JNK regulates dendrite and spine architecture in the central nervous system influencing spatial learning and motor tasks

JNK1 is a MAP-kinase that has proven a significant player in the central nervous system. It regulates brain development and the maintenance of dendrites and axons. Several novel phosphorylation targets of JNK1 were identified in a screen performed in the Coffey lab. These proteins were mainly involved in the regulation of neuronal cytoskeleton, influencing the dynamics and stability of microtubules and actin. These structural proteins form the dynamic backbone for the elaborate architecture of the dendritic tree of a neuron. The initiation and branching of the dendrites requires a dynamic interplay between the cytoskeletal building blocks. Both microtubules and actin are decorated by associated proteins which regulate their dynamics. The dendrite-specific, high molecular weight microtubule associated protein 2 (MAP2) is an abundant protein in the brain, the binding of which stabilizes microtubules and influences their bundling. Its expression in non-neuronal cells induces the formation of neurite-like processes from the cell body, and its function is highly regulated by phosphorylation. JNK1 was shown to phosphorylate the proline-rich domain of MAP2 in vivo in a previous study performed in the group. Here we verify three threonine residues (T1619, T1622 and T1625) as JNK1 targets, the phosphorylation of which increases the binding of MAP2 to microtubules. This binding stabilizes the microtubules and increases process formation in non-neuronal cells. Phosphorylation-site mutants were engineered in the lab. The non-phosphorylatable mutant of MAP2 (MAP2- T1619A, T1622A, T1625A) in these residues fails to bind microtubules, while the pseudo-phosphorylated form, MAP2- T1619D, T1622D, Thr1625D, efficiently binds and induces process formation even without the presence of active JNK1. Ectopic expression of the MAP2- T1619D, T1622D, Thr1625D in vivo in mouse brain led to a striking increase in the branching of cortical layer 2/3 (L2/3) pyramidal neurons, compared to MAP2-WT. The dendritic complexity defines the receptive field of a neuron and dictates the output to the postsynaptic cells. Previous studies in the group indicated altered dendrite architecture of the pyramidal neurons in the Jnk1-/- mouse motor cortex. Here, we used Lucifer Yellow loading and Sholl analysis of neurons in order to study the dendritic branching in more detail. We report a striking, opposing effect in the absence of Jnk1 in the cortical layers 2/3 and 5 of the primary motor cortex. The basal dendrites of pyramidal neurons close to the pial surface at L2/3 show a reduced complexity. In contrast, the L5 neurons, which receive massive input from the L2/3 neurons, show greatly increased branching. Another novel substrate identified for JNK1 was MARCKSL1, a protein that regulates actin dynamics. It is highly expressed in neurons, but also in various cancer tissues. Three phosphorylation target residues for JNK1 were identified, and it was demonstrated that their phosphorylation reduces actin turnover and retards migration of these cells. Actin is the main cytoskeletal component in dendritic spines, the site of most excitatory synapses in pyramidal neurons. The density and gross morphology of the Lucifer Yellow filled dendrites were characterized and we show reduced density and altered morphology of spines in the motor cortex and in the hippocampal area CA3. The dynamic dendritic spines are widely considered to function as the cellular correlate during learning. We used a Morris water maze to test spatial memory. Here, the wild-type mice outperformed the knock-out mice during the acquisition phase of the experiment indicating impaired special memory. The L5 pyramidal neurons of the motor cortex project to the spinal cord and regulate the movement of distinct muscle groups. Thus the altered dendrite morphology in the motor cortex was expected to have an effect on the input-output balance in the signaling from the cortex to the lower motor circuits. A battery of behavioral tests were conducted for the wild-type and Jnk1-/- mice, and the knock-outs performed poorly compared to wild-type mice in tests assessing balance and fine motor movements. This study expands our knowledge of JNK1 as an important regulator of the dendritic fields of neurons and their manifestations in behavior.

