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Cancer-associated fibroblasts (CAFs) are major components of the carcinoma microenvironment that promote tumor progression. However, the mechanisms by which CAFs regulate cancer cell migration are poorly understood. In this study, we show that fibronectin assembled by CAFs mediates CAF-cancer cell association and directional migration. Compared to normal fibroblasts (NFs), CAFs produce a fibronectin (Fn)-rich extracellular matrix (ECM) with anisotropic fiber orientation, which guides the cancer cells to migrate directionally. CAFs align the Fn matrix by increasing MyoII- and PDGFRa-mediated contractility and traction forces which are transduced to Fn through a5b1 integrin. We further show that prostate cancer cells use av integrin to migrate efficiently and directionally on CAF-derived matrices. We also demonstrate that aligned Fn is a prominent feature of invasion sites in human prostatic and pancreatic carcinoma samples. Collectively, we present a new mechanism by which CAFs organize the Fn matrix and promote directional cancer cell migration.

An exploited single-species population model with a density dependent reproductive function is constructed, in which recruitment to the adult breeding population may occur in one of several possible age classes. The parent is assumed capable of giving birth only once. It is also assumed that all density dependence is concentrated in the first year of life. A linearized stability analysis of the multiply-delayed difference equation model is carried out and a sufficient condition for stability is derived for the general case, while necessary and sufficient conditions are found in specific examples. Some indication of the complicated bifurcation structure of the model is given by a series of computer simulation plots. Finally, the method of Lagrange multipliers is used to find the optimal equilibrium escapement level for the original exploited population model. / Science, Faculty of / Mathematics, Department of / Graduate

Legume species nodulate and grow successfully in the Core Cape Subregion, a Mediterranean-climate ecosystem with fynbos vegetation found on infertile soils. The physiological mechanisms enabling tolerance of low availability of phosphorus (P) are yet to be reported in Cape legume species such as Aspalathus linearis and Podalyria calyptrata; species that demonstrated traits typical of plants from nutrient poor soils. In the three research chapters of the thesis, it was anticipated that low P supply would limit plant growth and increase expression of traits for P acquisition.

Moult is an energetically demanding process for birds, and the replacement of flight feathers impacts flight performance. As a result, few birds overlap moult with other key activities such as breeding or migrating. Feather growth rates show little change in relation to body size, so large birds with long flight feathers take a long time to grow individual feathers, making their moult even more challenging. Unless these birds can afford to become flightless for several weeks while they replace all their flight feathers simultaneously, many large birds lack sufficient time to breed and replace all their wing feathers each year. As a result, they have evolved complex moult strategies that replace a subset of feathers each year. Albatrosses and giant petrels are prime examples of birds facing this challenge. This study focusses on Wandering Albatrosses (Diomedea exulans) and Northern Giant Petrels (Macronectes halli) breeding at Marion Island and Southern Giant Petrels (M. giganteus) at Gough Island. I explore primary and secondary moult patterns in Wandering Albatrosses and secondary and greater secondary coverts in giant petrels in relation to breeding activity. I used digital photography to record the wear patterns in the wings of Wandering Albatrosses and giant petrels. Using photographs of upperwings of marked individuals over time allowed the opportunity to track changes in the wear pattern among specific feathers, although scoring feather wear from images works better for darker feathers. The rate of wear among secondaries and their coverts differed across the wing, with the inner feathers wearing faster than the central feathers. Photographing the extended wings of albatrosses and petrels incubating eggs had no impact on hatching success. Using this method I was able to test the often held assumption that wing feather moult is largely symmetrical. In Wandering Albatrosses, moult symmetry was greatest in outer flight feathers, especially primaries. However, the pattern of increasing asymmetry towards the body was not consistent; inner primaries showed less symmetry than outer secondaries and inner secondaries were moulted with greater symmetry than central secondaries. Giant petrels preferentially replaced the inner and outer secondaries and the inner and outer greater secondary coverts, and feather symmetry was greatest in these feathers. All three species indicated some asymmetry in all feathers that had an incomplete annual 2 moult. Depending on the question being asked, I recommend scoring both wings when investigating moult patterns. Wandering Albatrosses typically take a sabbatical year following a successful breeding attempt, and thus failed breeders usually have less time to moult between successive breeding attempts. Following a successful breeding attempt, Wandering Albatrosses from Marion Island replaced a similar number of primary feathers on average (males 7.9 and females 7.3) as birds from the Crozet Islands (males 8.8 and females 8.1) and South Georgia (males 8.6 and females 7.1). Wandering Albatrosses that do not skip a year following a failed breeding attempt, not only replaced fewer feathers on average, but showed a difference in number of feathers replaced between sexes at Marion Island (males 7.4, females 6.1), as previously reported at the Crozet Islands (males 8.3, females 6.5) and South Georgia (males 7.2, females 5.2). These results suggest that females are under greatest pressure when a breeding attempt fails. Because females from South Georgia replace fewer feathers, especially following a failed breeding attempt, they might be under more stress than females from populations breeding at islands in the Indian Ocean (Marion and Crozet). This parallels the contrasting population trends in these regions, with numbers increasing over the last few decades in the Indian Ocean (Marion and Crozet Islands) but decreasing steadily at South Georgia. General Linear Models (GLMs) showed that sex and time available to moult both influenced the number and mass of flight feathers replaced. Sex explained more variation in terms of number of feathers replaced (67%) than time available to moult (33%), but time available to moult explained 68% of the mass of flight feathers replaced. However, there is large variation among birds in the number of primaries and secodaries replaced, independent of time available for moult. Together, sex and time available to moult accounted for only 9.2% (number) and 11.9% (mass) of the variance in feathers replaced. Giant petrels are one of the largest birds that undergo a complete primary moult each year without losing the ability to fly. They do this by overlapping their moult with breeding and by moulting several primaries at once. Being annual breeders, individuals that fail a breeding attempt have more time to moult than successful breeders, and therefore replaced more flight feathers. Northern Giant Petrels having a successful breeding 3 attempt replaced on average the same percentage of secondary and greater secondary coverts in both sexes; Following a successful breeding attempt Southern Giant Petrels (both sexes) replaced more feathers (secondaries and greater secondary coverts) than Northern Giant Petrels. I found that in a failed breeding attempt giant petrels have more time to moult and therefore replaced more secondary feathers than successful breeders. GLMs showed that breeding outcome was the only variable that influenced the mass of feathers replaced in Northern Giant Petrels, accounting for 14% of the variance in feathers replaced, while sex was the only variable in Southern Giant Petrels, accounting for 6% of variance. When both species were modelled together with sex and breeding attempt as explanatory variales, only breeding attempt was significant, accounting for 11% of the variance in the mass of secondaries and coverts replaced. In summary, the assumption that breeding activity, and thus the time between breeding attempts, influences the extent of moult in large birds with incomplete wing moults was supported for Wandering Albatrosses and Northern Giant Petrels. However, time available for moult explained only a small proportion of individual variation in moult extent in these species. Southern Giant Petrels replaced a similar mass of flight feathers, irrespective of breeding outcome. My results suggest that factors other than time between breeding attempts are important in determining the extent of wing moult. My study highlights the important tradeoffs large birds are required to make when balancing moult and reproduction. Annual monitoring of moult patterns in known individuals provides a valuable tool to better understand moult patterns in these large, long-lived birds.

