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MOTIVATION Time series expression experiments are used to study a wide range of biological systems. More than 80% of all time series expression datasets are short (8 time points or fewer). These datasets present unique challenges. On account of the large number of genes profiled (often tens of thousands) and the small number of time points many patterns are(More)
Understanding the response of innate immune cells to pathogens may provide insights to host defenses and the tactics used by pathogens to circumvent these defenses. We used DNA microarrays to explore the responses of human macrophages to a variety of bacteria. Macrophages responded to a broad range of bacteria with a robust, shared pattern of gene(More)
The innate immune response is the first line of host defense against infections. This system employs a number of different types of cells, which in turn activate different sets of genes. Microarray studies of human and mouse cells infected with various pathogens identified hundreds of differentially expressed genes. However, combining these datasets to(More)
Self-renewal and differentiation of embryonic stem (ES) cells are regulated by cytokines and growth factors through tyrosine kinase-dependent signaling pathways. In murine ES cells, signals for self-renewal are generated by the leukemia inhibitory factor (LIF). LIF and other growth factors are linked to the activation of the Src family of cytoplasmic(More)
We engineered an efficient system to make Francisella tularensis deletion mutations using an unstable, poorly maintained plasmid to enhance the likelihood of homologous recombination. For counterselection, we adapted a strategy using I-SceI, which causes a double-stranded break in the integrated suicide vector, forcing a second recombination to mediate(More)
Viral and bacterial infections of the lower respiratory tract are major causes of morbidity and mortality worldwide. Alveolar macrophages line the alveolar spaces and are the first cells of the immune system to respond to invading pathogens. To determine the similarities and differences between the responses of mice and macaques to invading pathogens we(More)
Vaccination is a proven strategy to mitigate morbidity and mortality of infectious diseases. The methodology of identifying and testing new vaccine candidates could be improved with rational design and in vitro testing prior to animal experimentation. The tularemia vaccine, Francisella tularensis live vaccine strain (LVS), does not elicit complete(More)
Chronic inflammation and granuloma formation are associated with mononuclear cell infiltrates and are characteristic pathologic responses in tuberculosis. To identify host cell genes involved in tuberculous pathology, we screened macrophage cDNA libraries for genes induced by mycobacterial infection. One gene isolated in this screen, osteopontin (also known(More)
Expression of the cytokine osteopontin (OPN) is elevated in granulomas caused by Mycobacterium tuberculosis. We tested the hypothesis that OPN contributes to host protection in a mouse model of mycobacterial infection. When infected with Mycobacterium bovis BCG, mice lacking a functional OPN gene had more severe infections characterized by heavier bacterial(More)
In innate immune sensing, the detection of pathogen-associated molecular patterns by recognition receptors typically involve leucine-rich repeats (LRRs). We provide a categorization of 375 human LRR-containing proteins, almost half of which lack other identifiable functional domains. We clustered human LRR proteins by first assigning LRRs to LRR classes and(More)