So far in this course we have dealt entirely with the evolution of characters that are controlled by simple Mendelian inheritance at a single locus. There are notes on the course website about gametic disequilibrium and how allele frequencies change at two loci simultaneously, but we didn’t discuss them. In every example we’ve considered we’ve imagined that we could understand something about evolution by examining the evolution of a single gene. That’s the domain of classical population genetics. For the next few weeks we’re going to be exploring a field that’s actually older than classical population genetics, although the approach we’ll be taking to it involves the use of population genetic machinery. If you know a little about the history of evolutionary biology, you may know that after the rediscovery of Mendel’s work in 1900 there was a heated debate between the “biometricians” (e.g., Galton and Pearson) and the “Mendelians” (e.g., de Vries, Correns, Bateson, and Morgan). Biometricians asserted that the really important variation in evolution didn’t follow Mendelian rules. Height, weight, skin color, and similar traits seemed to

Human biochemical genetics

Background Full-thickness defects of articular cartilage in the knee have a poor capacity for repair. They may progress to osteoarthritis and require total knee replacement. We performed autologous chondrocyte transplantation in 23 people with deep cartilage defects in the knee. Methods The patients ranged in age from 14 to 48 years and had full-thickness cartilage defects that ranged in size from 1.6 to 6.5 cm2. Healthy chondrocytes obtained from an uninvolved area of the injured knee during arthroscopy were isolated and cultured in the laboratory for 14 to 21 days. The cultured chondrocytes were then injected into the area of the defect. The defect was covered with a sutured periosteal flap taken from the proximal medial tibia. Evaluation included clinical examination according to explicit criteria and arthroscopic examination with a biopsy of the transplantation site. Results Patients were followed for 16 to 66 months (mean, 39). Initially, the transplants eliminated knee locking and reduced pain and s...

Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation

Osteoprotegerin Ligand Is a Cytokine that Regulates Osteoclast Differentiation and Activation

This paper is concerned with the mathematical structure of the immersed boundary (IB) method, which is intended for the computer simulation of fluid–structure interaction, especially in biological fluid dynamics. The IB formulation of such problems, derived here from the principle of least action, involves both Eulerian and Lagrangian variables, linked by the Dirac delta function. Spatial discretization of the IB equations is based on a fixed Cartesian mesh for the Eulerian variables, and a moving curvilinear mesh for the Lagrangian variables. The two types of variables are linked by interaction equations that involve a smoothed approximation to the Dirac delta function. Eulerian/Lagrangian identities govern the transfer of data from one mesh to the other. Temporal discretization is by a second-order Runge–Kutta method. Current and future research directions are pointed out, and applications of the IB method are briefly discussed. Introduction The immersed boundary (IB) method was introduced to study flow patterns around heart valves and has evolved into a generally useful method for problems of fluid–structure interaction. The IB method is both a mathematical formulation and a numerical scheme. The mathematical formulation employs a mixture of Eulerian and Lagrangian variables. These are related by interaction equations in which the Dirac delta function plays a prominent role. In the numerical scheme motivated by the IB formulation, the Eulerian variables are defined on a fixed Cartesian mesh, and the Lagrangian variables are defined on a curvilinear mesh that moves freely through the fixed Cartesian mesh without being constrained to adapt to it in any way at all.

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The immersed boundary method

http://basicmed.med.ncku.edu.tw/admin/up_img/990319-2.pdf

Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling

PERSPECTIVES AND SUMMARy 717 LYSYL OXIDASE 719 COLLAGEN 720 Allysine and Hydroxyallysine Pathways 720 Hydroxypyridinium Residues... ... 724 Molecular Sites 730 Basement Membranes 733 Methods oj Analysis 734 Alternative M echanisms ..... ... 734

Cross-linking in collagen and elastin

Quantitation of hydroxypyridinium crosslinks in collagen by high-performance liquid chromatography.

