A Temporal Proteomic Map of Epstein-Barr Virus Lytic Replication in B Cells

Epstein-Barr virus (EBV) replication contributes to multiple human diseases, including infectious mononucleosis, nasopharyngeal carcinoma, B cell lymphomas, and oral hairy leukoplakia. We performed systematic quantitative analyses of temporal changes in host and EBV proteins during lytic replication to gain insights into virus-host interactions, using conditional Burkitt lymphoma models of type I and II EBV infection. We quantified profiles of >8,000 cellular and 69 EBV proteins, including >500 plasma membrane proteins, providing temporal views of the lytic B cell proteome and EBV virome. Our approach revealed EBV-induced remodeling of cell cycle, innate and adaptive immune pathways, including upregulation of the complement cascade and proteasomal degradation of the B cell receptor complex, conserved between EBV types I and II. Cross-comparison with proteomic analyses of human cytomegalovirus infection and of a Kaposi-sarcoma-associated herpesvirus immunoevasin identified host factors targeted by multiple herpesviruses. Our results provide an important resource for studies of EBV replication

Treatment of eccrine porocarcinoma with metastasis to the parotid gland using intensity-modulated radiation therapy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Cutaneous eccrine porocarcinomas are uncommon malignant tumors of the sweat gland.</p> <p>Case Presentation</p> <p>A 76-year-old Caucasian man presented to our hospital with a left temporal mass. We describe a case of eccrine porocarcinoma with metastasis to the parotid gland with special emphasis on the role of surgical resection and adjuvant radiation therapy.</p> <p>Conclusion</p> <p>Besides surgical resection, little is known about the role of adjuvant therapy in managing eccrine porocarcinomas. Radiation therapy should be considered within a multidisciplinary approach in patients with primary or recurrent eccrine porocarcinomas.</p

Shamanistic Shakespeare: Korea's Colonization of Hamlet

"Shamanistic Shakespeare: Korea's Colonization of Hamlet" offers a timely reminder about the dangers of imposing a reformulated national myth on international Shakespeare productions. Focusing on a London performance of Korea’s Yohangza Theatre Company’s shamanized Hamlet, this case study invites far broader consideration of the readability of global Shakespeares, and the cultural competence required by Western audiences to appreciate their political, historical, and local complexity. The Korean theatre industry’s colonizing of Hamlet is traced to a Seoul-based nationalist intellectual agenda to reinvent Korea’s mythic identity after a century of cultural oppression. The chapter demonstrates how this concretizing of shamanic symbolism, packaged for Westernized theatregoing consumption, has created a supposedly authentic Koreanized Shakespeare genre that is confusing to local and global audiences alike

Respiratory Dendritic Cell Subsets Differ in Their Capacity to Support the Induction of Virus-Specific Cytotoxic CD8+ T Cell Responses

Dendritic cells located at the body surfaces, e.g. skin, respiratory and gastrointestinal tract, play an essential role in the induction of adaptive immune responses to pathogens and inert antigens present at these surfaces. In the respiratory tract, multiple subsets of dendritic cells (RDC) have been identified in both the normal and inflamed lungs. While the importance of RDC in antigen transport from the inflamed or infected respiratory tract to the lymph nodes draining this site is well recognized, the contribution of individual RDC subsets to this process and the precise role of migrant RDC within the lymph nodes in antigen presentation to T cells is not clear. In this report, we demonstrate that two distinct subsets of migrant RDC - exhibiting the CD103+ and CD11bhi phenotype, respectively - are the primary DC presenting antigen to naïve CD4+ and CD8+ T lymphocytes in the draining nodes in response to respiratory influenza virus infection. Furthermore, the migrant CD103+ RDC subset preferentially drives efficient proliferation and differentiation of naive CD8+ T cells responding to infection into effector cells, and only the CD103+ RDC subset can present to naïve CD8+ T cells non-infectious viral vaccine introduced into the respiratory tract. These results identify CD103+ and CD11bhi RDC as critical regulators of the adaptive immune response to respiratory tract infection and potential targets in the design of mucosal vaccines

Liver Is Able to Activate Naïve CD8+ T Cells with Dysfunctional Anti-Viral Activity in the Murine System

The liver possesses distinct tolerogenic properties because of continuous exposure to bacterial constituents and nonpathogenic food antigen. The central immune mediators required for the generation of effective immune responses in the liver environment have not been fully elucidated. In this report, we demonstrate that the liver can indeed support effector CD8+ T cells during adenovirus infection when the T cells are primed in secondary lymphoid tissues. In contrast, when viral antigen is delivered predominantly to the liver via intravenous (IV) adenovirus infection, intrahepatic CD8+ T cells are significantly impaired in their ability to produce inflammatory cytokines and lyse target cells. Additionally, intrahepatic CD8+ T cells generated during IV adenovirus infection express elevated levels of PD-1. Notably, lower doses of adenovirus infection do not rescue the impaired effector function of intrahepatic CD8+ T cell responses. Instead, intrahepatic antigen recognition limits the generation of potent anti-viral responses at both priming and effector stages of the CD8+ T cell response and accounts for the dysfunctional CD8+ T cell response observed during IV adenovirus infection. These results also implicate that manipulation of antigen delivery will facilitate the design of improved vaccination strategies to persistent viral infection

