technologies, promoting the use of the repository by means of social networks and helping learners to develop their own learning paths.

Improved flooding of broadcast messages using extended multipoint relaying

A common operation in wireless ad hoc networks is the flooding of broadcast messages to establish network topologies and routing tables. The flooding of broadcast messages is, however, a resource consuming process. It might require the retransmission of messages by most network nodes. It is, therefore, very important to optimize this operation. In this paper, we first analyze the multipoint relaying (MPR) flooding mechanism used by the Optimized Link State Routing (OLSR) protocol to distribute topology control (TC) messages among all the system nodes. We then propose a new flooding method, based on the fusion of two key concepts: distance-enabled multipoint relaying and connected dominating set (CDS) flooding. We present experimental simulationsthat show that our approach improves the performance of previous existing proposals.

JXTAnonym: An anonymity layer for JXTA services messaging

With the evolution of the P2P research eld, new problems, such as those related with information security, have arisen. It is important to provide security mechanisms to P2P systems, since it has already become one of the key issues when evaluating them. However, even though many P2P systems have been adapted to provide a security baseline to their underlying applications, more advanced capabilities are becoming necessary. Speci cally, privacy preservation and anonymity are deemed essential to make the information society sustainable. Unfortunately, sometimes, it may be di cult to attain anonymity unless it is included into the system's initial design. The JXTA open protocols speci cation is a good example of this kind of scenario. This work studies how to provide anonymity to JXTA's architecture in a feasible manner and proposes an extension which allows deployed services to process two-way messaging without disclosing the endpoints'identities to third parties.

Técnicas de Anonimato para Securizar Redes Móviles Ad Hoc

Las redes móviles ad hoc son redes formadas por lainterconexión de terminales inalámbricos que de manera autónoma,sin ninguna administración central, establecen enlaces decomunicación entre ellos. La infraestructura de red la componenlos propios terminales de usuarios que actúan de gestores yencaminadores de paquetes. Así, un usuario cualquiera puedeconectarse con un terminal remoto a través de una conexiónmultisalto entre diferentes usuarios. En este tipo de redes tanabiertas, uno de los retos prioritarios es proteger el anonimatode los sujetos y sus localizaciones. En este artículo hacemos unrepaso de las técnicas existentes a través de los protocolos que sehan propuesto en la literatura, y exponemos los problemas queaun quedan abiertos.

Coste de los protocolos de seguridad en redes MANET

Los mecanismos de seguridad son uno de losrequisitos fundamentales para el buen funcionamiento de los protocolos de redes ad hoc móviles. En este artículo se analizan los problemas de seguridad de los protocolos de encaminamiento básicos, se describen las soluciones de seguridad existentes, y se hace un estudio del coste computacional y energético que supone para el sistema la inclusión de mecanismosde seguridad.