Inhibition of cellular protein secretion by norwalk virus nonstructural protein p22 requires a mimic of an endoplasmic reticulum export signal.

Protein trafficking between the endoplasmic reticulum (ER) and Golgi apparatus is central to cellular homeostasis. ER export signals are utilized by a subset of proteins to rapidly exit the ER by direct uptake into COPII vesicles for transport to the Golgi. Norwalk virus nonstructural protein p22 contains a YXΦESDG motif that mimics a di-acidic ER export signal in both sequence and function. However, unlike normal ER export signals, the ER export signal mimic of p22 is necessary for apparent inhibition of normal COPII vesicle trafficking, which leads to Golgi disassembly and antagonism of Golgi-dependent cellular protein secretion. This is the first reported function for p22. Disassembly of the Golgi apparatus was also observed in cells replicating Norwalk virus, which may contribute to pathogenesis by interfering with cellular processes that are dependent on an intact secretory pathway. These results indicate that the ER export signal mimic is critical to the antagonistic function of p22, shown herein to be a novel antagonist of ER/Golgi trafficking. This unique and well-conserved human norovirus motif is therefore an appealing target for antiviral drug development

Discussion of the selection and use of teaching aids and standard materials in the lower school at Perkins School for the Blind

Thesis (Ed.M.)--Boston Universit

Remote sensing applications to hydrologic modeling

An energy balance snowmelt model for rugged terrain was devised and coupled to a flow model. A literature review of remote sensing applications to hydrologic modeling was included along with a software development outline

Osteopontin upregulation in rotavirus-induced murine biliary atresia requires replicating virus but is not necessary for development of biliary atresia

AbstractBiliary atresia (BA) is a progressive fibro-inflammatory pediatric liver disease in which osteopontin (OPN), a glycoprotein with inflammatory and fibrogenic activity, may play a pathogenic role. The current studies were conducted in a mouse model of rotavirus-induced BA to test the hypotheses that live but not inactivated rotavirus causes antigenemia, upregulation of hepatic OPN expression, and induction of BA and fibrosis; and that OPN is necessary for development of BA. Prolonged or transient antigenemia developed in mice inoculated with live or inactivated virus, respectively, but only live virus upregulated hepatic OPN and caused BA and fibrosis. OPN was expressed in intra- and extrahepatic bile ducts in healthy mice and in mice with BA. OPN-deficient mice, similar to WT mice, developed BA. Together, these data show that live but not inactivated rotavirus causes upregulation of hepatic OPN expression and BA but that OPN is not necessary for development of BA

Guidelines for Energy Efficient Schools

Operational experience of several schools designed with energy efficiency as a design criteria is discussed in this paper. Actual monthly energy usage and cost are provided. Annual energy cost performance ($/ft^2-yr) and energy performance (BTU/FT^2-yr) of these example case study schools with flexible mechanical and electrical systems are compared to published design performance guidelines and similar schools constructed without energy efficiency as a design criteria. The authors have conducted energy studies of more than 400 schools which serve as a comparative data base range of performance. Of the schools compared, those with the lowest operating cost and energy usage employed flexible HVAC systems which inherently provided for control of electrical demand. The resulting electrical demand profile of most of theme case study schools were relatively constant throughout the year which is uncommon to most schools. The design approach employed to achieve lowar operating costs and inherent demand control is a hybrid HVAC system with a designed mixture or balance between electric and natural gas energy sources. The summary of this paper will compare operating cost performance, energy performance, HVAC system type of the case study schools, eight schools with water source heat pumps, and other data base schools with various other types of HVAC systems. Design guidelines for energy efficient schools are presented

Rotavirus Structural Proteins and dsRNA Are Required for the Human Primary Plasmacytoid Dendritic Cell IFNα Response

Rotaviruses are the leading cause of severe dehydrating diarrhea in children worldwide. Rotavirus-induced immune responses, especially the T and B cell responses, have been extensively characterized; however, little is known about innate immune mechanisms involved in the control of rotavirus infection. Although increased levels of systemic type I interferon (IFNα and β) correlate with accelerated resolution of rotavirus disease, multiple rotavirus strains, including rhesus rotavirus (RRV), have been demonstrated to antagonize type I IFN production in a variety of epithelial and fibroblast cell types through several mechanisms, including degradation of multiple interferon regulatory factors by a viral nonstructural protein. This report demonstrates that stimulation of highly purified primary human peripheral plasmacytoid dendritic cells (pDCs) with either live or inactivated RRV induces substantial IFNα production by a subset of pDCs in which RRV does not replicate. Characterization of pDC responses to viral stimulus by flow cytometry and Luminex revealed that RRV replicates in a small subset of human primary pDCs and, in this RRV-permissive small subset, IFNα production is diminished. pDC activation and maturation were observed independently of viral replication and were enhanced in cells in which virus replicates. Production of IFNα by pDCs following RRV exposure required viral dsRNA and surface proteins, but neither viral replication nor activation by trypsin cleavage of VP4. These results demonstrate that a minor subset of purified primary human peripheral pDCs are permissive to RRV infection, and that pDCs retain functionality following RRV stimulus. Additionally, this study demonstrates trypsin-independent infection of primary peripheral cells by rotavirus, which may allow for the establishment of extraintestinal viremia and antigenemia. Importantly, these data provide the first evidence of IFNα induction in primary human pDCs by a dsRNA virus, while simultaneously demonstrating impaired IFNα production in primary human cells in which RRV replicates. Rotavirus infection of primary human pDCs provides a powerful experimental system for the study of mechanisms underlying pDC-mediated innate immunity to viral infection and reveals a potentially novel dsRNA-dependent pathway of IFNα induction

Exposure to human and bovine noroviruses in a birth cohort in southern India from 2002 to 2006

Human and bovine norovirus virus-like particles were used to evaluate antibodies in Indian children at ages 6 and 36 months and their mothers. Antibodies to genogroup II viruses were acquired early and were more prevalent than antibodies to genogroup I. Low levels of IgG antibodies against bovine noroviruses indicate possible zoonotic transmission