Research resource: the dynamic transcriptional profile of sertoli cells during the progression of spermatogenesis.

Sertoli cells (SCs), the only somatic cells within seminiferous tubules, associate intimately with developing germ cells. They not only provide physical and nutritional support but also secrete factors essential to the complex developmental processes of germ cell proliferation and differentiation. The SC transcriptome must therefore adapt rapidly during the different stages of spermatogenesis. We report comprehensive genome-wide expression profiles of pure populations of SCs isolated at 5 distinct stages of the first wave of mouse spermatogenesis, using RNA sequencing technology. We were able to reconstruct about 13 901 high-confidence, nonredundant coding and noncoding transcripts, characterized by complex alternative splicing patterns with more than 45% comprising novel isoforms of known genes. Interestingly, roughly one-fifth (2939) of these genes exhibited a dynamic expression profile reflecting the evolving role of SCs during the progression of spermatogenesis, with stage-specific expression of genes involved in biological processes such as cell cycle regulation, metabolism and energy production, retinoic acid synthesis, and blood-testis barrier biogenesis. Finally, regulatory network analysis identified the transcription factors endothelial PAS domain-containing protein 1 (EPAS1/Hif2α), aryl hydrocarbon receptor nuclear translocator (ARNT/Hif1β), and signal transducer and activator of transcription 1 (STAT1) as potential master regulators driving the SC transcriptional program. Our results highlight the plastic transcriptional landscape of SCs during the progression of spermatogenesis and provide valuable resources to better understand SC function and spermatogenesis and its related disorders, such as male infertility.

The resource-based view of the firm - resources, capabilities and sustainable competitive advantage

The main objective of this research paper was to synthesize, integrate and analyze the theoretical foundation of the resource-based view of the firm on sustainable competitive advantage. Accordingly, this research was a literature research employing the methodology of interpretative study of concept and unobtrusive measures. The core and majority of the research data was gathered from the major online journal databases. Only peer-reviewed articles from highly-esteemed journals on the subject of competitive advantage were used. The theoretical core of the research paper was centred on resources, capabilities, and the sustainability dilemma of competitive advantage. Furthermore, other strategic management concepts relating to the resource-based view of the firm were used with reference to the research objectives. The resource-based view of the firm continues to be a controversial but important are of strategic management research on sustainable competitive advantage. Consequently, the theoretical foundation and the empirical testing of the framework needs further work. However, it is evident that internal organizational factors in the form of resources and capabilities are vital for the formation of sustainable competitive advantage. Resources and capabilities are not, however, valuable on their own - competitive advantage requires seamless interplay and complementarity between bundles of resources and capabilities.

Concentrative nucleoside transporter 1 (hCNT1) promotes phenotypic changes relevant to tumor biology in a translocation independent manner

Nucleoside transporters (NTs) mediate the uptake of nucleosides and nucleobases across the plasma membrane, mostly for salvage purposes. The canonical NTs belong to two gene families, SLC29 and SLC28. The former encode equilibrative nucleoside transporter proteins (ENTs), which mediate the facilitative diffusion of natural nucleosides with broad selectivity, whereas the latter encode concentrative nucleoside transporters (CNTs), which are sodium-coupled and show high affinity for substrates with variable selectivity. These proteins are expressed in most cell types, exhibiting apparent functional redundancy. This might indicate that CNTs play specific roles in the physiology of the cell beyond nucleoside salvage. Here, we addressed this possibility using adenoviral vectors to restore tumor cell expression of hCNT1 or a polymorphic variant (hCNT1S546P) lacking nucleoside translocation ability. We found that hCNT1 restoration in pancreatic cancer cells significantly altered cell-cycle progression and phosphorylation status of key signal-transducing kinases, promoted poly-(ADP ribose) polymerase hyperactivation and cell death, and reduced tumor growth and cell migration. Importantly, the translocation-defective transporter triggered these same effects on cell physiology. These data predict a novel and totally unexpected biological role for the nucleoside transporter protein hCNT1 that appears to be independent of its role as mediator of nucleoside uptake by cells, thereby suggesting a transceptor function. Cell Death & Disease Anastasis Stephanou Receiving Editor Cell Death & Disease 19th Apr 2013 Dr Perez-Torras Av/ Diagonal 643. Edif. Prevosti, Pl -1 Barcelona 08028 Spain RE: Manuscript CDDIS-13-0136R, 'CDDIS-13-0136R' Dear Dr Perez-Torras, It is a pleasure to inform you that your manuscript has been evaluated at the editorial level and has now been officially accepted for publication in Cell Death & Disease, pending you meet the following editorial requirements: 1) the list of the abbreviations is missing please include Could you send us the revised text as word file via e-mail and we will proceed and transfer the paper onto our typesetters. Please download, print, sign, and return the Licence to Publish Form using the link below. This must be returned via FAX to ++ 39 06 7259 6977 before your manuscript can be published:

