A signaling mechanism coupling netrin-1/deleted in colorectal cancer chemoattraction to SNARE-mediated exocytosis in axonal growth cones

Directed cell migration and axonal guidance are essential steps in neural development. Both processes are controlled by specific guidance cues that activate the signaling cascades that ultimately control cytoskeletal dynamics. Another essential step in migration and axonal guidance is the regulation of plasmalemma turnover and exocytosis in leading edges and growth cones. However, the cross talk mechanisms linking guidance receptors and membrane exocytosis are not understood. Netrin-1 is a chemoattractive cue required for the formation of commissural pathways. Here, we show that the Netrin-1 receptor deleted in colorectal cancer (DCC) forms a protein complex with the t-SNARE (target SNARE) protein Syntaxin-1 (Sytx1). This interaction is Netrin-1 dependent both in vitro and in vivo, and requires specific Sytx1 and DCC domains. Blockade of Sytx1 function by using botulinum toxins abolished Netrin-1-dependent chemoattraction of axons in mouse neuronal cultures. Similar loss-of-function experiments in the chicken spinal cord in vivo using dominant-negative Sytx1 constructs or RNAi led to defects in commissural axon pathfinding reminiscent to those described in Netrin-1 and DCC loss-of-function models. We also show that Netrin-1 elicits exocytosis at growth cones in a Sytx1-dependent manner. Moreover, we demonstrate that the Sytx1/DCC complex associates with the v-SNARE (vesicle SNARE) tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) and that knockdown of TI-VAMP in the commissural pathway in the spinal cord results in aberrant axonal guidance phenotypes. Our data provide evidence of a new signaling mechanism that couples chemotropic Netrin-1/DCC axonal guidance and Sytx1/TI-VAMP SNARE proteins regulating membrane turnover and exocytosis.

A signaling mechanism coupling netrin-1/deleted in colorectal cancer chemoattraction to SNARE-mediated exocytosis in axonal growth cones

Directed cell migration and axonal guidance are essential steps in neural development. Both processes are controlled by specific guidance cues that activate the signaling cascades that ultimately control cytoskeletal dynamics. Another essential step in migration and axonal guidance is the regulation of plasmalemma turnover and exocytosis in leading edges and growth cones. However, the cross talk mechanisms linking guidance receptors and membrane exocytosis are not understood. Netrin-1 is a chemoattractive cue required for the formation of commissural pathways. Here, we show that the Netrin-1 receptor deleted in colorectal cancer (DCC) forms a protein complex with the t-SNARE (target SNARE) protein Syntaxin-1 (Sytx1). This interaction is Netrin-1 dependent both in vitro and in vivo, and requires specific Sytx1 and DCC domains. Blockade of Sytx1 function by using botulinum toxins abolished Netrin-1-dependent chemoattraction of axons in mouse neuronal cultures. Similar loss-of-function experiments in the chicken spinal cord in vivo using dominant-negative Sytx1 constructs or RNAi led to defects in commissural axon pathfinding reminiscent to those described in Netrin-1 and DCC loss-of-function models. We also show that Netrin-1 elicits exocytosis at growth cones in a Sytx1-dependent manner. Moreover, we demonstrate that the Sytx1/DCC complex associates with the v-SNARE (vesicle SNARE) tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) and that knockdown of TI-VAMP in the commissural pathway in the spinal cord results in aberrant axonal guidance phenotypes. Our data provide evidence of a new signaling mechanism that couples chemotropic Netrin-1/DCC axonal guidance and Sytx1/TI-VAMP SNARE proteins regulating membrane turnover and exocytosis.

Classification supervisée multi-étiquette en actes de dialogue: analyse discriminante et transformations de Schoenberg

