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.

The Russian Empire in Europe, Asia and America

Kartta kuuluu A. E. Nordenskiöldin kokoelmaan

Russia in Europe

Kartta kuuluu A. E. Nordenskiöldin kokoelmaan

Promoting Growth in the Use of Bioenergy in Europe by Converting Existing Coal-Fired Power Plants to Biomass

Repowering existing power plants by replacing coal with biomass might offer an interesting option to ease the transition from fossil fuels to renewable energy sources and promote a fur-ther expansion of bioenergy in Europe, on account of the potential to decrease greenhouse gas emissions, as well as other pollutants (SOx, NOx, etcetera). In addition, a great part of the appeal of repowering projects comes from the opportunity to reuse the vast existing invest-ment and infrastructure associated with coal-based power generation. Even so, only a limited number of experiences with repowering are found. Therefore, efforts are required to produce technical and scientific evidence to determine whether said technology might be considered feasible for its adoption within European conditions. A detailed evaluation of the technical and economic aspects of this technology constitutes a powerful tool for decision makers to define the energy future for Europe. To better illustrate this concept, a case study is analyzed. A Slovakian pulverized coal plant was used as the basis for determining the effects on perfor-mance, operation, maintenance and cost when fuel is shifted to biomass. It was found that biomass fuel properties play a crucial role in plant repowering. Furthermore, results demon-strate that this technology offers renewable energy with low pollutant emissions at the cost of reduced capacity, relatively high levelized cost of electricity and sometimes, a maintenance-intensive operation. Lastly, regardless of the fact that existing equipment can be reutilized for the most part, extensive additions/modifications may be required to ensure a safe operation and an acceptable performance.

Russia in Europe / engraved by J. & C. Walker.

Janamittakaavat: Russian verstes ; English miles.

Moscovey in Europe. From latest observations. Humbly inscrib'd to Abel Ketelbey of the Inner Temple Esqz. By I. Senex.

[N. 1:4250000].

Russia in Europe.

Janamittakaava: Miles.

Russia or Moscovy in Europe.

Lehden oikeassa alakulmassa: T. Kitchin sculp.

Russia or Moscovy in Europe. Drawn by the latest authorities, by Tho.s Kitchin geo.r.

Janamittakaava: Russian wersts.

Russia in Europe.

Lehti nro 34 jostakin Philip & Sonin julkaisemasta kartastosta.

Development and Effect Analysis of the Asteri Consultative Auditing Process - Safety and Security Management in Educational Institutions

The Finnish legislation requires for a safe and secure learning environment. However, the comprehensive, risk based safety and security management (SSM) and the management commitment in the implementation and development of the SSM are not mentioned in the legislation. Multiple institutions, operators and researchers have studied and developed safety and security in educational institutions over the past decade. Typically the approach has been fragmented and without bringing up the importance of the comprehensive SSM. The development needs of the safety and security operations in universities have been studied. However, in universities of applied sciences (UASs) and in elementary schools (ESs), the performance level, strengths and weaknesses of the comprehensive SSM have not been studied. The objective of this study was to develop the comprehensive, risk based SSM of educational institutions by developing the new Asteri consultative auditing process and study its effects on auditees. Furthermore, the performance level in the comprehensive SSM in UASs and ESs were studied using Asteri and the TUTOR model developed by the Keski-Uusimaa Department for Rescue Services. In addition, strengths, development needs and differences were identified. In total, 76 educational institutions were audited between the years 2011 and 2014. The study is based on logical empiricism, and an observational applied research design was used. Auditing, observation and an electronic survey were used for data collection. Statistical analysis was used to analyze the collected information. In addition, thematic analysis was used to analyze the development areas of the organizations mentioned by the respondents in the survey. As one of the main contributions, this research presents the new Asteri consultative auditing process. Organizations with low performance levels on the audited subject benefit the most from the Asteri consultative auditing process. Asteri may be usable in many different types of audits, not only in SSM audits. As a new result, this study provides new knowledge on attitudes related to auditing. According to the research findings, auditing may generate negative attitudes and the auditor should take them into account when planning and preparing for audits. Negative attitudes can be compensated by producing added value, objectivity and positivity for the audit and, thus, improve the positive effects of auditing on knowledge and skills. Moreover, as the results of this study shows, auditing safety and security issues do not increase feelings of insecurity, but rather increase feelings of safety and security when using the new Asteri consultative auditing process with the TUTOR model. The results showed that the SSM in the audited UASs was statistically significantly more advanced than that in the audited ESs. However, there is still room for improvement in the ESs and the UASs as the approach to the SSM was fragmented. It can be assumed that the majority of Finnish UASs and ESs do not likely meet the basic level of the comprehensive, risk based the SSM.

Architecture at the service of ideology : William Morris, the Anglican Church and the destruction, restoration and protection of medieval architecture in victorian England

Résumé Cet ouvrage examine les fondements du mouvement de conservation architecturale moderne. Dans ce contexte, la création de la « Society for the Protection of Ancient Buildings » par William Morris est considéré comme le point culminant d’un processus historique qui mena à l’apparition du mouvement. Sa genèse est présentée comme ayant été le résultat d’une confrontation entre deux visions utopiques du moyen-âge; celle de l’Église Anglicane et celle de William Morris. Un survol détaillé des origines, des résultats et des effets de la « Renaissance Gothique » ouvre tout grand sur les sources littéraires, idéologiques et religieuses qui y donnèrent sa force. Les grands programmes de restaurations qui ont vu le jour en Angleterre à l’ère victorienne sont examinés en relation avec l’Église Anglicane et caractérisés par les motivations idéologiques de celle-ci. Bien que ce memoire ne réussit pas à démontré de manière sans équivoque que la création du mouvement de conservation architectural moderne par Morris fut essentiellement en reaction au programme idéologique de l’Église Anglicane au dix-neuvième siècle, nous y retrouvons néanmoins une réévaluation des causes et de l’impact de la « Renaissance Gothique » qui, de manière significative, allaient à l’encontre des croyances et des principes les plus chers à Morris. Il existe une quantité admirable d’ouvrages examinant les travaux et l’impact de William Morris en littérature et en arts, ainsi que son activisme socialiste. Cependant, il serait juste de constater qu’en comparaison, la grande contribution qu’il apporta à la protection de l’architecture patrimoniale a certainement été négligée dans les publications à son sujet. Ce projet de recherche examine les éléments et les conditions qui ont motivé Morris à créer un mouvement qui encore aujourd’hui continue de croitre en importance et en influence.

The reform of electronic consumer contracts in Europe: towards an effective legal framework?

Christine Riefa is a lecturer in Consumer Law and Intellectual Property Law at Brunel University in the UK. She is an elected board member of the International Association of Consumer Law and an academic correspondent to the Euro-American Chair for the legal protection of consumers (University of Cantabria, Spain). In 2009-2010, Dr Riefa is a Fulbright EU Scholar-in-Residence at Cleveland-Marshall College of Law, Ohio USA. A first version of this article was presented at the Summer School in Consumer Law, organised by the GREDICC (Groupe de recherche en droit international et comparé de la consummation), UQAM, Montréal, 29th June – 4th July 2009.