Universities as an Insourcing Resource in R&D Operations

Tutkimuksen tavoitteena on arvioida ja analysoida yliopistojen ja yritysten välistä yhteistyötä tutkimus- ja kehitystoiminnassa. Teoriapohjan ja kohdeyrityksen case esimerkin avulla on tarkoitus selvittää kriittiset tekijät yhteistyössä sekä rakentaa tulosten perusteella viitekehys näiden kahden osapuolen yhteistyön onnistumiseksi. Teoriatausta käsittelee osapuolten tärkeimpiä strategioita yhteistyön kannalta, yhteistyön yleisiä ominaisuuksia, vuorovaikutussuhteita niin ympäristöön, toimintoihin kuin osapuoliinkin. Teoriaosuus tukee empiiristä tutkimusta, jossa perehdytään yhteen kansalliseen 3G projektiin Soneran ja Jyväskylän yliopiston välillä. Yrityksen ja yliopiston välinen yhteistyö on hyvin yleistä Suomessa. Motivoivia tekijöitä ovat muun muassa Tekesin kannustava rahoitus ja yhteistyön edullisuus, osapuolten keskittyminen omaan ydinosaamiseensa, tiedon tuotteistuksen ja uusien teorioiden luomisen mahdollisuus, positiiviset vaikutukset markkina-arvoon, imagolliset tekijät sekä varautuminen tulevaisuuden trendeihin.

Radio Resource Management across UMTS Radio Network Subsystems

UMTS (Universal Mobile Telecommunication System), esimerkkinä kolmannen sukupolven matkapuhelinjärjestelmästä pyrkii toistamaan GSM:n (Global System for Mobile Communications) menestyksen. UMTS:n kaupallinen toiminta on parhaillaan alkamassa ja ensimmäinen kaupallinen verkko on jo aloittanut toimintansa Japanissa. Tämä diplomityö antaa yleiskuvan UMTS:stä keskittyen radioverkkojärjestelmän (UMTS Terrestrial Radio Access Network,UTRAN) radioresurssien hallintaan (Radio Resource Management, RRM). Työssä kuvataan radiorajapintojen toimintaa, mutta diplomityön pääaiheena on kuitenkin radioresurssien hallinta UMTS radioaliverkkojärjestelmien ylitse. Radioresurssien hallinta pitää sisällään joukon proseduureja, jotka vaikuttavat koko UTRAN:in rakenteen lävitse. On hyvin tärkeää saavuttaa oikea toiminnallisuus hajautettujen radioresurssien hallintaan jotta voitaisiin saavuttaa paras yhteyden laatu loppukäyttäjälle. Työssä käydään yksityiskohtaisesti lävitse radioresurssien hallinnan perusperiaatteet ja joukko proseduureja. RNSAP (Radio Network Subsystem Application Part) protokollaa tarkastellaan työssä esimerkkinä protokollasta joka osallistuu radioresurssien hallintaprosessiin.

