Not all digital word of mouth is created equal: Understanding the respective impact of consumer reviews and microblogs on new product success

The expansion of the Internet and social media have triggered a differentiation of the word-of-mouth (WOM) concept, with consumer communication about brands and products now taking place in various settings and forms. Two important digital WOM types are microblogs and consumer reviews. To clarify their differential roles for product success, this study offers a theoretical framework of the influence of these two types of WOM, drawing from consumer information search theory and diffusion theory. The tests of the proposed framework use a longitudinal data set of video game sales and weekly information gathered from microblogs (i.e., over 13 million tweets from Twitter) and consumer reviews (i.e., more than 17,000 Amazon consumer reviews). Analyzing a system of equations provides evidence that the influence of microblogs and consumer reviews on new product success changes over time. Prior to launch, the volumes of microblogs and consumer reviews, together with advertising, represent primary sales drivers. After launch, the volume of microblogs is initially influential, then loses impact, whereas the impact of the volume of consumer reviews continues to grow. The valence of consumer reviews gains significance only near the end of the observation period, but the valence of microblogging is never influential

Does Twitter matter? The impact of microblogging word of mouth on consumers’ adoption of new movies

This research provides an empirical test of the “Twitter effect,” which postulates that microblogging word of mouth (MWOM) shared through Twitter and similar services affects early product adoption behaviors by immediately disseminating consumers’ post-purchase quality evaluations. This is a potentially crucial factor for the success of experiential media products and other products whose distribution strategy relies on a hyped release. Studying the four million MWOM messages sent via Twitter concerning 105 movies on their respective opening weekends, the authors find support for the Twitter effect and report evidence of a negativity bias. In a follow-up incident study of 600 Twitter users who decided not to see a movie based on negative MWOM, the authors shed additional light on the Twitter effect by investigating how consumers use MWOM information in their decision-making processes and describing MWOM’s defining characteristics. They use these insights to position MWOM in the word-of-mouth landscape, to identify future word-of-mouth research opportunities based on this conceptual positioning, and to develop managerial implications

BAT3 Guides Misfolded Glycoproteins Out of the Endoplasmic Reticulum

Secretory and membrane proteins that fail to acquire their native conformation within the lumen of the Endoplasmic Reticulum (ER) are usually targeted for ubiquitin-dependent degradation by the proteasome. How partially folded polypeptides are kept from aggregation once ejected from the ER into the cytosol is not known. We show that BAT3, a cytosolic chaperone, is recruited to the site of dislocation through its interaction with Derlin2. Furthermore, we observe cytoplasmic BAT3 in a complex with a polypeptide that originates in the ER as a glycoprotein, an interaction that depends on the cytosolic disposition of both, visualized even in the absence of proteasomal inhibition. Cells depleted of BAT3 fail to degrade an established dislocation substrate. We thus implicate a cytosolic chaperone as an active participant in the dislocation of ER glycoproteins.United States. National Institutes of HealthBoehringer Ingelheim Fond

Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation

NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family

Exploitation of Herpesvirus Immune Evasion Strategies to Modify the Immunogenicity of Human Mesenchymal Stem Cell Transplants

BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent cells residing in the connective tissue of many organs and holding great potential for tissue repair. In culture, human MSCs (hMSCs) are capable of extensive proliferation without showing chromosomal aberrations. Large numbers of hMSCs can thus be acquired from small samples of easily obtainable tissues like fat and bone marrow. MSCs can contribute to regeneration indirectly by secretion of cytokines or directly by differentiation into specialized cell types. The latter mechanism requires their long-term acceptance by the recipient. Although MSCs do not elicit immune responses in vitro, animal studies have revealed that allogeneic and xenogeneic MSCs are rejected. METHODOLOGY/PRINCIPAL FINDINGS: We aim to overcome MSC immune rejection through permanent down-regulation of major histocompatibility complex (MHC) class I proteins on the surface of these MHC class II-negative cells through the use of viral immune evasion proteins. Transduction of hMSCs with a retroviral vector encoding the human cytomegalovirus US11 protein resulted in strong inhibition of MHC class I surface expression. When transplanted into immunocompetent mice, persistence of the US11-expressing and HLA-ABC-negative hMSCs at levels resembling those found in immunodeficient (i.e., NOD/SCID) mice could be attained provided that recipients' natural killer (NK) cells were depleted prior to cell transplantation. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate the potential utility of herpesviral immunoevasins to prevent rejection of xenogeneic MSCs. The observation that down-regulation of MHC class I surface expression renders hMSCs vulnerable to NK cell recognition and cytolysis implies that multiple viral immune evasion proteins are likely required to make hMSCs non-immunogenic and thereby universally transplantable

Human Cytomegalovirus Impairs the Function of Plasmacytoid Dendritic Cells in Lymphoid Organs

Human dendritic cells (DCs) are the main antigen presenting cells (APC) and can be divided into two main populations, myeloid and plasmacytoid DCs (pDCs), the latter being the main producers of Type I Interferon. The vast majority of pDCs can be found in lymphoid organs, where the main pool of all immune cells is located, but a minority of pDCs also circulate in peripheral blood. Human cytomegalovirus (HCMV) employs multiple mechanisms to evade the immune system. In this study, we could show that pDCs obtained from lymphoid organs (tonsils) (tpDCs) and from blood (bpDCs) are different subpopulations in humans. Interestingly, these populations react in opposite manner to HCMV-infection. TpDCs were fully permissive for HCMV. Their IFN-α production and the expression of costimulatory and adhesion molecules were altered after infection. In contrast, in bpDCs HCMV replication was abrogated and the cells were activated with increased IFN-α production and upregulation of MHC class I, costimulatory, and adhesion molecules. HCMV-infection of both, tpDCs and bpDCs, led to a decreased T cell stimulation, probably mediated through a soluble factor produced by HCMV-infected pDCs. We propose that the HCMV-mediated impairment of tpDCs is a newly discovered mechanism selectively targeting the host's major population of pDCs residing in lymphoid organs

Ubiquitylation in ERAD: Reversing to Go Forward?

Proteins are co-translationally inserted into the endoplasmic reticulum (ER) where they undergo maturation. Homeostasis in the ER requires a highly sensitive and selective means of quality control. This occurs through ER-associated degradation (ERAD).This complex ubiquitin-proteasome–mediated process involves ubiquitin conjugating enzymes (E2) and ubiquitin ligases (E3),lumenal and cytosolic chaperones, and other proteins, including the AAA ATPase p97 (VCP; Cdc48 in yeast). Probing of processes involving proteasomal degradation has generally depended on proteasome inhibitors or knockdown of specific E2s or E3s. In this issue of PLoS Biology, Ernst et al. demonstrate the utility of expressing the catalytic domain of a viral deubiquitylating enzyme to probe the ubiquitin system. Convincing evidence is provided that deubiquitylation is integral to dislocation of ERAD substrates from the ER membrane. The implications of this work for understanding ERAD and the potential of expressing deubiquitylating enzyme domains for studying ubiquitin-mediated processes are discussed

Сетевая система контроля технологического процесса выращивания полупроводниковых кристаллов и тонких пленок

Экспериментальное моделирование аппаратно-программного обеспечения показало достаточную надежность работы системы и значительное уменьшение трудоемкости контроля и управления параметрами технологического процесса