Abstract: This invention provides unique members of the Hect family of ubiquitin ligases that specifically target BMP and TGF?/activin pathway-specific Smads. The novel ligases have been named Smurf1 and Smurf2. They directly interact with Smads1 and 5 and Smad7, respectively, and regulate the ubiquitination, turnover and activity of Smads and other proteins of these pathways. Smurf1 interferes with biological responses to BMP, but not activin signaling. In amphibian embryos Smurf1 inhibits endogenous BMP signals, resulting in altered pattern formation and cell fate specification in the mesoderm and ectoderm. The present invention provides a unique regulatory link between the ubiquitination pathway and the control of cell fate determination by the TGF? superfamily during embryonic development. Thus, Smurf1 is a negative regulator of Smad1 signal transduction, by targeting Smad1, Smurf1 blocks BMP signaling.

Abstract: Medializing the middle turbinate in the nose has been realized as a solution to the common complication of adhesions following nasal and sinus surgery. The invention provides a system for medializing the middle turbinate by attaching the middle turbinate temporarily to the nasal septum. The attachment is performed using a wafer with means on both sides for attaching the wafer to a mucosal surface. The attachment may also be performed using a tissue adhesive, pins, or other medical devices described herein. The invention also provides a system for attaching the uvula to the nasopharyngeal side of the soft palate. The invention provides a medical device for use in the inventive procedures as well as methods for the procedures and kits for use by a physician.

Abstract: The invention provides implant plugs having a complex clinically acceptable proximal surface. The invention also provides multi-phase implant plugs which have a nonplanar proximal surface. Suitable implant proximal surface shapes include, but are not limited to, concave surfaces, convex surfaces, faceted domes and angled surfaces formed by the convergence of two facets. The implants of the invention are suitable for repair of tissue defects in articulating surfaces. The invention also provides delivery devices and methods for delivering the implants of the invention. The invention also provides methods for creating defects suitable for use with the implants of the invention.

Abstract: The invention provides orthopedic implants which are at least partially absorbable. The implants of the invention may include a biocompatible material in the form of a ring, which may be used in combination with a second, more porous, absorbable material. This second material may be a continuous body or discontinuous. The implant may also include a first material connected to a full or partial wedge of a second material, the wedge being connected to the inner surface of the more dense material. Suitable materials for the first and second materials include, but are not limited to, resorbable polymer composites. The implants of the invention may also include plates for anchoring of the implant.

Abstract: An implant for repairing soft tissue injuries is provided comprising at least one channel for receiving a soft tissue graft such as a tendon, ligament, or other soft tissue, to be implanted in a patient. The implant assembled with the graft is designed to fit into a bony defect, such as a graft tunnel, formed in bone of a patient. The implant can be biodegradable, and the implant-graft assembly has a pull-out strength sufficient to withstand everyday use during patient recovery.

Abstract: A new human gene, MADR2, has been cloned and sequenced, and has been identified as a tumour suppressor gene. The protein encoded by the gene, MADR2, has been shown to participate in the TGF.beta. signalling pathway and to be phosphorylated on stimulation of the TGF.beta. receptor.