Down to the origin: Cdc6 protein and the competence to replicate

In eukaryotes, DNA replication requires the regulated assembly of pre-replicative complexes (pre-RCs) onto DNA during G1 phase. Pre-RCs render the chromatin competent to replicate, yet it is only at the G1-S phase transition that protein-kinase complexes trigger the transition to DNA replication. Central to the formation of pre-RCs and regulation of DNA replication is the Cdc6 protein. Two recent studies have shown that Cdc6 is the long-sought factor that confers the competence to replicate in unfertilized Xenopus eggs.     

Development and Macroevolution: Introduction to the Symposium

Despite the historical relationship between embryology and evolutionarybiology, during most of the 20th century developmental biologyand evolutionary biology have existed as two separate subdisciplinesof biology. Recently a reunion of these subdisciplines beganto take place. This reunion involves the formulation of evolutionaryexplanations of developmental phenomena and the applicationof developmental processes as mechanisms of evolutionary change.The symposium speakers have considered both aspects of the reunionas well as some of the theoretical and methodological issuesthat are emerging from it.     

GLIA: listening and talking to the synapse

Glial cells are emerging from the background to become more prominent in our thinking about integration in the nervous system. Given that glial cells associated with synapses integrate neuronal inputs and can release transmitters that modulate synaptic activity, it is time to rethink our understanding of the wiring diagram of the nervous system. It is no longer appropriate to consider solely neuron-neuron connections; we also need to develop a view of the intricate web of active connections among glial cells, and between glia and neurons. Without such a view, it might be impossible to decode the language of the brain.     

Values and Valuables: From the Sacred to the Symbolic

Values and Valuables: From the Sacred to the Symbolic. Cynthia Werner and Duran Bell, eds. New York: AltaMira Press, 2004. 326 pp.     

Incentives and opportunism: from the carrot to the stick

Cooperation in public good games is greatly promoted by positive and negative incentives. In this paper, we use evolutionary game dynamics to study the evolution of opportunism (the readiness to be swayed by incentives) and the evolution of trust (the propensity to cooperate in the absence of information on the co-players). If both positive and negative incentives are available, evolution leads to a population where defectors are punished and players cooperate, except when they can get away with defection. Rewarding behaviour does not become fixed, but can play an essential role in catalysing the emergence of cooperation, especially if the information level is low.     

Proteolysis: from the lysosome to ubiquitin and the proteasome

How the genetic code is translated into proteins was a key focus of biological research before the 1980s, but how these proteins are degraded remained a neglected area. With the discovery of the lysosome, it was suggested that cellular proteins are degraded in this organelle. However, several independent lines of experimental evidence strongly indicated that non-lysosomal pathways have an important role in intracellular proteolysis, although their identity and mechanisms of action remained obscure. The discovery of the ubiquitin-proteasome system resolved this enigma.     

Stretch-activated channels in the heart: contributions to length-dependence and to cardiomyopathy

The stretch-induced increase in force production of ventricular muscle is biphasic. An abrupt increase in force coincides with the stretch, which is then followed by a slower response that develops over minutes (the slow force response or SFR). The SFR is accompanied by a slow increase in the magnitude of the intracellular Ca2+ transient, but the stretch-dependent mechanisms that give rise to this remain controversial. We characterized the SFR using right ventricular trabeculae from mouse hearts. Application of three different blockers of stretch-activated non-selective cation channels (SAC NSC) reduced the magnitude of the SFR 60s after stretch (400 microM streptomycin: from 86+/-25% to 38+/-14%, P<0.01, n=9; 10 microM GdCl3: from 65+/-21%, to 12+/-7%, P<0.01, n=7; 10 microM GsMTx-4 from 122+/-40% to 15+/-8%, P<0.05, n=6). Streptomycin also decreased the increase in Ca2+ transient amplitude 60s after the stretch from 43.5+/-12.7% to 5.7+/-3.5% (P<0.05, n=4), and reduced the stretch-dependent increase in intracellular Ca2+ in quiescent muscles when stretched. The transient receptor potential, canonical channels TRPC1 and TRPC6 are mechano-sensitive, non-selective cation channels. They are expressed in mouse ventricular muscle, and could therefore be responsible for stretch-dependent influx of Na+ and/or Ca2+ during the SFR. Expression of TRPC1 was investigated in the mdx heart, a mouse model of Duchenne's muscular dystrophy. Resting Ca2+ was raised in isolated myocytes from old mdx animals, which was blocked by application of SAC blockers. Expression of TRPC1 was increased in the older mdx animals, which have developed a dilated cardiomyopathy, and might therefore contribute to the dilated cardiomyopathy.     

Essential properties and the right to life: a response to Lee

In 'The Pro-Life Argument from Substantial Identity: A Defence', Patrick Lee argues that the right to life is an essential property of those that possess it. On his view, the right arises from one's 'basic' or 'natural' capacity for higher mental functions: since human organisms have this capacity essentially, they have a right to life essentially. Lee criticises an alternative view, on which the right to life arises from one's 'developed' capacity for higher mental functions (or development of some other accidental property). I argue that his criticisms of this alternative view are misguided or self-defeating, and that there are good reasons to hold we have a right to life accidentally rather than essentially.     

HIV-host interactions: vital to the virus and key to its inhibition

Much progress has been made in recent years in the investigation of the interplay between HIV-1 and its host cells. Most of these interactions are complex and have not yet been fully unraveled. Nevertheless, current knowledge on the molecular interactions between HIV and host-cell factors has substantially broadened our understanding of the viral life cycle and opened new investigative areas for drug intervention.     

HIV-host interactions: vital to the virus and key to its inhibition

Much progress has been made in recent years in the investigation of the interplay between HIV-1 and its host cells. Most of these interactions are complex and have not yet been fully unraveled. Nevertheless, current knowledge on the molecular interactions between HIV and host-cell factors has substantially broadened our understanding of the viral life cycle and opened new investigative areas for drug intervention.