Astrocytic αVβ3 integrin inhibits neurite outgrowth and promotes retraction of neuronal processes by clustering Thy-1.

Thy-1 is a membrane glycoprotein suggested to stabilize or inhibit growth of neuronal processes. However, its precise function has remained obscure, because its endogenous ligand is unknown. We previously showed that Thy-1 binds directly to α(V)β(3) integrin in trans eliciting responses in astrocytes. Nonetheless, whether α(V)β(3) integrin might also serve as a Thy-1-ligand triggering a neuronal response has not been explored. Thus, utilizing primary neurons and a neuron-derived cell line CAD, Thy-1-mediated effects of α(V)β(3) integrin on growth and retraction of neuronal processes were tested. In astrocyte-neuron co-cultures, endogenous α(V)β(3) integrin restricted neurite outgrowth. Likewise, α(V)β(3)-Fc was sufficient to suppress neurite extension in Thy-1(+), but not in Thy-1(-) CAD cells. In differentiating primary neurons exposed to α(V)β(3)-Fc, fewer and shorter dendrites were detected. This effect was abolished by cleavage of Thy-1 from the neuronal surface using phosphoinositide-specific phospholipase C (PI-PLC). Moreover, α(V)β(3)-Fc also induced retraction of already extended Thy-1(+)-axon-like neurites in differentiated CAD cells as well as of axonal terminals in differentiated primary neurons. Axonal retraction occurred when redistribution and clustering of Thy-1 molecules in the plasma membrane was induced by α(V)β(3) integrin. Binding of α(V)β(3)-Fc was detected in Thy-1 clusters during axon retraction of primary neurons. Moreover, α(V)β(3)-Fc-induced Thy-1 clustering correlated in time and space with redistribution and inactivation of Src kinase. Thus, our data indicates that α(V)β(3) integrin is a ligand for Thy-1 that upon binding not only restricts the growth of neurites, but also induces retraction of already existing processes by inducing Thy-1 clustering. We propose that these events participate in bi-directional astrocyte-neuron communication relevant to axonal repair after neuronal damage.

Feasibility of Using Automated Distress Data in the County Need Study, TR-418, 1998

The purpose of this project was to determine the feasibility of using pavement condition data collected for the Iowa Pavement Management Program (IPMP) as input to the Iowa Quadrennial Need Study. The need study, conducted by the Iowa Department of Transportation (Iowa DOT) every four years, currently uses manually collected highway infrastructure condition data (roughness, rutting, cracking, etc.). Because of the Iowa DOT's 10-year data collection cycles, condition data for a given highway segment may be up to 10 years old. In some cases, the need study process has resulted in wide fluctuations in funding allocated to individual Iowa counties from one study to the next. This volatility in funding levels makes it difficult for county engineers to plan and program road maintenance and improvements. One possible remedy is to input more current and less subjective infrastructure condition data. The IPMP was initially developed to satisfy the Intermodal Surface Transportation Efficiency Act (ISTEA) requirement that federal-aid-eligible highways be managed through a pavement management system. Currently all metropolitan planning organizations (MPOs) in Iowa and 15 of Iowa's 18 RPAs participate in the IPMP. The core of this program is a statewide data base of pavement condition and construction history information. The pavement data are collected by machine in two-year cycles. Using pilot areas, researchers examined the implications of using the automated data collected for the IPMP as input to the need study computer program, HWYNEEDS. The results show that using the IPMP automated data in HWYNEEDS is feasible and beneficial, resulting in less volatility in the level of total need between successive quadrennial need studies. In other words, the more current the data, the smaller the shift in total need.

SDF 1-alpha (CXCL12) triggers glutamate exocytosis from astrocytes on a millisecond time scale: Imaging analysis at the single-vesicle level with TIRF microscopy

Chemokines are small chemotactic molecules widely expressed throughout the central nervous system. A number of papers, during the past few years, have suggested that they have physiological functions in addition to their roles in neuroinflammatory diseases. In this context, the best evidence concerns the CXC-chemokine stromal cell-derived factor (SDF-1alpha or CXCL12) and its receptor CXCR4, whose signalling cascade is also implicated in the glutamate release process from astrocytes. Recently, astrocytic synaptic like microvesicles (SLMVs) that express vesicular glutamate transporters (VGLUTs) and are able to release glutamate by Ca(2+)-dependent regulated exocytosis, have been described both in tissue and in cultured astrocytes. Here, in order to elucidate whether SDF-1alpha/CXCR4 system can participate to the brain fast communication systems, we investigated whether the activation of CXCR4 receptor triggers glutamate exocytosis in astrocytes. By using total internal reflection (TIRF) microscopy and the membrane-fluorescent styryl dye FM4-64, we adapted an imaging methodology recently developed to measure exocytosis and recycling in synaptic terminals, and monitored the CXCR4-mediated exocytosis of SLMVs in astrocytes. We analyzed the co-localization of VGLUT with the FM dye at single-vesicle level, and observed the kinetics of the FM dye release during single fusion events. We found that the activation of CXCR4 receptors triggered a burst of exocytosis on a millisecond time scale that involved the release of Ca(2+) from internal stores. These results support the idea that astrocytes can respond to external stimuli and communicate with the neighboring cells via fast release of glutamate.

