Functional tissue engineering of tendon: Establishing biological success criteria for improving tendon repair

Improving tendon repair using Functional Tissue Engineering (FTE) principles has been the focus of our laboratory over the last decade. Although our primary goals were initially focused only on mechanical outcomes, we are now carefully assessing the biological properties of our tissue-engineered tendon repairs so as to link biological influences with mechanics. However, given the complexities of tendon development and healing, it remains challenging to determine which aspects of tendon biology are the most important to focus on in the context of tissue engineering. To address this problem, we have formalized a strategy to identify, prioritize, and evaluate potential biological success criteria for tendon repair. We have defined numerous biological properties of normal tendon relative to cellular phenotype, extracellular matrix and tissue ultra-structure that we would like to reproduce in our tissue-engineered repairs and prioritized these biological criteria by examining their relative importance during both normal development and natural tendon healing. Here, we propose three specific biological criteria which we believe are essential for normal tendon function: (1) scleraxis-expressing cells; (2) well-organized and axially-aligned collagen fibrils having bimodal diameter distribution; and (3) a specialized tendon-to-bone insertion site. Moving forward, these biological success criteria will be used in conjunction with our already established mechanical success criteria to evaluate the effectiveness of our tissue-engineered tendon repairs.     

Usefulness and limitations of normal mode analysis in modeling dynamics of biomolecular complexes

Various types of large-amplitude molecular deformation are ubiquitously involved in the functions of biological macromolecules, especially supramolecular complexes. They can be very effectively analyzed by normal mode analysis with well-established procedures. However, despite its enormous success in numerous applications, certain issues related to the applications of normal mode analysis require further discussion. In this review, the author addresses some common issues so as to raise the awareness of the usefulness and limitations of the method in the general community of structural biology.     

Effects of a trawling moratorium on the breeding success of the Yellow-legged Gull Larus cachinnans

The establishment of a two month commercial fishing moratorium, which overlapped each year with different stages of the breeding cycle of the Yellow-legged Gull Larus cachinnans at the Ebro Delta, Spain, provided the opportunity of testing the effects of food limitation on the breeding success of this species. The study was carried out in 1993, when the chick rearing stage occurred with normal commercial fishing activity and in 1994, when the chick rearing stage overlapped with the trawling moratorium. We recorded diet of the chicks, breeding phenology, clutch size, egg volume, hatching success and productivity of adult birds. There was a highly significant difference in the diet of the chicks between the two years and significantly lower productivity in 1994, whilst the other parameters examined did not change. These results show that a dependence on discards from commercial fishing activities may be a limiting factor in the breeding success of this seabird.     

Predicting by electromyography the results of nonsurgical treatment of temporomandibular joint syndrome.

This study of 308 patients demonstrated that reliance upon physical findings alone is not reliable for the diagnosis and the prediction of treatment success in TMJS. However, those patients who had a lengthened masseteric silent period on the EMG had a 93% success rate from treatment with occlusal splint and occlusal adjustment. In contrast, those patients who had a normal masseteric silent period on the EMG had only a 21 percent success rate from the same therapy.     

Live fast, die young: trade-offs between fitness components and sexually antagonistic selection on weaponry in Soay sheep

Males are predicted to compete for reproductive opportunities, with sexual selection driving the evolution of large body size and weaponry through the advantage they confer for access to females. Few studies have explored potential trade-offs of investment in secondary sexual traits between different components of fitness or tested for sexually antagonistic selection pressures. These factors may provide explanations for observed polymorphisms in both form and quality of secondary sexual traits. We report here an analysis of selection on horn phenotype in a feral population of Soay sheep (Ovis aries) on the island of Hirta, St. Kilda, Scotland. Soay sheep display a phenotypic polymorphism for horn type with males growing either normal or reduced (scurred) horns, and females growing either normal, scurred, or no (polled) horns; further variation in size exists within horn morphs. We show that horn phenotype and the size of the trait displayed is subject to different selection pressures in males and females, generating sexually antagonistic selection. Furthermore, there was evidence of a trade-off between breeding success and longevity in normal-horned males, with both the normal horn type and larger horn size being associated with greater annual breeding success but reduced longevity. Therefore, selection through lifetime breeding success was not found to act upon horn phenotype in males. In females, a negative association of annual breeding success within the normal-horned phenotype did not result in a significant difference in lifetime fitness when compared to scurred individuals, as no significant difference in longevity was found. However, increased horn size within this group was negatively associated with breeding success and longevity. Females without horns (polled) suffered reduced longevity and thus reduced lifetime breeding success relative the other horn morphs. Our results therefore suggest that trade-offs between different components of fitness and antagonistic selection between the sexes may maintain genetic variation for secondary sexual traits within a population.     

