The RIG-I-like Receptor LGP2 Controls CD8+ T Cell Survival and Fitness

SummaryThe RIG-I-like receptors (RLRs) signal innate immune defenses upon RNA virus infection, but their roles in adaptive immunity have not been clearly defined. Here, we showed that the RLR LGP2 was not essential for induction of innate immune defenses, but rather was required for controlling antigen-specific CD8+ T cell survival and fitness during peripheral T cell-number expansion in response to virus infection. Adoptive transfer and biochemical studies demonstrated that T cell-receptor signaling induced LGP2 expression wherein LGP2 operated to regulate death-receptor signaling and imparted sensitivity to CD95-mediated cell death. Thus, LGP2 promotes an essential prosurvival signal in response to antigen stimulation to confer CD8+ T cell-number expansion and effector functions against divergent RNA viruses, including West Nile virus and lymphocytic choriomeningitis virus

IRF-3, IRF-5, and IRF-7 coordinately regulate the type I IFN response in myeloid dendritic cells downstream of MAVS signaling

Although the transcription factors IRF-3 and IRF-7 are considered master regulators of type I interferon (IFN) induction and IFN stimulated gene (ISG) expression, Irf3(-/-)×Irf7(-/-) double knockout (DKO) myeloid dendritic cells (mDC) produce relatively normal levels of IFN-β after viral infection. We generated Irf3(-/-)×Irf5(-/-)×Irf7(-/-) triple knockout (TKO) mice to test whether IRF-5 was the source of the residual induction of IFN-β and ISGs in mDCs. In pathogenesis studies with two unrelated positive-sense RNA viruses (West Nile virus (WNV) and murine norovirus), TKO mice succumbed at rates greater than DKO mice and equal to or approaching those of mice lacking the type I IFN receptor (Ifnar(-/-)). In ex vivo studies, after WNV infection or exposure to Toll-like receptor agonists, TKO mDCs failed to produce IFN-β or express ISGs. In contrast, this response was sustained in TKO macrophages following WNV infection. To define IRF-regulated gene signatures, we performed microarray analysis on WNV-infected mDC from wild type (WT), DKO, TKO, or Ifnar(-/-) mice, as well as from mice lacking the RIG-I like receptor adaptor protein MAVS. Whereas the gene induction pattern in DKO mDC was similar to WT cells, remarkably, almost no ISG induction was detected in TKO or Mavs(-/-) mDC. The relative equivalence of TKO and Mavs(-/-) responses suggested that MAVS dominantly regulates ISG induction in mDC. Moreover, we showed that MAVS-dependent induction of ISGs can occur through an IRF-5-dependent yet IRF-3 and IRF-7-independent pathway. Our results establish IRF-3, -5, and -7 as the key transcription factors responsible for mediating the type I IFN and ISG response in mDC during WNV infection and suggest a novel signaling link between MAVS and IRF-5

Proceedings of the Sixth International Workshop on Web Caching and Content Distribution

OVERVIEW The International Web Content Caching and Distribution Workshop (WCW) is a premiere technical meeting for researchers and practitioners interested in all aspects of content caching, distribution and delivery on the Internet. The 2001 WCW meeting was held on the Boston University Campus. Building on the successes of the five previous WCW meetings, WCW01 featured a strong technical program and record participation from leading researchers and practitioners in the field. This report includes all the technical papers presented at WCW'01. Note: Proceedings of WCW'01 are published by Elsevier. Hardcopies of these proceedings can be purchased through the workshop organizers. As a service to the community, electronic copies of all WCW'01 papers are accessible through Technical Report BUCS‐TR‐2001‐017, available from the Boston University Computer Science Technical Report Archives at http://www.cs.bu.edu/techreps. [Ed.note: URL outdated. Use http://www.bu.edu/cs/research/technical-reports/ or http://hdl.handle.net/2144/1455 in this repository to access the reports.]Cisco Systems; InfoLibria; Measurement Factory Inc; Voler

Coordinated but physically separable interaction with H3K27-demethylase and H3K4-methyltransferase activities are required for T-box protein-mediated activation of developmental gene expression

During cellular differentiation, both permissive and repressive epigenetic modifications must be negotiated to create cell-type-specific gene expression patterns. The T-box transcription factor family is important in numerous developmental systems ranging from embryogenesis to the differentiation of adult tissues. By analyzing point mutations in conserved sequences in the T-box DNA-binding domain, we found that two overlapping, but physically separable regions are required for the physical and functional interaction with H3K27-demethylase and H3K4-methyltransferase activities. Importantly, the ability to associate with these histone-modifying complexes is a conserved function for the T-box family. These novel mechanisms for T-box-mediated epigenetic regulation are essential, because point mutations that disrupt these interactions are found in a diverse array of human developmental genetic diseases

