Prolyl Oligopeptidase Regulates Dopamine Transporter Phosphorylation in the Nigrostriatal Pathway of Mouse

Alpha-synuclein is the main component of Lewy bodies, a histopathological finding of Parkinson's disease. Prolyl oligopeptidase (PREP) is a serine protease that binds to alpha-synuclein and accelerates its aggregation in vitro. PREP enzyme inhibitors have been shown to block the alpha-synuclein aggregation process in vitro and in cellular models, and also to enhance the clearance of alpha-synuclein aggregates in transgenic mouse models. Moreover, PREP inhibitors have induced alterations in dopamine and metabolite levels, and dopamine transporter immunoreactivity in the nigrostriatal tissue. In this study, we characterized the role of PREP in the nigrostriatal dopaminergic and GABAergic systems of wild-type C57Bl/6 and PREP knockout mice, and the effects of PREP overexpression on these systems. Extracellular concentrations of dopamine and protein levels of phosphorylated dopamine transporter were increased and dopamine reuptake was decreased in the striatum of PREP knockout mice, suggesting increased internalization of dopamine transporter from the presynaptic membrane. Furthermore, PREP overexpression increased the level of dopamine transporters in the nigrostriatal tissue but decreased phosphorylated dopamine transporters in the striatum in wild-type mice. Our results suggest that PREP regulates the function of dopamine transporter, possibly by controlling the phosphorylation and transport of dopamine transporter into the striatum or synaptic membrane.Peer reviewe

Muutosjohtamisen keinot henkilöstön tukena organisaatiomuutoksessa

Laitoshoidon purkaminen ja organisaation palvelurakenteen muuttuminen vaikuttavat työelämään niin työyhteisön kuin esimiestenkin kannalta. Pohjois-Karjalan sairaanhoito- ja sosiaalipalvelujen kuntayhtymässä haluttiin kehittää sosiaalipalvelujen esihenkilöiden muutosjohtamista. Tämän opinnäytetyön tarkoitus oli kehittää Pohjois-Karjalan sairaanhoito- ja sosi-aalipalvelujen kuntayhtymän sosiaalipalvelujen esihenkilöille muutosjohtamisen suunnitelma. Aluksi tutkittiin hoitohenkilöstön mielipidettä siitä, millaista tukea he kokevat tarvitsevansa esihenkilöltä organisaatiomuutoksessa. Tutkimus toteutettiin järjestämällä hoitohenkilöstölle avoimia muutospajoja syksyllä 2013 ja keväällä 2014. Muutospajoihin osallistui yhteensä 89 henkilöä. Muutospajat toteutettiin Learning cafe -menetelmällä, ja tutkimustulosten pohjalta kehitettiin esihenkilöille muutosjohtamisen suunnitelma, joka liitettiin osaksi esihenkilöiden kehittämissuunnitelmaa. Muutosjohtamisen keinot, jotka tukevat hoitohenkilöstöä organisaatiomuutokses-sa, ovat dialogiseen johtamiseen liittyviä. Hoitohenkilöstö odottaa esihenkilöltä hyvää tiedottamista, keskustelua, ja tukea yhteisöllisyyteen.Dismantling of institutional care and the changes in the organisation's service structure affects the working life from the standpoint of the work community as well as the superiors. The Joint Municipal Authority for Medical and Social Services in North Karelia wanted to improve change management among superiors in Social Services. The aim of this study was to develop a model of change management for the supervisory personnel employed in Social Services at North Karelia Central Hospital and Honkalampi Centre. At first, the nursing staff was interviewed and asked what kind of support they need from their superiors during the change process. The survey was carried out by organising change workshops open to all in autumn 2013 and spring 2014. Altogether 89 persons participated in the workshops. The change workshops were carried out by using the Learning Cafe method. On the basis of the results, a model of change management was developed for the supervisory personnel and added into their development plan. The means of change management that support nursing staff through organisational change are connected with dialogic management. The nursing staff expects the supervisor to disseminate information effectively, engage in conversations and support the sense of community. In a further research, change management could be studied and developed from the perspective of the supervisory personnel by applying resource-oriented approach

Health Promotion Interventions:Lessons from the Transfer of Good Practices in CHRODIS-PLUS

Health promotion and disease prevention often take the form of population- and individual-based interventions that aim to reduce the burden of disease and associated risk factors. There is a wealth of programs, policies, and procedures that have been proven to work in a specific context with potential to improve the lives and quality of life for many people. However, the challenge facing health promotion is how to transfer recognized good practices from one context to another. We present findings from the use of the implementation framework developed in the Joint Action project CHRODIS-PLUS to support the transfer of health promotion interventions for children’s health and older adults identified previously as good practices. We explore the contextual success factors and barriers in the use of an implementation framework in local contexts and the protocol for supporting the implementation. The paper concludes by discussing the key learning points and the development of the next steps for successful transfer of health promotion interventions

Omaehtoisen muistamisen materiaalisuus ja monimediaisuus : muistitietotutkimus ja uusmaterialismi

Peer reviewe

Omaehtoisen muistamisen materiaalisuus ja monimediaisuus: Muistitietotutkimus ja uusmaterialismi

