Colorectal Cancer: Molecular Features and Clinical Opportunities

Colorectal cancer is a heterogeneous disease. There are three main pathways to colorectal cancer: the chromosomal instability pathway, the CpG island methylator phenotype pathway and the pure microsatellite instability pathway. Each of these is characterised by specific pathological precursors, mechanisms of carcinogenesis and natural history. The molecular features of these pathways have been exploited clinically in the diagnosis, screening and management of patients and families with colorectal cancer. This review summarises recent developments in our understanding of colorectal carcinogenesis and examines the interface between scientific discovery and the clinical application of molecular techniques in inherited and sporadic colorectal cancer.     

War and peace: social interactions in infections

One of the most striking facts about parasites and microbial pathogens that has emerged in the fields of social evolution and disease ecology in the past few decades is that these simple organisms have complex social lives, indulging in a variety of cooperative, communicative and coordinated behaviours. These organisms have provided elegant experimental tests of the importance of relatedness, kin discrimination, cooperation and competition, in driving the evolution of social strategies. Here, we briefly review the social behaviours of parasites and microbial pathogens, including their contributions to virulence, and outline how inclusive fitness theory has helped to explain their evolution. We then take a mechanistically inspired ‘bottom-up’ approach, discussing how key aspects of the ways in which parasites and pathogens exploit hosts, namely public goods, mobile elements, phenotypic plasticity, spatial structure and multi-species interactions, contribute to the emergent properties of virulence and transmission. We argue that unravelling the complexities of within-host ecology is interesting in its own right, and also needs to be better incorporated into theoretical evolution studies if social behaviours are to be understood and used to control the spread and severity of infectious diseases.     

The influence of calcium deficiency on the translocation of photosynthetically fixed 14C in soybeans

Summary Soybean (Glycine max (L.) Merr.) plants were grown at two levels of Ca (0.05 and 2.5 mM Ca) with and without an inorganic source of N in a growth chamber and in the greenhouse. The fourth leaf from the top of the plant was labeled with ¹⁴C, and the distribution of ¹⁴C was measured 24 hours after labeling. The translocation of ¹⁴C out of the labeled leaf was decreased at the low Ca level in both experiments. This decrease occurred before there were any visual Ca deficiency symptoms and before the low Ca level had any effect on dry weight accumulation. The effect of the low Ca level on translocation was the same for plants exposed to an inorganic N source and those that were nodulated. The reduced rate of translocation from the labeled leaf had no measurable effect on the nodule activity as measured by the acetylene reduction method. The data demonstrate the importance of an adequate supply of Ca to the soybean plant for maximum translocation of carbohydrates from the leaves.This paper (76-3-110) is published with the approval of the Director of the Kentucky Agric. Exp. Stn.This paper (76-3-110) is published with the approval of the Director of the Kentucky Agric. Exp. Stn.     

Citrate synthase, sarcoplasmic reticular calcium ATPase, and choline acetyltransferase activities of specific pelvic floor muscles of the rabbit

There is a clear relationship between the pelvic floor muscles and urinary systems, which relates to urgency, frequency, incontinence, pelvic pain, and bowel complaints. The specific mechanisms which relate these two systems are not clear. Improved understanding of the relation between the pelvic floor muscles and bladder function is clinically relevant in establishing effective treatments to such problems as incontinence, secondary to birth. The following tissues were collected from normal adult female rabbits: pubococcygeus (Pc) and ischiocavernosus/bulbospongiosus (Ic/Bs) pelvic floor muscles. Bladder body muscle and mucosa, bladder base muscle and mucosa, and leg skeletal muscle were also collected. The following enzymatic assays were performed on each tissue: citrate synthase (CS), sarcoplasmic–endoplasmic reticular ATPase (SERCA), and choline acetyltransferase (ChAT). CS and SERCA activities were significantly higher in the Pc compared with the Ic/Bs pelvic floor muscles, whereas the ChAT activity of the Ic/Bs was higher than that of the Pc muscle. Based on our results, the Pc muscle is expected to have a significantly greater capacity to contract and a higher metabolic activity than those of the Ic/Bs muscles. We believe that an understanding of the biochemical activities of these three biomarker enzymes in normal pelvic floor muscles is essential in evaluating the effects of specific experimental dysfunctions created in pelvic floor muscle activity.