Extracellular deposition of matrilin-2 controls the timing of the myogenic program during muscle regeneration.

Here, we identify a role for the matrilin-2 (Matn2) extracellular matrix protein in controlling the early stages of myogenic differentiation. We observed Matn2 deposition around proliferating, differentiating and fusing myoblasts in culture and during muscle regeneration in vivo. Silencing of Matn2 delayed the expression of the Cdk inhibitor p21 and of the myogenic genes Nfix, MyoD and Myog, explaining the retarded cell cycle exit and myoblast differentiation. Rescue of Matn2 expression restored differentiation and the expression of p21 and of the myogenic genes. TGF-β1 inhibited myogenic differentiation at least in part by repressing Matn2 expression, which inhibited the onset of a positive-feedback loop whereby Matn2 and Nfix activate the expression of one another and activate myoblast differentiation. In vivo, myoblast cell cycle arrest and muscle regeneration was delayed in Matn2(-/-) relative to wild-type mice. The expression levels of Trf3 and myogenic genes were robustly reduced in Matn2(-/-) fetal limbs and in differentiating primary myoblast cultures, establishing Matn2 as a key modulator of the regulatory cascade that initiates terminal myogenic differentiation. Our data thus identify Matn2 as a crucial component of a genetic switch that modulates the onset of tissue repair.

Multiple processes regulate long-term population dynamics of sea urchins on Mediterranean rocky reefs

We annually monitored the abundance and size structure of herbivorous sea urchin populations (Paracentrotus lividus and Arbacia lixula) inside and outside a marine reserve in the Northwestern Mediterranean on two distinct habitats (boulders and vertical walls) over a period of 20 years, with the aim of analyzing changes at different temporal scales in relation to biotic and abiotic drivers. P. lividus exhibited significant variability in density over time on boulder bottoms but not on vertical walls, and temporal trends were not significantly different between the protection levels. Differences in densities were caused primarily by variance in recruitment, which was less pronounced inside the MPA and was correlated with adult density, indicating density-dependent recruitment under high predation pressure, as well as some positive feedback mechanisms that may facilitate higher urchin abundances despite higher predator abundance. Populations within the reserve were less variable in abundance and did not exhibit the hyper-abundances observed outside the reserve, suggesting that predation effects maybe more subtle than simply lowering the numbers of urchins in reserves. A. lixula densities were an order of magnitude lower than P. lividus densities and varied within sites and over time on boulder bottoms but did not differ between protection levels. In December 2008, an exceptionally violent storm reduced sea urchin densities drastically (by 50% to 80%) on boulder substrates, resulting in the lowest values observed over the entire study period, which remained at that level for at least two years (up to the present). Our results also showed great variability in the biological and physical processes acting at different temporal scales. This study highlights the need for appropriate temporal scales for studies to fully understand ecosystem functioning, the concepts of which are fundamental to successful conservation and management.

A gain-of-function allele of TPC1 activates oxylipin biogenesis after leaf wounding in Arabidopsis.

Jasmonates, potent lipid mediators of defense gene expression in plants, are rapidly synthesized in response to wounding. These lipid mediators also stimulate their own production via a positive feedback circuit, which depends on both JA synthesis and JA signaling. To date, molecular components regulating the activation of jasmonate biogenesis and its feedback loop have been poorly characterized. We employed a genetic screen capable of detecting the misregulated activity of 13-lipoxygenase, which operates at the entry point of the jasmonate biosynthesis pathway. Leaf extracts from the Arabidopsis fou2 (fatty acid oxygenation upregulated 2) mutant displayed an increased capacity to catalyze the synthesis of lipoxygenase (LOX) metabolites. Quantitative oxylipin analysis identified less than twofold increased jasmonate levels in healthy fou2 leaves compared to wild-type; however, wounded fou2 leaves strongly increased jasmonate biogenesis compared to wounded wild-type. Furthermore, the plants displayed enhanced resistance to the fungus Botrytis cinerea. Higher than wild-type LOX activity and enhanced resistance in the fou2 mutant depend fully on a functional jasmonate response pathway. The fou2 mutant carries a missense mutation in the putative voltage sensor of the Two Pore Channel 1 gene (TPC1), which encodes a Ca(2+)-permeant non-selective cation channel. Patch-clamp analysis of fou2 vacuolar membranes showed faster time-dependent conductivity and activation of the mutated channel at lower membrane potentials than wild-type. The results indicate that cation fluxes exert strong control over the positive feedback loop whereby JA stimulates its own synthesis.