Antinociceptive properties in mice of a lectin isolated from the marine alga Amansia multifida Lamouroux

The antinociceptive effects of a lectin (LEC) isolated from the marine alga Amansia multifida were determined in Swiss mice. The LEC (1, 5, and 10 mg/kg) inhibited acetic acid-induced abdominal writhings in a dose-dependent manner after intraperitoneal or oral administration. A partial but significant inhibition of writhings was observed after the combination of LEC (10 mg/kg) with avidin (1 mg/kg), a potent inhibitor of the hemmaglutinant activity of the lectin. However, total writhing inhibition was demonstrable in the group of mice treated with LEC plus mannose (1 mg/kg), as compared to LEC alone or to control groups. Furthermore, avidin and mainly mannose also play a role in antinociception, somehow facilitating the interaction of LEC with its active cell sites. In the formalin test, although both phases of the response were significantly inhibited, the effect of LEC was predominant during phase 2, causing inhibition of licking time that ranged from 48 to 88% after oral (5 and 10 mg/kg) and intraperitoneal (1 to 5 mg/kg) administration. As is the case with morphine, the effect of LEC (2 mg/kg) was reversed by naloxone (2 mg/kg), indicating the involvement of the opioid system. LEC was also effective in the hot-plate test, producing inhibitory responses to the thermal stimulus, and its effects were blocked by naloxone. In the pentobarbital-induced sleeping time, although LEC did not alter the onset of sleep significantly, it increased the time of sleep within the same dose range compared to control. These results show that LEC presents antinociceptive effects of both central and peripheral origin, possibly involving the participation of the opioid system.

Dynamics of gas levels inside packages containing minimally processed Pera orange

The purpose of this study was to evaluate the changes in concentrations of O2 and CO2 inside packages of minimally processed Pera orange. Previously selected oranges that were washed, sanitized, and chilled were peeled using hydrothermal treatment (immersion of fruits in water at 50 °C for 8 minutes). The peeled oranges were then packed in five different plastic packages under passive and active modified atmosphere (5% O2 + 10% CO2 + 85% N2). The fruits were stored at 6 °C and 12 °C. The package headspace gas composition was evaluated for twelve days at 6 °C and nine days at 12 °C. The polypropylene film (32 µm) promoted modified atmosphere similar to that initially injected (5% O2 + 10% CO2 + 85% N2) at 6 °C and 12 °C. With regard to the atmosphere modification system, the injection of a gas mixture anticipated achieving an equilibrium atmosphere inside the packages at 12 °C. At 6 °C, the gas composition inside the packages was kept close to that of the injection, but the equilibrium was not verified.

Studies of rotor dynamics using a multibody simulation approach

The non-idealities in a rotor-bearing system may cause undesirable subcritical superharmonic resonances that occur when the rotating speed of the rotor is a fraction of the natural frequency of the system. These resonances arise partly from the non-idealities of the bearings. This study introduces a novel simulation approach that can be used to study the superharmonic vibrations of rotor-bearing systems. The superharmonic vibrations of complex rotor-bearing systems can be studied in an accurate manner by combining a detailed rotor and bearing model in a multibody simulation approach. The research looks at the theoretical background of multibody formulations that can be used in the dynamic analysis of flexible rotors. The multibody formulations currently in use are suitable for linear deformation analysis only. However, nonlinear formulation may arise in high-speed rotor dynamics applications due to the cenrrifugal stiffening effect. For this reason, finite element formulations that can describe nonlinear deformation are also introduced in this work. The description of the elastic forces in the absolute nodal coordinate formulation is studied and improved. A ball bearing model that includes localized and distributed defects is developed in this study. This bearing model could be used in rotor dynamics or multibody code as an interface elements between the rotor and the supporting structure. The model includes descriptions of the nonlinear Hertzian contact deformation and the elastohydrodynamic fluid film. The simulation approaches and models developed here are applied in the analysis of two example rotor-bearing systems. The first example is an electric motor supported by two ball bearings and the second is a roller test rig that consists of the tube roll of a paper machine supported by a hard-bearing-type balanceing machine. The simulation results are compared to the results available in literature as well as to those obtained by measuring the existing structure. In both practical examples, the comparison shows that the simulation model is capable of predicting the realistic responses of a rotor system. The simulation approaches developed in this work can be used in the analysis of the superharmonic vibrations of general rotor-bearing systems.

Model of Big Data Failure: Review of Information System Failure

In the new age of information technology, big data has grown to be the prominent phenomena. As information technology evolves, organizations have begun to adopt big data and apply it as a tool throughout their decision-making processes. Research on big data has grown in the past years however mainly from a technical stance and there is a void in business related cases. This thesis fills the gap in the research by addressing big data challenges and failure cases. The Technology-Organization-Environment framework was applied to carry out a literature review on trends in Business Intelligence and Knowledge management information system failures. A review of extant literature was carried out using a collection of leading information system journals. Academic papers and articles on big data, Business Intelligence, Decision Support Systems, and Knowledge Management systems were studied from both failure and success aspects in order to build a model for big data failure. I continue and delineate the contribution of the Information System failure literature as it is the principal dynamics behind technology-organization-environment framework. The gathered literature was then categorised and a failure model was developed from the identified critical failure points. The failure constructs were further categorized, defined, and tabulated into a contextual diagram. The developed model and table were designed to act as comprehensive starting point and as general guidance for academics, CIOs or other system stakeholders to facilitate decision-making in big data adoption process by measuring the effect of technological, organizational, and environmental variables with perceived benefits, dissatisfaction and discontinued use.