Determinants of consumers’ intentions to share knowledge and intentions to purchase on s-commerce sites: incorporating attitudes toward persuasion attempts into a social exchange model

This research explores s-commerce users’ intentions to purchase and to share knowledge by incorporating ‘attitudes toward persuasion attempts,’ ‘ease of use,’ and ‘perceived usefulness’ into a social exchange theory model. A survey using an on-site purposive sampling technique was used to recruit the respondents, and an interception technique was used to approach the consumers. A total of 471 Korean consumers participated in this research. Based on 471 Korean social-commerce users, our results reveal that social exchange belief factors and a site’s usability affect user satisfaction, which subsequently affects users’ intentions to purchase and to share knowledge. In addition, attitudes toward persuasion attempts moderate the effect of satisfaction on users’ purchase intentions. Keywords: social exchange theory, attitudes toward persuasion attempts, intention to share knowledge, social exchange belief

The ongoing pursuit of neuroprotective therapies in Parkinson disease

Many agents developed for neuroprotective treatment of Parkinson disease (PD) have shown great promise in the laboratory, but none have translated to positive results in patients with PD. Potential neuroprotective drugs, such as ubiquinone, creatine and PYM50028, have failed to show any clinical benefits in recent high-profile clinical trials. This 'failure to translate' is likely to be related primarily to our incomplete understanding of the pathogenic mechanisms underlying PD, and excessive reliance on data from toxin-based animal models to judge which agents should be selected for clinical trials. Restricted resources inevitably mean that difficult compromises must be made in terms of trial design, and reliable estimation of efficacy is further hampered by the absence of validated biomarkers of disease progression. Drug development in PD dementia has been mostly unsuccessful; however, emerging biochemical, genetic and pathological evidence suggests a link between tau and amyloid-β deposition and cognitive decline in PD, potentially opening up new possibilities for therapeutic intervention. This Review discusses the most important 'druggable' disease mechanisms in PD, as well as the most-promising drugs that are being evaluated for their potential efficiency in treatment of motor and cognitive impairments in PD

Cheek Tooth Morphology and Ancient Mitochondrial DNA of Late Pleistocene Horses from the Western Interior of North America: Implications for the Taxonomy of North American Late Pleistocene Equus

Horses were a dominant component of North American Pleistocene land mammal communities and their remains are well represented in the fossil record. Despite the abundant material available for study, there is still considerable disagreement over the number of species of Equus that inhabited the different regions of the continent and on their taxonomic nomenclature. In this study, we investigated cheek tooth morphology and ancient mtDNA of late Pleistocene Equus specimens from the Western Interior of North America, with the objective of clarifying the species that lived in this region prior to the end-Pleistocene extinction. Based on the morphological and molecular data analyzed, a caballine (Equus ferus) and a non-caballine (E. conversidens) species were identified from different localities across most of the Western Interior. A second non-caballine species (E. cedralensis) was recognized from southern localities based exclusively on the morphological analyses of the cheek teeth. Notably the separation into caballine and non-caballine species was observed in the Bayesian phylogenetic analysis of ancient mtDNA as well as in the geometric morphometric analyses of the upper and lower premolars. Teeth morphologically identified as E. conversidens that yielded ancient mtDNA fall within the New World stilt-legged clade recognized in previous studies and this is the name we apply to this group. Geographic variation in morphology in the caballine species is indicated by statistically different occlusal enamel patterns in the specimens from Bluefish Caves, Yukon Territory, relative to the specimens from the other geographic regions. Whether this represents ecomorphological variation and/or a certain degree of geographic and genetic isolation of these Arctic populations requires further study

Impact of 3D cell culture on bone regeneration potential of mesenchymal stromal cells

As populations age across the world, osteoporosis and osteoporosis-related fractures are becoming the most prevalent degenerative bone diseases. More than 75 million patients suffer from osteoporosis in the US, the EU and Japan. Furthermore, it is anticipated that the number of patients affected by osteoporosis will increase by a third by 2050. Although conventional therapies including bisphosphonates, calcitonin and oestrogen-like drugs can be used to treat degenerative diseases, they are often associated with serious side effects including the development of oesophageal cancer, ocular inflammation, severe musculoskeletal pain, and osteonecrosis of the jaw. The use of autologous mesenchymal stromal cells/mesenchymal stem cells (MSCs) is a possible alternative therapeutic approach to tackle osteoporosis while overcoming the limitations of traditional treatment options. However, osteoporosis can cause a decrease in the numbers of MSCs, induce their senescence, and lower their osteogenic differentiation potential. Three-dimensional (3D) cell culture is an emerging technology that allows a more physiological expansion and differentiation of stem cells compared to cultivation on conventional flat systems. This review will discuss current understanding of the effects of different 3D cell culture systems on proliferation, viability, osteogenic differentiation, as well as on the immunomodulatory and anti-inflammatory potential of MSCs