Artikkelissa tarkastellaan muistelun materiaalisuutta, monimediaisuutta sekä medioiden yhteistoimintaa ja tarjoumia (affordance) kolmen tapausesimerkin kautta, jotka kaikki edustavat omaehtoista muistamista. Tämän lisäksi artikkelissa sovelletaan väljästi uusmaterialismin teorioita omaehtoisen muistamisen tutkimukseen. Artikkelissa kysytään ensinnäkin, mitä muistelun materiaalisuus ja monimediaisuus tarkoittaa? Toiseksi kysytään, minkälaisia merkityksiä muistamisen medioiden yhteistoiminnan ja tarjoumien analyysi tuo esiin omaehtoisesta muistelusta ja historian tuottamisesta? Artikkelin tavoitteena on myös pohtia, mitä uusia näkökulmia uusmaterialismin teoriat avaavat muistitietotutkimukselle ja sitä kautta monipuolistaa suomalaisen muistitietotutkimuksen piirissä käytyjä, voimakkaasti muistelun kielelliseen ja kerronnalliseen ulottuvuuden keskittyviä keskusteluja.</p

Sanidad pone en marcha dos importantes iniciativas para fomentar en nuestro país la investigación sobre las enfermedades raras, los medicamentos huérfanos y la investigación independiente

Nota de prensa sobre dos importantes iniciativas para fomentar en nuestro país la investigación sobre las enfermedades raras, los medicamentos huérfanos y la investigación independiente que propone Sanidad.Las enfermedades raras afectan en su conjunto a entre el 6 y el 8% de la población, es decir, entre 24 y 36 millones de personas en Europa y aproximadamente tres millones en España.Sin embargo, el reducido número de pacientes de cada una de las entre 5.000 y 8.000 enfermedades raras identificadas hasta el momento hace que la industria farmacéutica no siempre pueda dedicar los fondos necesarios para investigar fármacos para estas patologías, debido a que no son rentables en términos económicos.Por ello, y para ofrecer una respuesta a estos pacientes desde los sistemas sanitarios públicos, la investigación sobre este tipo de patologías se ha convertido en una prioridad en la Unión Europea y el Ministerio de Sanidad y Consumo quiere dar un fuerte impulso a estos programas en el Sistema Nacional de Salud. Sanidad va a convocar en enero un nuevo programa de ayudas para la promoción de la investigación independiente, dotado con 20 millones de euros, que contribuirá a que los científicos puedan trabajar en el campo de los medicamentos huérfanos y otras áreas prioritarias con fondos públicos.Además, se ha procedido a la constitución del Centro de Investigación Biomédica en Red (CIBER) de enfermedades raras, integrado por 467 investigadores y dotado con 6,2 millones de euros para 2006, que servirá para aumentar el conocimiento de estas enfermedades

Early-life residential exposure to moisture damage is associated with persistent wheezing in a Finnish birth cohort

Background and Aims Moisture damage increases the risk for respiratory disorders in childhood. Our aim was to determine whether early age residential exposure to inspector-observed moisture damage or mold is associated with different wheezing phenotypes later in childhood. Methods Building inspections were performed by civil engineers, in a standardized manner, in the children's homes-mostly single family and row houses (N = 344)-in the first year of life. The children were followed up with repeated questionnaires until the age of 6 years and wheezing phenotypes-never/infrequent, transient, intermediate, late onset, and persistent-were defined using latent class analyses. The multinomial logistic regression model was used for statistical analysis. Results A total of 63% (n = 218) had infrequent or no wheeze, 23% (n = 80) had transient and 9.6% (n = 21) had a persistent wheeze. Due to the low prevalence, results for intermediate (3.8%, n = 13) and late-onset wheeze (3.5%, n = 12) were not further evaluated. Most consistent associations were observed with the persistent wheeze phenotype with an adjusted odds ratio (95% confidence intervals) 2.04 (0.67-6.18) for minor moisture damage with or without mold spots (present in 23.8% of homes) and 3.68 (1.04-13.05) for major damage or any moisture damage with visible mold in a child's main living areas (present in 13.4% of homes). Early-age moisture damage or mold in the kitchen was associated with transient wheezing. Conclusion At an early age, residential exposure to moisture damage or mold, can be dose-dependently associated especially with persistent wheezing phenotype later in childhood.Peer reviewe

Time variability of the core-shift effect in the blazar 3C 454.3

Using VLBI to measure a so-called core shift effect is a common way of obtaining estimates of the jet magnetic field strength. The VLBI core is typically identified as the bright feature at the jet's base, and the position of the core changes with the observed frequency, $r_\mathrm{core} \propto \nu^{-1/k_r}$. In this work, we investigated the time variability of the core-shift effect in the blazar 3C 454.3. We employed self-referencing analysis of multi-frequency (5, 8, 15, 22-24, and 43 GHz) VLBA data covering 19 epochs from 2005 until 2010. We found significant core shift variability ranging from 0.27 to 0.86 mas between 5 and 43 GHz, confirming the core-shift variability phenomenon observed before. Time variability of the core-shift index ($k_r$) was found typically below one, with an average value of $0.85 \pm 0.08$ and a standard deviation of $0.30$. $k_r<1$ values were found during flaring and quiescent states and our results indicate that commonly assumed conical jet shape and equipartition conditions do not always hold simultaneously. Still, these conditions are often assumed when deriving magnetic field strengths from core shift measurements, leading to unreliable results if $k_r$ significantly deviates from unity. Therefore, it is important to verify that $k_r = 1$ holds before using core shift values and the equipartition assumption to derive physical parameters in the jets. When $k_r = 1$ epochs are selected in the case of 3C 454.3, the magnetic field estimates are indeed quite consistent, even though the core shift varies with time. Additionally, our estimations of the jet's magnetic flux in 3C 454.3 show that the source is indeed in the magnetically arrested disk state. Finally, we found a good correlation of the core position with the core flux density, $r_\mathrm{core}\propto S_\mathrm{core}^{0.7}$, which is consistent with increased particle density during the flares.Comment: 53 pages, 6 tables, 57 figures. Article submitted to Astronomy and Astrophysic