Thesis (M.Eng.)--Massachusetts Institute of Technology, Biological Engineering Division, 2003. / Includes bibliographical references (leaves 126-134). / by Tomoko Iida. / Thesis (M.Eng.)--Massachusetts Institute of Technology, Biological Engineering Division, 2003.

Although there are many studies on mammalian bone histology, there are only a few that have examined the bone histology of artiodactyls, or focused specifically on osteohistological changes during ontogeny. The current study investigates the microanatomy and histology of giraffe limb bones through ontogeny. Mid-diaphyseal sections of humeri, radii, metacarpals, femora, and tibiae of 14 individuals representing individuals of known sex, as well as at different ontogenetic stages (foetal, juveniles, subadults, and adults). Thin sections were prepared for all the bones, and microanatomical (using Bone Profiler) and histological analyses were conducted on each of the sections. The study examined three main aspects, 1) Crosssectional shape changes in limb bones through ontogeny, 2) Histological changes through ontogeny in each of the limb bones, and 3) Histovariability among skeletons. The results of the study show that the foetus and juvenile individuals have round cross-sections, with small vacant medullary cavities, while cross sections of older individuals tend to be oval with variable amounts of cancellous bone surrounding the medullary cavity. The highest bone compactness values were obtained for the humerus and femur of the foetus, whereas the radius, metacarpal, and tibia bone compactness values are similar across the age classes. In terms of histology, this study found that the earlier ontogenetic stages had highly vascularised fibrolamellar bone in their cortices, which contrasts with that of the subadults and adults where more slowly deposited bone tissue occurs. These observations indicate that after rapid initial growth during early ontogeny, osteogenesis (and overall growth) slows down. This research also documents the fusion of the metacarpal III and IV, and the associated changes that occur in the histology. The study also highlights that the tibia is the only bone that has long radial vascular canals in the cortex. Overall the results of this study have provided a much better understanding of the bone histology of giraffes during ontogeny and has therefore filled an important gap in our knowledge of mammalian bone tissues. Furthermore, this study has direct implications for any future palaeohistological studies of fossil giraffids from Langebaanweg in South Africa.