It is now generally accepted that cancers contain a sub-population, the cancer stem cells (CSCs), which initiate and drive a tumour's growth. At least until recently it has been widely assumed that only a small proportion of the cells in a tumour are CSCs. Here we use a mathematical model, supported by experimental evidence, to show that such an assumption is unwarranted. We show that CSCs may comprise any possible proportion of the tumour, and that the higher the proportion the more aggressive the tumour is likely to be.
Structure of the mouthparts and foregut of Panulirus ornatus phyllosomata (stages I-VI hatchery reared, IX-X wild caught) were examined using scanning electron microscopy and histology to gain an understanding of ingestive and digestive processing mechanisms, to identify potential shifts in diet during development, and to suggest appropriate physical characteristics for the development of a suitable formulated diet for commercial aquaculture of this species such as size, texture, and buoyancy. Mouthpart and foregut structure indicates that P. ornatus phyllosomata are capable of ingesting zooplankton of any hardness during this life history stage and are only limited by their ability to capture and manipulate prey as the mandibular molars are well developed to masticate prey further. Mouthpart morphology changes little during development, however, the disposition of the mouthparts and size of the mouth aperture increases with each successive stage of development, suggesting a greater capacity to manipulate and ingest larger prey. ne foregut of all developmental stages consists of a single chamber, with well-developed grooves, channels and setae, but lacks a gastric mill. Presence of well-developed main brushes, lateral setae, and development of a functional filter press at stage IV suggests an increased ability to triturate and filter prey internally, reducing both the time spent externally manipulating prey with the mouthparts and the vulnerability to predation in the open ocean. The results presented here suggest that formulated diets larger than > 428 mu m, with a firm/hard consistency that allow the dactyli of the second and third maxillipeds to penetrate the diet without causing fouling of the setae would be suitable.
Colorectal cancer (CRC) is responsible for nearly half a million deaths annually worldwide [11]. We present a series of mathematical models describing the dynamics of the intestinal epithelium and the kinetics of the molecular pathway most commonly mutated in CRC, the Wnt signalling network We also discuss how we are coupling such models to build a multiscale model of normal and aberrant guts. This will enable us to combine disparate experimental and clinical data, to investigate interactions between phenomena taking place at different levels of organisation and, eventually, to test the efficacy of new drugs on the system as a whole.
Mathematical modeling is being increasingly recognized within the biomedical sciences as an important tool that can aid the understanding of biological systems. The heavily regulated cell renewal cycle in the colonic crypt provides a good example of how modeling can be used to find out key features of the system kinetics, and help to explain both the breakdown of homeostasis and the initiation of tumorigenesis. We use the cell population model by Johnston et al.5 to illustrate the power of mathematical modeling by considering two key questions about the cell population dynamics in the colonic crypt. We ask: how can a model describe both homeostasis and unregulated growth in tumorigenesis; and to which parameters in the system is the model most sensitive? In order to address these questions, we discuss what type of modeling approach is most appropriate in the crypt. We use the model to argue why tumorigenesis is observed to occur in stages with long lag phases between periods of rapid growth, and we identify the key parameters.
This study is a preliminary assessment of suitable binders and formats of potential formulated diets for hatchery growout of early-stage western spiny lobster, Panulirus cygnus, phyllosomata. Six dry meal (each bound with a different binder) and three gelatinous (all bound using gelatine) diets were tested for stability in water over increasing periods of time (4, 8, and 12 h), and the feeding response to each was observed by video analysis. The gelatinous krill diet appears most suited to the larval feeding biology of P. cygnus phyllosomata as it elicited a heightened feeding response immediately following immersion, was most stable in water up to 4 h, and did not foul the maxillae during ingestion. The dry meal diets were not as stable in water and contributed to excessive fouling of the maxillae during ingestion. Of the dry meal diets, the most suitable was bound with 5% k-carrageenan, presumably because of high moisture content and softer texture.
Mathematical modeling is being increasingly recognized within the biomedical sciences as an important tool that can aid the understanding of biological systems. The heavily regulated cell renewal cycle in the colonic crypt provides a good example of how modeling can be used to find out key features of the system kinetics, and help to explain both the breakdown of homeostasis and the initiation of tumorigenesis.We use the cell population model by Johnston et al. (2007) Proc. Natl. Acad. Sci. USA 104, 4008-4013, to illustrate the power of mathematical modeling by considering two key questions about the cell population dynamics in the colonic crypt. We ask: how can a model describe both homeostasis and unregulated growth in tumorigenesis; and to which parameters in the system is the model most sensitive? In order to address these questions, we discuss what type of modeling approach is most appropriate in the crypt.We use the model to argue why tumorigenesis is observed to occur in stages with long lag phases between periods of rapid growth, and we identify the key parameters.
