Climate Extremes Promote Fatal Co-Infections during Canine Distemper Epidemics in African Lions

Extreme climatic conditions may alter historic host-pathogen relationships and synchronize the temporal and spatial convergence of multiple infectious agents, triggering epidemics with far greater mortality than those due to single pathogens. Here we present the first data to clearly illustrate how climate extremes can promote a complex interplay between epidemic and endemic pathogens that are normally tolerated in isolation, but with co-infection, result in catastrophic mortality. A 1994 canine distemper virus (CDV) epidemic in Serengeti lions (Panthera leo) coincided with the death of a third of the population, and a second high-mortality CDV epidemic struck the nearby Ngorongoro Crater lion population in 2001. The extent of adult mortalities was unusual for CDV and prompted an investigation into contributing factors. Serological analyses indicated that at least five “silent” CDV epidemics swept through the same two lion populations between 1976 and 2006 without clinical signs or measurable mortality, indicating that CDV was not necessarily fatal. Clinical and pathology findings suggested that hemoparsitism was a major contributing factor during fatal epidemics. Using quantitative real-time PCR, we measured the magnitude of hemoparasite infections in these populations over 22 years and demonstrated significantly higher levels of Babesia during the 1994 and 2001 epidemics. Babesia levels correlated with mortalities and extent of CDV exposure within prides. The common event preceding the two high mortality CDV outbreaks was extreme drought conditions with wide-spread herbivore die-offs, most notably of Cape buffalo (Syncerus caffer). As a consequence of high tick numbers after the resumption of rains and heavy tick infestations of starving buffalo, the lions were infected by unusually high numbers of Babesia, infections that were magnified by the immunosuppressive effects of coincident CDV, leading to unprecedented mortality. Such mass mortality events may become increasingly common if climate extremes disrupt historic stable relationships between co-existing pathogens and their susceptible hosts

Lifecycle Cost Analysis RealCost User Manual

DTFH61-07-D-00028-T-09004DTFH6117D00005L/693JJ318F000355Lifecycle cost analysis (LCCA) is an engineering economic analysis tool that compares the relative merit of competing project implementation alternatives. LCCA considers both the agency and user costs incurred during the service life of an asset and helps transportation officials select the most preferred alternative. Additionally, LCCA introduces a structured methodology that accounts for the effects of agency activities on transportation users and provides a means to balance those effects with the system\u2019s construction, rehabilitation, and preservation needs. This manual aims to help users of the Federal Highway Administration\u2019s (FHWA\u2019s) RealCost 3.0, a Microsoft\uae Excel\uae-based LCCA tool to conduct LCCA. This user manual reflects the updated and enhanced RealCost 3.0\u2019s input data requirements, functions, analysis features, and user interface. The RealCost 3.0 tool has been updated to work on both Excel 32- and 64-bit versions and avoids the need for installation or availability of any third-party or other commercial components other than Excel 2010 or newer on end users\u2019 computers. The user manual contains a brief introduction to LCCA and adheres to the LCCA methodology explained in detail within FHWA\u2019s Life-Cycle Cost Analysis in Pavement Design Interim Technical Bulletin (Walls and Smith 1998). It also explains the steps to install and operate RealCost 3.0. Appendix A details the procedure to compute LCCA using examples of three pavement and one bridge projects. Appendix B helps users understand the customization of RealCost 3.0 for their specific needs. The user manual will interest State highway agency personnel and consultants responsible for conducting and reviewing LCCA

Latent membrane protein 1 encoded by Epstein-Barr virus modulates directly and synchronously cyclin D1 and p16 by newly forming a c-JunJun B heterodimer in nasopharyngeal carcinoma cell line

Recently we confirmed that latent membrane protein 1 (LMP1) encoded by Epstein-Barr virus (EBV) accelerates a newly forming active c-Jun/Jun B heterodimer, a transcription factor, but little is known about the target gene regulated by it. In this paper, results indicated that a c-Jun/Jun B heterodimer induced by LMP1 upregulated cyclin D1 promoters activity and expression, on the contrary, downregulated p16, and maladjustment of cyclin D1 and p16 expression accelerated progression of cell cycle. Firstly, we found a c-Jun/Jun B heterodimer regulated synchronously and directly cyclin D1 and p16 in the Tet-on-LMP1-HNE2 cell line, in which LMP1 expression is regulated by Tet-on system. This paper investigated in depth function of the newly forming active c-Jun/Jun B heterodimer, and built new connection between environmental pathogenic factor, signal transduction and cell cycle. (c) 2005 Elsevier B.V. All rights reserved

Heterodimer formation between c-Jun and Jun B proteins mediated by Epstein Barr virus encoded latent membrane protein 1

Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) may trigger the transcription factor AP-1 including c-Jun and c-fos. In this report, using a Tet-on LMP1 HNE2 cell line which is a dual-stable LMP1 integrated nasopharyngeal carcinoma (NPC) cell line and the expression of LMP1 in which could be regulated by the Tet-on system, we show that Jun B can efficiently form a new heterodimeric complex with the c-Jun protein under the regulation of LMP1, phosphorylation of c-Jun (ser 63, ser 73) and Jun B is involved in the process of the new heterodimeric formation. We also find that this heterodimeric form can bind to the AP-1 consensus sequence. Transfection studies suggest that JNK interaction protein (JIP) could inhibit the heterodimer formation of c-Jun and Jun B through blocking the AP-1 signaling pathway triggered by LMP1. The interaction and function between c-Jun protein and Jun B protein increase the repertoire of possible regulatory complexes by LMP1 that could play an important role in the regulation of transcription of specific cellular genes in the process of genesis of nasopharyngeal carcinoma