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Toll-like receptor 2 (TLR2) is required for the recognition of numerous molecular components of bacteria, fungi and protozoa. The breadth of the ligand repertoire seems unusual, even if one considers that TLR2 may form heteromers with TLRs 1 and 6 (ref. 12), and it is likely that additional proteins serve as adapters for TLR2 activation. Here we show that(More)
The recessive mutation 'Heedless' (hdl) was detected in third-generation N-ethyl-N-nitrosourea-mutated mice that showed defective responses to microbial inducers. Macrophages from Heedless homozygotes signaled by the MyD88-dependent pathway in response to rough lipopolysaccharide (LPS) and lipid A, but not in response to smooth LPS. In addition, the(More)
In humans, ten Toll-like receptor (TLR) paralogues sense molecular components of microbes, initiating the production of cytokine mediators that create the inflammatory response. Using N-ethyl-N-nitrosourea, we induced a germline mutation called Lps2, which abolishes cytokine responses to double-stranded RNA and severely impairs responses to the endotoxin(More)
Several subsets of dendritic cells have been shown to produce type I IFN in response to viral infections, thereby assisting the natural killer cell-dependent response that eliminates the pathogen. Type I IFN production can be induced both by unmethylated CpG-oligodeoxynucleotide and by double-stranded RNA. Here, we describe a codominant CpG-ODN unresponsive(More)
Here we have identified 'triple D' (3d), a recessive N-ethyl-N-nitrosourea-induced mutation and phenotype in which no signaling occurs via the intracellular Toll-like receptors 3, 7 and 9 (sensors for double-stranded RNA, single-stranded RNA and unmethylated DNA, respectively). The 3d mutation also prevented cross-presentation and diminished major(More)
AIMS Studies have used myriad measures of family history of alcoholism (FH) making it difficult to compare them directly. Commonly used FH measures partition samples into the well known positive (FH+) and negative (FH-) dichotomy, although quantitative measures of density potentially provide more information. A standard FH measure would facilitate(More)
Hepcidin, a liver-derived protein that restricts enteric iron absorption, is the key regulator of body iron content. Several proteins induce expression of the hepcidin-encoding gene Hamp in response to infection or high levels of iron. However, mechanism(s) of Hamp suppression during iron depletion are poorly understood. We describe mask: a recessive,(More)
The treatment outcome literature suggests that alcoholics with coexisting drug dependence have worse prognoses. We compared three groups of inpatients treated on the same hospital unit for disorders of alcohol only (n = 51), cocaine only (n = 27), or both disorders (dual group, n = 27). At follow-up, we contacted 105 (81%) of 129 patients at a mean of 13.4(More)
Few prospective studies have examined older problem-drinkers not currently in treatment to determine the stability in alcohol problems over time. Seventy-eight currently drinking, older adults meeting a diagnosis of alcohol abuse or dependence were recruited via advertising to complete a health interview; 48 were reinterviewed approximately 3 years later.(More)