A Novel Recombinant Peste des Petits Ruminants-Canine Adenovirus Vaccine Elicits Long-Lasting Neutralizing Antibody Response against PPR in Goats

BACKGROUND: Peste des petits ruminants (PPR) is a highly contagious infectious disease of goats, sheep and small wild ruminant species with high morbidity and mortality rates. The Peste des petits ruminants virus (PPRV) expresses a hemagglutinin (H) glycoprotein on its outer envelope that is crucial for viral attachment to host cells and represents a key antigen for inducing the host immune response. METHODOLOGY/PRINCIPAL FINDINGS: To determine whether H can be exploited to generate an effective PPRV vaccine, a replication-competent recombinant canine adenovirus type-2 (CAV-2) expressing the H gene of PPRV (China/Tibet strain) was constructed by the in vitro ligation method. The H expression cassette, including the human cytomegalovirus (hCMV) promoter/enhancer and the BGH early mRNA polyadenylation signal, was inserted into the SspI site of the E3 region, which is not essential for proliferation of CAV-2. Infectious recombinant rCAV-2-PPRV-H virus was generated in transfected MDCK cells and used to immunize goats. All vaccinated animals produced antibodies upon primary injection that were effective in neutralizing PPRV in vitro. Higher antibody titer was obtained following booster inoculation, and the antibody was detectable in goats for at least seven months. No serious recombinant virus-related adverse effect was observed in immunized animals and no adenovirus could be isolated from the urine or feces of vaccinated animals. Results showed that the recombinant virus was safe and could stimulate a long-lasting immune response in goats. CONCLUSIONS/SIGNIFICANCE: This strategy not only provides an effective PPR vaccine candidate for goats but may be a valuable mean by which to differentiate infected from vaccinated animals (the so-called DIVA approach)

Growth regulation of simian and human AIDS-related non-Hodgkin's lymphoma cell lines by TGF-β1 and IL-6

BACKGROUND: AIDS-related non-Hodgkin's lymphoma (AIDS-NHL) is the second most frequent cancer associated with AIDS, and is a frequent cause of death in HIV-infected individuals. Experimental analysis of AIDS-NHL has been facilitated by the availability of an excellent animal model, i.e., simian Acquired Immunodeficiency Syndrome (SAIDS) in the rhesus macaque consequent to infection with simian immunodeficiency virus. A recent study of SAIDS-NHL demonstrated a lymphoma-derived cell line to be sensitive to the growth inhibitory effects of the ubiquitous cytokine, transforming growth factor-beta (TGF-beta). The authors concluded that TGF-beta acts as a negative growth regulator of the lymphoma-derived cell line and, potentially, as an inhibitory factor in the regulatory network of AIDS-related lymphomagenesis. The present study was conducted to assess whether other SAIDS-NHL and AIDS-NHL cell lines are similarly sensitive to the growth inhibitory effects of TGF-beta, and to test the hypothesis that interleukin-6 (IL-6) may represent a counteracting positive influence in their growth regulation. METHODS: Growth stimulation or inhibition in response to cytokine treatment was quantified using trypan blue exclusion or colorimetric MTT assay. Intracellular flow cytometry was used to analyze the activation of signaling pathways and to examine the expression of anti-apoptotic proteins and distinguishing hallmarks of AIDS-NHL subclass. Apoptosis was quantified by flow cytometric analysis of cell populations with sub-G1 DNA content and by measuring activated caspase-3. RESULTS: Results confirmed the sensitivity of LCL8664, an immunoblastic SAIDS-NHL cell line, to TGF-beta1-mediated growth inhibition, and further demonstrated the partial rescue by simultaneous treatment with IL-6. IL-6 was shown to activate STAT3, even in the presence of TGF-beta1, and thereby to activate proliferative and anti-apoptotic pathways. By comparison, human AIDS-NHL cell lines differed in their responsiveness to TGF-beta1 and IL-6. Analysis of a recently derived AIDS-NHL cell line, UMCL01-101, indicated that it represents immunoblastic AIDS-DLCBL. Like LCL-8664, UMCL01-101 was sensitive to TGF-beta1-mediated inhibition, rescued partially by IL-6, and demonstrated rapid STAT3 activation following IL-6 treatment even in the presence of TGF-beta1. CONCLUSION: These studies indicate that the sensitivity of immunoblastic AIDS- or SAIDS-DLBCL to TGF-beta1-mediated growth inhibition may be overcome through the stimulation of proliferative and anti-apoptotic signals by IL-6, particularly through the rapid activation of STAT3