Model of Big Data Failure: Review of Information System Failure

In the new age of information technology, big data has grown to be the prominent phenomena. As information technology evolves, organizations have begun to adopt big data and apply it as a tool throughout their decision-making processes. Research on big data has grown in the past years however mainly from a technical stance and there is a void in business related cases. This thesis fills the gap in the research by addressing big data challenges and failure cases. The Technology-Organization-Environment framework was applied to carry out a literature review on trends in Business Intelligence and Knowledge management information system failures. A review of extant literature was carried out using a collection of leading information system journals. Academic papers and articles on big data, Business Intelligence, Decision Support Systems, and Knowledge Management systems were studied from both failure and success aspects in order to build a model for big data failure. I continue and delineate the contribution of the Information System failure literature as it is the principal dynamics behind technology-organization-environment framework. The gathered literature was then categorised and a failure model was developed from the identified critical failure points. The failure constructs were further categorized, defined, and tabulated into a contextual diagram. The developed model and table were designed to act as comprehensive starting point and as general guidance for academics, CIOs or other system stakeholders to facilitate decision-making in big data adoption process by measuring the effect of technological, organizational, and environmental variables with perceived benefits, dissatisfaction and discontinued use.

Parameter estimation for Chaotic or Stochastic Dynamics

Since its discovery, chaos has been a very interesting and challenging topic of research. Many great minds spent their entire lives trying to give some rules to it. Nowadays, thanks to the research of last century and the advent of computers, it is possible to predict chaotic phenomena of nature for a certain limited amount of time. The aim of this study is to present a recently discovered method for the parameter estimation of the chaotic dynamical system models via the correlation integral likelihood, and give some hints for a more optimized use of it, together with a possible application to the industry. The main part of our study concerned two chaotic attractors whose general behaviour is diff erent, in order to capture eventual di fferences in the results. In the various simulations that we performed, the initial conditions have been changed in a quite exhaustive way. The results obtained show that, under certain conditions, this method works very well in all the case. In particular, it came out that the most important aspect is to be very careful while creating the training set and the empirical likelihood, since a lack of information in this part of the procedure leads to low quality results.

Stochastic particle models: mean reversion and burgers dynamics. An application to commodity markets

The aim of this study is to propose a stochastic model for commodity markets linked with the Burgers equation from fluid dynamics. We construct a stochastic particles method for commodity markets, in which particles represent market participants. A discontinuity in the model is included through an interacting kernel equal to the Heaviside function and its link with the Burgers equation is given. The Burgers equation and the connection of this model with stochastic differential equations are also studied. Further, based on the law of large numbers, we prove the convergence, for large N, of a system of stochastic differential equations describing the evolution of the prices of N traders to a deterministic partial differential equation of Burgers type. Numerical experiments highlight the success of the new proposal in modeling some commodity markets, and this is confirmed by the ability of the model to reproduce price spikes when their effects occur in a sufficiently long period of time.

Dynamics AX -toiminnanohjausjärjestelmän jatkuvuudenhallinta ja toipumissuunnitelma - Simulaatiotestausmalli: case CGI Suomi Oy

Nyky-yhteiskunta nojautuu vahvasti tietojärjestelmiin luoden laajemman arkkitehtuurisen kokonaisuuden, kybertoimintaympäristön. Liiketoimintaa tukevat tietojärjestelmät tukevat myös organisaatioiden prosesseja kokonaisvaltaisesti. Jotta näitä tärkeitä kyberympäristön tietojärjestelmä- sekä liiketoimintaympäristöresursseja pystytään käyttämään, tulee järjestelmien olla luotettavia ja sovellusten saatavilla vuorokauden ympäri tai aina tarvittaessa. Tilanteet, joissa järjestelmän käytettävyys vaarantuu, voivat eskaloitua yllättäen suuremmiksi, jos poikkeustilanteisiin ei ole varauduttu. Poikkeustilanteisiin varautumiseen tarvitaan jatkuvuudenhallintaa, joka on kiinteästi osa kattavampaa IT-strategiaa ja koko yhteiskunta-/yrityskulttuuria. Työ on toteutettu yhdistäen empiriaa ja teoriaa eli tavoitteena on teoreettisen tietämyksen ja käytännön kokemuksellisen oppimisen ja tietämyksen kautta luoda konstruktiivisella otteella toipumissuunnitelman testauksessa käytettävä simulaatiotestausmalli. Dynamics AX -toiminnanohjausjärjestelmän toipumissuunnitelman simulaatiotestausmallista rakentui selkeä ja kevyt työkalu asiakasyritysten toipumissuunnitelman simulaatiotestauksiin. Diplomityössä kuvatuilla keinotekoisilla järjestelmän häiriötilanteilla pystytään simuloimaan Dynamics AX:n toipumissuunnitelman testauksissa oikeita häiriötilanteita suhteellisen kattavalla tasolla.

