How do so few control so many?

The separation of sister chromatids at the metaphase-to-anaphase transition is triggered by a protease called separase that is activated by the destruction of an inhibitory chaperone (securin). This process is mediated by a ubiquitin protein ligase called the anaphase-promoting complex or cyclosome (APC/C), along with a protein called Cdc20. It is vital that separase not be activated before every single chromosome has been aligned on the mitotic spindle. Kinetochores that have not yet attached to microtubules catalyze the sequestration of Cdc20 by an inhibitor called Mad2. Recent experiments shed important insight into how Mad2 molecules bound to centromeres through their association with a protein called Mad1 might be transferred to Cdc20 and thereby inhibit securin's destruction.     

Ribozymes--why so many, why so few?

The RNA world scenario posits the existence of catalytic and genetic networks whose reactions are catalyzed by RNAs. Substantial progress has been made in recent years in the selection of RNA catalysts by SELEX, thus verifying one prediction of the model. However, many selected catalysts are long molecules, leading to a question of whether they could have been synthesized by a primitive replicator. It is proposed that the efficiency of some small ribozymes may have been augmented by other RNAs acting as transactivators.     

Water transporters: how so fast yet so selective?

A high-resolution X-ray structure of an aquaporin has revealed water molecules bound within the transmembrane pore and provided new clues to the mechanisms of rapid water transport and high selectivity in this important class of membrane proteins.     

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 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 are there so few smart mammals (but so many smart birds)?

The expensive brain hypothesis predicts an interspecific link between relative brain size and life-history pace. Indeed, animals with relatively large brains have reduced rates of growth and reproduction. However, they also have increased total lifespan. Here we show that the reduction in production with increasing brain size is not fully compensated by the increase in lifespan. Consequently, the maximum rate of population increase (rmax) is negatively correlated with brain mass. This result is not due to a confounding effect of body size, indicating that the well-known correlation between rmax and body size is driven by brain size, at least among homeothermic vertebrates. Thus, each lineage faces a 'grey ceiling', i.e. a maximum viable brain size, beyond which rmax is so low that the risk of local or species extinction is very high. We found that the steep decline in rmax with brain size is absent in taxa with allomaternal offspring provisioning, such as cooperatively breeding mammals and most altricial birds. These taxa thus do not face a lineage-specific grey ceiling, which explains the far greater number of independent origins of large brain size in birds than mammals. We also predict that (absolute and relative) brain size is an important predictor of macroevolutionary extinction patterns.     

What's so special about Osler?

Sir William Osler was an outstanding figure in American and British Medicine during the early years of this century. Over fifty years after his death, his name is still remembered and honored, whereas other leaders who were equally important in the eyes of their contemporaries have been relegated to the realm of history. This brief review attempts to discover what special qualities have kept Osler''s memory vivid. No single characteristic of his skill, science, or personality seems in itself to explain his continuing reputation. Rather, a combination of his eminence in several different medical schools, his presence at a time of revolution in medical teaching and thought, his authorship of one of the most successful medical textbooks, and an enthusiastic claque of ex-students and colleagues seem to have combined to maintain his memory as a leader of medicine.     

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 are so many trees hollow?

In many living trees, much of the interior of the trunk can be rotten or even hollowed out. Previously, this has been suggested to be adaptive, with microbial or animal consumption of interior wood producing a rain of nutrients to the soil beneath the tree that allows recycling of those nutrients into new growth via the trees roots. Here I propose an alternative (non-exclusive) explanation: such loss of wood comes at very little cost to the tree and so investment in costly chemical defence of this wood is not economic. I discuss how this theory can be tested empirically.     

Why are mammalian tendons so thick?

The maximum stresses to which a wide range of mammalian limb tendons could be subjected in life were estimated by considering the relative cross-sectional areas of each tendon and of the fibres of its muscle. These cross-sectional areas were derived from mass and length measurements on tendons and muscles assuming published values for the respective densities. The majority of the stresses are low. The distribution has a broad peak with maximum frequency at a stress of about 13 MPa, whereas the fracture stress for tendon in tension is about 100 MPa. Thus, the majority of tendons are far thicker than is necessary for adequate strength. Much higher stresses are found among those tendons which act as springs to store energy during locomotion. The acceptability of low safety factors in these tendons has been explained previously (Alexander, 1981). A new theory explains the thickness of the majority of tendons. The muscle with its tendon is considered as a combined system which delivers mechanical energy: the thickness of the tendon is optimized by minimizing the combined mass. A thinner tendon would stretch more. To take up this stretch, the muscle would require longer muscle fibres, which would increase the combined mass. The predicted maximum stress in a tendon of optimum thickness is about 10 MPa, which is within the main peak of the observed stress distribution. Individual variations from this value are to be expected and can be understood in terms of the functions of the various muscles.     

Pollen grains: Why so many?

My objective is the examination of selective forces that affect pollen number. Relationships among other floral traits of animalpollinated plants, including pollen size, stigma area and depth, and the pollen-bearing area of the pollinator may affect pollen number and also provide a model to examine how change in one trait may elicit change in other traits. The model provides a conceptual framework for appreciating intra- and inter-specific differences in these traits. An equivalent model is presented for wind-pollinated plants. For these plants the distance between putative mates may be the most important factor affecting pollen number. I briefly consider how many pollen grains must reach a stigma to assure fruit set. I use pollen-ovule ratios (P/Os) to examine how breeding system, sexual system, pollen vector, and dispersal unit influence pollen grain number. I also compare the P/Os of plants with primary and secondary pollen presentation and those that provide only pollen as a reward with those that provide nectar as part or all of the reward. There is a substantial decrease in P/O from xenogamy to facultative xenogamy to autogamy. Relative to homoecious species the P/Os of species with most other sexual systems are higher. This suggests that there is a cost associated with changes in sexual system. The P/Os of wind-pollinated plants are substantially higher than those of animal-pollinated plants, and the available data suggest there is little difference in the pollination efficiency of the various animal vectors. The P/Os of plants whose pollen is dispersed in tetrads, polyads, or pollinia are substantially lower than those of species whose pollen is dispersed as monads. There was no difference in the P/Os of plants with primary and secondary pollen presentation. The P/Os of plants that provide only pollen as a reward were higher than those that provide nectar as a reward. All of these conclusions merit additional testing as they are based on samples that are relatively small and/or systematically biased.