Tubulin Tyrosination Is Required for the Proper Organization and Pathfinding of the Growth Cone

International audienceBACKGROUND: During development, neuronal growth cones integrate diffusible and contact guidance cues that are conveyed to both actin and microtubule (MT) cytoskeletons and ensure axon outgrowth and pathfinding. Although several post-translational modifications of tubulin have been identified and despite their strong conservation among species, their physiological roles during development, especially in the nervous sytem, are still poorly understood. METHODOLOGY/FINDINGS: Here, we have dissected the role of a post-translational modification of the last amino acid of the alpha-tubulin on axonal growth by analyzing the phenotype of precerebellar neurons in Tubulin tyrosin ligase knock-out mice (TTL(-/-)) through in vivo, ex vivo and in vitro analyses. TTL(-/-) neurons are devoid of tyrosinated tubulin. Their pathway shows defects in vivo, ex vivo, in hindbrains open-book preparations or in vitro, in a collagen matrix. Their axons still orient toward tropic cues, but they emit supernumerary branches and their growth cones are enlarged and exhibit an emission of mis-oriented filopodia. Further analysis of the TTL(-/-) growth cone intracellular organization also reveals that the respective localization of actin and MT filaments is disturbed, with a decrease in the distal accumulation of Myosin IIB, as well as a concomitant Rac1 over-activation in the hindbrain. Pharmacological inhibition of Rac1 over-activation in TTL(-/-) neurons can rescue Myosin IIB localization. CONCLUSIONS/SIGNIFICANCE: In the growth cone, we propose that tubulin tyrosination takes part in the relative arrangement of actin and MT cytoskeletons, in the regulation of small GTPases activity, and consequently, in the proper morphogenesis, organization and pathfinding of the growth cone during development

A systematic review evaluating the psychometric properties of measures of social inclusion

Introduction: Improving social inclusion opportunities for population health has been identified as a priority area for international policy. There is a need to comprehensively examine and evaluate the quality of psychometric properties of measures of social inclusion that are used to guide social policy and outcomes. Objective: To conduct a systematic review of the literature on all current measures of social inclusion for any population group, to evaluate the quality of the psychometric properties of identified measures, and to evaluate if they capture the construct of social inclusion. Methods: A systematic search was performed using five electronic databases: CINAHL, PsycINFO, Embase, ERIC and Pubmed and grey literature were sourced to identify measures of social inclusion. The psychometric properties of the social inclusion measures were evaluated against the COSMIN taxonomy of measurement properties using pre-set psychometric criteria. Results: Of the 109 measures identified, twenty-five measures, involving twenty-five studies and one manual met the inclusion criteria. The overall quality of the reviewed measures was variable, with the Social and Community Opportunities Profile-Short, Social Connectedness Scale and the Social Inclusion Scale demonstrating the strongest evidence for sound psychometric quality. The most common domain included in the measures was connectedness (21), followed by participation (19); the domain of citizenship was covered by the least number of measures (10). No single instrument measured all aspects within the three domains of social inclusion. Of the measures with sound psychometric evidence, the Social and Community Opportunities Profile-Short captured the construct of social inclusion best. Conclusions: The overall quality of the psychometric properties demonstrate that the current suite of available instruments for the measurement of social inclusion are promising but need further refinement. There is a need for a universal working definition of social inclusion as an overarching construct for ongoing research in the area of the psychometric properties of social inclusion instruments

