December 15, 2006
Vol. 10 - Number 49
We have entered the cell, the mansion of our birth, and have started the inventory of our acquired wealth.
-- Albert Claude (1899-1983)
NEUROSCIENCE: ON DENDRITE SPINE SIZE AND FUNCTION
The following points are made by C. Kopec and R. Malinow (Science 2006 314:1554):
1) From the overall body plan of an organism to the intricate three-dimensional fold of proteins, structure is a key determinant of function. Neurons, the fundamental cells of the nervous system, are no exception. The architecture of their dendritic and axonal arbors -- the cellular extensions that receive and transmit information -- determines which neurons they can connect to, whereas the diameter of these extensions determines the speed and filtering of electrical signals that travel down them. Tiny femtoliter [10^(-15) liter]-sized protrusions from neuronal dendrites, called spines, receive a functional connection from another neuron's axon at a specialized area of contact known as a synapse. New work (1) marks a large step forward in our understanding of how spine size and synaptic strength are balanced.
2) A neuron can have up to 100,000 spines, each generally forming a single synapse. Spines function as chemical compartments for signaling molecules that become activated by specific patterns of synaptic transmission (2-4). This organization provides each synapse with a miniature caldron in which to concoct a chemical brew to effect changes in connections between neurons (5).
3) Large spines contain strong synapses (robust transmission) and small spines have weak synapses. A spine is at least an order of magnitude larger than a synapse, and thus there is no physical requirement for this correlation. The reason for this correlation between structure and function remains elusive, but an abundance of circumstantial evidence points to its importance. Stimuli that cause stable changes in synaptic strength lead to corresponding stable changes in spine volume. Heritable forms of mental retardation can present abnormalities in spine morphology as well as synaptic function. Furthermore, Alzheimer's disease may involve a loss of spines that is fundamentally linked to a decrease in the number of neurotransmitter receptors at the synapse. Therefore, understanding how and why this correlation between synapse strength and spine size exists will not only expand our understanding of how synapses work, but may have clinical relevance as well.
4) Park et al (1) combine serial section electron microscopy and live cell fluorescence microscopy to afford a view of the inner workings of spines. The authors stimulated cultured mammalian neurons to generate a stable increase in synaptic strength known as long-term potentiation (LTP), and confirmed that the rapid increase in synaptic strength is accompanied by a matched increase in spine volume. They then probed the molecular and cellular mechanisms behind this correlation. They focused on the role of the recycling endosome, an intracellular membrane-bound compartment that is part of the system that transports membrane- bound proteins onto and off the cell surface. Previous work by this group showed that the protein GluR1 is delivered to the neuronal surface from the recycling endosome through exocytosis, the cell's secretory process. GluR1 is a glutamate receptor subunit that is inserted into synapses during LTP and plays an important role in mediating the increase in synaptic strength. Blocking this delivery by expressing mutant proteins that specifically inhibit this exocytosis prevented the stable increase in synaptic strength. In the present work, Park et al (1) provide evidence that the lipids delivered to the neuron's surface from the vesicles carrying GluR1 are the raw materials that allow the spine to enlarge.
1. M. Park et al., Neuron 52, 817 (2006).
2. K. Svoboda, D. W. Tank, W. Denk, Science 272,  (1996).
3. B. L. Bloodgood, B. L. Sabatini, Science 310,  (2005).
4. A. Zador, C. Koch, T. H. Brown, Proc. Natl. Acad. Sci. U.S.A. 87, 6718 (1990).
5. M. Sheng, M. J. Kim, Science 298,  (2002).
EVOLUTION: ON HUMAN SOCIALITY
The following points are made by Robert Boyd (Science 2006 314:1555):
1) The scale and complexity of human societies present an important evolutionary puzzle. In every human society, people cooperate with many unrelated individuals. Division of labor, trade, and large-scale conflict are common. The sick, hungry, and disabled are cared for, and social life is regulated by commonly held moral systems that are enforced, albeit imperfectly, by third-party sanctions. In contrast, in other primate species, cooperation is limited to relatives and small groups of reciprocators. There is little division of labor or trade, and no large-scale conflict. No one cares for the sick, or feeds the hungry or disabled. The strong take from the weak without fear of sanctions by third parties. New work (1) offers one explanation for the commonness of costly, prosocial behavior in human societies.