Inhibitory effect of neuropeptide Y on stimulated renin secretion of awake rats.

1. (1-36)-NPY is a vasoconstrictor peptide widely distributed in sympathetic nerve terminals. This peptide exerts an inhibitory action on renin release induced by various stimuli. Post-synaptic neuropeptide Y (NPY) receptors show a high affinity for (1-36)-NPY as well as for the agonist (Pro34)-NPY, while presynaptic receptors bind preferentially (13-36)-NPY. 2. This study was undertaken to assess whether the NPY induced renin suppression in awake normotensive rats infused with the beta-adrenoceptor stimulant isoproterenol is mediated by activation of pre- or post-synaptic receptors. 3. Non-pressor doses of (1-36)-NPY and (Pro34)-NPY markedly attenuated the renin secretion triggered by isoproterenol whereas (13-36)-NPY had no effect. This suggests that the effect of NPY on renin release is due to the stimulation of post-synaptic receptors. However it remains unknown whether NPY acts directly on juxtaglomerular cells or indirectly by modifying intraglomerular haemodynamics.

Production of Asphalt Rubber Concrete by the Dry Process, HR-1062, 1994

Disposal of used tires has been a problem throughout the United States. The 1991 Intermodal Surface Transportation Efficiency Act (ISTEA) requires the use of recycled rubber in asphalt concrete starting in FY94. A moratorium has delayed this requirement until FY95. The Iowa DOT has researched six projects using crumb rubber modifier in asphalt concrete using the wet process. This process involves using a blender-reactor to blend the asphalt cement and crumb rubber. Using the wet process the asphalt cement has to reach a hotter temperature, than is normally required, for reaction to occur. The wet process is also much more expensive than conventional asphalt. This research deals with using a dry process to incorporate crumb rubber into the asphalt concrete mix. The project was constructed by Western Engineering of Harlan, Iowa, on IA 37 between Earling, Iowa and US 59. It was completed in September 1993. Western Engineering used a double drum mixer to produce the crumb rubber modified asphalt concrete by the dry process. The production and construction went well with minor difficulty and the dry process is a less expensive procedure for producing crumb rubber modified asphalt concrete.

PSD-95 promotes synaptogenesis and multiinnervated spine formation through nitric oxide signaling

Postsynaptic density 95 (PSD-95) is an important regulator of synaptic structure and plasticity. However, its contribution to synapse formation and organization remains unclear. Using a combined electron microscopic, genetic, and pharmacological approach, we uncover a new mechanism through which PSD-95 regulates synaptogenesis. We find that PSD-95 overexpression affected spine morphology but also promoted the formation of multiinnervated spines (MISs) contacted by up to seven presynaptic terminals. The formation of multiple contacts was specifically prevented by deletion of the PDZ(2) domain of PSD-95, which interacts with nitric oxide (NO) synthase (NOS). Similarly, PSD-95 overexpression combined with small interfering RNA-mediated down-regulation or the pharmacological blockade of NOS prevented axon differentiation into varicosities and multisynapse formation. Conversely, treatment of hippocampal slices with an NO donor or cyclic guanosine monophosphate analogue induced MISs. NOS blockade also reduced spine and synapse density in developing hippocampal cultures. These results indicate that the postsynaptic site, through an NOS-PSD-95 interaction and NO signaling, promotes synapse formation with nearby axons.

DRIS norms for 'Valencia' sweet orange on three rootstocks

Diagnosis and Recommendation Integrated System (DRIS) applies nutrient ratios instead of the isolated concentration values of each nutrient in interpretation of tissue analysis. The objectives of this research were to establish adequate DRIS norms for 'Valencia' sweet orange irrigated commercial groves budded on three rootstocks and correlate indexes of nutrition balance with yield. Experiments were conducted in São Paulo State, Brazil. Rootstocks Rangpur lime, Caipira sweet orange, and Poncirus trifoliata, with more than six years old and yield above 40 ton ha-1 were utilized. Data referred to yield, tree spacing, rootstock and foliar concentrations of N, P, K, Ca, Mg, S, Fe, Mn, Cu, Zn, and B in non fruiting terminals for each grove were processed for the years 1994 through 1998. DRIS indexes were calculated by Nick criterion for choosing the ratio order of the nutrients and Jones calculation method of the ratio functions. Indexes of nutritional balance calculated from DRIS norms presented high correlation with yield for the three scion/rootstock combinations. DRIS norms defined in this research are valid, since leaf sampling is done on non fruiting terminals and the grove is irrigated.