Abstract This work studies the multi-label classification of turns in simple English Wikipedia talk pages into dialog acts. The treated dataset was created and multi-labeled by (Ferschke et al., 2012). The first part analyses dependences between labels, in order to examine the annotation coherence and to determine a classification method. Then, a multi-label classification is computed, after transforming the problem into binary relevance. Regarding features, whereas (Ferschke et al., 2012) use features such as uni-, bi-, and trigrams, time distance between turns or the indentation level of the turn, other features are considered here: lemmas, part-of-speech tags and the meaning of verbs (according to WordNet). The dataset authors applied approaches such as Naive Bayes or Support Vector Machines. The present paper proposes, as an alternative, to use Schoenberg transformations which, following the example of kernel methods, transform original Euclidean distances into other Euclidean distances, in a space of high dimensionality. Résumé Ce travail étudie la classification supervisée multi-étiquette en actes de dialogue des tours de parole des contributeurs aux pages de discussion de Simple English Wikipedia (Wikipédia en anglais simple). Le jeu de données considéré a été créé et multi-étiqueté par (Ferschke et al., 2012). Une première partie analyse les relations entre les étiquettes pour examiner la cohérence des annotations et pour déterminer une méthode de classification. Ensuite, une classification supervisée multi-étiquette est effectuée, après recodage binaire des étiquettes. Concernant les variables, alors que (Ferschke et al., 2012) utilisent des caractéristiques telles que les uni-, bi- et trigrammes, le temps entre les tours de parole ou l'indentation d'un tour de parole, d'autres descripteurs sont considérés ici : les lemmes, les catégories morphosyntaxiques et le sens des verbes (selon WordNet). Les auteurs du jeu de données ont employé des approches telles que le Naive Bayes ou les Séparateurs à Vastes Marges (SVM) pour la classification. Cet article propose, de façon alternative, d'utiliser et d'étendre l'analyse discriminante linéaire aux transformations de Schoenberg qui, à l'instar des méthodes à noyau, transforment les distances euclidiennes originales en d'autres distances euclidiennes, dans un espace de haute dimensionnalité.

Economic and social convergence in Colombia

GDP has usually been used as a proxy for human well-being. Nevertheless, other social aspects should also be considered, such as life expectancy, infant mortality, educational enrolment and crime issues. With this paper we investigate not only economic convergence but also social convergence between regions in a developing country, Colombia, in the period 1975-2005. We consider several techniques in our analysis: sigma convergence, stochastic kernel estimations, and also several empirical models to find out the beta convergence parameter (cross section and panel estimates, with and without spatial dependence). The main results confirm that we can talk about convergence in Colombia in key social variables, although not in the classic economic variable, GDP per capita. We have also found that spatial autocorrelation reinforces convergence processes through deepening market and social factors, while isolation condemns regions to nonconvergence.

Yhteiskuntavastuu puheen tuotteena : yritysten ja kansalaisaktivistien perusteluissa esiintyvät yhteiset arvot

Abstract: Corporate social responsibility as the product of talk : shared values present in the arguments of business and civil activists

Mechanisms involved in down-regulation of intestinal IgA in rats by high cocoa intake

Previous studies have shown that rat intestinal immunoglobulin A (IgA) concentration and lymphocyte composition of the intestinal immune system were influenced by a highly enriched cocoa diet. The aim of this study was to dissect the mechanisms by which a long-term high cocoa intake was capable of modifying gut secretory IgA in Wistar rats. After 7 weeks of nutritional intervention, Peyer's patches, mesenteric lymph nodes and the small intestine were excised for gene expression assessment of IgA, transforming growth factor ß, C-C chemokine receptor-9 (CCR9), interleukin (IL)-6, CD40, retinoic acid receptors (RAR¿ and RARß), C-C chemokine ligand (CCL)-25 and CCL28 chemokines, polymeric immunoglobulin receptor and toll-like receptors (TLR) expression by real-time polymerase chain reaction. As in previous studies, secretory IgA concentration decreased in intestinal wash and fecal samples after cocoa intake. Results from the gene expression showed that cocoa intake reduced IgA and IL¿6 in Peyer's patches and mesenteric lymph nodes, whereas in small intestine, cocoa decreased IgA, CCR9, CCL28, RAR¿ and RARß. Moreover, cocoa-fed animals presented an altered TLR expression pattern in the three compartments studied. In conclusion, a high-cocoa diet down-regulated cytokines such as IL-6, which is required for the activation of B cells to become IgA-secreting cells, chemokines and chemokine receptors, such as CCL28 and CCR9 together with RAR¿ and RARß, which are involved in the gut homing of IgA-secreting cells. Moreover, cocoa modified the cross-talk between microbiota and intestinal cells as was detected by an altered TLR pattern. These overall effects in the intestine may explain the intestinal IgA down-regulatory effect after the consumption of a long-term cocoa-enriched diet.

The autonomic nervous activity of hostile acting

The present talk aims to examine the heart-rate variability (HRV) indexes of two populations known to be particularly sensitive to stress condition: violent offenders and intellectually impaired patients. For both, difficulties in managing stressful and emotional events could lead to unpredictable and hostile acting. Results in favour of specific HRV baseline patterns and emotional control will be developed, as the proposition of precursors of agitation in the physiological fluctuations preceding high tensed episodes. The improvement offered by coherent breathing trainings will be discussed for both groups.