2) The behavior of other primates is easy to understand. Natural selection only favors individually costly, prosocial behavior when the beneficiaries of the behavior are disproportionately likely to share the genes that are associated with the behavior. Selection can favor altruism toward close relatives because recent common descent provides a cue of genetic similarity. The small size of primate families limits the size and complexity of the groups that can be formed through this process. Thus, standard evolutionary theory provides a perfectly good explanation for the behavior of other primates, but not humans.
3) Bowles proposes that competition between genetically differentiated groups led to the evolution of our prosocial psychology. Limited migration between groups can lead to the buildup of genetic relatedness (which measures how much the possession of a particular gene in one individual predicts the presence of the same gene in a second individual) among group members. This means that group membership can also be a cue that allows assortative interaction--genes that cause you to help members of your group can be favored because other group members are disproportionately likely to carry the same genes, even though you do not share a recent common ancestor. This is an old idea. A version appears in The Descent of Man (2) and has reappeared many times since then. It has never gained much traction, however, because there have been good reasons to doubt its importance. First, theoretical work raised doubts about levels of genetic relatedness being high enough to favor prosocial behavior toward group members (3). Second, limited migration generates more competition within groups than between groups. This means that helping others in your own group reduces your own relative fitness and the fitness of your descendants. In some plausible models of the evolution of altruism when migration is limited, this effect exactly balances increases in relatedness, eliminating selection for altruism toward group members (4). Finally, the benefits of success in intergroup competition seems too small and the costs too large to allow cooperation to evolve. After all, other primates live in similar groups, but show little evidence of group-level cooperation.
4) Bowles meets these objections with a combination of data and theory. First, he has assembled data on the amount of genetic differentiation among human hunter-gatherer groups (or put another way, the level of relatedness within such groups). These data show that the level of relatedness within such groups is substantially higher than previously supposed, a bit below that of cousins. This means that the cooperation will be favored as long as the benefits to individuals are about 10 times the cost. Second, because competition occurs between groups and successful groups are able to colonize the territories of extinct groups, competition among relatives does not attenuate the benefits derived from cooperation. Third, intergroup competition is common in small-scale societies, so the benefits derived from collective efforts to compete with other groups are plausibly substantial. Finally, Bowles notes that human foraging groups typically have culturally transmitted norms and practices, including food sharing and socially imposed monogamy, which reduce fitness differences within groups. He makes the original and interesting argument that such "leveling mechanisms" act like redistributive taxes to reduce the disadvantage of engaging in costly prosocial behavior. The absence of these kinds of leveling mechanisms in primate groups may explain why human societies differ from those of other primates.
5) Make no mistake. This is not a "group selection" hypothesis that competes with "kin selection" hypotheses [see the Review by Nowak (5) for a discussion of conditions that favor the evolution of cooperative behavior]. Both concepts are equivalent frameworks for describing the same evolutionary process. The group (also known as multilevel) selection approach describes all natural selection as going on in a series of nested levels: among genes within an individual, among individuals within a group, and among groups. The kin selection approach accounts all fitness effects back to the individual gene. Bowles adopts the multilevel selection framework, but you can pose exactly the same argument in a kin selection framework and if you do your sums properly, you will get exactly the same answer. The real questions are: Are amounts of genetic variation observed among contemporary human foraging groups representative of the Pleistocene hominin populations in which distinctively human behavior probably evolved? Were the benefits of success (survival) from intergroup competition in ancestral human populations large enough to compensate for the individual costs of participating in such contests? And, do the kinds of leveling mechanisms observed among contemporary foragers exist and work in the same way in ancestral populations?
