ZBP1 and TRIF trigger lethal necroptosis in mice lacking caspase-8 and TNFR1.

Necroptosis is a lytic form of cell death that is mediated by the kinase RIPK3 and the pseudokinase MLKL when caspase-8 is inhibited downstream of death receptors, toll-like receptor 3 (TLR3), TLR4, and the intracellular Z-form nucleic acid sensor ZBP1. Oligomerization and activation of RIPK3 is driven by interactions with the kinase RIPK1, the TLR adaptor TRIF, or ZBP1. In this study, we use immunohistochemistry (IHC) and in situ hybridization (ISH) assays to generate a tissue atlas characterizing RIPK1, RIPK3, Mlkl, and ZBP1 expression in mouse tissues.

Epigenetic loss of heterozygosity of Apc and an inflammation-associated mutational signature detected in Lrig1-driven murine colonic adenomas.

Background: The loss of a single copy of adenomatous polyposis coli (Apc) in leucine-rich repeats and immunoglobulin-like domains 1 (Lrig1)-expressing colonic progenitor cells induces rapid growth of adenomas in mice with high penetrance and multiplicity. The tumors lack functional APC, and a genetic loss of heterozygosity of Apc was previously observed.

Methods: To identify genomic features of early tumorigenesis, and to profile intertumoral genetic heterogeneity, tumor exome DNA (n = 9 tumors) and mRNA (n = 5 tumors) sequences were compared with matched nontumoral colon tissue.

RIP1 kinase activity is critical for skin inflammation but not for viral propagation.

Receptor interacting protein kinase 1 (RIP1) is a critical effector of inflammatory responses and cell death activation. Cell death pathways regulated by RIP1 include caspase-dependent apoptosis and caspase-independent necroptosis. The kinase activity of RIP1 has been associated with a number of inflammatory, neurodegenerative, and oncogenic diseases.

Cochlear Implant Mapping Through Telemedicine-A Feasibility Study.

Objective: Access to postoperative aural rehabilitation limits cochlear implant (CI) penetration to the candidate population. The purpose of this study was to evaluate the effectiveness of remote CI programming and aural rehabilitation via telehealth.

Study Design And Setting: Retrospective study of one cochlear implant center.

High-specificity detection of rare alleles with Paired-End Low Error Sequencing (PELE-Seq).

Background: Polymorphic loci exist throughout the genomes of a population and provide the raw genetic material needed for a species to adapt to changes in the environment. The minor allele frequencies of rare Single Nucleotide Polymorphisms (SNPs) within a population have been difficult to track with Next-Generation Sequencing (NGS), due to the high error rate of standard methods such as Illumina sequencing.

Results: We have developed a wet-lab protocol and variant-calling method that identifies both sequencing and PCR errors, called Paired-End Low Error Sequencing (PELE-Seq).

Genome-wide identification of hypoxia-induced enhancer regions.

Here we present a genome-wide method for de novo identification of enhancer regions. This approach enables massively parallel empirical investigation of DNA sequences that mediate transcriptional activation and provides a platform for discovery of regulatory modules capable of driving context-specific gene expression. The method links fragmented genomic DNA to the transcription of randomer molecule identifiers and measures the functional enhancer activity of the library by massively parallel sequencing.

A consensus process on the use of exercises and after action reports to assess and improve public health emergency preparedness and response.

Introduction: The objective of disaster preparedness is to ensure that appropriate systems, procedures, and resources are in place to provide prompt, effective assistance to disaster victims, thus facilitating relief measures and rehabilitation of services. Disaster preparedness efforts include the identification of possible health scenarios based on the probability of hazards and vulnerability of the population as a basis for creating a disaster plan. Exercises that simulate emergency response, involving the health and other sectors, have been suggested as useful tools to test the plans on a regular basis and measure preparedness efforts; the absence of actual testing is likely to negate even the best of abstract plans.

Eribulin: a novel cytotoxic chemotherapy agent.

Objective: To review the chemistry, pharmacology, pharmacokinetics, safety, and efficacy of eribulin (Halaven).

Data Sources: A literature search (up to December 2011) using the terms eribulin, Halaven, ER-086526, and E7389 was performed with PubMed, Google Scholar, selected Ovid bibliography searches, and the abstract search tool from the American Society of Clinical Oncology Annual Meetings and the San Antonio Breast Cancer Symposia. Additional references from the bibliographies of these articles were also assessed.

Local de novo assembly of RAD paired-end contigs using short sequencing reads.

Despite the power of massively parallel sequencing platforms, a drawback is the short length of the sequence reads produced. We demonstrate that short reads can be locally assembled into longer contigs using paired-end sequencing of restriction-site associated DNA (RAD-PE) fragments. We use this RAD-PE contig approach to identify single nucleotide polymorphisms (SNPs) and determine haplotype structure in threespine stickleback and to sequence E.

Public health emergency preparedness exercises: lessons learned.

The Harvard School of Public Health Center for Public Health Preparedness exercise program has two aims: (1) educating the public health workforce on key public health system emergency preparedness issues, and (2) identifying specific systems-level challenges in the public health response to large-scale events. Rigorous evaluation of 38 public health emergency preparedness (PHEP) exercises employing realistic scenarios and reliable and accurate outcome measures has demonstrated the usefulness of PHEP exercises in clarifying public health workers' roles and responsibilities, facilitating knowledge transfer among these individuals and organizations, and identifying specific public health systems-level challenges.