Assessment in CLIL

The aim of this talk is to explore assessment in higher education and support for learners during their academic education. It investigates the assessment methods that provide success for universities and learners. Universities which implement CLIL should assess learners who would like to attend a programme in English without taking account of their English language qualifications. This assessment should be done in writing, listening and comprehension, speaking and reading and comprehension. In the literature, formative and summative assessments are considered. Formative assessment is ongoing, 'more complex as its intention is to be directly diagnostics with a view to immediately impacting on learner's next steps' (Coyle et al, 2010). Summative assessment occurs at the end of the term or course. McKay, 2006 divides assessment into three phases: design, operationalization and administration phase. If these three phases can't be embedded in the classroom as they are, they can be introduced as a set of questions; why?, how? and what?

La metodologia d'intervenció dels treballadors socials en el sistema de les cures pal·liatives

L’atenció a l’etapa final de la vida de les persones és un dels pilars fonamentals de les cures pal·liatives i és des de la professió del treball social que es pot promoure aquesta atenció en concepte de qualitat, tranquil·litat i preservació dels valors de les persones en situació terminal. És per aquesta raó que s’ha elaborat el present document d’investigació, el qual compta inicialment amb un recull bibliogràfic que abraçarà la metodologia d’intervenció dels treballadors socials en el sistema de les cures pal·liatives de l’Estat espanyol i del Regne Unit, país pioner en la creació de les unitats de cures pal·liatives. En aquest recull s’emmarcaran detalladament les diferències existents en termes d’intervenció i de desenvolupament d’aquest àmbit en els dos territoris. La descripció detallada dels dos models d’intervenció pretén donar la resposta a l’interrogant sobre quina és la metodologia d’intervenció que realitzen els treballadors socials en el sistema de cures pal·liatives. Per assolir aquesta resposta, s’adrecen qüestions com els objectius que lideren el treball d’aquests professionals, les funcions que realitzen en la seva pràctica professional diària i les habilitats de les que han de disposar per tal d’aconseguir que la seva intervenció sigui òptima, tant per als mateixos professionals com per a les persones amb les quals intervenen. Posteriorment a la revisió bibliogràfica, es realitzaran tres entrevistes exploratòries a tres treballadors socials de diferents nivells sanitaris que promoguin les cures pal·liatives a Catalunya. S’analitzaran les qüestions treballades en el recull bibliogràfic (objectius, funcions i habilitats dels treballadors socials), les quals permetran comparar la perspectiva teòrica cercada amb la informació primària obtinguda. Finalment, es planteja una proposta de projecte que permetrà aprofundir en la intervenció dels treballadors socials de Catalunya i del Regne Unit, realitzant una comparació entre els dos models a través de la realització de quaranta-vuit entrevistes repartides homogèniament per els dos territoris. D’aquesta manera, s’especificaran totes aquelles accions que es puguin millorar i les intervencions que siguin més òptimes per la tipologia d’atenció que es requereix en els sistemes de les cures pal·liatives d’avui en dia.

What young people with spina bifida want to know about sex and are not being told.

OBJECTIVE: The aim of this paper was to examine sexual knowledge, concerns and needs of youth with spina bifida (SB) to inform the medical community on ways to better support their sexual health. METHODS: As part of the Video Intervention/Prevention Assessment (VIA) - transitions, a prospective cohort study, 309 h of video data were collected from 14 participants (13-28 years old) with SB. Participants were loaned a video camcorder for 8-12 weeks to shoot visual narratives about any aspects of their lives. V/A visual narratives were analysed with grounded theory using NVivo. RESULTS: Out of 14 participants, 11 (six women) addressed issues surrounding romantic relationships and sexuality in their video clips. Analysis revealed shared concerns, questions and challenges regarding sexuality gathered under four main themes: romantic relationships, sexuality, fertility and parenthood, and need for more talk on sexuality. CONCLUSIONS: Youth with SB reported difficulties in finding answers to questions regarding their sexuality, romantic relationships and fertility. This study revealed a need for help from the medical community to inform and empower youth with SB in the area of sexual health. Through sexual and reproductive health education with patients and parents starting at an early age, medical providers can further encourage healthy emotional and physical development in adolescents transitioning into adulthood.

El Grafisme al parvulari. Observació i anàlisi de l’espai en els dibuixos dels infants.