Age-related decrease in male reproductive success and song quality in Drosophila montana

In the present paper, we have studied the effects of aging onmale reproductive success and song quality in Drosophila montana.We analyzed the reproductive success of wild-caught males attheir normal breeding age during the mating season and aftermaintaining the males in laboratory from 1 to 5 months. In linewith the mutation accumulation theory of aging, none of thefactors affecting the reproductive success of wild-caught malesduring the mating season were related to male longevity. However,mating activity and progeny production of the males decreasedwith male age. Interestingly, there was no significant variationin progeny production between males at their normal breedingage, whereas at older age, the variation between males becomessignificant. The quality of sexually selected song traits deterioratedwith male age in concert with the decrease in male reproductivesuccess. The size of the males did not have an effect on malereproductive success at the normal breeding age, but at olderage, larger males were able to maintain the sexually selectedcarrier frequency of the song at higher level than the smallermales. We conclude that by experimentally extending the reproductiveage of the males beyond that which they normally experiencein nature, it is possible to expose relationships between reproductivesuccess, sexually selected characters, and body size that arenot apparent when analyzed for the males at their normal breedingage.     

The ins and outs of EBV infection

Epstein-Barr virus (EBV) infects almost the entire adult population of the world. The success of this virus appears to be based on its ability to infect the B cell, rather than any other cell type. We review EBV B-cell tropism, and discuss the mechanisms by which the virus may gain access to, and egress from, B cells in the normal host.     

Transformations of osteoclast phenotype in ia rats cured of congenital osteopetrosis

The reduced bone resorption characteristic of osteopetrosis is accompanied in the incisors-absent (ia) rat mutation by a significant increase in osteoclasts of inactive (mutant) phenotype. Restoration of bone resorption in ia rats by transfer of spleen cells from normal littermates is preceded by a transformation of osteoclasts from mutant to normal phenotype. In this investigation the proportions of osteoclasts of normal phenotype have been determined by light microscopy in untreated ia and normal rats and in ia rats treated with various cell populations from normal rats. Significant increases in numbers of osteoclasts of normal phenotype were seen in the mutant skeleton soon after cell treatments that eventually restored bone resorption and cured the disease. No changes in osteoclast phenotype were seen after cell transfers that did not cure the disease. These data establish transformation of osteoclast phenotype as an early event in the recovery from osteopetrosis and suggest that determination of osteoclast phenotype is a reliable predictor of the success of normal cell populations to restore bone resorption in this mutation.     

Predator‐mediated effects of severe drought associated with poor reproductive success of a seabird in a cross‐ecosystem cascade

Despite the profound impacts of drought on terrestrial productivity in coastal arid ecosystems, only a few studies have addressed how drought can influence ecological cascades across ecosystem boundaries. In this study, we examine the consequences of rainfall pulses and drought that subsequently impact the breeding success of a threatened nocturnal seabird, the Scripps's Murrelet (Synthliboramphus scrippsi). On an island off the coast of southern California, the main cause of reduced nest success for one of their largest breeding colonies is egg predation by an endemic deer mouse (Peromyscus maniculatus elusus). Mice on the island have an opportunistic diet of primarily terrestrial sources, but drastic declines in terrestrial productivity from drought might be expected to increase their reliance on marine resources, including murrelet eggs. We compiled data on terrestrial and marine productivity between 1983 and 2013 to determine how conditions in these ecosystems influence murrelet nest success. We found that the severity of drought had the strongest negative impact on murrelet nest success. We calculated that the reduction in fecundity during drought years due to increased egg predation by mice was substantial enough to produce a declining population growth rate. Nest success was much higher under normal or high rainfall conditions, depending on whether oceanic conditions were favorable to murrelets. Therefore, the more frequent and severe drought that is projected for this region could lead to an increased risk of murrelet population decline on this island. Our study highlights the need for understanding how species interactions will change through the effects of increasing drought and altered rainfall regimes under global change.     

Mortality during dispersal and the cost of host-specificity in parasites: how many aphids find hosts?