An induction programme for Bologna first-year bachelor’s degree students in Spain

Introduction. The current study describes the planning process and aims of the university reforms in Spain and suggests an innovative proposal, namely the design and evaluation of a week-long induction programme for first-year bachelor‟s degree students at the University of Lleida (Spain), organised within the European higher education framework. The purpose of this induction programme is to help new students adapt to university life. Method. A total of 102 students and ten lecturers were involved in the study. These participants responded questionnaires and interviews. We contrasted all the results in order to obtain some results that were useful to evaluate the induction programmee which the University introduced in the first four degrees. Results. Findings of the study revealed that participants gave very positive feedback regarding the programme, and the results also highlighted areas which could be improved. Conclusion. The new proposals clearly require a higher level of staff participation to make them work, highlighting the need for appropriate training of university staff and improving coordination with appropriate systems.

Ostoreskontra –moduulin suunnittelu ja toteutus Sähkömies –taloushallinto-ohjelmistoon

Sähkömies -taloushallinto-ohjelmisto on pienille sähköalan yrityksille suunnattu valmisohjelmisto. Se on tarkoitettu tehostamaan talous- ja materiaalihallinnon tehtäviä yrityksessä. Tämän työn tavoitteena oli suunnitella ja toteuttaa ostoreskontra –moduuli Sähkömies –taloushallinto-ohjelmistoon. Ostoreskontra -ominaisuuden lisääminen ohjelmistoon on saanut alkunsa useiden asiakkaiden palautteesta saada automatisoitua yrityksen ostoreskontra -toiminto. Samalla ohjelmistosta saadaan kilpailukykyisempi tuote sähköalalla. Työssä on ensiksi tutkittu ostoreskontran yleistä toimintamallia. Ohjelmiston kehitysprosessissa on sovellettu vesiputous –ohjelmistoprosessimallia. Ostoreskontra –moduulin vaatimukset on määritelty yhdessä avainasiakkaiden kanssa. Ohjelmiston toiminnallisuuden määrittelyssä on käytetty use case –menetelmää. Vaatimusmäärittelyyn ja toiminnalliseen määrittelyyn perustuen on suunniteltu tietokantataulut, käyttöliittymälomakkeet sekä tehty ohjelmamäärittelyt. Ohjelmiston toteutukseen on käytetty Visual Basic –sovelluskehitintä sekä Access 2000 –tietokanta-ohjelmistoa.Työn lopullista onnistumista on vielä aikaista arvioida, koska ohjelmiston ostoreskontra –moduulin sisältävää versiota ei ole vielä toimitettu asiakkaille. Lupaavaa palautetta on kuitenkin tullut projektissa tiiviisti mukana olleilta asiakkailta.

Spontaneous Cdc42 polarization independent of GDI-mediated extraction and actin-based trafficking.

The small Rho-family GTPase Cdc42 is critical for cell polarization and polarizes spontaneously in absence of upstream spatial cues. Spontaneous polarization is thought to require dynamic Cdc42 recycling through Guanine nucleotide Dissociation Inhibitor (GDI)-mediated membrane extraction and vesicle trafficking. Here, we describe a functional fluorescent Cdc42 allele in fission yeast, which demonstrates Cdc42 dynamics and polarization independent of these pathways. Furthermore, an engineered Cdc42 allele targeted to the membrane independently of these recycling pathways by an amphipathic helix is viable and polarizes spontaneously to multiple sites in fission and budding yeasts. We show that Cdc42 is highly mobile at the membrane and accumulates at sites of activity, where it displays slower mobility. By contrast, a near-immobile transmembrane domain-containing Cdc42 allele supports viability and polarized activity, but does not accumulate at sites of activity. We propose that Cdc42 activation, enhanced by positive feedback, leads to its local accumulation by capture of fast-diffusing inactive molecules.