Els dibuixos dels infants són petites marques de la personalitat i del caràcter de cadascú. Cada infant tendeix a representar i a dibuixar d’una determinada manera i és això el que fa que els seus dibuixos siguin únics. Aquest treball és un estudi qualitatiu sobre l’evolució de la percepció de l’espai en els dibuixos dels infants d’entre tres i cinc anys. L’estudi està format a partir de la recerca i comparació de teories de diferents autors sobre el dibuix i d’un mostreig de 61 dibuixos de diferents infants. Els instruments que s’utilitzen són l’observació directe, a partir de graelles d’observació, notes de camp, fotografies i gravacions. Un cop fetes les intervencions convenients s’extreuen uns resultats, analitzant dibuix per dibuix, per més tard, fer una comparació del que s’ha vist amb el mostreig obtingut i amb el que deien els autors.

Els altres parlants i la història social de la llengua

The social history of language is usually focused on collective actors. This article aims to reflect both on the speakers as individual subjects of the social history of language and on the sources which allow an approach to speakers, more precisely immigrants of the contemporary Catalonia. In very different narratives, immigrants talk about their territory of origin or economic conditions, and also about languages expressing the most varied language attitudes. Prejudices or language uses, common topics of these narratives, are fully within the field of social history of the language. Speakers cannot be always out of disciplines whose narrative axis is the time

Uptake and factors that influence the use of ‘sit less, move more’ occupational intervention strategies in Spanish office employees

Background Little is known about the types of ‘sit less, move more’ strategies that appeal to office employees, or what factors influence their use. This study assessed the uptake of strategies in Spanish university office employees engaged in an intervention, and those factors that enabled or limited strategy uptake. Methods The study used a mixed method design. Semi-structured interviews were conducted with academics and administrators (n = 12; 44 ± 12 mean SD age; 6 women) at three points across the five-month intervention, and data used to identify factors that influenced the uptake of strategies. Employees who finished the intervention then completed a survey rating (n = 88; 42 ± 8 mean SD age; 51 women) the extent to which strategies were used [never (1) to usually (4)]; additional survey items (generated from interviewee data) rated the impact of factors that enabled or limited strategy uptake [no influence (1) to very strong influence (4)]. Survey score distributions and averages were calculated and findings triangulated with interview data. Results Relative to baseline, 67% of the sample increased step counts post intervention (n = 59); 60% decreased occupational sitting (n = 53). ‘Active work tasks’ and ‘increases in walking intensity’ were the strategies most frequently used by employees (89% and 94% sometimes or usually utilised these strategies); ‘walk-talk meetings’ and ‘lunchtime walking groups’ were the least used (80% and 96% hardly ever or never utilised these strategies). ‘Sitting time and step count logging’ was the most important enabler of behaviour change (mean survey score of 3.1 ± 0.8); interviewees highlighted the motivational value of being able to view logged data through visual graphics in a dedicated website, and gain feedback on progress against set goals. ‘Screen based work’ (mean survey score of 3.2 ± 0.8) was the most significant barrier limiting the uptake of strategies. Inherent time pressures and cultural norms that dictated sedentary work practices limited the adoption of ‘walk-talk meetings’ and ‘lunch time walking groups’. Conclusions The findings provide practical insights into which strategies and influences practitioners need to target to maximise the impact of ‘sit less, move more’ occupational intervention strategies.

”Kyllähän nyt pitäs olla jo semmonen aika, että pääsis niin kö keskustelemhan näistä asioista.” Tutkimus lappilaisten sotavankien, partisaanien uhrien ja huutolaisten elämänkulusta, voimavaroista, terveydestä ja sairauksista

