Why is melanoma so metastatic?

Malignant melanoma is one of the most aggressive cancers and can disseminate from a relatively small primary tumor and metastasize to multiple sites, including the lung, liver, brain, bone, and lymph nodes. Elucidating the molecular and genetic changes that take place during the metastatic process has led to a better understanding of why melanoma is so metastatic. Herein, we describe the unique features that distinguish melanoma from other solid tumors and contribute to the malignant phenotype of melanoma cells. For example, although melanoma cells are highly antigenic, they are extremely efficient at evading host immune response. Melanoma cells share numerous cell surface molecules with vascular cells, are highly angiogenic, are mesenchymal in nature, and possess a higher degree of ‘stemness’ than do other solid tumors. Finally, analysis of melanoma mutations has revealed that the gene expression profile of malignant melanoma is different from that of other cancers. Elucidating these molecular and genetic processes in highly metastatic melanoma can lead to the development of improved treatment and individualized therapy options.     

Why is celiac disease so common in Ireland?

Celiac disease (gluten sensitive enteropathy) is a condition affecting the small bowel, characterized by permanent intolerance to dietary gluten, and giving rise to varying degrees of malabsorption and diarrhea. With the advent of sensitive screening tests, the condition is being increasingly diagnosed. Celiac disease is more common in the Irish and in those of Irish descent. Simoons (1978, 1981) hypothesized that the present-day prevalence of celiac disease across Europe is related to the interaction between genetic gradients, largely determined by the advance of agriculture, and historical patterns of cereal ingestion. This essay examines Simoons' hypothesis as it relates to Ireland, reviews the ethnic and genetic mix of those living on the island of Ireland and aspects of Irish dietary history, and considers how these factors may have combined to result in a high frequency of celiac disease.     

Why are there so many mimicry rings? Correlations between habitat,behaviour and mimicry in Heliconius butterflies

In the new world tropics there is an extravagant array of sympatric butterfly mimicry rings. This is puzzling under strictly coevolutionary (Müllerian) mimicry: all unpalatable species should converge as ‘co-mimics' to the same pattern. If mimicry has usually evolved in unpalatable species by one-sided (Batesian) evolution, however, it is easy to see that mimicry rings centred on different models could remain distinct. If mimicry rings were also segregated by habitat, a diversity of mimicry rings could be stabilized. In this paper we report correlations between behaviour and mimicry of nine unpalatable Heliconius species. It is already known that co-mimics fly in similar habitats, and non-mimics fly in different habitats, although there is much overlap. Contrary to a previous report, we find little difference in flight heights of heliconiine mimicry rings; all species fly from ground level to the canopy. However, co-mimics roost at night in similar habitats and at similar heights above the ground, but in different habitats and at different heights from species in other mimicry rings. Heliconius (especially the erato taxonomic group) are renowned for roosting gregariously; and co-mimics roost gregariously with each other more often than with non-mimics. Gregarious roosting is therefore common between species, as well as within species. There are thus strong links between mimicry and behavioural ecology in Heliconius. The paradoxical correlation between nocturnal roosting and visual mimicry is presumably explained by bird predation at dusk when roosts are forming, or at dawn before they have disbanded. Direct evidence of predation is lacking, but there are high rates of disturbance by birds at these times. These results, together with knowledge of the phylogeny of Heliconius, suggest that species from the melpomene-group of Heliconius have radiated to occupy mimetic niches protected by model species in the Ithomiinae and the erato-group of Heliconius. A variety of sympatric mimicry rings is apparently maintained because key models fail to converge, while more rapidly-evolving unpalatable mimics evolve towards the colour patterns of the models. The maintenance of mimetic diversity would be aided by the habitat and behavioural differences between mimicry rings revealed here, provided that different predators are found in different habitats. This explanation for the maintenance of multiple mimicry rings is more plausible for Heliconius mimicry than alternatives based on visual mating constraints, thermal ecology, or camouflage.     

Why is there so little intragenic linkage disequilibrium in humans?

The efficient design of association mapping studies relies on a knowledge of the rate of decay of linkage disequilibrium with distance. This rate depends on the population recombination rate, C. An estimate of C for humans is usually obtained from a comparison of physical and genetic maps, assuming an effective population size of approximately 10(4). We demonstrate that under both a constant population size model and a model of long-term exponential growth, there is evidence for more recombination in polymorphism data than is expected from this estimate. An important contribution of gene conversion to meiotic recombination helps to explain our observation, but does not appear to be sufficient. The occurrence of multiple hits at CpG sites and the presence of population structure are not explanations.     

Why is dracunculiasis eradication taking so long?