Multiple processes regulate long-term population dynamics of sea urchins on Mediterranean rocky reefs

We annually monitored the abundance and size structure of herbivorous sea urchin populations (Paracentrotus lividus and Arbacia lixula) inside and outside a marine reserve in the Northwestern Mediterranean on two distinct habitats (boulders and vertical walls) over a period of 20 years, with the aim of analyzing changes at different temporal scales in relation to biotic and abiotic drivers. P. lividus exhibited significant variability in density over time on boulder bottoms but not on vertical walls, and temporal trends were not significantly different between the protection levels. Differences in densities were caused primarily by variance in recruitment, which was less pronounced inside the MPA and was correlated with adult density, indicating density-dependent recruitment under high predation pressure, as well as some positive feedback mechanisms that may facilitate higher urchin abundances despite higher predator abundance. Populations within the reserve were less variable in abundance and did not exhibit the hyper-abundances observed outside the reserve, suggesting that predation effects maybe more subtle than simply lowering the numbers of urchins in reserves. A. lixula densities were an order of magnitude lower than P. lividus densities and varied within sites and over time on boulder bottoms but did not differ between protection levels. In December 2008, an exceptionally violent storm reduced sea urchin densities drastically (by 50% to 80%) on boulder substrates, resulting in the lowest values observed over the entire study period, which remained at that level for at least two years (up to the present). Our results also showed great variability in the biological and physical processes acting at different temporal scales. This study highlights the need for appropriate temporal scales for studies to fully understand ecosystem functioning, the concepts of which are fundamental to successful conservation and management.

A cellular system for spatial signal decoding in chemical gradients.

Directional cell growth requires that cells read and interpret shallow chemical gradients, but how the gradient directional information is identified remains elusive. We use single-cell analysis and mathematical modeling to define the cellular gradient decoding network in yeast. Our results demonstrate that the spatial information of the gradient signal is read locally within the polarity site complex using double-positive feedback between the GTPase Cdc42 and trafficking of the receptor Ste2. Spatial decoding critically depends on low Cdc42 activity, which is maintained by the MAPK Fus3 through sequestration of the Cdc42 activator Cdc24. Deregulated Cdc42 or Ste2 trafficking prevents gradient decoding and leads to mis-oriented growth. Our work discovers how a conserved set of components assembles a network integrating signal intensity and directionality to decode the spatial information contained in chemical gradients.

Ammatti-identiteetin rakentuminen sairaanhoitajilla

Ammatti-identiteetti luo pohjan henkilön ammattitaidolle, oman, henkilökohtaisen ammatillisen osaamisen arvostamiselle sekä koko ammattikuvalle, sille millaisena työntekijänä jokainen itsensä näkee. Vahva ammatti-identiteetti aikaansaa positiivisen takaisinkytkennän, kun hyvin tehdyn työn seurauksena saadaan kannustavaa palautetta, mikä kasvattaa itsetuntoa, joka puolestaan luo positiivinen omakuvan, jonka seurauksena syntyy vahva ammatti-identiteetti. Tämän tutkimuksen tarkoituksena on selvittää millä tavoin ammatti-identiteetti rakentuu ja muotoutuu, ja millaisia ovat sitä muovaavat tekijät. Samalla pyritään selvittämään millainen merkitys ammatti-identiteetillä on työn suorittamiseen, työssä viihtymiseen sekä omaan näkemykseen itsestään tietyn alan ammattilaisena. Tutkimuksen kontekstina on terveydenhoitoala, ja empiriassa tutkitaan sairaanhoitajien ammatti-identiteettiä. Tutkimuksen perusteella näyttää siltä, että sairaanhoitajat arvostavat ammattiaan ja ammattitaitoaan huolimatta yhteiskunnallisesta aliarvostuksesta. Tämä tukee käsitystä sairaanhoitajien vahvasta ammatti-identiteetistä. Tutkimuksen tulokset osoittavat, että sairaanhoitajan ammatti-identiteetti on moniulotteinen ilmiö. Ammatti-identiteetti ei ole irrallinen henkilön persoonallisesta identiteetistä, vaan ne tukevat toinen toistaan.

Interleukin-6 and chondrocyte mineralisation act in tandem to promote experimental osteoarthritis.