Fab Lab (Semester Unknown) IPRO 333

Fabrication Laboratories (Fab Labs) were started as a community outreach program by the Massachusetts Institute of Technology to provide digital fabrication tools for rapid prototyping to the general public. The Museum of Science and Industry in Chicago (MSI) has partnered with this IPRO to further develop their existing Fab Lab. IPRO 333 has been assigned the task of working with the Fab Lab administrators to design methodologies for furthering the use of the laboratory and determining its end goals for both the museum and the community. Once these goals are established, we will support them with a list of projects that we will create and execute. By working with the lab directors to broaden the possible uses of the lab, we hope to encourage hands-on learning in local schools. This will promote membership at MSI and involve the community in science and technology programs and education. To accomplish this, we have broken into two teams, each of which will focus on a different audience. The first team will be responsible for designing and creating programs for more advanced and knowledgeable users of the equipment specific to the Fab Lab, such as the students enrolled in the Science Achievers program as well as museum members; the second team will be responsible for designing and implementing programs for less advanced users with more constrained timeframes, such as visiting families or groups of school children.Deliverable

Fab Lab (Semester Unknown) IPRO 333: Fab Lab IPRO 333 Poster3 F08

Fabrication Laboratories (Fab Labs) were started as a community outreach program by the Massachusetts Institute of Technology to provide digital fabrication tools for rapid prototyping to the general public. The Museum of Science and Industry in Chicago (MSI) has partnered with this IPRO to further develop their existing Fab Lab. IPRO 333 has been assigned the task of working with the Fab Lab administrators to design methodologies for furthering the use of the laboratory and determining its end goals for both the museum and the community. Once these goals are established, we will support them with a list of projects that we will create and execute. By working with the lab directors to broaden the possible uses of the lab, we hope to encourage hands-on learning in local schools. This will promote membership at MSI and involve the community in science and technology programs and education. To accomplish this, we have broken into two teams, each of which will focus on a different audience. The first team will be responsible for designing and creating programs for more advanced and knowledgeable users of the equipment specific to the Fab Lab, such as the students enrolled in the Science Achievers program as well as museum members; the second team will be responsible for designing and implementing programs for less advanced users with more constrained timeframes, such as visiting families or groups of school children.Deliverable

Fab Lab (Semester Unknown) IPRO 333: Fab Lab IPRO 333 Mid Term Presentation F08

Fabrication Laboratories (Fab Labs) were started as a community outreach program by the Massachusetts Institute of Technology to provide digital fabrication tools for rapid prototyping to the general public. The Museum of Science and Industry in Chicago (MSI) has partnered with this IPRO to further develop their existing Fab Lab. IPRO 333 has been assigned the task of working with the Fab Lab administrators to design methodologies for furthering the use of the laboratory and determining its end goals for both the museum and the community. Once these goals are established, we will support them with a list of projects that we will create and execute. By working with the lab directors to broaden the possible uses of the lab, we hope to encourage hands-on learning in local schools. This will promote membership at MSI and involve the community in science and technology programs and education. To accomplish this, we have broken into two teams, each of which will focus on a different audience. The first team will be responsible for designing and creating programs for more advanced and knowledgeable users of the equipment specific to the Fab Lab, such as the students enrolled in the Science Achievers program as well as museum members; the second team will be responsible for designing and implementing programs for less advanced users with more constrained timeframes, such as visiting families or groups of school children.Deliverable

Fab Lab (Semester Unknown) IPRO 333

Fabrication Laboratories (Fab Labs) were started as a community outreach program by the Massachusetts Institute of Technology to provide digital fabrication tools for rapid prototyping to the general public. The Museum of Science and Industry in Chicago (MSI) has partnered with this IPRO to further develop their existing Fab Lab. IPRO 333 has been assigned the task of working with the Fab Lab administrators to design methodologies for furthering the use of the laboratory and determining its end goals for both the museum and the community. Once these goals are established, we will support them with a list of projects that we will create and execute. By working with the lab directors to broaden the possible uses of the lab, we hope to encourage hands-on learning in local schools. This will promote membership at MSI and involve the community in science and technology programs and education. To accomplish this, we have broken into two teams, each of which will focus on a different audience. The first team will be responsible for designing and creating programs for more advanced and knowledgeable users of the equipment specific to the Fab Lab, such as the students enrolled in the Science Achievers program as well as museum members; the second team will be responsible for designing and implementing programs for less advanced users with more constrained timeframes, such as visiting families or groups of school children.Deliverable