A hyperelastic fibre-reinforced continuum model of healing tendons with distributed collagen fibre orientations

The healing process of ruptured tendons is problematic due to scar tissue formation and deteriorated material properties, and in some cases, it may take nearly a year to complete. Mechanical loading has been shown to positively influence tendon healing; however, the mechanisms remain unclear. Computational mechanobiology methods employed extensively to model bone healing have achieved high fidelity. This study aimed to investigate whether an established hyperelastic fibre-reinforced continuum model introduced by Gasser, Ogden and Holzapfel (GOH) can be used to capture the mechanical behaviour of the Achilles tendon under loading during discrete timepoints of the healing process and to assess the model’s sensitivity to its microstructural parameters. Curve fitting of the GOH model against experimental tensile testing data of rat Achilles tendons at four timepoints during the tendon repair was used and achieved excellent fits (\(0.9903 < R^{2 }<0.9986\)). A parametric sensitivity study using a three-level central composite design, which is a fractional factorial design method, showed that the collagen-fibre-related parameters in the GOH model—\(\kappa , {k_{{1}}}^{{\prime }}\) and \({k_{{2}}}^{{\prime }}\)—had almost equal influence on the fitting. This study demonstrates that the GOH hyperelastic fibre-reinforced model is capable of describing the mechanical behaviour of healing tendons and that further experiments should focus on establishing the structural and material parameters of collagen fibres in the healing tissue.     

Simultaneous expression of salivary and pancreatic amylase genes in cultured mouse hepatoma cells.

The tissue-specific expression of two types of mouse amylase genes does not overlap in vivo; the Amy-1 locus is transcribed in the parotid gland and the liver, while expression of Amy-2 is limited to the pancreas. We identified a mouse hepatoma cell line, Hepa 1-6, in which both amylase genes can be simultaneously expressed. Amy-1 is constitutively active in these cells and is inducible by dexamethasone at the level of mRNA. We demonstrated that the liver-specific promoter of Amy-1 is utilized by the dexamethasone-treated hepatoma cells, and that glucocorticoid consensus sequences are present upstream of this promoter. Amy-2 is not detectable constitutively, but can be activated if the cells are cultured in serum-free medium containing dexamethasone. Expression of Amy-2 in a nonpancreatic cell type has not previously been observed. We speculate that induction of Amy-1 and activation of Amy-2 may involve different regulatory mechanisms. Hepa 1-6 cells provide an experimental system for molecular analysis of these events.     

Herpesvirus Envelopment

The growth and envelopment processes of three representative herpesviruses, equine abortion, pseudorabies, and herpes simplex, were examined in baby hamster kidney (BHK 21/13) cells by bioassay (plaque-forming units) and electron microscopy. The envelopment process was identical for all three viruses. After assembly in the nucleus, the nucleocapsid acquired an envelope by budding from the inner nuclear membrane. This membrane was reduplicated as the enveloped particle was released so that the budding process did not result in disruption of the continuity of the nuclear membrane. That portion of the nuclear membrane which comprised the viral envelope was appreciably thicker than the remainder of the membrane and exhibited numerous projections on its surface. Once enveloped, the viral particles were seen in vesicles and vacuoles in the cell cytoplasm. These appeared to open at the cytoplasmic membrane, releasing the virus from the cell. There was no detectable difference in the size or appearance of enveloped particles in intra- or extracellular locations.     

Use of Analogues and the Substrate-Sensitivity of Mutants in Analysis of Purine Uptake and Breakdown in Aspergillus nidulans

Aspergillus mutants resistant to various purine analogues (purine, 8-azaguanine, 2-thioxanthine, and 2-thiouric acid) are defective in at least one step of purine uptake or breakdown. The properties of these mutants show that there are two uptake systems for purines, one which mediates the uptake of hypoxanthine, guanine, and adenine, and the other, xanthine and uric acid. Allantoinase-less strains are sensitive to the toxic effects of allantoin accumulation. They are severely inhibited when grown in the presence of naturally occurring purines. Mutant strains derived from these, resistant to naturally occurring purines, may be isolated. These are either wild-type revertants, or carry a second metabolic block in the uptake or breakdown of purines. The properties of these double mutants confirm the interpretation of the nature of the analogue-resistant mutants.     

Regression modelling of HLA haplotype sharing in affected siblings

A link between the HLA system and disease susceptibility can be assessed through the observation of families containing two or more affected siblings. Departures from Mendelian inheritance of the parental haplotypes among the affected siblings are an indication of such a relationship. Other variables, such as environmental factors, may also be related to disease susceptibility. An approach to examining the degree of haplotype sharing and the effect of other variables of interest on observed sharing is presented and two examples analyzed.