The biology of breast tumor progression : acquisition of hormone independence and resistance to cytotoxic drugs

Many breast tumors appear to follow a predictable clinical pattern, being initially responsive to endocrine therapy and to cytotoxic chemotherapy but ultimately exhibiting a phenotype resistant to both modalities. Using the MCF-7 human breast cancer cell line as an example of an 'early' phenotype (estrogen and progesterone receptor positive, steroid responsive, low metastatic potential), we have isolated and characterized a series of hormone-independent but hormone-responsive variants (MIII and MCF7/LCC1). However, these variants remain responsive to both antiestrogens and cytotoxic drugs (methotrexate and colchicine). MIII and MCF7/LCCl cells appear to mimic some of the critical aspects of the early progression to a more aggressive phenotype. An examination of the phenotype of these cells suggests that some hormone-independent breast cancer cells are derived from hormone-dependent parental cells. The development of a hormone-independent phenotype can arise independently of acquisition of a cytotoxic drug resistant phenotype.

Choosing an appropriate modelling framework for analysing multispecies co-culture cell biology experiments

In vitro cell biology assays play a crucial role in informing our understanding of the migratory, proliferative and invasive properties of many cell types in different biological contexts. While mono-culture assays involve the study of a population of cells composed of a single cell type, co-culture assays study a population of cells composed of multiple cell types (or subpopulations of cells). Such co-culture assays can provide more realistic insights into many biological processes including tissue repair, tissue regeneration and malignant spreading. Typically, system parameters, such as motility and proliferation rates, are estimated by calibrating a mathematical or computational model to the observed experimental data. However, parameter estimates can be highly sensitive to the choice of model and modelling framework. This observation motivates us to consider the fundamental question of how we can best choose a model to facilitate accurate parameter estimation for a particular assay. In this work we describe three mathematical models of mono-culture and co-culture assays that include different levels of spatial detail. We study various spatial summary statistics to explore if they can be used to distinguish between the suitability of each model over a range of parameter space. Our results for mono-culture experiments are promising, in that we suggest two spatial statistics that can be used to direct model choice. However, co-culture experiments are far more challenging: we show that these same spatial statistics which provide useful insight into mono-culture systems are insuffcient for co-culture systems. Therefore, we conclude that great care ought to be exercised when estimating the parameters of co-culture assays.

The biology of an isolated population of American Flamingo Phoenicopterus ruber in the Galapagos Islands

A genetically and morphologically divergent population of c.500 American Flamingos, isolated from the parental Caribbean stock of Phoenicopterus ruber, occurs in the Galapagos archipelago. Based primarily on data from a 3-year study, we provide the first description of the feeding and breeding biology of this population. Galapagos provides a suitable habitat comprising lagoons on a number of islands, among which the flamingos travel in response to food and nest site availability. The occurrence and qualnity of some food species was associated with the chlorosity of lagoon water, as was the distribution of flamingos. They bred opportunistically at five lagoons on four islands, sometimes simultaneously on more than one island. Group display usually involved approx 20 birds and colonies contained as few as three nests. Laying occurred during nine months of the year... We review potential dangers to this unique population and suggest conservation measures.

Biology Aotearoa : Unique Flora, Fauna and Fungi

As a large, isolated and relatively ancient landmass, New Zealand occupies a unique place in the biological world, with distinctive terrestrial biota and a high proportion of primitive endemic forms. Biology Aotearoa covers the origins, evolution and conservation of the New Zealand flora, fauna and fungi. Each chapter is written by specialists in the field, often working from different perspectives to build up a comprehensive picture. Topics include: the geological history of our land origins, and evolution of our plants, animals and fungi current status of rare and threatened species past, present and future management of native species the effect of human immigration on the native biota. Colour diagrams and photographs are used throughout the text. This book is suitable for all students of biology or ecology who wish to know about the unique nature of Aotearoa New Zealand and its context in the biological world.

In silico biology : making the most of parallel computing

Biological systems are typically complex and adaptive, involving large numbers of entities, or organisms, and many-layered interactions between these. System behaviour evolves over time, and typically benefits from previous experience by retaining memory of previous events. Given the dynamic nature of these phenomena, it is non-trivial to provide a comprehensive description of complex adaptive systems and, in particular, to define the importance and contribution of low-level unsupervised interactions to the overall evolution process. In this chapter, the authors focus on the application of the agent-based paradigm in the context of the immune response to HIV. Explicit implementation of lymph nodes and the associated lymph network, including lymphatic chain structure, is a key objective, and requires parallelisation of the model. Steps taken towards an optimal communication strategy are detailed.

Complexity and high-end computing in biology and medicine

Biomedical systems involve a large number of entities and intricate interactions between these. Their direct analysis is, therefore, difficult, and it is often necessary to rely on computational models. These models require significant resources and parallel computing solutions. These approaches are particularly suited, given parallel aspects in the nature of biomedical systems. Model hybridisation also permits the integration and simultaneous study of multiple aspects and scales of these systems, thus providing an efficient platform for multidisciplinary research.