Extrasynaptic neurotransmission in the modulation of brain function. Focus on the striatal neuronal glial networks

Extrasynaptic neurotransmission is an important short distance form of volume transmission (VT) and describes the extracellular diffusion of transmitters and modulators after synaptic spillover or extrasynaptic release in the local circuit regions binding to and activating mainly extrasynaptic neuronal and glial receptors in the neuroglial networks of the brain. Receptor-receptor interactions in G protein-coupled receptor (GPCR) heteromers play a major role, on dendritic spines and nerve terminals including glutamate synapses, in the integrative processes of the extrasynaptic signaling. Heteromeric complexes between GPCR and ion-channel receptors play a special role in the integration of the synaptic and extrasynaptic signals. Changes in extracellular concentrations of the classical synaptic neurotransmitters glutamate and GABA found with microdialysis is likely an expression of the activity of the neuron-astrocyte unit of the brain and can be used as an index of VT-mediated actions of these two neurotransmitters in the brain. Thus, the activity of neurons may be functionally linked to the activity of astrocytes, which may release glutamate and GABA to the extracellular space where extrasynaptic glutamate and GABA receptors do exist. Wiring transmission (WT) and VT are fundamental properties of all neurons of the CNS but the balance between WT and VT varies from one nerve cell population to the other. The focus is on the striatal cellular networks, and the WT and VT and their integration via receptor heteromers are described in the GABA projection neurons, the glutamate, dopamine, 5-hydroxytryptamine (5-HT) and histamine striatal afferents, the cholinergic interneurons, and different types of GABA interneurons. In addition, the role in these networks of VT signaling of the energy-dependent modulator adenosine and of endocannabinoids mainly formed in the striatal projection neurons will be underlined to understand the communication in the striatal cellular networks

Quines són les necessitats espirituals en els adolescents afectats de càncer en situació de malaltia avançada-terminal, en una unitat de cures pal·liatives?

En les cures pal·liatives pediàtriques es contemplen les dimensions essencials de la persona: la física, la psicològica, la social i l’espiritual. Tot i que s’han fet estudis sobre la dimensió espiritual, en la revisió bibliogràfica es mostra que és un àmbit poc desenvolupat. És important conèixer l’aspecte de creences i valors per tal que la infermera oncològica, juntament amb altres professionals, puguin proporcionar una atenció holística. L’objectiu d’aquest estudi és identificar les necessitats espirituals en adolescents (13 a 18 anys) malalts de càncer en situació avançada-terminal. S’utilitza la metodologia qualitativa. La mostra és de vuit adolescents, que són seleccionats d’acord amb els criteris d’inclusió. Aquests seran entrevistats per la infermera, la investigadora, la qual realitzarà entrevistes semiestructurades i un fotomuntatge depenent de la predisposició de l’adolescent. L’àmbit de realització d’aquest estudi és en un hospital de tercer nivell on es proporcioni atenció especialitzada amb pediatria oncològica i, concretament, en una unitat de cures pal·liatives pediàtriques. Per finalitzar, és important tenir en compte que les entrevistes i el fotomuntatge poden tenir les seves limitacions i que no sempre s’obtingui el resultat esperat.

