Missense mutations in TENM4, a regulator of axon guidance and central myelination, cause essential tremor.

Essential tremor (ET) is a common movement disorder with an estimated prevalence of 5% of the population aged over 65 years. In spite of intensive efforts, the genetic architecture of ET remains unknown. We used a combination of whole-exome sequencing and targeted resequencing in three ET families. In vitro and in vivo experiments in oligodendrocyte precursor cells and zebrafish were performed to test our findings. Whole-exome sequencing revealed a missense mutation in TENM4 segregating in an autosomal-dominant fashion in an ET family. Subsequent targeted resequencing of TENM4 led to the discovery of two novel missense mutations. Not only did these two mutations segregate with ET in two additional families, but we also observed significant over transmission of pathogenic TENM4 alleles across the three families. Consistent with a dominant mode of inheritance, in vitro analysis in oligodendrocyte precursor cells showed that mutant proteins mislocalize. Finally, expression of human mRNA harboring any of three patient mutations in zebrafish embryos induced defects in axon guidance, confirming a dominant-negative mode of action for these mutations. Our genetic and functional data, which is corroborated by the existence of a Tenm4 knockout mouse displaying an ET phenotype, implicates TENM4 in ET. Together with previous studies of TENM4 in model organisms, our studies intimate that processes regulating myelination in the central nervous system and axon guidance might be significant contributors to the genetic burden of this disorder.

Occlusal and dentofacial characteristics of the deciduous dentition and treatment effects of the eruption guidance appliance in the early mixed dentition

The aim of this investigation was to analyze the dental occlusion in the deciduous dentition, and the effects of orthodontic treatment carried out in the early mixed dentition with the eruption guidance appliance. The deciduous occlusion and craniofacial morphology of 486 children (244 girls and 242 boys) were investigated at the onset of the mixed dentition period (mean age 5.1 years, range 4.0-7.8 years). Treatment in the treatment group and follow-up in the control group were started when the first deciduous incisor was exfoliated (T1) and ended when all permanent incisors and first molars were fully erupted (T2). The mean age of the children was 5.1 years (SD 0.5) at T1 and 8.4 years (SD 0.5) at T2. Treatment was carried out with the eruption guidance appliance. Occlusal changes that took place in 167 children were compared with those of 104 untreated control children. Pre- and post-treatment cephalometric radiographs were taken, and the craniofacial morphology of 115 consecutively treated children was compared with that of 104 control children. The prevalence of malocclusion in the deciduous dentition was 68% or 93% depending on how the cut-off value between the acceptable and non-acceptable occlusal characteristic was defined. The early dentofacial features of children with distal occlusion, large overjet and deepbite differed from those with normal occlusion. However, the skeletal pattern of these three malocclusions showed considerable similarity each being characterized by a retrusive mandible, small maxillo-mandibular difference, convex profile, retrusive lower incisors, and large interincisal angle. In the treatment group, overjet and overbite decreased significantly from T1 to T2. Following treatment, a tooth-to-tooth contact was found in 99% of the treated children but only in 24% of the controls. A Class I molar relationship was observed in 90% of the children in the treatment group, and in 48% in the control group. Good alignment of the incisors was observed in 98% of the treated children, whereas upper crowding was found in 32% and lower crowding in 47% of the controls. A significant difference between the groups was found in the mandibular length, midfacial length and maxillo-mandibular differential. The occlusal correction, brought about by the eruption guidance appliance, was achieved mainly through changes in the dentoalveolar region of the mandible. In addition, the appliance seemed to enhance the growth of the mandible. Treatment in the early mixed dentition using the eruption guidance appliance is an effective method to normalize occlusion and reduce further need of orthodontic treatment. Only few spontaneous corrective changes can be expected without active intervention.

Towards Innovative Virtual Learning in Vocational Teacher Education: Narratives as a Form of Meaningful Learning

http://www.eurodl.org/.

