Myeloid DAP12-associating lectin (MDL)-1 regulates synovial inflammation and bone erosion associated with autoimmune arthritis.

DNAX adaptor protein 12 (DAP12) is a trans-membrane adaptor molecule that transduces activating signals in NK and myeloid cells. Absence of functional Dap12 results in osteoclast defects and bone abnormalities. Because DAP12 has no extracelluar binding domains, it must pair with cell surface receptors for signal transduction. There are at least 15 known DAP12-associating cell surface receptors with distinct temporal and cell type-specific expression patterns. Our aim was to determine which receptors may be important in DAP12-associated bone pathologies. Here, we identify myeloid DAP12-associating lectin (MDL)-1 receptor (also known as CLEC5A) as a key regulator of synovial injury and bone erosion during autoimmune joint inflammation. Activation of MDL-1 leads to enhanced recruitment of inflammatory macrophages and neutrophils to the joint and promotes bone erosion. Functional blockade of MDL-1 receptor via Mdl1 deletion or treatment with MDL-1-Ig fusion protein reduces the clinical signs of autoimmune joint inflammation. These findings suggest that MDL-1 receptor may be a therapeutic target for treatment of immune-mediated skeletal disorders

Myeloid DAP12-associating lectin (MDL)-1 regulates synovial inflammation and bone erosion associated with autoimmune arthritis

DNAX adaptor protein 12 (DAP12) is a trans-membrane adaptor molecule that transduces activating signals in NK and myeloid cells. Absence of functional Dap12 results in osteoclast defects and bone abnormalities. Because DAP12 has no extracelluar binding domains, it must pair with cell surface receptors for signal transduction. There are at least 15 known DAP12-associating cell surface receptors with distinct temporal and cell type–specific expression patterns. Our aim was to determine which receptors may be important in DAP12-associated bone pathologies. Here, we identify myeloid DAP12-associating lectin (MDL)-1 receptor (also known as CLEC5A) as a key regulator of synovial injury and bone erosion during autoimmune joint inflammation. Activation of MDL-1 leads to enhanced recruitment of inflammatory macrophages and neutrophils to the joint and promotes bone erosion. Functional blockade of MDL-1 receptor via Mdl1 deletion or treatment with MDL-1-Ig fusion protein reduces the clinical signs of autoimmune joint inflammation. These findings suggest that MDL-1 receptor may be a therapeutic target for treatment of immune-mediated skeletal disorders

Perceptions of wood in rivers and challenges for stream restoration in the United States

This article reports a study of the public perception of large wood in rivers and streams in the United States. Large wood is an element of freshwater aquatic ecosystems that has attracted much scientific interest in recent years because of its value in biological and geomorphological processes. At the heart of the issue is the nature of the relationship between scientific recognition of the ecological and geomorphological benefits of wood in rivers, management practices utilizing wood for river remediation progress, and public perceptions of in-channel wood. Surveys of students' perceptions of riverscapes with and without large wood in the states of Colorado, Connecticut, Georgia, Illinois, Iowa, Missouri, Oregon, and Texas suggest that many individuals in the United States adhere to traditionally negative views of wood. Except for students in Oregon, most respondents considered photographs of riverscapes with wood to be less aesthetically pleasing and needing more improvement than rivers without wood. Analysis of reasons given for improvement needs suggest that Oregon students are concerned with improving channels without wood for fauna habitat, whereas respondents elsewhere focused on the need for cleaning wood-rich channels for flood risk management. These results underscore the importance of public education to increase awareness of the geomorphological and ecological significance of wood in stream systems. This awareness should foster more positive attitudes toward wood. An integrated program of research, education, and policy is advocated to bridge the gap between scientific knowledge and public perception for effective management and restoration of river systems with wood