The long time needed for global eradication of dracunculiasis (Guinea worm disease) was not anticipated at the outset. The successful eradication of smallpox in 10 years compares with the target date set in 1985 for dracunculiasis eradication - 1995. Seventeen years after that date, transmission continues. Why? Various factors are responsible, mainly lack of resources, or resources ineffectively used. The example of Ghana, where the programme stagnated for a decade, sheds light on this delay. When more resources were put into Ghana's programme in 2007, transmission of the disease was interrupted in 3 years. The variable success of dracunculiasis eradication in different countries provides lessons for future disease eradication programmes.     

Why is revitalizing clinical research so important, yet so difficult?

We believe that support for academic clinical research has greatly declined in recent decades. Here we discuss our views on why this has happened. We define clinical or patient-oriented research as limited to the study of human beings or populations of individuals, and argue that its eclipse in favor of basic and "translational" research is the result of inappropriate conceptual paradigms or "models" for medical advances. We believe that medical history shows that the "bench-to-bedside" model is inadequate to explain most recent progress and that clinical advances themselves often lead to new basic research. Discussion of alternate conceptual frameworks for biomedical research should help lead to changes in funding and organizational structures that might finally revitalize clinical research.     

Why is stress so deadly? An evolutionary perspective

The reaction of the body to prolonged stress has many harmful effects. Classical theory assumes that stress responses have evolved due to their short-term selective advantages ('flight or fight'), and despite their adverse long-term effects. In contrast, we demonstrate that the adverse effects of stress responses may have a selective advantage. Using an analytical model we show that a gene that causes the early death of a relatively unfit individual can increase in frequency in a structured population even if it has no positive effect on that individual. This result offers a new perspective on the relations between stress factors, stress responses and stress-related diseases.     

Why is the house mouse karyotype so variable?

rates of robertsonian chromosomal evolution in the Western European house mouse are about two orders of magnitude greater than for most other mammals. This has resulted in a remarkable diversity of karyotypic races in a very short period of time. Recent studies are beginning to shed light on the relative contributions of mutation, drift, selection and meiotic drive in producing this pattern.     

Why is the cystic fibrosis gene so frequent?

Summary The high incidence of cystic fibrosis (CF) in most European populations (and populations of European descent) can be explained by different hypotheses that can be tested using the available data concerning this disorder. Among the five hypotheses discussed (genetic heterogeneity, high rate of mutation, meiotic drive, drift and heterozygote advantage), only the last is supported by experimental data. The following conclusions can be drawn from the evidence that we have reviewed: (1) CF is a single gene disorder (genetically homogeneous). (2) Haplotypes associated with the CF gene suggest that only a few mutations (the same gene located in 7q13 is always affected) are responsible for the disorder. (3) CF with pancreatic insufficiency is mainly associated with a single haplotype, whereas CF with pancreatic sufficiency is more frequently associated with different haplotypes. (4) A selective advantage consisting of higher resistance to Cl^–-secreting diarrhoeas might have favored, in the past, survival of infants heterozygous for the CF gene.     

Why so few?

Nobel Prize Women in Science: Their struggles and momentous discoveries (1998). S. Bertsch McGrayne. Carol Publishing Group, 448 pp. $19.95 paper ISBN 0806520256.     

Why do Luehdorfia butterflies lay eggs in clusters?

Luehdorfia butterflies lay eggs in clusters. Clones of their host plants (Asiasarum and Heterotropa) are distributed pacthily among the understory of deciduous forests. Groups of Luehdorfia larvae often exhaust the clones and may wander over the forest floor seeking new clones. The highest mortality observed is during this wandering period. To elucidate why Luehdorfia butterflies lay eggs in clusters, a simulation experiment was made for hypothetical populations which lay eggs in clusters or singly. Field data on larval mortality, consumption, density of host clones and leaf weight for Luehdorfia japonica were incorporated into the model. The predictions of the simulation were: (1) When the egg density is low, the single egg type could leave many more pupae than the egg clustering type, but when the egg density is high, the former might leave smaller number of pupae than the latter; and (2) There are optimal sizes of egg clusters for different egg densities and the optimal size becomes larger as the egg density increased.     

Why do in utero stem cell transplants sometimes fail?

In utero stem cell transplantation promises a novel therapeutic approach to those genetic disorders that can be diagnosed in early pregnancy and that could lead to either severe disability or death. Available scientific evidence suggests that such procedures could achieve clinically relevant levels of engraftment with donor cells and that the resulting sustained chimerism is potentially long lived. However, the relatively few cases performed so far have not borne out initial hopes, and both the source and the type of cell preparation to be transplanted and the choice of disorders to target with this therapy remain controversial.