Adult education policy in the European Union during the Lisbon decade : the shift to vocational adult learning and work skills matching

This doctoral dissertation investigates the adult education policy of the European Union (EU) in the framework of the Lisbon agenda 2000–2010, with a particular focus on the changes of policy orientation that occurred during this reference decade. The year 2006 can be considered, in fact, a turning point for the EU policy-making in the adult learning sector: a radical shift from a wide--ranging and comprehensive conception of educating adults towards a vocationally oriented understanding of this field and policy area has been observed, in particular in the second half of the so--called ‘Lisbon decade’. In this light, one of the principal objectives of the mainstream policy set by the Lisbon Strategy, that of fostering all forms of participation of adults in lifelong learning paths, appears to have muted its political background and vision in a very short period of time, reflecting an underlying polarisation and progressive transformation of European policy orientations. Hence, by means of content analysis and process tracing, it is shown that the new target of the EU adult education policy, in this framework, has shifted from citizens to workers, and the competence development model, borrowed from the corporate sector, has been established as the reference for the new policy road maps. This study draws on the theory of governance architectures and applies a post-ontological perspective to discuss whether the above trends are intrinsically due to the nature of the Lisbon Strategy, which encompasses education policies, and to what extent supranational actors and phenomena such as globalisation influence the European governance and decision--making. Moreover, it is shown that the way in which the EU is shaping the upgrading of skills and competences of adult learners is modeled around the needs of the ‘knowledge economy’, thus according a great deal of importance to the ‘new skills for new jobs’ and perhaps not enough to life skills in its broader sense which include, for example, social and civic competences: these are actually often promoted but rarely implemented in depth in the EU policy documents. In this framework, it is conveyed how different EU policy areas are intertwined and interrelated with global phenomena, and it is emphasised how far the building of the EU education systems should play a crucial role in the formation of critical thinking, civic competences and skills for a sustainable democratic citizenship, from which a truly cohesive and inclusive society fundamentally depend, and a model of environmental and cosmopolitan adult education is proposed in order to address the challenges of the new millennium. In conclusion, an appraisal of the EU’s public policy, along with some personal thoughts on how progress might be pursued and actualised, is outlined.

Extracellular matrix molecules play diverse roles in the growth and guidance of central nervous system axons

Axon growth and guidance represent complex biological processes in which probably intervene diverse sets of molecular cues that allow for the appropriate wiring of the central nervous system (CNS). The extracellular matrix (ECM) represents a major contributor of molecular signals either diffusible or membrane-bound that may regulate different stages of neural development. Some of the brain ECM molecules form tridimensional structures (tunnels and boundaries) that appear during time- and space-regulated events, possibly playing relevant roles in the control of axon elongation and pathfinding. This short review focuses mainly on the recognized roles played by proteoglycans, laminin, fibronectin and tenascin in axonal development during ontogenesis.

Oppisopimuskoulutus yritysten tuottamana koulutuspalveluna: tavoitteista vaikutuksiin