1. For a full assessment of explanations for the evolution of host-specificity it is necessary to estimate the probability that a dispersing parasite finds a host. We develop a method of estimating this success rate from samples of dispersing parasites and populations resident on hosts.
2. Applying this method to data on the bird cherry-oat aphid, Rhopalosiphum padi (L.), from southern Scotland in 1984–92, we estimate that 0·6% of the autumn migrants find hosts.
3. With such a low success rate, there should be selection for a broadening of host range, to include any host on which the colonist's fitness is more than about 0·6% of that on the normal hosts. We argue that neither nutrition nor the need for 'enemy-free space' are sufficient explanations of the host-specificity of this animal, and propose instead that it is the host's role as a rendezvous for mating that constrains the migrants to their costly host-specificity.
4. We also discuss the implications of this low success rate for the hypothesis that aphids speciate sympatrically through the formation of host races.     

The feasibility of using the sterile insect technique against Liriomyza trifolii (Diptera: Agromyzidae) infesting greenhouse chrysanthemum

Liriomyza trifolii is a serious pest of chrysanthemum greenhouses and other crops around the world. The larvae feed within the leaves of the host plants and create serpentine mines. The Sterile Insect Technique (SIT) has been successfully used against some Dipteran species in the field, and it is especially efficient against isolated populations like those on islands. Therefore, SIT against pest populations in confined environments such as greenhouses should have high potential for success. The objectives of this study were to determine the optimum gamma‐irradiation dosage required for the sterilisation of L. trifolii adults, and to determine the quality (emergence percentage, flight ability, longevity, copulatory success, and sperm transfer) of the irradiated males compared with that of non‐irradiated (normal) males. We found that sterility (< 0.7 mine per female) was achieved with the dose of 170 ± 5% Gy. The copulatory success and sperm transfer during copulation of the sterile males were not significantly different from those of normal males. Moreover, the longevity, emergence percentage and flight ability of irradiated males were also not significantly different from normal males. The SIT experiments suggest that the release of sterile L. trifolii can significantly reduce the reproductive capacity of a wild leafminer population. Our studies indicate that sterilisation of L. trifolii flies is feasible and that sterile males are of high quality and competitive with normal males. Based on these data, research on the use of SIT against L. trifolii populations in greenhouses is ongoing.     

Lentiviral mediated transgenesis by in vivo manipulation of spermatogonial stem cells

This report describes a technique for the generation of transgenic mice by in vivo manipulation of spermatogonial stem cells with a high rate of success. Spermatogonial stem cells (SSCs) in pre-pubescent animals were infected in vivo with recombinant lentiviruses expressing EGFP-f and mated with normal females. All male pre-founder mice produced transgenic pups with an overall success rate of over 60%. The transgene was heritable and the pre-founder mice could be used in multiple mating experiments. This technology could be used to perform overexpression/knockdown screens in vivo using bar-coded lentiviruses, thus permitting the design of genetic screens in the mouse. Further, this technology could be adapted to other laboratory animals resulting in the generation of model systems that closely approximate human development and disease.     

A new technique of coronary artery ligation: Experimental myocardial infarction in rats in vivo with reduced mortality

In vivo models of myocardial infarction following coronary artery ligation in the rat still suffer from high early mortality and a low rate of success of myocardial infarction. This study investigated the possibility of reducing early mortality and increasing the rate of myocardial infarction by modifications of surgical techniques. Eighteen rats were divided into two groups: normal control (3 rats) and ligation (15 rats). The major modifications of surgical techniques used in this study include: (1) no exteriorization of the heart, (2) ligation of the origins of the branches rather than the main trunk of the left coronary artery, (3) removal of air from the chest after closure, (4) supplying oxygen immediately after extubation. Following surgery, the rats recovered uneventfully and 11 rats were alive after 16 weeks. One rat, with a large myocardial infarction, died 2 h after surgery. Early mortality (during surgery and 1 week after surgery) was 6.7% with a success rate of myocardial infarction of 85%. The left ventricle in the ligation group showed significant dilation relative to normal and shamoperated control hearts (317% of control hearts, p < 0.001). However, myocardial mass did not increase. The average infarct size was 33%. These results demonstrate that a reduction in early mortality and an increased success rate of myocardial infarction can be achieved by modifications of surgical techniques.     

Technique of foot lengthening and shaping with free vascularized iliac osteocutaneous flap.