OBJECTIVES: Basic calcium phosphate (BCP) crystal and interleukin 6 (IL-6) have been implicated in osteoarthritis (OA). We hypothesise that these two factors may be linked in a reciprocal amplification loop which leads to OA. METHODS: Primary murine chondrocytes and human cartilage explants were incubated with hydroxyapatite (HA) crystals, a form of BCP, and the modulation of cytokines and matrix-degrading enzymes assayed. The ability of IL-6 to stimulate chondrocyte calcification was assessed in vitro. The mechanisms underlying the effects of HA on chondrocytes were investigated using chemical inhibitors, and the pathways mediating IL-6-induced calcification characterised by quantifying the expression of genes involved in chondrocyte mineralisation. The role of calcification in vivo was studied in the meniscectomy model of murine OA (MNX), and the link between IL-6 and cartilage degradation investigated by histology. RESULTS: In chondrocytes, BCP crystals stimulated IL-6 secretion, further amplified in an autocrine loop, through signalling pathways involving Syk and PI3 kinases, Jak2 and Stat3 molecules. Exogenous IL-6 promoted calcium-containing crystal formation and upregulation of genes involved in calcification: the pyrophosphate channel Ank, the calcium channel Annexin5 and the sodium/phosphate cotransporter Pit-1. Treatment of chondrocytes with IL-6 inhibitors significantly inhibited IL-6-induced crystal formation. In meniscectomised mice, increasing deposits of BCP crystals were observed around the joint and correlated with cartilage degradation and IL-6 expression. Finally, BCP crystals induced proteoglycan loss and IL-6 expression in human cartilage explants, which were reduced by an IL-6 inhibitor. CONCLUSIONS: BCP crystals and IL-6 form a positive feedback loop leading to OA. Targeting calcium-containing crystal formation and/or IL-6 are promising therapeutic strategies in OA.

CDK4 is an essential insulin effector in adipocytes.

Insulin resistance is a fundamental pathogenic factor that characterizes various metabolic disorders, including obesity and type 2 diabetes. Adipose tissue contributes to the development of obesity-related insulin resistance through increased release of fatty acids, altered adipokine secretion, and/or macrophage infiltration and cytokine release. Here, we aimed to analyze the participation of the cyclin-dependent kinase 4 (CDK4) in adipose tissue biology. We determined that white adipose tissue (WAT) from CDK4-deficient mice exhibits impaired lipogenesis and increased lipolysis. Conversely, lipolysis was decreased and lipogenesis was increased in mice expressing a mutant hyperactive form of CDK4 (CDK4R24C). A global kinome analysis of CDK4-deficient mice following insulin stimulation revealed that insulin signaling is impaired in these animals. We determined that insulin activates the CCND3-CDK4 complex, which in turn phosphorylates insulin receptor substrate 2 (IRS2) at serine 388, thereby creating a positive feedback loop that maintains adipocyte insulin signaling. Furthermore, we found that CCND3 expression and IRS2 serine 388 phosphorylation are increased in human obese subjects. Together, our results demonstrate that CDK4 is a major regulator of insulin signaling in WAT.

Transient shear banding in time-dependent fluids

We study the dynamics of shear-band formation and evolution using a simple rheological model. The description couples the local structure and viscosity to the applied shear stress. We consider in detail the Couette geometry, where the model is solved iteratively with the Navier-Stokes equation to obtain the time evolution of the local velocity and viscosity fields. It is found that the underlying reason for dynamic effects is the nonhomogeneous shear distribution, which is amplified due to a positive feedback between the flow field and the viscosity response of the shear thinning fluid. This offers a simple explanation for the recent observations of transient shear banding in time-dependent fluids. Extensions to more complicated rheological systems are considered.

Sisäinen yrittäjyys ja yksilötason motivaatio

Tutkimuksessa tarkastellaan sisäistä yrittäjyyttä ja motivaatiota yksilön näkökulmasta katsottuna. Tutkimuksen kohteena on Tapiola-ryhmän Kouvolan toimiston henkilökunta. Haastateltavina oli 10 toimihenkilöä. Tutkimuksen aineisto kerättiin puolistrukturoidulla teemahaastattelulla. Tämän kvalitatiivisin menetelmin tehdyn tutkimuksen analysointitapa on ymmärtävä. Tutkimustulokset osoittavat, että henkilökunta on vahvasti sitoutunut työn tekemiseen. Itsenäisiä tavoitteita asetetaan paljon, työstä otetaan vastuuta ja omaa työtä halutaan jatkuvasti kehittää. Näyttää siltä, että motivaatiota sisäiseen yrittäjyyteen vähentävät liian haastavat tavoitteet, usein tapahtuvat muutokset, oman päätösvallan rajallisuus sekä liian vähäinen palautteen määrä. Motivaatio sisäiseen yrittäjyyteen näyttäisi lisääntyvän jos esimerkiksi esimiehiltä tulisi useammin rakentavaa ja postiivista palautetta, sekä työtehtäviä olisi mahdollisuus vaihdella enemmän.