Implantació d'una plataforma informàtica en una entitat financera fusionada

Els darrers anys han estat molt convulsos en el món financer. De tots és coneguda la crisi, immobiliària en un primer moment, i financera més tard. Reestructuracions, fusions, absorcions, intervencions i nacionalitzacions han estat a l’ordre del dia en el món de les entitats financeres els últims 3 anys. El mapa financer ha passat de més de 50 entitats a poc menys de 10 en tan sols 3 anys. Els departaments de tecnologia de bancs i caixes no han estat aliens a aquests moviments. Tot i estar relativament al marge del negoci financer de l’entitat, cada fusió ha atorgat un paper protagonista a tota la plantilla informàtica. Ja que cada reestructuració ha suposat un gran esforç per integrar entitats molt diferents entre si en una de sola. Intentant que l’impacte a clients i a usuaris fos el menor possible. Caixa Manlleu és un exemple proper de la reestructuració del món financer, i ha protagonitzat, juntament amb Caixa Sabadell i Caixa Terrassa, la creació d’Unnim. Aquest cas real serà la base del treball. El projecte consisteix en la creació d’una plataforma informàtica per a la nova entitat resultant de la fusió. Una plataforma amb un doble objectiu: d’una banda, que reculli el millor de les tres plataformes d’origen i que compleixi tots els requestis que la nova entitat exigeix per tal que els usuaris puguin continuar fent les tasques diàries. I de l’altra, una plataforma que posi al dia i actualitzi tecnològicament l’entitat amb el mínim cost possible. Així doncs, cal analitzar per separat cadascuna de les 3 plataformes existents, inventariar les aplicacions comunes i les departamentals, així com les llicències de software vigents existents i no caducades. Decidir quines aplicacions es faran servir, si se’n poden aprofitar o si per contra en calen de noves. També cal analitzar quins equips informàtics (terminals) es necessitaran per tal de treure el màxim rendiment de la plataforma. Entre les conclusions obtingudes en el projecte, cal destacar els grans avantatges d’utilitzar aplicacions virtualitzades en lloc de les tradicionals aplicacions instal·lades físicament a cada terminal. Faciliten la feina i el manteniment, estalvien recursos i fan guanyar temps. A més a més s’aconsegueix una plataforma àgil, lleugera i ràpida.

Role of glutathione deficit in the disconnectivity syndrome in schizophrenia: from pathogenetic mechanisms to therapeutic interventions

In the cerebrospinal fluid of 26 drug-naive schizophrenics (DSM-III- R), we observed that the level of glutathione ([GSH]) and of its metabolite γ-Glu-Gln was decreased by 27% and 16% respectively. Using a new in-vivo method based on magnetic resonance spec- troscopy, [GSH] was measured in the medial prefrontal cortex of 18 schizophrenics and found to be 52 % lower than in controls (n = 20). This is consistent with the recently observed decreased mRNA levels in fibroblasts of patients (n=32) of the two GSH synthesizing en- zymes (glutathione synthetase (GSS), and glutamate-cysteine ligase M (GCLM) the modulatory subunit of glutamate-cysteine ligase). Moreover, the level of GCLM expression in fibroblasts correlates neg- atively with the psychopathology (positive, general and some nega- tive symptoms). Thus, the observed difference in gene expression is not only the cause of low brain [GSH], but is also related to the sever- ity of symptoms, suggesting that fibroblasts are adequate surrogate for brain tissue. A hypothesis was proposed, based on a central role of GSH in the pathophysiology of schizophrenia. GSH is an important endogenous redox regulator and neuroactive substance. GSH is pro- tecting cells from damage by reactive oxygen species generated, among others, by the metabolism of dopamine. A GSH deficit-in- duced oxidative stress would lead to lipid peroxidation and micro-le- sions in the surrounding of catecholamine terminals, affecting the synaptic contacts on dendritic spines of cortical neurones, where ex- citatory glutamatergic terminals converge with dopaminergic ones. This would lead to spines degeneration and abnormal nervous con- nections or structural disconnectivity, possibly responsible for posi- tive, perceptive and cognitive symptoms of schizophrenia. In addi- tion, a GSH deficit could also lead to a functional disconnectivity by depressing NMDA neurotransmission, in analogy to phencyclidine effects. Present experimental biochemical, cell biological and behav- ioral data are consistent with the proposed mechanism: decreasing pharmacologically [GSH] in experimental models, with or without blocking DA uptake (GBR12909), induces morphological and behav- ioral changes similar to those observed in patients. Dendritic spines: (a) In neuronal cultures, low [GSH] and DA induce decreased density of neural processes; (b) In developing rats (p5-p16), [GSH] deficit and GBR induce a decrease in normal spines in prefrontal pyramids and in GABA-parvalbumine but not of -calretinine immunoreactivity in anterior cingulate. NMDA-dependant synaptic plasticity: GSH deple- I/13 tion in hippocampal slices impairs long-term potentiation. Develop- ing rats with low [GSH] and GBR have deficit in olfactory integration and in object recognition which appears earlier in males than fe- males, in analogy to the delay of the psychosis onset between man and woman. In summary, a deficit of GSH and/or GSH-related enzymes during early development could constitute a major vulnerability fac- tor in schizophrenia.

