Bone morphogenetic proteins (BMPs) are members of the transforming growth factor ,B superfamily. Bone morphogenetic proteins (BMPs) are a family of proteins that induce bone formation at extraskeletal sites in vivo (reviewed in refs. 1-3). BMPs act on osteoblasts and chondrocytes (4) as well as other cell types, including neural cells (5, 6), and they play important roles in the embryonal development (3). More than a dozen proteins belong to the BMP family, including BMP-2 to -6, osteogenic protein (OP)-1 (also termed BMP-7), OP-2 (BMP-8), and growth/differentiation factors 5 to 7.BMPs belong to the transforming growth factor ,B (TGF-f3) superfamily, which includes TGF-,3s, activins/inhibins, Miillerian inhibiting substance (MIS), and glial cell line-derived neurotrophic factor (GDNF) (7). TGF-13s and activins transduce their signals through the formation of heteromeric complexes of two different types of serine(threonine) kinase

The adult cuticle of the soil nematode, Caenorhabditis elegans, is a proteinaceous extracellular structure elaborated by the underlying layer of hypodermal cells during the final molt in the animal's life cycle . The cuticle is composed of an outer cortical layer connected by regularly arranged struts to an inner basal layer. The cuticle can be isolated largely intact and free of all cellular material by sonication and treatment with 1% sodium dodecyl sulfate (SDS) . Purified cuticles exhibit a negative birefringence due to ordered material in the basal cuticle layer . The cuticle layers differ in their solubility in sulfhydryl reducing agents, susceptibility to various proteolytic enzymes and amino acid composition. The struts, basal layer, and internal cortical layer are composed of collagen proteins that are extensively cross-linked by disulfide bonds . The external cortical layer appears to contain primarily noncollagen proteins that are extensively cross-linked by nonreducible covalent bonds . The collagen proteins extracted from the cuticle with a reducing agent can be separated by SDS-polyacrylamide gel electrophoresis into eight major species differing in apparent molecular weight.

Following surgery to treat major trauma-related fractures, deep wound infection rates are high. It is not known if negative pressure wound therapy can reduce infection rates in this setting. OBJECTIVE To assess outcomes in patients who have incisions resulting from surgery for lower limb fractures related to major trauma and were treated with either incisional negative pressure wound therapy or standard wound dressing. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial conducted at 24 trauma hospitals representing the UK Major Trauma Network that included 1548 patients aged 16 years or older who underwent surgery for a lower limb fracture caused by major trauma from

Recombinant interferon alpha-2 (IFN-alpha2) is used clinically to treat a variety of viral diseases and cancers. IFN-alpha2 has a short circulating half-life, which necessitates frequent administration to patients. Previous studies showed that it is possible to extend the circulating half-life of IFN-alpha2 by modifying lysine residues of the protein with amine-reactive poly(ethylene glycol) (PEG) reagents. However, amine-PEGylated IFN-alpha2 comprises a heterogeneous product mixture with low specific activity due to the large number and critical locations of lysine residues in IFN-alpha2. In an effort to overcome these problems we determined the feasibility of creating site-specific, mono-PEGylated IFN-alpha2 analogues by introducing a free (unpaired) cysteine residue into the protein, followed by modification of the added cysteine residue with a maleimide-PEG reagent. IFN-alpha2 cysteine analogues were expressed in Escherichia coli and purified, and their in vitro bioactivities were measured in the human Daudi cell line growth inhibition assay. Several cysteine analogues were identified that do not significantly affect in vitro biological activity of IFN-alpha2. Certain of the cysteine analogues, but not wild-type IFN-alpha2, reacted with maleimide-PEG to produce mono-PEGylated proteins. The PEG-Q5C analogue retained high in vitro bioactivity (within 3- to 4-fold of wild-type IFN-alpha2) even when modified with 20- and 40-kDa PEGs. Pharmacokinetic experiments indicated that the 20-kDa PEG-Q5C and 40-kDa PEG-Q5C proteins have 20-fold and 40-fold longer half-lives, respectively, than IFN-alpha2 following subcutaneous administration to rats. These studies demonstrate the feasibility of using site-specific PEGylation technology to create a long-acting, mono-PEGylated IFN-alpha2 protein with high specific activity.