From bio-inspired computing to e-Biology

Several algorithms and techniques widely used in Computer Science have been adapted from, or inspired by, known biological phenomena. This is a consequence of the multidisciplinary background of most early computer scientists. The field has now matured, and permits development of tools and collaborative frameworks which play a vital role in advancing current biomedical research. In this paper, we briefly present examples of the former, and elaborate upon two of the latter, applied to immunological modelling and as a new paradigm in gene expression.

The genetics and structure of the O-specific polysaccharide of Yersinia pseudotuberculosis serotype O:10 and its relationship with Escherichia coli O111 and Salmonella enterica O35

The O-specific polysaccharide (OPS) is a variable constituent of the lipopolysaccharide of Gram-negative bacteria. The polymorphic nature of OPSs within a species is usually first defined serologically, and the current serotyping scheme for Yersinia pseudotuberculosis consists of 21 O serotypes of which 15 have been characterized genetically and structurally. Here, we present the structure and DNA sequence of Y. pseudotuberculosis O:10 OPS. The O unit consists of one residue each of d-galactopyranose, N-acetyl-d-galactosamine (2-amino-2-deoxy-d-galactopyranose) and d-glucopyranose in the backbone, with two colitose (3,6-dideoxy-l-xylo-hexopyranose) side-branch residues. This structure is very similar to that shared by Escherichia coli O111 and Salmonella enterica O35. The gene cluster sequences of these serotypes, however, have only low levels of similarity to that of Y. pseudotuberculosis O:10, although there is significant conservation of gene order. Within Y. pseudotuberculosis, the O10 structure is most closely related to the O:6 and O:7 structures.

Plant biology: Coding in non-coding RNAs

The discovery of peptides encoded by what were thought to be non-coding – or 'junk' – regions of precursors to microRNA sequences reveals a new layer of gene regulation. These sequences may not be junk, after all.

Inventing life: Patent law and synthetic biology

With promises of improved medical treatments, greener energy and even artificial life, the field of synthetic biology has captured the public imagination and attracted significant government and commercial investment. This excitement reached a crescendo on 21 May 2010, when scientists at the J Craig Venter Institute in the United States announced that they had made a “self-replicating synthetic bacterial cell”. This was the first living cell to have an entirely human-made genome, which means that all of the cell’s characteristics were controlled by a DNA sequence designed by scientists. This achievement in biological engineering was made possible by combining molecular biotechnology, gene synthesis technology and information technology.

Convergence of regenerative medicine and synthetic biology to develop standardized and validated models of human diseases with clinical relevance

In order to progress beyond currently available medical devices and implants, the concept of tissue engineering has moved into the centre of biomedical research worldwide. The aim of this approach is not to replace damaged tissue with an implant or device but rather to prompt the patient's own tissue to enact a regenerative response by using a tissue-engineered construct to assemble new functional and healthy tissue. More recently, it has been suggested that the combination of Synthetic Biology and translational tissue-engineering techniques could enhance the field of personalized medicine, not only from a regenerative medicine perspective, but also to provide frontier technologies for building and transforming the research landscape in the field of in vitro and in vivo disease models.

Female Reproductive Biology and Spawning Periodicity of Two Species of King Prawns, Penaeus longistylus Kubo and Penaeus latisulcatus Kishinouye, from Queensland's East Coast Fishery

In the coastal region of central Queensland female red-spot king prawns, P. longistylus, and the western or blue-leg king prawns, P. latisulcatus, had high mean ovary weights and high proportions of advanced ovary development during the winter months of July and August of 1985 and 1986. On the basis of insemination, both species began copulating at the size of 26-27 mm CL, but P. longistylus matured and spawned at a smaller size than P. latisulcatus. Abundance of P. longistylus was generally three to four times greater than that of P. latisulcatus but the latter was subject to greater variation in abundance. Low mean ovary weight and low proportions of females with advanced ovaries were associated with the maximum mean bottom sea-water temperature (28.5ºC) for both species. Population fecundity indices indicated that peaks in yolk or egg production (a) displayed a similar pattern for both species, (b) varied in timing from year to year for both species and (c) were strongly influenced by abundance. Generally, sample estimates of abundance and commercial catch rates (CPUE) showed similar trends. Differences between the two may have been due to changes in targeted commercial effort in this multi-species fishery.

Reproductive Biology and Spawning Periodicity of Endeavour Shrimps Metapenaeus endeavouri (Schmitt, 1926) and Metapenaeus ensis (de Haan, 1850) from a Central Queensland (Australia) Fishery

Metapenaeus endeavouri and M. ensis from coastal trawl fishing grounds off central Queensland, Australia, have marked seasonal reproductive cycles. Female M. endeavouri grew to a larger size than female M. ensis and occurred over a wider range of sites and depths. Although M. ensis was geographically restricted in distribution to only the shallowest sites it was highly abundant. Mating activity in these open thelycum species, indicated by the presence or absence of a spermatophore, was relatively low and highly seasonal compared with closed thelyeum shrimps. Seasonal variation in spermatophore insemination can be used as an independent technique to study spawning periodicity in open thelycum shrimps. Data strongly suggest an inshore movement of M. endeavouri to mature and spawn. This differs from most concepts of Penaeus species life cycles, but is consistent with the estuarine significance in the life cycle of Metapenaeus species. Monthly population fecundity indices suggest summer spawning for both species, which contrasts with the winter spawning of other shrimps from the same multispecies fishery.