Elementary steps in aqueous proton transfer reactions : a first principles molecular dynamics study

La nature des acides dans un environnement aqueux est primordiale dans de nombreux aspects de la chimie et de la biologie. La caractéristique principale d'un acide est sa capacité à transférer un proton vers une molécule d'eau ou vers n'importe quelle base, mais ce procédé n'est pas aussi simple qu'il y paraît. Il peut au contraire être extrêmement complexe et dépendre de manière cruciale de la solvatation des différents intermédiaires de réaction impliqués. Cette thèse décrit les études computationnelles basées sur des simulations de dynamique moléculaire ab initio qui ont pour but d'obtenir une description à l'échelle moléculaire des divers procédés de transferts de proton entre acide et bases dans un milieu aqueux. Pour cela, nous avons étudié une serie de système, dont l'acide hydrofluorique aqueux, l'acide trifluoroacétique aqueux, et un système modèle constitué d'un phénol et d'une entité carboxylate reliés entre eux par une molécule d'eau en solution aqueuse. Deux états intermédiaires ont été identifiés pour le transfert d'un proton depuis un acide. Ces intermédiaires apparaissent stabilisés par un motif local de solvatation via des ponts H. Leurs signatures spectroscopiques ont été caractérisées au moyen de la spectroscopie infrarouge, en utilisant le formalisme de la dynamique moléculaire ab initio, qui inclut l'effet quantique nucléaire de manière explicite. Cette étude a aussi identifié trois chemins de réaction élémentaire, qui sont responsable pour le transfert d'un proton d'un acide à une base, ainsi que leurs échelles de temps caractéristiques. Les conclusions tirées de ces études sont discutées dans les détails, au niveau moléculaire, avec une emphase sur les comparaisons entre les résultats théoriques et les mesures expérimentales obtenues dans a littérature ou via des collaborateurs.

Study of baleen whales’ ecology and interaction with maritime traffic activities to support management of a complex socio-ecological system

Thesis written in co-mentorship with Robert Michaud.

A computational fluid dynamic study on the filtering mechanics in suspension feeding marine invertebrates

Les suspensivores ont la tâche importante de séparer les particules de l'eau. Bien qu'une grande gamme de morphologies existe pour les structures d'alimentation, elles sont pratiquement toutes constituées de rangées de cylindres qui interagissent avec leur environnement fluide. Le mécanisme de capture des particules utilisé dépend des contraintes morphologiques, des besoins énergétiques et des conditions d'écoulement. Comme nos objectifs étaient de comprendre ces relations, nous avons eu recours à des études de comparaison pour interpréter les tendances en nature et pour comprendre les conditions qui provoquent de nouveaux fonctionnements. Nous avons utilisé la dynamique des fluides numérique (computational fluid dynamics, CFD) pour créer des expériences contrôlées et pour simplifier les analyses. Notre première étude démontre que les coûts énergétiques associés au pompage dans les espaces petits sont élevés. De plus, le CFD suggère que les fentes branchiales des ptérobranches sont des structures rudimentaires, d'un ancêtre plus grande. Ce dernier point confirme l'hypothèse qu'un ver se nourrit par filtration tel que l'ancêtre des deuterostomes. Notre deuxième étude détermine la gamme du nombre de Reynolds number critique où la performance d'un filtre de balane change. Quand le Re est très bas, les différences morphologiques n'ont pas un grand effet sur le fonctionnement. Cependant, une pagaie devient une passoire lorsque le Re se trouve entre 1 et 3,5. Le CFD s’est dévoilé être un outil très utile qui a permis d’obtenir des détails sur les microfluides. Ces études montrent comment la morphologie et les dynamiques des fluides interagissent avec la mécanisme de capture ou de structures utilisées, ainsi que comment des petits changements de taille, de forme, ou de vitesse d'écoulement peuvent conduire à un nouveau fonctionnement.