Teknologia-alustasta innovaatioekosysteemiksi

Platform businesses are disrupting and transforming industries. With platform businesses, the value creation process shifts from relying on companies’ internal resources to harnessing resources from ecosystems. This kind of new value creation system has been argued to be the key driver for the success of platforms. Technology companies are currently opening some of their boundary resources: the access to some of the functionalities of their key technologies. These open interfaces invite companies to co-create new digital innovations and build their own complementary solutions on top of the key technology. Thus, the innovation ecosystem becomes the most valuable asset for platform companies. However, building an ecosystem is one of the biggest challenges for platform owners. The main questions are 1) how to attract diverse actors to the platform and 2) how to engage them to co-creation of value. Even though platforms have been widely studied in different literature streams, the formation and evolution of innovation ecosystems around platforms have remained unexplored. The motivation for this thesis is to increase the understanding how innovation ecosystems emerge around platforms and how the platform owner can facilitate the co-creation of innovation in its platform. The empirical part of this thesis presents a comparative case study of two innovation ecosystems that are forming around a technology platform. Research data was collected through semi-structured interviews with potential members of the ecosystems and with the representatives of the platform owner organization. Data analysis was conducted in an iterative process that included transcription, coding and categorization of the data as well as comparison of the two cases. Since no previous literature exists specifically on formation of innovation ecosystems around technology platforms, the empirical study is supported with a comprehensive literature review on platforms as well as evolution and management of innovation networks. As a result, this thesis presents new theoretical framework on factors that support the emergence of an innovation ecosystem around a technology platform. The findings suggest that a platform owner should create a clear vision of the platform and industry evolution. In addition, organizational culture that embraces open innovation as well as flexible organizational processes support the collaboration in the ecosystem. Understanding partners’ diverse motivations of joining the ecosystem supports platform owners to design the platform and ecosystem activities as attractive as possible for potential platform contributors. Furthermore, building and managing ecosystem relationships becomes a strategic competence for platform owners, in order to accelerate the early-growth of ecosystems. Thus, in addition to platform design, platform owners should also focus on ecosystem orchestration processes in order to support the value creation and equitable value capture in the ecosystem.Digitaalisten alustojen kehitys on radikaalisti muuttanut kilpailua perinteisillä toimialoilla. Alustat mahdollistavat uudenlaisen arvonluonnin, jossa yritysten fokus siirtyy organisaation omien resurssien koordinoimisesta kokonaisten ekosysteemien resurssien hyödyntämiseen. Tällä hetkellä teknologiayritykset ovatkin avaamassa rajapintojaan yritysten keskeisten teknologioiden ympärille, mikä houkuttelee kolmansia osapuolia luomaan omia komplementaarisia innovaatioitaan alustan päälle. Näin muodostuvista innovaatio- ekosysteemeistä onkin tullut kaikista arvokkain voimavara alustan omistajille. Ekosysteemien rakentaminen on kuitenkin yksi suurimpia haasteita alustojen omistajille. Alustan omistajan tuleekin keskittyä 1) houkuttelemaan erilaisia toimijoita alustalle ja 2) tukemaan toimijoita arvonluonnin yhteiskehittämisessä. Vaikka alustoja on tutkittu laajalti kirjallisuudessa, innovaatioekosysteemien muodostuminen teknologia-alustojen ympärille on tutkimusaiheena uusi ja vaatii lisää tutkimusta. Tämän työn tavoitteena on lisätä ymmärrystä innovaatioekosysteemin muodostumisesta teknologia-alustojen ympärille ja selvittää, miten alustan omistaja voi tukea arvonluontia alustalla. Tutkimuksen empiirinen osuus toteutettiin tapaustutkimuksena, jossa tutkittiin kahden innovaatioekosysteemin muodostumista teknologia-alustan ympärille. Tutkimusaineisto kerättiin haastattelemalla ekosysteemien jäseniä ja alustan omistajaa. Lisäksi havainnointia hyödynnettiin aineistonkeruussa. Datan analysointi toteutettiin iteratiivisena prosessina, johon kuului aineiston litterointi, koodaus, kategorisointi ja ekosysteemien tuloksien vertailu. Koska tutkimusaiheesta ei löytynyt aiempaa kirjallisuutta, tutkimuksen teoriapohjana on laaja kirjallisuuskatsaus alustoista sekä innovaatioverkostojen muodostumisesta ja koordinoinnista. Tutkimuksen tulos on uusi teoreettisen viitekehys tekijöistä, jotka tukevat innovaatioekosysteemin muodostumista teknologia-alustan ympärille. Tulosten mukaan alustan omistajan tulisi luoda selkeä visio alustasta. Lisäksi organisaatiokulttuuri, joka tukee avointa innovaatiota sekä joustavat ja läpinäkyvät prosessit edistävät yhteistyön kehittymistä ekosysteemissä. Potentiaalisten ekosysteemin jäsenten erilaisten motivaatioiden ymmärtäminen puolestaan auttaa alustan omistajaa suunnittelemaan teknologia-alustan ja ekosysteemin aktiviteetit mahdollisimman houkuttelevaksi potentiaalisille jäsenille. Tutkimus osoittaa myös, että ekosysteemin suhteiden luominen ja ylläpitäminen ovat strategisia kyvykkyyksiä. Alustan teknisen arkkitehtuurin lisäksi alustan omistajan tulisi siten myös keskittyä yhteistyön kehittämiseen ekosysteemissä