Estressors i ansietat en els cuidatges pal·liatius: Una proposta de canvi en el pla d'estudis d'Infermeria

Néixer, créixer, madurar, envellir i morir, són les etapes que travessa l’ésser humà al llarg de la seva vida, però no necessàriament s’ha d’envellir per arribar a la mort. Hi ha persones que la vida biològica s’acaba abans de la mort. Són els pacients terminals. Per tenir cura dels malalts al final de la seva vida, s’implanten els cuidatges pal·liatius. A partir d’aquests cuidatges, es proporciona una atenció global, activa i continuada als pacients i als seus familiars, amb l’objectiu de millorar la qualitat de vida i cobrir totes les necessitats d’aquests pacients.

Iowa In Motion: State Transportation Plan, 1997

What is Iowa in Motion? The Iowa Department of Transportation is continuing the journey to develop Iowa’s future transportation system. This ongoing planning process, known as Iowa in Motion, was developed in response to the Intermodal Surface Transportation Efficiency Act (ISTEA) and Iowa’s changing transportation needs. The completion of Parts I, II and III of Iowa in Motion has led to development of this State Transportation Plan. Part IV includes activities, both current and future, to support the plan. This State Transportation Plan represents the thoughts and concerns of thousands of Iowans. Individuals, metropolitan planning organizations (MPOs), regional planning affiliations (RPAs), associations and organizations have become involved and have made recommendations concerning which direction should be followed regarding transportation investments. This plan represents their extensive input into the Iowa in Motion process and consensus building as we moved towards adoption of this State Transportation Plan. The adopted plan serves as a guide for development of transportation policies, goals, objectives, initiatives and investment decisions through the year 2020.

Transportation and Iowa's Economic Future, 1993

This is a study of how transportation policy can be fashioned to improve Iowa's long-term economic prospects. The research focuses on the state level and covers pricing, resource allocation, investment, and other issues that directly affect the performance of public facilities that support transportation of goods and people to and from points in Iowa. Chapter 1 is an introduction. Chapter 2 begins with an assessment of how Iowa's economy is changing, both functionally and spatially. Commuting patterns and methods of goods movement are then discussed. The purpose of this analysis is to provide a context for the exploration of transportation policy issues in subsequent chapters. In Chapter 3 a framework is established for evaluating changes in transportation policies. A working definition of economic development is given and the role of government policies in making an area more attractive to economic activity is considered. Chapter 4 analyzes public policy options for Iowa's roads and highways. These policy options are intended to help the state compete for economic activity. Chapter 5 assesses alternative investment strategies for major navigational facilities on the upper Mississippi River. Chapter 6 examines major transportation policy issues in Iowa's agricultural sector. The current magnitude of agricultural shipments and the roles of several modes are presented. After focusing on issues related to railroad competitiveness, the analysis turns to how Iowa's rural roads should be financed. The need for joint investment and pricing decisions affecting waterways, railroads, and rural roads is stressed. Chapter 7 examines the current status of freight transportation in Iowa. An assessment is made of issues related to trucking and of intermodal transportation and its potential for cost-effective shipping to and from businesses in Iowa. Chapter 8 summarizes the key findings of this study, offering ten recommendations. These recommendations relate to transportation as a means of facilitating economic development.

Increased anandamide induced relaxation in mesenteric arteries of cirrhotic rats. Role of cannabinoid and vanilloid receptors

Background and aims: Anandamide is an endocannabinoid that evokes hypotension by interaction with peripheral cannabinoid CB1 receptors and with the perivascular transient receptor potential vanilloid type 1 protein (TRPV1). As anandamide has been implicated in the vasodilated state in advanced cirrhosis, the study investigated whether the mesenteric bed from cirrhotic rats has an altered and selective vasodilator response to anandamide. Methods: We assessed vascular sensitivity to anandamide, mRNA and protein expression of cannabinoid CB1 receptor and TRPV1 receptor, and the topographical distribution of cannabinoid CB1 receptors in resistance mesenteric arteries of cirrhotic and control rats. Results: Mesenteric vessels of cirrhotic animals displayed greater sensitivity to anandamide than control vessels. This vasodilator response was reverted by CB1 or TRPV1 receptor blockade, but not after endothelium denudation or nitric oxide inhibition. Anandamide had no effect on distal femoral arteries. CB1 and TRPV1 receptor protein was higher in cirrhotic than in control vessels. Neither CB1 mRNA nor protein was detected in femoral arteries. Immunochemistry showed that CB1 receptors were mainly in the adventitia and in the endothelial monolayer, with higher expression observed in vessels of cirrhotic rats than in controls. Conclusions: These results indicate that anandamide is a selective splanchnic vasodilator in cirrhosis which predominantly acts via interaction with two different types of receptors, CB1 and TRPV1 receptors, which are mainly located in perivascular sensory nerve terminals of the mesenteric resistance arteries of these animals.