The iliac osteocutaneous flap has been used widely to replace bony defects of the mandible and the extremities. We report a further application of this flap in foot reconstruction. The iliac osteocutaneous flap proved to be of value to augment both soft tissue and bone in a transmetatarsally amputated foot. This resulted in satisfactory function and an appealing cosmetic result, allowing the patient to wear normal shoes. Flap design and secondary contouring procedures are described for the success of this reconstruction.     

Reaching new heights: insights into the genetics of human stature

Human height is a highly heritable, classic polygenic trait. Until recently, there had been limited success in identifying the specific genetic variants that explain normal variation of human height. The advent of large-scale genome-wide association studies, however, has led to dramatic progress. In the past 18 months, the first robust common variant associations were identified and there are now 44 loci known to influence normal variation of height. In this review, we summarize this exciting recent progress, discuss implicated biological pathways, the overlap with monogenic growth and skeletal dysplasia syndromes, links to disease and insights into the genetic architecture of this model polygenic trait. We also discuss the strong probability of finding several hundred more such loci in the near future.     

蜜环菌菌种分离新法——天麻组织分离法

报道了一蜜环菌菌种分离方法——天麻组织分离法,并对此法与常用分离法——菌索分离法进行比较试验。结果发现,天麻组织分离法分离成功率高（78％）,远高于常用的菌索分离法（16％）,且前者操作简便、难度低,所得菌种生活活力、生长形态均优于后法。     

May random processes explain mating success in leks?

The object of this paper is to verify whether in specific cases the variance of mating success among lekking males may be due exclusively to a random mechanism, as opposed to the adaptive mechanisms of mate choice which are usually postulated in the literature in the framework of sexual selection theory. In fact, some studies attempted to compare observed distributions of male mating success with a Poisson ‘null’ distribution based on the conjecture of random mating; the conjecture is usually rejected. In this paper we construct a plausible model (the ‘null’ hypothesis) for a strictly random non-adaptive pattern of social behaviour of lekking males and females and we perform several simulations for reasonable choices of parameter values. It should be observed that some of the simulations based on our random model lead to a distribution of male mating success which is Poisson-like. However, contrary to predictions, in several simulations a random process of mate choice lead to non-Poissonian distributions. Accordingly, the fact that, when performing a statistical test on several sets of field data, we find both cases which are in agreement with Poisson distribution, or a normal one, and cases which are not, does not allow us to reject the assumption of random male reproductive success. Thus it is legitimate to conjecture that in many cases the inter-individual variability of male mating success might indeed be determined by random processes. If this conjecture were to be confirmed by further studies, the actual significance of sexual selection in the evolution of lekking species should be reassessed, and a novel approach in the analysis of field data would be called for.     

Fluctuating asymmetry, size and mating success in males of Ischnura elegans (Vander Linden) (Odonata: Coenagrionidae)

Fluctuating asymmetry (FA) is thought to be an indicator of developmental stability and negatively related to male mating success in many animal taxa. We investigated the relationships between mating success of males, body size and FA for both wing length and number of setae on the legs in the damselfly Ischnura elegans. Males were classified as mated or unmated at the time of sampling. Fluctuating asymmetry, expressed as right-left differences, showed normal distributions without evidence of directional asymmetry or antisymmetry. Univariate analyses showed a significant negative correlation between size and mating success, and significant negative correlations between FA and mating success for both characters. On the other hand, with a multivariate analysis, new to studies on FA, the effect of body size was still significant but FA did not reach significance for either character. We conclude that the multivariate analysis should be used to assess the role of the different factors affecting mating success. Copyright 2000 The Association for the Study of Animal Behaviour.     

Climate fluctuation effects on breeding of blue penguins (Eudyptula minor)

Abstract

El Niño and La Niña climate perturbations alter sea currents and food availability for seabirds in many areas of the world. This changes their breeding success and mortality. Blue penguin (Eudyptula minor) breeding success is dependent upon whether one or two clutches per season are laid, and the hatching and fledging success of these clutches. This study uses six years of data from five blue penguin breeding colonies, three from Taiaroa Head, Otago Peninsula and two from Oamaru, to examine whether annual variation in breeding success correlates with El Niño/La Niña perturbations. When La Niña conditions prevailed, penguins started breeding later, and there was a lower proportion of double breeders than in El Niño and normal years. The probability of a newly hatched chick surviving to fledging was also dependent on whether large‐scale climatic conditions prevailed, whereas hatching success and overall breeding success (number of fledged chicks per breeding pair) showed no correlation with climate perturbations.