Virulence and genotype-associated infectivity of interferon-treated macrophages by porcine reproductive and respiratory syndrome viruses.

The polarization into M1 and M2 macrophages (MΦ) is essential to understand MΦ function. Consequently, the aim of this study was to determine the impact of IFN-γ (M1), IL-4 (M2) and IFN-β activation of MΦ on the susceptibility to genotype 1 and 2 porcine reproductive respiratory syndrome (PRRS) virus (PRRSV) strains varying in virulence. To this end, monocyte-derived MΦ were generated by culture during 72h and polarization was induced for another 24h by addition of IFN-γ, IL-4 or IFN-β. MΦ were infected with a collection of PRRSV isolates belonging to genotype 1 and genotype 2. Undifferentiated and M2 MΦ were highly susceptible to all PRRSV isolates. In contrast, M1 and IFN-β activated MΦ were resistant to low pathogenic genotype 1 PRRSV but not or only partially to genotype 2 PRRSV strains. Interestingly, highly virulent PRRSV isolates of both genotypes showed particularly high levels of infection compared with the prototype viruses in both M1 and IFN-β-treated MΦ (P<0.05). This was seen at the level of nucleocapsid expression, viral titres and virus-induced cell death. In conclusion, by using IFN-γ and IFN-β stimulated MΦ it is possible to discriminate between PRRSV varying in genotype and virulence. Genotype 2 PRRSV strains are more efficient at escaping the intrinsic antiviral effects induced by type I and II IFNs. Our in vitro model will help to identify viral genetic elements responsible for virulence, an information important not only to understand PRRS pathogenesis but also for a rational vaccine design. Our results also suggest that monocyte-derived MΦ can be used as a PRRSV infection model instead of alveolar MΦ, avoiding the killing of pigs.

The porcine innate immune system: an update.

Over the last few years, we have seen an increasing interest and demand for pigs in biomedical research. Domestic pigs (Sus scrofa domesticus) are closely related to humans in terms of their anatomy, genetics, and physiology, and often are the model of choice for the assessment of novel vaccines and therapeutics in a preclinical stage. However, the pig as a model has much more to offer, and can serve as a model for many biomedical applications including aging research, medical imaging, and pharmaceutical studies to name a few. In this review, we will provide an overview of the innate immune system in pigs, describe its anatomical and physiological key features, and discuss the key players involved. In particular, we compare the porcine innate immune system to that of humans, and emphasize on the importance of the pig as model for human disease.

The immunology of the porcine skin and its value as a model for human skin.

The porcine skin has striking similarities to the human skin in terms of general structure, thickness, hair follicle content, pigmentation, collagen and lipid composition. This has been the basis for numerous studies using the pig as a model for wound healing, transdermal delivery, dermal toxicology, radiation and UVB effects. Considering that the skin also represents an immune organ of utmost importance for health, immune cells present in the skin of the pig will be reviewed. The focus of this review is on dendritic cells, which play a central role in the skin immune system as they serve as sentinels in the skin, which offers a large surface area exposed to the environment. Based on a literature review and original data we propose a classification of porcine dendritic cell subsets in the skin corresponding to the subsets described in the human skin. The equivalent of the human CD141(+) DC subset is CD1a(-)CD4(-)CD172a(-)CADM1(high), that of the CD1c(+) subset is CD1a(+)CD4(-)CD172a(+)CADM1(+/low), and porcine plasmacytoid dendritic cells are CD1a(-)CD4(+)CD172a(+)CADM1(-). CD209 and CD14 could represent markers of inflammatory monocyte-derived cells, either dendritic cells or macrophages. Future studies for example using transriptomic analysis of sorted populations are required to confirm the identity of these cells.

Npro of classical swine fever virus contributes to pathogenicity in pigs by preventing type I interferon induction at local replication sites

Classical swine fever (CSF) caused by CSF virus (CSFV) is a highly contagious disease of pigs. The viral protein Npro of CSFV interferes with alpha- and beta-interferon (IFN-α/β) induction by promoting the degradation of interferon regulatory factor 3 (IRF3). During the establishment of the live attenuated CSF vaccine strain GPE-, Npro acquired a mutation that abolished its capacity to bind and degrade IRF3, rendering it unable to prevent IFN-α/β induction. In a previous study, we showed that the GPE- vaccine virus became pathogenic after forced serial passages in pigs, which was attributed to the amino acid substitutions T830A in the viral proteins E2 and V2475A and A2563V in NS4B. Interestingly, during the re-adaptation of the GPE- vaccine virus in pigs, the IRF3-degrading function of Npro was not recovered. Therefore, we examined whether restoring the ability of Npro to block IFN-α/β induction of both the avirulent and moderately virulent GPE--derived virus would enhance pathogenicity in pigs. Viruses carrying the N136D substitution in Npro regained the ability to degrade IRF3 and suppress IFN-α/β induction in vitro. In pigs, functional Npro significantly reduced the local IFN-α mRNA expression in lymphoid organs while it increased quantities of IFN-α/β in the circulation, and enhanced pathogenicity of the moderately virulent virus. In conclusion, the present study demonstrates that functional Npro influences the innate immune response at local sites of virus replication in pigs and contributes to pathogenicity of CSFV in synergy with viral replication.

