![]() These findings are consistent with phase separation models of nucleolar formation and physical protein properties being a major contributing mechanism for eukaryotic nucleolar targeting, conserved from the last eukaryotic common ancestor. Using protein truncations and addition of candidate targeting sequences to proteins, we show both homopolymer runs and distributed basic amino acids give nucleolar partition, further aided by a nuclear localisation signal (NLS). brucei nucleolar proteins have similar properties to those in common model eukaryotes, specifically basic amino acids. Here, we exploit a new genome-wide analysis of protein localisation in the early-branching eukaryote Trypanosoma brucei to analyse general nucleolar protein properties. Nucleolar targeting relies on positively charged localisation signals and has received rejuvenated interest since the widespread recognition of liquid–liquid phase separation (LLPS) as a mechanism contributing to nucleolus formation. The combination of a nondamaging process, successful removal of cells, and reduction of xenogeneic -Gal antigens from the porcine dermal matrix are critical for producing a material with the ability to remodel and integrate into host tissue and ultimately support soft tissue regeneration.The compartmentalised eukaryotic cell demands accurate targeting of proteins to the organelles in which they function, whether membrane-bound (like the nucleus) or non-membrane-bound (like the nucleolus). Serum ELISA revealed an initial anti-Gal induction that decreased to baseline levels over time in the primates implanted with WT-PADM, whereas no or minimal anti-Gal activity was detected in the primates implanted with PADM or Gal-reduced PADM. Explants from the abdominal wall showed evidence of remodeling, notably fibroblast cell repopulation and revascularization, as early as 1 month. ![]() Minimal modification to the extracellular matrix was assessed by evaluation of intact structure as demonstrated by staining patterns for type I and type VII collagens, laminin, and fibronectin similar to native porcine skin tissues. Anti-Gal activity in the serum of monkeys implanted subcutaneously was assessed by ELISA. In vivo performance was evaluated by implantation into the abdominal wall of Old World primates in an exisional repair model. Extracellular matrix composition and integrity was assessed by histological, immunohistochemical (IHC), and ultrastructural analysis. In addition, the WT tissue was subjected to an enzymatic treatment to minimize the presence of -Gal (Gal-reduced PADM). Dermal tissue from wild-type (WT-porcine-derived acellular dermal matrix ) or Gal-deficient ( PADM) pigs was processed to remove cells and DNA while preserving the structural integrity of the extracellular matrix. The ability to produce a porcine-derived graft that retains the structural integrity of the extracellular matrix and minimizes potential antigenic response to galactose-(1,3)-galactose terminal disaccharide (-Gal) may allow the scaffold to support regeneration of native tissue. ![]() Abstract : Sub-optimal clinical outcomes after implantation of animal-derived tissue matrices may be attributed to the nature of the processing of the material or to an immune response elicited in response to xenogeneic epitopes. ![]()
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