We have evaluated the potential of a formulated diet as a replacement for live and fresh feeds for 7-day post-hatch Panulirus ornatus phyllosomata and also investigated the effect of conditioning phyllosomata for 14–21 days on live feeds prior to weaning onto a 100% formulated diet. In the first trial, the highest survival (>55%) was consistently shown by phyllosomata fed a diet consisting of a 50% combination of Artemia nauplii and 50% Greenshell mussel, followed by phyllosomata fed 50% Artemia nauplii and 50% formulated diet and, thirdly, by those receiving 100% Artemia nauplii. The second trial assessed the replacement of on-grown Artemia with proportions of formulated diet and Greenshell mussel that differed from those used in trial 1. Phyllosomata fed a 75% combination of formulated diet and 25% on-grown Artemia and 50% on-grown Artemia and 50% Greenshell mussel consistently showed the highest survival (>75%). Combinations of Greenshell mussel and formulated diet resulted in significantly (P < 0.05) reduced survival. In trial 3, phyllosomata were conditioned for 14, 18 or 21 days on Artemia nauplii prior to weaning onto a 100% formulated diet, which resulted in survival rates that were negatively related to the duration of feeding Artemia nauplii. In the final trial, phyllosomata were conditioned for 14 days on live on-grown Artemia prior to weaning onto one of three formulated diets (one diet with 44% CP and two diets with 50%). Phyllosomata fed a 44% CP diet consistently showed the highest survival (>35%) among all treatments, while those fed a 50%-squid CP diet showed a significant (P < 0.05) increase in mortality at day 24. The results of these trials demonstrate that hatcheries can potentially replace 75% of live on-grown Artemia with a formulated diet 7 days after hatch. The poor performance associated with feeding combinations of Greenshell mussel and formulated diet, and 100% formulated diet as well as conditioning phyllosomata for 14–21 days on live feeds prior to weaning onto a formulated diet highlights the importance of providing Artemia to stimulate feeding.
Colorectal cancer is initiated in colonic crypts. A succession of genetic mutations or epigenetic changes can lead to homeostasis in the crypt being overcome, and subsequent unbounded growth. We consider the dynamics of a single colorectal crypt by using a compartmental approach [Tomlinson IPM, Bodmer WF (1995) Proc Natl Acad Sci USA 92: 11130–11134 ], which accounts for populations of stem cells, differentiated cells, and transit cells. That original model made the simplifying assumptions that each cell population divides synchronously, but we relax these assumptions by adopting an age-structured approach that models asynchronous cell division, and by using a continuum model. We discuss two mechanisms that could regulate the growth of cell numbers and maintain the equilibrium that is normally observed in the crypt. The first will always maintain an equilibrium for all parameter values, whereas the second can allow unbounded proliferation if the net per capita growth rates are large enough. Results show that an increase in cell renewal, which is equivalent to a failure of programmed cell death or of differentiation, can lead to the growth of cancers. The second model can be used to explain the long lag phases in tumor growth, during which new, higher equilibria are reached, before unlimited growth in cell numbers ensues.
A new genus, Caudacanthus, is established for the species previously known as Irodes narcini (Pillai 1963) based on a redescription of newly collected material from the west and east coasts of Australia. Caudacanthus narcini (Pillai 1963) comb. nov. is distinguished from other members of the Taeniacanthidae by possession of (1) spinules on the ventral surface of each abdominal somite, (2) a maxilliped with a short terminal claw pressed close to the basis, (3) inner coxal seta on legs 2 and 3, and (4) a caudal ramus with a distolateral, bifid spine bearing a flagellum. A description of male C. narcini is provided for the first time.
Structural adaptations of the mouthparts and digestive tract of four talitrid amphipods were examined in relation to diet, habitat and phylogeny. The species differed in their habitat relative to the shoreline and also in their diet: a 5-dentate ‘sandrunner’, Talorchestia species II (a mid to low shore intertidal diatom feeder), a 5-dentate sandhopper, Talorchestia marmorata (a strandline kelp feeder); a 4-dentate sandhopper, Talorchestia species I (extreme high shore, feeding on spinifex grasses), and a 4-dentate landhopper, Keratroides vulgaris (forest leaf litter, litter feeding). Gross structural characteristics of the mouthparts were similar among all three Talorchestia species reflecting their phylogenetic relatedness. Increased setation and minor structural differences among the Talorchestia species could be attributed to dietary differences, reflecting the zones across the shoreline that they inhabit. Mouthparts of K. vulgaris were elongate, with markedly different setation to the Talorchestia species, reflecting its more distant phylogenetic position and its diet of decaying leaf litter. Digestive tract structure was more conserved among all species due to their phylogenetic relatedness. The gross digestive structure conformed to the general plan exhibited by most gammaridean amphipods. However, an additional pair of lateral pyloric caeca was evident in all species, the function of which is uncertain.
Digestive enzyme activities of three talitrid amphipods were examined to investigate the relationship between their digestive capabilities and diet. Laminarinase, cellobiase, carboxymethyl-cellulase, xylanase, α- and β-glucosidase and lipase were detected in all three species suggesting talitrid amphipods can readily digest dietary carbohydrate and lipid, including complex polysaccharides. Relatively high specific enzyme activity (Units (mg−1 digestive tract protein)−1) of laminarinase and lipase was detected in Talorchestia marmorata, a supralittoral kelp feeder which is coherent with the digestion of lipid-esters and β-glucans (laminarin) which are the main lipid and storage polysaccharides of brown seaweeds. Talorchestia sp., a low shore intertidal feeder, had high enzymatic activity of α- and β-glucosidase, cellobiase and xylanase, which is consistent with the digestion of diatoms. Keratroides vulgaris, a forest litter feeder had a relatively low specific activity of all enzymes. It is possible that leaf litter is partially digested prior to ingestion by bacteria and fungi present in the rotting vegetation, with bacterial and fungal enzymes contributing to this species' ability to hydrolyse its diet. This study provides the first quantitative data on digestive capacity in these three talitrid amphipods and confirms the relationship between dietary preference and digestive enzyme complement.