Työpaikoilla tapahtuvan koulutuksen merkitys korostuu yhteiskunnassa kaikilla tasoilla nyt ja tulevaisuudessa. Tämä väitöstutkimus määrittelee oppisopimuskoulutuksen yritysten tuottamana koulutuspalveluna osana ammatillista tutkintoon johtavaa koulutusta, jota tuotetaan työpaikoilla ja yrityksissä. Väitöstutkimuksessa tarkastellaan niitä tavoitteita, joita yrityksissä oppisopimuskoulutukseen liittyy ja vaikutuksia, joita koulutusta tuottamalla yrityksessä syntyy. Tutkimuksen kohteena ovat eri alojen pienet ja keskisuuret yritykset (pk-yritykset), jotka ovat tuottaneet oppisopimuskoulutusta ja joilla on siitä vuosien kokemus. Lisäksi tutkimukseen osallistui pk-yrityksiä, joille oppisopimuskoulutus ja siihen liittyvä toiminta on vierasta. Tutkimus tuo uutta tietoa vain vähän tutkittuun aikuisten oppisopimuskoulutukseen, mutta ei sulje pois nuorten oppisopimuskoulutukseen liittyviä kysymyksiä. Tutkimus yhdistää oppisopimuskoulutuksen ja koulutuksen tuottamisen yrityksissä, mikä uudistaa sekä oppisopimuskoulutukseen, ammatilliseen koulutukseen, palvelun tuottamiseen että osaamiseen liittyvää teoreettista viitekehystä. Lisäksi tutkimus tuo yrityksille sekä oppisopimuskoulutuksen hallinnollisille tahoille palvelun tuottamisen ja siihen liittyvien tavoitteiden ja vaikutusten näkökulman. Väitöstutkimuksen teoreettinen viitekehys perustuu ja jakautuu kolmeen osaan: palveluun ja sen tuottamiseen, osaamispääomiin ja niiden eri muotoihin sekä vaikutuksiin palvelutuotannossa. Teoreettinen viitekehys kuvaa monimuotoisesti oppisopimuskoulutuksen ilmiötä, jonka olemus muuttuu sen mukaan, miten, kuka tai mikä taho sitä arvioi tai tarkastelee. Väitöstutkimus on empiiriseltä luonteeltaan kvalitatiivinen tutkimus, jonka aineisto on kerätty teemahaastatteluilla vuoden 2013 lopulla ja vuoden 2014 alussa. Aineisto on analysoitu sisällönanalyysillä aineistolähtöisesti. Tutkimusote pohjautuu abduktiiviseen päättelyyn. Tutkimustulokset esitetään ja luokitellaan niin tavoitteiden kuin vaikutusten osalta inhimillisen, rakenteellisen ja suhdepääoman kautta. Tutkimuksen mukaan oppisopimuskoulutuksen vaikutukset nähdään positiivisina ja neutraaleina, eikä alakohtaisia eroja vaikutusten osalta juuri ole. Myönteisten vaikutusten saavuttamiseen liittyy tärkeänä osana arvon luomisen ja tuottamisen kokemus molemmilla koulutukseen osallistuvilla osapuolilla. Lisäksi myönteisten vaikutusten taustalla ovat yrityksen sitoutuminen sekä työn ja koulutuksen johtamisosaaminen. Yrityksissä on tärkeää, että imago kouluttajana on hyvä. Oppisopimuskoulutuksen tuottamisesta syntyneet vaikutukset ovat asetettuja tavoitteita laajemmat, erityisesti rakenteelliseen pääomaan liittyvien vaikutusten osalta. Oppisopimuskoulutuksen vaikuttavuus yrityksessä syntyy asetettujen tavoitteiden ja vaikutusten välisestä suhteesta. Kokonaisuutena voidaan todeta, että oppisopimuskoulutuksen vaikuttavuus ja suorituskyky yrityksissä ovat hyvät, vaikka koulutuksen laatu vaihtelee jonkin verran. Oppisopimuskoulutuksen käynnistäminen, aloittaminen ja tuottaminen liittyvät usein niin sanottuihin oppisopimusagentteihin eli sellaisiin kehityshakuisiin henkilöihin, joilla jossakin elämäntilanteessa on ollut myönteisiä kokemuksia oppisopimuskoulutuksen mahdollisuuksista. Tutkimuksen mukaan oppisopimuskoulutuksen kustannukset koostuvat työsuhteesta, tietopuolisen koulutuksen aikaisesta työstä poissaolosta sekä ohjauksesta ja arvioinnista, mutta koulutusta pidetään taloudellisesti kannattavana. Oppisopimuskoulutuksen tuottamista estävät pääasiassa viestinnän ja tiedottamisen puute, koulutusmahdollisuuden tunnistamatta jääminen, yritysten heikko koulutuskulttuuri sekä epäselvät mielikuvat ja käsitykset. Nuorten oppisopimuskoulutuksen toteuttamisen hidasteina ovat tutkimuksen mukaan työsuhteeseen ja talouteen liittyvät seikat, nuorten kasvun vaiheeseen sisältyvät tekijät sekä monenlaiset pedagogiset ja eettiset kysymykset. Lisäksi tutkimuksessa havaittiin, että nuori on käsitteenä ja viiteryhmänä epämääräinen. Ammatillisen koulutuksen ja oppisopimuskoulutuksen eri muodot ja monet käsitteet myös aiheuttavat epäselvyyttä molemmissa tutkimuksen konteksteissa eli yrityksissä, joissa oppisopimuskoulutusta tuotetaan sekä yrityksissä, joissa sitä ei tuoteta.