Practical Framework for Monitoring the Performance of Agile IT Projects in an Output-Based Outsourcing Context

Over the past decade, organizations worldwide have begun to widely adopt agile software development practices, which offer greater flexibility to frequently changing business requirements, better cost effectiveness due to minimization of waste, faster time-to-market, and closer collaboration between business and IT. At the same time, IT services are continuing to be increasingly outsourced to third parties providing the organizations with the ability to focus on their core capabilities as well as to take advantage of better demand scalability, access to specialized skills, and cost benefits. An output-based pricing model, where the customers pay directly for the functionality that was delivered rather than the effort spent, is quickly becoming a new trend in IT outsourcing allowing to transfer the risk away from the customer while at the same time offering much better incentives for the supplier to optimize processes and improve efficiency, and consequently producing a true win-win outcome. Despite the widespread adoption of both agile practices and output-based outsourcing, there is little formal research available on how the two can be effectively combined in practice. Moreover, little practical guidance exists on how companies can measure the performance of their agile projects, which are being delivered in an output-based outsourced environment. This research attempted to shed light on this issue by developing a practical project monitoring framework which may be readily applied by organizations to monitor the performance of agile projects in an output-based outsourcing context, thus taking advantage of the combined benefits of such an arrangement Modified from action research approach, this research was divided into two cycles, each consisting of the Identification, Analysis, Verification, and Conclusion phases. During Cycle 1, a list of six Key Performance Indicators (KPIs) was proposed and accepted by the professionals in the studied multinational organization, which formed the core of the proposed framework and answered the first research sub-question of what needs to be measured. In Cycle 2, a more in-depth analysis was provided for each of the suggested Key Performance Indicators including the techniques for capturing, calculating, and evaluating the information provided by each KPI. In the course of Cycle 2, the second research sub-question was answered, clarifying how the data for each KPI needed to be measured, interpreted, and acted upon. Consequently, after two incremental research cycles, the primary research question was answered describing the practical framework that may be used for monitoring the performance of agile IT projects delivered in an output-based outsourcing context. This framework was evaluated by the professionals within the context of the studied organization and received positive feedback across all four evaluation criteria set forth in this research, including the low overhead of data collection, high value of provided information, ease of understandability of the metric dashboard, and high generalizability of the proposed framework.

Asiantuntijan suorituskykyyn vaikuttavien tekijöiden mittaaminen

Tutkimuksen tavoitteena oli tutkia asiantuntijaorganisaation henkilöstön työmotivaatioon vaikuttavia tekijöitä. Konkreettisena tavoitteena oli kehittää asiantuntijaorganisaation olemassa olevaan suorituskykymittaristoon uusia mittareita, joiden avulla yrityksessä pyritään luomaan asiantuntijoille mahdollisimman motivoiva työskentelyilmapiiri. Tutkimus toteutettiin kvalitatiivisena tapaustutkimuksena. Tutkimuksen teoreettisessa osuudessa tutkittiin asiantuntijan työmotivaatioon vaikuttavia tekijöitä sekä aineettoman pääoman mittaamista. Empiirisessä osuudessa tutkittiin pienen asiantuntijaorganisaation työskentelyolosuhteita. Aineistonkeruumenetelmänä toimi vanha tutkimustieto, puolistrukturoidun haastattelun piirteitä omaavat teemahaastattelut sekä tutkijan oma havainnointi. Asiantuntijan motivaatioon vaikuttaa erityisen paljon henkilökohtainen kasvu, autonomisuus, merkityksellinen työ, haasteelliset ja vaihtelevat työtehtävät sekä työstä saatu palaute. Vähemmän merkittäviä motivaattoreita ovat raha, työsuhteen jatkuvuus, ystävälliset työtoverit, kunnioitus ja oikeudenmukainen kohtelu. Urakehitystä asiantuntija ei koe erityisen motivoivana asiana. Tutkimuksen kohdeyrityksen haasteiksi ilmeni erityisesti palautteen antaminen, osaamisen ja koulutuksen johtaminen, autonomian vähyys projektin käyttöönotto vaiheessa sekä työn kuormittavuuden jakautuminen. Uudet mittarisuoritukset kohdeyrityksessä ovat: projektipalautteen antaminen, positiivisen palautteen määrä, projektien edistymispalaverit, projektikatselmukset, suunnittelun tuntiarviot, sisäisten kehitysideoiden toteutuminen, työntekijöiden kuormituksen jakautuminen sekä koulutuksen ja osaamisen jakautuminen.