Dynamics of Infaunal Benthic Community of the Contenental Shelf of North-Eastern Arabian Sea

In this study dynamics of infaunal benthic community of the continental shelf of north-eastern Arabian sea. The benthic (under water sea) organisms play an important role in the marine food chain. It can be concluded that seasonal differences in the benthic community was observed in lower depths and absent in deeper depths. Increased richness and diversity during pre-monsoon may be related to the increased primary production which inturn influenced by the increased nutrient input due to winter convection. No single ecological factor could be considered as a master factor. In general the area supports moderately high benthic production and diversified community.

STUDIES ON TAXONOMY, DISTRIBUTION, ECOLOGY AND REPRODUCTIVE POTENTIAL OF ROTIFERS FROM SELECTED CENTRES IN COCHIN BACKWATER SYSTEM, KERALA

The studies were conducted in nine stations with varying ecological characteristics along Cochin backwaters and adjoining canals. Many workers opined that the distribution of rotifers is cosmopolitan. The significance of rotifers as first food for early larvae was indicated by Fujita. Aquaculture is a fast growing field in fisheries sector and it is gaining more importance as the fish landings and supply are getting irregular. A consistent supply of fish/shellfish can only be achieved through aquaculture. The success of any culture activity depends on the timely production of seeds of finfishes/shellfishes. The availability of wild seed is seasonal and erratic. So, a dependable source of seed of fishes and shellfishes is possible only through large scale production in hatchery. A successful seed production activity depends on the availability of a variety of suitable live feed organisms in sufficient quantities at the proper time for use in the larval stages. As the live feeds promote high growth rates, easy digestion, assimilation and the quality of not contaminating the culture water when compared to other artificial feeds, make the culture of live feed organisms the principal means of providing food for the larvae of finfishes and shellfishes. Rotifers are considered to be an excellent and indispensable food for larvae of many finfishes and crustaceans. It (1960) was the first to culture Brachionus plicatilis for feeding marine fish larvae, and now it is being extensively used as live feed in hatcheries all over the world. They are a group of microscopic organisms coming under the Phylum Rotifera which comprises of about 2000 species. Their slow swimming habits, ability to tolerate a wide range of salinities, parthenogenetic mode of reproduction and ability to get enriched easily, make rotifers an ideal live feed organism. The major factors such as temperature, salinity and food that influence the reproductive potential and thereby the population size of rotifer, Salinity is one of the most important aspect influencing the reproductive rate of rotifers. The feed type and feed concentration play a vital role in influencing the reproductive rate of rotifers. For culture of rotifers, the commonly used micro algae belong to Chlorella, Nannochloropsis, Isochrysis and Tetraselmis. While some studies have suggested that, algal diet has little effect on reproductive rates in 1979 while using the rotifer, Brachionus plicatilis as feed for the larvae of red sea bream, Pagrus major. It is generally accepted that rotifers play a pivotal role in the successful rearing of marine fish larvae.

Dynamics of Land Use in Recently Settled Forest Areas: a Case Study of Attappady , Kerala

The present study on the dynamics of land use in recently settled forest areas. In the course of events, tribals lost their land; the demographic structure of Attappady changed; the cropping pattern got diversified; traditional techniques of production were ruined; new crops and new techniques of cultivation came to stay; and the entire cost and return structure of production underwent radical change. Migration to Attappady is essentially a continuation of the Malabar migration process from Travancore, through, some people from Tamil Nadu also had migrated to this region earlier. The demographic structure, along with land structure, has changed in favour of the settlers within a short span of time. Lack of security of ownership has acted as a strong reason for wanton exploitation of land resources. The major influencing factors on crop choices among settlers were labour endowment, date of settlement and education. Attappady is an unique ecosystem in Kerala characterized by many interdependables. The latest hand of environmental degradation is a grave danger especially on sloppy terrains,which are under cultivation of tapioca and dry annual crops like groundnuts, cotton, grams etc. Soil erosion as a result of the unplanned cultivation of these crops has resulted in dramatic decline in soil fertility and hence low crop productivity. This calls for a watershed management approach for the sustainable development of the region. A progressive agrarian transformation is warranted to maintain the homegarden as a sustainable production system in ecological and socio-economic terms.