1. S. Bowles, Science 314, 1569 (2006).
2. C. Darwin, The Descent of Man (1871).
3. A. R. Rogers, Am. Nat. 135, 398 (1990).
4. P. D. Taylor, Evol. Ecol. 6, 352 (1992).
5. M. A. Nowak, Science, 314, 1560 (2006).
CANCER: STEM CELLS AND BRAIN TUMORS
The following points are made by Peter B. Dirks (Nature 2006 444:687):
1) Cancers are notorious for their ability to survive treatment and recur. Hopes of understanding how they can do so, however, have grown with the prospective identification of rare populations of cancer stem cells in solid tumours (1,2). New work (3,4) marks a step towards realizing these hopes, and provides further insight into the stem-cell nature of human glioblastoma, an especially nasty type of brain cancer. Both studies build on the identification2 of a tumour-initiating subpopulation of cells that express a cell-surface marker, CD133, that is a hallmark of neural precursor cells.
2) Bao et al (3) show that glioblastoma cells expressing CD133 (CD133+ cells) are resistant to ionizing radiation because they are more efficient at inducing the repair of damaged DNA than is the bulk of the tumour cells. Radiation therapy has been the mainstay of glioblastoma treatment for more than 40 years, but although it is transiently effective, it offers no lasting cure. The implication of these results is that radiation treatment fails in the long run because it cannot kill the subpopulation of CD133+ tumour-initiating cells.
3) Piccirillo et al (4) describe their work with bone morphogenetic proteins (BMPs), soluble factors that normally induce neural precursor cells to differentiate into mature astrocytes -- a subtype of brain cells called glial cells. The authors show that BMPs can also prompt the differentiation of CD133+ brain tumour cells, critically weakening their tumour- forming ability. The results further imply that tumour populations at least partially retain a developmental hierarchy based on stem cells, and remain able to respond to the normal signals that induce them to mature. These findings should lead to renewed interest in devising therapies that promote the differentiation of cancer cells.
4) Both groups (3,4) arrived at their findings by considering the functional hierarchy of the heterogeneous population of tumour cells. In doing so, they add weight to the importance in this research of dissociating solid-tumour samples into single-cell suspensions, purifying the stem-cell fractions, and testing their response to treatment. Crucially, both groups verified their in vitro results with in vivo studies. A true demonstration that human tumour-initiating cells can act as such requires use of the "gold standard" assay (5) of transplanting them into immunodeficient mice to see if they retain their stem-cell capacity.
1. Al-Hajj, M. et al. Proc. Natl Acad. Sci. USA 100, 3983-3988 (2003).
2. Singh, S. K. et al. Nature 432, 396-401 (2004).
3. Bao, S. et al. Nature 444, 756-760 (2006).
4. Piccirillo, S. G. M. et al. Nature 444, 761-765 (2006).
5. Bonnet, D. & Dick, J. E. Nature Med. 3, 730-737 (1997).
OCEANOGRAPHY: PLANKTON AND GLOBAL WARMING
The following points are made by Scott C. Doney (Nature 2006 444:695):
1) Oranges in Florida, wildfires in Indonesia, plankton in the North Pacific -- what links these seemingly disparate items is that they are all affected by year-to-year fluctuations in global-scale climate. New work (1) describes how such fluctuations, especially in temperature, are connected to the productivity of phytoplankton in the world's oceans. The analyses are based on nearly a decade of satellite data, and for much of the oceans they find that recent warmer surface temperatures correspond to lower oceanic biomass and productivity. Behrenfeld et al (1) argue that these patterns arise because climate-induced changes in ocean circulation reduce the supply of nutrients needed for photosynthesis.