Der Satzakzent im Hebräischen : eine Erwiderung auf eine Rezension meines Buches "Die massoretischen Akzente"

Artur Spanier

Dynamische Fähigkeiten und Unternehmenserfolg: Untersuchung des Mediationseffekts der Unternehmensinnovativität

Veränderung ist eine Konstante im heutigen unternehmerischen Wettbewerb - sei es eine Veränderung der Kundenbedürfnisse, eine Veränderung im Sinne des technologischen Fortschritts oder eine Veränderung des Wettbewerberumfelds. Dadurch werden Unternehmen kontinuierlich vor die Herausforderung gestellt, ihre unternehmerische Wertschöpfung regelmässig an die jeweilige Veränderung anzupassen. Nur wenn diese Anpassung gelingt, können Unternehmen einen nachhaltigen Unternehmenserfolg erzielen. Für die Anpassung der unternehmerischen Wertschöpfung ist ein abgestimmtes Set an Fähigkeiten erforderlich. So müssen Unternehmen zunächst in der Lage sein, Veränderung in den verschiedenen Dimensionen – Kunden, Technologie, Wettbewerber – zu erkennen. Anschliessend müssen Unternehmen aus der erkannten Veränderung angemessene Handlungskonzepte ableiten können, anhand derer die unternehmerische Wertschöpfung angepasst werden kann. Schliesslich müssen Unternehmen über Fähigkeiten verfügen, die Handlungskonzepte realisieren zu können. Diese drei Arten von Fähigkeiten bilden das Grundgerüst des Konzepts dynamischer Fähigkeiten („Dynamic Capabilities“) nach David J. Teece. Mit dem Konzept der Rekonfiguration unternehmerischer Wertschöpfung anhand dynamischer Fähigkeiten hat Teece eine Möglichkeit geschaffen, nachhaltigen Unternehmenserfolg in veränderlichen Märkten zu erklären. Durch das Konzept wird allerdings noch nicht die Frage beantwortet, wie sich die Rekonfiguration konkret manifestiert und zum Unternehmenserfolg beiträgt. In der vorliegenden Untersuchung wird eine Antwort auf diese Frage entwickelt. Es wird die These aufgestellt und überprüft, nach der die dynamischen Fähigkeiten positiv auf die Unternehmensinnovativität wirken. Als Resultat der verbesserten Unternehmensinnovativität sollten Unternehmen dann einen nachhaltigen Erfolg erzielen können. Dazu werden im ersten Teil der Untersuchung (Kapitel 1-4) die Forschungsfragen aus der Literatur abgeleitet, und es werden die zu überprüfenden Hypothesen entwickelt. Im zweiten Teil (Kapitel 5-9) werden zunächst die Ergebnisse einer qualitativen Vorstudie vorgestellt. Danach folgen die Erläuterungen der Operationalisierungen sowie der Untersuchungsmethodik. Im Anschluss werden die Ergebnisse der quantitativen Untersuchung präsentiert und erläutert. Abschliessend werden die Ergebnisse kritisch diskutiert und Schlussfolgerungen für die Forschung sowie die unternehmerische Praxis abgeleitet.

Jüdische Sprichwörter

hrsg. von Artur Landsberger

Lichtstrahlen aus dem Talmud : Offener Brief an den Landes-Rabbiner von Sachsen-Weimar-Eisenach

von Artur Dinter

A longitudinal cross-country study of entrepreneurial orientation

As recent research documents, there has been an impressive effort of studying the entrepreneurial orientation construct and its nomological role. However, most research has been very context specific and based on the analyses of cross-sectional information. We study causal performance effects from entrepreneurial orientation and its key dimensions in two economic contexts–developed and emerging markets. Gathering data on a sample of 94 firms in developed market context and 108 in emerging market context at two time-points we explore our hypotheses. The results suggest that in a developed economy entrepreneurial orientation has a positive impact on firm performance, whereas in the emerging market context this effect is negative. Furthermore, we assess the contribution of each dimension to the aggregate construct and reveal the importance of risk-taking in both contexts. Finally, we highlight the role of environmental dynamism and explain its varying effect

The Strategic Role of the Sales Force: Perceptions of Senior Sales Executives

Current models of sales force strategy imply formidable information processing demands, which leads us to take a cognitive approach to studying the issue of sales force strategy. We focus on how top-level executives use mental models of sales force performance to simplify the issue of sales force strategy. We interviewed 74 senior executives responsible for their firms’ selling function using the repertory grid approach, as this methodology has been shown to be particularly effective at uncovering the collective cognitive maps on which executives’ decisions and behaviors are based. Executives identified a broad set of 37 strategic concepts that they felt distinguish the sales force efforts of directly competing companies. A second set of sales executives classified the 37 concepts into capabilities, resources, and organizational context concepts. Based on the classification results and feedback from both sets of executives, we developed research propositions for examining sales force strategy and provide directions for future research.

The influence of formal and informal sales controls on customer-directed selling behaviors and sales unit effectiveness

Adaptive selling (AS) and customer-oriented selling (COS) constitute two key customer-directed selling behaviors for the success of the modern sales force. However, knowledge regarding the organizational factors that can induce salespeople to engage in those behaviors is strikingly limited. Against this background, we develop a comprehensive model that delineates the influences of formal and informal sales controls on AS and COS and, through them, on sales unit effectiveness. Based on a sample of sales managers in a major European Union country, we present new evidence that (a) formal and informal sales controls exert differential impact on salespeople's AS and COS behaviors; (b) AS directly and positively influences sales unit effectiveness; (c) COS affects sales unit effectiveness only indirectly, i.e. by fostering AS; and (d) outcome and cultural controls directly improve sales unit effectiveness. We conclude with a discussion of our findings for academics and practitioners.