Research into the course of life, mental stamina and health status of wartime prisoners, victims of Soviet partisan attacks, and paupers in Finnish Lapland The basis of this research comprised the issues raised during the interviews conducted in my work as a general practitioner in Lapland, regarding factors that have possibly affected the life stories and health conditions of Lappish people who had lived through the war as war prisoners, victims of partisan attacks, or paupers. The purpose of the study was to describe how the different life phases and experiences emerged from the interviewees’ stories and to identify their mental stamina. Another goal was to make observations on their health status, in which the main emphasis became to address mental symptoms. The cohort consisted of elderly Finns who lived in Lapland during the war and experienced war imprisonment, pauperism, or became victims of partisan attacks. All three groups consisted of 12 interviewees. The interview transcripts were read several times and then investigated using the content analysis methods applicable to the material. The research methodology was based on building awareness and understanding. Thematic tagging and data coding were used as structured analysis tools. In all three groups most of the interviewees clearly identified their mental stamina, the most fundamental of which were home, family and work. The war prisoners’ injuries and nervous sensibility symptoms had been shown in earlier studies on war prisoners, and on this basis they had been granted disability pensions. However, many of them had suppressed their traumatic experiences and mental difficulties, and they could not talk about these issues until at the time of these interviews held at old age. Four of them still suffered from a post-traumatic stress disorder. The victims of Soviet partisans had had to carry their mental load alone for decades before the cruel ravages on civilians in remote areas of Lapland became publicly known. Most of them still had disturbing nervous sensibility symptoms. Four interviewees had a post-traumatic stress disorder, and in addition to these, the mental symptoms of one had developed into a post-traumatic stress disorder during old age. Many of the interviewees who had been left paupers remembered their childhood as filled with grief and feelings of inferiority, and had nightmares relating to their wartime experiences. Yet none of them suffered from post-traumatic stress disorder. The results showed that the exceptional suffering caused by the war, the wartime imprisonment and the devastating attacks by Soviet partisans had led especially to mental difficulties. These were left almost completely unnoticed in the post-war conditions, and the war victims were unable to seek help on their own. Based on the results, our health care for the elderly should focus on familiarization with the individual experiences and life stories of each elderly person. This can facilitate geriatric diagnostics and individual therapy planning. Empathic familiarization with the life experiences of the elderly may strengthen their mental stamina and improve the quality of successful aging.

"Mitähän mä seuraavaks sanoisin..." : keskusteluntutkimuksen keinoja soittotunnin puheen tarkasteluun

Soittotunnin vuorovaikusta on tutkittu hyvin vähän, ja puhetta tunneilla ei oikeastaan lainkaan. Puhe on olennaisen tärkeä osa soitonopetusta, joten tunnin puhutun osuuden tarkempi tarkastelu olisi opettajille ja opettajaksi opiskeleville hyödyksi. Tässä opinnäytetyössä esittelen keinoja soittotunnin kielellisen osuuden tutkimiseen. Tutkimuskohteina ovat erityisesti palaute sekä korjauspuhe. Työn aineistona on reilu kaksi tuntia pääosin Stadian opetusharjoittelun puitteissa koottua videokuvaa. Teoreettisen taustan muodostavat kaksi kielitieteen suuntausta, diskurssianalyysi ja keskustelunanalyysi. Näitä menetelmiä on aiemmin sovellettu monenlaisten keskustelutilanteiden tutkimiseen. Työ jakautuu taustan kuvailuun, aineiston esittelyyn sekä sen analyysiin kahta erilaista menetelmää soveltaen. Lopuksi pohdin, miten hyvin menetelmät sopivat soittotuntikielen käsittelyyn. Diskurssianalyyttisessa tarkastelussa sovellan soittotuntikieleen analyysimenetelmää, joka on alunperin kehitetty koululuokan kielen tutkimista varten, ja vertailen palautetta soittotuntiaineistossa ja koulu-luokkakeskustelussa. Menetelmä on sovellettavissa soittotuntikielen tutkimiseen ja sen avulla saa selkeitä, taulukoitavia tuloksia. Siinä on kuitenkin myös hankaluutensa, kuten analyysin tulkinnanvaraisuus ja se, ettei soittotunnin kieli ole yhtä selkeän kaavamaista kuin koululuokan. Keskustelunanalyyttisessa tarkastelussa vertailukohtanani on tutkimus, joka käsittelee korjauspuhetta orkesteriharjoituksissa. Opinnäytetyössäni keskityn selvittämään kyseisen mallin sopivuutta soittotuntipuheen tarkasteluun, joten menetelmä ei tuota selkeitä tuloksia. Se huomioi hyvin musiikillisen tilanteen erikoispiirteet, mutta rajaa tarkastelun ulkopuolelle kaiken paitsi korjauspuheen. Kaiken kaikkiaan opinnäytteeni osoittaa, että soittotunnin puhetta on mahdollista tarkastella monella eri tavalla. Työssä esitellyillä keinoilla on hyvät ja huonot puolensa, eikä kumpikaan niistä ole sellaisenaan täydellinen soittotunnin kielen kuvaamiseen. Mahdollisimman hyvän, tarkan ja hyödyllisen soittotuntipuheen analyysimenetelmän kehittäminen vaatisikin vielä paljon lisätutkimusta.