2) Small photosynthetic phytoplankton grow in the well- illuminated upper ocean, forming the base of the marine food web and supporting the fish stocks we harvest. They also form the basis of the biogeochemical cycling of carbon and many other elements in the sea. Phytoplankton growth depends on temperature and the availability of light and nutrients, including nitrogen, phosphorus, silicon and iron. Most of this nutrient supply to the surface ocean comes from the mixing and upwelling of cold, nutrient-rich water from below, with an additional source of iron from mineral dust swept off the continental deserts. Phytoplankton biomass can vary by a factor of 100 in surface waters; its geographical distribution is determined largely by ocean circulation and upwelling, with the highest levels being found along the Equator, in temperate and polar latitudes, and along the western boundaries of continents.
3) Although the broad spatial patterns of phytoplankton biomass and productivity are well documented (2), large-scale temporal variations have only recently become quantifiable with the advent of satellite ocean-colour sensors (3). The ocean is vast, and the limited number of research ships move at about the speed of a bicycle, too slow to map the ocean routinely on ocean-basin to global scales. By contrast, a satellite can observe the entire globe, at least the cloud-free areas, in a few days. Phytoplankton biomass and growth rates can be estimated remotely from space because chlorophyll, the main photosynthetic pigment in phytoplankton, absorbs blue and red sunlight more readily than green sunlight. Ocean-colour sensors measure, by wavelength band, the small fraction of sunlight scattered back to space from below the surface. The resulting surface-chlorophyll data can be combined with empirical relationships to estimate phytoplankton growth rates or net primary production (4).
4) Not that this procedure is straightforward: other constituents of sea water absorb light; many photons reaching the satellite sensor come from atmospheric aerosols or reflection at the water surface; and optical detectors on satellites degrade with time. But with careful calibration, high-quality, long-term records of ocean-colour data can be constructed for detecting climate-driven trends. The best such record at present is from GeoEye and from NASA's Sea-viewing Wide Field-of-view Sensor (SeaWiFS) (3), launched in 1997. In the SeaWiFS time series, global chlorophyll and productivity increase sharply during 1997-98 and then decline gradually to 2005. Behrenfeld et al (1) show that these trends closely follow changes in climate.
1. Behrenfeld, M. J. et al. Nature 444, 752-755 (2006).
2. Longhurst, A. Ecological Geography of the Sea 2nd edn (Academic, New York, 2006).
3. McClain, C. R., Feldman, G. C. & Hooker, S. B. Deep-Sea Res. II 51, 5-42 (2004).
4. Carr, M.-E. et al. Deep-Sea Res. II 53, 741-770 (2006).
5. Polovina, J. J., Mitchum, G. T. & Evans, G. T. Deep-Sea Res. I 42, 1701-1716 (1995).
Giới thiệu Sách
Concepts in Thermal Physics. Stephen J. Blundell and Katherine M. Blundell. Oxford University Press, Oxford, 2006. Paperback: 482 pp., illus. ISBN 0198567707. More information at: http://www.amazon.com/exec/obidos/ASIN/0198567707/scienceweek
Louis Bachelier's Theory of Speculation. The Origins of Modern Finance. Translated. Commentary by Mark Davis and Alison Etheridge. Princeton University Press, Princeton, NJ, 2006. Hardback: 204 pp., illus. ISBN 0691117527. More information at: http://www.amazon.com/exec/obidos/ASIN/0691117527/scienceweek
The Meaning of the 21st Century. A Vital Blueprint for Ensuring Our Future. James Martin. Riverhead (Penguin), New York, 2006. Hardback: 443 pp. ISBN 1573223239. More information at: http://www.amazon.com/exec/obidos/ASIN/1573223239/scienceweek
The Creation. An Appeal to Save Life on Earth. Edward O. Wilson. Norton, New York, 2006. Hardback: 185 pp., illus. ISBN 0393062171. More information at: http://www.amazon.com/exec/obidos/ASIN/0393062171/scienceweek
The Physics of Phase Transitions. Concepts and Applications. 2nd ed. P. Papon, J. Leblond, and P. H. E. Meijer. Springer, Berlin, 2006. Hardback: 427 pp., illus. ISBN 3540333894. More information at: http://www.amazon.com/exec/obidos/ASIN/3540333894/scienceweek