The motivation of vocational students in a college setting /

This qualitative study explores the motivation of College Vocational Program (CVP) students at one campus of a large College of Applied Arts and Technology (CAAT a) in urban southern Ontario. The study is in response to my close involvement with the CVP students as an instructor for five years, and my observation that a greater understanding of the motivational influences affecting the students' involvement in the program would strengthen teaching and learning, and enhance the CVP educational experience for students and instructors. This study was limited to one CVP program, and a small sample of convenience of 9 CVP male and female students and 6 instructors selected from two classes. The students were chosen based on their verbal abilities to communicate their thoughts, feelings, and experiences in regard to answering the research questions posed. Through interviews with students, instructors, and ajob coach, this study addressed four main questions relevant to college vocational students and motivation: defining student success, encouragement, discouragement, and perceptions about academic and vocationalleaming. The interview questions for both students and instructors were designed by me and were based on themes derived from the literature and from my experience in the program. The findings identify that the students and instructors see success in the program in a slightly different way, the importance of relationships and structure, the hindering effect of disabilities and the importance of accommodation, and the strong aspiration of the students wanting to learn in a supportive accepting environment. The study concludes with implications for further research and theory development.

A Study of role conflict, role ambiguity, locus of control, job satisfaction and participation in decision making among front-line vocational service workers for mentally retarded adults

This study was an investigation of individual and organizational factors, as perceived by front-line vocational service workers from Adult Rehabilitation Centres (ARC Industries) for mentally retarded adults. The specific variables which were measured included role conflict/role ambiguity (role factors), internal/external locus of control (individual differences), job satisfaction with work and supervision (job attitudes) and participation in deci~ion making (organizational factor). The exploration of these constructs was conducted by means of self-report questionnaires which were completed by sixty-nine out of a total of ninety front-line employees. The surveys were distributed in booklet form to nine distinct rehabilitation facilities from St. Catharines, West Lincoln, Greater Niagara, Port Colborne, WeIland, Fort Erie, Hamilton, Guelph and Brantford. The survey data was evaluated by the statisti.cal Package for the Social Sciences (SPSS) which used the Pearson Product Moment Correlation procedure and a compar~son of means test. A comparison of correlation coefficients test was also conducted. This statistical procedure was calculated mathematically. The results obtained from the statistical evaluation confirmed the prediction that self-reported measures of participation in decision making and satisfaction (work and supervision) would be negatively correlated with role conflict and role ambiguity. As well, the speculation that perceived satisfaction (work and supervision) would be positively correlated with participation in decision making was empirically supported. Internal and external locus of control did not contribute to a significant difference in r~sponses to role perceptions (conflict and ambiguity) , satisfaction (work and supervision) or the correlational relationship between participation in decision making and satisfaction (work and supervision). Overall, the findings from this study substantiated the importance of examining employee perceptions in the workplace and the interrelationships among individual and organizational variables. This research was considered a contribution to the general area of occupational stress and to the study of individuals in work organizations.

Elucidation of the Retinoid Signalling Pathway Involved in Axon Guidance in Lymnaea stagnalis and Xenopus laevis

The vitamin A metabolite, retinoic acid (RA), is known to play a crucial role in several developmental processes including axial patterning and differentiation. More recently, RA has been implicated in the regenerative process acting through its classical signaling pathway, the nuclear receptors, retinoic acid receptor (RAR) and retinoid X receptor (RXR), to mediate gene transcription. Moreover, RA has been shown to act as a guidance molecule for growth cones of regenerating motorneurons of the pond snail, Lymnaea stagnalis. Our lab has recently shown that RA can induce this morphological response independent of nuclear transcription, however, the role of the retinoid receptors in RA-induced chemoattraction is still unknown. Here, I show that the retinoid receptors, RXR and RAR, may mediate the growth cones response to the metabolically active retinoic acid isomers, all-trans and 9-cis RA, in Lymnaea stagnalis. Data presented here show that both an RXR and RAR antagonist can block growth cone turning in response to application of both isomers. Because no prior investigations have shown growth cone turning of individual vertebrate neurons, I aimed to show that both retinoic acid isomers were capable of inducing growth cone turning of embryonic spinal cord neurons in the frog, Xenopus laevis. For the first time in Xenopus, I showed that both all-trans and 9-cis RA were able to induce significantly more neurite outgrowth from cultured embryonic spinal cord neurons and induce positive growth cone turning of individual growth cones. In addition, I showed that the presence of the RXR antagonist, HX531, blocked 9-cis RA-induced growth cone turning and the RARβ antagonist, LE135, blocked all-trans RA-induced growth cone turning in this species. Evidence provided here shows for the first time, conservation of retinoic acid-induced growth cone turning in a vertebrate model system. In addition, these data show that the receptors involved in this morphological response may be the same in vertebrates and invertebrates.