Transport Resource Management within UMTS Radio Network Subsystem

Tällä hetkellä haastavin telekommunikaatioteollisuuden tutkimus – ja kehitystoiminta on keskittynyt kolmannen sukupolven matkapuhelinjärjestelmien ympärille. Järjestelmien standardointityössä on saatu aikaiseksi ensimmäiset vakaat spesifikaatioversiot ja kaupallista toimintaa ollaan parhaillaan aloittelemassa Japanissa ja Euroopassa. Eräs kolmannen sukupolven järjestelmistä on UMTS (Universal Mobile Telecommunications System). Tämä diplomityö antaa yleiskuvan UMTS järjestelmästä ja sen eri verkkoelementtien toiminnallisuuksista. Päähuomio on kiinnitetty radioverkkojärjestelmään (UMTS Terrestrial Radio Access Network) ja erityisesti sen radioaliverkkojärjestelmään (Radio Network Subsystem), joka koostuu radioverkonohjaimesta (Radio Network Controller) ja joukosta siihen kuuluvia tukiasemia (Node B). Radioverkonohjain ja tukiasemat on yhdistetty avoimen rajapinnan kautta jota kutsutaan Iub -rajapinnaksi. Rajapinta tarjoaa radioverkonohjaimelle mahdollisuuden kontrolloida tukiasemia signalointiviestien avulla ja mahdollistaa tehokkaan ja luotettavan käyttäjätiedon siirron radioaliverkkojärjestelmän sisällä. Tämän diplomityön pääasiallinen sisältö on siirtoresurssien hallinta Iub -rajapinnan ylitse. Työssä esitellään ja selitetään siirtoverkon arkkitehtuuri. Myös kaikki Iub:ssä sijaitsevat protokollat ja toiminnalliset yksiköt jotka vaikuttavat siirtoresurssien hallintaan esitellään ja kuvataan yksityiskohtaisesti. Päähuomio on kiinnitetty sovellusprotokolliin sekä rajapinnan siirtoverkko- että radioverkkokerroksella sekä näiden protokollien väliseen vuorovaikutukseen. Kyseiset protokollat ovat Node B Application Part (NBAP) ja Access Link Control Application Part (ALCAP). Työn toteutusosassa käydään lävitse NBAP –protokollan prototyypin ja Node B Manager –toiminnallisen yksikön prototyypin implementaatio.

Success Factors of an Enterprise Resource Planning System

Työn tarkoituksena oli tutkia yrityksen eri yksiköiden toiminnaohjausjärjestelmiä sekä verrata niiden menestystekijöitä Adelakunin malliin tietojärjestelmien laatuulottuvuuksista. Siinä järjestelmän kokonaislaatu jaetaan liiketoiminnalliseen, tekniseen ja käyttäjän kokemaan laatuun. Tulosten perusteella oli myös tavoitteena kehittää kyseisen toiminnanojausjärjestelmän kehittämistä varten malli onnistumistekijöiden keskinäisestä riippuvuudesta. Tutkittavista järjestelmistä ja niiden käytöstä kerättiin tietoja käyttöönottoprojektien dokumentaatiosta, haastatteluin, kyselylomakkein ja järjestelmäanalyysein. Sekä loppukäyttäjät että yritysjohto olivat kyselyjen ja haastattelujen kohderyhmänä. Saatuja tietoja arvioitiin Adelakunin kolmiulotteisen tietojärjestelmän laatutekijämallin mukaisesti ja keskeisiä menestystekijöitä etsittiin. Tutkituissa tapauksissa tietojärjestelmien menestyksen taustalta löytyi alan kirjallisuuden kanssa yhtäpitäviä tekijöitä. Myös Adelakunin laatu-ulottuvuusmalli osoittautui validiksi tutkituissa tapauksissa. Keskeisten menestystekijöiden välisistä vuorovaikutussuhteista rakennettiin malli, jota voidaan hyödyntää kyseisen järjestelmän jatkokehityksessä.

Short stature and primary ovarian insufficiency possibly due to chromosomal position effect in a balanced X;1 translocation.

BACKGROUND: Primary ovarian insufficiency (POI) is defined as a primary ovarian defect characterized by absent menarche (primary amenorrhea), a decrease in the initial primordial follicle number, high follicle-stimulating hormone (FSH) levels and hypoestrogenism. Although the etiology of a majority of POI cases is not yet identified, several data suggest that POI has a strong genetic component. Conventional cytogenetic and molecular analyses have identified regions of the X chromosome that are associated with ovarian function, as well as POI candidate genes, such as FMR1 and DIAPH2. Here we describe a 10.5-year-old girl presenting with high FSH and luteinizing hormone (LH) levels, pathologic GH stimulation arginine and clonidine tests, short stature, pterygium, ovarian dysgenesis, hirsutism and POI. RESULTS: Cytogenetic analysis demonstrated a balanced reciprocal translocation between the q arms of chromosomes X and 1, with breakpoints falling in Xq21 and 1q41 bands. Molecular studies did not unravel any chromosome microdeletion/microduplication, and no XIST-mediated inactivation was found on the derivative chromosome 1. Interestingly, through immunofluorescence assays, we found that part of the Xq21q22 trait, translocated to chromosome 1q41, was late replicating and therefore possibly inactivated in 30 % metaphases both in lymphocytes and skin fibroblasts, in addition to a skewed 100 % inactivation of the normal X chromosome. These findings suggest that a dysregulation of gene expression might occur in this region. Two genes mapping to the Xq translocated region, namely DIAPH2 and FMR1, were found overexpressed if compared with controls. CONCLUSIONS: We report a case in which gonadal dysgenesis and POI are associated with over-expression of DIAPH2 gene and of FMR1 gene in wild type form. We hypothesize that this over-expression is possibly due to a phenomenon known as "chromosomal position effect", which accounts for gene expression variations depending on their localization within the nucleus. For the same effect a double mosaic inactivation of genes mapping to the Xq21-q22 region, demonstrated by immunofluorescence assays, may be the cause of a functional Xq partial monosomy leading to most Turner traits of the proband's phenotype.