Peptides of low molecular weight that contain pyridinoline cross-links were isolated from adolescent human urine. A fraction was selected that was enriched in the N-telopeptide-to-helix intermolecular cross-linking domain of bone type I collagen. Mouse monoclonal antibodies were generated against these urinary peptides conjugated to a carrier protein as immunogen. A high-affinity antibody was identified that specifically bound to the trivalent peptides derived from the N-telopeptide-to-helix pyridinoline cross-linking site in type I collagen of human bone. This was confirmed by the direct isolation from human bone collagen of similar fragments recognized selectively by the antibody. A sensitive inhibition ELISA was established on microtiter plates that could quantify the bone-derived peptides in human urine. The assay, which can be run directly on untreated urine, was thoroughly tested against samples from normal subjects and from patients with metabolic bone disease. For example, strong correlations with urinary hydroxyproline and total pyridinoline cross-links were found in patients with Paget's disease of bone. The method shows considerable promise as a rapid and specific index of human bone resorption rates, with greatly improved specificity and convenience over total pyridinoline analysis. Potential applications include the study of normal metabolism, the diagnosis and monitoring of bone disease, and evaluating the effectiveness of antiresorption therapies.

A specific immunoassay for monitoring human bone resorption: quantitation of type I collagen cross-linked N-telopeptides in urine

The extracellular framework and two-thirds of the dry mass of adult articular cartilage are polymeric collagen. Type II collagen is the principal molecular component in mammals, but collagens III, VI, IX, X, XI, XII and XIV all contribute to the mature matrix. In developing cartilage, the core fibrillar network is a cross-linked copolymer of collagens II, IX and XI. The functions of collagens IX and XI in this heteropolymer are not yet fully defined but, evidently, they are critically important since mutations in COLIX and COLXI genes result in chondrodysplasia phenotypes that feature precocious osteoarthritis. Collagens XII and XIV are thought also to be bound to fibril surfaces but not covalently attached. Collagen VI polymerizes into its own type of filamentous network that has multiple adhesion domains for cells and other matrix components. Collagen X is normally restricted to the thin layer of calcified cartilage that interfaces articular cartilage with bone.

/pdf/articular-cartilage-and-changes-in-arthritis-collagen-of-2w6asmcvjk.pdf

Articular cartilage and changes in Arthritis: Collagen of articular cartilage

Wounds penetrating articular cartilage to bone heal with cartilage described variably as either fibrous or hyaline. In the present study, such repair cartilage was induced in the rabbit for biochemical comparison with normal articular cartilage. The main collagen in the repair tissue after three weeks was type I. By six to eight weeks, type II had become predominant and continued to be enriched up to one year; but type I still persisted as a significant constituent of the repair tissue even after a year, so the repair cartilage never fully resembled normal articular cartilage. From radiochemical analysis, type II was determined to be the major collagen synthesized by the repair tissue after three to four weeks. After six months, the repair cartilage contained more collagen and less hexosamine than control cartilage, suggesting that the fibrous texture that often developed was due to a loss of proteoglycans rather than to a change in the type of collagen. Clinical Relevance: Procedures capable of inducing the differentiation of authentic articular cartilage to resurface degenerated human joints would be invaluable. Surgical methods, such as drilling through to subchondral bone, are often attempted. It is not known, however, whether the cartilage that forms is true articular cartilage or, for example, fibrocartilage. The present experimental study in rabbits compared the properties of such repair cartilage with those of normal articular cartilage.

David R. Eyre

Papers

Cross-linking in collagen and elastin

Quantitation of hydroxypyridinium crosslinks in collagen by high-performance liquid chromatography.

A specific immunoassay for monitoring human bone resorption: quantitation of type I collagen cross-linked N-telopeptides in urine

Articular cartilage and changes in Arthritis: Collagen of articular cartilage

Biochemical studies on repair cartilage resurfacing experimental defects in the rabbit knee.