Endovascular treatment of pulmonary arteriovenous malformations in hereditary haemorrhagic telangiectasia.

PRINCIPLES: To assess the efficiency and complication rates of vaso-occlusion of pulmonary arteriovenous malformations (PAVMs) in Rendu-Osler-Weber disease (hereditary haemorrhagic telangectasia; HHT). METHODS: Seventy-two patients were investigated in our institution for HHT between March 2000 and November 2011. Sixteen presented PAVMs (22.2%), and 11 (68.8%) were treated with vaso-occlusion for a total of 18 procedures. Procedures included coils, plugs and combined approaches. Immediate success and recurrence rate, complication were recorded, as well as persistent and new PAVMs during clinical and computed tomography (CT) follow-up. RESULTS: Eighteen procedures were performed and a total of 37 PAVMs were treated, 19 with coils, 16 with plugs and 2 with combined treatment. Mean CT follow-up time was 41 months (1‒164). No major complication was observed. One distal translocation was treated during the same intervention. Two PAVMs persisted after treatment (5.7%), both treated by means of plug embolisation. One new PAVM was observed during follow-up CT. PAVMs with an afferent artery of less than 3mm or asymptomatic PAVMs were not treated. CONCLUSION: Recent studies have demonstrated that vaso-occlusion has become the gold standard treatment for PAVM. This study is in accordance with previous results and shows a minimal complication rate and little recurrence, whether by coils, plugs, or combined treatments.

Peatlands and plantations in Sumatra, Indonesia : Complex realities for resource governance, rural development and climate change mitigation

Peatlands play a crucial role in Indonesia's economic development, and in its stated goal of reducing greenhouse gas emissions. Improved peatland management - including a national moratorium on the granting of any new conversion licenses - forms a cornerstone of Indonesia's climate change mitigation commitment. At the same time, rapid expansion of the plantation sector is driving wide-scale drainage and conversion of peat swamp ecosystems. The province of Riau, in central Sumatra, finds itself at the crossroads of these conflicting agendas. This essay presents a case study of three islands on Riau's east coast affected by industrial timber plantation concessions. It examines the divergent experiences, perceptions and responses of communities on the islands. A mix of dramatic protests, localised everyday actions and constructive dialogue has succeeded in delaying or perhaps halting one of the concessions, while negotiations and contestation with the other two continue. With the support of regional and national non-governmental organisations and local government, communities are pursuing alternative development strategies, including the cultivation of sago, which requires no peat drainage. While a powerful political economy of state and corporate actors shapes the contours of socio-environmental change, local social movements can alter trajectories of change, promoting incremental improvements and alternative pathways.

Hope as a Resource for Career Exploration : Examining Incremental and Cross-Lagged Effects

Hope is believed to be beneficial for vocational pursuits, but the question of how and why hope is related to pivotal career development variables remains largely unaddressed. In a series of three studies,we investigated the relationship between hope and career exploration. Study 1 examined at-risk adolescents (N = 228) in Switzerland and showed that hope explains variance in career exploration beyond the significant effects of generalized self-efficacy beliefs and perceived social support. Study 2 found the same result among a group (N=223) of first-year students at a Swiss university with a measure of state hope. Study 3 applied a one-year cross-lagged design with a diverse group of students (N = 266) at a German university to investigate the mutual effects of dispositional hope and career exploration over time. Although both variables were found to be related within and over time, we could not confirm lagged effects in either direction. The results suggest that hope is significantly correlated with career exploration because both are related to personality and social-contextual variables.